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23 juni 2010 University of Twente Erik van Bussel, Marjolein Heuvelmans, Michiel Klitsie, Joeke Nollet Medical supervisor: dr. P. Dik Technical supervisor: dr. ir. B. ten Haken Tutor: dr. F. Verhoeven IMAGING CHILDREN’S PLEXUS SACRALIS: TOWARDS AN OPTIMAL METHOD Bachelor Thesis Technical Medicine

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Page 1: Imaging Children’s plexus sacralis: Towards an optimal method€¦ · Imaging the plexus sacralis is the first step in confirming this hypothesis. For depicting the nerves of the

23 juni 2010 University of Twente

Erik van Bussel, Marjolein Heuvelmans, Michiel Klitsie, Joeke Nollet Medical supervisor: dr. P. Dik Technical supervisor: dr. ir. B. ten Haken Tutor: dr. F. Verhoeven

IMAGING CHILDREN’S PLEXUS SACRALIS: TOWARDS AN

OPTIMAL METHOD Bachelor Thesis Technical Medicine

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PREFACE This is the Bachelor Thesis (MDO) “Imaging children’s plexus sacralis: towards an optimal method”. This

Bachelor Thesis is part of the bachelor of Technical Medicine and is commissioned by the University Medical

Center Utrecht (UMCU).

The original assignment was about testing the hypothesis if anatomical variations in the plexus sacralis could be

responsible for bladder dysfunction, by the means of depicting these anatomical variations. It was a

“hypothesis that might give an entirely new vision of neurogenic bladder dysfunction”. We naively thought that

in the end we would have a new way of diagnosing a group of patients. But, like real pioneers, we had to start

at the beginning: the depicting of the plexus sacralis.

As we made the first steps in this field, we had to contact many specialists that might give us some insight in

this subject. For the assistance in our research and for the many enthusiastic and sympathetic reactions we

received, we would like to thank some people who helped us during our research.

First of all we would like to thank our medical supervisor dr. P. Dik and our technical supervisor dr. ir. B. ten

Haken. We would like to thank dr. P. Dik for sending in and trusting us with this assignment, his creative spirit,

e.g. for forming this new hypothesis, and his enthusiasm that never ceased to inspire us. We would like to

thank dr. ir. B. ten Haken for his constructive criticism, his scientific approach and his exactitude. Both found

the time in their busy schedules for guiding us.

Speaking of guidance, we also we like to thank our tutor, dr. F. Verhoeven. She supported us nine weeks long

and gave us much support and directives about how to work together. The contact was always on a personal

level and her enthusiasm motivated us.

In searching information, we also had appointments with many specialists. For their time and information we

would like to thank Prof. dr. W Mali, drs. J. Avenarius and dr. K. Poortema. We especially would like to thank

drs. T. Kwee: in his free time he made our practical research possible and he always responded with extensive

answers to our e-mails.

Last but not least, we would like to thank the following people from who gave us answers by e-mail, drs. M.

Vargas, dr. T. Takahara, dr. W. Freund, dr. R. Nievelstein and van dr. A Cappellen van Walsum, who gave their

reactions from all over the world.

We hope this Thesis is a first step to future research which will help the group of patients.

Enschede, 23 juni 2010,

Erik van Bussel,

Marjolein Heuvelmans,

Michiel Klitsie,

Joeke Nollet

"Een tocht van 1000 mijl moet beginnen met een eerste stap." - a fitting Dutch translation of a quote by Lao-Tse, Chinese philosopher (+/- 600 v. Chr.)

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SUMMARY

This Thesis is based on the hypothesis that variations in the plexus sacralis could be responsible for bladder

dysfunction. Imaging the plexus sacralis is the first step in confirming this hypothesis.

For depicting the nerves of the plexus sacralis, MRI is the best technique because of the excellent soft tissue

discrimination and the high resolution. A lot of different sequences are known, some can be used to image

nerves and these seem very promising.

Sequences that can possibly be used for imaging the plexus sacralis are SE or FSE that are T1- or T2-weighted,

STIR, BTFE, MP-RAGE and DW-MRN. Since the standard protocol already includes T2-weighted FSE, T1-

weighted and STIR sequences and because only few literature about BTFE and MP-RAGE could be found and

research experiences on the topic of DW-MRN in the UMCU was present, we decided to focus our study on

DW-MRN.

A practical research has been done: DW-MRN scans have been made at a 1,5 T MRI scanner, which is never

been investigated before on the plexus sacralis. Following the results of this practical research, it can be

concluded that DW-MRN, performed at a 1,5 T MRI scanner, images the nerves of the plexus sacralis. However,

the third and fourth sacral nerve can hardly be visualized and optimization is required.

For this optimization further research is needed and therefore this Thesis shall be completed by a research

proposal for a third year master internship for students of the study Robotics and Imaging of Technical

Medicine elaborating on the results of the analysis of the new sequence.

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CONTENT

Introduction ..................................................................................................................................................... 5

Anatomy & Imaging techniques ....................................................................................................................... 6

Anatomy ............................................................................................................................................................. 7

The bladder and the plexus sacralis ................................................................................................................ 7

Histology of nerves .......................................................................................................................................... 8

Structures surrounding the plexus sacralis ..................................................................................................... 9

Anatomical variations of the plexus sacralis ................................................................................................. 11

Ultrasonography ............................................................................................................................................... 13

Sub-conclusion .............................................................................................................................................. 14

Projectional radiography and Computed Tomography .................................................................................... 15

Sub-conclusion .............................................................................................................................................. 15

Electrophysiology ............................................................................................................................................. 16

Sub-conclusion .............................................................................................................................................. 16

Magnetic resonance imaging ........................................................................................................................... 17

Advantages and disadvantages ..................................................................................................................... 18

Imaging the plexus sacralis ........................................................................................................................... 18

Sub-conclusion .............................................................................................................................................. 18

Main conclusion imaging techniques ............................................................................................................... 19

Anatomy & MRI sequences ............................................................................................................................ 20

Introduction...................................................................................................................................................... 21

Anatomical comparisons .................................................................................................................................. 23

A comparison of the plexus sacralis and plexus brachialis............................................................................ 23

MR-neurography of the plexus sacralis in children and adults ..................................................................... 24

General parameters ......................................................................................................................................... 26

Relaxation times of nerves and the use of contrast agents .......................................................................... 26

SNR, ultra high fields and resolution ............................................................................................................. 27

Sub-conclusion .............................................................................................................................................. 28

Spin Echo Sequences ........................................................................................................................................ 29

Standard SE and Fast SE in relation to the plexus sacralis ............................................................................ 29

Sub-conclusion .............................................................................................................................................. 30

Inversion recovery MRI .................................................................................................................................... 31

Short tau inversion recovery (STIR) ............................................................................................................... 31

Fluid attenuated inversion recovery (FLAIR) ................................................................................................. 31

Sub-conclusion .............................................................................................................................................. 31

Gradient Echo Sequences ................................................................................................................................. 32

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Coherent GE sequences ................................................................................................................................ 32

Incoherent GE sequences .............................................................................................................................. 33

Steady state free precession (SSFP) .............................................................................................................. 33

Sub-conclusion .............................................................................................................................................. 33

Diffusion weighted MR imaging ....................................................................................................................... 34

Applications of DW-MRI ................................................................................................................................ 34

Advantages and disadvantages of DW-MR neurography ............................................................................. 35

Sub-conclusion .............................................................................................................................................. 36

Diffusion tensor imaging (DTI) .......................................................................................................................... 37

Applications ................................................................................................................................................... 37

Limitations ..................................................................................................................................................... 37

Sub-conclusion .............................................................................................................................................. 38

Magic Angle ...................................................................................................................................................... 39

Application of the magic angle in nerves and the plexus sacralis ................................................................. 39

Disadvantages and points of attention ......................................................................................................... 41

Sub-conclusion .............................................................................................................................................. 41

Post-processing ................................................................................................................................................ 42

Sub-conclusion .............................................................................................................................................. 42

Conclusion MRI Sequences and Techniques .................................................................................................... 43

Towards a new protocol… .............................................................................................................................. 44

Introduction...................................................................................................................................................... 45

Standard protocol............................................................................................................................................. 46

The protocol .................................................................................................................................................. 46

Analysis ......................................................................................................................................................... 46

A new protocol: DW-MRN in practice .............................................................................................................. 47

Goal ............................................................................................................................................................... 47

Materials and methods ................................................................................................................................. 47

Results ........................................................................................................................................................... 49

Discussion ...................................................................................................................................................... 50

Conclusion ..................................................................................................................................................... 51

Discussion ...................................................................................................................................................... 52

General discussion ........................................................................................................................................ 53

Alternative hypotheses ................................................................................................................................. 53

Alternative research proposals ..................................................................................................................... 53

Conclusion ...................................................................................................................................................... 54

References ..................................................................................................................................................... 56

Appendix A: Research proposal ...................................................................................................................... 60

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INTRODUCTION This Bachelor Thesis is aimed at patients with bladder symptoms by which no abnormalities are found in

conventional studies. More specific, this study is directed to children with a broad range of bladder symptoms,

without a known anatomic substrate. The hypothesis is that these symptoms may be caused by anatomical

variations of the plexus sacralis.

The given assignment is actually a bipartite research assignment. The first part is about the depiction of the

plexus sacralis and its anatomical variations. The second research is about the relation between the bladder

symptoms and the anatomical variations. Because the field of the anatomical variations of the plexus sacralis

and the depiction of the normal anatomy of the plexus sacralis are both completely new, this paper will be

focused at the depiction of the plexus sacralis.

The purpose of this study is to find a technique to visualize the plexus sacralis in a detailed, distinctive way, and

to write a research proposition for future (master)students based on these findings.

Our main question is: What is the most suitable imaging technique to depict the variations of the plexus sacralis

in children? Here, a suitable imaging technique is defined as a technique that can image the plexus sacralis and

his branches with a resolution and signal to noise ratio that allows to follow the nerves.

For finding an answer at this question, we divided the main question in sub-questions with the use of a layered

structure of three levels to build towards the final answer, see Table 1. First, we will revise the most used

imaging techniques in general and then we will revise different subcategories of the most suitable technique.

Finally we will perform a practical research to test a promising imaging technique and give recommendations

for further research in the form of a research proposal.

TABLE 1 - OVERVIEW RESEARCH QUESTIONS

Anatomy &

Techniques

What is known about anatomical variations of the plexus sacralis in different individuals?

What types of tissues may be important in imaging the plexus sacralis?

What imaging techniques are currently available for imaging the plexus sacralis?

Which of the available imaging techniques is best suited for imaging the plexus sacralis?

Anatomy &

Sequences

What is the comparison between the plexus sacralis and the plexus brachialis with respect to imaging and anatomy?

What is the comparison between children and adults in the chosen imaging technique of the plexus sacralis?

Which scanning methods or sequences are possible within the chosen imaging technique?

Which scanning methods or sequences are most suitable for the depiction of the plexus sacralis within the chosen imaging technique?

Practical

research

What is the current protocol for imaging the plexus sacralis?

Which sequence is best suited for further research?

How could further research look like?

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ANATOMY & IMAGING TECHNIQUES

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ANATOMY

First, the anatomy will be discussed to give an overview of the anatomical surrounding of the plexus sacralis

and the variations of the plexus sacralis. The choice for an imaging method can depend on the anatomical

surrounding and anatomical properties, such as the histology, of the structure you want to depict. The

anatomical surrounding can also influence images of an imaging technique and because of this, a solid

understanding of the anatomy is preferable.

THE BLADDER AND THE PLEXUS SACRALIS The plexus sacralis is the nerve plexus which provides motor and sensory nerves for the posterior thigh, most

of the lower leg, and, important for this research, most structures of the pelvis like the bladder. The plexus is

comprised of the ventral rami L4 and L5, the truncus lumbosacralis, and S1-S4 and converge towards the lower

part of the foramen ischiadicum majus to unite into a flattened band, see Figure 1. The plexus sacralis is

located retroperitoneal on the posterolateral wall of the lesser pelvis and is closely related to the anterior

surface of the m. piriformis. The m. psoas major has a craniolateral location towards the plexus. Often, the

plexus sacralis is merged with the superior plexus lumbalis. This connection is formed mainly by the truncus

lumbosacralis [1].

The main nerves that arise from the plexus sacralis and their functions are:

the n. ischiadicus. This nerve innervates the gluteal region and the legs and arises from the anterior

rami of spinal nerves L4-S3. The diameter of this nerve is about 1 cm;

the n. pudendus. This nerve is a mix of somatic and autonomic nerves and arises from the anterior

rami of S2-S4, and originates in Onuf’s nucleus. It is the main nerve of the perineum and the most

important sensory nerve of the external genitali. The nerve also innervates the external sphincter of

the bladder. The diameter of this nerve is about 3 mm;

the n. pelvicus. This nerve arises from the anterior rami of S2-S4. It exists of parasympathetic fibres

and their function is to contract the m. detrusor vesicae. In this way, activation of the n. pelvicus

enables emptying of the bladder [1, 2].

FIGURE 1 - THE PLEXUS SACRALIS [3]

Another nerve that innervates the bladder, but is not included in the plexus sacralis, is the n. hypogastricus

(Th10-L2). It is a sympathetic nerve that innervates the bladder neck, which function is opposite to the n.

pelvicus since it prevents emptying of the bladder [1, 2]. An overview of nerves innervating the bladder is given

in Table 2.

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TABLE 2 - OVERVIEW OF THE NERVES WHICH INNERVATE THE BLADDER

Nerve Character Target Function

n. pelvicus (S2-S4) parasympathetic bladder urinate

n. pudendus (S2-S4) somatic sphincter urinate

n. hypogastricus (Th10-L2) sympathetic bladder neck storage

HISTOLOGY OF NERVES The primary structure of a nerve consists of neurons, which are the cells that carry the action potentials. Many

neurons, and also those of which the plexus sacralis is composed, are wrapped in single or multilayered folds of

Schwann cells. These folds largely consist of membrane instead of cytoplasma. These membrane folds are

called the myeline, a lipoprotein complex [4].

Different nerve fibers with myelin sheds are surrounded by a delicate connective tissue, known as the

endoneurium. Within the endoneurium, the axons are bathed in endoneurial fluid, which is a low-protein

liquid. This endoneurial fluid may increase during development of nerve edema due to irritation or injury [5].

This is something to take into account when imaging nerves.

The different nerve fibers in the endoneurium are bundled in groups called fascicles. These fascicles have a

protective sheat which is the perineurium, a thin shell of dense connective tissue. This layer of connective

tissue protects the neurons from infections and toxins. The epineurium is the outermost layer of dense

irregular connective tissue surrounding a peripheral nerve. This outermost layer consists of collagen, elastine,

and variable amount of fat and small blood vessels supplying the nerve [4]. See Figure 2 for an overview of the

composition of a nerve fiber.

FIGURE 2 - COMPOSITION OF A NERVE FIBER [6]

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STRUCTURES SURROUNDING THE PLEXUS SACRALIS

The nerve roots of the plexus sacralis ascend from the fourth lumbar vertebra till the fourth sacral ‘vertebra’.

The plexus sacralis is for a major part surrounded by bone structure: the lateral pelvis bone and the foramen

ischiadicus major in which the plexus sacralis descends. The depth of the plexus sacralis in anterior-posterior

direction is 8 – 15 cm in adults and 5 – 8 cm in children, depending of the posture of the patient [1, 7].

