PowerPoint Presentation

CSF flow imaging in Chiari 1 malformationWende Gibbs, MD, Department of NeuroradiologyGabriel Zada, MD, Department of NeurosurgeryJohn Liu, MD, Department of NeurosurgeryPatrick Hsieh, MD, Department of NeurosurgeryMeng Law, MD, MBBS, Department of Neuroradiology

University of Southern California, Keck School of MedicineControl # 1775eEdE-227

1DisclosuresWende Gibbs: noneGabriel Zada: noneJohn Liu: nonePatrick Hsieh: noneMeng Law: Toshiba Grant Speakers Bureau; Bracco speaker and consultant; Guerbet Medical Advisory Board; Prism Stock; Fuji speaker and consultant2PurposeChiari 1 malformation (CM1) has traditionally been defined by morphologic criteria: cerebellar tonsil herniation 3-6mm below the foramen magnumIt is increasingly clear that CM1 is a complex disorder resulting from not only abnormal anatomy, but disordered CSF flowThis exhibit will review static and dynamic imaging tools applied to the study of CM1, including new techniques that may improve diagnostic accuracy, patient management and surgical outcome

3ApproachReview theories of pathogenesis of CM1, focusing on the interplay of anatomy and CSF flow dynamicsDescribe established and recently developed neuroimaging tools used to study CM1: traditional MRI sequences and dynamic techniques including phase contrast MR and Time-spatial labeling inversion pulse technique (Time-SLIP) Demonstrate the utility of Time-SLIP in providing a rapid, individualized assessment of CSF flow before and after surgical treatment4IntroductionCM1 has historically been described as a change in hindbrain morphology characterized by cerebellar tonsil herniation 3-6mm* below the foramen magnum on sagittal MRI or CT images1-3However, 30 - 50% of individuals with tonsillar herniation greater than 5mm are asymptomatic4In those individuals with symptoms, the degree of herniation does not correlate well with symptom severity5Further, a subset of patients with CM1 symptoms have no tonsillar herniation, suggesting abnormal morphology alone cannot explain CM1 symptomatology6*The degree of herniation is not universally agreed upon, and depends upon age5IntroductionBoth abnormal anatomy and aberrant CSF flow dynamics contribute to the pathophysiology of CM16IntroductionSuboccipital decompressive surgery is a standard treatment for CM135-45% of patients have minimal or no relief years after surgery7,8The search for a noninvasive method of selecting patients with CM1 symptoms who will benefit from surgical intervention is an active area of research across many fields7CM1 ImagingHeadache (typically suboccipital)Neck, back, face painCape pain: neck, upper back, shouldersNonradicular limb painWeaknessDizzinessVertigoSlurred speechSyncopeDifficulty swallowingTinnitusCranial nerve:DysphagiaDysarthriaHoarsenessCoughNystagmusCerebellarAtaxiaDysmetriaBrainstemNystagmusSleep apneaSensorineural hearing lossHypertensionSinus bradycardia/tachycardiaSyncopeSpinal cordHyperactive reflexesBabinski, Hoffman reflexSpastic gaitUrinary incontinence, frequencyExtremity weakness

SymptomsSignsThe observation of cerebellar tonsillar ectopia in the absence of syrinx, hydrocephalus, or suggestive signs and symptoms has uncertain clinical significanceWhen signs and symptoms are present, neuroimaging is vital to diagnosis and management8CM1 ImagingRoutine imaging sequences are obtained to evaluate for hydrocephalus, syrinx, or other craniocervical junction (CCJ) pathologyThe midline sagittal image is used to quantify cerebellar tonsillar ectopia in relation to a line connecting the basion and opisthion (McRaes line, foramen magnum)

Menick Neurosurg focus 20019CM1 Imaging: ClassificationChiari 0: Tonsils descend 3mm or less below the foramen magnumSyrinx+/- crowding at foramen magnumChiari 1:Greater than 5mm tonsillar descent in age >15 yearGreater than 6mm tonsillar descent in age < 15 years3-5 mm is borderline, and abnormal if syrinx or symptoms4th ventricle remains in normal positionChiari 1.5:Herniation of tonsils Elongation and displacement of 4th ventricle and brainstemChiari 0 and Chiari 1.5 are controversial classifications

