Non-invasive tissue thermometry system and method

It has been observed that attenuation of a transmitted or reflected beam of ultrasound in tissue irradiated with such a beam having a power intensity in the tissue in the non-linear range will change measurably as the tissue temperature changes. Based upon this observation, a method and apparatus for non-invasive thermometry include periodically interrogating the tissue with an ultrasonic beam having a power intensity sufficient such that the power intensity of the beam in the tissue is in the non-linear range. Attenuation coefficients based upon the attenuation of the power intensity of the ultrasonic beam due to the tissue are then periodically determined. Temperature changes in the tissue are determined based upon differences between the determined attenuation coefficients.

This invention relates to a method and apparatus for non-invasively 
measuring temperature changes in tissue and more particularly, to a 
thermometry system and method which utilizes an ultrasound interrogating 
beam to determine temperature rise in tissue. 
Treatment of cancer by hyperthermia is becoming an accepted manner of 
treatment. An ultrasound beam can be used to elevate the temperature of a 
malignant tumor in order to destroy it. For this treatment to be 
effective, the temperature of the tumor must be raised by something on the 
order of six to eight degrees Centigrade. By selecting the appropriate 
frequency of the ultrasonic beam to irradiate tissue containing the tumor, 
and by appropriate beam forming and/or sweeping, the temperature of the 
tissue at any given depth can be caused to rise without causing a 
significant increase in temperature in the surrounding tissue. 
In order to utilize hyperthermic treatment effectively, the temperature of 
the tissue being heated must be carefully and accurately controlled. In 
existing hyperthermic treatment systems, thermocouples or other 
temperature sensors are actually implanted in the tissue which is to be 
heated. The outputs of these temperature sensors provide a temperature 
profile of the tissue being heated. This profile is used to control the 
power intensity of the ultrasonic beam heating the tissue in order to 
control the temperature of the heated tissue carefully. 
A major disadvantage of this invasive technique of thermometry is that the 
thermocouples must be implanted in the body. The risk of infection or 
other complications always exists when invasive procedures must be 
performed in treatment. Additionally, hyperthermia cannot practically be 
used to treat cancerous tissue by techniques requiring invasive 
thermometry in some instances due to tumor location. The trauma which can 
accompany invasive thermometry creates a significant impediment to the use 
of ultrasound hyperthermia treatment. 
Tissue which is irradiated by an ultrasonic beam has what is known as an 
ultrasonic attenuation coefficient. The attenuation coefficient is 
indicative of the power intensity loss of the ultrasonic beam due to its 
passage through the tissue. The attenuation coefficient thus reflects the 
difference between the power intensity of the ultrasonic beam at the point 
at which it enters the body being treated and the power intensity of the 
ultrasonic beam at any point inside the body, including the point at which 
it leaves the body being treated. One contributing factor to the 
attenuation coefficient is the power absorbed by the tissue being 
irradiated. 
Non-invasive thermometry techniques are known. However, these known 
techniques utilize ultrasonic beams having spatial peak, temporal peak 
(SPTP) intensities sufficient to produce SPTP intensities on the order of 
1 W/cm.sup.2 in the tissue being measured. It has been observed in the 
laboratory that tissue exhibits a very minimal change in its attenuation 
coefficient for ultrasonic beams having power intensities on the order of 
1 W/cm.sup.2. Consequently, the attenuation coefficient of the beam is 
essentially constant for non-invasive thermometry schemes utilizing such 
low SPTP beams. This makes such thermometry methods difficult to use to 
measure temperatures accurately in the human clinical setting. For 
non-invasive human clinical thermometry, what are needed are SPTP powers 
in the so-called "high intensity-" or "non-linear-" or "finite amplitude-" 
range. This range includes SPTP powers on the order of, for example, 100 
W/Cm.sup.2 to 300 W/cm.sup.2. In this finite amplitude range, temperature 
coefficients of ultrasound absorption and additional losses change by 
significant, readily detectable amounts, so that the received beam data 
can be compared against these changing coefficients to recover the 
temperature information by comparing the transmitted beam and the received 
beam. The spatial peak temporal average (SPTA) of the thermometry 
interrogating beam operating in pulse mode is to be maintained in the low 
milliwatt range so that this beam does not itself introduce a significant 
temperature rise. 
It is an object of this invention to provide a non-invasive tissue 
thermometry system and method which has practical utility in the human 
clinical setting. 
It is further an object of this invention to utilize an ultrasound 
interrogating beam to determine temperature rise in tissue accurately 
enough to control hyperthermic treatment means to achieve controlled 
therapeutic results. 
