BARKER
MASSACHUSES $sTITUTE
OF TECHNOLOGY
OCT 2
2002
I I

In Vivo Characterization of the Mechanical Behavior of
Intra-Abdominal Tissues for Surgical Simulation by
Boon Kiat Tay
Submitted to the Department of Mechanical Engineering on
January 18, 2002 in Partial Fulfillment of the Requirements for the
Degree of Master of Science in Mechanical Engineering
Abstract
For a surgical simulator to function effectively as a trainer, in vivo material properties of biological tissues are required for simulating the deformations and the reaction forces from the virtual tool-tissue interactions. In this thesis, the in vivo static and dynamic mechanical properties of the liver and lower esophagus of pigs were characterized for surgical simulation. These organs were characterized in their linear and non-linear regions under compressive and shear loadings.
The Phantom was programmed to function as a mechanical stimulator with a 2mm flat-tipped cylindrical probe attached to its tip. A series of ramp and hold as well as sinusoidal indentation stimuli were delivered to the organs and reaction forces measured. The conditions for these indentation stimuli were designed such that they are similar to conditions in an operating room.
Experiments were also carried out on the organs for ex vivo and in-vitro conditions.
Results from experiments show that breathing and pulse rate of the animal significantly affects the organ force responses. From the force-displacement relationships obtained, steady state stiffness and impedance as well as power dissipation rates of both the organs were inferred.
Results show that in vivo steady state stiffness of the lower esophagus is significantly higher than that of the liver. The in vivo steady state stiffness of the liver however, exhibits greater degree of non-linearity than that of the lower esophagus. In vivo steady state stiffness of the lower esophagus in the three orthogonal directions also do not indicate that the lower esophagus is significantly anisotropic. The impedance and power dissipation loss of both organs to dynamic indentations are fairly similar. Magnitudes of the impedance over the stimulus frequencies are fairly constant. The impedance phase angles decrease and power dissipation rate increase over the range of stimulus frequencies applied.
Comparing between the measurements obtained from the in vivo, ex vivo and in-vitro experiments show that mechanical properties of biological tissues change significantly after the death of the animal. The tissues generally become stiffer and exhibit greater non-linearity. The degree of change in their mechanical properties is dependent on the amount of time after the death of the animal.
Thesis Supervisor: Dr. Mandayam A. Srinivasan
Title: Principal Research Scientist

