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(inf—w.- uxl-wr; ‘ l W ‘ "tr 0; '4‘ ; 4'. . 1w J MICH'GM STATE WNEHSWY LIBRARIES 2 8 5’9 3—2/2 X, lllllllllllllllHllllllllllllllllllllllllllllHllllllllllllll : 3 1293 00788 4046 ; USERARY l :t-l Q ' “ ' I 585 ngclzsgan $3.1, ; University 3 L— This is to certify that the thesis entitled NON-INVASIVE TEMPERATURE MEASUREMENT BY ULTRASONIC TECHNIQUES presented by Di Ye has been accepted towards fulfillment of the requirements for Mr S. degree in__E|echjggl Engineering 7 Major p essor Date June 26, 1989 0-7639 MS U is an Affirmative Action/Equal Opportunity Institution PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. DATE DUE DATE DUE DATE DUE l , , ] MSU Is An Affirmative Action/Equal Opportunity Institution cAcIrchma-pd NON -INVASIVE TEMPERATURE MEASUREMENT BY ULTRASONIC TECHNIQUES By Di Ye A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Electrical Engineering and Systems Science 1989 (90501;!) ABSTRACT NON-INVASIVE TEMPERATURE MEASUREMENT BY ULTRASONIC TECHNIQUES By Di Ye Non-invasive temperature measurement utilizing a micro-computer based ultrasonic imaging system for in- vitro tissue studies has been investi- gated. This work is based on the theory that the velocity of ultrasound in a medium is a function of temperature, and on previous experimental results of temperature dependent sensing in biological tissues. The work reported here represents a special technique developed recently to monitor the rela- tive temperature change in tissues in a simulated hyperthermia treatment situation. The technique involves wave pattern matching to detect the echo phase change due to temperature variation in the tissue. A 40 MHz sampling rate data aquisition system is used to obtain high resolution in velocity change so that a 0.20C temperature change may be identified. Temperature profile imaging of an experimental model has been obtained. The techniques used and experimental results obtained are presented. Acknowledgements I wish to thank Dr. Bong Ho, my advisor, for his timely guidance and support. I wish to thank Dr. H. Roland Zapp and Dr. R. O. Barr for their suggestions relevant to this research. I wish to thank Mr. Nai Hsien Wang and Mr. Mo Zhang for their aid in the use of the computer software developed in the Ultrasound Research Laboratory and in assistance with equipment operation. I would like to thank my parents and my wife for their constant help and encouragement. iii Table of Contents List of Tables ............................................................................... vi List of Figure ............................................................................... vii Chapter 1 Introduction ................................................................. 1 Chapter 2 Theoretical Considerations ......................................... 5 2.1 Review of Ultrasound Principles .................................... 5 2.2 Temperature Dependence of Ultrasonic Propagation ...................................................................... 9 Chapter 3 Acoustic Considerations for Temperature Monitoring ........................................................................ 18 3.1 Ideal Step-Function Temperature Distribution Model ........................................................... 18 3.2 Effect of Realistic Temperature Distribution ................. 21 3.3 Effect of the Nonlinear Relationship Between Temperature and Velocity ................................ 25 Chapter 4 Velocity Measurement Techniques ............................ 30 4.1 Review of Temperature Measurement ........................... 30 4.1.1 Interferometric Techniques .......................................... 30 4.1.2 Pulse-echo Overlap Technique .................................... 31 4.1.3 Phase-slope Method ..................................................... 32 4.1.4 Cross-correlation Method ............................................ 36 4.1.5 Acoustic Phase Shift Technique .................................. 39 4.1.6 Other Techniques ......................................................... 43 iv 4.2 Temperature Measurement Technique in This System ............................................................... 47 Chapter 5 System Configuration and Operation ......................... 49 5.1 Hardware Description ..................................................... 49 5.1.1 Non-intrusive Temperature Measurement System ...... 49 5.1.2 Intrusive Temperature Measurement System .............. 55 5.2 Software Description ...................................................... 58 5.3 System Operation ............................................................ 63 Chapter 6 Experiment Design and Procedures ............................ 65 6.1 Experiment 1: The Ultrasound Velocity Change of Oil due to Temperature Variation ............................... 65 6.2 Experiment 2: Temperature Profile in Water ................. 72 6.3 Experiment 3: Temperature Profile Probing . of a Layered Model .......................................................... 79 6.4 Experiment 4: Design Considerations and Procedural Aspects for Biomedical Tissue Studies ......... 86 Chapter 7 Analysis of Experiment Results .................................. 94 7.1 Analysis and Discussion ................................................. 94 7.1.1 Accuracy and Time Resolution ................................... 94 7.1.2 Medical Applications ................................................... 98 7.2 Conclusion and Future Study .......................................... 101 Bibliography ................................................................................ 103 List of Tables Table 2.1.1 Approximate values of ultrasonic velocities of various media ........................................................ 8 Table 7.1.1 Change in ultrasonic velocity as a function of temperature elevation and path length .................. 97 vi List of Figures Figure 2.2.1 Temperature variation of the velocity of ultrasound in water ............................................... 14 Figure 2.2.2 Speed of sound vs. temperature in-vivo runs ......... 15 Figure 2.2.3 Variation of velocity of sound with temperature in various tissues ....................................................... 16 Figure 2.2.4 Variation of velocity of sound with temperature in breast tissues ......................................................... 17 Figure 3.1.1 The step-ftmction temperature profile .................... 20 Figure 3.2.1 Temperature - Duration threshold for histological damage .................................................. 24 Figure 3.3.1 (a and b) Illustration of sound velocity as a function of temperature across a non-uniform temperature profile .................................................... 28 Figure 3.3.1 (c and (1) As above ................................................... 29 Figure 4.1.1 The phase - slope method ....................................... 34 Figure 4.1.2 The phase - slope method ....................................... 35 ' Figure 4.1.3 Cross - correlation method ..................................... 38 Figure 4.1.4 The system operation for phase shift technique ................................................................... 40 Figure 4.1.5 Phase shift technique .............................................. 41 Figure 4.1.6 Acoustic phase shift with temperature ................... 42 Figure 4.1.7.a Ultrasound computerized tomography system ..... 45 Figure 4.1.7.b Data collection geometry for ultrasonic computerized tomography ....................................... 48 vii Figure 5.1.1 Non-intrusive temperature profile probing system 53 Figure 5.1.2 Typical ultrasound pulse waveform ...................... 54 Figure 5.1.3 Invasive temperature measurement system ............ 57 Figure 5.2.1 The flow chart of scanning and data acquisition program ................................................. 61 Figure 5.2.2 The flow chart of data averaging program ............. 62 Figure 5.2.3 Program for processing B-scan data ...................... 64 Figure 6.1.1 The set up of experiment 1 ..................................... 68 Figure 6.1.2 A typical echo return with noise ............................ 69 Figure 6.1.3 An echo return after averaging process .................. 70 Figure 6.1.4 The autocorrelation results of the acoustic velocity change ........................................... 71 Figure 6.2.1 3-dimensional image for flat temperature gradient in water ....................................................... 75 Figure 6.2.2 Temperature profile of water without the use of reference signal .............................................. 76 Figure 6.2.3 Temperature profile in water with the use of reference signal .................................................... 77 Figure 6.2.4 Temperature profile in water by using fluoroptic thermometer ............................................. 78 Figure 6.3.1 A layered temperature gradient model ................... 81 Figure 6.3.2.a B-scan image to show a boundary shifting .......... 82 Figure 6.3.2.b B-scan image for temperature measurement ........ 83 Figure 6.3.3 Temperature profile of the upper region viii of the model .................. 