10CM1 ImagingDegree of tonsillar herniationTonsillar shapePosterior fossa volumePosterior fossa crowdednessLinear Posterior Fossa Measures:ClivusSupraocciutTwining lineMcRae Line

CSF velocityCSF stroke volumeTonsil and cord movementPressureResistance to flowCraniospinal compliance

Static features of CM1 - anatomy and morphology are studied with traditional MRI and CT sequencesDynamic aspects of CM1 are evaluated with CSF flow techniques and computational fluid dynamic simulations11CM1 Imaging: MorphologyThe morphologic abnormality in CM1 is diverseIn general, CM1 is characterized by:Pointed configuration of the tonsilsMore vertically oriented cerebellar foliaCrowded foramen magnumNarrowed retrocerebellar and premedullary subarachnoid spaceLower limits of normal or small posterior fossaShort clivusInferior elongation of the 4th ventricle with mildly low-lying nucleus gracilis (the demarcation of obex and central canal)40-80% of symptomatic CM1 have a syrinx4

Menick Neurosurg focus 200112CM1 Imaging: MorphologyPosterior cranial fossa (PCF) volumetry is a potential predictor of surgical outcome9,10Alpern et. al. studied 20 morphologic and physiologic measures, of which 10 were found to discriminate CM1 from healthy controls better than tonsillar herniation aloneThe three parameters that best characerized CM1:Cord displacementPosterior cranial fossa crowdednessNormalized posterior cranial fossa volumeUsing these three parameters, 37 healthy subjects and 35/36 CM1 subjects were correctly classified10

Alpern 201413CM1 Imaging: MorphologyComplex CMI (cCMI) has recently been described in the neurosurgical literature as a CMI variant with more severe clinical phenotypeRecognition by the radiologist is useful as cCMI may require more extensive or repeat neurosurgical proceduresMoore and Moore evaluated a number of morphologic measures and found that obex level was the most important differentiating factor between CMI and cCMI11Inferior herniation of the obex below the foramen magnum (FM) and a prominent dorsal bump was observed in all patients with cCMI in their studyTypical CMI is characterized by obex above or at the FM

Complex CMI: The obex lies just below the FM (arrow).

Alpern 201414CM1 Imaging: DynamicCSF dynamics in the cranial and spinal subarachnoid space may be equally important to morphology in the pathophysiology of CM1CSF velocity, resistance to flow, pressure, and craniospinal compliance cannot be measured with static MR techniquesDynamic evaluation of CSF flow has primarily been studied with 2D phase contrast MRINew techniques developed to study flow include 4D PC MRI and Time inversion recovery pulse (Time-SLIP)

Alpern 201415Abnormal morphology of cerebellar tonsils at the FM:-crowding of neural structures-narrowed subarachnoid spaceObstruction of CSF pulsationsElevated CSF velocityIncreased resistance to CSF flowAltered craniospinal complianceCranial arterial driving pressure forces same volume of CSF against obstructionIncreased pressure: over time may alter neural elasticity, permeability, water contentIncreased pressure: may further displace or damage neural structuresMorphologyHydrodynamicsIncreased pressure gradientSurgical decompression alleviates crowding, results in decreased peak CSF velocity, and alters craniocervical CSF complianceCM1 Imaging: Phase Contrast2D PC MRI in axial and/or sagittal orientation has been used to quantitatively and qualitatively evaluate dynamic CSF features such as:Direction of flowPeak CSF velocityPulse wave velocity in the subarachnoid spaceRelative timing of CSF and arterial pulsationsBefore PC MR images are acquired, maximum CSF velocity must be anticipated in order to set the Venc (velocity encoding)To optimize signal, CSF velocity should be the same or slightly below the vencVelocities above the Venc produce aliasing artifactVelocities significantly below the Venc have weak signal17CM1 Imaging: Phase ContrastMagnitude and phase images provide information about anatomy and velocityThe phase image, reflecting spin phase shifts, is the most sensitive to flowQuantitative information is acquired with images in the axial plane with through-plane velocity encoding in the craniocaudal directionQualitative features of flow are observed in the sagittal plane with in-plane velocity encodingPeripheral cardiac gating allows for collection of 12-24 phases during the repetition interval, depending on HRBy convention, bright signal reflects caudal motion during systole and dark signal represents cranial motion during diastole18