I would like to thank all those who have helped to contribute to the successful completion of this thesis in one way or another:
My advisor, Srini for giving me the guidance and opportunity to work in the Touchlab. The past one and a half year has been the most enriching and fulfilling.
The staff at the Harvard Center for Minimally Invasive Surgery, Jeff and Cindy for helping me out with my experiments.
Nick, for all his help in setting up in each and every experiment and making sure that they were able to proceed smoothly. Special thanks go out to him.
All my lab-mates who have made the lab a more enjoyable and conducive place to work in. In particular, Raju for all the help on Matlab. Jung, Mani, Hyun and Louis for all the enriching and stimulating discussions on both lab-related and unrelated topics.
Kathy, for her continual encouragement and motivation
Last, but not least, my parents for their unrelenting support and the Singapore EDB-PLE scholarship program for funding my stay at MIT and undergraduate work at UIUC.
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A bstract ..............................................................................................................................
A cknow ledgem ents......................................................................................................
Table of Contents ........................................................................................................
List of Figures....................................................................................................................5
List of Tables....................................................................................................................10
Chapter 1..........................................................................................................................11
1.1 Introduction ....................................................................................................
1.2 Previous W ork................................................................................................
11
13
Chapter 2..........................................................................................................................20
2.1 Experim ental Setup ......................................................................................
2.2 Indentation Stim uli.........................................................................................
2.3 Experim ental Procedure ...............................................................................
C hapter 3..........................................................................................................................27
3.1 Results from Ramp and Hold Indentation Stimuli....................27
3.1.1 Force Responses to Ramp and Hold Indentations................................. 28
3.1.2 Variations in Force Responses to Ramp and Hold Indentations ........... 38
3.2 Results from Sinusoidal Indentation Stim uli .................................................... 43
3.2.1
3.2.2
Force Responses to Sinusoidal Indentations ........................................ 43
Variations in Force Responses to Sinusoidal Indentations ................... 46
Chapter 4..........................................................................................................................51
4.1 Static M echanical Behavior ...........................................................................
4.2 D ynam ic M echanical Behavior ....................................................................
4.3 Sum m ary of D ata ...........................................................................................
20
21
23
51
58
64
Chapter 5..........................................................................................................................67
5.1 Conclusions ....................................................................................................
5.2 Future W ork .................................................................................................
67
69
2
3
4
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Figure 1.1: Dundee Single Point Compliance Probe (Carter et al., 2000). ......................... 15
Figure 1.2: The Force Feedback endoscopic Grasper with a Babcock grasper (Carl Storz Inc., m odel #30420 BL, H annaford et al., 1998). .............................................................................. 16
Figure 1.3: The instrumented endoscopic surgical grasper (Rosen et al., 1999).................16
Figure 1.4: Uniaxial tensile machine (Brouwer et. al., 2001). ........................................... 17
Figure 1.5: Intra-abdominal organs and their locations in the human abdominal cavity. The left lobe of the liver in this figure covers the lower esophagus and the esophagogastric junction.
........................................................................................................... . . .. 1 8
Figure 1.6: The esophagus and stom ach .............................................................................
F igu re 1.7 : T h e liver ................................................................................................................
19
19
Figure 2.1: Schem atic of equipm ent setup........................................................................... 21
Figure 2.2: Input signal to the Phantom for ramp and hold indentation stimuli. (a) ramp velocity =8 mm/s, displacement =8 mm; (b) ramp velocity =6 mm/s, displacement =6 mm; (c) ramp velocity =4 mm/s, displacement =4 mm; (d) ramp velocity =2 mm/s, displacement =2 mm;
(e) ramp velocity =1 mm/s, displacement=1 mm.................................................................... 22
Figure 2.3: Input signal to the Phantom for 2.0 Hz indentation stimuli, superimposed over a pre-indentation of 6mm. This is the typical form for all sinusoidal input signals. .................. 23
Figure 2.4: Experimental setup for in vivo and ex vivo experiments...................................24
Figure 2.5: Force response of liver. Large peaks in the force response are forces generated from motions of the animal due to breathing. The smaller sinusoidal pulses along the force response are due to the forces generated from the pulse rate of the animal superimposed on the force response. ......................................................................................... . . 25
Figure 3.1: Traces of Phantom displacements for ramp and hold indentation. (a) ramp velocity=8 mm/s, displacement=8 mm; (b) ramp velocity=6 mm/s, displacement=6 mm; (c) ramp velocity=4 mm/s, displacement=4 mm; (d) ramp velocity=2 mm/s, displacement=2 mm; (e) ramp velocity=1 m m /s, displacem ent=1 m m . ................................................................................... 28
Figure 3.2: In vivo force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm; (c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm; (e) velocity of indentation=1 mm/s, depth of
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indentation=1 mm. Raw data is shown in the top panel and the effect of pulse filtered from the force response in the bottom panel........................................................................................... 29
Figure 3.3: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the Z-direction. Plots have the same format as Figure 3.2.................................................... 29
Figure 3.4: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the X-direction (across outer muscular fibers). (a) velocity of indentation=6 mm/s, depth of indentation=6 mm; (b) velocity of indentation=4 mm/s, depth of indentation=4 mm; (c) velocity of indentation=2 mm/s, depth of indentation=2 mm; (d) velocity of indentation=1 mm/s, depth of indentation=1 mm. Raw data is shown in the top panel and the effect of pulse filtered from the force response in the bottom panel........................................................................................... 30
Figure 3.5: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the Y-direction (along outer muscular fibers). Plots have the same format as Figure 3.4........30
Figure 3.6: Ex vivo force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation= mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm; (c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm; (e) velocity of indentation=1 mm/s, depth of in den tation = 1 m m . ........................................................................................................................ 3 1
Figure 3.7: Ex vivo force responses of lower esophagus to ramp and hold indentation stimuli.
Plots have the sam e form at as Figure 3.6.................................................................................. 31
Figure 3.8: Frequency spectrum of the in vivo force response of liver for ramp and hold indentation at 8mm. Peak at approximately 1.4 Hz corresponds to the main frequency component of the sinusoidal variations due to the pulse rate of the animal. .............................................. 32
Figure 3.9: Frequency spectrum of the ex vivo force response of liver for ramp and hold in den tation at 8 m m ....................................................................................................................... 32
Figure 3.10: In-vitro force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm; (c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm; (e) velocity of indentation=1 mm/s, depth of indentation= 1 m m . ..................................................................................................... 33
Figure 3.11: In-vitro force responses of lower esophagus to ramp and hold indentation stimuli in the Z-direction. Plots have the same format as Figure 3.10......................................34
Figure 3.12: In-vitro force responses of lower esophagus to ramp and hold indentation stimuli in the X-direction. (a) velocity of indentation=6 mm/s, depth of indentation=6 mm; (b) velocity of indentation=4 mm/s, depth of indentation=4 mm; (c) velocity of indentation=2 mm/s, depth of indentation=2 mm; (d) velocity of indentation=1 mm/s, depth of indentation=1 mm. .. 34
Figure 3.13: In-vitro force responses of lower esophagus to ramp and hold indentation stimuli in the Y-direction. Plots have the same format as Figure 3.12. .................................... 35
Figure 3.14: In vivo force responses of lower esophagus to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=1 mm/s, depth of indentation=8 mm; (c) velocity of indentation=6 mm/s, depth of indentation=6 mm; (d) velocity of indentation=2 mm/s, depth of indentation=6 mm..............37
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Figure 3.15: In vivo force responses of the liver to ramp and hold indentation stimuli. Data was obtained from experiments conducted on A2, A4, A5, A6 and A7 (data from 5 animals).
Depth of indentation = 8 mm, velocity of indentation = 8 mmIs (top row), depth of indentation =
6 mm, velocity of indentation = 6 mm/s (second row), depth of indentation=4 mm, velocity of indentation=4 mm/s (third row), depth of indentation =2 mm, velocity of indentation=2 mm/s
(fourth row), depth of indentation=1 mm, velocity of indentation=1 mm/s (bottom row). Force responses are shown with the effect of pulse filtered................................................................ 39
Figure 3.16: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Z-direction. Data was obtained from from experiments conducted on A3, A4, A5 and A6 (data from 5 animals). Plots have the same format as Figure 3.15...............................40
Figure 3.17: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the X-direction. Data was obtained from experiments conducted on A4, A5 and A6
(data from 3 animals). Depth of indentation = 6 mm, velocity of indentation = 6 mm/s (top row), depth of indentation = 4 mm, velocity of indentation = 4 mm/s (second row), depth of indentation = 2 mm, velocity of indentation = 2 mm/s (third row), depth of indentation = 1 mm, velocity of indentation = 1 mm/s (bottom row). Force responses are shown with the effect of pulse filtered . ........................................................................................... . . 4 1
Figure 3.18: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Y-direction. Data was obtained from experiments conducted on A4, A5 and A6
(data from 3 animals). Plots have the same format as Figure 3.17. ......................................... 42
Figure 3.19: Trace of the Phantom displacement for 2.0 Hz indentation, superimposed over a pre-indentation of 6mm. This is the typical form for sinusoidal indentation stimuli.............43
Figure 3.20: In vivo force responses (left column) and force-displacement profiles (right column) of liver to sinusoidal indentation at 3.0 Hz (top row), 2.0 Hz (second row), 1.0 Hz (third row ) and 0 .5 H z (bottom )..............................................................................................................44
Figure 3.21: In vivo force responses (left column) and force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 2.0 Hz (top panel), 1.0 Hz (middle panel) and 0.5 H z (low er panel). .............................................................................................. 44
Figure 3.22: In vitro force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 3.0 Hz (top row), 2.0 Hz (second row), 1.0 Hz (third row) and 0.5 Hz (bottom row).................................................................... 45
Figure 3.23: In vitro force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation stimuli at 3.0 Hz (top row),
2.0 Hz (second row), 1.0 Hz (third row) and 0.5 Hz (bottom row)........................................... 45
Figure 3.24: In vivo force response (left column) and corresponding force-displacement profile (right column) of liver to sinusoidal indentation at 3.0 Hz. Data was obtained from experiments conducted on A6 (data from 1 animal) ................................................................. 46
Figure 3.25: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 2.0 Hz. Data was obtained from experiments conducted on A4, A6 and A7 (data from 3 animals)..........................................47
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Figure 3.26: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 1.0 Hz. Data was obtained from experiments conducted on Al, A4, A6 and A7 (data from 4 animals)....................................47
Figure 3.27: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 0.5Hz. Data was obtained from experiments conducted on Al, A4, A6 and A7 (data from 4 animals)....................................48
Figure 3.28: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 3.0 Hz. Data was obtained from experiments conducted on A3 and A4 (data from 2 animals). ......................................... 48
Figure 3.29: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 2.0Hz. Data was obtained from experiments conducted on Al, A3, A4 and A6 (data from 4 animals). ........................... 49
Figure 3.30: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 1.0 Hz. Data was obtained from experiments conducted on Al, A3, A4 and A6 (data from 4 animals). ........................... 49
Figure 3.31: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 0.5Hz. Data was obtained from experiments conducted on Al, A3, A4 and A6 (data from 4 animals). ........................... 50
Figure 4.1: In vivo steady state stiffness of the liver (data from 5 animals)............52
Figure 4.2:
5 animals).
Figure 4.3:
3 animals).
In vivo steady state stiffness of the lower esophagus in the Z-direction (data from
.......................................................................................... . . .. 5 3
In vivo steady state stiffness of the lower esophagus in the X-direction (data from
.......................................................................................... . . .. 5 3
Figure 4.4:
4 animals).
In vivo steady state stiffness of the lower esophagus in the Y-direction (data from
........................................................................................... . .. 54
Figure 4.5: Ex vivo steady state stiffness of the liver (data from 2 animals). ............ 54
Figure 4.6:
4 animals).
Ex vivo steady state stiffness of the lower esophagus to displacements (data from
........................................................................................... . .. 5 5
Figure 4.7: In-vitro steady state stiffness of the liver. Data was obtained from experiments conducted on A5, A6 and A7 (data from 3 animals). .............................................................. 55
Figure 4.8: In-vitro steady state stiffness of the lower esophagus in the Z-direction. Data was obtained from experiments conducted on A5, A6 and A7 (data from 3 animals). ................... 56
Figure 4.9: In-vitro steady state stiffness of the lower esophagus in the X-direction. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals). ......................... 56
Figure 4.10: In-vitro steady state stiffness of the lower esophagus in the Y-direction. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals). ................... 57
Figure 4.11: In vivo impedance of the liver (data from 4 animals). .................................. 59
Figure 4.12: In vivo impedance of the lower esophagus (data from 4 animals)................60
Figure 4.13: In vivo power dissipation of the liver (data from 4 animals).........................60
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Figure 4.14: In vivo power dissipation of the lower esophagus (data from 4 animals).........61
Figure 4.15: In vitro impedance of the liver. Data was obtained from experiments conducted on A 6 and A 7 (data from 2 pigs)................................................................................................ 61
Figure 4.16: In vitro impedance of the lower esophagus. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals)..................................................62
Figure 4.17: In vitro power dissipation of the liver. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals). ..................................................................... 62
Figure 4.18: In vitro power dissipation of the lower esophagus. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals)..................................................63
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Table 2.1: Conditions for ramp and hold indentation stimuli. ............................... 22
Table 2.2: Indentation stimuli applied to both organs for different experimental co n d itio n s. ........................................................................................... 2 6
Table 4.1: Summarized values for the liver under different experimental conditions.
Table on the first row shows the steady state force responses with displacements. Tables in the second, third and fourth row respectively show the magnitudes of impedance, impedance phase angles and power dissipation rates with frequency...........................64
Table 4.2: Summarized values for the esophagus in the Z-direction under different experimental conditions. Table has the same format as Table 4-1. ............................. 65
Table 4.3: Steady state force responses of the esophagus with displacements in the Xdirection under different experimental conditions. ...................................................... 66
Table 4.4: Steady state force responses of the esophagus with displacements in the Ydirection under different experimental conditions. ...................................................... 66
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Laparoscopic surgeries are minimally invasively surgeries performed using customized surgical tools and a high-resolution endoscopic camera. The patient's abdomen is first insufflated with carbon dioxide, following which the surgical tools and camera are inserted through tiny skin incisions made at the abdomen or chest wall. Utilizing these surgical tools and video images, the surgeon is able to explore the entire abdominal cavity and conduct operations without the need to make large openings.
Major advantages of such minimally invasive surgeries are less patient trauma, shorter hospital stay, less scarring and earlier resumption to normal and full activities. The advantages of such surgical techniques have captured the attention of the media and the growing demand for such alternatives from patients. In the first decade of introducing laparoscopic surgeries into the operating room, laparoscopic cholecystectomy was successfully employed as the standard in treating gallbladder disease in the United States and around the world. The acceptance of such alternative surgical techniques over open surgeries greatly encouraged the development of other advanced laparoscopic techniques by the medical community. These advanced laparoscopic techniques (hernia repairs, antireflux procedures and colectomy) require the surgeons to be significantly more proficient in their skills than the simple extirpative procedures (e.g
cholecystectomy, splenectomy, adrenalectomy). Surgeons would not only have to be proficient with operating using mostly visual feedback but would also have to be proficient with two handed dissection techniques, laparoscopic suturing, knot tying skills and the use of advanced laparoscopic instruments.
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However, surgeons are often limited by the state of technology employed in laparoscopic surgeries [1-3]. View from the endoscopic camera is monoscopic and the images are 2dimensional in nature. These images are not able to provide the surgeon with the vital depth information required to perform operations efficiently. Visual feedback shows movements of the tools and anatomical landmarks that are mirror-imaged of the surgeon's hand movements.
Surgeons are thus required to have a high level of hand and eye coordination to navigate efficiently around the operation sites. Haptic feedback from the instrument-tissue interaction is also limited due to the long and thin surgical tools. Besides these technological challenges, the laparoscopic setup presents kinematics and space constraints to the surgeon. Translational motions of the surgical tools are limited as they are pivoted about trocars at the point of incision.
Between manipulating the abdominal organs with the surgical tools and coordinating with the images, the surgeon also has to ensure that the surgeries are carried out in a safe manner.
Introduction of advanced laparoscopic surgical procedures further complicate and challenge the surgeons in carrying out such operations safely and efficiently.
The traditional "apprenticeship" model, in which the novice surgeon learns on a "see one, do one, teach one" paradigm began to show signs of breaking down with the advent of laparoscopic surgeries. The lack of generalized guidelines for training and credentialing surgeons for laparosopic surgeries have resulted in operative complications. Technical errors resulting from inadequate training often result in perforation of tissues, recurrence of symptoms, need for open surgeries or even death [4]. A study made by the Institute of Medicine in November 1999 entitled "To Err is Human: Building a Safer Health System", concluded that human errors contributed to a large percent of medical costs. Inadequacy in training and education of surgeons was cited as one of the main reasons for the increase in medical costs. The three key problem areas identified in the report were 1) inexperienced beginners 2) inexperienced experts with new techniques and 3) rare medical situations.
A computer-based multi-modal virtual environment surgical simulator can improve the adequacy of training surgeons for laparoscopic surgeries. Recent works have focused on incorporating visual and haptic feedback into the simulator as an effective training tool for laparoscopic surgeries [5-15]. These simulators can allow a surgeon to practice and refine his/her surgical techniques on virtual patients before operating on live ones. Integrating force-feedback devices into the simulator enable the trainee to interact naturally with the virtual organs using
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his/her senses of vision as well as touch. Custom software can be used to simulate different and even rare surgical procedures. Furthermore, these simulators provide a training platform where both novice and experienced surgeons may be trained, assessed and certified for specific laparoscopic operations.
For the surgical simulator to provide positive training transfer, the trainee on the simulator should be fully "immersed" in the training. Visual and haptic cues should be as realistic as possible. Deformations of the virtual organs due to the interaction between the surgical tools and the organs, as well as reaction forces felt by the user due to these interactions should also be realistic.
To simulate these organ deformations and reaction forces accurately, it is generally expected that physically based models of the virtual organs and tissues are required. The visual deformations and reaction forces should conform to physical laws governing the behavior of the tissues. Apart from the consideration of force equilibrium and boundary conditions, in vivo mechanical properties of the organs are needed. These properties govern the way the organs deform and their corresponding force responses to external interactions. By effectively integrating these material properties into the simulation, deformations of the organs and the reaction forces felt by the surgeon during operations can be approximated realistically.
Soft tissues exhibit complicated mechanical properties [16, 17]. Some characteristics of biological tissues include 1) non-linearity in force responses to displacements, 2) rate dependency of force responses due to the viscoelastic nature of biological tissues, 3) inhomogenity in mechanical behavior across tissue, 4) multi-layered, 5) anisotropic force responses and 6) hysteresis in force responses with continually increasing and decreasing displacements.
Studies have been carried out to characterize the mechanical behaviors of intraabdominal organs, muscles, tendons and other biological tissues in vitro [18-21]. In some of these studies, extensive measurements of the various biological tissues were made. However, data obtained from these tests are not suitable for the development of the surgical simulator, as among other factors, mechanical properties of biological tissues change after the death of the
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animal through loss of blood pressure, oxygen, and degeneration of tissue. Boundary conditions of these tissue samples have also been altered from their natural state and potentially affecting estimates of their associated mechanical properties.
Recently, many investigators have also performed tests to characterize the in vivo mechanical properties of various biological tissues. These in vivo measurements were performed on the finger pad of humans and primates [22-24], thigh, lower calf and heel of humans [25, 26], porcine brain [27] and the intra-abdominal organs of pigs [28-36]. Of specific interest for the development of the surgical simulator were the measurements made on intra-abdominal tissues.
The measurements were made on the liver, spleen, intestines and stomach of pigs.
Conventional measurement methods and equipment for characterizing engineering material properties, such as using a tensile testing machine, are not suitable for in vivo tissue samples. Most of the above-mentioned methods for the characterization of biological tissues in
vivo, especially for intra-abdominal tissues, were made using specially designed instruments [26,
37].
The TeMPeST 1-D (Ottensmeyer et al., 2002) is designed to measure the linear viscoelastic properties of solid organs, such as the liver and spleen during a laparoscopic surgery.
With a 5 mm circular indenter, the device records both displacement and force data from the organs during the periods of indentation. It can indent with amplitude of up to 500 gm and can apply a maximum force of 300 mN. It has an open loop bandwidth of about 100 Hz, making it possible to measure the frequency response of solid organs to indentation over a large range of frequency. Assuming the organs to be semi-infinite bodies, the linear elasticity of the organs at the different frequencies are inferred. Preliminary studies have been made with the TeMPeST 1-
D to characterize the viscoelastic properties of the porcine liver over frequencies spanning three orders of magnitude.
The Dundee Single Point Compliance Probe (Carter et al., 2000) is designed to measure force response of organs to indentation stimuli during an open surgery (See Figure 1.1). As a hand-held probe, it can indent up to a maximum depth of 6mm and measure the corresponding reaction forces. Force-displacement curves of the organs can be produced from the corresponding data and stiffness of the tissues inferred. It has been used to obtain forcedisplacement relationship data of the human liver.
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Figure 1.1: Dundee Single Point Compliance Probe (Carter et al., 2000).
In vivo material properties of organs were also measured using modified versions of laparoscopic instruments (Hannaford et al., 1998). The Force Feedback endoscopic Grasper
-
FREG makes use of standard laparoscopic instruments with the tool shaft of the instrument mounted onto the slave subsystem and the tool handle attached to the master subsystem. Figure
1.2 shows the FREG with a standard Babcock grasper from Carl Storz Inc.. Using either teleoperation or software, the FREG is able to control grasping forces at the tool tip. The FREG was used with software control in experiments to palpate tissues at 1Hz. Quasi-static stiffness information was inferred for the porcine colon, small bowel, spleen, stomach and lung.
Rosen et. al. (1999) instrumented a laparoscopic grasper with force/torque sensors to measure force and torque at the surgeon hand/tool interface when the instrument was used to perform laparoscopic surgeries on pigs. Figure 1.3 shows a picture of the instrumented laparoscopic grasper. This force/torque data was correlated with visual feedback from the endoscopic camera to create a database for surgical simulation and the optimization of performance in robotic surgeries.
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Figure 1.2: The Force Feedback endoscopic Grasper with a Babcock grasper (Carl Storz Inc., model #30420
BL, Hannaford et al., 1998).
Figure 1.3: The instrumented endoscopic surgical grasper (Rosen et al., 1999).
Brouwer et. al. (2001) inferred the in vivo mechanical properties of various abdominal tissues such as the stomach, spleen and liver using a uniaxial tensile machine that grasped the abdominal tissues and measured the forces corresponding to different stretch ratios. Figure 1.4
shows a schematic drawing of the unaxial tensile machine. In addition, in vivo reaction forces of abdominal tissue samples were measured using the haptic interface device, Phantom. It was programmed to indent the various abdominal tissues at constant velocity. Contact forces corresponding to displacements of suturing needles through abdominal tissues were also measured.
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Stepper
Mot
4J%
Adusurment ts a b
A ustr e Sen
Ci V Fijorce ieo
Figure 1.4: Uniaxial tensile machine (Brouwer et. al., 2001).
Although useful, the in vivo measurements made on the intra-abdominal tissues in the previous works are not entirely sufficient for our applications. In many cases, measurements beyond the range, resolution and frequency bandwidth of measurements made by the previous investigators are required. Furthermore, measurements were also required from organs that were not tested previously. For realistic simulation of laparoscopic procedures, we would require a systematic study of the in vivo mechanical behavior of organs to obtain data suitable for the development of the simulator. We require both static and dynamic mechanical properties of the organs for conditions similar to those in an operating room. Specifically, we are interested in the linear as well as the nonlinear responses of the soft tissues and their viscoelastic properties under compressive and shear loading. We are also interested in the behaviors of the tissues when subjected to low frequency stimulations.
In this study, experiments were performed to characterize the in vivo mechanical behavior of the liver and lower esophagus of pigs. In vivo data from the lower esophagus are being used for the development of a surgical simulator for laparoscopic Heller myotomy [38].
Additionally, ex vivo as well as in vitro mechanical properties of the above organs were also characterized. Comparisons were also made between the readings obtained to determine the changes in the mechanical properties due to changes in the boundary conditions and the effects of death.
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Oral caity Tonge
Oropharyonx
Esophagus
Liver
Galt~adder
DuFodenum wrses
Ileums/leuu
AccesingTransvese
Ap~pendixSgci
Stomach
Pancrea j
Wion
Rectum
Anal/ randib!J
Figure 1.5: Intra-abdominal organs and their locations in the human abdominal cavity. The left lobe liver in this figure covers the lower esophagus and the esophagogastric junction.
of the
The Esophagus
The esophagus is the tubular organ connecting the pharynx to the stomach and is responsible for the transport of bolus (chewed food in the alimentary canal) to the stomach. Two different layers of muscles form the exterior of the esophagus. The outer muscle layer is aligned longitudinally along the esophagus and the second layer round the esophagus. The esophagus is divided into three sections, with the upper third composed of striated muscles, the middle third a combination of smooth and skeletal muscle and the lower third entirely of smooth muscles. A layer of mucosa forms the innermost layer of the esophagus. Contractions along the esophagus in the form of peristaltic waves form the mechanism to force the bolus through the esophagus into the stomach.
The esophagus is able to bulge and expand to allow the bolus to move through it.
The lower third of the esophagus is the lower esophagus. It is the portion of the esophagus in the abdominal cavity. It is tubular in nature and is about 15 mm in diameter, 40 mm in length suspended between the diaphragm and the stomach. The region of the esophagus just above the stomach is known as the esophagogastric junction or the esophagogastric vestibule.
This region maintains a zone of high pressure and prevents regurgitation from the stomach.
Malfunctioning of the esophagogastric junction results in the reflux of acid to the esophagus and causes coughing and heartburn [39-42].
18