84 Figure 6.3.4 Temperature profiles of the lower region of the model ............................................................. 85 Figure 6.4.1 The set up for experiment 4 ................................... 91 Figure 6.4.2 The echo waveform of a pork kidney .................... 92 Figure 6.4.3 B-scan image of a pork kidney to show the boundary shift due to temperature changes .............. 93 Figure 7.1.1 Effect of time-of-flight resolution on detectability of local ultrasound speed change ......... 97 ix CHAPTER 1 Introduction Non-invasive temperature monitoring has many important applications in areas of hyperthennia treatment of cancer, studying physical properties of materials, power generation and nuclear reactor safety monitoring. The use of focused ultrasound to induce localized hypenhermia in malignant tissue is currently being investigated in many places. The purpose of these investigations is to selectively damage malignant tissue in order to inhibit its growth and ultimately cause its disappearance. The ideal tempera- ture for hyperthermia treatment is to have the tumor at the threshold level (425°C) or above and the surrounding healthy tissues at normal levels (37°C ). Temperature distributions have been produced in tissue which come very near to this desired distribution so that lab experiment may be per- formed [1]. During hyperthermia the treated region requires accurate temperature monitoring to ensure that normal tissue is not damaged. Current practice is to insert thermocouples or thennistors encased in hypodermic needles to make the necessary measurements. The invasiveness of this technique limits the number of temperature probes used and in some cases makes it very 2 cumbersome because repeated insertion can result in other hazards such as infection and tissue destruction. In addition, placing temperature probes into the treated region often complicates the heating process [2]. A method of monitoring the temperature rise during hyperthermia without intrusion into the body would clearly be beneficial. Non-invasive temperature measurements are also widely used to deter- mine. properties and states of materials. There has been an increasing use of ultrasonic temperature measurements for nondestmctive characterization of material microstructures and mechanical properties. Therefore, it is impor- tant to have appropriate practical methods for making temperature measure- ments for a variety of purposes. A number of approaches to non-invasive temperature measurement have been used. Among the approaches are those that use single-frequency continuous waves, tone bursts, and broadband pulse-echo waveforms. In the latter case, the basic problem is to determine the time delay between succes- sive echoes, from which the velocity change as a function of temperature could be measured. The pulse-echo approach using a single transducer as both transmitter and receiver has many practical advantage over the transmission methods and therefore will be treated exclusively in this thesis. The measurement technique developed in this thesis is theoretically 3 based on the ultrasonic velocity as a function of temperature. The technique is also based on computer digitization of broadband pulse-echo waveforms. A number of software routines have been implemented in the ultrasonic imaging system in the Ultrasonic Research Laboratory for the purpose of non-invasive temperature measurement. The immediate objectives of the work reported here are to monitor tem- perature distributions inside a layered material and to obtain temperature profiles of experimental models with well-defined boundary and temperature gradients. The work described here provides a base for future research and applications in medicine and engineering. This research is to seek the feasi- bility of using ultrasound as a supplemental or primary mode of non- invasive temperature monitoring during simulated hyperthermia treatment. Techniques to be developed include the use of higher data sampling rate, calibration of standard materials for absolute temperature mapping. The most common used medical imaging techniques use X-rays or ultrasound. X-ray technology, including CAT scans, and ultrasound tech- nology present images which essentially show differences in density. This is generally easy to visualize. ( More specifically, ultrasonic B-scan images show sharp differences in the acoustic impedance pc , or density times pro- pagation velocity and radiography using X-ray radiation shows the spatial distribution of X-ray attenuation coefficients which are highly density 4 dependent.) The difficulty with any thermal imaging technique is to present an image with various temperature gradients. For infra-red imaging, digital signal processing techniques are used for color coding to display the regions of different temperature. This type of imaging display could very well be employed by ultrasonic non-invasive temperature monitoring. The contents of this thesis are organized as follows. First, the theoreti- cal foundations of the temperature dependence of ultrasound propagation are reviewed. Second, judging from published research results, theoretical con- siderations for temperature monitoring will be described as the experimen- tal basis. Third, a variety of non-invasive temperature measurement tech- niques are briefly described for overviewing and comparison. The remainder of the thesis will devote to the details of the research work in ultrasonic tem- perature monitoring, including system configuration, experiment design, result and analysis. The system limitations and suggestions for future study will also be discussed. CHAPTER 2 Theoretical Consideration This chapter provides the necessary theoretical background for the proposed techniques of non-invasive measurement of temperature . In the first section, some related ultrasound principles are reviewed. It is followed by the theoretical foundations of ultrasonic propagation on temperature profiles. Some new measurement techniques are proposed and imple- mented based on literature review and laboratory experiments. 2.1 Review of Ultrasound Principles It is useful to examine the theoretical foundations of temperature dependence on ultrasonic propagation. This information is well docu- mented in the literature and is included here for completeness and con- venience. 2.1.1 Wave Motion Ultrasonic energy travels through a medium in the form of shear and longitudinal waves. The simplest type to be studied is a longitudinal sin- gle frequency displacement in an isotropic medium which is perfectly elas- tic. The energy is transmitted continuously, and the vibration is simple 6 harmonic lattice displacement about a mean particle position. A particle is an element of volume which is continuous with its surroundings, but small enough for quantities which are variable within the medium to be constant within the particle. The movement of the particles is resisted by elastic forces due to the molecular structure of the medium. Let us consider plane, non-spreading longitudinal waves. The dis- placement amplitude u from the mean position of particles in simple har- monic motion, at any instant t, and at a fixed point along the direction of the wave, where u=0 when t=0, is given by u = “0 sintot (2.1.1) where u 0: maximum displacement amplitude, and (0:21: f , where f is the frequency of the wave. Velocity is equal to rate of change of position, and so it may be found by differentiating the particle displacement with respect to time. Thus v u = uom cosmt (2.1.2) =3? Similarly, the acceleration a of the particle towards its mean position may be found by differentiating the particle velocity with respect to time. Thus _9v a — E = —u omzsinmt (2.1.3) 7 The significance of the negative sign is that the particle is decelerating as it moves away from its mean position. From Equations (2.1.1),(2.1.2) and (2.1.3), the phase of the particle velocity leads that of the particle displacement by a time interval corresponding to 3%- radians of phase-angle difference, while the accelera- tion is it out of phase with the displacement. Ultrasonic energy is transported by mechanical vibrations at frequen- cies above the upper limit of human audibility. The ultrasound consists of a propagating periodic disturbance in the elastic medium, causing the parti- cles of the medium to vibrate about their mean (equilibrium) positions. The vibratory motion of the particles is essential to energy propagation. The transmission through the medium is strongly dependent on the ultrasound frequency, temperature and the state of the medium such as gas, liquid, or solid. The velocity values listed in Table (2.1.1) are under the assumption of constant temperature of some fixed value. The table illustrates the velocity dependency on the medium composition. Below some temperature, the speed at which ultrasonic vibrations are transmitted through a medium is inversely proportional to the square root of the product of the density and the adiabatic compressibility of the material. The speed of sound ( c ), along with frequency (f) determine Table 2.1.1 Approximate values of ultrasonic Velocities of various media [1] 1 Medium Sound Velocity (m/sec) Dry air (20°C )%343.6 Water (37°C )% 1524 Amniotic fluid 1530 Brain 1525 Fat 1485 Liver 1570 Muscle 1590 Tendon 1750 Skull bone 3360 Uterus 1625 the wavelength (A), from the relationship 7. = 5- (2.1.4) f The knowledge of the speed at which ultrasound is transmitted through a medium is used in the conversion of echo-retum time into depth of material being imaged. 