The method of this invention for non-invasive thermometry in tissue 
comprises the step of periodically interrogating the tissue with an 
ultrasound beam having sufficient power intensity that the power intensity 
of the beam in the tissue is in the non-linear range. The method further 
comprises the step of periodically determining attenuation coefficients. 
The method further comprises the step of determining temperature changes 
in the tissue based upon differences between the determined attenuation 
coefficients. 
A table of attenuation coefficients can be determined empirically by 
comparing the power intensity of the ultrasonic beam at the point it is 
generated, or enters a tissue sample, with the power intensity of the 
ultrasonic beam as it leaves a tissue sample, and measuring invasively the 
temperature of the tissue sample. 
The system of the present invention comprises means for periodically 
interrogating tissue with an ultrasound beam having sufficient power 
intensity to create in the tissue a beam power intensity in the non-linear 
range. The apparatus further comprises means for periodically determining 
tissue attenuation coefficients. Temperature changes in the tissue are 
then determined based upon differences between determined attenuation 
coefficients. 
This invention relates to applicant's discovery that the attenuation 
coefficient for tissue being irradiated with an ultrasonic beam having a 
power intensity level in the non-linear range in the tissue being 
irradiated changes in a readily detectable manner as the temperature of 
the tissue changes. This characteristic has heretofore not been 
appreciated by those skilled in the art to which this invention pertains.

An apparatus and method for non-invasively measuring temperature changes in 
tissue utilize an ultrasound interrogating beam to determine the 
temperature rise in tissue being heated. The interrogating beam must be 
operated in the finite amplitude range where the temperature coefficient 
of ultrasound absorption and related additional attenuation losses are 
sufficiently large to permit construction of practical devices useful for 
human clinical purposes. Applicant has discovered that operating the 
interrogating beam such that it has a power intensity level in the 
non-linear range in the tissue being heated causes the attenuation 
coefficient of the tissue to exhibit measurable changes as the temperature 
of the tissue changes. The attenuation coefficient is defined as the 
difference between the power intensity level of the ultrasound 
interrogating beam at its point of origination and the power intensity 
level of the ultrasound beam at a point where it leaves the tissue. It 
should be understood that the attenuation coefficient could also be 
determined by the difference between the power intensity level of the 
ultrasound interrogating beam at the point at which it enters the tissue 
and the point at which it leaves the tissue. Additionally, although the 
invention is described in the context of devices useful for human clinical 
purposes, this is illustrative only and is not meant to limit the scope of 
the invention. 
Referring to FIG. 1, a non-invasive thermometry system 10 includes a means 
12, such as an ultrasound transducer, for producing an ultrasound beam 14 
for irradiating a target 16 such as a malignant tumor beneath the skin 18 
of a patient. The power intensity of beam 14 is such that beam 14 will 
have a spatial peak, temporal peak (SPTP) intensity in the non-linear 
range, illustratively 200 W/cm.sup.2, within target 16. Target 16 is 
illustratively a tissue mass within the body of a human patient undergoing 
hyperthermic treatment, such as by irradiation by an ultrasound transducer 
19 operating in the linear range, illustratively at 1-10 W/cm.sup.2 at 
target 16, and wherein target 16 is at some depth beneath skin 18. 
Ultrasonic beam 14 is reflected by the target 16 at points 20, 22 by 
scattering and/or specular reflection. The temperature in the tissue of 
target 16 is initially T.sub.n (normal body temperature). For this 
temperature, an attenuation coefficient (with components due to 
absorption, scattering, etc.) can be derived for the region between points 
20, 22 of target 16. If the temperature in target 16 changes by 
.sup..DELTA. T to T.sub.n +.sup..DELTA. T, the change in the attenuation 
coefficient due to the change in temperature of the target 16 can be 
ascertained and the change in temperature of the target 16 can be found. 
The magnitude of the absorption coefficient change for sound in the 
non-linear intensity range of 150 to 500 W/cm.sup.2 SPTP is approximately 
10 times as great as for sound intensities in the linear intensity range, 
typically below 10 W/cm.sup.2 SPTP. This makes it much easier to use the 
ultrasound beam intensities in the non-linear range to determine 
temperature changes to the degree of accuracy required for human clinical 
hyperthermia treatment. 
Referring to FIG. 1, a change in the pressure absorption coefficient alpha 
(.alpha.) was experimentally determined. Letting the distance from point 
20 to point 22 of target 16 be one centimeter and .sup..DELTA. T be 
1.degree. C., the change in the pressure absorption coefficient alpha for 
a 200 W/cm.sup.2 sensing beam is approximately 4.6% per degree C. For 
liver tissue, the change in alpha was measured empirically by directly 
measuring alpha, irradiating the target 16, and measuring the temperature 
of the tissue. Table 1 contains the results of the measurements. 