Btopbagus-
1ophagop-astr
I lawus
Figure 1.6: The esophagus and stomach
The Liver
The liver is the soft organ located at the upper-right of the abdominal cavity. It is the largest gland in the human body and is dark reddish-brown in appearance. In an adult male, the liver weighs 1.4 1.6 kg. The liver, along its greatest traverse length is about 20 to 22.5 cm.
Vertically, it measures 15 to 17.5 cm with a maximum thickness of about 10 to 12.5 cm. The liver is composed of a mass of lobules held together by a fine areolar tissue. It is responsible for the secreting and synthesizing as well as the storage of vital vitamins, minerals and glucose in the body. It is also responsible for the purification of harmful compounds in the body into less harmful compounds [43, 44].
R'gght k,0_eLe of hver .
Figure 1.7: The liver
19

Animal and experimental protocols for this study were in accordance with approvals obtained from both the Harvard Medical Area Standing Committee on Animals and the MIT Committee on Animal Care.
To characterize the mechanical behavior of the lower esophagus and liver of pigs, a series of indentation stimuli were applied to the organs and reaction forces were measured. The indentation stimuli were delivered using the haptic interface device, Phantom Premium-T 1.0
(SensAble Technologies) that was programmed to perform as a mechanical stimulator. Using position feedback control, the Phantom was programmed to deliver the required stimuli to the organs. The Phantom has a nominal position resolution of 30 gm and a frequency bandwidth that significantly exceeds the stimulus frequencies that were being employed in this experiment [45-
47].
Reaction forces were measured using a six-axis force transducer, Nano 17 (ATI Industrial
Automation) that was attached to the tip of the Phantom. The transducer has a force resolution of
0.781 mN along each of the three orthogonal axes when connected to a 16-bit A/D converter.
The indenter was a 2 mm diameter flat-tipped cylindrical probe that was fixed to the tip of the
Phantom with the force transducer mounted in-between to accurately sense the reaction forces
(See Figure 2.1). Reaction force and indenter displacement data samples were time-coded and recorded 200 times per second using custom software. Phantom control and data acquisition was
20

performed using an 850 MiHz Pentium III PC. Time coding was carried out using the on-board timer with a resolution of 0.84 ptsec. Figure below shows a schematic of the equipment setup.
Phantom Haptic
Irderf2.e DIda
ATI Farce
TMaroducer
Figure 2.1: tipe d enter
Schematic of equipment setup.
Phantom
Amplifier Box
16-bit
PC
Ramp and hold as well as sinusoidal indentation stimuli were used in this study. The ramp and hold indentation stimuli were delivered in the vertically downward (Z) direction as well as in the other two orthogonal directions (X and Y). Ramp and hold indentation stimuli in the Z-direction were delivered to both the organs while the indentation stimuli in the X and Y-direction were only delivered to the lower esophagus. The sinusoidal indentation stimuli were only in the Zdirection. These sinusoidal stimuli were delivered to both the liver and lower esophagus.
For the ramp and hold stimuli, different ramp velocities were used in driving the indenter to the different desired depth of displacements. The stimuli were delivered by ramping the indenter to the desired depth of displacement in one second. The indenter was then held steady at the displacement depth for 20 seconds before it was withdrawn. Thus, for the ramp and hold stimulus with displacement depth of 8 mm, a ramp velocity of 8 mm/s was achieved. Stimuli in the Z-direction were delivered normally to the organs while in the X and Y-direction over preindentations of 4 6mm in the Z-direction before displacing in the required direction. Figure
2.2
shows the input signals to the Phantom for ramp and hold indentation stimuli.
21

(a)
7-
6
(b)
E
5
(c)
C,
M
3
2
(d)
00
0 2 4 6
1
8 10
Time[sec]
12 14 16 18 20
Figure 2.2: Input signal to the Phantom for ramp and hold indentation stimuli. (a) ramp velocity =8 mm/s, displacement =8 mm; (b) ramp velocity =6 mm/s, displacement =6 mm; (c) ramp velocity =4 mm/s, displacement
=4 mm; (d) ramp velocity =2 mm/s, displacement =2 mm; (e) ramp velocity =1 min/s, displacement=1 mm.
Table below presents the conditions for the different ramp and hold indentation stimuli that were applied to the organs in the three orthogonal directions.
Displacement Depth (mm)
1.0
2.0
4.0
6.0
8.0
Ramp Velocity (mni/s)
1.0
2.0
4.0
6.0
8.0
Direction
Z, X, Y
Z, X, Y
Z, X, Y
Z, X, Y
Z
Table 2.1: Conditions for ramp and hold indentation stimuli.
Low frequency sinusoidal indentation stimuli (0.5, 1.0, 2.0 and 3 Hz) were delivered with amplitude of 2.0 mm. These sinusoidal stimuli were superimposed over pre-indentations in the
Z-direction to ensure that the indenter stayed in contact with the organ over the entire course of stimulation application. The indenter was first ramped into the organ at 6 mm/s to a depth of
6mm and was held steady for 2 seconds before the sinusoidal stimuli were applied. The sinusoidal stimuli were applied over a period of 20 seconds on the organ. Figure 2.3 shows the input signal to the Phantom for the 2.0 Hz indentation stimuli. This is the typical form for all sinusoidal input signals.
22