2.2 The temperature dependence of ultrasonic propagation It is important to realize that, although energy is transmitted through the medium as the result of a wave motion, no net movement of the medium is required for this to occur. In reality, the whole of the curve in Figure (2.1.1) is moving forward with a velocity c , which is measured by the distance which any particular part of the curve travels in unit time. For this reason, it is sometimes called a travelling or progressive wave. The phase of the wave indicates in what part of the vibrational cycle the wave happens to be at any partic- ular instant of time. The transmission of the disturbance is not infinitely ' fast, because a delay occurs between the movements of neighbour parti- cles. The velocity of propagation is controlled by the density of the medium and its elasticity. The relationship depends upon the kind of material and the wave mode. It can be shown that, for longitudinal waves in fluids c = — (2.2.1) where K a = adiabatic bulk modulus, and p = mean density of medium. The adiabatic bulk modulus (which is the reciprocal of the adiabatic compressibility) is not the same as the isothermal bulk modulus K i 10 obtained by static measurements, although for most liquids the two quanti- ties are almost equal. Thus K a = 'y K,- (2.2.2) where y = the ratio of specific heat at constant pressure to that at constant volume. In the case of longitudinal bulk waves in isotropic solids, the situation is complicated by the fact that the shear rigidity of the medium couples some of the energy of the longitudinal wave into a transverse mode. The appropriate modulus for calculating the velocity contains not only a term which depends upon the bulk modulus, but also one which depends upon the shear modulus. The formula is c = \l K “:30 (2.2.3) where G = shear modulus. The bulk and shear moduli are related to Young’s modulus Y and Poisson’s ratio 0 as follows: _ __Y_ K " \/ 3(1—2o) _ , / Y G " 2(1+o) Substitution of these values in Equation (2.7) gives 6 .-_- \/ “1“” (2.2.4) (1-20)(1+G)P 11 The elastic constants are temperature-dependent, and so the velocity alters with temperature. The relationship can be quite complicated; for example, Figure (2.2.1) shows the temperature variation of the velocity of ultrasound in distilled water at atmospheric pressure. The temperature dependency of ultrasound has been also investigated by Isaak Elpiner [3], who provided the basic laws governing the propaga- tion of ultrasound waves in gases, liquids, and solids. The velocity of sound waves c in gases is given by the Laplace for- mula if the amplitude of the vibrations is relatively small: = 4/15. = «’1. c p MRT (2.2.5) ~ c where P is the pressure, p is the density of the gas, 7:};- is the ratio of V the specific heat at constant pressure (cp) to the specific heat at constant volume (CV ), M is the molecular weight, R is the gas constant, and T is the absolute temperature. The velocity of sound in liquids depends on the compressibility and density of the medium and is calculated from the formula = _L.= _L 226 c Vfiadp Vfizsp (") where [3 is the compressibility, [3 = ——- (2.2.7) 12 that is, [3 is the relative change in volume when the pressure changes by dP; and Bad is the adiabatic compressibility, Bis is the isothermic compressibility, i.e., the compressibility at constant temperature. In a slender solid rod the velocity of longitudinal waves is E = — 2.208 c ' \l p ( ) where E is Young’s modulus and p is the density of the solid. In a rod where the cross-sectional dimensions are large in comparison with the wavelength (or in a solid of large dimensions), the velocity of sound will not be determined by Young’s modulus, but by the so-called bulk modulus. For the same material the latter slightly exceeds Young’s modulus. The velocity of ultrasound in air is 344 m/sec at room temperature (20°C). The velocity of sound in a liquid is generally greater than in a gas under the same conditions. The velocity of ultrasonic waves in a liquid diminishes with increase in temperature. Water is an exception. The velo- city of ultrasound in water increases at first, reaches a maximum at a tem- perature close to 80°C , and then diminishes with further increase in tem- perature. 13 The velocity of ultrasonic waves in solids is greater than in gases and liquids. For instance, the velocity of sound in nickel is 5000 m/sec, and in iron 5850 m/sec. In heavy. and inelastic metals (lead, for instance) the velocity of sound is 2169 m/sec. For soft biological tissues ( muscle, fat, nerves, liver ), the velocity of ultrasound is 1490-1610 m/sec, while for bone tissue it is 3300-3380 m/sec. As has been noted by Kinsler and others (1982), "theoretical predic- tion of the speed of sound for liquids is considerably more difficult than for (ideal) gases. However, it is possible to show theoretically that [3:157- where BT is the isothermal bulk modulus. Since no simple theory is avail- able for predicting these variations, they must be measured experimentally and the resulting speed of sound expressed as a numerical ( empirical) for- mula." Based on this point of view, it is essential that empirical relation- ships or point values based on experimentally determined values be used. Important results obtained for propagation velocity as a function of temperature for tissues are presented in Figures (2.2.2 - 2.2.4)[4]. 1575 14 l550 1525 1500 Volocity.m s" 1475 I450 I425 1400 l l l l O 20 4O 60 80 100 Temperature °C Figure 2.2.1 The temperature variation of the velocity of ultrasound in distilled water at atmospheric pressre. SPEED OF SOUND VS. TEMPERATURE IN VIVO RUNS 1600' .J.‘ o": 0' .- o ,- V .’0’ . .' 1590L ,-’ tn ' ’. \ ’0’ 2 . ,° auscuu . - ' ,- 0 .' . KIDNEY o I $1580 .v' ,‘ LIVER _.—._.. Q. 3‘ / SPLEEH --.-. U3 " BLOOD -.-.- .- .~/ 5'0““0’ ruuon ...... 32 36 40 . 44 TEMPERATURE c (Data from Nasoni, R. L., et a1. 1980) Figure 2.2.2 Speed of sound vs. temperature in-vivo runs. (Data from Nasoni, R.L., et a1, 1980) 16 L070! Paces Uncle Solon Sumo! Cord K0600] rum h a: 0 I Debno< U 0 H \ E x. I~ ‘ U 0 .1 In 5 L500 - [.460 L ' 1 ' ' J I6 24 32 40 TEMPERATURE,°C Figure 2.2.3 Variation of velocity of sound with temperature in various tissues. (Data from Johnson, S. A., et a1, 1977) 17 O Hose“ 0 Parencnymc A Salt Solution. 2.59/100 a: Son Soouhoa [£5.80 - O Baczqraund. 0.9g.’tao a: Son Selene. Q o L a \ E >~ .. I. 1.540 '9‘ Q 0 .J In > .- [.500 P L 1 I l J 20 28 35 “ TEMPERATURE,'C Figure 2.2.4 Variation of velocity of sound with temperature in breast tis- sues. (Data from Johnson, S. A., et a1, 1977) CHAPTER 3 Acoustic Consideration For Temperature Monitoring It is useful to review the literature on the topic of acoustic temperature monitoring. Conclusions from either theoretical or experimental studies can be used in the design of our temperature monitoring system. 3.1 Ideal Step-Function Temperature Distribution Model The ideal temperature for hyperthermia treatment is to have the tumor at a temperature of 425°C or above and the surrounding healthy tissue at the normal temperature of 37°C. The temperature distribution for this ideal situation was assumed using a step-function in some tissue studies. An example of the step-function distribution is shown in Figure (3.1 .1).[1] The step-function distribution lends itself readily to calculating tem- perature changes for non-invasive temperature monitoring because of its sifirplicity. With the lateral distance of the distribution, 2R , specified by the rotation of the scanning focused ultrasound, an initial speed of ultrasound, c , through the tissue determined experimentally before the hyterthermia treat- ment or by using an assumed value, the rise in temperature can be deter- mined from the change in the propagation velocity. The following equation can be used : 18 19 _ 2R _ AC — tl+A¢/md C1 (3.”) where 2R - outside diameter of the area of scanning focused ultrasound. t1 - initial propagation time across the distance 2R. Ad) - measured phase shift in radians. (ad - angular frequency of the diagnostic beam. c1 - the initial propagation velocity over the distance 2R 2. To determine the temperature change by using above equation, the rela- tionship between the propagation velocity and temperature must be known. 