d7.1 – ex vivo kidney and liver model with pulsatile blood ... · fusimo d7.1 – ex vivo kidney...

FUSIMO Project, 270186, 2011‐12‐30 of 20

D7.1–Exvivokidneyandlivermodelwithpulsatilebloodflowand

respiratorymotion

Authors: Timur Saliev, Helen McLeod, Alexander Volovick,

Ioannis Karakitsios, Professor Andreas Melzer

Status: Released

Date: 2011‐12‐30

Project co‐funded by the European Commission Service under the 7th Framework Programme

Dissemination Level

PU Public X

PP Restricted to other programme participants (including the Commission Services)

RE Restricted to a group specified by the consortium (including the Commission Services)

CO Confidential, only for members of the consortium (including the Commission Services)

FUSIMO D7.1 – Ex vivo kidney and liver model Released


TableofContents

VERSION HISTORY ...................................................................................................................... 2

OVERVIEW OF THE DELIVERABLE ................................................................................................ 3

DESCRIPTION OF WORK ......................................................................................................................... 3

INTRODUCTION .......................................................................................................................... 3

REPERFUSION TECHNIQUES ........................................................................................................ 4

REPERFUSION OF VENOUS AND ARTERIAL SYSTEMS ..................................................................................... 4

FORMING A CONNECTION ...................................................................................................................... 5

ARTIFICIAL ANASTOMOSIS CREATION ....................................................................................................... 8

EXPERIMENTATION OF PERFUSED LIVER MODEL ........................................................................ 9

IMAGING IN WHOLE CADAVERS SUPPORTED BY THE MRC GRANT DPFS ................................... 11

IMAGING OF TARGET ORGANS IN WHOLE EMBALMED CADAVERS ................................................................. 12

SUMMARY ............................................................................................................................... 13

EXPERIMENTAL WORK: SONICATION OF ORGAN (LIVER) OF EMBALMED CADAVER WITH MR–

GUIDED FOCUSED ULTRASOUND (MRGFUS) DURING RESPIRATORY MOTION ........................... 13

THE SIMULATION OF RESPIRATORY MOTION ON CADAVERS .................................................... 14

IMAGES OF ORGANS DURING RESPIRATORY MOTION .............................................................. 15

DESCRIPTION OF SONICATION PROCEDURE .............................................................................. 16

EXPERIMENTAL RESULTS .......................................................................................................... 17

CONCLUSION AND PLANS ......................................................................................................... 20

VersionHistory2011‐12‐30 Released as FUSIMO Deliverable 7.1



OverviewoftheDeliverable

DescriptionofWorkTask 7.1 – Development of ex‐vivo model of kidney and liver with respiratory motion and

reperfusion (M1 –M18) UNIVDUN

This task will concern the design and manufacture of the hard and software of the simulator and

includes

(i) Flow pump and choice of the pipe, connectors and sensors for flow;

(ii) Design of connecting parts to the liver portal vein, arteries and veins, Kidney arteries

and veins;

(iii) Manufacturing or required specialized connector and tubing by technicians at IMSaT;

(iv) Connection of the components (pump, compressed air, hydraulic to the anatomy);

(v) Reperfusion including thrombolectomy (removal of blood clots) and vascular occlusion

in the case of leakages;

(vi) Installation of respiratory motion and assessment of movement of organs and MR

ultrasound imaging testing;

(vii) Approval of preclinical experimental procedure for interventions and focussed

ultrasound.

(viii) Adjustment of the simulator and computer control to the findings. In this phase the

function, MRI –compatibility and signal behaviour and angiography of the bodies will

be investigated. Testing use of available prototype models, and pulsatile systems from

the other research project will be followed by testing in the 1.5T in the experimental

MRI with MRgFUS unit and angio/surgical suite at IMSaT.

The MRI compatible robotic system Innomotion which is installed at UNIVDUN and going to be

produced by IBSMM will be utilised to position the MR compatible Ultrasound system and the

mobile MRg Focused Ultrasound array CBS (ExAblate2001, Insightec). This setup would allow also

evaluating dual source sonication combining the table system and the mobile system and the

value for motion compensation.” (Seventh Framework Programme – Annex 1 –“Description of

work”, FUSIMO, pp27).