In diagnostical images, nerve structures are often confused with the vascular system, because of their size,

course and location. The plexus sacralis is surrounded by arteries, arterioles and capillaries from the a. and v.

iliaca internus, which weave through the muscles, organs and nerves of the pelvic area. Of the viscera, it is

mainly the rectum that is located close to the (roots of the) plexus sacralis, although within the feminine body,

the uterus and vagina are also located between the bladder and sacrum [5], see Figure 3.

Next to bones and viscera, the plexus sacralis is also surrounded by muscles: for example, the m. piriformis is

located behind the plexus sacralis, see Figure 4. This muscle originates at the sacrum S2-S4, runs behind the

plexus sacralis, and inserts at the trochantor major. Posterior from the sacrum, down to the anterior side of the

pelvic bone, the pelvic area is enclosed by the mm. levator ani and m. coccygeus, which support the rectum

and bladder and cover the plexus sacralis. The anterior side of the plexus is shielded by the m. psoas major,

which runs craniolateral of the plexus. More lateral and superior, the m. obturator internus is situated more

lateral and superior of the plexus and is, like the muscles defined above, innervated by the plexus sacralis [1].

Another type of tissue in relation with the plexus sacralis is fat. This type of tissue can surround both viscera

and nerves: the plexus sacralis is therefore always, embedded in a layer of fat tissue. This fat can be used in

imaging techniques for a better discrimination between the nerves and their surroundings [1, 5, 8].

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FIGURE 3 - VESSELS AND VISCERA SURROUNDING THE PLEXUS SACRALIS [1]

FIGURE 4 - THE PLEXUS SACRALIS AND ITS SURROUNDING STRUCTURES, MEDIAL VIEW [1]

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ANATOMICAL VARIATIONS OF THE PLEXUS SACRALIS

The background thought of this Thesis is that anatomical variations can be a cause of variable bladder

dysfunction and therefore, a research about these variations could not be missed. Visualizing the variations

described here, is the final goal for imaging the plexus sacralis.

Few scientific literature could be identified regarding anatomical variations of the plexus sacralis. Only one

recently published study, conducted by Matejčík [9] was detected. Matejčík, demonstrated anatomical

variations in the plexus lumbosacralis in 50 fresh human cadavers. These plexi showed a high degree of

diversity. The most important findings will be highlighted.

The first noteworthy variation observed by Matejčík concerns the cranial beginning of the plexus lumbalis. Two

types of plexi are described. First, there is a variation in Th12 roots which do or do not converge into the plexus

lumbalis, described as prefixed and postfixed. The boundary root participating in the plexi formation is the L4

root, which in some cases is largely involved in lumbal plexus formation and sacral in others. In addition, the

article describes that Th12 and L1 are thicker in prefixed types and S3/S4 roots are absent when L4 contributes

more significantly to the plexus sacralis, instead of the plexus lumbalis. On the other side, when L4 only

minorily contributes to the plexus sacralis, S1-3 roots are thicker and S4 is present as well.

Second, variations in the area of plexus sacralis and plexus lumbalis were most frequently observed at the level

of neural root formation. The research showed two types of formation from the ascension of the roots, which

are described as double or plexiform. The double ascension involves a root that splits into two branches and

the plexiform ascension is a root that splits into a more complex plexus.

Third, the plexus research showed that foramen intervertebrale is at its most narrow at the level of L5/S1 and

was usually completely filled with the L5 root. Moreover, the plexus sacralis and plexus lumbalis were

connected by L4 in almost every investigated cadaver, although this did not hold for all cases (<10 %) where

both plexi were connected by other nerves.

The article also described a high variety in diameter and origin of the truncus lumbosacralis, in which the roots

of L4, L5 and S1 have a variable level of share and connection. Remarkably, Matejčík found that the innervation

of the first two sacral nerves is quite constant. Almost none variations has been found in S1 and S2.

In conclusion, it can be stated that there exists a broad range of anatomical variations in the plexus sacralis.

The different types of plexi can be a combination of the aforementioned variations, as shown in Figures 5A-5G,

which depict a front view of the plexus lumbosacralis in craniocaudal direction. These anatomical variations

possibly correlate with bladder dysfunction, although this has not been proven yet.

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FIGURE 5A - PREFIXED TYPE OF PLEXUS LUMBOSACRALIS, RIGHT SIDE [9]

FIGURE 5B - THICK TRUNCUS LUMBOSACRALIS, LEFT SIDE [9]

FIGURE 5C - THICK TRUNCUS LUMBOSACRALIS, LEFT SIDE [9]

FIGURE 5D - POSTFIXED TYPE OF PLEXUS LUMBOSACRALIS, RIGHT SIDE [9]

FIGURE 5E - DOUBLE ASCENSION OF L5 ROOT, LEFT SIDE [9]

FIGURE 5F - PLEXIFORM ASCENSION OF L5 ROOT, LEFT SIDE [9]

FIGURE 5G - DOUBLE S1 ROOT, RIGHT SIDE [9]

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ULTRASONOGRAPHY

Ultrasonography (US) produces two- or three-dimensional anatomic or flow images. Applications of this

imaging technique include in the pelvic area prenatal diagnostic among pregnant woman and anaesthesia, like

the use of parasacral sciatic blocks, and imaging of peripheral nerves in an arm or a leg [10].

The use of sonography by parasacral sciatic blocks could rise the hypothesis that it could be possible to image

nerves in the sacral region and the plexus sacralis. However, according to the literature, these nerves are

detected because of other anatomical structures the researchers recognized. Ben-Ari et al. described the

feasibility of locating the plexus sacralis using a parasacral approach and an ultrasound-guided technique. The

parasacral region was scanned using a low frequency curved probe (2-5 MHz) to reach the depth of the plexus

sacralis among 17 patients. First, the researchers searched the medial border of the os ischium and the lateral

border of the sacrum, representing the boundary of the foramen ischiadicum majus. This enabled the

researchers to identify the plexus sacralis: it appeared as a round hyperechoic bundle, see Figure 6. The

researchers verified this opinion by eliciting and measure a mediated motor response trough a pulse. In other

words: with just the image it was not sure that the bundle really represented the plexus, because no plexus

details could be (clearly) observed. According to the study results, imaging the separate nerves of the plexus is

impossible [10].

FIGURE 6 - SONOGRAPHY OF THE PLEXUS SACRALIS [10]

A problem of Ben-Ari was the low resolution, because of the lower selected frequency. This relation between

resolution, penetration depth and frequency is the result of the physics of sonography: sonography is based on

pulses of ultrasound, generated by a transducer and sent into the patient. These ultrasound pulses reflect on

tissue boundaries and produce echoes, based on the different acoustic impedances of the different tissues. The

transducer detects these echoes which are depicted in a computer image shown on a screen [11]. Commonly

used ultrasound frequencies vary from 2 MHz till 20 MHz. A higher frequency provides a better resolution.

However, a higher frequency simultaneously implies a lower penetration depth, because of the rise of

absorption and scattering of the ultrasound at higher frequencies [12, 13]. This implies that more deeply

situated nerves, such as the plexus sacralis, are more difficult to visualize, because the need of as well a high

penetration depth, as a relative high resolution.

Moreover, the suggested difficulties in imaging (deeper situated) nerves in the human body are confirmed by

another interesting study. An anesthetical study that tried to localize the n. pudendus showed that it is not

possible to detect structures smaller than 3,5 mm at a depth of 5 cm in the pelvic area with a 3.5-MHz curved-

array probe, where probes with higher frequencies cannot be used (due to penetration depth). Because the

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plexus sacralis lies, as mentioned before, at a depth of 8 – 15 cm in adults and 5 – 8 cm in children, it is very

hard or even impossible to image the nerves of the plexus with ultrasound. The article confirmed our claim

because the n. pudendus was transversely depicted in less than half the cases [14].

Because sonography can be used for imaging (larger) peripheral nerves and this technique has a lot of

advantages, such as the low costs, the ease of use, real time imaging and its non-invasive character, this

technique is commonly used in anaesthetics. Together these benefits advocate the deployment of this

technique in clinical practice, but unfortunately there are, next to the low penetration depth by using high

frequencies for resolution, a few more problems by imaging peripheral nerves with ultrasound [13].

First, it may be difficult to visualize nerves when they are surrounded by fat, since the echogenic properties of

both nerves and fat are almost similar. The fact that the plexus sacralis is embedded in fat possibly impedes

imaging the plexus via ultrasound [13].

Second, nerves that lie behind or beneath bones may become invisible because of an acoustic shadow

produced by bone. Therefore, the presence of the sacrum has to be considered. A correct positioning of the

probe is needed. This is also required given the possibility that the ultrasound beam does not hit the nerve

perpendicularly, implying that the nerve may falsely be interpreted as being hypoechoic. This artifact is called

anisotropy. In order to create the most optimal signal, constant steering of the probe is of vital importance

[13].

Another disadvantage hat should be taken into account when imaging nerves with ultrasound, is the relatively

small field of view. Furthermore, skin pressure caused by the probe in an attempt to image more deeply, could

lead to artificial deformation and thus artifacts [13].

Despite of these disadvantages, satisfactory results were reached by imaging the complete plexus brachialis

with high frequency linear transducers, ranging from 10 to 13 MHZ [15, 16]. For most patients, a complete

image of the plexus brachialis was possible, in which the a. subclavia and the a. cervicalis profunda were used

as landmarks for this mapping. However, it was not possible to depict the eighth cervical nerve root and the

first thoracic nerve root of the plexus brachialis because of their deep location. Given that the nearby apical

pleural surface was situated only 2,19 cm deep and most sacral structures lie deeper, this high resolution

technique is not useful for the plexus sacralis, due to the small penetration depth.

SUB-CONCLUSION In conclusion, according to the literature, imaging the plexus sacralis with US is currently impossible, although,

it would be great to deploy US for the purpose of imaging the plexus sacralis, considering the multiple benefits

described in this paragraph. Unfortunately, the current state of technology does not yet enable adequate

imaging of plexus sacralis yet, mainly because of the need for a high penetration depth in combination with the

required resolution.

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PROJECTIONAL RADIOGRAPHY AND COMPUTED TOMOGRAPHY

Projectional radiography (also called X-ray radiography) is a diagnostic imaging technique that relies on the

attenuation of X-rays. Because projectional radiography is widely used for medical diagnostics, an evaluation

for its possible role in imaging the plexus sacralis was made.

X-ray radiation exits the tube through what is known as the primary beam. Denser anatomy has a higher rate

of attenuation than anatomy with fewer density, so bone will absorb more x-rays compared to soft tissue.

What remains of the primary beam after attenuation is known as the remnant beam. The remnant beam is

responsible for exposing the image receptor. The highly attenuated beams that passed through denser material

will light up at the image [12, 17, 18].

The attenuation will be visible on the image if density differences are present. The bigger the difference, e.g.

between bone and air, the bigger the contrast displayed by the image. Subtle density differences between soft

tissues will result in little contrast. X-ray radiography cannot reveal detailed microstructure of nerves because

of the similar density to its surrounding and small structure. Therefore, nerves of the plexus sacralis are not

visible on a X-ray, due to limited spatial resolution and poor contrast [12, 17, 18].

Computed tomography (CT) is a projectional radiography technique that provides two- or three-dimensional

information of the body by the use of tomographic reconstructions. However, because of the fact that CT uses

X-rays and X-rays cannot discriminate soft tissues, CT initially seems not suitable for imaging the plexus sacralis.

The literature on this topic confirms this hypothesis. Two articles about imaging nerves with CT were published,

that described the imaging of nerves in the head by depicting the n. opticus by Becker et al. [19] and the n.

facialis by Burmeister et al. [20]. Both studies concluded that the nerves cannot be identified at a regular CT

scan. The CT scan can just be applied to detect abnormalities in dense tissues, like bone fractures. Visualization

of the nerves is difficult because direct demonstration of nerves does not show a big contrast compared to the

rest of the soft tissues, like X-ray. In the pelvis, CT is used as a guidance for nerve blocks [21, 22]. Again, the

authors concluded here that the nerves are hard to be identified at a CT scan. They used the surrounding

tissues, like vessels, muscles and bone, to determine the expected location of the nerves. To enable

identification of the plexus sacralis components on axial CT sections, the radiologist has to know the location of

the nerve and the relationships of this structure to vascular, muscular and osseous structures that can be more

easily demonstrated [23, 24]. For this reason, CT can impossible be deployed to image the plexus sacralis.

Contrast agents are used in clinical practice to obtain a CT scan with enhanced contrast due to the increase in

distinction of different tissues. However, there is no appropriate contrast agent for CT to generate a clearer

image of the nerves, so contrast cannot be used to obtain a better depiction of the plexus sacralis.

Recent developments in CT scanners enable an improved soft tissue discrimination such as the recently

developed Dual Energy CT (DECT). With this technique, that makes use of a double energy source, a better soft

tissue discrimination is possible, but the most useful application lies in the bony regions with high attenuation

differences and in the differentiation of contrast iodine. However, since the softer tissues are mostly composed

of hydrogen-, carbon-, nitrogen- and oxygenatoms, which show very similar X-ray attenuation behaviour at

different photon energies, differentiation remains a rather ambitious objective at this moment. A disadvantage

is the use of a double energy source that will double the radiation dose [25]. It could be possible that, when the

soft tissue discrimination will be improved in the future, CT scanner can be used for imaging nerves. However,

at this moment it is not possible to image nerves with CT.

SUB-CONCLUSION Although X-ray radiography and CT, are fast and widely available techniques that is little stressful for the

patient, it provides no information about the plexus sacralis. The densities of the soft tissues are too close apart

to generate an image with adequate contrast and because of that, the plexus sacralis cannot be visualized.

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ELECTROPHYSIOLOGY

Electrophysiology is the study of the electrical properties of biological cells and tissues, based on the

phenomenon of bio-electricity. Bio-electricity originates from biochemical reactions which can generate an

electric potential difference between the inside and outside of a cell, alongside a cell membrane.

Communication between neurons and activation of muscle fibres is based on this phenomenon [12]. Electric

potential differences or electrical signals can be measured in nerves or muscles for diagnoses.

Deviations of normal signals can be measured and analysed to diagnose pathology or organ dysfunction. These

deviations can be measured non-invasively at the skin surface, during which the potential difference between

different points is measured. Requirements for this type of measurement are a relative big potential and a

strong noise suppression from the environment. A relative big potential difference is found in the

electrocardiogram (ECG) and a strong noise suppression is provided by an electro-encephalogram (EEG).

Another way of measuring potential differences is invasively, as can be done in an electromyogram (EMG),

where the signal of the muscles are measured by needle sensors. Electrophysiology can also be used in

treatment: muscles or nerves can be stimulated by small electric currents [12].

Although the aforementioned techniques are useful and broadly applied, it is questionable whether they can

be deployed as an imaging technique for imaging the plexus sacralis. The word electrophysiology itself includes

the difficulty of using it as an imaging technique; electrophysiology is about investigating the physiology (and

pathology) of a specific neuron, nerve or muscle and not about investigating the anatomy and precise location

of a neuron. Although it is possible to determine the global location of a signal, as EEG can depict from which

lobe the signal origins, it is not possible to determine the exact anatomy, location and structure of nerve tissue.