TABLE 1 
______________________________________ 
.alpha..sub.36.degree. C. = 0.0315 
.alpha..sub.37.degree. C. = 0.030 
.alpha..sub.38.degree. C. = 0.0285 
______________________________________ 
For a pulse-echo interrogation, wherein the power intensity level of the 
ultrasonic beam after it leaves the tissue is measured by a transducer 
placed at the point at which the beam is generated, the path length for 
the above example is 2 cm. The sound pressure amplitude (P) can be defined 
as 
EQU P.sub.out =P.sub.in e.sup.-2.alpha. 
where 
P=pressure 
.alpha.=pressure absorption coefficient in cm.sup.-1. 
2=tissue path length in cm. 
EQU For 37.degree. C., P.sub.out37 =P.sub.in e.sup.-0.030(2) 
EQU For 38.degree. C., P.sub.out38 =P.sub.in e.sup.-0.0285(2) 
EQU P.sub.out38 /P.sub.out37 =e.sup.0.003 =1.003 
Therefore, it can be seen that as the temperature of the tissue being 
heated rises, the amount of sound which is absorbed by the tissue 
decreases which increases the power intensity level of the ultrasonic beam 
leaving the tissue. 
Referring to FIG. 2, a set of experiments was conducted to determine all 
attenuation losses due to the tissue being heated. The system of FIG. 2 
has a means 24 for producing an ultrasonic beam 26 which illustratively 
has a SPTP of 200 W/cm.sup.2 in target 28. Target 28 is illustratively a 
mass of tissue disposed between a skin layer 30 on one side of a body 
member and skin layer 32 on the opposite side of the body member. A phase 
insensitive thermocouple probe 34 is disposed on the side of the body 
member opposite the ultrasonic beam producing means 24 as a receiver. 
Using this setup, sample data on attenuation for the tissue of target 28 
was determined, attenuation being defined as the total loss in power 
intensity of ultrasonic beam 26, including absorption losses, as the beam 
passes through the body, including target 28. Table 2 shows the change in 
transmitted intensity data due to the absorption coefficient change and 
other insertion losses. 
______________________________________ 
Thermocouple Probe Reading 
Temperature 
______________________________________ 
0.94 37.degree. C. 
1.40 48.6.degree. C. 
______________________________________ 
Thus, an approximate 40% increase in the transmission of sound intensity 
was observed for an 11.6.degree. C. temperature rise. Therefore, assuming 
a linear relationship between output temperature and output sound 
intensity for each 1.degree. C. temperature rise, the transmitted sound 
intensity increases approximately 3.5%. 
In order to control the temperature for hyperthermia treatment of human 
cancer, it is necessary to know the tissue temperature of the tissue being 
heated within .+-.0.5.degree. C., preferrably .+-.0.1.degree. C. in both 
the normal, abnormal, and transition tissue regions. This objective can be 
accomplished with the non-invasive finite amplitude ultrasound 
interrogation of this invention utilizing a number of beam spatial 
formats. 
Referring to FIG. 3, a pulse-echo method of non-invasively measuring the 
temperature of the tissue being irradiated is shown. Non-invasive 
thermometry system 36 includes means 38 for producing an ultrasonic 
interrogation beam having a power intensity level in target 40 in the 
non-linear range. System 36 also includes an echo transducer 42 which is 
mounted substantially at the point where means 36 generates ultrasonic 
beam 39. Target 40, which is illustratively a tumor region, is located at 
some depth beneath the skin 44. 
Means 36 produces a plurality, c.sub.1 . . . c.sub.n, of ultrasonic 
interrogating beams 38 such that pulse-echo line-by-line data can be taken 
before hyperthermia induction. Illustratively, an A-mode scanner is 
utilized to produce the pulse-echo line-by-line data. This interrogation 
of target 40, c.sub.1 to c.sub.n, yields an attenuation profile for the 
normal temperature distribution. The normal temperature distribution for 
target 40 would be the normal body temperature. During the heating phase 
of the hyperthermia treatment as well as during the entire treatment 
period, pulse-echo data is continually acquired and an attenuation profile 
related to the temperature rise induced is determined based upon a priori 
information of attenuation loss versus temperature rise for similar 
tissue. Basically, for each type of tissue which undergoes hyperthermia 
treatment, changes in the attenuation profile related to various 
temperature rises are experimentally determined and stored. Then, during 
hyperthermia treatment, the changes in the attenuation profile as 
determined during treatment are compared with the experimentally 
determined changes in attenuation profiles and the change in temperature 
is determined based upon a comparison between the changes in the 
attenuation profiles determined during treatment and the experimentally 
determined changes in attenuation profiles. 