IntroductionThe primary aim of deliverable WP 7.1 was to develop an ex‐vivo liver (and kidney model: at the

kick off meeting 1st March 2011 in Dundee the consortium decided to work primarily on liver) with

respiratory motion and reperfusion. UNIVDUN has successfully achieved the key elements of this

deliverable, with some alterations due to insurmountable problems with certain aspects of the

Thiel embalmed cadavers, and the more specific direction of the project as agreed by the

consortium which has evolved over time guiding the direction of this research toward the liver as

primary target organ.

UNIVDUN has developed the required ex vivo model with perfusion on a Thiel embalmed cadaver

liver. The experience gained has been used to establish these techniques of perfusion to be

combined with respiratory motion in whole embalmed cadavers.



Establishing the model with the liver and kidney conjoined, in the explanted embalmed organs has

been problematic (as described in the description of work). The liver and right kidney are “joined”

in the human body by the hepato‐renal ligament, and the surrounding anatomy such as the

vasculature of these systems, peri‐renal fat, diaphragm and intestine. The removal of the liver and

kidney from a cadaver to produce the individual organ destroys these structures; therefore, the

close geographical association between the two organs and the biological attachments are lost. To

reconstruct the functional and natural relationship between the two organs artificially has as yet

been impossible, and for the purposes of the project, considered inappropriate. Aside from the

time and cost, the development of an artificial structure would require, it was hypothesized that

this structure would not necessarily imitate the natural in vivo structure and would possibly

introduce air or other impermeable barrier which would prohibit the successful use of MRgFUS,

which is ultimately the purpose of developing this model. This rationale has driven the focus of

the experimentation within UNIVDUN to the development of the “model” within a whole, intact

embalmed cadaver; with the explanted organ models developed being separate liver and kidney

models.

In addition to the difficulty simulating the anatomical relationship between the liver and kidney,

the FUSIMO consortium agreed that the primary focus of the project would be to develop the liver

model(FUSIMO Kick off meeting Dundee, 1st March 2011, and annual Project Meeting Tel Aviv, 12

– 13th September 2011). Therefore, the focus of the UNIVDUN group has been to establish the

fully functional cadaver, which will fulfil the project requirements adequately.

This report details the methodology developed at UNIVDUN to fulfil the deliverable requirements.

ReperfusionTechniques

ReperfusionofvenousandarterialsystemsTo establish any perfusion of embalmed tissue, there has to be a mechanism of transferring fluid

from an external source into the tissue. To achieve this, UNIVDUN has developed various devices

and techniques to gain access to the blood vessels and to simultaneously connect to a source of

fluid, either mechanical such as a flow‐rig or a manual or gravitational perfusion source. The

devices which make a connection to the tissue to produce perfusion or flow, form an anastomosis,

between a synthetic tube and the embalmed blood vessel, essentially an artificial anastomosis.

The key problem to overcome was that cadaver tissue does not heal and that there is no blood

clotting mechanism that facilitates the sealing of vascular connections and leakages.

The development of these specialised connectors and tying techniques has facilitated the

development of fluid delivery into the blood vessels and demonstrated perfusion within target

tissues within explanted organs such as liver. These techniques have also been used in whole

embalmed cadavers to perfuse targeted organs such as liver and kidney. The types of flow or

“reperfusion” that is created are varied and can be selected according to the experimental aim.

Three primary methods have been developed.

Manual flow: a continuous slow flow which is physically pushed by the researcher using a

device such as a syringe. This has been used to perfuse contrast media, X‐ray or MR

contrast into the target tissue. This can also be used in conjunction with gravitational flow



or pump derived flow to deliver bolus of required fluid. Fig 1 show an explanted organ

with syringes attached to deliver flow to allow X‐ray to be taken.

Gravitational flow: a reservoir of the perfusate that is driven by gravity down to the target

tissue.

Pump driven flow: pump system such as Braveheart (Fig2) can introduce continuous or

pulsatile flow into blood vessels. This technique has been established in small vessels such

as the superficial femoral artery. Future plans at UNIVDUN are to introduce flow into the

entire vasculature of cadaver; this will require more pump development to achieve this

aim.

Figure 1. a) Flow established through the explanted embalmed liver via hepatic artery. b) Visualised on GE

OEC9900 C‐Arm via X‐ray spot and Digital Subtraction Angiography using 50% diluted Ultrasvist (Schering)

Figure 2. Braveheart Flow‐rig. a) Braveheart flow‐rig has been modified allows MR; Ultrasound and X‐ray

imaging and blood mimicking fluids to be pumped at various velocities, with continuous flow or pulsatile

flow delivered in specific waveforms into the target tissue. b) The pump can be connected to the

artificialanastomosis developed at IMSaT to re‐perfuse embalmed cadaver organs.