CM1 Imaging: Phase ContrastPhase images in sagittal orientation in cine mode

White flow is moving caudally during systole

Black flow is moving cranially during diastole

In this patient with CMI, there is craniocaudal flow ventral to the brainstem and upper cervical cord Craniocaudal flow dorsal to the tonsils and cord is minimal.Click to play cine clip.CM1 Imaging: Phase ContrastThe majority of studies utilizing 2D PC MRI show that CM1 is characterized by elevated peak CSF flow velocity at the foramen magnum, and that peak velocity decreases after decompressionHowever, there is not an established correlation between change in velocity and the degree of clinical improvementCM1 is characterized by inhomogeneous flow patterns and simultaneous bidirectional flow: important findings confirmed in subsequent studies using different techniques, including 4D PC MRI and computation flow models5,12,1320CM1 Imaging: Phase ContrastMcGirt et al. found that pediatric CM1 patients with normal CSF flow at the FM as assessed by PC MR were 4.8-fold more likely to experience symptom recurrence following surgery regardless of the degree of tonsillar herniation or presence of syrinx8Abnormal ventral and dorsal flow was associated with a 2.6-fold reduction in risk of symptom recurrence after surgeryThese findings support the role of inhomogeneous flow patterns in CM1 pathophysiology21CM1 Imaging: Phase ContrastTime-resolved three directional velocity encoded phase contrast MRI (4D PC MRI) is a recent advance that can better assess the three dimensional complexities of the CSF flow fieldUsing 4D PC MRI, Bunck et al. showed that in CM1, the anterior subarachnoid space (SAS) is markedly narrowed, with CSF flow diversion to the anterolateral SASThis results in flow jets with elevated velocities and flow vortices14

Coronal 4D PC MRI images in control (A) and CM1 (B). Compare uniform, homogeneous flow in A, with lateral flow diversion and left sided flow jet in B.

Bunck et al, Eur Radiology (2012) 22:1860-1870.AB22CM1 Imaging: Phase ContrastPeak CSF velocities were significantly greater at the craniocervical junction in CM1 patients than in controls, a finding in most, but not all prior studies using the 2D PC MR techniqueThe volumetric measurement facilitated by the 4D technique demonstrated variability among patients as to the level where peak systolic flow was foundInconsistent results in prior studies may relate to the inability of the 2D technique to capture the correct level for peak flow measurement23CM1 Imaging: Time-SLIPAnother recently developed MR technique applied to the study of CSF flow dynamics is Time-spatial labeling inversion pulse (Time-SLIP)Time-SLIP is based upon the arterial spin labeling conceptIn this case, instead of flowing blood, CSF is used as an endogenous tracerAdvantages over phase contrast include:Superior anatomic detail Shorter acquisition timeImproved evaluation of non periodic or turbulent flow

24CM1 Imaging: Time-SLIPFirst the background signal is suppressed with a non selective inversion recovery pulse This is followed by a second, spatially selective pulse perpendicular to the direction of flowWhen images are acquired, the labeled CSF flows into regions of suppressed background with high conspicuityCSF bulk flow can be observed for up to 5 seconds before contrast between tagged and non tagged CSF is lost25Time-SLIP

A nonselective IR pulse is applied, inverting all signal in the field of view

A second, spatially selective inversion pulse is applied to the region of interest

After a short period of time, tagged CSF is seen moving into the non-tagged background (red arrow)26CM1 Imaging: Time-SLIPTime-SLIP in CM1 after surgical decompression. The initial image (A) shows the location of the selective pulse (gold lines). Tagged CSF is bright in this slice. All other CSF is suppressed (dark). After several seconds (B) tagged CSF is seen above and below the slice (gold lines), ventral to the brainstem and cord and dorsal to the cerebellum and cord (orange arrows). *Note the exquisite anatomic detail of the images allowing precise localization of CSF flow, a significant advantage over PC MR images.