Either a phase sensitive (piezoelectric crystal) pulse-echo system can be 
used, for a non-phase sensitive pressure receiver system can be used. 
Since the pulse repetition frequency of the interrogating beam typically 
is on the order of 1 KHz, the attenuation loss can be averaged rapidly in 
real time over a great number of pulses. Illustratively, 5-10 pulses can 
be used to generate each attenuation loss figure, although more pulses can 
be utilized within the real time constraints of the data processor being 
used, if more accuracy is desired. Illustratively, the frequency of the 
interrogating beam is in the 1 MHz-10 MHz range. Further gains in accuracy 
can be achieved by interrogating target 40 from a variety of angles. 
The pulse-echo method requires a known geometric registration between the 
transducer beam axis and the tissue region being interrogated. However, 
this registration accuracy generally will not be as stringent as that 
required for other computer tomographic methods (X-ray computer tomography 
(CT) and nuclear magnetic resonance computer tomography (NMR-CT)). 
Referring to FIG. 4, a non-invasive method of measuring temperature rise in 
tissue undergoing temperature change utilizing pulse transmission is 
shown. The non-invasive thermometry system 46 includes a transducer 48 for 
generating ultrasonic beam 50. Ultrasonic beam 50 passes through skin 52 
on one side of a body member, through target 54, which is illustratively a 
tumor, and through skin 56 on the other side of the body member. A 
receiver 58 is disposed on the side of the body member opposite the side 
on which transducer 48 is disposed. Illustratively, transducer 48 and 
receiver 58 move in the same direction, that is, either clockwise or 
counterclockwise around the body member as shown by arrows 60, 62, 
respectively. Ultrasonic beam 50 has a power intensity in the non-linear 
range. This method is similar to X-ray CT in that a sender and receiver 
are used and the attenuation profile (which is directly related to the 
temperature profile) is computed throughout the region interrogated. 
Implementation of this temperature profiling method requires interrogation 
of the tissue before the temperature increase is started. This 
interrogation should preferrably begin at the coupler-tissue interface and 
progress inwardly to the desired site. This inward progression is 
accompanied by attenuation correction for each frequency component of the 
interrogating beam so that the normal base temperature attenuation for 
each frequency component at each tissue depth can be recorded for 
reference before the temperature change is initiated. Knowledge of this 
frequency spectrum of attenuation at each tissue depth is used to compute 
the delivered intensity at each tissue site and to compute the insertion 
loss in the tissue on the returned echo from each site. Both the forward 
(to a receiver) and reverse (deteched echo) insertion losses as functions 
of frequency are needed for the final computation of temperature change at 
each tissue site. 
Referring to FIG. 5, this technique is particularly useful where a mass 70 
of tissue is desired to be treated which lies in line with another mass 72 
of tissue which is also being heated. That is, in order to determine the 
temperature changes at the first "hot spot," 70 it is necessary to know 
what is happening at the other "hot spot" 72. In FIG. 5, the source 68 of 
ultrasound energy and its coupler are moved relative to the localized 
heated regions 70, 72. By moving the source 68 and receiver 78 into the 
orientation illustrated in broken lines, the temperature of hot spot 70 
can be isolated. The temperature information thus obtained can be used to 
recover the temperature of hot spot 72 as well. 
The necessity and virtue of this interrogating format lies in the direct 
experimental determination of the base temperature values which are 
obtained at a high acquisition rate. Illustratively, the interrogating 
beam has a 1 KHz pulse repetition frequency. Once the frequency spectrum 
of losses is determined for the tissue region of interest, hyperthermic 
treatment can be initiated. Again, during hyperthermic treatment, the 
interrogating beam is used to interrogate the tissue region non-invasively 
starting at the surface. 
Changes in the attenuation profile after correction for continually 
changing insertion losses can be interpreted in terms of a temperature 
change based upon a priori knowledge of tissue attenuation loss as a 
function of temperature for the specific spectral distribution of 
frequencies when the site of interrogation is subjected to finite 
amplitude ultrasound. Typically, the beam 50 has a power intensity level 
of 200 W/cm.sup.2 and above in SPTP acoustic intensity in target 54. 
Alternatively, a thermocouple can be invasively placed at a selected point 
so that one absolute internal temperature can be obtained at one point in 
the tissue. This absolute temperature reference is then used to provide 
data needed for all subsequent measurements in the tissue volume. 
Illustratively, a thermocouple can be placed just beneath the skin to 
minimize the trauma caused by the invasive placement of the thermocouple. 
Although the invention has been described in detail with reference to 
certain preferred embodiments and specific examples, variations and 
modifications exist within the scope and spirit of the invention as 
described and as defined in the following claims.