FormingaconnectionTo facilitate reperfusion with the aim to reproduce physiological flow in vasculature of embalmed

organs and whole embalmed cadavers, the following process and equipment was developed at

UNIVDUN. The images demonstrate the method of connecting a vessel (either artery or vein) to a

synthetic tube soft silicone and sealed with modified cable ties. The tube is connected to either a

gravitational, manual device or a flow rig to create the flow. This connection is a synthetic



anastomosis, essentially a connection formed between two tubes, one silicone (other materials

can be selected depending upon the properties required) and one embalmed blood vessel.

Figure 3. a) Modified Silione Tubing which is the basis of the artificial anastomosis. Tubing of various sizes

has been used to provide access to vasculature (3, 5 and 7mm). The image above is of 5mm internal

diameter tubing. b) This tubing is adapted by the addition of two mounts, the blood vessel is pushed along

passed both mounts and a cable tie is used in between these two mounts to secure the vessel and secure

the anastomosis.

Coupling mounts sealed with silicone



Figure 4. a) Check‐Flo 12Fr and Check‐Flo 16Fr introducer sets (Cook Medical, Bloomington, USA) each

adapted and then joined to manufacture the artificial anastomosis with the cadaver vessel b) which has the

tube to make an external connection to a flow device.

The two vascular access devices have been modified and joined to form the access. This

adaptation also has the advantage of having a port to add fluids such as contrast medium

depending on the desired effect.

These innovative solutions have enabled a system of perfusion of embalmed organs and sections

of whole embalmed cadavers.

12Fr and 16 Fr altered and joined to provide vascular access and connection for pump tubing

PTFE tape to make secure seal with flow‐rig connection tubes

Part of 16Fr Introducer set

12 Fr Sheath set (with introducer port present). Blue section of sheath cut short to reduce length in vessel.

port



ArtificialAnastomosisCreationThe technique developed has been used to create an artificial anastomosis, in most cases between

the proximal vessel and the silicone tubing. Depending upon the type of tissue and the

experimental aim, the anastomosis is secured with cable ties or sutures, depending upon the

pressure created from flow, and the resilience of the tissue to withstand the pressure created by

cable tie. The following images show the process for connecting an explanted embalmed liver.

Image shows insertion of silicone tube (7mm internal diameter) into the inferior vena cava, using

the guide‐wire.

Figure 5. Location of inferior vena cava. The

inferior vena cava is located and has guide‐wire

inserted to allow the artificial anastomosis to be

formed with the silicone tubing (7 mm internal

Figure 6. Insertion of connection to vessel. Synthetic

anastomosis formation between silicone tubing and

inferior vena cava of embalmed human liver

Figure 7. Anastomosis is secured to vena cava: it is sealed

using cable ties in this example. The pipes can be

attached to return to the pump reservoir in a similar

fashion to venous blood returning to the vena cava.

Figure 8. Artificial Anastomosis of liver portal vein:

synthetic anastomosis formation between portal artery

and silicone tubing.



Figure 9. a) Preparation of synthetic anastomosis in hepatic artery of embalmed liver. Small yellow cable tie

is used to secure anastomosis and allows easy identification of the hepatic artery; b) Balloon catheter used

for intra hepatic sealing of branches.

A balloon catheter can be inserted to seal right or left hepatic artery for selective filling of the

respective live lobe. This technique similar to super selective catheterization will used in the whole

cadaver and allow embolization to provide marking of a liver territory for sonication.

Currently these techniques and equipment have been successfully used in explanted embalmed

liver. The explanted organs have the advantage of having blood vessels which are easily accessed

for this technique (providing they have been excised sympathetically to permit easy access).

Arguably, this approach does not fit as easily in the whole cadavers, where normally all the blood

vessels are internal and a vessel has to be excised and exposed to gain access in this fashion.

Deeper vessels cannot be accessed to prepare this anastomosis without resulting in damage to the

cadaver, which is at times possible, depending upon the “life‐cycle” of the cadaver. However, in

most cases it is not desirable to create a huge amount of damage to get access to vessels near the

target organ the liver. Currently the approach selected is determined by the experimental aim,

UNIVDUN has successfully accessed the liver and kidneys of whole cadavers via the femoral artery

with guide‐wires and other radio‐graphical interventions, to produce both X‐ray contrast images

and MR images.