8
7
6-
5 --
E 4-
!
-1 --
3--
2
0 L
0
5 10
Time[sec]
15 20
Figure 2.3: Input signal to the Phantom for 2.0 Hz indentation stimuli, superimposed over a pre-indentation of
6mm. This is the typical form for all sinusoidal input signals.
2.3
Experiments were performed on the liver and lower esophagus of pigs in vivo (animal is alive), ex vivo (animal is dead but with the organs in-situ) and in-vitro (organs harvested).
In vivo and ex vivo experiments were performed at the Harvard Center for Minimally
Invasive Surgery. In-vitro experiments were performed at Touchlab in MIT. A total of 7 female pigs, each weighing 27 kgs to 70 kgs were used in these experiments. The animals are approximately 62, 70, 27, 32, 32, 45 and 43 kgs and are respectively labeled Al A7 in this thesis. For the in vivo experiments, the pigs were first put under general anesthesia and placed on the surgical table. A midline incision was then made at its abdominal region and dissection carried out on the anatomical structures to expose the organs.
For the in vivo and ex vivo experiments, the surgical table was adjusted such that indentation stimuli in the Z-direction were normal to the organ surface at the point of contact and in the X and Y-direction, across and along the outer longitudinal muscular fibers of the lower esophagus respectively. The indentation sites were kept sufficiently moist throughout the experiment to ensure that the organs were maintained as closely as possible to their natural state.
Indentation site on the liver was chosen to be at the thickest part of the middle lobe and on the
23

lower esophagus, at the esophagogastic junction. Figure 2.4 shows a picture taken of the experimental setup for both in vivo and ex vivo experiments.
Phantom
Figure 2.4: Experimental setup for in vivo and ex vivo experiments.
The tip of the Phantom, with the indenter attached was then lowered into the abdominal region with care taken for each indentation stimulus to be delivered to the same site on the organs. To ensure that all indentation displacements were with respect to the same initial reference position, the indenter was lowered at slight increment till it was visually determined to be just barely touching the surface of the organs before force collections were started and the stimuli delivered. An average time of about 3 minutes was allowed between trials to ensure that the organ has sufficiently reformed from the indentation before the next stimuli was delivered.
Preliminary experiments showed that breathing of the animal caused motions and forces that greatly exceeded the force responses of the organs. Figure 2.5 shows the force response from the liver to ramp and hold indentation at 8 mm with the animal breathing. Sudden peaks in the force response are forces generated from motion of the animal due to breathing. To observe the inherent force responses of the organs to the indentation stimuli, the animal was first saturated with oxygen and prevented from respiration during the periods of stimuli application.
24

0
20.08-
0.06-
0.04-
0.02-
0.14-
0.12-
0.1 -
0
2 4
6 8
10
Time[sec]
12 14 16 18 20
Figure 2.5: Force response of liver. Large peaks in the force response are forces generated from motions of the animal due to breathing. The smaller sinusoidal pulses along the force response are due to the forces generated from the pulse rate of the animal superimposed on the force response.
Effective management of breathing was a crucial issue when measuring the in vivo force responses. The amount of time required for each indentation stimuli and time for which breathing of the animal was held had to be optimized. Increased period of breath holding increased the CO
2 concentration in the bloodstream of the animal and caused the animal to undergo spontaneous breathing. This caused motions that resulted in the force responses similar to those seen in the figure above. Alternatively, the complete relaxation effect of the organs to a steady state force would not be observed if the indentation periods were kept too short.
After all the proposed in vivo indentation stimuli were delivered to the organs, the animal was euthanized and ex vivo experiments carried out. In the ex vivo experiments, only ramp and hold indentation stimuli in the Z-direction were delivered. Since the boundary conditions of the organs are kept the same as in the in vivo experiments, comparing the data obtained between the
in vivo and ex vivo experiments would determine the effect of death on the mechanical properties of the organs. At the conclusion of the experiment, the entire liver and the section of the esophagus in the abdominal cavity (lower esophagus) were harvested.
In-vitro experiments were performed on the tissue samples at approximately 6, 24 and 48 hours after the animal had been euthanized. These in-vitro experiments were carried out with the excised organs placed in a dish. In between the periods of experiments, the tissue samples were stored well below room temperature in saline bath. The tissue samples were brought out from the
25

bath into room temperature at approximately 20 minutes before the commencement of any experiment. Since it was impossible to replicate the exact natural boundary conditions of the organs, the tissue samples were constrained in such a way that global motions of the organs were prevented. All ramp and hold as well as sinusoidal indentation stimuli as described in the above section were delivered to the tissue samples and similar data acquired.
Table below shows the experimental protocol for both organs. Entries into the matrix represent the corresponding directions for delivering the indentation stimuli to the organs.
Liver
Conditions
In vivo
Ex vivo
In-vitro at 6 hours after euthanasia
In-vitro at 24 hours after euthanasia
In-vitro at 48 hours after euthanasia
Ramp and Hold Indentations
Z
Z
Z
Z
Z
Sinusoidal Indentations
Z
---
Z
Z
Z
Esophagus
Conditions
In vivo
Ex vivo
In-vitro at 6 hours after euthanasia
In-vitro at 24 hours after euthanasia
In-vitro at 48 hours after euthanasia
Table 2.2:
Ramp and Hold Indentations
Z, X, Y
Z
Z, X, Y
Z, X, Y
Z, X, Y
Sinusoidal Indentations
Indentation stimuli applied to both organs for different experimental conditions.
Z
---
Z
Z
Z
Data Processing
Force and displacement data obtained from all experiments were processed offline using
MATLAB before any analysis was carried out. By utilizing the recorded time-codings, an interpolation scheme was employed to correlate the variation in the force responses to the displacements. Both the displacement and force response signals are then filtered using zero phase digital filters to reduce the noise content.
26

In this chapter, force responses of the liver and lower esophagus to ramp and hold as well as sinusoidal indentation stimuli are presented. In Section 3.1, in vivo, ex vivo and in-vitro force responses of both the organs to ramp and hold indentations are presented. Variations in the force responses to ramp and hold indentations for different animals are also presented. Section 3.2 shows the in vivo and in-vitro force responses and force-displacement profiles of both the organs to sinusoidal indentations. Variations in the force responses and force-displacement profiles to sinusoidal indentations for different animals are also presented.
Figure below shows the typical traces of the Phantom displacements corresponding to different ramp and hold indentation stimuli. Displacements are made in one second, achieving a ramp velocity of 8 mm/s for the 8 mm displacement and ramp velocity of 1 mm/s for the 1 mm displacement.
27

9
8-
7-
(a)
E (b)
E
(C)
03-
2
(d)
0
0 2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.1: Traces of Phantom displacements for ramp and hold indentation. (a) ramp velocity=8 mm/s, displacement=8 mm; (b) ramp velocity=6 mm/s, displacement=6 mm; (c) ramp velocity=4 mm/s, displacement=4 mm; (d) ramp velocity=2 mm/s, displacement=2 mm; (e) ramp velocity=1 mm/s, displacement=1 mm.
In this section, in vivo, ex vivo and in-vitro force responses of the liver and esophagus to ramp and hold indentation stimuli are shown. Force responses shown in this section are obtained from experiments conducted on A6. These figures represent the typical force responses of the organs to the different ramp and hold indentation stimuli.
Figure 3.2 shows the in vivo force responses of liver to ramp and hold indentation stimuli in the Z-direction. Figures 3.3 3.6 show the in vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Z, X and Y-direction respectively.
28

0.15
0.1
(a)
0
IL
0.05
S(b)
(c)
-0.05
2 4 6 8 10
Time[sec]
12 14 16 18 20
0.15
0.1
z
0.05
0
U-
0 a) to)
-0.05 -
0
La)
2 4 8 10
Time[sec]
12 14 16 18 20
Z
Figure 3.2: In vivo force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm; (c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm;
(e) velocity of indentation=1 mm/s, depth of indentation=1 mm. Raw data is shown in the top panel and the effect of pulse filtered from the force response in the bottom panel.
0.15
0.1
-
L-
0
0.05-
0
(a)
(C) d
-0.05
0 2 4 6 8 10
Time[sec
12 14 16 18 20
0.15
0.1
(a
(b
(C)
0
U-
0.05
0
.
0
2 4 6 8 10 12 14 16 18 20
Time[sec]
Figure 3.3: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the Zdirection. Plots have the same format as Figure 3.2.
29

0.15
0.1
-(a
_(b)
0
L-
U0.05
0.15
0
2 4
6
8 10 12 14 16 18 20
Time[sec]
0.15
0.1
(a-
U
0
LL
0.05
(d)
-0.05 -
0 2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.4: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the Xdirection (across outer muscular fibers). (a) velocity of indentation=6 min/s, depth of indentation=6 mm; (b) velocity of indentation=4 mm/s, depth of indentation=4 mm; (c) velocity of indentation=2 mm/s, depth of indentation=2 mm; (d) velocity of indentation=1 mm/s, depth of indentation=1 mm. Raw data is shown in the top panel and the effect of pulse filtered from the force response in the bottom panel.
0.08
0.06
-0.04
LL o 0.02
0
-0.02
0
(b)
(c)
2
0.08
0.06
0.04
g( o 0.02
0
-0.02 L
0
(C)
(a)
(b
2
4 6 8 10
Time[sec]
12 14 16 18 20
(d--
4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.5: In vivo force responses of lower esophagus to ramp and hold indentation stimuli in the Ydirection (along outer muscular fibers). Plots have the same format as Figure 3.4.
Figures 3.6 3.7 show the ex vivo force responses of the liver and lower esophagus to ramp and hold indentations in the Z-direction.
30

0.35
0.3-
0.25-
(a)
0.2z
0
IL 0.15 -
0.1 )
0.05
0
0
(d)
(e)
2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.6: Ex vivo force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation= mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm;
(c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm; (e) velocity of indentation= 1 mm/s, depth of indentation= 1 mm.
0.18
0.16
0.14-
0.12-
0.1 -
0
0.08 -
0.06- (b)
0.04-
0.02 -
0
(C)
(d)--
(0)-
0 2 4 6
- -
-
8 10
Time[sec]
12 14 16 18 20
Figure 3.7: Ex vivo force responses of lower esophagus to ramp and hold indentation stimuli. Plots have the same format as Figure 3.6.
The above figures show the in vivo and ex vivo force responses of the liver and lower esophagus to ramp and hold indentations. In the in vivo force responses, the approximately
31

sinusoidal force variations seen in the upper panel of each figure were forces generated due to the pulse of the animal superimposed on the reaction forces from the organs. To observe the inherent force response of the organ, a zero phase low pass filter was designed with a cutoff frequency just below the main frequency component of the pulse rate to generate the plots in the lower panel. Figures 3.8 3.9 show the frequency spectrum of the in vivo and ex vivo force responses of the liver to ramp and hold indentations at 8mm.
15-
10
5-
0-
0
30
25
20
40
35
50
45
0.5 1 1.5 2 2.5
Frequency (Hz)
3 3.5 4 4.5 5
Figure 3.8: Frequency spectrum of the in vivo force response of liver for ramp and hold indentation at 8mm.
Peak at approximately 1.4 Hz corresponds to the main frequency component of the sinusoidal variations due to the pulse rate of the animal.
Figure 3.9:
35-
30 -
E 25 -
20-
50
45-
40-
15-
10 -
5 -
0 0.5 1 1.5 2 2.5 3
Frequency (Hz)
3.5 4 4.5 5
Frequency spectrum of the ex vivo force response of liver for ramp and hold indentation at 8 mm.
32

Figure 3.10 shows the in-vitro force responses of the liver to ramp and hold indentation stimuli in the Z-direction. Figures 3.11 3.13 show the in-vitro force responses of the lower esophagus to ramp and hold indentation stimuli in the Z, X and Y-direction respectively. These
in-vitro force responses were taken from experiments conducted on the organs at approximately
6 hours after the animal has been euthanized.
0.15
0.15
0.1
z
U
0
IL
0.05-
(b)
0 c)
(d) e
-0.05L
0 2 4 6 8 10
Time[sec]
16 18 20
Figure 3.10: In-vitro force responses of liver to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=6 mm/s, depth of indentation=6 mm;
(c) velocity of indentation=4 mm/s, depth of indentation=4 mm; (d) velocity of indentation=2 mm/s, depth of indentation=2 mm; (e) velocity of indentation=1 mm/s, depth of indentation=1 mm.
33

V.
0.25 -
0.2z.
0.15-
0
U. 0.1 -
0.05 -
(b)
C)
0 0
0 2 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.11: In-vitro force responses of lower esophagus direction. Plots have the same format as Figure 3.10. to ramp and hold indentation stimuli in the Z-
0.08
0.07-
0.06
0.05
Z 0.04
(a-
(b
0.03
0.02
0.01
0
-0.011
0
(C)
(d)
2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.12: In-vitro force responses of lower esophagus to ramp and hold indentation stimuli in the Xdirection. (a) velocity of indentation=6 mm/s, depth of indentation=6 mm; (b) velocity of indentation=4 mm/s, depth of indentation=4 mm; (c) velocity of indentation=2 mm/s, depth of indentation=2 mm; (d) velocity of indentation=1 mm/s, depth of indentation=1 mm.
34