In addition, even if it would be possible to determine the anatomy by such signals, it is only possible when

receiving clear signals. The small peripheral nerves of the deeper plexi are surrounded by electrical active

tissues as muscles and organs, which lead to noise ratios that impede the measurement of the small neuron

signals from the skin surface [26].

Another hypothesis of the implementation of electrophysiology could be the use concentration differences of

[Na] and [Ka], arisen from action potentials. Then, it could be possible to visualize nerves by stimulating those

nerves one wants to depict. Studies of the physiology of nerves bring this hypothesis in doubt, because a single

action potential is responsible for just a concentration difference of 1/100000 ions and is compensated by the

Na/Ka pump. Other mechanisms have far more influence at the concentrations [27]. These reasons suggest

that electrophysiology is not useful as an imaging technique for imaging the nerves of the plexus sacralis.

SUB-CONCLUSION The only way to implement electrophysiology for imaging the plexus sacralis is to measure the muscle activity

that innervates these nerves. This can be realized by EMG, although this provides information about a possible

pathology (about the innervations) of the muscle and not about the plexus’ anatomy.

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MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) is well-known for the great contrast it depicts between the different soft

tissues of the body, like muscles, fat and possibly neurons. Therefore it could be an adequate technique for

imaging the plexus sacralis. Because MRI is a complicated technique and offers a lot of possibilities in imaging

soft tissue, this technique is explained in more detail.

MRI is based on the spinning of atoms. Especially hydrogen atoms are used, because of the high abundancy in

the human body, like nerves, and because its solitary proton gives a high magnetic moment. The nucleus itself

spins around its own axis in atoms which have an unequal pair of neutrons and protons. It is said that this

nucleus has a net spin or angular momentum, and is named MR active nuclei. These nuclei have a tendency to

align their axis of rotation to an applied external magnetic field (B0). MR active nuclei that have a net charge

and are spinning, acquire a magnetic moment and can align along an external magnetic field, parallel of anti-

parallel. The stronger the magnetic field, the more protons align with the field. The magnetic effect of all the

nuclei together is the net magnetization vector (NMV).

Each hydrogen nucleus is spinning around its own axis, but the influence of the external magnetic field (B0)

produces an additional spin. This is called precession. This secondary spin follows a circular path around B0, the

precessional path. The speed at which they make a full circle around B0 is called the precessional frequency,

which can be calculated by applying the Larmor equation: ω0 = B0 * λ.

ω0 = precessional frequency

B0 = the magnetic field strength

λ = gyro-magnetic ratio, which is a constant that expresses the relationship between the magnetic

moment and the angular momentum. It is expressed as the precessional frequency of a active nucleus

at 1 Tesla (T).

An image can be obtained by application of a radiofrequency (RF) pulse, which is called excitation. A pulse of

energy at exactly the Larmor frequency of hydrogen will cause resonance of hydrogen. The nuclei obtain

energy by resonance and become high-energy nuclei, which are called spin-down nuclei and align anti-parallel

to the magnetic field. Because of resonance of hydrogen the NMV moves out of alignment away from B0, with a

specific angle, the flip angle. Depending on the amplitude and duration of the RF pulse, the magnitude of the

flip angle can vary. The angle is usually 90°. The second important result of the RF pulse is that the magnetic

moments of hydrogen nuclei move into phase with each other.

The moment that the RF pulse is switched off, the nuclei want to align the magnetic field B0 and lose energy,

which is called relaxation. When the nuclei lose energy they send electromagnetic waves with a wavelength the

same as the Larmor frequency. A coil receives these waves and a voltage is induced in the coil. These voltages

can be evaluated and then an image can be created [12, 28, 29].

After the excitation pulse the NMV will have two different kind of relaxations: the relaxation in the Z-

component of magnetization and the precession relaxation (phase difference) in the XY-component. In the

longitudinal plane the amount of magnetization gradually increases, this is called recovery. In the transverse

plane the amount of magnetizations gradually decreases, this is called decay. The time in which 63% of the

protons have recovered the Z-component magnetization is called the spin-lattice relaxation time (T1). The time

in which 37% of the protons have decayed the XY- or phase magnetization is called spin-spin relaxation time

(T2) [29, 30]. Every tissue in the human body does have its own T1 and T2, depending on their quantity of

hydrogen atoms. This difference between tissues can be seen in Figure 7. Because water has a different proton

density than fat, this will result in different signals intensities in time.

The most important parameters for determining contrast in a MR image are the Repetition Time (TR) and the

Echo Time (TE). The TR is the time between two excitations (thus between two 90° RF pulses) and the TE is the

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time between the 90° RF pulse and MR signal sampling, corresponding to maximum of echo. These two

parameters are used to generate the different contrasts in the MR-image, because different tissues react

differently when these parameters are changed. This is a consequence of the variations in T1 and T2.

FIGURE 7 - EXAMPLES OF RELAXATION TIMES OF TWO TISSUES. A) T1 RELAXATION TIMES, B) T2 RELAXATION TIMES [31]

ADVANTAGES AND DISADVANTAGES MRI is a technique for imaging soft tissues. It provides information that differs from other imaging modalities: it

can discriminate among tissues using physical and biochemical properties. This is a major advantage of MRI:

the majority of imaging techniques like CT and X-ray cannot discriminate among tissues like MRI and cannot

image soft tissue as well as MRI can. Furthermore, MRI produces images with high levels of resolution in

multiple planes. It is a widely used technique for different pathologies like strokes and tumours. Another major

advantage is that MRI does not use ionizing radiation.

Possible disadvantages of the MRI include that the small magnet bore possibly causes claustrophobia among

patients, its long scan time during which patient cannot move to avoid movement artifacts, there is a small

change of tissue heating or induction in the body and patients with pacemakers and certain ferromagnetic

appliances cannot be studied. Another problem is the difficulty of the interpretation of data, due to similarities

in properties of tissues, artifacts and contrast. Finally, the technique is relatively expensive.

IMAGING THE PLEXUS SACRALIS In MRI, there are different sequences or techniques for imaging the nerves and the various plexi. Most of the

available articles on this topic discuss the MR imaging of the plexus brachialis. Despite some differences such as

the distance between the nerves of the plexus and the skin, it is likely that these methods can be applied for

imaging the plexus sacralis, possibly with some parameter adjustments [32]. Examples of studies in which the

depiction of the plexus brachialis is well managed are the studies of Zhang et al. [33] and Viallon et al. [34].

Zhang depicted the plexus brachialis with segmented echo planar MRI with inversion recovery magnetization

preparation (seg-IR-EPI), whereas Viallon used 3D short-tau inversion recovery (STIR). In addition, another

method for MR imaging the plexi is imaging with the use of T1/T2 MR [8], whether or not combined with STIR

MR [32]. One of the sequences that might provide perspective for this study is diffusion-weighted (DW) MR.

Studies by Takahara et al. [35] and Zhang et al. [36] confirmed this.

SUB-CONCLUSION

MRI is a great technique for imaging soft tissue, because of the great visual discrimination this technique

enables. A lot of measurement techniques and sequences to image nerves have been described and some of

them seem very promising.

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MAIN CONCLUSION IMAGING TECHNIQUES

In this section the anatomy of the plexus sacralis was described and it was stated which structures could be of

influence for imaging the anatomy of the plexus. Then several imaging techniques where described with

respect to their possibilities in imaging the anatomy of the plexus sacralis.

US has proven to be useful in the imaging of peripheral nerves, such as the plexus brachialis. On the other

hand, imaging the plexus sacralis with US is currently impossible. This is mainly because of the need for a high

penetration depth.

X-ray radiography is a fast, cheap and widely available technique that is little stressful for the patient, but it

provides no information about the plexus sacralis. The densities of the soft tissues are too close apart to

generate an image with adequate contrast. Analogous to the argumentation of X-ray radiography, CT in its

current state is also not suitable for imaging the plexus sacralis.

As for electrophysiology, the only way to implement this technique to aid in the imaging the plexus sacralis is to

measure the muscle activity of the muscles which are innervated by the nerves. This can be realized by EMG,

although this only provides information about a possible pathology (of the innervations) of the muscle and not

about the plexus’ anatomy.

Unlike the aforementioned imaging techniques, MRI is a great technique for imaging soft tissue, because of the

great visual discrimination that this technique enables and the high resolution.

Considering all the advantages and disadvantages of the various imaging techniques, MRI seems the most

suitable technique for imaging the plexus sacralis. The most important reason is the excellent soft tissue

contrast one can achieve with MRI.

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ANATOMY & MRI SEQUENCES

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INTRODUCTION

In the previous section, the most important imaging techniques were discussed with respect to imaging the

plexus sacralis. Based on the results, MRI emerged to be the best available technique for imaging the plexus

sacralis, given its high spatial resolution and the clear soft-tissue discrimination.

In this section the MR imaging technique will be discussed into more detail. Before the MRI will be discussed,

relevant anatomical comparisons will be made. First, the differences between the plexus brachialis and plexus

sacralis will be described, because the large quantity of research literature about MR imaging of the plexus

brachialis compared to the plexus sacralis. Results and recommendations in this literature could be of use for

imaging the plexus sacralis, if both plexi are sufficient compatible. Also, the differences of MR imaging in

children and adults will be discussed, because this Thesis is primarily directed to imaging the plexus sacralis

among children.

Second, different sequences will be presented. For each of these sequences a small summary is given of the

relevant physics in relation to the depicting of the plexus sacralis and their suitability to image the plexus

sacralis will be determined. As stated in the previous section, a suitable imaging technique is defined as a

technique that can image the plexus sacralis and his branches with a resolution and signal to noise ratio that

allows to follow the nerves. The subdivisions of these sequences will be organized in relation to their physical

properties, see Figure 8. As a note, not all existing subdivisions are described, but only those on what relevant

literature could be found.

Spin Echo

Standard Spin

Echo

Inversion

Recovery

FLAIR

STIR

Gradient Echo

Coherent (Steady

State) Gradient

Echo

SSFP

Spin Echo Gradient EchoT1

Special imaging

DW, DTI

Magic Angle

Contrast Agents

T2 T1/T2*

Fast Spin Echo

Balanced GE

(3D CISS)

SPIR

Incoherent

(Spoiled) Gradient

Echo

FIGURE 8 – MRI SEQUENCES AND SUBDIVISIONS

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The central theme in this section are the sequences. There are three main physical classes of sequences: the

first two are Spin Echo sequences and Gradient Echo sequences, see Figure 8. These can be subdivided in

different sequences that are alternated to provide extra information about a specific tissue or to suppress a

certain tissue. The current divisions are usually used in combination with a certain type of weighting, which will

be discussed in more detail in the general parameters section. On top of the figure, the third class, is special

imaging

As seen in Figure 8, Spin Echo sequences are used in general for producing T2-weighted images, Gradient Echo

sequences for a T1/T2*-weighted images and Inversion Recovery for T1-weighted images. These differences

will be explained in the corresponding sections.

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ANATOMICAL COMPARISONS

A COMPARISON OF THE PLEXUS SACRALIS AND PLEXUS BRACHIALIS For a complete integral advice about imaging the plexus sacralis, an evaluation and comparison of the plexus

sacralis with the plexus brachialis cannot be absent. Not only because of size and structure, but also in

perspective to the quantity of research and literature, because there is more known about imaging the plexus

brachialis than the plexus sacralis.

The plexus brachialis is the plexus serving the shoulders, arms and hands, ascending from C5-T1, trough the

shoulder, resulting in the n. medialis, n. radialis and n. ulnaris. The plexus brachialis has been the topic of a lot

of imaging research. The main reason for this is the relative superficial location and the high mobility of the

area, which makes it vulnerable for injuries. These literature and consequential imaging recommendations

could be of use for imaging the plexus sacralis [1, 32].

To give a complete overview of the differences between the plexus sacralis and plexus brachialis, a comparison

can be made for the histological nerve properties and the anatomy of the surrounding. In Figure 9 and 10 the

plexus sacralis and brachialis can be seen respectively.

Both plexi consist of peripheral nerves and are constructed by an epineurium, perineurium and endoneurium,

in which nerve fascicles are embedded, as described at page 8. Both plexi also descend from the spinal nerve,

innervate muscles (of organs) more peripheral and have a comparable image size, imaged with a field of view

in the range of 24 to 26 cm [37].

Differences in organization are distinguished at a more detailed level. First, the plexus sacralis is partly

interwoven with another plexus, the plexus lumbalis and has a broader (potential) range of roots, L4-S5 versus

C5-T1. Second, the plexus brachialis innervates solely skeletal muscles, while the plexus sacralis also innervates

smooth muscle and organs. Last, the plexus brachialis has a clear posterior and anterior part which is not that

clear distinguishable in the plexus sacralis.

FIGURE 9 - THE PLEXUS SACRALIS [3]

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FIGURE 10 - THE PLEXUS BRACHIALIS [3]

The most obvious differences in anatomy which influence imaging, is the depth of the plexus. The plexus

brachialis in very superficial situated, just posterior of the clavicula, m. pectoralis major and m. deltoideus. The

plexus sacralis is located deeper, surrounded by more muscle and bone. This makes it impossible to image the

plexus sacralis, unlike the plexus brachialis, with ultrasonography.

The main other differences influencing imaging both plexi are the different movement artifacts at both

locations. Imaging the plexus brachialis is subjected to movement artifacts of the respiratory system, heart and

aorta, while imaging the plexus sacralis can be influenced mainly by movement artifact due to the intestine.

Images of both plexi are also affected by signal intensities from flowing blood, although this can be decreased

by spatial RF pulses are placed superior and inferior to the imaging volume [32]. The plexus brachialis, as well

as the plexus sacralis, face susceptibility artifacts due to their environmental anatomy [37]. Especially air,

located in the sigmoid and rectum closely to the plexus sacralis and in the lungs closely to the plexus brachialis

can create susceptibility artifacts.

MR-NEUROGRAPHY OF THE PLEXUS SACRALIS IN CHILDREN AND ADULTS MRI is an important diagnosticum in medicine for children, because it is, unlike CT, without radiation exposure

[38]. The MRI technique requires patients to lie still, to avoid movement artifacts on the images. Some young

children have to lie still for up to 60 minutes – the scan time relies to the parameter settings – to perform the

study successfully. Adults often follow instructions better and quicker. In addition, holding breath can be a

problem by imaging children, because they are unable to hold their breath satisfactorily until they are about 8

years of age. However, because holding breath is not necessary for imaging the plexus sacralis, you do not have

to take this problem into account [39].

The confined space and the noise sometimes distress the children and they may require general anaesthesia

[40]. Sedation or anaesthesia involves some risk, requires specialised staff and anaesthetic and monitoring

equipment what will lead to higher costs [39]. Besides this, another difference in the anatomy between

children and adults is that children contain less fat, which you have to take in mind when analysing a T1 or T2

image.

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In addition, for imaging the plexus sacralis you also have to keep in mind that children are smaller than adults

and that their normal structures and organs are smaller [39]. In adults, the diameter of the n. pudendus is

about 3 mm. In children, this diameter is a little smaller, but does not differ that much [7]. When you want to

depict children’s plexus sacralis, you probably need a higher resolution. For this reason, the slice thickness and

the field of view in children are smaller and it seems better to make a MRI scan with a higher field strength. The

benefit of using a MRI scanner with a high field strength is the increased SNR, the acquisition of thinner slices

and the improved spatial and temporal detail of the structures. However, at higher field strengths, you have to

deal with more susceptibility artifacts and a smaller slice thickness gives a lower SNR [39].