In addition interventional radiological techniques have been assessed and established to

catheterize liver veins and hepatic artery and renal arteries, for selective perfusion of organs,

described in the next section.

ExperimentationofperfusedlivermodelOnce the vascular access was established the explanted liver was prepared for perfusion. In this

model, the liver has been perfused with manual flow, which allowed DSA angiograms to be

prepared. The characteristics of hepatic flow and portal flow are being researched, once

identified; experimentation can begin to re‐create the desired flow and filling of the liver.

Manual reperfusion using syringes ranging from 2.5ml to 50ml have been used to re‐perfuse the

tissue using the above connections. This has allowed DSA series to be produced and with the

further development of the MR techniques to image tissue this future work will enable the

identification of landmarks, essential to the development of the liver model by other groups in the

consortium.



Figure 10. a) Digital Spot Angiogram of cadaver embalmed liver. X‐ray contrast (Omnipaque 300, GE

Healthcare, Princetown, USA), 50:50 dilutions with Thiel fluid, perfused via the portal vein to the liver tissue.

b) DSA post perfusion image

Figure 11. a) Partialperfusion ofright liver lobevia righthepatic artery selective catheterization with balloon

catheter. b) DSA post perfusion image (Omnipaque 300, GE Healthcare, Princetown, USA), 50:50 dilution

with Thiel Fluid)

This image shows hepatic artery perfusion, of the right liver lobe and sub‐segment so only a small

portion was visualised by the X ‐ray contrast. The image shows a PTA balloon catheter which is

being used to seal the arterial branch. This technique will be further explored to selectively mark

certain liver areas for sonication.

This image demonstrates the success of the catheterization technique. During the experiment the

artery was sealed using a 4 cm PTA balloon catheter (TEGwire, Medi‐tech,Boston Scientific,

Watertown). Standard radiological techniques have been successfully used at IMSaT to remove

coagulations, to block leaking and vessels and to direct flow, to the target tissue. These

techniques have been established in both explanted organs and whole cadaver tissue.



ImaginginwholecadaverssupportedbytheMRCgrantDPFSUsing the flow connectors previously described (Fig. 3, Fig. 4) to produce an artificial anastomosis,

to the embalmed blood vessels has been successful in full cadavers. Initial experimentation

selected the superficial femoral artery of whole cadavers as it allows easy access and causes

minimal damage to the cadaver.

After this preparation the artificial anastomosis can be connected to a source of flow. Many

experiments have used the Braveheart pump to create pulsatile flow in a femoral waveform. The

following figures show X‐ray contrast of flow in the superficial femoral artery of whole cadavers.

Figure 14. a) Digital Spot imaging of Xray contrast enhanced left superficial femoral artery of a whole

embalmed cadaver b) DSA (Omnipaque 300, GE Healthcare, Princetown, USA), 50:50 dilution with Thiel

fluid

Figure 12. The proximal and distal artificial anastomosis to

the superficial femoral artery in whole cadaver

Figure 13. A close‐up image of the distal artificial

anastomosis



The technique of accessing the superficial femoral artery in whole cadavers has been established

at UNIVDUN in the MRC funded DPFS project. This vessel was selected for initial experimentation

because of the relative ease of access, the minimal trauma to cadaver, the vessel size, (diameter is

approximately 4 – 6 mm. The adapted Check Flo Introducers (size 12 Fr and 16 Fr, Cook Medical,

Bloomington, USA) allow a direct connection between the Braveheart flow‐rig and the blood

vessel. This has allowed pulsatile flow to be established and both angiographic, and 1.5 T MR

images of this vessel to be obtained.

The further development of flow in whole cadaver liver is planned at UNIVDUN for the next stage

of the project.

Imagingoftargetorgansinwholeembalmedcadavers

Figure15. a) X‐ray contrast digital spot image of left accessed by “standard” radiological techniques

b)DSA(Omnipaque 300, GE Healthcare, Princetown, USA), 50:50 dilution with Thiel fluid

The arterial system of the left kidney of an embalmed cadaver was accessed from the right

superficial femoral artery using a guide‐wire ( TEGwire, Medi‐tech,Boston Scientific, Watertown).