0.18-
0.16 -
0.14-
0.12
--
W
0.1
(b
0
U-
0.08
--
0.06
-
0.04
--
(C)
(d)
0.02
0 2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.13: In-vitro force responses of lower esophagus to ramp and hold indentation stimuli in the Ydirection. Plots have the same format as Figure 3.12.
All force responses of the liver to ramp and hold indentation stimuli show similar forms.
Reaction forces increased with displacements as the indenter was ramped towards the desired displacement depth. For each of the force response, a peak reaction force was observed when the indenter first reached the desired depth of indentation. During the holding phase of the stimuli, the tissue relaxed and the decay in reaction force indicates viscoelastic relaxation of the organ. This similar form was also seen in the in-vitro force responses of the lower esophagus for indentations in Z, X and Y-direction.
In vivo and ex vivo force responses of the lower esophagus in Z, X and Y-direction for ramp and hold indentations of 8mm, 6mm and 4mm were different from the form mentioned above. Force responses showed increases to peak forces as the indenter reached the desired depth of displacements. This was followed by slight viscoelastic decay in the forces before a low frequency, high amplitude oscillation was observed in the force responses. This additional peak in the force response was observed during the holding phase of the stimuli. For ramp and hold indentations of 2mm and 1mm, this additional peak was not observed at all. Visual observations of the indentation process during the experiment did not indicate that there were any incidents of the indenter slipping off the esophagus, contact with other organs or external disturbance, which could have caused the emergence of the peaks.
35

Possible causes for the occurrence of the peak are the combined effects of the unique boundary conditions and the physiological structure and behavior of the lower esophagus. Two hypotheses are made to explain the observation of the additional peak. 1) The motion of the outer muscular layer surrounding the lower esophagus might have caused this peak in the force response. 2) Stress activation of the lower esophagus might have resulted in the initiation of peristalsis wave. The movement of this wave might have caused this peak.
According to the first hypothesis, ramp and hold indentation on the lower esophagus caused both local and global deformations. When the indenter was ramped into the lower esophagus, the lower esophagus was deformed locally and displaced globally. The esophagus was compressed locally at the indentation site and moved as a rigid body in the direction of force application. For high ramping forces corresponding to ramp velocities of 8mm/s, 6mm/s and 4mm/s, muscle layer on the posterior of the esophagus was dislodged from the mucosa layer. As this muscular layer slowly reformed against the mucosa, it imposed additionally forces on the indenter, resulting in the additional peaks with low frequency oscillations as observed.
According to the second hypothesis, a high ramp velocity would rapidly stretch of the lower esophagus. This rapid stretching caused an immediate increase in the frequency of the action potential and a corresponding increase in the contractile tension (stress activation). As this tension decreased to the original level (stress relaxation), peristalsis waves were initiated.
The motion of this peristaltic wave to the stomach might have imposed additional forces and resulted in the additional peak [48]. This wave moved slowly through the esophagus to the stomach and caused the additional peak as observed at about 2 seconds after the indenter reached the desired depth of displacement.
Experiments were carried out to test this hypothesis. Ramp and hold indentation stimuli of low ramp velocities were applied to the lower esophagus and reaction forces recorded. Figure
3.14 shows the comparison of in vivo force responses of the lower esophagus to different ramp velocities.
36

0.18
0.16-
0.14-
0.12 -
0.1 -
(C)
0 0.08 -
0.06-
0.04 -
(d)
0.02
--
0 2 4 6 8 10
Time[sec]
12 14 16 18 20
Figure 3.14: In vivo force responses of lower esophagus to ramp and hold indentation stimuli. (a) velocity of indentation=8 mm/s, depth of indentation=8 mm; (b) velocity of indentation=1 mm/s, depth of indentation=8 mm;
(c) velocity of indentation=6 mm/s, depth of indentation=6 mm; (d) velocity of indentation=2 mm/s, depth of indentation=6 mm.
Comparisons made between similar depth of displacements, (a) and (b) as well as (c) and (d), show the difference in the force responses due to ramp velocity. In (a) and (c), increase in reaction forces to a peak and the initial viscoelastic relaxation before the additional peak was observed. (b) and (d) only show increase in reaction forces and viscoelastic relaxation. There was no indication of secondary peaks in the force responses during the holding phase of the stimuli for (b) and (d). These above experiments show that ramping forces is critical in producing the additional peaks seen. Observations of the force responses are consistent with the hypotheses suggested. However, they do not completely prove the validity of the hypotheses.
More extensive experiments need to be carried out.
In the in-vitro force response of the esophagus, the additional peak was also not observed. This is a further prove that the emergence of the additional peak as seen in the in vivo and ex vivo force responses from the esophagus could be due to either or both of the hypotheses.
Since the in-vitro experiments on the lower esophagus were conducted with the excised organ being placed on a dish, the lower esophagus was only allowed to deform locally. Global motion of the esophagus was suppressed and thus the additional peak was not observed in the force response. Peristalsis waves would also not be present in in-vitro tissue samples.
37

In this section, in vivo force responses and force-displacement relationships of both the organs to ramp and hold indentations are presented for experiments conducted on different animals.
The force responses shown are typical force responses obtained for each of the animal. A more concise representation of the variation in the force responses will be presented in the next chapter.
Figures are presented with plots on the left columns as the force responses with time and on the right columns, the corresponding force-displacement relationships of the indentation stimuli. Figure 3.15 show the in vivo force responses and force-displacement relationships of the liver to ramp and hold indentations.
38

0.2
.
0.15
0.1
0.05
0
0
-
I
0.1
.
.
.
5 10
Time[sec]
15 20
.
0.2
0.15,
LL
0.1
0.05-
0.1
0
0 2 4 6
Displacement [mm]
8
0.05.
0
0
0.04
0.03
0.02
0
U.
0.01
0
0
0.02
0.015
0.01
0
0.005
5
5
V
V.
0
X 10-3
10 r---
5
10
Time[sec]
15
10
Time[sec]
15
10
Time[sec]
15
5 a
0
U0
-5'
0 5 10
Time[sec]
15
20
20
20
20
0
U-
0.05
0
0
04
.0
0.03
0.02
0.01
2 4
Displacement [mm]
0
0.02 j
0.015
0.01
1 2 3
Displacement [mm]
0.005
0
0
O OA
0.5 1 1.5
Displacement [mm]
10 x 10-3
F
4
2
6
2.5
5
5 a
0
U0
00i
-50
0
I I
0.5 1
Displacement [mm]
1.5
Figure 3.15: In vivo force responses of the liver to ramp and hold indentation stimuli. Data was obtained from experiments conducted on A2, A4, A5, A6 and A7 (data from 5 animals). Depth of indentation = 8 mm, velocity of indentation = 8 mm/s (top row), depth of indentation = 6 mm, velocity of indentation = 6 mm/s (second row), depth of indentation=4 mm, velocity of indentation=4 mm/s (third row), depth of indentation =2 mm, velocity of indentation=2 mm/s (fourth row), depth of indentation=1 mm, velocity of indentation=1 mm/s (bottom row). Force responses are shown with the effect of pulse filtered.
39

Figures 3.16 3.18 show the in vivo force responses with time and the corresponding force-displacement relationships of the lower esophagus in the Z, X and Y-direction respectively.
0.2
0.15
0
U-
0.1
0.05
0
5 10
Time[sec]
15 20
0.1
0
U.
0.05
0
0.08
0.06
U.
0
0.04
0.02
U.
0
0.04
0.03
0.02
0.01
5
5
0 x 10'
5
10
Time[sec]
15
10
Time[sec]
15
10
Time[sec]
15
20
20
20
10
0-
0 5 10
Time[sec]
15 20
0.2
0
U-
0.15
0.1
0.05
0
'
3 2 4 6
Displacement [mm]
8
0.1
.2 005
0.08
0
0
0.06
U
0
LL
0.04
0.02
0.04
0
0
0.03
0
U.
8 0.02
0.01
2 4
Displacement [mm]
1 2 3
Displacement [mm]
4
15
0
0 0.5 1 x 10-3
1.5
Displacement [mm]
2
10
5
0
U-
0
-5
0 0.5 1
Displacement [mm]
6
5
2.
5
1.5
Figure 3.16: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Zdirection. Data was obtained from from experiments conducted on A3, A4, A5 and A6 (data from 5 animals). Plots have the same format as Figure 3.15.
40

0.2
0.
15F
0.1
U.
0.05
0
'
0
0.05
0.04 [
F0.03
0 0.02
0.01
0
0
0.1
0.08
0.06
U 0.04
0.02
0
0
0.03
0.02
a
0.01
0
U.
0
-0.01 L
0
5 10
Time[sec]
15 20
5 10
Time[sec]
15 20
.
.
0.2
0.15
0.1
U.
0.05
0
0 2 4
Displacement [mm]
0.1
0.08[
0.06
0.04
0.02
0-
L
1 2 3
Displacement [mm]
4
6
.
5
5 10
TIme[sec]
15
5 10
TIme[sec]
'_
15
20
' '
20
0.04
0.03
O 0.02
0.01
0.
03
0.
02-
0
0.
01
0
0
-0.
0
0.5 1 1.5
Displacement [mm]
2 2.
5
0.5 1
Displacement [mm]
1.5
Figure 3.17: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Xdirection. Data was obtained from experiments conducted on A4, A5 and A6 (data from 3 animals). Depth of indentation = 6 mm, velocity of indentation = 6 mm/s (top row), depth of indentation = 4 mm, velocity of indentation = 4 mm/s (second row), depth of indentation = 2 mm, velocity of indentation = 2 mm/s (third row), depth of indentation = 1 mm, velocity of indentation = 1 mm/s (bottom row). Force responses are shown with the effect of pulse filtered.
41

0.1
0.08
F0.06
U.0.04
0.02
0
0
-
.
.
.
5 10
Time[sec]
15 20
.
0.1
0.08
9 0.06
.
21
0.02
0
0 2 4
Displacement [mm]
6
0.1
0
I.
0.05
0.1
IL
0.05
0.04
0
L
0.02
0.03
0
'
0
0.02
0
IL
0.01
0
-0.01 '
0
0.06
0
' 0
5 10 15 20
Time[sec]
5 10
TIme[sec]
15
5 10
Time[sec]
15
0
0
0.06 r-
1 2 3
Displacement [mm]
4
0.04
0
I.
0.02
0
20
'
20
1
0.03
0.02
0 a.
0.01
0
-0.01
0
0.5
A
1 1.5
Displacement [mm]
2
0.5 1
Displacement [mm]
2.
5
1.5
5
Figure 3.18: In vivo force responses of the lower esophagus to ramp and hold indentation stimuli in the Ydirection. Data was obtained from experiments conducted on A4, A5 and A6 (data from 3 animals). Plots have the same format as Figure 3.17.
42