AB27CM1 imaging: Time-SLIP

In this cine clip, we watch the movement of CSF over 5 seconds. Gold lines mark the selective pulse with tagged (bright) CSFNotice the movement of CSF above and below the slice with time We observe features of flow not possible by any other technique:CSF moves from the 4th ventricle superiorly into the aqueductTurbulent flow is seen in the 4th ventricle (moving dark lines in the midst of bright CSF)CSF moves within the cervical syrinxAt the end of 5 seconds, contrast between tagged and untagged CSF is lost

Click to play cine clip.28CM1 Imaging: Time-SLIP

2D Phase ContrastTime-SLIP2D PC demonstrates the presence and direction of flow. Time-SLIP allows better visualization of location of flow, as well as periodic and turbulent flow.Click to play cine clip.Click to play cine clip.Walker 9/5 and 9/1229A. Initial imaging. Sagittal T1-W image shows ectopic, pointed cerebellar tonsils and crowding at the foramen magnum (FM).B. The preoperative Time-SLIP image demonstrates flow ventral the cervical cord (blue arrow). No flow is seen dorsal to the cord below the FM (gold arrow). Yellow lines indicate the tagged slice. All bright CSF above and below the lines has flowed from the tagged slice.C. Post decompression sagittal T2-W image reveals relief of crowding at the FM. More CSF is seen dorsal and inferior to the tonsils. A small amount of fluid is seen posterior to the duraplasty.D. Post operative Time-SLIP image again shows CSF flow ventral to cervical cord (blue arrow). There is now flow dorsal to the cord at this level (gold arrow).Case 1: 35 year-old man with 2 years of worsening headache, facial pain, and developing slurred speech. MRI demonstrated tonsillar herniation 16mm below the foramen magnum. After decompression with C1 and partial C2 laminectomies and duraplasty, the patient had marked improvement of his headaches and resolution of his facial pain.

ABCD30The pre-operative Time-SLIP image demonstrates flow ventral to the cord, but only trace flow dorsal to the cord at the tagged level (level marked by gold dots). A small amount of flow is also seen within the syrinx.

AClick to play cine clip.

BClick to play cine clip.The high intrinsic signal to noise and temporal resolution of Time-SLIP in comparison to 2D PC MRI allows visualization of CSF movement in response to respiration. Respiratory motion may have a greater effect on CSF flow than cardiac pulsation.15The post-decompression study reveals increased flow dorsal to the cord. Craniocaudal flow within the syrinx has also increased. Interestingly, there is a small amount of cranial flow of fluid within the pseudomeningocele. This may relate to respiration. Case 2: 43-year-old man with 10 year history of upper and lower extremity weakness and numbness, ataxia, increasing difficulty with fine motor control.31Case 3: 58-year-old man with complicated history of cervical stenosis with myelopathy post C6-T1 laminectomy and fusion one year ago. Increasing difficulty with gait, balance, and left leg weakness prompted imaging. He was found to have an increase in his pre-existing tonsillar ectopia. He underwent posterior fossa decompression, C1 laminectomy, and duraplasty.8/2014 and 12/2014. The patient had only partial improvement in symptoms. Time-SLIP shows that there is no flow dorsally at the FM. The brisk ventral flow is already apparent on the first image. 4 months later, the pseudomeningocele is noted to be larger. There is no change in CSF flow pattern. There is no cranial flow in the fourth ventricle, an abnormal finding.5/2014. The preoperative image shows crowding at the FM, increased from prior studies. The focus of abnormal T2 signal in the cord at C7/T1 reflects myelomalacia. The post decompression image shows relief of crowding. There is a large pseudomeningocele.

Click to play cine clip.ABCDClick to play cine clip.32

Case 4. 49-year-old woman with history of suboccipital headaches.Note the short clivus, small posterior fossa, and superiorly oriented straight sinus, typical of CM1. Crowding at the FM is minimal but there is a large cervical syrinx (Chiari 0?)

Note the change in shape of the syrinx in relation to the flow in the ventral and dorsal SAS at that level. No flow is seen dorsally at the FM. Note the cranially-directed flow through the aquaduct into the third ventricle, a normal finding.