The histology of the nerves is the same in adults and children. The myelinisation of the white matter tracts

develop rapidly after birth [39].

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GENERAL PARAMETERS

Different parameters are responsible for the generation of contrast when imaging the plexus sacralis with MR.

For example, different magnetic field intensities give rise to different spatial resolutions. In this section we will

discuss the main parameters that cause important differences within the scope of anatomical imaging of the

plexus sacralis.

RELAXATION TIMES OF NERVES AND THE USE OF CONTRAST AGENTS The most important parameter that generates contrast between different tissues in MR images concerns the

weighing of the different relaxation times. As described in the section about MRI, see page 17-18, every tissue

in the human body can be characterized by its own T1 and T2 relaxation times, depending on their quantity of

hydrogen atoms. Depending on when the echo signal or the acquisition takes place, the image is T1- or T2-

weighted.

The following rule of thumb holds for MR imaging: T1 is used for the purpose of anatomical imaging (such as

fascicular structures in the median nerve [41]) and T2 is used for pathological imaging purposes [42]. A T2

image depicts a bright appearance of water and edema is usually present at a pathological site. Thus, for

imaging the anatomical variations of the plexus sacralis it would straightforward to suggest T1-weighting as the

most adequate technique. However, things are a bit more complicated.

In order to acquire an optimal image of the plexus sacralis and its environment, the different relaxation times

of nerves, fat and muscle are highly important. For example: in a 1 T field, fat has a T1 of 180 ms and a T2 of 90

ms. Muscles have a T1 of 600 ms and a T2 40ms [43]. Because of this, fat will have more signal in the same time

and therefore will be depicted brighter than muscle in a T1-weighted image. Normal peripheral nerves appear

isointense in the image, compared to muscle tissue, but reveal a fascicular pattern and are frequently

surrounded by a small rim of fat tissue [44]. The isointensity implies the difficulty to show a nerve in the plexus

sacralis, as it is surrounded by the m. psoas and the m. piriformis. Only with a very high resolution you can

distinguish the variable but small (a few millimeters) fatty layer around the nerve, the nerve itself and the

adjacent muscles.

However, as described in the histology section, see page 8, the structure of a nerve is more complex than

portrayed above. Nerves are a mixture of different tissues, including protein-laden axoplasmic water, myelin,

fatty interfascicular epineurium and connective tissues. Because of this mixture, a fat suppressed T2-weighted

image also provides interesting features for imaging the plexus sacralis. Several pieces of evidence suggest that

the low-protein endoneurial fluid is what is seen most prominently in T2 neurography images [45]. Fat

suppression enables to suppress much of the fat signal around nerves and from within nerves. With an

appropriate echo time, a T2 weighting can be achieved that results in the suppression of muscle signal, leaving

most of the signal from the endoneurial fluid intact. The use of fat suppressed T2 weighing in combination with

the suppressed bright fluid signals from flowing blood will eventually depict the plexus sacralis.

This complex histological structure of nerves makes it difficult to determine T1 and T2 values of nerves in

general. As stated above, structural parts of nerves such as the endoneurial fluid or the fatty rim, could be tried

to highlight out, although there is a lot of variation in these and it becomes more difficult in smaller nerves. The

n. medianus is the only nerve of the human body of which the T2 relaxation time is known, which is about 50

ms. The T1 relaxation time is unknown [41]. Nerves in general, especially the smaller ones, have overlapping

relaxation times with muscle [43] and thus, as Stoll et al. describes [44], appears isointense to muscle tissues.

Another structure which is often difficult to distinguish from small nerves are small blood vessels. Both may

appear hyperintense on T2-weighted sequences. However these structures can be discriminated with a blood

contrast agent.

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The use of contrast agents in MRI could be of use in specifying diagnoses and depict structures. In neurography,

especially gadofluorine and iron oxide particles (SPIO) are commonly used [46-48].

As Stoll et al. stated, superparamagnetic iron oxide (SPIO) particles and gadofluorine are used for the imaging

of neuropathies because of respectively accumulating at degeneration sites of acute focal demyelination and

the phagocytise of the SPIO particles by macrophages, resulting in an accumulation at the nerve inflammation.

These processes result in signal loss on T2 weighted images [49, 50]. However, because our study focuses on

children with potential anatomical variations of the plexus sacralis, these types of contrast media are not

appropriate, because they diagnose neuropathies and do not adhere to normal nerves.

The only potential use of contrast agents in imaging the plexus sacralis could be in MRI sequences in which no

discrimination between small nerves and blood vessels can be made, such as in Spin Echo T2 images. SPIO, in

this respect also know as black blood contrast, could be used for coloring the blood vessels.

SNR, ULTRA HIGH FIELDS AND RESOLUTION A particular point of interest in every MR sequence when imaging nerves and plexi is the Signal to Noise Ratio

(SNR). In order to obtain a high-quality image of the plexus sacralis, the ratio of the truly desired signal from

the target tissue and the random supplementary signals ('background noise'), must preferably be as high as

possible.

The main source of noise in a MR image is the patient’s body, due to radiofrequent emission from thermal

motion. When imaging the plexus sacralis, a high-quality image of the nerves in the pelvis is desired, whereas

depicting surrounding adjacent structures is considered less important. Because of this, and to obtain a high

SNR ratio, coils with a small local coil volume are preferred. With the smaller Field of View (FOV) where

anatomy exists outside of FOV, it must be taken in consideration that artifacts of wrap-around can occur. The

smaller the sensitive volume of a coil, the lower the noise from the adjacent structures from and around the

selected slice plane will be. This will result in a better SNR. An additional way to improve the SNR is by using

phased array coils [5]. With the use of more than one antenna to receive the desired signals, random noise

signal can be better filtered out. For the plexus sacralis for example, one or more abdominal/pelvic coils in

combination with spinal coils could be used [51]. Moreover, a thoracic wrap-around coil is advised by Moore et

al. If a larger FOV is required, in case of imaging the plexus sacralis together with the sciatic nerve [52].

Another source of noise is the MRI scanner itself, for example as a consequence of electronics, coils and field

inhomogeneities. The use of high magnetic fields enables noise reduction produced by the body and the MRI

scanner. By using a higher magnetic field, the number of spins in parallel state in the body increases and by this

more signal is generated, increasing the SNR (following the Boltzmann distribution) [30]. Higher magnetic fields

also allow better resolutions, because more signal per measured unit is obtained.

When imaging the small nerves of the plexus sacralis, a relative small FOV and a high spatial resolution is

required to depict the details, resulting in a low voxel size. However, this need is unfavorable for a high SNR as

the number of excited spins is proportional to the voxel size and thus, signal intensity. This can be partly

reduced by increasing the number of excitations, given the fact that noise will change throughout the

excitations and the signal will remain mostly identical during all measurements. When the random noise is

substracted, the SNR is increased [53-55]. The major drawback of this technique concerns a prolonged scanning

time due to more measurements.

Although the higher resolution and the higher SNR due to higher magnetic fields are favorable in imaging the

plexus sacralis, the use of ultrahigh fields has a major weakness. One of the main artifacts that becomes more

important in high fields are the local differences in magnetic susceptibility. For instance, the air in the pelvis’

intestine has a significant higher magnetic susceptibility difference in comparison to most other tissues. This

magnetic susceptibility differences influences the main (static) magnetic field, resulting in disturbances in the

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received signal. In a MRI scan of the plexus sacralis, these disturbances are more important than in a complete

body scan. Because of that, the air in the bladder and intestine are a risk factor for this artifact. It is important

to reduce the amount of air and other possible magnetic susceptible materials around the plexus sacralis in the

FOV, for example by decreasing the FOV [56].

SUB-CONCLUSION Based on the aforementioned information, it can be derived that a T1-weighted or fat-suppressed T2-weighted

images could be used for imaging the plexus sacralis. Contrast agents are not useful in imaging the anatomy of

the plexus sacralis, because it is currently not possible to adhere these agents to healthy nerves. The only

potential use of contrast agents is in sequences in which discrimination of blood vessels and nerves forms an

imaging problem. The SNR for the plexus sacralis is a compromise between resolution, scanning time and

limitations in (present) scanning materials. Within the scope of the plexus sacralis, it can be advised to use

multiple local phased array coils, a high magnetic field with a small voxel size necessary to depict the smallest

nerves and a number of excitations that does not lengthen the scan time too much. With these higher fields

and a smaller FOV it must be taken in account that susceptibility artifacts can occur.

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SPIN ECHO SEQUENCES

The most classical type of MRI sequences, and one of the three main classes, see Figure 8, is the Spin Echo (SE)

sequence. As stated in Figure 8, Spin Echo can be subdivided in standard, fast and inversion recovery

sequences, but only the first two are described in this paragraph as inversion recovery has its own paragraph,

see page 31. When imaging children’s plexus sacralis, Spin Echo is the most frequently used sequence in

protocols. This most commonly used pulse sequence of MR imaging is based on the detection of a spin echo. It

uses 90° radio frequency (RF) pulses to excite the magnetization and one or more 180° pulses to refocus the

spins to generate signal echoes named spin echoes [28].

As in the other two classes of MRI sequences, see Figure 8, SE sequences have specific Repetition Times and

Echo Times that are used to generate the different contrasts in the MR-image. With the imaging focus on

different tissues due to variations in T1 and T2, these distinctive weighting values are listed in Table 3:

TABLE 3 - SPIN ECHO PARAMETERS

Sequence TE (ms) TR (ms)

T1 short TE (10-20 ms) short TR (300-600 ms)

Proton Density short TE (20 ms) long TR

T2 long TE (greater than 60 ms) long TR (greater than 1600 ms)

STANDARD SE AND FAST SE IN RELATION TO THE PLEXUS SACRALIS Standard SE sequences are generally used to generate T1- weighted images as can be seen in Figure 8. T2-

weighted images have a longer TR and consequently demand a long scan-time in a normal SE sequence. The

T1-weighted images display regional anatomy, including the various muscles, blood vessels, and nerves

outlined by a fat shell, sometimes also visible around the nerves of the plexus sacralis [37, 52]. The SE T1-

images have a high SNR and are the golden standard for most imaging [28]. A major disadvantage of a standard

SE-sequence is the relatively long scan time. Another drawback concerns the difficulty of discriminating muscle,

vessels and nerves, because of overlapping T1/T2 values. With respect to the plexus sacralis, this technique can

thus be used [32], but the possibility for motion artifacts, because of the long scan time and the difficulties in

discriminating structures must be considered and are major disadvantages.

A Fast or Turbo Spin Echo (FSE or TSE) is, as the name suggests, a fast SE sequence. With the use of multiple

echoes with different phase encodings during one TR (called an echo train), this sequence makes it possible to

scan faster. For example, if 9 echoes per TR are being used, this implies a scan time of nine times faster. FSE

sequences are normally used to generate T2-weighted images, because of T2-weighted sequences have a

longer TR and TE and it thus have longer scan time in standard SE sequences. There are two contrast-related

differences between SE and FSE which are due to the repeating 180⁰. First, fat remains bright due to changes in

spin-spin interactions when multiple RF pulses are used. Second, muscle remains dark, because of a similar

effect. In addition to the faster scanning time, another advantage is that FSE is less sensitive for susceptibility

artifacts, although these artifacts occur less in the pelvic area in contrast to the thorax. Therefore, the plexus

sacralis should be imaged without these artifacts [28, 32]. Besides this preferable properties of FSE, it has to be

regarded that the amplitude of echoes results in long echotrains and the last echoes contain less signal.

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SUB-CONCLUSION

SE sequences and FSE sequences are usually implemented in magnetic resonance neurography protocols. A SE

T1-weighted sequence can be used to depict normal anatomy, because of its fat-enlightening properties. A FSE

sequence can be used to provide T2-weighted images, possibly with fat suppression, to depict endoneurial fluid

in nerves. FSE sequences provide a reduced scanning time in comparison to SE sequences and that is why using

FSE sequences is preferred. A big disadvantage of these classical sequences is the difficulty of discriminating

tissues with overlapping imaging properties, like nerves and muscles, which impedes the ease of distinguishing

and interpreting different structures. In conclusion, nerves can be visualized with SE and FSE sequences,

although not very clearly.

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INVERSION RECOVERY MRI

As described before, the anatomy of nerves can be observed on T1-weighted images thanks to their fatty

surrounding. Because of that, it is preferable to produce images with the best possible T1 contrast. The

inversion recovery sequence, part of the spin echo class, see figure 8, provides these images with better T1

contrast, in comparison to ‘normal’ spin echo T1 images, and nerves may become better observable [28, 30].

However, a disadvantage is the longer scan time compared to the other Spin Echo sequences, what increases

the risk at moving artifacts. That is why the majority of existing systems now use inversion recovery fast spin

echo, what reduces the scan time [28]. Two main sequences of inversion recovery MRI were identified in the

literature on which will be elaborated on below.

SHORT TAU INVERSION RECOVERY (STIR)

Short tau inversion recovery (STIR), also called short T1 inversion recovery, is a sequence which leads to fat

suppression on T2-weighted images. This technique could be useful for imaging the plexus sacralis, because the

plexus is embedded in fat which causes a high signal. The contrast will be optimized between the nerves and

the fat around the plexus, because the nerves only contain little fat so their signal remains mostly

unsuppressed [52, 57, 58]. The fat suppression, also called fat saturation, is dependent of the selected TI, which

corresponds to the time which takes fat to recover from full inversion to the transverse plane. A consequence

is that there is no longitudinal magnetization corresponding to fat and this will lead to the suppression of fat

[28]. The largest advantage of using STIR to image the plexus sacralis is the uniform fat suppression and the fact

that this technique has proven to be very reliable, even when applied to difficult areas of the body with

excellent T2 contrast, like cerebrospinal fluid (pathologies) of the spinal cord. In addition, STIR has a strong

insensitivity to B0 inhomogeneities. This is a big advantage, because for the purpose of imaging the plexus

sacralis, a relatively high field of view of about 24-26 cm is required, which includes a bigger range of magnetic

field inhomogeneities [37, 59, 60].

FLUID ATTENUATED INVERSION RECOVERY (FLAIR) Fluid Attenuated Inversion Recovery (FLAIR) is featured here because it is closely related to STIR and therefore

could as well be suitable for imaging the plexus sacralis. However, no studies about imaging peripheral nerves

or the plexus sacralis with FLAIR MR are published yet, to our knowledge.

FLAIR MR imaging is usually used to depict lesions of the spine and the brain [61]. The difference between STIR

and FLAIR, is that FLAIR can remove the effects of fluid from the resulting images by setting the inversion time

(long TI) to the zero crossing point of fluid, resulting in the signal being 'erased'. For this reason, it can

discriminate fluid and other anatomies clearly, providing improved contrast between lesions and normal

anatomical structures. This technique can be used when the structure to be depicted is embedded in fluid [61].

Because the plexus sacralis is not embedded in spinal fluid or other liquid, it is unlikely that FLAIR can be used

to depict the plexus sacralis.

SUB-CONCLUSION STIR seems to be suitable for imaging the plexus sacralis. When imaging the plexus a relatively high field of

view is required. STIR is insensitive for field inhomogeneities and provides a uniform fat suppression, which is

preferable because of the fatty surrounding of the plexus sacralis. STIR is preferred to be used above FLAIR,

because FLAIR is particularly suitable for imaging structures in a watery surrounding.