In this section, force responses of the organs to sinusoidal indentation stimuli are shown. Figure below shows the trace of the Phantom displacement for sinusoidal indentation at 2.0 Hz. This is the typical displacement trace for sinusoidal indentation stimuli. The sinusoidal indentations are superimposed over an indentation of 6 mm.
E4
3
2 -
8
7-
6-
0
5 10
Time[sec]
15 20
Figure 3.19: Trace of the Phantom displacement for 2.0 Hz indentation, superimposed over a pre-indentation of 6mm. This is the typical form for sinusoidal indentation stimuli.
Force responses and force-displacement profiles presented in this section represent typical responses of the organs to sinusoidal indentations. Data is shown for the last 10 seconds of the stimuli application. Force responses shown in this section are data obtained from experiments conducted on A6. Force responses to sinusoidal indentations from other animals are similar in form and are shown in the following section.
Plots on the left of figures show the force responses with time while plots on the right show the force-displacement profiles of the corresponding indentation stimuli. A bandpass filter centered on the various frequencies of indentation stimuli was applied to the force and displacement signals to obtain the data shown.
43

Figures 3.20 and 3.21 show the in vivo force responses and force-displacement profiles of the liver and lower esophagus to sinusoidal indentation stimuli.
F
0.05
0
0.1
0
.
2
0
0 2
Ie~ 1
4
-Time[secl
6
4 6
-
8
08
10
0
F
.
0.05
0-
-0.05
0
-2
0
8 10
-0.1
-2
0.1
0
0.05
0
2 lime[ze'? 8 10
0
L-0.05,
0 2
V
4
Tlme[sec]
6 8 10
-0.1
-2
-0.05
-2
-1
DIsplacement[mm]
1
-1 0
Displacementimm]
1
-1 0
Displacement[mm]
1
-1 0
Dlsplacement~mm]
1
2
2
2
2
Figure 3.20: In vivo force responses (left column) and force-displacement profiles (right column) of liver to sinusoidal indentation at 3.0 Hz (top row), 2.0 Hz (second row), 1.0 Hz (third row) and 0.5 Hz (bottom).
0.05
0
0
0.05
0
-0.0'ese]
S 0
2 4 6
Time[sec]
-0.05
0
-0.1
0
2 4 6
Tlme~sec]
2 4 6
Time~sec]
8
8
8
8
10
10
10
0
0.1
0.05
0~
0
-0.05-
-2
1
-0.1
-2
0.04
0.02
0~
0 02
-0.04
-2
0.5
-1 0
Displacement[mm]
1
0.
0
0
-1
-1
0
0
0
0
Displacement[mm]
Dlsplacement[mm]
1
1
0
2
0 2
2
Figure 3.21: In vivo force responses (left column) and force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 2.0 Hz (top panel), 1.0 Hz (middle panel) and 0.5 Hz (lower panel).
Figures 3.22 and 3.23 show the in-vitro force responses and force-displacement profiles of the liver and lower esophagus to sinusoidal indentation stimuli.
44

() 1
0
0
0.1
0
0
0.1
0
0
-01
0
0.1
0
2
2
4
Timesec
6
4 6
Timelsec)
8
8
10
10
0 1
-2
-0-
-2
0.1
-
0-
-1 0 1 -
Displacementfmm
2
2
-1 0
Displacementmm]
1
-01
0
0.1
2 4 6
Timersec)
8 10 -01-2
0.1
-1 0
Displacementrmml
1
0
-01
-0
0
2 4 6 8 10 -2 -1
__
0 1 2
Timesec]
Dlsplace.entimmj
2
2
Figure 3.22: In vitro force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 3.0 Hz (top row), 2.0 Hz (second row), 1.0 Hz (third row) and 0.5 Hz
(bottom row).
01
0~ 0~
0
0 1
2 4
Timesec1
6 8 10
7
0.1
-0
-0.1
-2
0.1
-
-1 0
Displacementimm]
1 2
-0.
U-0.1
-2
0 2 4 6 8 10
0
0 2 4
Time[.ec
6 8 10
Timelsec)
F
0.2
-0.2
-2
-1
-1
0
Dlsplacemen[mmI
1
1
2
2
Figure 3.23: In vitro force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation stimuli at 3.0 Hz (top row), 2.0 Hz (second row), 1.0 Hz
(third row) and 0.5 Hz (bottom row).
45

All in vivo and in-vitro force responses of the liver and esophagus show sinusoidal forces with frequency corresponding to the different frequencies of indentation. The forcedisplacement profiles are elliptically shaped and enclose a non-zero area. The shape of the force-displacement profiles is a consequence of the viscoelastic nature of the material and the area enclose by the loop is known as the hysteresis. This non-zero area represents the amount of viscous energy dissipated per cycle of the indentation.
All force responses over the period shown are fairly similar except for the in vivo force response from the lower esophagus at 0.5 Hz. The force response shows an increase in the second and fourth loop. This periodic increase in the forces might be a consequence the hypotheses as explained in the above section. The periodic increase in the force response is not observed in the in-vitro force responses at 0.5 Hz indentation.
3.2.2
In this section, in vivo force responses of the organs to sinusoidal indentations for experiments conducted on different animals are presented. Figures are presented with plots on the left columns as the force responses with time and plots on the right columns as the corresponding force-displacement profiles for the indentation stimuli. Data is shown for the last 10 seconds of the stimuli application. Figures 3.24 3.27 show the in vivo force responses of the liver to sinusoidal indentation at 3.0 Hz, 2.0 Hz, 1.0 Hz and 0.5 Hz respectively.
0.05 0.05
0
-0.05 MMI
0 2 4 6
Time[secj
8 10
0 -
-0.051
-2 -1 0
Displacement[mm]
1 2
Figure 3.24: In vivo force response (left column) and corresponding force-displacement profile (right column) of liver to sinusoidal indentation at 3.0 Hz. Data was obtained from experiments conducted on A6 (data from 1 animal).
46

0.05
z
0 z
0
-0.05
0 2 4 6
Time~sec]
0.1
0.05 FAAAAAAAA
0
8
-0.05
2 4 6
TlmefsecJ
8
0.04
0
0
-0.02
M
-0.04
0 2 4 6
Tlme[sec]
8
10
0.04-
0.02-
0
0u--0.02
-0.04-
-2
0.1
0.05-
0u--0.05.
-1 0
Dlsplacemsnt[mm]
1
10
10
-0.1
-2 -1 0
Dlsplacement[mm]
0.04-
-0.02-
1
U
002
0-
-0.04-
-2 -1 0
Displacement[mm]
1
2
2
2
Figure 3.25: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 2.0 Hz. Data was obtained from experiments conducted on A4, A6 and
A7 (data from 3 animals).
0.
0 5
0
-0.05
0
0.1
2
0
4 6
Tlme[sec1
8 10
0.05
0.
-0.05
-2
0
0.1
-
1
Displacenmentmm] 1 2
0
-0.1 0
2
0.05 AmOE~Sec
8 10 o
-0.05
0
0.05
2 4 6
Timersecl
8 10
0
-0.1
-2
0.05
0 -
-0.05
-2
0.05
-1 0
Dizplacement~mm]
1
-1 0
Dlsplacement[mm]
1
2
2
0
0 2 4 6
Time[sec]
8 10
0
-2 -1 0
Displacementtmm]
1 2
Figure 3.26: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 1.0 Hz. Data was obtained from experiments conducted on Al, A4, A6 and A7 (data from 4 animals).
47

0.05
0
-0.05
)
0.05
-0.05
0.05
0
2
0
-0.05
3
0.05
0
-0.t
2
3 mecsec
TVme seL
4
4
Tmsel0.05
6 8 10
6
8
0.05
0
10
. 1 -0.051-
-2
05mese-
-1 0
Dlsplacement[mm]
1
0
8 10
01-2-
-005
0-
-0.05
-2
-1
Displacement[mmj
0 1
-1
Dlsplacenment[mmj
0 1
Dlsplacement[mm]
Time[sec]
2
2
2
Figure 3.27: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of liver to sinusoidal indentation at 0.5Hz. Data was obtained from experiments conducted on Al, A4, A6 and A7 (data from 4 animals).
Figures 3.28 3.31 below show the in vivo force responses of the lower esophagus to sinusoidal indentation at 3.0 Hz, 2.0 Hz, 1.0 Hz and 0.5 Hz respectively.
0.05
0
-0.05
0
0.05
0
-000
2
2
4mse
8
8 U 0
0.05
-
1C
0
0
U.
-0.05
-
-2
4=::::
-1 0
DisplacementImm
1
-1 0
Displacaentmm]
1
Figure 3.28: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 3.0 Hz. Data was obtained from experiments conducted on
A3 and A4 (data from 2 animals).
48

0.05
-0.05'
0
0.05
0
-0.05
.50
2
2
0.05
-0.05
0.05
8 10
.50
0
2
2
4melseq
-0.05
-2
0.05
0
-0.05
-2
0.05 iIme[ssh 8 10 ime[seh 8 10
.5.
0.~
0.05
-0.05'
-2 0 2 4m reme[sec]
6 8 10
-1 Displacer~ent[mm] 1
-1 0
Displacementqmm]
1
-1 0
Displacement~mml
1
-1 0
Displacement[mm]
1
2
2
2
2
Figure 3.29: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 2.0Hz. Data was obtained from experiments conducted on
Al, A3, A4 and A6 (data from 4 animals).
0.05
0.05
LL
-0.05
0
0 2 4
Timelsec]
6 me[sec
8 1C
0
9L
-0.05
-2
0.05
8 10
0
LL
0-
-U.Z
-2
0
-2
0 1
0
0.05
0 2 4 rimo[Sec)
6 8 10
05
0
2 4 6 8 10
Time[sec]
0
LL
0.05
-2
0
U.
0
-0.05
-2
-1 0
Displacement[mm]
1
-1 0
Displacement[mm]
1
-1 DispIacen~ent[mm] 1
-1 0
Displacementfmm]
1
2
2
2
2
Figure 3.30: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 1.0 Hz. Data was obtained from experiments conducted on
Al, A3, A4 and A6 (data from 4 animals).
49

01 0.1
oL
-0.1
0
0.05
2 4
Tlme[sec]
6
00
0
U.
-V.Z
OVWU.
0
0
2 me[se
0
0
0.1 riesc
2
-0.1-0.1
4
0
0
LL.
-U. I
0 2
6
4
Time[sec]
6
8 10
IL
-0.1
-2
0.05
00
-1 0
Displacement[mm]
1
8
8 10
8 10
10
0 -
-2
0
-1 01
Displacement~mml
0-r
-2
0.1 r
-1 0
Displacement~mm]
1
0
L.
10.
-U. 1
-2 -1 0
Displacement[mm]
2
2
2
2
Figure 3.31: In vivo force responses (left column) and corresponding force-displacement profiles (right column) of lower esophagus to sinusoidal indentation at 0.5Hz. Data was obtained from experiments conducted on
Al, A3, A4 and A6 (data from 4 animals).
50

Analysis was carried out to determine the static and dynamic mechanical properties of the liver and lower esophagus. In this section, the steady state stiffness, impedance and power dissipation of the organs were inferred from the data obtained. A qualitative comparison was also made between the mechanical properties of the two organs as well as between the different experimental conditions.
The static mechanical properties of the organs were inferred from the data obtained from ramp and hold indentation experiments. From data recorded, steady state force responses of the organs and displacements were obtained. These data are presented as corresponding force-displacement relationships. We shall call these force-displacement relationships the steady state stiffness of the organs. The steady state stiffness is the elastic response of the organs, which characterizes the amount of force necessary for maintaining displacements of the organ at steady state. This steady state stiffness of the organs should not be confused with the transient stiffness of the organs, which is rate and time dependent.
Steady state force responses are calculated as the median force response in the last 5 seconds during the holding phase in each ramp and hold indentation stimuli trial. The desired displacement depths in each indentation stimulus are the corresponding displacements. These steady state force responses and displacements were averaged for each animal. In interpolating between the input displacements, a linear relationship was assumed.
51