44 42 4O 38 20 DOG LEG IN VIVO - DEPTH 1cm i- 4 3 2 I o T 2 3 4 DISTANCE. cm Figure 3.1.1 The above temperature profile, which closely resembles a step-function, is the simplest model from which many calculations for non-invasive temperature monitoring are derived. The most important of these calculations includes the determination of the required system accu- racy. 21 3.2 Effect of Realistic Temperature Distribution If the step-function model for the temperature profile were precise, then the change in propagation velocity could be used to determine the tempera- ture rise directly and would involve ultrasonic scanning in one direction only. Since this is not the case, the next important consideration in the analysis of monitoring temperature distributions by acoustic means is then the examination of the temperature distribution as it deviates from a step- function. In fact, such an ideal temperature distribution is not possible because the heat flux -k(%-Zl;) would be discontinuous at the boundaries. That is, the prescribed temperature distribution would be nondifferentiable at the boundaries and thus could not exist. This is illustrated by noting the "smooth" edges of the temperature distribution in Figure (3.1.1). For hyperthermia treatment, the actual temperature profiles are unfor- tunately not always approximated well by step-functions, due to variable blood flow through tumors, their irregular shapes, and possible inhomo- geneities in the associated acoustic and heat transfer properties such as den- sity, thermal capacitance and conductivity. Thus the average temperature across a temperature profile may not necessarily correspond to the maximum temperature as is the case with a step-function-like distribution. Knowledge of the maximum and average temperatures is important in the treatment of 22 tumors by hyperthermia because of the known variable response of tissues to thermal doses. This effect is best illustrated by the results of a study done by Lele (1977) [5] shown in Figure (3.2.1). These results are also used in the formation of the protocol for treatment of tumors by focused ultrasound. As a consequence of these facts, it is useful to determine analytically the average temperature across a more realistic model of the temperature distri- bution as it relates to the maximum temperature in a step-function tempera- ture profile. This analytical determination is useful because it indicates the deviation of the real temperature profile and can subsequently be used to evaluate the utility of one-dimensional ultrasonic scanning in this applica- tion. As the conclusion of the study by Abramowitz, et a1 (1964) [6]. the ratio of the average temperature in the more realistic temperature profile and the average temperature across the ideal profile does not differ by much more than a factor of two. The range of values for TT/Tmam is 0.46 to 1.55. Since T/Tmax does not differ by much more than a factor of two, the use of the step-function model to approximate the required system accuracies is appropriate. In addition, if a thermocouple is used to determine Tmax while a tumor is being insonated with scanning focused ultrasound, the step-function model is still a good first approximation. The goal is, however, to use the change in propagation velocity across the insonation volume as a means to 23 calculate the maximum temperature directly. The conclusion is that if the temperature profile is indeed nearly a step-function, then the change in pro- pagation velocity can indeed be used to calculate the maximum temperature directly given c = f (T). But if the temperature profile evaluated is the more realistic one, T, the average excess temperature across the distribution, can only be determined from the change in propagation velocity if: (1) c =f(T) is known and (2) c = f (T) is linear over the temperature range investigated. The value T, if determined, does not give as much information concem- ing the temperature profile in the realistic model as the value Tmax does in the step-function model. This fact coupled with the third condition above are the major obstacles which limit the temperature profile information obtained by ultrasonic scanning in one-directin only. 24 TEAM-DURATION THRESHOLDS FOR 10 L00 HISTOLOGICAL DAMAGE BY DEEP LOCALIZED NEATING. uauuaum aura, In SPINAL CORD. my“. menu. SKELUAL a g CARDIAC MUSCLE. SKIN, in nu I 60 L x .U a F 1‘ 1.: ® ' ' a: g I: ' pun“ 3 . "i o ('5 so - ' Q I innate“: 5 cu, ooo. Mount? .— 2 HUMAN cum, 5. c INTRA-OPERAIWC 0 ma «or dis!!!“ ® 40 - O PIPPERS or or 'CORNEA A RODNEY-REC ® ® ® H ntumours no new: . Sam (9 one orrtcnett came: 0.1 I to: ID Irma. IO the ID secto“ 10° 10' to2 to’ to‘ to’ INSONATION OR HEATING DURATION (Data from Lele, 1977) Figure 3.2.1 Temperature - Duration threshold for histological damage by deep localized heating ( Mammalian brain, spinal cord, liver, kidney, skeletal and cardiac muscle, skin). 25 3.3 Effect of the Nonlinear Relationship Between Temperature and Velocity Another complication is the fact that many equations relating propaga- tion velocity to temperature are nonlinear. The influence of this nonlinearity is best illustrated by examining a simplified model, which exists for the temperature distributions, for the empirical relationships between propaga- tion velocity and temperature. To demonstrate this point, consider a simple nonuniform temperature distribution as shown in Figure (3.3.1.a). Note that the average excess tem- perature through the distribution is T. The approximate relationship between c and T is given in Figure (3.3.1.b). Figure (3.3.l.d) is obtained by switch- ing the axes of Figure (3.3.1.a) and Figure (3.3.1.b). The estimate of the average temperature across the distribution is made and is compared to the average velocity. The simple result of the nonlinearity is that E ref—(T) although c = f (T) for nonuniform distributions. (The bar notation above the variables represents the average value of that variable over the distribu- tion). This is a very important point that does not seem to have been stressed in previous work done on the determination of c = f (T) in tissues. In fact, in some studies a great deal of effort was expended using regression analysis to fit higher order polynomials with coefficients of three significant figures to the obtained data. It was assumed that the average temperature across a 26 nonuniform temperature profile could be used to determine the propagation velocity as a function of temperature even if this functional relationship were nonlinear. This error can further be illustrated analytically. Consider the functional notation for the temperature distribution and propagation velocity as a function of temperature given below: (1) T = g (x) is the temperature distribution. (2) c = f (T) is the propagation velocity as a function of temperature (non- linear). The current average velocity over the temperature distribution from a to b is: 1 b 75:; if [g(x)ldx (3.3.1) and this is correct average velocity provided that c = f (T) is known. If c has a linear relationship to T, i.e., C =A1T +A2 (3.3.2) where A1 and A2 are constant, then the average velocity may also be obtained from 1 b dx . 3.3.3 fl'b—_a£g(x) 1 < ) The impact of the nonlinearity between c and T with regard to ultra- sonic non—invasive temperature monitoring is that when there exists a 27 nonuniform temperature distribution, the change in ultraSonic propagation velocity cannot be used to determine the average change in temperature across the temperature profile unless (l) the temperature distribution is ,in fact known to be uniform or (2) the velocity distribution is determined by B-scan or C-scan. In either case, c = f (T) must be known and the distribution prior to insonation must be uniform and known. 7]: __ T(x) . l , X=O x=b x c 11 b a T Figure 3.3.1 (a and b) Illustration of the problem associated with deter— mining sound velocity as a function of temperature using the average tem- perature across a non-uniform temperature profile. T 4’ 6.6c c T t A C(x) '5' __... T __ T00-a d i \ o x b 29 T = 8(4) c =f(T) 6(4) =11 8(4) 1 1 b figment: <1) 2:- b 1 M11 [gram-1 (2) a (T: Figure 3.3.1 (0 and CI) Note: This is generally true for nonuniform tem- perature distributions and nonlinear relationships between c and '1‘. 111 some lmnted eases (l)=(2), but (1) is the correct expression for Fund (2) is not. CHAPTER 4 Velocity Measurement Techniques A variety of techniques have been developed for measuring ultrasound propagation velocity. Methods are used for either detecting temperature variation or determing characteristics of materials. 4.1 Review of Temperature Measurement 4.1.1 Interferometric techniques Interferometric techniques are usually use continuous waves and only one transducer in a reflection mode. The velocity is'measured by setting up a standing wave between the transducer and the reflector and varying the dis- tance between the two, producing minima corresponding to integral numbers of half wavelengths. This technique relies on an accurate measurement of the distance between reflector and transducer and also on accurate measure- ment of the frequency. The velocity is then calculated from the known fre- quency and measured wavelength. As noted by Wells (1977)[7], “the accuracy of the method depends on the parallelism of the opposite ends of the interferometer, and a high degree of mechanical precision is necessary." 30 31 Interferometric techniques suffer from several drawbacks when attempting to apply them to non-invasive thermometry. It is difficult to vary and measure, in living tissue, the change in distance associated with integral numbers of half wavelengths without altering the physical shape of the tis- sue. It does not seem to offer the advantages for non-invasive temperature monitoring during hyperthermia treatment. 