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GRADIENT ECHO SEQUENCES

Another type of MRI sequences concerns Gradient Echo. When imaging children’s’ plexus sacralis, one of the

anticipated problems could involve scan time. A relatively short scan time is the main advantage of the gradient

echo sequences.

The Gradient Echo (GE) sequences differ from the Spin Echo (SE) sequence because the flip angle (FA) usually is

below 90° and there is no 180° RF rephasing pulse. The consequence of a low-flip angle excitation is a faster

recovery of longitudinal magnetization that allows shorter TR and TE which decreases scan time. This could be

beneficial when scanning the plexus sacralis of children, because the image is less susceptible to motion

artifacts. The rephasing of the spins that creates the echo is, generated by reversing the direction of the spins

rather than flipping them over to the other side of the x-y plane, as occurs with the SE sequence. In general, GE

sequences are more sensitive to field inhomogeneities, but have a reduced crosstalk (the overlap of signal

between different slices) so that a small or no slice gap can be used. The reduced cross talk enables the

generation of a more detailed image or a smaller partial volume effect [28, 31, 62].

In GE sequences, altering the FA and the TE contributes to the weighting of the image, see Table 4. For the

purpose of imaging the plexus sacralis, T1-weighted images can provide anatomical information such as loss of

fascicular structure, deformation and loss of perineural fat rim, and can be used to show contrast enhancement

[63, 64].

TABLE 4 - GRADIENT ECHO PARAMETERS

Sequence TE (ms) FA (degrees) TR (ms)

T1 2~14(no T2*) 60~90 short (less than 50)

Proton Density 2~14 (no T2*) 30~60 (no T1) long (no T1) T2* 20~34 5~30 (no T1) some longer (about 100)

As GE techniques use just a single RF pulse and no 180° rephasing pulse, the relaxation due to fixed causes is

not reversed and the loss of signal results from T2* effects, constructed from pure T2 and static field

inhomogeneities. The signal obtained with GE sequences is thus rather T2*-weighted than T2-weighted, with as

only exception SSFP [28].

In GE, the reduction of the TR below the T2 and T1 relaxation times may result in a transverse magnetization

that will not have completely disappeared at the onset of the following repetition. Due to this effect, three

main classes of GE sequence can be distinguished, depending on how residual transverse magnetization is

managed: incoherent (spoiled) GE sequences, coherent (steady state) GE sequences and steady state free

precession GE sequences [28, 31, 62].

COHERENT GE SEQUENCES In the first class of GE sequences, the coherent GE sequences, residual transverse magnetization is conserved

by a process known as rewinding. The residual magnetization is in phase at the beginning of the next

repetition. This will contribute to the signal and the contrast, and as these images are T2* weighted, most of

the applications are in angiographic, myelographic or arthrograhic fields [28]. In general, these scans are very

fast. A type of coherent GE sequence is the balanced GE sequence, in which balanced and symmetrical

gradients in the three spatial directions are being applied, which null out the phase shift linked to rapid flows.

With these sequences, an image is obtained ultrafast (roughly one second per slice) with an adequate

liquid/tissue contrast and an excellent signal to noise ratio. A CISS (Constructive Interference Steady State)

sequence is a combination of two balanced acquisitions. This technique allows to obtain a high resolution T2*-

weighted 3D gradient echo [28, 65].

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The 3D CISS technique has been used to obtain high resolution images of the nerve roots in the plexus

brachialis [66]. These images mainly depend on the flow compensation of pulsatile cerebrospinal fluid (CSF)

and the contrast between the CSF and the nerve roots. This method depicts nerve roots that are compressed at

the level of the foramina very well [34, 51]. Although 3D CISS provide good quality images, the direct

environment of the plexus sacralis is mainly composed of muscle and fat and is not embedded in a flowing

fluid. Here, we conclude that balanced gradient echo sequences (such as TrueFisp or CISS) are not suitable for

imaging the total anatomy of the plexus sacralis.

INCOHERENT GE SEQUENCES In the second class of GE sequences, the incoherent GE sequences, residual transverse magnetization are

spoiled with the use of a dephasing gradient at the end of the sequence. Because only the transverse

magnetization from the previous excitation is used, T1 contrast dominates. In general, these images have an

adequate SNR and show anatomical detail in volume [28].

One of this type of sequences is the Spoiled Gradient Recalled sequence (SPGR). In imaging the n. facialis the

use of high-resolution, high signal-to-noise ratio (with 3 T MRI), thin-section contrast-enhanced 3D SPGR

sequences showed enhancement of the normal n. facialis along the whole course of the nerve [67]. As for the

plexus sacralis, the environment of the n. facialis is very different and it is difficult to compare this with the

pelvis.

Another incoherent GE sequence, is the Magnetization Prepared Rapid Gradient Echo (MP-RAGE). This

sequence was used in imaging the n. ischiadicus and the n. alveolaris inferior. Freund et al. concluded that with

MP-RAGE T1-weighted sequence, the n. ischiadicus was depicted reliably and objectively in great anatomical

detail over the whole length of the thigh. Freund et al. used a resolution of 1 mm in every direction, a sufficient

resolution to depict nerve roots and the small nerves of the plexus sacralis. They suggested that other anatomic

regions such as the plexus brachialis or the plexus lumbosacralis could also be depicted [64], although they

claim the depiction of nerve in a muscle could be more difficult. Deng et al. reported that when imaging the n.

alveolaris inferior, the 3D MP-RAGE sequence with or without contrast agent can clearly and directly show this

nerve, and can show the relationship between the nerve and local anatomical landmark [68].

STEADY STATE FREE PRECESSION (SSFP) In the third class of GE sequences, the Steady State Free Precession (SSFP) GE sequences, an almost true T2

weighting is achieved due to a longer possible TE. SSFP sequences are useful in the brain and joints and can be

used with both 2D and 3D volumetric acquisitions [28].

Tsang et al. reviewed two different GE sequences with respect to the course of the n. facialis in parotid tissue:

the Gradient Recalled Acquisition in Steady State sequence (GRASS), which is a incoherent GE sequence and the

Balanced Turbo Field Echo (BTFE), a SSFP sequence [69]. The GRASS sequence is similar to the SPGR sequence,

thus GRASS mostly contributes to T1 and has little T2* effects [70]. Their conclusion was that the n. facialis can

be consistently seen in normal volunteers on 1.5 and 3 T MRI systems. In clinical practice, BTFE may perform

better than GRASS on both 1.5 T and 3 T systems, due to its better identification rate of n. facialis and shorter

image acquisition time. The plexus sacralis on the other hand is not situated in parotid tissue and will possibly

demonstrate a different contrast with the environment.

SUB-CONCLUSION In conclusion, within the GE sequences, the BTFE and MP-RAGE seems to be the most promising, because these

sequences are capable of depicting different nerves in the body. Unfortunately, the studies about both

sequences were conducted in different environments than plexus sacralis depiction, with the n. ischiadicus

showing the most similarities with the plexus sacralis in respect to the surrounding structures. Studies about

Balanced GE sequences mostly demonstrate a flow-compensation and a great liquid/tissue contrast, which is

not the case with the plexus sacralis.

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DIFFUSION WEIGHTED MR IMAGING

Most MR sequences that are commonly used in clinical practice to image peripheral nerves, such as T1- and fat-

suppressed T2-weighted imaging, are capable to visualize nerves. However, they are not capable to clearly

visualize them and to track them over long trajectories. This is because of the close anatomic relationship

between these peripheral nerves and structures with almost similar signal intensities on a MR image, like blood

vessels. Consequently, interpretation of images is time-consuming and false-negative diagnoses are not

uncommon. Diffusion-weighted MR neurography (DW-MRN) was recently introduced. It overcomes the

aforementioned drawbacks inherent to conventional MR sequences. With this technique, peripheral nerves are

highlighted and can be visualized over long trajectories [71, 72].

Diffusion weighted imaging (DWI) is based on the brownian motion or random movement of water molecules

caused by their thermal energy. This motion can be restricted or limited in biological tissues by boundaries such

as membranes, vascular structures and nerves. The motion here is not truly random, implying that some

restrictions in diffusion are directional. This depends on the structure of tissues [73, 74]. A sequence can be

sensitized to diffusion motion by applying two gradients on either side of a 180° RF, see Figure 11, The first

pulse dephases the spins and the second rephases the spins, if no net movement occurs. Signal attenuation

occurs when net movement of spins or water molecules occurs between the gradient pulses, because

rephasing will be incomplete. The degree of attenuation depends on the magnitude of molecular translation

and diffusion weighting [73].

FIGURE 11 - STANDARD PULSED FIELD GRADIENT (PFG) WAVEFORM FOR DIFFUSION SENSITIZATION

Fast types of spins, such as SS-SE-EPI, are commonly used as a base for DW sequences, because other types of

motion such as flow need to be reduced in order to ensure that solely motion from diffusion is measured [28].

APPLICATIONS OF DW-MRI DW-MRI imaging offers a high sensitivity of acute ischaemic damage in the brain. This is the most commonly

application of DW-MRN in the brain. Next to the brain, DW imaging offers good sensitivity to detect cellular-

dense lesions in the body and may have several applications for the purpose of oncological imaging, like in the

evaluation of lymph nodes or malignant bone diseases [74]. DW imaging can also be used to differentiate

malignant from benign lesions and tumour from edema and infarction [28].

Besides for the detection of pathologies, DW-MRN can be used to visualize anatomical structures like

peripheral nerves and the plexi. Some research about depiction of the brachialis has been performed, like a

research by Takahara et al. and Adachi et al. [35, 71, 75]. Takahara et al. focused on the anatomy of the plexus

brachialis and concluded that an overview of the plexus brachialis can be provided with coronal MIP

presentation. Unlike Takahara, Adachi et al. concentrated on imaging neuropathies. He stated that DW-MRN is

able to detect pathological changes in swollen plexi. Further, DW-MRN is used in diagnosing neurogenic

tumours, nerve injuries and mechanical nerve compression in the plexus brachialis.

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The plexus (lumbo)sacralis was imaged with DW-MRN by Takahara et al. and Zhang et al.. Takahara et al.

imaged the plexus sacralis by using unidirectional motion probing gradients (MPGs) [35], see Figure 12. By

deploying this technique, structures of high signal intensity on fat-suppressed T2- and T1-weighted images

adjacent to the nerves such as veins, can be well suppressed.

FIGURE 12 - NORMAL PLEXUS LUMBOSACRALIS (A) DW-MR NEUROGRAPHY (B) SCHEMATIC DRAWING [74]

Takahara et al. also imaged the plexus brachialis by using a special post-processing technique, called SUSHI:

Subtraction of Unidirectionally encoded images for Suppression of Heavily Isotropic objects for selective

visualization of peripheral nerves. This allows better suppression of background structures [72]. Zhang et al.

used 3D DW-SSFP for imaging the plexus lumbosacralis [36], which is a high-resolution diffusion-weighted T2-

weighted method of steady-state gradient-echo imaging combined with fat suppression and flow-

compensation techniques. This study showed that 3D DW-SSFP clearly revealed detailed anatomy of the plexus

lumbosacralis and its branches.

In DW-MRN, peripheral nerves can be highlighted and visualized over long trajectories, by using diffusion-

weighted whole-body imaging with background body signal suppression (DWIBS). Most background body

signals (e.g., fat signals, vessels, muscles and most of the organs) can be suppressed. Then is it possible to

follow nerves over longer trajectories [76].

ADVANTAGES AND DISADVANTAGES OF DW-MR NEUROGRAPHY DW MR neurography implies several benefits with regard to imaging the nerves compared to conventional T2-

and T1-weighted MR imaging. One of the major advantages of DW-MRN is that vascular structures, such as

veins adjacent to nerves, which are difficult to distinguish from the nerves of the plexus brachialis on T2- and

T1-weighted MR images because of their similar signal intensity, can be distinguished more easily by DW-MRN

[71, 72]. This sequence provides a better view on the anatomy of the plexus and the nerves.

Besides, Zhang et al. showed that the detection of small nerve structures, especially those located near large

vessels, is largely improved by the ability of the Steady State Free Precession (SSFP) technique to completely

eliminate the signal intensity from the vessels [36]. Nerves produce signal intensity because they can construct

the steady-state condition and because this technique heavily depends on the steady-state condition, they are

visible. On the other hand, vessels cannot construct the steady-state condition and will be suppressed on a 3D

DW-SSFP image.

Another major advantage of DW-MRN compared to other MR sequences, is its capability to visualize nerves

over long trajectories because of excellent suppression of background structures such as fat, muscles, and

vascular structures [36, 72]. Nevertheless, although many unwanted structures are suppressed at DW-MRN,

several normal structures that have a relatively long T2 value and an impeded diffusion (among which lymph

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nodes, bone marrow, veins with slow blood flow, and particular fluids) maintain a high signal intensity. The

presence of these structures in the near proximity of the nerves and superimposition of these structures on the

nerves on projection images may hinder the evaluation of the nerves [72].

The DW-MRN technique, as all other techniques, also has several drawbacks. For instance, a limitation of the

proposed DW-MRN technique, proved by the study of Takahara et al., is that the anterior divisions of the third

and fourth sacral nerve cannot always been well visualized. Reducing the slice thickness may allow better

visualization of these nerve roots, but this will consequently require a prolonged examination time. Another

limitation in the study of Takahara is that only healthy volunteers were included and that the clinical impact of

the proposed DW-MRN technique had not been evaluated among patients [35].

Other disadvantages of the MR neurography of the plexus sacralis are the motion, pulsation and ghost artifacts

in the lower abdomen. These artifacts can degrade or even disturb the quality of the images, particularly the

quality of images on the nerves close to the abdominal wall [36]. At the higher field 3 T, these artifacts will be

more prominent than at a 1,5 T field, because the 3 T-system still suffers from considerable image distortion

and poor fat suppression. In addition higher field strength leads to an increased level of susceptibility artifacts

and increased blurring, due to more field inhomogeneities. However when in the near future the 3 T-system

will be combined with improved fat-suppression schemes and further enhancements to the shimming

technology, they may offer superior image quality over 1,5 T-systems [74, 77].

SUB-CONCLUSION DW-MRN seems to be a suitable technique for imaging the plexus sacralis because it provides an excellent

contrast between nerves and other tissues. It is easy to distinguish nerves from blood vessels on DW images. In

addition, DW provides excellent suppression of background structures, due to the DWIBS technique, and that is

why this technique is capable of visualize nerves over longer trajectories.

There are different DW-MRN techniques. Zhang et al. used the 3D DW-SSFP technique and Takahara et al. used

the SUSHI technique. Both techniques seem appropriate to image the plexus sacralis, according to the

literature. However, there is little known about the 3D DW-SSFP technique.

It should be taken in mind that in current daily practice the third and fourth sacral nerves cannot always been

well visualized at this moment. Probably, this is a consequence of the limited state of knowledge regarding this

relatively new but promising imaging technique. Possibly, optimization of the DW technique is required in

resolution and in the balance between suppressed and highlighted tissues.

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DIFFUSION TENSOR IMAGING (DTI)

The aforementioned principles of DW-MRI also allow diffusion tensor imaging (DTI). DTI differs from DW-MRI in

its tracking of the anisotropy of nerves [72]. DTI performs neural tracking, called tractography, which is more

difficult to perform and analyse than DW. DTI attempts to study the directionality of water diffusion, instead of

solely obtaining a high-quality neurographic dataset for three-dimensional evaluation and image display [30].