Figures below show the steady state in vivo, ex vivo and in vitro stiffness of the respective organs. The in vivo and ex vivo steady state stiffness for each animal and their median are shown in the figures. The steady state force-displacement relationship for each animal is shown as dashed lines and the median force-displacement relationship is plotted as bold solid lines in the figures. The in-vitro steady state stiffness plots show the median for the respective organs at 6,
24 and 48 hours after the euthanasia of the animal. They are plotted as dashed, dotted and solid lines respectively.
Figure 4.1 shows the in vivo steady state stiffness of the liver. Figures 4.2 4.4 show the
in vivo steady state stiffness of the lower esophagus in the Z, X, and Y-direction respectively.
0.08-
-0- Median Force
--- A2
0.07
-+
A4
--- A5
,Ar-
A6
A7
0.06
Figure 4.1:
0.05 -
0
0.04
-
0.03-
0.02 -
0.01
~
0
0 1 2 3 4 5
Displacement[mm]
6 7 8
In vivo steady state stiffness of the liver (data from 5 animals).
9
52

0.08
0
LL
0.06
0.04-
0.
14 r-
0.12
-f- Median Force
4- A3
- -
A4
~ A5
AC
A7
0.1
Figure 4.2:
0.02-
0-
0
2
1 2
36'
3 4 5
Displacement[mm]
6 7 8 9
In vivo steady state stiffness of the lower esophagus in the Z-direction (data from 5 animals).
Figure 4.3:
0.06
-
Z 0.05
-
L 0.04
-
0.03
0.09 -
0.08k
-0- Median Force
-- A4
-a- A5
-a- A6
0.07-
0.02
0.01-
~~1
7.-
0
1
2 3 4
Displacement[mm]
5 6 7
In vivo steady state stiffness of the lower esophagus in the X-direction (data from 3 animals).
53

Figure 4.4:
0)
U-
0.08-
0.06-
0.04-
0.16
0.14
-0Median Force
A3
A4
A5
A6
0.12
0.1 k
0.02-
-----------
C1
0
1 2 3 4
Displacement[mm]
5 6 7
In vivo steady state stiffness of the lower esophagus in the Y-direction (data from 4 animals).
Figures 4.5 4.6 shows the ex vivo steady state stiffness of the liver and the lower esophagus in the Z-direction respectively.
0.16-
0.14-
-4- Median Force
-9- A6
-a- A7
Figure 4.5:
0.12-
0.1 k r"
0.08-
0
L-
0.06-
0.04-
/ ,
0.02
0
0 1 2 3 4 5
Displacement[mm]
6 7 8
Ex vivo steady state stiffness of the liver (data from 2 animals).
9
54

0.1-
0
L-
0.08
0.06
0.04
0.16-
0.14-
-4- Median Force
A2
A3
-v- A6
-a- A7
0.12-
7,-
---
Figure 4.6:
0.02
0-
0 1 2 3 4 5
Displacement[mm]
6 7 8 9
Ex vivo steady state stiffness of the lower esophagus to displacements (data from 4 animals).
Figure 4.7 shows the in-vitro steady state stiffness of the liver. Figures 4.8 4.10 show
the in-vitro steady state stiffness of the lower esophagus in the Z, X and Y-direction. The plots in dashed, dotted and solid correspond to the median force response of the organs at approximately
6, 24 and 48 hours after the euthanasia of the animal.
0.25F-
-0- Median Force at 6 hours after euthanasia
.,0 Median Force at 24 hours after euthanasia
-0-
M
0.2
F
0.15-
0
0L
0.1 p0
....
.
0.05 -
0 1 2 3 4 5
Displacement[mm)
6 7 8
9
Figure 4.7: In-vitro steady state stiffness of the liver. Data was obtained from experiments conducted on A5,
A6 and A7 (data from 3 animals).
55

0.35-
-0- Median Force at 6 hours after euthanasia
0 Median Force at 24 hours after euthanasia
-0- Median Force at 48 hours after euthanasia
0.3-
0.25-
0.2z
0
L0.15-
"" ...
0.1
0.05-
0 1 2
I
3
I
4
I
5
Displacement[mm]
I
6 7 8 9
Figure 4.8: In-vitro steady state stiffness of the lower esophagus in the Z-direction. Data was obtained from experiments conducted on A5, A6 and A7 (data from 3 animals).
0.08-
0.07-
-0- Medi
0" Medi
-,- Medi an Force at 6 hours after euthansia an Force at 24 hours after euthansia an Force at 48 hours after euthansia
0.06-
0.05z
0.04 -
0
U-
0.03-
0.02
---
0.01 01r
0
L_
0 1 2 3 4
Displacement[mm]
5 6 7
Figure 4.9: In-vitro steady state stiffness of the lower esophagus in the experiments conducted on A6 and A7 (data from 2 animals).
X-direction. Data was obtained from
56

0.16-
-a- Median Force at 6 hours after euthansia
0 Median Force at 24 hours after euthansia
0.14 -e- Median Force at 48 hours after euthansia
0.12-
0.1
0.08 -
0
0.02-
0 1 2 3 4
Displacement[mm]
5 6 7
Figure 4.10: In-vitro steady state stiffness of the lower esophagus in the Y-direction. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals).
From the above plots, it can be seen that the in vivo steady state stiffness of the lower esophagus is significantly higher than the liver. The esophagus has a higher force response than the liver when displaced to the same depth. However, the liver exhibits a higher degree of nonlinearity while the esophagus is fairly linear within the limits of the experimental conditions in all three orthogonal directions. Force responses of the esophagus in the three directions are also fairly similar, indicating that the organ is not significantly anisotropic.
Effect of death on the steady state stiffness of these biological tissues is shown by the increase in the steady state force response at the same displacement depth and the increasing non-linearity. For both liver and lower esophagus, steady state force responses are significantly higher and increasingly non-linear in the ex vivo and in-vitro experiments than in the in vivo experiments. In-vitro steady state force responses of both the organs show increasing force responses and non-linearity with time. The force responses of both organs are higher and exhibit greater non-linearity for the measurements made with time after the euthanasia of the animal.
The above results are clear indications that mechanical properties of biological tissues change after the death of the animal. The amount by which the mechanical properties differ of biological tissues from the in vivo mechanical properties is highly dependent on the time after the death of the animal.
57

In this section, we present the in vivo and in-vitro impedance and power dissipation of the liver and lower esophagus. These frequency dependent material properties were inferred from the data obtained from sinusoidal indentation experiments.
When a viscoelastic material is subjected to sinusoidal varying strain, the relaxation modulus of the material, which relates the stress to the strain can be described by a complex function, E(o) of the form:
E(w) = E'(w) + iE"() =1 E(w)Ied"5
The real part of this function describes the in phase stress-strain ratio while the imaginary part of the function describes the 900 out of phase ratio. Loss angle, 6 characterizes the amount of mechanical damping in the system. Loss tangent, Tan(8) is proportional to the ratio of the dissipated energy to the energy stored in the material and is a measure of the internal friction in the system. Stress-strain relationship of the viscoelastic material plots an elliptical loop that encloses a finite area. The area enclosed by this hysteresis loop represents the energy dissipated per volume, per cycle of the material [49]. Without taking the geometry of the organs or indenter into account, the relaxation of the material can be described by the impedance. Similar to the relaxation modulus, the impedance is a complex function and has a magnitude and an associated phase angle
In this experiment, magnitude of impedance for a single cycle of indentation is calculated as the ratio of the peak-to-peak magnitude of the force response to the peak-to-peak magnitude of the displacement. $ is calculated as follows:
= 2/7Atf where At f = the time lag between the displacement and the force response.
frequency of indentation.
For the purpose of data analysis, At was calculated as the mean value of time difference between the maximum displacement and maximum force response and time difference between the minimum displacement and minimum force response in the cycle. Since the area enclosed by the force-displacement profile represents the dissipated energy per cycle, power dissipation is the product of the area within the hysteresis loop and the frequency of indentation.
58

The above analysis was performed on every cycle in the last 10 seconds of each data set.
Since frequency of indentation is different, the number of cycles analyzed in each data set is different. The values of the various parameters for each set were taken as the median value for all cycles analyzed. The median parameter value for each animal was then taken. A linear relationship was assumed between the various data points.
For the in vivo plots, the values for the individual animals are shown as dotted lines.
Median values over all animals are shown as bold solid lines. For the data obtained from in vivo experiments, median values between 2.0 Hz and 3.0 Hz were plotted as dotted lines to represent a higher degree of uncertainty. For the in-vitro plots, median values of the different parameters at
6, 24 and 48 hours after the euthanasia of the animal are plotted as dashed, dotted and solid lines.
Figures 4.11- 4.12 show the in vivo impedance of the liver and the lower esophagus. Figures 4.13
-
4.14 show their respective power dissipation.
0.03-
.0.025 ------
0.02
-
-.
0.015-
-0- Median
0.01
- -0 + A1
-- A4
0.005
A6
4-
A7
0
L
0 0.5
0-
1 1.5
Frequency[Hz]
2 2.5 3
S-0.4 -
4
-0- Median
+
Al
-+- A4 ch+ A6
S -0.6 -- A7 a..N
-0.8
0 0.5 1 1 5
Frequency[Hz]
2
Figure 4.11: In vivo impedance of the liver (data from 4 animals).
I
2.5 3
59

0.05 r g0.04
E
0.03
2
0.02
0.01
01
0
-0-
Median
-o-
Al
A3
+- A4
-- A6
0.5
0-
-0.5-
1 1.5
Frequency[Hz]
2
- - - - - - - - - - - - - - - - - --
- - - - - - - - ---------
2.5 3
Figure 4.12:
-e- Median
0
2
1.5 - <-A3
A4
-e- A6
0 0.5
1 1.5
Frequency[Hz]
2 2.5
In vivo impedance of the lower esophagus (data from 4 animals).
*0
3
E
0.2-
0 0.15
0.1 -
0.35-
0.3-
-- Media
+ Al
+ A4
-- A6
A7 n Force
0.25
0.05-
Figure 4.13:
0 0.5 1 1.5
Frequency[Hz]
2 2.5
In vivo power dissipation of the liver (data from 4 animals).
3
60

0.4
0 0.3
0.2-
0.1 -
0.7-
-0- Median Force
-*- Al
-+- A3
0.6 -+- A4
-e- A6
0.5
Figure 4.14:
0
0 0.5 1 1.5
Frequency[Hz]
2 23
In vivo power dissipation of the lower esophagus (data from 4 animals).
Figures 4.15 4.16 show the in-vitro impedance of the liver and the esophagus. Figures
4.17 - 4.18 show their respective power dissipation.
0.12 z
0.1 -
0.08
,
0o..0
------------------.------------------S0.06-
0.04-
-0- Median at 6 hours after euthansia
0.02- "0, Median at 24 hours after euthansia
0
0
-4- Median at 48 hours after euthansia
1
0.5 1 1.5
Frequency[Hz]
2
I
2.5
0
-0.2 -
3
Cn
CU
= -0.6 - -
Median
"." at 6 hours after euthansia
Median at 24 hours after euthansia
-6- Median at 48 hours after euthansia
-0.8
0 0.5 1 1.5
Frequency[Hz]
2 2.5
0
3
Figure 4.15:
(data from 2 pigs).
In vitro impedance of the liver. Data was obtained from experiments conducted on A6 and A7
61