4.1.2 Pulse-echo Overlap Technique The pulse-echo overlap technique has been used widely [8] and has been analyzed extensively with regard to the effects of diffraction . The technique relies on measuring the period between a transmitted and received pulse either in the pulse-echo or pulse-transmit mode. The pulses are typi- cally overlapped on an oscilloscope and the period measured with a counter. The period yields the propagation time and with known distance the propa- gation velocity can thus be determined. The pulse-echo overlap method can be implemented by analog or digital instrumentation. In either case, the echoes must have similar waveforms so that corresponding features can be readily identified and brought into coin- cidence (i.e., overlapped). The method suffers when pulse-echo signals are weak or distorted by attenuation or other factors that render them unsuitable for the overlap approach. 32 4.1.3 The Phase-slope Method As noted by D.R.Hull (1985)[9], with the phase-slope method, time between echoes is found by use of phase spectra of echo waveforms. After the echoes are digitized, a Fourier transform of each is obtained by a discrete FFT algorithm. The amplitude and continuous phase spectra for a pair of typical echoes are illustrated in Figure (4.1.1). After Fourier transformation, both the amplitude and phase spectra are used to define a central zone within the frequency domain. For example, this zone may consist of only a narrow range near the center frequency or a frequency range for which the amplitude exceeds some fraction of the peak value, and/ or the zone may consist only of the frequency range for which the phase spectrum is linear. These restrictions eliminate the low and high frequency extremes where the signal-to-noise ratio is low. The group velocity is given by U(f)=7-99—Lz“ 23W (4.1.1) 717' where f is frequency, 0 is phase angle in radians, and W is the time delay between echo windows. In—window time delays for each echo can be calcu- lated by setting W=0 and solving for T(f ) = (d 0/df )/(21t). Assume the phase spectra are linear functions of frequency in the central zone, their slopes are constants, M = %7°.-, and the in-window time delays are T1 = 32% 33 M2 ' . . for echo B1 and T2: -2— for echo BZ. The total time delay rs 11: T = W+(T2-T1). (Figure 4.1.2) The frequency domain phase-slope method eliminates problems encountered in the time domain, e.g., the need to account for echo inver- sions. In addition, it provides convenient criteria for selecting an appropriate frequency range in cases where the major portion of the phase spectra of the echoes are mutually linear. Generally, for nonlinear dispersive cases, the phase-slope method can determine group velocities as functions of fre- quency. However, if signal-to-noise ratio is low, as was the case for the composite samples, poor results are obtained. \l TACK Ulll 34 1.0 -— 1,0 __ > S t.— > .5 :3 23' L12 ——J << 3 :3. e o .2 e o ___/\ /\~_ -5 l l J -,, 1 1 1 J ' 0 so too 150 200 0 so 100 150 200 TIME. nsec TIME, nsec (3) Echo 81. lb) (£110 32. 151119;9 60 __ a :3 4° - >'. 10 .— :5 20 .— -° :4 3 < i s— g 5. a "1 1 °- 'éU ' i | l J 0 20 ~10 60 80 It!) 0 20 40 60 80 too FREQUENCY. MHz FREQUENCY. MHz 1:) Amplitude spectra. :01 Phase szectra. Figure 4.1.1 The Phase-slope Method. Typical back-surface echoes, Bl (solid) and BZ (dotted), and their amplitude and phase spectra. 35 F5 3:1 I :2 e :5 6 > me Time domain trace of princmle ecnoes. Figure 4.1.2.a Time domain trace of principle echoes. Echo FS is returned by the front surface of specimen, and B1 and BZ are successive echoes returned by the back surface. Time T is the round-trip time delay between echoes B1 and 82. l— AAAV ..._ UV -400__ 600- VOLTAGE . mV 0 -600 l l l l 0 50 100 150 200 TIME. nsec Figure 4.1.2.b Result of digital overlap method for determining delay between echoes 81 (solid) and 82 (dotted) using echoes. 36 4.1.4 Cross-correlation Method Unlike the overlap or phase-slope methods, the digital cross-correlation method does not require explicit criteria for accepting or rejecting specific features in echoes affected by distortion or signal-to-noise ratios. The method is illustrated in Figure (4.1.3) , which shows the normalized cross-correlation function for three cases of echo positions. The cross- correlation function of two time domain signals is obtained by conjugate multiplication using their Fourier transforms in the frequency domain and retransformation back to the time domain. The cross-correlation function possesses a maximum in the time domain. The displacement of this max- imum relative to a zero reference gives the time interval C, which for the ideal case should equal T2-Tl as measured by the digital overlap method. Cross-correlation gives this quantity whether the echoes appear in the same or separate windows. If the echoes B1 and B2 are separately windowed, then T==W+C. For the relatively simple and undistorted echoes of Figure (4.1.3), cross-correlation gives results similar to those obtained by the two previous methods. The validity of the cross-correlation method depends on the fact that the displacement of the maximum of the cross-correlation function equals the time delay between the two successive echoes. 37 The advantages of the cross-correlation method are apparent when the signal-to-noise ratio is low and/or random noise is superpositioned on the echoes. One of the properties of the cross-correlation function is that it is (statistically) weighted by dominant frequencies common to the waveforms being correlated. Therefore, it returns a group velocity within the frequency bandwidth of the signals analyzed. ECHO BI [CPO l2 H-II-fi 9' \ § S 7 % am < 4 -m 1 4m - - 0 so to) 150 an 0 so too Tsoxj 1M. nut ll) 1% w a: caoss-coantwrcu tuwcnm l n—-C -.1 .s « 12 - ll . 99. 2 nsec ° ~ C - 99. b nsec I- w . C '.5 4 -l - -2m —Lso -tm use 0 so tar no 250 "Mi. nscc (b) TI T2. Figure 4.1.3 Result of generating the normalized cross-correlation func- tion for two cases of echo positions. The displacement of the absolute maximum of the cross-correlation function relative to the zero reference guves the time delay C. For these ideal echoes. C was equal to T2-Tl as measured by digital overlap within the data-sampling interval error of 0.4 ITS. 38 39 4.1.5 Acoustic phase shift technique An acoustic phase shift technique for non-invasive measurement of temperature changes in tissues was developed by B.J.Davis and P. Lele (1985).[10] The phase shift of an interrogating pulsed ultrasonic sine wave (diag- nostic beam) is used to measure changes in its pr0pagation velocity through the heated region corresponding to the temperature change. The system operation is in pulse-transmit mode, which use two transducers, for transmitting and receiving respectively. As shown in Figure (4.1.4), (4.1.5) and (4.1.6), the data recorder is triggered from the transmitting pulse and has a variable time delay which is held constant during and after the hyperther- mia treatment. The change in propagation time is measured by determining the change in total delay time. The change in propagation velocity Aa and other known parameters is given by the following: ._ 2R2 AC --t1+—E?-Cl (4.1.2) where t1 is the initial propagation time, At is the change in propagation time, Cl is initial propagation velocity over the distance 2R2, 2R2 is the dis- tance over which the temperature rise occurs (insonation pattern diameter). 40 -2282: sham SEE 8% 53330 829?. E aoocoo 2F 02:23: «GALE. mmoz.. m /\.I . _ 5. ll .wEUE 4.2. 2:5 ILSPII 02F<>> 98:26 pzmazék 35$: 38% 828mm x mmoaomzqgt\ |\ A. » ZoermEHmE mmDH<§ wzfi ommqad QwHtEmZ/‘mh IL<<¢II .mwoaomzxxm... 41 .mouamuoqEB 208:6 024 Sec £58032: 820:6 o>c .8 Soto “tam 89E 0:4 ouswE AmHoHE more 8:83.055. E: 7..” 1 i t t Gaunt 1 - - (GUMm 1 CONN. OO.m q q a d - 1 l4 1 - _ - - A t t t l” B+N4t .. it; . “a. .2 1.. _ . L _\Ve_. f. p: C; 5 “8.9m- :__ r: f .1... __ .... .. 2. j . _____. i» 2 m: 1 .12 _ _ w._ s; in 56.? a; m. i w. _:__ _.__.._....,_ -. fl __ _ _ _M @. _._ _ _.________ a. .\ .n/tuwmfiem 85.0 _ :1 .. ._ r. E . A E“ 2...; 3 1 ,._ M .._ Z _ i g _ -U as... ._ i. w __ 2., ._ .__.___ f” P w .. ” _____ ,1 w _ .U 5...... __ Z. ; Q ... . c. m .. .84.. 83> Qq MQLWEHELH 42 Adam: .55 93 282: .«o @5532: c888 magnum £3, 59885 38:835.“ mew—.6 3288 203 mew—£0225 26% 2.5 Saw—383. .23 £5 83m 05.59% 0.34 anfi 03E . 68;: E mazooumtomuE. wt: 84. Ed. -85 BE ave. - am.» I one. «O+®.mt ~®+D.VI I Aml “4’. l‘_ - 2 00.0.0 LIL-2L2 ll- ~O+O.7 A A A l dO+O.m A L .L A A L L ... 