Selective tagging pulses can be performed at multiple levels and in different orientations, as long as the slice is perpendicular to the flow direction of interest. A coronal orientation can evaluate flow between the lateral and third ventricles.Click to play cine clip.Click to play cine clip.33Time-SLIP

Investigators are currently devising methods to quantify flow velocity on Time-SLIP16PC MR and Time-SLIP provide complementary information for the characterization of pathologies with aberrant CSF flow dynamicsCSF dynamics visualized with Time-SLIP differ from classic CSF circulation theories, and the development of this method has advanced knowledge of CSF physiology A better understanding of CSF dynamics in health and disease may lead to increased diagnostic accuracy and better patient selection for surgical interventionsyamada34SummaryHistorically and currently, neuroimaging is vital to diagnosis and management of CM1The search for a noninvasive method of selecting patients with CM1 symptoms who will benefit from surgical intervention is an active area of research across many fieldsEmerging techniques such as 4D PC MRI and Time-SLIP are providing unique insights into CSF flow dynamics in CM1 and other pathologies resulting from disordered CSF flow dynamics35References1. Barkovich AJ, Wippold FJ, Sherman JL, Citrin CM. Significance of cerebellar tonsillar position on MR. AJNR Am J Neuroradiol. 1986;7(5):795-9.2.Elster AD, Chen MY. Chiari I malformations: clinical and radiologic reappraisal. Radiology. 1992;183(2):347-53.3.Milhorat TH, Chou MW, Trinidad EM, et al. Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery. 1999;44(5):1005-17.4.Osborn AG. Osborn's Brain, Imaging, Pathology, and Anatomy. Lippincott Williams & Wilkins; 2012.5.Iskandar BJ, Quigley M, Haughton VM. Foramen magnum cerebrospinal fluid flow characteristics in children with Chiari I malformation before and after craniocervical decompression. J Neurosurg. 2004;101(2 Suppl):169-78.6.Sekula RF, Jannetta PJ, Casey KF, Marchan EM, Sekula LK, Mccrady CS. Dimensions of the posterior fossa in patients symptomatic for Chiari I malformation but without cerebellar tonsillar descent. Cerebrospinal Fluid Res. 2005;2:11.7. Aliaga L, Hekman KE, Yassari R, et al. A novel scoring system for assessing Chiari malformation type I treatment outcomes. Neurosurgery. 2012;70(3):656-64.8.Mcgirt MJ, Nimjee SM, Fuchs HE, George TM. Relationship of cine phase-contrast magnetic resonance imaging with outcome after decompression for Chiari I malformations. Neurosurgery. 2006;59(1):140-6.9. Badie B, Mendoza D, Batzdorf U. Posterior fossa volume and response to suboccipital decompression in patients with Chiari I malformation. Neurosurgery. 1995;37(2):214-8.10.Alperin N, Loftus JR, Oliu CJ, et al. Magnetic resonance imaging measures of posterior cranial fossa morphology and cerebrospinal fluid physiology in Chiari malformation type I. Neurosurgery. 2014;75(5):515-22.11.Moore HE, Moore KR. Magnetic resonance imaging features of complex Chiari malformation variant of Chiari 1 malformation. Pediatr Radiol. 2014;44(11):1403-11.12.Haughton VM, Korosec FR, Medow JE, Dolar MT, Iskandar BJ. Peak systolic and diastolic CSF velocity in the foramen magnum in adult patients with Chiari I malformations and in normal control participants. AJNR Am J Neuroradiol. 2003;24(2):169-76.13. Haughton V, Mardal KA. Spinal fluid biomechanics and imaging: an update for neuroradiologists. AJNR Am J Neuroradiol. 2014;35(10):1864-9.14. Bunck AC, Kroeger JR, Juettner A, et al. Magnetic resonance 4D flow analysis of cerebrospinal fluid dynamics in Chiari I malformation with and without syringomyelia. Eur Radiol. 2012;22(9):1860-70.15. Yamada S, Miyazaki M, Yamashita Y, et al. Influence of respiration on cerebrospinal fluid movement using magnetic resonance spin labeling. Fluids Barriers CNS. 2013;10:36.16.Shiodera T, Nitta S, Takeguchi T, et al. Automated flow quantification for spin labeling MR imaging. MAGMA. 2014;27(5):425-33.36