The aorta was accessed via the right superficial femoral artery. This vessel was perfused with fluid

and contrast until the left kidney was reached. The X‐ray contrast was injected to visualise the

arterial system of the kidney. In a similar manner selective catherization of the kidney arteries can

take place to mark certain areas for sonication



SummaryIn summary, both the reperfusion of embalmed organs and targeted organs within whole

embalmed cadavers has been achieved. Improvements to these techniques are planned,

particularly in the whole cadaver which is the primary focus of research. UNIVDUN plans to

develop a method of reperfusing the liver in a whole intact embalmed cadaver over a longer

period of time, to improve the MR imaging which is pivotal to the liver model development.

Experimentalwork:Sonicationoforgan(liver)ofembalmedcadaverwithMR–guidedFocusedUltrasound(MRgFUS)duringrespiratorymotionObjectives:

Improve cadaver MR planning imaging properties.

Improve cadaver MR thermal feedback.

Assess feasibility of trans‐costal sonications to liver using embalmed Cadavers.

Assess possible treatment techniques (to sonicate with the lungs full of air ‐> increasing

trans‐costal space vs no air in lungs).

Assess feasibility of using the Body (UF) system for trans‐costal treatments.

Cadavers: Thiel embalming technique makes the cadaver an ideal model for validation, testing and

training of the MRgFUS technique with the ExAblate system due to its distinctive properties such

as life‐like colouring, muscle‐joint flexibility and relative long‐time preservation.Four embalmed

cadavers were used for the experiments.

Equipment:

MRI GE Signa 1.5 Tesla (Figure 16)

High Intensity Focused Ultrasound (HIFU) of Conformal Bone System (CBS) ExAblate 2100

and ExAblate 2000 system(InSightec, Haifa, Israel) (Figure1).

Figure 16.a) The HIFU ExAblate2100 Conformal Bone System (CBS). b) The HIFU ExAblate2000system

(InSightec, Haifa, Israel)



ThesimulationofrespiratorymotiononcadaversThe ventilation technique of embalmed cadaver (under MR‐control) has been established at

UNIVDUN in the MRC funded DPFS project. For that purpose, the cadavers were intubated by

using laryngoscope with Macintosh blade and endotracheal tube (size 7 or 8) (Figure 17). The

orotracheal route was used for intubation, where the tube was inserted through the mouth and

then the vocal cords into trachea.

Figure 17. a) Laryngoscope with Macintosh blade and cuffed endotracheal tube b) Manual resuscitator

(Ambu® SPUR® II, UK) to establish breathing motion in embalmed cadavers. The user can easily apply

constant and uniform compression, through the compression bag, allowing air pass through the tube inside

the body.

After this, the tube was connected to a bag‐resuscitator (Ambu® SPUR® II, UK) for manual

ventilation, imitating breathing motion of a human body (Figure17).

As to confirm the placement of endotracheal tube the cadaver’s lungs were inflated under MR‐

supervision.

After visual MR‐confirmation of correct position, the tube was fixed and experiment was

performed.

During experiments, free breathing and breath‐hold imaging methods were used. The MR images

demonstrated an excursion of lungs along with organ displacement during breathing cycle

(Fig.18and 19).

Besides of manual breathing, it is planned to use the portable MR‐compatible ventilator VentiPAC

200 D (PneuPAC Ltd, UK) for further experiments.



Imagesoforgansduringrespiratorymotion

Coronal MR images

Figure 18. a) lung during inhalation phase; b) exhalation phaseMR parameters: Echo Time (TE) = 1.68 msec,

Repetition Time (TR) = 5.976 msec. Slice thickness= 8 mm, spacing = 8 mm, and an acquisition matrix of 256

x 256. Liver has been shifted during respiration cycle

Axial MR images

Figure 19. lung during a) inhalation phase; b) exhalation phaseMR parameters: Echo Time (TE) = 1.68 msec,

Repetition Time (TR) = 5.976 msec, and FOV= 480mm x 480mm. Slice thickness= 8 mm, spacing = 8 mm, and

an acquisition matrix of 256 x 256.



DescriptionofsonicationprocedureMRI provides an ability to locate abnormal tissue and precise positioning of the HIFU transducer

over a desired site. After obtaining MR images the P (posterior), S (superior), and R (right)

coordinates of the transducer can be derived and accurately located so as to avoid the beam

passing through obstacles (air or ribs), which would reflect the ultrasound signal. Stitches and

implants also need to be excluded from the beam path.