8&4 34% Pa 82355 43 4.1.6 Other Techniques Greenleaf, Johnson, and co-workers [11] have shown that a reconstruc- tion method similar to that used by X-ray reconstruction may be used to reconstruct the spatial variation of attenuation and refractive index in a spe- cial class of data collection geometries. The spatial distribution of the value of many measurable parameters may be determined by inverting the line integrals of a related acoustic variable along a set of refracted and/or reflected ray paths; in particular, the propagation time along a ray is the line integral of a specific function of acoustic refractive index. Based on above theoretical approach, which indicates that high resolu- tion reconstruction images may be obtained by accounting for the refracted or curved ray, a joint program between S.A.Johnson at the Mayo Clinic and DA. Christensen at Utah resulted in experimental evidence that internal temperature distributions of static materials could be reconstructed with ultrasound techniques. An example of the reconstruction of the temperature of three water-filled balloons was demonstrated. The experimental configuration is shown in Figure (4.1.7). Ultrasound reconstruction methods for determining temperature depend on theories developed for analysis of transmission data. These theories limit the use of the body, such as the breast, where reflection and absoption 44 effects are minimal. This technique also suffered from the inaccessibility of in-vivo experiments in medical applications. A method used by Dunn and Fry (1961) to determine the acoustic velo- city in the lung relied on determining the change in acoustic impedance, pc , from the reflection at a lung-water interface. Barlow and Yazgan (1965) determined the phase difference between a modulated r.f. pulse propagated through a known liquid path and the incident pulse reflected from a solid-liquid interface by cancelling each pulse separately against a continuous-wave signal which was adjustable in phase and amplitude. From two such measurements at slightly different fre- quency the total phase shift in the liquid is calculated and then related to the propagation velocity. 45 905:8 can 538:8 See .9533 Eafiwofioh wontousanU 925355 «.546 oSwE fill] 9:20: - - 23m :m...l|lL : 53:. d w :3qu ...vv .1“ vvv mimumm eouomsk .6523 a 53$. :33... .3. 2.2% 3.3.5 .3» 328 A , t -_ J. 2 \ ~n\s r :20: 2:28 22.: .28 . . a _o __ 2...: 3:25 bcu cotuozou 3.5. ”Emsmxm xtmvéuoxak QwN~mmgbmzou Ozaomquq: m but“ EBB 0:00 5.. 0.0 oeswi 2 >> NV duq 0 .dc § 71 donut? 2290088 9 0:0 :0 C0 owcano .9023 0300000 2: C0 3.3.8 00220000032“ 05. 04.0 2:me «>A—> .0 com 3.322.th 95.833» 28.2 TS ~>r¢mu©~w> .0 com "239.380... .38: _ 1.8 g > :Eéfibfi _ ular- c. marl; wu—Smom comum—QCOQOH=< . . flak-MD? 72 6.2 Experiment 2: Temperature profile in water The purpose of this experiment with water was to verify that the system could indeed monitor a change in temperature and also could obtain a tem- perature profile in a medium by means of transducer scanning. The experimental configuration is shown in Figure (5.1.1). A 2.25 MHz piezoelectric focused transducer was mounted to a, scanner which was driven by stepmotors for 2-dimensional scanning in a degassed water tank. A plastic ice container for cooling and an electric heater were put at two opposite sides in the water tank. A plastic plate was located on the scan area to the system reflections from equal distances between the reflector and transducer. Thus the system should be able to detect any velocity change due to temperature change when an ultrasound wave propagates in the medium. The data from every position can then be used to obtain a tem- perature profile in the medium. Again, a physical reference ( the mask previ- ously discussed) is used to eliminate uncertainty in signal triggering. During scanning, both the specimen and transducer are kept under water in the degassed water tank. The transducer is held above the specimen, usually at a height determined by the focal length of the transducer. The transducer is moved parallel to the surface of the plastic plate by two step- ping motors which control movements in the X and Y directions. 73 Initially, the area of the specimen to be scanned is selected. The move- ment units are dependent on the step size of the motors , which is about 1mm/step. The spatial resolution is defined by specifying the intervals at which measurements will be recorded, the minimum spacing being 1mm. Once the initial parameters are set, the scanning process can begin. During the scanning, the system controller triggers the transducer and receives all the echo signals from the specimen. Only the first echo is identified and stored into a file, accompanied by the X and Y location. This data file is then displayed as a three- dimensional image to represent the temperature profile in the medium. Figure (6.2.1) shows the constant tem- perature profile response. To obtain a temperature gradient in water, an ice cooler was put on one side and an electric heater was tumed on at the other side of the tank. A scan over this temperature profile give the results shown in Figure (6.2.2) when no reference signal is used. When the reference is used the results are as shown in Figure (6.2.3). As mentioned before, because of the triggering uncertainty, the travel time from the transducer to the reflector plate was affected by both system triggering uncertainty and velocity change. The triggering uncertainty is removed by the use of the reference signal, leaving only a variation due to temperature. 74 To compare the non-invasive measurement, with an invasive tempera- ture measurement, as described in Chapter 5, the image in Figure (6.2.4) was obtained. The temperature profile for the invasive measurement looks smoother than that in Figure (6.2.3). One reason for this difference is that the probe of the fluoroptic thermometer not affected by the heat stream inside the water tank. 75 Figure 6.2.1 Three dimensional imaging for the constant temperature in water, using a reference signal. 76 .3:me 8:288 .8 3.: 05 :55; 833 Mo 0503 2333809 flab unswE can no: 98 ECU mucouwfih MO 0m: OS“ 8053, 8:25 a8 058 oeambmfiofi 77 .3: -wa 8:882 mo 8: 05 53, 333 E oan 2333th. m.m.o uSwE Figure 6.2.4 Temperature profile in water by using fluoroptic thermome- ter. 78 79 6.3 Experiment 3: Temperature profile probing of a layered model In this experiment, only the non-invasive measurement system is viable, the invasive measurement system, though it has higher resolution and more sensitivity, is impractical. The layered temperature gradient model was built using two plastic boxes. As shown in Figure (6.3.1), one box was glued to the top of the other. Two 25 ohm resistors connected to a variable voltage source were used as heaters. These two heater were placed at opposite sides to allow different temperature distributions. Scanning of the this model was initially done without a voltage applied. A program was developed to detect the boundary shift due to the temperature gradient in each layer. Since the data include 3-dimensional location information, the X and Y represent a certain cross section in a B-scan, while the Z is the boundary location. Fig- ure (6.3.2.a) and (6.3.2.b) show the conventional B-scan displays for dif- ferent temperature conditions. To present the experiment results as velo- city profiles, the program processes the original data file and calculates the time interval between any two boundaries and stores it into a new data file along with the X and Y co-ordinates which then can be interpreted as the velocity at each position. The velocity change will be found by comparing the data files at different locations, and these difference can then be inter- preted as relative temperature difference. The results for the first step are shown in Figure(6.3.3.a) and Fig. (6.3.4.a), in which the temperature profile 80 shows an almost constant temperature throughout the entire region. In the second step, 50 volts was applied to each resistor for five minutes to create a temperature gradient inside the two boxes. As depicted in Figure (6.3.3.b) and Figure (6.3.4.b), the heater in the upper region was placed on the right-hand side, thus the temperature gradient results obtained were as expected. After heating, the temperature increases toward the right-hand side where the heater is located. By comparing two images, an exact tem- perature gradient or a relative temperature change can be identified. This relative temperature change monitoring alone would be a valuable tool for many applications. For the lower region, the heater was installed on the opposite side. Similarly, Figure (6.3.4.b) shows a temperature increment toward the left-hand side because of the position of the heater. The significance of Figure (6.3.4) is enhanced by the fact that it is a temperature profile of a sublayer, which is a more difficult region to monitor by conven- tional methods. 81 water \/ upper region / \ Q [0% region /r l \ / \/ heaters Figure 6.3.1 A layered temperature gradient model. 82 At low temperature (' 5° C) Z «In . v “SJ-”Mav- a...- 412 i 424 n - . m:m—VP 436 _-- WH5-s- n “3 1 4“ O 16 32 48 64x 80 96 112 1238 2 At room temperature (" 220 C) m 412 1 MW 424 436 _ 3.5—..- a WNW. W HM «a 460 O 16 32 48 64x 89 96 112 1218 g“ Companson MM 1 __,——H—l-sv-—t__r— 4.12 n1 w - l . WNEHMM— 424 r 1 At I'OOm r- —J_r5\-fi—-~M--- l tem CBature 436 a“ H—H—H t. ( ~ 2 C) r , g-H 4- WW?- W HM 448 At low - 460 ‘ terrrggrnge 9—": ( ) 48 54,11 16 32 48 54! so 96 m 123 ptenoilZJ X-nin : O Y : O liniISJ X'Iin : 0 Y : 9 12:59:36. 95-31-1988 Figure 6.3.2.a B-scan image to show a boundary shift due to temperature change (X and Z coordrnates are distance and wave traveling time respec- tively). 83 4582338 233352 .8.“ ”was: Swarm n.m.m.o oSmE .\ 1‘ 222383 :52 3 .295 ~23 xon a 58m .533 ...O_ \ l 533 can 8m 5MB “89 a gum eaoqrqn-na .«nuoruv— and wad ea so vo av o u a o u 53-x mm on 32-3.3 .