This technique is based on a tensor model to characterize diffusion anisotropy. To depict the direction and

degree of the anisotropy it is necessary to consider diffusion as a tensor quantity, such as a 3x3 matrix, and not

as a scalar. DTI differs also from DW in that DTI is performed with encoding in various directions, allowing to

investigate the diffusion tensor. To “solve” the tensor, at least six various directions are needed. With this

information it is possible to determine the degree and direction of anisotropy per pixel. Usually the tensor is

described in terms of a three coordinate axis. The axis of preferred diffusion is denominated as the “principal

eigenvector”. The most likely direction of diffusion is calculated, see Figure 13. Different algorithms can be

used for tracking and one of the most commonly used is fiber assignnment by continues tracking (FACT) [78].

FIGURE 13 - FIBER TRACKING OR TRACTOGRAPHY: THE PRINCIPAL EIGENVECTOR FOR EACH PIXEL IS SHOWN. FIBERPATHS ARE THEN

IDENTIFIED BY FOLLOWING THE DIRECTION OF THE PRINCIPAL EIGENVECTOR [78]

APPLICATIONS

DTI was firstly applied to depict the brain, followed by the spinal cord. DTI or tractography is especially valuable

in the context of congenital brain abnomalies. It also aids condiserably in presurgical evaluation, primarily in

patients with tumours and epilepsy [78, 79].

DTI is also useful to evaluate peripheral nerves such as the n. medialis, n. radialis, n. ulnaris and n. ischiadicus

and the plexus brachialis. DTI is able to demonstrate normal tracts of these nerves and pathologies like tract

displacement, deformation, infiltration, disruption and disorganization of fibers, for example due to tumours

located in the neighboorhood of the nerve [78, 79]. The question however is to what degree DTI MRI is

valuable for the purpose of evaluating the anatomy of the plexus sacralis? As was mentioned earlier, the plexus

brachialis was imaged by Vargas et al. with DTI. Because of the plexus sacralis consists also of nerve fibers in

the same order of size, it is reasonable to assume that the plexus sacralis can be imaged as well with DTI.

However, one has to consider the following limitations and challenges when imaging the plexus sacralis with

this technique:

LIMITATIONS Vargas et al. claimed that tractography reconstructions of the fibers in the plexus to be technically challenging.

Because of the small size of the nerve fibers, the orientation and the localization of the plexus brachialis it is

difficult to obtain reproducible fiber tracking [79]. Also, the fact that peripheral nerves have a lower water

proton density, less homogeneity and a short T2 time than the brain impede reproducible fiber tracking in

which imaging is done already. Khadil et al. stated that it is highly important to obtain sufficient signal to noise

ratio (SNR) in order to image these small structures. Therefore, acquisition parameters have to be optimized.

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Because of an increase in SNR, a higher field strength should be preferred, although it should be kept in mind

that an an increase in b value, the degree of diffusion weighting, causes a decrease in SNR. An optimal b value

has to be determined, since it is the primary parameter determining sensitivity in a diffusion-weighted

sequence [80].

Another difficulty involved the geometric distortion and artifacts, resulting in motion, respiration, swalling and

CSF pulsation artifacts. A major advantage of imaging the plexus sacralis is that these difficulties do not play a

role, because of the localization. Only motion of the bowel and the presence of moving air in the intestines

could hinder optimal imaging the plexus sacralis. Field inhomogeneity can be present at the interface of air and

tissue [79].

A disadvantage of using DTI is that, because of the finite spatial resolution, particular anatomic situations limit

the utility of this technique, because they are described by a single tensor. When a voxel contains multiple

fibers of multiple orientations, the calculated net anisotropy can be reduced so that fiber tracking terminates.

An algorithm cannot distinguish crossing and kissing fibers. More sophisiticated approaches and algorithms are

needed to improve this technique like high angular resolution diffusion imaging and diffusion spectrum

imaging. However, a major disadvantage is the limited widespread adoption of these technique, because of the

time penalty and the increased complexity of analysis [78].

As described above, DTI is based on algorithms to calculate the most likely diffusion direction. The fibertracking

technique performed by algorithms is a major drawback of this approach since the direction of the fibers is not

primarily measured. Therefore, this technique is perceived less reliable than diffusion-weighted MRI.

SUB-CONCLUSION The DTI technique can be very useful in diagnosing certain pathologies of the brain and peripheral nerves.

However, a couple of important limitations are inherent to DTI. DTI is a technique for image processing but

does not replace anatomic plexus imaging as provided with two-dimensional T1- and T2-weighted sequences or

with the DW-MRN sequence. DTI instead may give additional information regarding the direction of plexus

fibers. At this moment, however, DTI cannot been used for visualizing the plexus sacralis.

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MAGIC ANGLE

A known artifact in MR imaging is the magic angle artifact in tendons and ligaments. These structures are

visualized as bright spots when they are oriented at or near 55° to the main magnetic field at a T2 image with a

short TE. These bright spots were and still are sometimes confused with diseases and thus regarded as

artifacts, which should be avoided if possible. However, when insight in the causes of these artifacts was

obtained, research was performed to investigate whether these remarkable artifacts could be of use to image

tendons and ligaments. Recent research discovered that this phenomenon has potential for imaging peripheral

nerves and plexi as well.

The magic angle phenomenon is visible in collagen rich tissues containing water that is bound to collagen. The

protons within this water display dipolar interactions whose strength depends on the orientation of the fibers

to B0, the main magnetic field. These interactions usually result in rapid dephasing of the MR signal after

excitation and a very short T2. As a consequence, these tissues typically produce little or no detectable signal

intensity and appear dark when imaged with most MR pulse sequences [81].

This dipolar interaction is not static and is minimized at certain ‘magic’ angles, according to the term 3cos² θ – 1

= 0 (with θ is 55⁰, 125⁰ etc.) with the result that the T2 relaxation times of these tissues increase and signal

intensity may become evident when they are imaged with conventional pulse sequences.

It has nowadays been broadly demonstrated that this technique is useful for imaging tendons without the use

of contrast agents [82, 83]. However, the possible effect of a magic angle in nerves was never investigated until

Chapell et al. brought the hypothesis that it might work for peripheral nerves as well. Unlike the central

nervous system, in which axons are embedded in a network of oligodendrocytes and astrocytes, the peripheral

nerves and plexi are surrounded by a matrix of which collagen is one of the primary proteins. According to

Chapell et al. 49% of the total protein in the whole nerve structure is collagen, primarily type I, and most of the

collagen is located in epineurium, which occupies 22–88% of the nerve cross-sectional area. Therefore, the

magic angle effect could possibly used for imaging nerves as well.

APPLICATION OF THE MAGIC ANGLE IN NERVES AND THE PLEXUS SACRALIS

Chappell et al. provided evidence of a magic angle effect for peripheral nerves by imaging the n. ulnaris, n.

medialis and n. ischiadicus, as well as the plexus brachialis, which showed higher signal intensity in images at

angles near 55⁰. The effect was a 46–175% increase in signal intensity in the n. medialis’ orientation relative to

the main B0 magnetic field changes from 0° (parallel to B0) to 55° (the magic angle), accompanied by an

increase in mean T2 relaxation times from 47.2 to 65.8 ms. This supports the hypothesis that it could be

suitable for the purpose of imaging the plexus sacralis.

The changes in peripheral nerves by Chapell et al. are typically seen with STIR or heavily T2-weighted fast spin-

echo sequences with a relative long TE. They may appear as a more gradual transition over a wider range of

angles rather than just those closely related to 55°, see Figure 14. However, abrupt changes in signal intensity

were seen of a nerve that was sharply angulated. This could influence the plexus sacralis as well, which does

not lie in a completely straight line either. With tendons increasing TE the magic angle effects are reduced,

because the level of detectable signal intensity decreases. Research showed that a TE beyond about 38 ms

makes tendons not observable at all [84]. With peripheral nerves, magic angle effects were seen at longer TEs

(eg, 66 ms) with a STIR sequence [85]. In addition, as illustrated in Figure 14 from Chapell et al. and as

described by other research [81] the mean T2 for tendons is generally short enough, and the range of visible

angles narrow enough for tendons to remain dark on STIR or T2-weighted images even as the magic angle is

approached. As stated above, the mean T2 for the n. medialis, is longer than the value for tendons, and as the

magic angle is approached, these peripheral nerves becomes visibly brighter as a result of the increase in signal

intensity.

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The contradiction that the n. medialis shows an obvious magic angle effect and tendons do not with STIR

sequences in this figure, is probably due to the use of a relatively long TE for tendons in this test (30 ms) next to

the fact that tendons have relatively short T1 relaxation times so that the signal from tendons is partly nulled

out by the STIR sequence.

FIGURE 14 - INTENSITIES OF THE MEDIAN NERVE, MUSCLE, AND FLEXOR TENDON AT DIFFERENT ANGLES [85]

As our research focuses on the plexus sacralis, the outcome of imaging the plexus brachialis has the main focus,

because this structure is most closely related to the plexus sacralis. Chapell et al. used an orientation of the

plexus brachialis, in which the roots, trunks, divisions, cords, and terminal branches were orientated at

different angles within this general range of 40–60° to B0, see Figure 15. This enables brightening of the nerves

of the plexus brachialis in contrast to the surrounding skeletal muscle and tendons. This feeds the hypothesis

that it could be a supporting phenomenon when imaging the plexus sacralis, although a critical evaluation is

necessary.

FIGURE 13 – THE USED LINE TO DETERMINE MAGIC ANGLE IN THE PLEXUS BRACHIALIS [85]

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DISADVANTAGES AND POINTS OF ATTENTION

When the magic angle effect would be tested for the plexus sacralis, there is a number of issues that require

attention. First, there is the orientational dependence of the angle effect in combination with the undulating

courses that the plexus can have. Although the magic angle effect in nerves is visible in a relative broad range

of angles, it can be difficult to image a significant nerve length in a single plane. Second, peripheral nerves are

often small in relation to the thickness of sections used in MR imaging. They therefore might show a relatively

large partial volume effect, although this problem decreases in a high Tesla MRI. Third, the signal intensity of

nerves can be influenced by small unwanted inhomogeneities in the gradients of the surface coils, limiting the

value of skeletal muscle signal intensity as a general reference standard for nerve signal intensity and

differences in chosen (pulse sequence) parameters. Fourth, nerve lesions and disorders are often surrounded

by collagen-rich scar and connective tissue. It is very difficult to distinguish these cases from the issues above

[81, 85].

SUB-CONCLUSION From the above can be derived that the magic angle effect could have a supporting role in imaging the plexus

sacralis, although few relevant research has been done so far. Moreover, possible confounders, due to

described orientational dependence and small field inhomogeneities have to be taken into consideration.

Before the magic angle effect can be used for imaging nerves, more research has to be done.

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POST-PROCESSING

Besides the use of other sequences for imaging the plexus sacralis, another point that should be taken into

account is the post-processing of the MR images. An example of this is 3D T2 STIR Sampling Perfection with

Application optimized Contrast using different flip angle Evolutions (SPACE) [34].

Imaging with 3D T2 STIR SPACE, high-quality MR neurography of the plexus brachialis is possible. This has been

studied by Viallon et al. [34]. They used thin maximum intensity projection (MIP) and multiplanar

reconstruction to obtain a 3D image. MIP uses an algorithm to convert 2D images in 3D images. The 3D T2 STIR

SPACE sequence appeared to have better capacity to depict the course of the nerves of the plexus brachialis

from the spinal cord to the distal area than the conventional 2D-STIR sequence. Vargas described also that this

technique is valuable not only because of the adequate contrast and the high resolution, but because of the

possibility of tracking the nerves exists now [51]. However, experienced radiologists do not need this extra 3D

information. They can follow the nerves on conventional 2D STIR images.

Besides conventional MIP post-processing, in DW images the soap bubble MIP technique is used for post-

processing the images. Thanks to the points seeded by radiologists on the nerves in the axial plane, the nerves

can even better be tracked [71].

SUB-CONCLUSION Post-processing by MIP or other post-processing techniques could be useful for imaging the plexus sacralis,

because of the better possibility for tracking the nerves.

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CONCLUSION MRI SEQUENCES AND TECHNIQUES

After careful consideration of the aforementioned techniques, it is not easy to select the most optimal one for

the purpose of imaging the plexus sacralis. We can definitely indicate that some sequences are suitable for

imaging the plexus sacralis, but no single technique can be pointed out as the most optimal because the

various sequences each provide different information about the plexus sacralis and are all important in order to

obtain a comprehensive view.

Sequences and techniques that are definitely not very suitable to image the plexus sacralis are 3D CISS, GE,

SPIR, FLAIR, DTI and the use of contrast agents. The magic angle effect needs to be more closely investigated

before a decent conclusion on this topic can be drawn. Sequences that can possibly be used for imaging the

plexus sacralis are SE/FSE T1/T2, STIR, BTFE, MP-RAGE and DW. Also, post-processing of the images obtained

with the chosen imaging technique would provide better results.

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TOWARDS A NEW PROTOCOL…

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INTRODUCTION In this section a systematic analysis of both the standard protocol for imaging the plexus sacralis and the most

suitable sequence for further research will be given.

First, the standard protocol will be discussed to determine the specific objectives of the protocol used in daily

practice. In addition, it will be investigated if it is possible to analyze the anatomy of the plexus sacralis with the

standard protocol and if it is useful to implement a new sequence to optimize the visualization of the plexus.

After analyzing the standard protocol, the sequence with the highest contribution to imaging the plexus sacralis

will be identified. When the choice was made, a practical research was set up to investigate the suitability of

this sequence for further research in practice. The results of this research will be described.

Elaborating on the results of the analysis of the new sequence, a research proposal for a third year master

internship for students of the study Robotics and Imaging of Technical Medicine will be provided, see Appendix

A.

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STANDARD PROTOCOL

An analysis of the current standard protocol used for imaging the plexus sacralis in the UMCU is described here.

First, this protocol will be introduced and described per sequence. In addition, the function and application of

this protocol in the hospital will be investigated. Then, it will be explored whether or not this protocol should

be changed for optimizing imaging the plexus sacralis.

THE PROTOCOL The standard protocol, used for imaging the plexus sacralis in the UMCU, has been in use for a few years and

has not been modified recently. The choice of the sequences within a protocol is always a tradeoff between the

optimal imaging, the clinical question and the (available) scan time. The chosen scan time depends on the time

available for scanning a patient (usually 30 minutes) and the fact that more motion artifacts appear when the

scan time increases [86].

Looking at the protocol in consecutive sequence, the first scan made is the m SURVEY, an overview scan in

order to determine the exact planes of scanning. Then, a series of scans is made, see Table 5, consisting of T2

and T1 images. As mentioned before, see page 29, a T2-weighted image is often provided by a TSE sequence,

because of a long scan time when used with normal SE, as reflected in the protocol. T1-weighted images are

provided by the SE sequence, because they do not suffer of a long scan time.

The T1- and T2-weighted images are implemented, because they enable analysis of the anatomy. The various

depicted grey values in the body due to different structures (e.g., fat, water and nerves) provide an adequate

analysis. As was mentioned before at page 26, at T1-weighted images, the anatomy can be clearly observed

and at T2-weighted images, pathologies are clearly shown. This combination takes into account most possible

scenarios.