Two types of HIFU transducers were used for sonication: ExAblate 2100 Conformal Bone

System(Figure 21) and ExAblate 2000 Body (UF) system (Figure 22).

Figure 20. a) The HIFU water transducer (ExAblate2100, InSightec, Haifa, Israel) b)The HIFU transducer is

covered with plastic transparent film to avoid contact with fluid.

Figure 21. a) The UF table, where the interface has been created, with coupling gel, phantom, and degassed

water. b) Maximized picture of the interface. ‘Pillows’ have been placed at the sides to facilitate the moving

of cadavers on the table.

For each cadaver (4 in total) the sonication procedure was performed in the following order:

After establishing the respiratory motion and planning MR imaging, the liver was sonicated at two

different breath holding positions: lungs full (with air) and empty lungs. The experiments were

repeated both for Conformal Bone (ExAblate 2100) and Body (ExAblate 2000) systems.



ExperimentalResults1. The optimal parameters for the embalmed cadavers MR imaging were identified as:

a. Planning imaging: Fast Spoiled Gradient Echo (FSPGR), TE=min, TR>1000msec. It

was established that the Bandwidth (BW) value plays a crucial role in optimization

of image quality (up to 5kHz). This is basically proton density imaging with short

BW. The short BW results in long scanning time, which makes this technique

unsuitable for real time imaging. Planning images using 8channel body coil (with

CBS) and Single channel InSightec Pelvic coil (with the Body system) are presented

in Figures 20and 21 respectively.

b. Temperature measurements Pelvic Coil: for the thermometry mapping using the

body system, the lowering BW made a significant difference (Figure 22), However,

it increased the acquisition time to 20.5 sec (instead of 3.5sec). We are using long

time sonications with small power, to reduce cavitation activity; such long

acquisition time is tolerable.

c. Temperature measurements 8ch body coil: Using standard InSightec EPI protocol

for 3 slices scan provided acceptable images (Figure 24).

2. We have observed heating of the liver behind the rib‐cage using both (CBS and Body HIFU)

systems. For the same acoustic powers the heating of the Body system (UF) is higher (as

expected) due to high ultrasonic frequency (1 MHz).

3. Sonication through the rib‐cage without elements closure causes the rib heating. In this

case, the heat of the ribs by the body system is higher due to higher energy density on the

ribs.

The positions of HIFU transducer relative to organ‐target (liver) are depicted on Figures22and 23:

Figure 22. Planning imaging using 8ch body coil and CBS system.Scan parameters: FSPGR, BW=5kHz,

TE=3.8msec, TR=400msec

HIFU

transducer

Liver



Figure 23. Planning imaging using InSightec Pelvic coil and Body system. Scan parameters: FSPGR, BW=2kHz,

TE=7.5msec, TR=600msec.

The sonication of liver and temperature rise at the focal point (liver) are presented on figures 24

and 25:

Figure 24:Typical trans‐costal sonication, using the Body system a) Thermal map of the sonication. b)

Magnitude image of the sonication. c) Thermal rise in the focus.

a

b

c

HIFU

transducer

Liver

Rib



Figure 25. Typical trans‐costal sonication, using the CBS system: a) Thermal map of the sonication.

b) Magnitude image of the sonication. c) Thermal rise in the focus.

a

b

c



ConclusionandplansThe functional cadaver model has been established at UNIVDUN, which incorporates the

respiratory motion and reperfusion of embalmed organs. The experiments with MR‐guided high‐

focused ultrasound ablation of abdominal organ demonstrated feasibility and reliability of Thiel

embalmed cadavers as a preferable model for validation studies.

The next steps will involve the sonication of explanted tissue followed by the assessment and

monitoring of thermal effect so as to optimize the treatment protocol. It will include evaluation of

heat conductivity, acoustic propagation and impedance. The effect of blood perfusion and

absorption rate on ultrasound treatment will be assessed as well. After establishing the model for

extracted organ, the experiments for sonication of perfused organ inside the cadaver will be

performed (Fig.26). In this case, the liver will be connected to the perfusion machine for simulation

of pulsatile flow, while the lungs will be inflated in a controlled manner. This set‐up will provide

the perfect model of respiratory organ motion for further validation of ultrasound treatment.

Figure 26. Sonication of perfused liver inside the body with combination with lungs ventilation.

Acoustic Energy

Heating effect

Organ perfusion machine

Lungs ventilation

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