~—"3“nu x ¢- ~«u «a as vo av on, one}; «a mu 9.2822 x: can con ave a~n oo~ c.6283; 3. saw aem ave omn uo~ 84 tempgrature ( F ) B-scan I ILZC) * 95 p H — 7 O weremv—um- - - I 45 i 1 W B 32 64 96 128x 160 192 224 258 ( 1/64 inch ) (a) Temperature Profile of Upper Region without Heating temperature B-scan 125 100 L _.._.H-' 7 5 "I'll —'a'-'I 50 ‘L W B 32 54 SS 128 163 192 24 256 x ( 1/64 inch) (b) Temperature Profile of Upper Region with Heating- Figure 6.3.3 Temperature profiles of the upper region of the model. 85 Temperature B-scan mm = Now- 170 i 120 H |-.In-.—'_.I.}-.-I-I|- '70 1:""°- r—T‘H 20 ‘ l‘ s} 8 32 64 96 128x 160 192 24 258 ( 1/64 inch ) (a) temperature profile of lower region without heating Temperature B-scan ~&-* L “- 175 ‘ i. L'. n 125 .-'I':I I'II t ' u I I a an: I l I — .--0.I'I ‘ 75 H I 25 ~ 54 I, :5 'n J: _—‘ r 4. x —=1 8 32 64 SS 128x 168 192 224 256 ( 1/64 inch) Figure 6.3.4 Temperature profiles of the lower region of the model. 86 6.4 Experiment 4: Design Considerations and Procedural Aspects for Biomedical Tissue Studies Ultrasonic non-invasive temperature measurement has become increas- ingly important as a monitoring method in hyperthermia treatment. Ultra- sonic properties of many tissues have been reported by numerous authors which provide the experimental basis for measurement techniques. Many techniques developed in principle, however, still have not been implemented in medical applications despite the efforts of many investigators. The effect of temperature on ultrasonic velocity in biomedical tissues has been exam- ined by Carstensen [13] and Bamber[14] and others. Preliminary findings indicate that ultrasound velocity in nonfatty tissues increases with tempera- ture in the range from 5°C to 50°C for ultrasonic frequencies between 1 and 7 MHz. Figure (2.2.2) and (2.2.3) show that the expected temperature coefficients of velocity range is from 0.5 to 1.6 m /s 0C . This experiment was designed to simultaneously simulates hyperther- mia treatment and to monitor the change in propagation velocity as a func- tion of temperature (which could be used for monitoring the temperature variation during hyperthermia treatment). The experimental set up is shown in Figure (6.4.1). A specially designed degassed water tank was used for both hyterthermia treatment 87 simulation and for non-invasive measurements. A 2.25 MHz focused trans- ducer which was 19 mm in diameter was fixed to the bottom of water tank to represent the treaunent transducer. A constant amplitude signal generator, which generates continuous sine waves from 60 KHz to 100 MHz, and a power amplifier, were used to drive the transducer. The acoustic power out- put was calibrated experimentally by the radiation force method. A holder in the water tank is for mounting a specimen between the treatment transducer and the diagnostic transducer. Similar to previous experiments, a 2.25 MHz diagnostic transducer of 0.5 inch in diameter were above the specimen. A modified ultrasonic imaging system was utilized in this experiment. A state- of-art data acquisition board with a sampling frequency up to 40 MHz was installed in a PC micro-computer. This data acquisition board has less triggering uncertainty than the system used in previous experiments. As depicted in Figure (6.4.1), the diagnostic transducer was aligned with the ultrasound treatment transducer on the bottom. A pork kidney was used as the specimen on a holder between the two transducers. A pulse was launched into the specimen by the diagnostic transducer before treatment insonation. The data acquisition board received, sampled the echos and stored them a file for later processing. The real time echo waveform is shown in Figure (6.4.2). The time interval between boundaries was used to 88 represent the velocity within the specimen, which can be mapped to tem- perature difference. The boundary defined here is the maximum peak in a local area, where the local area is defined as a period of 100 sampling points or so, depending on the echo waveform pattern. The starting point of a local area is the first peak whose amplitude is above the threshold. After the first data file is stored, a ultrasonic insonation was done by the transducer on the bottom. A 2.25 MHz continuous sine wave was used for a duration of 15 minutes. The reading on the meter of the power amplifier was 20 watts which corresponded to 1 watt of acoustic power. A second data file was generated from data taken after the insonation. The velocity- temperature transformation algorithm described above was used for process- ing the two data files to find the velocity change inside the specimen caused by ultrasound induced heating. The results listed below are the boundary positions before insonation and the positions after. The positions represent the relative temperature change inside a pork kidney due to 15 minutes of ultrasonic insonation. The data before insonation at water temperature of 210 C resulted in the following boundaries: boundary 1: 272 samples (each sample equals 25 ns) 89 boundary 2: 517 samples boundary 3: 1064 samples The data after insonation at higher water temperature and higher kidney temperature gave: boundary 1: 252 samples boundary 2: 447 samples boundary 3: 1031 samples The time interval inside the specimen is 792 sampling points in the pre- insonation data and 779 sampling points after insonation. Assuming that the thickness of the specimen (about 2.5 cm) has not be changed, the velo- city change through the travel region inside the specimen can be calculated as: AV = 2.5*10-2 2.5*1o-2 779* 25* 10-9 792* 25* 10-9 It is readily simple to get relative temperature change from this velocity = 21m/sec. change if a calibrated relationship of velocity vs. temperature is available. Note that the surface boundary and bottom boundary are also shifted because of the temperature change along the water path. This result shows that the pulse-echo method used here is capable of detecting the temperature change inside a biomedical specimen provided that it does have clear boun- 90 daries. In addition to the above experiment, several one-dimensional scans were done across the pork kidney. A round flat shape, electric heater was used below the kidney for heating. Again, the first scan was done before the heater was turned on to obtain a B-scan image. The second scan was done after the heater was turned on for 10 minutes. Figure (6.4.3) shows B-scan images of the kidney specimen for both cases. Since the heat conduction inside the specimen is slower than that of the water outside the specimen, all of the boundaries are shifted in the same direction which indicates that the temperature has risen in water, but the temperature change inside the specimen is not as obvious. 91 L_.J\ EIN 310 1.. RF Power Amplifier Scanner Pulser Data aqui- sition PC comput- Transducer er Specrmen ._.__. Holder \ Transducer Constant Ampli- tude Signal Generator Figure 6.4.1 Experiment 4 set up for biomedical applications. 92 2nd boundary 51"“ 511111!“ 112121): ii i ML ,in. - r i \“M - :mt .. tl. t 513113.41"ng1 “11"";filifililfi‘tl’hn'aw i’rl‘th-Jilul‘ 'Mh\\\’wwmawv 7* 31121:? I if? 'f lst boundary 3rd boundary reference . transducer srgnal at bottom Display range 10. 19??) tion Hag 22 15:40:40 1989 ( A pulse launched by a 2.25 MHz transducer, the echo was sampled at 40 MHz. i.e. l sampling point = 25 ns. ) Figure 6.4.2 The echo waveform of a pork kidney specimen. 93 298 B-scan , fi 368 - —.—___._._.__ - L ' - I, .. ms _ ----:-- _;:_:_:g_ 784 _ _::"I—:-E—:E::=l __ , m " 23:2?" ‘‘‘‘ " 1948 16 32 48 64x 33 95 112 128 The image before heater turned on ( temperature 220 C). 380 B-scan 368 ——————-:-..T-_-_.-——-_——-’-Z--=—:- - .- LI 535 _.- ........ -___ ‘.-- .- - - - - _ ._ -- - ..__.._ 794 ..____..-.....:. ::--..:_:EE:;-; ; :.: 3.3.1.: _ _ 872 -—-- , - ,-.--~.—'_-E—=::: --- ~- 1qu e rs 3?:3'5—1fi4x 89 96 1122—7128 The image after heated for 15 minutes ( temperature 290 C ). Figure 6. 4. 3 B- -scan images of a pork kidnc ' s )ecimen to show th - dary shift due to temperature changes. ) I e boun CHAPTER 7 Analysis of Experiment Results 7.1 Analysis and Discussion The experiments with water demonstrated the ease with which a change in temperature can be detected by a change in the speed of ultrasound. Even though the experiments here were in a preliminary stage, without calibration for real application, it is necessary to investigate the accuracy and resolution possible and consider the requirements for future medical applications. 