The STIR sequence is deployed to suppress fat, in order to provide a better discrimination between the fat

around the plexus sacralis and the nerves of the plexus. In addition, pathologies like tumours, oedema and

inflammations are visualized brightly at these images.

The T2 FFE, or SSFP, sequence provides an adequate distinction between cartilage and other tissue, like bone.

This is helpful when investigating a possible sacral hernia.

TABLE 5 - STANDARD PROTOCOL PLEXUS SACRALIS

ANALYSIS The standard protocol is particularly used for diagnosing some of the aforementioned pathologies (e.g.

tumours, oedema, inflammation) around the plexus sacralis. The protocol is set up to provide as many

information as possible about these pathologies. The goal of using this protocol is investigating pathologies,

and it is not made to investigate the normal anatomy of the plexus sacralis. Therefore, the protocol is not

designed to visualize small nerves, because affected nerves always are enlarged [86]. Because the goal of this

thesis is to visualize the plexus sacralis and its branches, it is necessary to change and optimize this protocol for

imaging the anatomy of the plexus sacralis so that smaller nerves also become visible.

m Survey

s T2 TSE pl sagittal plane s T1 SE pl sagittal plane c T2 STIR pl coronal plane t T1 SE pl transversal plane t T2 FFE pl transversal plane

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A NEW PROTOCOL: DW-MRN IN PRACTICE In the previous section, several appropriate techniques for imaging the plexus sacralis were described: SE/FSE

T1/T2, STIR, BTFE, MP-RAGE and DW. The standard protocol for imaging the plexus sacralis includes SE T1, FSE

T2 and T2 STIR. Since our study concentrates on modifying the protocol towards optimal imaging of the plexus

sacralis and because we assume that the sequences of the protocol are already optimized for the regular

clinical use, these sequences are left out of consideration. More result is to be expected in modifying the

protocol with other sequences. Therefore, a choice had to be made between BTFE, MP-RAGE and DW. Because

few papers regarding BTFE and MP-RAGE could be identified in the literature, we decided to focus our study on

DW, despite the possible usefulness of BTFE and MP-rage for imaging the plexus sacralis. Furthermore, from a

more pragmatic point of view, the research will be conducted at the University Medical Center Utrecht

(UMCU). This academic hospital has plenty of experience in DW-MRN. Therefore, DW seems to be more

suitable for further research compared to the other sequences.

In Appendix A, a research proposal for this further research is described, in order to seek an answer to the

following question: what parameter settings of the DW-MRN sequence in imaging the plexus sacralis provide

the most adequate anatomical information, in comparison with the parameters settings in the current protocol?

As was mentioned before, there are multiple DW variations: DW with unidirectional motion probing gradients,

3D DW-SSFP and DW in combination with SUSHI. In addition, a DW image can be optimized by adapting the

parameters.

Within the scope of our current study, we made a standard protocol MRI scan complemented with a DW

protocol. The aim of this practical research was investigating the possibility of making DW scans on a 1,5 T MRI

scanner and exploring the possibilities of improving DW imaging. This knowledge is helpful in setting up the

research proposal that will be presented in the next section. The practical research that we conducted will now

be described.

GOAL The primary goal of this practical study was to investigate the possibility of imaging the plexus sacralis on a 1,5

T MRI scanner as a pre-research for the described proposal. Several studies about imaging the plexus sacralis

and brachialis with DW imaging were identified with a 3 T MRI scanner [35, 71, 72]. However, only imaging the

plexus brachialis and not of the plexus sacralis has been done on 1,5 T. Other reasons to investigate this, are

because DW-MRN on a higher field strength is more sensitive to susceptibility artifacts [77] and for a pragmatic

reason: not every hospital possess a 3 T MRI scanner, although almost every Dutch hospital does have a 1,5 T

MRI scanner. Therefore, an optimized protocol based on a 1,5 T MRI scanner would be more widely useful than

a protocol based on a 3 T MRI scanner, because the new protocol can then be directly translated into daily

clinical practice.

The secondary goal of this research is to optimize imaging the plexus sacralis with a 1,5 T MRI. As was

mentioned before, Takahara et al. investigated imaging the plexus sacralis at 3 T. He stated that further

optimization is required because of the limited visualization of the plexus [35]. In fact, the complete plexus

cannot be observed yet. Here, it is questioned whether optimization by changing parameter settings is possible

at a 1,5 T MRI scanner. If so, a study can be set up for optimizing the DW-MRN protocol.

MATERIALS AND METHODS Two healthy volunteers [one man, one woman, aged 22 years] underwent a scan with the standard protocol for

imaging the plexus sacralis, complemented by a DW-MRN. Both subjects were examined with a 1,5 T MR unit

(Achieva, Philips Medical Systems, Best, the Netherlands) and with a SENSE-XL-Torso phased array body coil.

Imaging a part of the plexus lumbalis and plexus sacralis, from L4 to the inguinal region, was performed.

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DW images were obtained by using DWIBS (diffusion-weighted whole-body imaging with background body

signal suppression) [76]. An advantage of the DWIBS technique is that imaging can be performed without the

patient having to hold his/her breath. This enables a longer effective imaging time, which allows acquisition of

a larger number of thin sections and 3D analysis.

The DW protocol that was used can be seen in Table 6. DW image acquisition was performed in the axial plane,

because Takahara et al. showed that direct coronal imaging tends to suffer from severe image distortion since

it requires a larger field view [35, 74]. The images of the axial plane were post-processed by maximum intensity

projection (MIP). On MIP images, the trajectory of the nerves is well visualized [35].

TABLE 6 - IMAGING PARAMETERS FOR DW-MRN, SCAN 1

Abbreviations: EPI: echo-planar imaging ETL: echo train length FOV: field of view TR: repetition time TI: inversion time TE: echo time

After assessing the first results of our male volunteer, we tried to optimize the images. Therefore, some

parameters were changed which were expected that influence image quality. The FOV was decreased to

provide a higher spatial resolution. Also, the TE and the b value were decreased, providing increased SNR and

less suppression of body signals, including signals of the nerves, respectively. The number of averages was

increased, proving a higher signal to noise ratio. For an overview of the new parameters, see Table 7. The

choice for changing parameters was made, because of the expected positive influence on the resolution and

our study is about the possibility of optimizing DW images. The SNR is also important, but subordinate to the

resolution, because much signal is already suppressed at DW-scans which reduces the need for a higher SNR.

TABLE 7 - IMAGING PARAMETERS FOR DW-MRN, SCAN 2

Abbreviations: EPI: echo-planar imaging ETL: echo train length FOV: field of view TR: repetition time TI: inversion time TE: echo time

Sequence Single shot EPI

Acquisition plane Axial

FOV (mm) 400

% FOV 82,5%

TR/TI/TE (ms) 5122/180/84

EPI factor (ETL) 57

SENSE factor 2

Acquisition matrix 160 x 130

Slice thickness/gap (mm) 4/3

Number of averages 16

b value (s/mm2) 1000

Acquisition time (s) 676

Sequence Single shot EPI

Acquisition plane Axial

FOV (mm) 400

% FOV 75%

TR/TI/TE (ms) 5122/180/77

EPI factor (ETL) 51

SENSE factor 2

Acquisition matrix 160 x 127

Slice thickness (mm) 4

Number of averages 32

b value (s/mm2) 700

Acquisition time (s) 338

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RESULTS

To investigate whether it is possible to image the plexus sacralis on a 1,5 T MRI scanner, the DW images of both

volunteers will be analyzed. Next, the two DW-images of the male volunteer will be compared and then the

possibility of optimizing the images by changing the FOV, NSA, TE and the b-value will be investigated.

DW-MRN AT 1,5 T

Representative DW-MRN images of the plexus sacralis of the volunteers, post-processed by MIP, are shown in

Figures 16 to 18. The myelum and kidneys can be clearly observed. Caudal of these structures nerves of the

plexus lumbalis and sacralis can be seen. The third and fourth sacral nerve can hardly be identified. The bright

spots along the course of the nerves are ganglia.

OPTIMIZING DW-MRN

Figures 17 and 18 represent DW-MRN of the same volunteer with different parameter settings, see Tables 6

and 7. Nerves can be observed more clearly on Figure 18 compared to Figure 17, due to the better contrast.

The third sacral nerve can be seen on Figure 18 and not on Figure 17. The fourth sacral nerve cannot be seen

on both images. In addition, artifacts are less pronounced in Figure 18 and the SNR seems to be enhanced.

FIGURE 16 – DW-MRN MIP RECONSTRUCTION FEMALE

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DISCUSSION In the performed study, two DW scans at one subject were made in which several parameters were changed.

The reason for this was that the duration of our scanning time only allowed one second DW-MRN scan. But

more important, this made it possible to get an understanding of the possibilities of influencing the image

quality. In future research, the parameters should be changed one by one to investigate their independent

influences on the image quality.

During our study, we did not use the soap-bubble MIP approach, but the conventional MIP approach due to the

limited time. Takahara et al. stated that the soap-bubble MIP approach is superior to the conventional MIP

approach in visualizing the plexus sacralis [35]. In further research, the use of soap-bubble MIP approach is

recommended.

The volunteers of the present study were adults. The goal of further research would be imaging variations of

children’s plexus sacralis. Therefore, children should be subject of future research. We assume that imaging the

FIGURE 18 - DW-MRN MIP RECONSTRUCTION MALE WITH CHANGED PARAMETERS

FIGURE 17 - DW-MRN MIP RECONTRUCTION MALE

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plexus sacralis with DW-MRN at a 1,5 T MRI scanner is possible among children too, because the diameter of

the nerves in children does not differ that much of the diameter of the nerves in adults, see page 25.

The presented study included both a male and a female volunteer. We observed that adequately depicting the

plexus sacralis with DW-MRN was easier in case of the female volunteer. The experience of the radiologist was

that in DW-MRN, women’s plexus sacralis often is more photogenic than men’s. In addition, the bony

structures, e.g. the pelvis, of the female volunteer is brighter than male’s bony structures. The brightness of the

bony structures depends on the composition of the bone marrow, that differs between persons. When bone

marrow contains more red marrow, the bony structures will be depicted more brightly on DW images because

of the higher signal intensity of red marrow on DW-MRN. When setting the parameters, one has to consider

that the possessing of more red marrow may decrease the nerve distinction because of the increased

background signal.

A limitation of our study is that the third and fourth sacral nerve could hardly be visualized, like Takahara

experienced as well. Because we analyzed only two volunteers and three scans in total, we cannot claim that

these nerves never can be visualized with these parameter settings. The study was too small-scaled to draw

such general conclusions. Further research among more volunteers is required. Other optimization possibilities

that can be taken into account are the use of another coil and reducing the slice thickness to image smaller

structures.

CONCLUSION Following our results, it can be concluded that DW-MRN, performed at a 1,5 T MRI scanner can image the

nerves of the plexus sacralis. However, the third and fourth sacral nerve can hardly be visualized. That is the

reason why optimization is definitely required.

The secondary goal was exploring the possibility of optimizing imaging the plexus sacralis by changing the

parameter settings. We hypothesized that changing the parameter settings would result in a clearer

visualization of the plexus sacralis which indeed happened, due to more contrast and a higher SNR. However,

the exact parameter settings in order to obtain the best possible image of the plexus sacralis are not known

yet. This should be the subject of future research.

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DISCUSSION

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GENERAL DISCUSSION

No Thesis is complete without a critical review about the followed direction and made choices. First point of

regard concerns the part of the discussed sequences. There has been tried to evaluate as much different

sequences as possible and to discuss all the possible candidates found in the literature that could image the

plexus sacralis. However, it was soon clear that these discussed sequences did not include all sequences, but

the ones of which scientific literature was found, according to imaging nerves, and of which an argued

evaluation could be made. The group of other, not described, sequence variations is very broad. It is

recommended to keep an eye of new scientific publications of these sequences in relation to imaging nerves. A

second point of interest is the fact that we finished our research with the practical part of a first DW-MRN scan

session. Although the results were hopeful and formed an additional conformation for the need of extra DW

research, it is important to keep in mind that it was just a single scanning session and the outcome of further

research can still be very diverse. Last, an important disadvantage of MRI is not described in its technique

evaluation, although it is important in clinical practice; MRI is such a complex technique that it often difficult to

determine its optimal parameters. Although this should not be expected from a MRI specialist, incorrect

settings can have a great influence in evaluating MRI for specific purposes.

ALTERNATIVE HYPOTHESES In this study we only reviewed one hypothesis for explanation of the broad range of bladder symptoms; the

anatomical variations in the plexus sacralis. This hypothesis justifies the research about imaging the plexus

sacralis. However, as a note of caution, there are other hypotheses possible that could explain those bladder

symptoms.

One of them is the clinical example of chronically degenerated peripheral nerves in which the increased signal

on a T2-weighted scan eventually normalized over months, even in the absence of functional recovery. Thus, a

lesion of a peripheral nerve involved in the regulation of the bladder function that shows no abnormality on a

MRI scan could also be responsible for bladder symptoms, but because some time has passed since the

degeneration was initiated, this cause is not visible anymore.

Another point of discussion is based on the hypothesis that anatomical variations of the plexus sacralis can be

responsible for bladder symptoms. It can be discussed if the cause in another part of the nerve system is

undoubtedly ruled out. Urinating is a very complex process in which different central brain parts play a role,

such as the pontine miction centre and supraspinal systems as the hypothalamus and limbic system. Although

it is difficult to investigate such an alternative hypothesis, this should be taken into account.

ALTERNATIVE RESEARCH PROPOSALS This Bachelor Thesis attempted to investigate and evaluate as much depicting techniques and sequences as

possible. As a result, the MRI sequence for the research proposal is chosen, that is expected to apply the most

added value. This is done, based on the literature and possibilities of the different MRI sequences at the UMCU.

However, the fact remains that more sequences have potential of imaging the plexus sacralis in detail than

DW-MRN. As stated in the conclusion of MRI sequences and techniques, see page 43, high field FSE, STIR, BTFE,

MP-RAGE can have added value as well. An alternative proposal could be focused on one of these sequences.

One of the most obvious of these is high magnetic field T1/T2. The reason for this is because the UMCU has a 7

T MRI available with many unexplored research areas. However, in this paper is chosen for DW-MRN, because

there is already some research experience in imaging the plexus sacralis with this technique and the first results

were hopeful. STIR is already used in the current protocol, so the ‘added’ value is expected to be less, although

the settings could be optimized. BTFE and MP-RAGE are very new recent sequences with limited research

published. There is not chosen to investigate these for now, because future research will show if they could be

serious candidates. In addition, there is one other alternative which has to be kept in mind; editing of the

sequences of the current protocol, without adding a new sequence.

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CONCLUSION

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In can be concluded that among the different imaging techniques, magnetic resonance imaging (MRI) has the

most potential for imaging the plexus sacralis. As well because of its possibility of depicting soft tissue

structures, as because of the diversity in the different sequences. Among the different sequences, the diffusion

weighted (DW) sequence seems the most promising option as an addition to the current protocol. Although

there are some possible alternatives, the literature and research experience in the University Medical Center

Utrecht (UMCU) points towards DW-MRN as the most promising one.

The first practical test as a pre-research strengthens this presumption; with a first 1,5 T DW-MRN scan session,

hopeful results were obtained. In these images, the plexus sacralis is visible and with some straightforward

adjustments, more detailed pictures are possible. However, to be useful for testing the hypothesis of the

relation between bladder symptoms and anatomical variations of the plexus sacralis, further research is

necessary. A concrete completion of this future research is added as Appendix A, in the form of a research

proposal.