Gp z
E 0.1
-
20.05
0-- .... -.--
01
0 0.5 1 1.5
Frequency[Hz]
-0- Median at 6 hours after euthansla
"0"
Median at 24 hours after euthansia
-*- Median at 48 hours after euthansia
2 2.5 3
0
0.2
-0.4
IL
.c-0.6
0.
-- - Median
-- " Median
6 hours after euthansia at 24 hours after euthansia at 48 "ours after eut ai
0.5
1 .5
Frequency[Hz]
'at
2.5 3
Figure 4.16: and A7 (data
In vitro impedance of the lower esophagus. Data was obtained from experiments conducted on A6 from 2 animals).
0.7
0.6 -
-0- Median at 6 hours after euthansia
*," Median at 24 hours after euthansia
-e- Median at 48 hours after euthansia
0.5
S0.4
E
6
.
o00.3
0.
F.
00A
0 -
0
0.5 1 1.5
Frequency[Hz]
2 2.5 3
Figure 4.17: In vitro power dissipation of the liver. Data was obtained from experiments conducted on A6 and
A7 (data from 2 animals).
62

0.7-
-0- Median at 6 hours after euthansia
-o- Median at 24 hours after euthansia
-e- Median at 48 hours after euthansia
0.6-
0.5 -
0
0.3
0.2-
S
03.
0.1
1152 .
4P
0'
0 0.5 1 152
Frequency [Hz]
253
Figure 4.18: In vitro power dissipation of the lower esophagus. Data was obtained from experiments conducted on A6 and A7 (data from 2 animals).
The above results for both organs show that magnitude of impedance stays fairly constant within the limits of the experimental conditions. Phase angle decreases and power dissipation increases with frequency. Thus, as damping in the system, which is characterized by the phase angle, increases, power dissipation by the system also increases.
The esophagus and liver show fairly similar dynamic mechanical properties. Comparing between the impedances and power dissipation rates for both organs, it is seen that these parameters for both organs are fairly similar within the experimental range for both in vivo and
in-vitro conditions. However, in vivo impedance of the esophagus shows a sharp dip in the magnitude when increasing from 0.5 Hz to 1.0 Hz. This could be due to the effects of boundary or the physiological responses of the esophagus as explained in Section 3.1.1.
Both organs exhibit higher magnitudes of impedance in their respective in-vitro measurements. However, the in-vitro phase angle and power dissipation does not differ much from the in vivo measurements.
63

Tables below summarize the values of the various material parameters obtained from the analysis carried out in this chapter. Numbers entered into the matrices below are the median values inferred.
Liver
Steady State Force Responses
Displacement
[mm]
1
2
4
6
8
In vivo [N]
0.0048
0.0079
0.0196
0.0396
0.0718
Magnitudes of Impedance
Frequency [Hz]
0.5
1
2
3
In vivo [N/mm]
0.0199
0.0218
0.0207
0.0238
Ex vivo [N]
0.0083
0.0187
0.0573
0.0961
0.1403
In-vitro at 6 hours [N]
0.0024
0.0084
0.0318
0.0666
0.1395
In-vitro at 24 hours [N]
0.0029
0.0073
0.0203
0.0595
0.1332
In-vitro at 48 hours [N]
0.0024
0.0078
0.0313
0.0979
0.2241
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[N/mm] [N/mm] [N/mm]
0.0561
0.0642
0.0622
0.0714
0.0838
0.1016
0.0631
0.0591
0.0832
0.1156
0.1109
0.1177
Impedance Phase Angles
Frequency [Hz]
0.5
1
2
3
In vivo [rad]
0.0000
-0.0845
-0.3931
-0.6604
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[rad]
-0.0020
-0.1395
-0.4088
-0.7252
[rad]
0.0000
-0.1022
-0.3774
-0.6604
[rad]
-0.0115
-0.1238
-0.4088
-0.7075
Power Dissipation Rates
Frequency [Hz]
0.5
1
2
3
In vivo [mW]
0.0062
0.0130
0.1287
0.3276
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[mW] [mW] [mW]
0.0060
0.0568
0.0031
0.0463
0.0133
0.0790
0.2575
0.5455
0.2415
0.5411
0.3043
0.4604
Table 4.1: Summarized values for the liver under different experimental conditions. Table on the first row shows the steady state force responses with displacements. Tables in the second, third and fourth row respectively show the magnitudes of impedance, impedance phase angles and power dissipation rates with frequency.
64

Esophagus in Z-direction
Steady State Force Responses
Displacement
[mm]
1
2
4
6
8
In vivo [N]
0.0072
0.0182
0.0427
0.0791
0.1114
Ex vivo [N]
0.0044
0.0142
0.0270
0.0640
0.0932
In-vitro at 6 hours [N]
0.0040
0.0098
0.0253
0.0482
0.1225
In-vitro at 24 hours [N]
0.0053
0.0112
0.0413
0.0883
0.1731
In-vitro at 48 hours [N]
0.0040
0.0130
0.0382
0.1191
0.3006
Magnitudes of Impedance
Frequency [Hz]
0.5
1
2
3
In vivo [N/mm]
0.0332
0.0231
0.0246
0.0213
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[N/mm] [N/mm] [N/mm]
0.0423 0.0606 0.1128
0.0512
0.0640
0.0590
0.0690
0.0695
0.0736
0.1205
0.1253
0.1260
Impedance Phase Angles
Frequency [Hz]
0.5
1
2
3
In vivo [rad]
-0.0019
-0.1061
-0.3774
-1.2028
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[rad] [rad] [rad]
0.0000 0.0000
-0.1101
0.0000
-0.1140
-0.0668
-0.3774
-0.6604
-0.3931
-0.6840
-0.4088
-0.7075
Power Dissipation Rates
Frequency [Hz]
0.5
1
2
3
In vivo [mW]
0.0089
0.0173
0.1238
0.3478
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[mW]
0.0080
[mW]
0.0061
[mW]
0.0041
0.0305
0.2623
0.0514
0.2906
0.0660
0.2796
0.5285 0.5258 0.3867
Table 4.2: Summarized values for the esophagus in the Z-direction under different experimental conditions.
Table has the same format as Table 4.1.
65

Esophagus in X-direction
Steady State Force Responses
Displacement [mm]
1
2
4
6
In vivo [N]
0.0076
0.0189
0.0383
0.0611
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[N] [N] [N]
0.0100 0.0201 0.0203
0.0159 0.0284 0.0361
0.0224 0.0461 0.0581
0.0287 0.0625 0.0797
Table 4.3: Steady state force responses of the esophagus with displacements in the X-direction under different experimental conditions.
Esophagus in Y-direction
Steady State Force Responses
Displacement [mm]
1
2
4
6
In vivo [N]
0.0069
0.0244
0.0464
0.0844
In-vitro at 6 hours In-vitro at 24 hours In-vitro at 48 hours
[N] [N] [N]
0.0233
0.0409
0.0269
0.0490
0.0185
0.0521
0.0765
0.1134
0.0957
0.1325
0.0903
0.1480
Table 4.4: Steady state force responses of the esophagus with displacements in the Y-direction under different experimental conditions.
66

5
This thesis provides an overall framework for the measurement of in vivo mechanical properties of intra-abdominal organs for surgical simulation. In vivo static and dynamic mechanical behaviors of the liver and lower esophagus of pigs were characterized in the linear and nonlinear regions. The organs were also measured under ex vivo and in-vitro conditions and comparisons were made between the respective mechanical properties. Specific contributions of this thesis are as follows:
The Phantom was programmed to function as a mechanical stimulator for delivering indentation stimuli to intra-abdominal organs in vivo. A 2 mm flat-tipped cylindrical probe was attached to its tip with a force transducer in-between to accurately measure the reaction forces.
This experimental setup can be used to conduct future tissue measurement experiments.
An experimental protocol was developed for the systematic measurement of the mechanical properties of biological tissues for surgical simulation. Ramp and hold as well as sinusoidal indentation stimuli were used in this study. These indentation stimuli were delivered to the organs and reaction forces measured. Conditions for the stimuli were designed such that they closely mimicked the conditions in an operating room.
Preliminary in vivo experimental results showed that breathing of the animal significantly affects the organ force responses from the indentation stimuli. Breathing of the animal creates motions and forces that greatly exceed the organ force responses from the stimuli. Holding the respiration of the animal during the course of stimuli application prevented these artifacts during data collection.
67

Pulse rate of the animal generates sinusoidal varying forces that are superimposed on the force responses from the organs. These sinusoidal forces can be subsequently filtered offline using a digital low pass filter.
Preliminary results showed that the boundary conditions of the lower esophagus in-situ might have resulted in the additional peak observed in the in vivo and ex vivo force responses.
This additional peak is not apparent in the in-vitro force responses of the lower esophagus. This peak might also have been due to the psychological response of the esophagus to rapid stretching.
Steady state stiffness of the organs was inferred from the data collected from ramp and hold indentation. Results from experiments show that in vivo steady state stiffness of the lower esophagus is significantly higher than that of the liver. The in vivo steady state stiffness of the liver however, exhibits a greater degree of non-linearity than that of the lower esophagus.
Comparing the in vivo steady state stiffness of the lower esophagus in the three orthogonal directions do not indicate that the lower esophagus is significantly anisotropic.
Comparing between the in vivo, ex vivo and in-vitro steady state stiffness of the respective organs indicate that the mechanical behaviors of biological tissues change after the death of the animal.
Ex vivo and in-vitro steady stiffness of both organs are much higher than for their respective in
vivo measurement. The amount of change is highly dependent on the time after the death of the animal. The steady state stiffness also becomes increasingly non-linear with time after the euthanasia of the animal. This conclusion is reached by comparing between the in-vitro measurements made.
Impedance and power dissipation of the organs to dynamic indentations are inferred from the sinusoidal indentation data. Measurements indicate that the in vivo magnitudes of impedance, impedance phase angles and power dissipation for both organs are fairly similar over the range of stimulus frequencies. The magnitudes of impedance stay fairly constant for the range of frequencies applied. Phase angles between the force responses to displacements decrease while power dissipating increases with frequency. This trend is observed for the dynamic responses of both organs. Comparing between the in vivo and in-vitro measurements for both organs show that their respective magnitudes of impedance increase for the in-vitro measurements. Phase angles and power dissipations of the organs do not seem to differ significantly between the respective in vivo and in-vitro organ measurements.
68

This thesis is an initial attempt at characterizing the in vivo mechanical properties of the liver and lower esophagus for surgical simulation. However, data obtained from the experiments cannot be directly integrated into the simulator, as they are indenter-dependent. We require parameters independent of the indenter geometry for surgical simulation. These parameters can then be utilized for calculating the amount of visual deformations and forces to be presented to the user from the virtual tool-tissue interactions. Efforts are currently being made to derive a best-fit mathematical model for describing the force response as a function of displacement and velocity.
A finite element model incorporating the geometry of the organs can also be developed. Material parameters associated with the model can be fine-tuned with the inputs and outputs from the experiment to infer accurate material properties.
This work was concerned with correlating the force-displacement relationship of organs to indentation stimuli. For developing an accurate finite element model, not only the force displacement relationship has to be known. Deformation of the organs in the region of the indentation site have to be quantified so that these data can also serve as inputs into the model.
Quantification of the deformation areas around the indentation sites can be realized by capturing stereoscopic images of the organ deformations as they are being indented.
The effects of death of the animal on the mechanical properties of organs were determined through comparing between measurements on the respective organs under different experimental conditions. However, this change in the mechanical properties of the organs might be due to degeneration of the tissues or loss of blood pressure or a combination of both. To more quantitatively infer the effects of tissue degeneration on the mechanical properties of biological tissues, the in-vitro experiments can be carried out with the organs suitably perfused with fluids to simulate blood flow. This would decouple the change in mechanical properties due to tissue degeneration and loss of blood pressure. Possibly, future experiments to determine the mechanical properties of biological tissues could even be carried out on cadavers if experimental results were to show that tissue degeneration does not significantly change the mechanical properties of biological tissues.
69

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