7.1.1 Accuracy and Time Resolution The results described in Chapter 6 are actually an average temperature variation along the wave travel region. The accuracy is dependent upon the time resolution and the ultrasound wave travel region. Based on previous results by BJ. Davis [10] and SA. Johnson, the requirement for time resolution to determine temperature difference of vari- ous tissue sample widths is given in Figure (7.1.1)[15]. Extrapolation of the graph in the Figure to smaller ordinat values shows that with a time resolu- tion of 1 ns for example, a 0.20C temperature change in a 4 mm diameter region can be detected in a tissue with a temperature coefficient of 3 94 95 m/secoC ( typical for water and biological tissues). With a time resolution capability of 1 ns, an 8 mm diameter or larger region is necessary to produce a 1 as change in time-of-flight when the temperature changes by 0.10C within that region. The graph in Figure(7.1.l) shows the behavior of __ 5t . . . D — W, where D rs the smallest diameter of a regron where a specific change in acoustic speed, (EV/V), due to heating is just detectable by a time resolution of St. The average speed of sound, , is taken to be 1500 meters per second. In table (7.1.1), the limitations of the system with respect to detectable temperature changes are presented. For those temperature change values listed in the table where the change in propagation time is less than 25 ns (40 MHz sampling rate), the current system cannot detect the associated temperature changes. Con- versely, for changes in propagation time greater than 25 ns, the current sys- tem can measure the associated temperature change. The heated area in the kidney experiment 6.4 consisted of an area with 2 cm in diameter and had a path length of about 3-4 cm. The resolution of temperature change in this specimen would be about 1.00 C . The final error in temperature determination in hyperthermia production is a combination of calibration error and measurement error. A precision of 0.20C to 0.50C might be required for useful systems. Clearly larger tem- 96 perature measurement errors can be tolerated below 42°C while greater accuracy is required when approaching higher temperature where tissue damage can occur. Acoustic velocity measurement techniques generally are able to meas- ure changes in velocity much more accurately than absolute velocities. Some previous research concluded that the temperature coefficient of velocity is fairly constant for most tissues, but absolute propagation velocity is known to vary. From the point of view of medical application, information regard- ing initial body temperatures prior to treatment is important in order to determine the temperature rise from the therapy. Temperature measurements need to be done twice, before and after the therapy, to control the treatment procedure. 97 Table 7.1.1 Change in Ultrasonic Wave Propagation Times as a Function of Temperature Elevation and Path Length ( All values in nanoseconds) Path Length through the Region of Temperature Elevation AT(0C) 1.0 cm 2.0 cm 3.0 cm 4.0 cm 5.0 cm 10.0 cm 0.1 0.67 1.33 2.00 2.67 3.33 6.66 0.2 1.33 2.67 4.00 5.33 6.66 13.33 0.5 3.33 6.66 10.00 13.30 16.70 33.30 1.0 6.66 13.30 20.00 26.60 33.30 66.60 2.0 13.30 26.60 39.90 53.20 66.50 133.10 5.0 33.10 66.30 99.50 132.70 165.80 331.70 10.0 66.00 132.00 198.00 264.00 330.00 660.00 53 a 0 r f- 1- > C ,3 § 0.0: - 3. 3 5 o a O.) - E 3 a a: t- 1 g g 0.0! :- -: w 3 C ' a a ,. .. s. S 0003:- -‘ E g 0.00: n 4 2 a 1:: 0.002 - - 1 0.00, r L Llurr r 1 1 ins“ 0.0: 0.02 0.05 0.: r 2 s Figure 7.1.1 Otauutrtn cl armor: mm curve: in sou~o spun Graph of the smallest specific change in acouStic speed 5v/v which can be detected in a region of diameter D using a time of flight detector of resolution 5!. The average speed of ulu'asound is taken to be 1500 m/sec. ultrasound speed change in small region of given diameter. Effect of time-of-flight resolution on detectability of local 98 7.1.2 Medical Applications Medical application of the technique is not expected to be as straightfor- ward as the experiments on biomedical tissues described above due to p—s 0 temperature gradients occurring within the body, 2. unknown values of the temperature coefficient of velocity, 3. patient movement, and 4. complex boundary identification due to the degree of impedance mismatch and multiple echo returns. For the pulse-echo measurement, in order to make relative velocity measurement it is necessary that: (1) there exist a strong acoustic impedance mismatch at the treatment region from which a signal can be reflected, (2) the capability of identifying boundary position despite complex waveforms from different tissues (due to the degree of impedance mismatch, wave dispersion and attenuation). (3) an initial propagation velocity must be obtained prior to treatment, so the change in propagation time of the reflected signal can be related to a change in propagation velocity. Impedance mismatch beyond the treatment region is assured by the presence of bone or air. In general, tumors which are accessible for 99 ultrasonic heating or visualization are also accessible for velocity measure- ment. Some less impedance mismatch problem did happen in experiment 6.4 when a pork liver specimen was used. There was no clear surface boundary appeared which was necessary for boundary shift detecting. In this case, as a compensative way, a reference signal might be used to obtain major boun- dary shifting information. As has been stated, common values of the temperature coefficient of velocity range from 0.8 to 1.6 m/(secoC) depending on tissue. In medical applications, the tumor temperature would be determined non-invasively by measuring the change in ultrasonic velocity in the tumor, calculating the corresponding temperature change from the known temperature coefficient of velocity and adding this value to the known initial temperature assumed to be at 37°C for most circumstances. For the technique to be exclusively non-invasive and accurate, a better knowledge of the temperature coefficient of velocity is necessary. Another problem which can limit the medical application of the above techniques is patient movement during hyperthermia treatment. The boun- dary echo shift is assumed to occur over a constant path length and is con- sidered to be due to temperature changes alone. If the path length varies, however, the boundary shift can be misinterpreted as due to temperature change even if no change has occurred. Even movements as small as a few 100 tenths of a millimeter can lead to false temperature change calculations. A possible way to overcome this problem is to make velocity measurements synchronous with the respiratory or cardiac cycles. Another way to limit the false temperature reading is to ensure that the transducer and the internal body interface, serving as a reflector for the ultrasonic wave such as between bone and tissue are firmly fixed with respect to one another. This would allow some movement of intervening tissue but ensure that the ultrasonic propagation distance is constant as required. The greater the movement of the tumor during hyperthermia, the less likely these proposed correction methods will be effective. Treatment areas which are least effected by the movement problem are the limbs, lower abdomen, head and neck. It is possible that in .the cases where knowledge of the temperature coefficient of velocity is good and patient movement is minimal, that the described non-invasive technique could be used as the exclusive means of non-invasive temperature measurement. In those cases where the tempera- ture dependence is not well-known, the described technique could aid in the determination of tumor temperature using supplemental information obtained from invasive probes, 101 7.2 Conclusion and Future Study Monitoring temperature variation inside material during processing is quite important in many applications. Since the non-accessibility in those cases where invasive measurement techniques using thermistors and/or thermal-couples are impractical, the non-invasive ultrasonic velocity method is a promising technique. This thesis outlined technique to measure ultra- sonic velocity changes during hyperthermia (produced by scanning focused ultrasound). The pulse-echo mode is used to monitor the boundary shift due to velocity change, indicating the relative temperature change. This tech- nique will not disturb the environment and will be benefit for patients in medical treatment. The pulse-echo method will provide greater potential than the transmitting method since it is more accessible in the human body. The precision of the temperature measurement is directly related to the time resolution of the echo. Additional improvement can be achieved by using the data acquisition equipment with higher sampling rate and less triggering uncertainty. More experiments with biomedical tissues in-vitro under simulated hyperthermia, to get experimental models and data for future in-vivo experiments, are necessary. To calibrate the measurement system, high precision fluoroptic ther- mometry should be used for comparison of temperature images. The tem- 102 perature coefficient of velocity in different tissues and the absolute tempera- ture mapping algorithm must still be refined. [1] [2] [3] [4] [5] [6] [7] [8] [9] 103 Bibliography Lele, P. F., Physical Aspects and Clinical Studies with Ultrasonic Hyperthermia, F.K. Storm Editor, G.K. Hall & Co. Boston, MA, 1983. Cetas, T. C. and Connor, W. G., Thermometry Considerations in Localized Hyperthermia, Medical Physics, 5, p79-9l , 1978. Isaak E. Elpiner, Physical, Chemical, and Biological Ejfects, Con- sultants Bureau, N.Y., 1964. Wells P. N. T., Physical Principles of Ultrasonic Diagnosis, Academic Press. N. Y. p23, 1969. Lele, P.P., Thresholds and Mechanisms of Ultrasonic Damage to Organized Animal, Tissues, In Proceedings of a symposium of Biological Effects and Characterizations of Ultrasound Sources, 1977. Abramowitz, M. and Stegun, I.A., Handbook of Mathematical Functions, National Bureau of Standards, Applied Mathematics Series, p55, June, 1964. 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