This Bachelor Thesis and formed research proposal set a hopefully line for further research, all with the goal of

helping children with non diagnosed, unpleasant bladder complaints.

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REFERENCES

Page 58: Imaging Children’s plexus sacralis: Towards an optimal method€¦ · Imaging the plexus sacralis is the first step in confirming this hypothesis. For depicting the nerves of the

57

1. Moore, K.L., Clinically Oriented Anatomy. 5 ed. 2006, Baltimore: Lippincott Williams & Wilkins. 1209. 2. Heesakkers, J., Thema 10: Blaasafwijkingen, in Reader Urologie, Water en Zout huishouding. 2007:

Nijmegen. p. 18. 3. Gray, H., et al., Gray's anatomy : the anatomical basis of clinical practice. 39th ed. 2005, Edinburgh ;

New York: Elsevier Churchill Livingstone. xx, 1627 p. 4. Junqueira, J.C., Functionele Histologie. 10 ed. 2004, Maarssen: Elsevier gezondheidszorg. 648. 5. Filler, A.G., K.R. Maravilla, and J.S. Tsuruda, MR neurography and muscle MR imaging for image

diagnosis of disorders affecting the peripheral nerves and musculature. Neurol Clin, 2004. 22(3): p. 643-82, vi-vii.

6. Histology Nerves. 2010 [cited 2010 22-06]; Available from: http://training.seer.cancer.gov/module_anatomy/unit5_3_nerve_org2_pns.html.

7. Dik, P., Gesprek 15-06-2010. 2010: Utrecht. 8. Gierada, D.S., et al., MR imaging of the sacral plexus: normal findings. AJR Am J Roentgenol, 1993.

160(5): p. 1059-65. 9. Matejcik, V., Anatomical variations of lumbosacral plexus. Surg Radiol Anat, 2010. 32(4): p. 409-14. 10. Ben-Ari, A.Y., et al., Ultrasound localization of the sacral plexus using a parasacral approach. Anesth

Analg, 2009. 108(6): p. 1977-80. 11. Kremkau, F.W., Diagnostic Ultrasound Principles and Instruments. 7 ed. 2006, Philadelhia: Saunders

Elsevier. 521. 12. Oosterom, A.v., Medische Fysica. 3 ed. 2008, Maarssen: Elsevier gezondheidszorg. 198. 13. Beekman, R. and L.H. Visser, High-resolution sonography of the peripheral nervous system -- a review

of the literature. Eur J Neurol, 2004. 11(5): p. 305-14. 14. Kovacs, P., et al., New, simple, ultrasound-guided infiltration of the pudendal nerve: ultrasonographic

technique. Dis Colon Rectum, 2001. 44(9): p. 1381-5. 15. Cash, C.J., et al., Spatial mapping of the brachial plexus using three-dimensional ultrasound. Br J Radiol,

2005. 78(936): p. 1086-94. 16. Demondion, X., et al., Sonographic mapping of the normal brachial plexus. AJNR Am J Neuroradiol,

2003. 24(7): p. 1303-9. 17. Bushberg, J.T., The essential physics of medical imaging. 2nd ed. 2002, Philadelphia: Lippincott

Williams & Wilkins. xvi, 933 p. 18. Eastman, G.W., C. Wald, and J. Crossing, Getting started in clinical radiology: from image to diagnosis.

1 ed. 2006, Stuttgart: Georg Thieme Verlag. 355. 19. Becker, M., et al., Imaging of the optic nerve. Eur J Radiol, 2009. 74(2): p. 299-313. 20. Burmeister, H.P., et al., CT and MR imaging of the facial nerve. HNO, 2010. 58(5): p. 433-42. 21. Di Benedetto, P., et al., Anatomy and imaging of lumbar plexus. Minerva Anestesiol, 2005. 71(9): p.

549-54. 22. Hough, D.M., et al., Chronic perineal pain caused by pudendal nerve entrapment: anatomy and CT-

guided perineural injection technique. AJR Am J Roentgenol, 2003. 181(2): p. 561-7. 23. Dietemann, J.L., et al., Anatomy and computed tomography of the normal lumbosacral plexus.

Neuroradiology, 1987. 29(1): p. 58-68. 24. Lanzieri, C.F. and S.K. Hilal, Computed tomography of the sacral plexus and sciatic nerve in the greater

sciatic foramen. AJR Am J Roentgenol, 1984. 143(1): p. 165-8. 25. Johnson, T.R., et al., Material differentiation by dual energy CT: initial experience. Eur Radiol, 2007.

17(6): p. 1510-7. 26. Blum, A.S. and S.B. Rutkove, The clinical neurophysiology primer. Methods in molecular biology. Vol.

388. 2007, New Jersey: Humana Press Inc. 526. 27. Silverthorn, Human Physiology: An Integrated Approach. 3 ed. 2004, San Francisco: Pearson Education,

Inc. 878. 28. Westbrook, C., MRI in practice. 3 ed. 2005, Oxford: Blackwell Science Ltd. 410. 29. Blink, E.J., MRI: Principes. 2004. 30. Hornak, J.P., The Basics of MRI. 2010. 31. IMAIOS: Gradient Echo. 2010 [cited 2010 22-06]; Available from: http://www.imaios.com/en/e-

Courses/e-MRI/MRI-Sequences/gradient-echo. 32. Holz, A. and B. Bowen, Peripheral nerve MR: Imaging of the brachial and sacral plexuses. Applied

Radiology, 1999. 28(11): p. 31-40. 33. Zhang, Z., et al., Segmented echo planar MR imaging of the brachial plexus with inversion recovery

magnetization preparation at 3.0T. J Magn Reson Imaging, 2008. 28(2): p. 440-4.

Page 59: Imaging Children’s plexus sacralis: Towards an optimal method€¦ · Imaging the plexus sacralis is the first step in confirming this hypothesis. For depicting the nerves of the

58

34. Viallon, M., et al., High-resolution and functional magnetic resonance imaging of the brachial plexus using an isotropic 3D T2 STIR (Short Term Inversion Recovery) SPACE sequence and diffusion tensor imaging. Eur Radiol, 2008. 18(5): p. 1018-23.

35. Takahara, T., et al., Diffusion-weighted MR neurography of the sacral plexus with unidirectional motion probing gradients. Eur Radiol, 2009. 20(5): p. 1221-6.

36. Zhang, Z.W., et al., High-resolution diffusion-weighted MR imaging of the human lumbosacral plexus and its branches based on a steady-state free precession imaging technique at 3T. AJNR Am J Neuroradiol, 2008. 29(6): p. 1092-4.

37. Maravilla, K.R. and B.C. Bowen, Imaging of the peripheral nervous system: evaluation of peripheral neuropathy and plexopathy. AJNR Am J Neuroradiol, 1998. 19(6): p. 1011-23.

38. Darge, K., D. Jaramillo, and M.J. Siegel, Whole-body MRI in children: current status and future applications. Eur J Radiol, 2008. 68(2): p. 289-98.

39. Dagia, C. and M. Ditchfield, 3T MRI in paediatrics: challenges and clinical applications. Eur J Radiol, 2008. 68(2): p. 309-19.

40. Hallowell, L.M., et al., Reviewing the process of preparing children for MRI. Pediatr Radiol, 2008. 38(3): p. 271-9.

41. Gambarota, G., et al., NMR properties of human median nerve at 3 T: proton density, T1, T2, and magnetization transfer. J Magn Reson Imaging, 2009. 29(4): p. 982-6.

42. Grant, G.A., et al., The utility of magnetic resonance imaging in evaluating peripheral nerve disorders. Muscle Nerve, 2002. 25(3): p. 314-31.

43. Dam, T., Techniek in de radiologie. 2 ed. 2003, Maarssen: Elsevier gezondheidszorg. 622. 44. Stoll, G., et al., Magnetic resonance imaging of the peripheral nervous system. J Neurol, 2009. 256(7):

p. 1043-51. 45. Zhou, L., D.M. Yousem, and V. Chaudhry, Role of magnetic resonance neurography in brachial plexus

lesions. Muscle Nerve, 2004. 30(3): p. 305-9. 46. Weinmann, H.J., et al., Tissue-specific MR contrast agents. Eur J Radiol, 2003. 46(1): p. 33-44. 47. MR-Tip: MRI Contrast Agents. 2010 [cited 2010 22-06]; Available from: http://www.mr-

tip.com/serv1.php?type=coa&sub=1. 48. MR-Tip: Contrast agents. 2010 [cited 2010 22-06]; Available from: http://www.mr-

tip.com/serv1.php?type=db1&dbs=Contrast%20agents. 49. Stoll, G. and M. Bendszus, Imaging of inflammation in the peripheral and central nervous system by

magnetic resonance imaging. Neuroscience, 2009. 158(3): p. 1151-60. 50. Wessig, C., et al., Gadofluorine M-enhanced magnetic resonance nerve imaging: comparison between

acute inflammatory and chronic degenerative demyelination in rats. Exp Neurol, 2008. 210(1): p. 137-43.

51. Vargas, M.I., et al., New approaches in imaging of the brachial plexus. Eur J Radiol, 2010. 74(2): p. 403-10.

52. Moore, K.R., J.S. Tsuruda, and A.T. Dailey, The value of MR neurography for evaluating extraspinal neuropathic leg pain: a pictorial essay. AJNR Am J Neuroradiol, 2001. 22(4): p. 786-94.

53. MR-Tip: Field Strength. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=db1&dbs=Field%20Strength.

54. MR-Tip: Resolution. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=db1&dbs=Resolution.

55. MR-Tip: SNR. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=db1&dbs=SNR.

56. Zwanenburg, J.J.M., Magnetic Resonance Imaging bij ultra-hoge veldsterkte (7 tesla). Nederlands Tijdschrift voor Natuurkunde, 2008. 74(06): p. 194-197.

57. Lee, F.C., et al., High-resolution ultrasonography in the diagnosis and intraoperative management of peripheral nerve lesions. J Neurosurg, 2010

58. Lewis, A.M., et al., Magnetic resonance neurography in extraspinal sciatica. Arch Neurol, 2006. 63(10): p. 1469-72.

59. McRobbie, D.W., M.E. A., and M.J. Graves, MRI from picture to proton. 1 ed. 2003, Cambridge: Cambridge University Press. 359.

60. Purdy, D., The Skinny on FatSat, in MRI Hot Topics, S. Medical, Editor. 2010: Malvem. 61. Lavdas, E., et al., Comparison of T1-weighted fast spin-echo and T1-weighted fluid-attenuated

inversion recovery images of the lumbar spine at 3.0 Tesla. Acta Radiol, 2010. 51(3): p. 290-5.

Page 60: Imaging Children’s plexus sacralis: Towards an optimal method€¦ · Imaging the plexus sacralis is the first step in confirming this hypothesis. For depicting the nerves of the

59

62. MR-Tip: Gradient Echo. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=db1&dbs=Gradient%20Echo.

63. Bendszus, M., et al., Assessment of nerve degeneration by gadofluorine M-enhanced magnetic resonance imaging. Ann Neurol, 2005. 57(3): p. 388-95.

64. Freund, W., et al., MR neurography with multiplanar reconstruction of 3D MRI datasets: an anatomical study and clinical applications. Neuroradiology, 2007. 49(4): p. 335-41.

65. MR-Tip: Coherent Gradient Echo. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=seq&sub=1.

66. van Ouwerkerk, W.J., et al., Detection of root avulsion in the dominant C7 obstetric brachial plexus lesion: experience with three-dimensional constructive interference in steady-state magnetic resonance imaging and electrophysiology. Neurosurgery, 2005. 57(5): p. 930-40; discussion 930-40.

67. Hong, H.S., et al., Enhancement pattern of the normal facial nerve at 3.0 T temporal MRI. Br J Radiol, 2009. 83(986): p. 118-21.

68. Deng, W., et al., High-resolution magnetic resonance imaging of the inferior alveolar nerve using 3-dimensional magnetization-prepared rapid gradient-echo sequence at 3.0T. J Oral Maxillofac Surg, 2008. 66(12): p. 2621-6.

69. Tsang, J.C., et al., Visualization of normal intra-parotid facial nerve on MR: BTFE or GRASS? Clin Radiol, 2009. 64(11): p. 1115-8.

70. MR-Tip: GRASS similar to SPGR. 2010 [cited 2010 22-06]; Available from: http://www.mr-tip.com/serv1.php?type=db1&dbs=Spoiled%20Gradient%20Recalled.

71. Takahara, T., et al., Diffusion-weighted MR neurography of the brachial plexus: feasibility study. Radiology, 2008. 249(2): p. 653-60.

72. Takahara, T., et al., Subtraction of unidirectionally encoded images for suppression of heavily isotropic objects (SUSHI) for selective visualization of peripheral nerves. Neuroradiology, 2010.

73. Diffusion & Perfusion Imaging. 2010; Available from: http://spinwarp.ucsd.edu/NeuroWeb/Text/br-710epi.htm.

74. Koh, D.M. and Y. Amoozadeh, Diffusion-Weighted MR Imaging: Applications in the Body. 1 ed. Medical Radiology / Diagnostic Imaging Series. 2009, New York: Springer-Verlag. 299.

75. Adachi, Y., et al., Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient. Neuroradiology, 2010.

76. Takahara, T., et al., Diffusion weighted whole body imaging with background body signal suppression (DWIBS): technical improvement using free breathing, STIR and high resolution 3D display. Radiat Med, 2004. 22(4): p. 275-82.

77. Porter, D.A. and R.M. Heidemann, High resolution diffusion-weighted imaging using readout-segmented echo-planar imaging, parallel imaging and a two-dimensional navigator-based reacquisition. Magn Reson Med, 2009. 62(2): p. 468-75.

78. Roberts, T.P. and E.S. Schwartz, Principles and implementation of diffusion-weighted and diffusion tensor imaging. Pediatr Radiol, 2007. 37(8): p. 739-48.

79. Vargas, M.I., et al., Diffusion tensor imaging (DTI) and tractography of the brachial plexus: feasibility and initial experience in neoplastic conditions. Neuroradiology, 2010. 52(3): p. 237-45.

80. Khalil, C., et al., Tractography of peripheral nerves and skeletal muscles. Eur J Radiol, 2010. 81. Bydder, M., et al., The magic angle effect: a source of artifact, determinant of image contrast, and

technique for imaging. J Magn Reson Imaging, 2007. 25(2): p. 290-300. 82. Hayes, C.W. and J.A. Parellada, The magic angle effect in musculoskeletal MR imaging. Top Magn

Reson Imaging, 1996. 8(1): p. 51-6. 83. Marshall, H., et al., Contrast-enhanced magic-angle MR imaging of the Achilles tendon. AJR Am J

Roentgenol, 2002. 179(1): p. 187-92. 84. Peh, W.C. and J.H. Chan, The magic angle phenomenon in tendons: effect of varying the MR echo time.

Br J Radiol, 1998. 71(841): p. 31-6. 85. Chappell, K.E., et al., Magic angle effects in MR neurography. AJNR Am J Neuroradiol, 2004. 25(3): p.

431-40. 86. Nievelstein, R.A., E-mail conversation dr. Nievelstein. 2010.

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APPENDIX A: RESEARCH PROPOSAL