Biomedical subjects
Publications and source records attributed to F M Waterman.
Neutron energy spectra were measured at 0 degrees from 83.7-MeV deuteron bombardment of a 2.0-cm-thick beryllium target and 100.2-MeV proton bombardment of a 60-MeV-thick beryllium target backed with aluminum.
The energy spectra of neutrons produced by 35 and 46 MeV protons, 16 and 28 MeV deuterons, and 44 MeV 3He ions on thick beryllium were measured at angles of 0 degrees, 15 degrees, and 45 degrees with respect to the incident beams. The spectra were measured by the time-of-flight method for neutrons from the maximum energy down to 1 MeV. Neutron dose rates obtained from the zero-degree spectra by use of available tissue kerma factors agree with TE-TE ionization chamber measurements.
Iodine-125 implants are being used to boost external beam treatments of unresectable pancreas and lung tumors. Calculations of the 125I activity required to achieve a specific average peripheral dose are presented as a function of the average tumor dimension for spherical, ellipsoidal, and cylindrical implants. Both uniform and random seed spacings are investigated. The results indicate that the average peripheral dose is relatively insensitive to the seed distribution as well as to the seed activity. The average tumor dose is typically 20% greater than the average peripheral dose.
The time constants of three commercially available thermometer probes were measured when inserted into catheters commonly used in hyperthermia. The catheter typically increases the time constant by a factor of 3. Following the transition from a constant to continuously changing temperature, the rate of change of temperature indicated by such a probe is initially incorrect, but it attains the true rate of change of temperature after an elapsed time that depends on the rate of change of temperature and the time constant of the probe. This elapsed time varies from 3.5 to 8 time constants, as the rate of change of temperature increases from 0.05 to 10 degrees C/min. The specific absorption rate determined from a least-squares fit to temperatures recorded during the first 30 s following such a transition, are typically in error by 1%, 3%, and 6% when thermometer probes having time constants of 1, 2, and 3 s are used. These errors can be reduced to less than 0.1% by excluding the data recorded during an initial period of the first 3 time constants following the transition. Errors of similar magnitude result when blood flow is determined from the first 30 s of thermal clearance. These errors are similarly reduced to typically less than 1% by excluding the data recorded during the first 3 time constants from the determination.
Deionized water is commonly used to couple microwave applicators to the patient surface in the administration of local hyperthermia. Profiles of the specific absorption rate (SAR) at 1-cm depth show that deionized water coupling significantly distorts the SAR distributions of the Clini-Therm 915-MHz 10 X 10 and 15 X 15 cm2 applicators. Maxima and minima that are discernible in the SAR profiles obtained by direct applicator load contact are amplified producing unexpected hot and cold regions in the heating pattern. An exception is coupling achieved by use of the Clini-Therm cooling pad, oriented such that the direction of deionized water flow is perpendicular to the electric field. The distortion in the SAR distribution can also be eliminated by replacing deionized water with mineral oil, a material having a much lower dielectric constant (epsilon = 2). The SAR profiles for mineral oil coupling are comparable to those obtained for direct contact; however, the efficiency of power transfer is slightly less (70%) and the level of microwave leakage is approximately four times greater.
Temperature artifacts produced by very small uncoated thermocouples during ultrasonic heating are evaluated by backward extrapolation of the linear portion of the temperature rise curve or by backward extrapolation of the exponential portion of the temperature decay curve. The accuracy of these techniques for larger clinically used thermocouples is investigated by use of a two-dimensional model of the bioheat equation which simulates the transfer of heat radially from a probe 1 mm in diameter. The accuracy of these techniques is found to depend upon the perfusion rate. In the absence of perfusion, both extrapolation techniques underestimate the artifact by nearly 40%. Extrapolation of the temperature rise curve is very sensitive to the perfusion rate and this technique results in errors exceeding 100% when the perfusion rate is high. Extrapolation of the temperature decay curve produces more consistent results. Over a blood flow range of 0-100 ml/100 g per min, the artifact is underestimated by an amount that varies from approximately 40% to 30% respectively. Thus, the artifact can be determined to within 5% by this technique by increasing the extrapolated value by 35%.
Temperature artifacts were evaluated at 72 different sensor locations in 10 different tumour sites heated by use of planar ultrasound transducers operated at 1 and 3 MHz. Thermometry was carried out by single- and multisensor thermocouple probes inserted into 19- and 16-gauge polyurethane catheters, respectively. Nearly all catheters were oriented approximately perpendicular to the ultrasound beam. The artifacts were determined by backward extrapolation of the thermal decay 30-60s after the power was turned off. The effective blood flow and specific absorption rate (SAR) at the sensor locations were determined from the rate of decay and the steady-state temperature. The sample mean steady-state temperature, effective blood flow, and SAR were 41.4 degrees C, 17.5 ml/100 g/min, and 46.3 W/kg, respectively. The most frequent artifact was in the range 0-0.2 degrees C and the mean artifact was 0.6 degrees C. Less than 15% of the artifacts were above 1 degree C. The magnitude of the artifact correlates with the SAR of ultrasonic power, the effective blood flow rate, and the steady-state temperature. These results indicate that the artifact produced at 1 MHz by a multisensor, Teflon-sheathed thermocouple inserted into a 16-gauge polyurethane catheter is 1.7 +/- 0.4 degrees at an SAR of 100 W/kg.
The relative temperature artifacts produced by a selection of commercially available thermocouples and catheters were evaluated in radiation bolus and beef phantoms heated by 1 and 3 MHz continuous ultrasound. The thermocouples included a 23 gauge needle microprobe inserted directly into the phantoms, polyurethane-sheathed, Teflon-sheathed, and exposed-tip thermocouples, each inserted into a 19 gauge polyurethane closed-end catheter, a multisensor Teflon-sheathed probe inserted into a 16 gauge polyurethane catheter and a Teflon-sheathed single-sensor probe without a catheter. The needle microprobe and the polyurethane-sheathed thermocouple produce equivalent artifacts. The artifacts produced by the Teflon and exposed-tip thermocouples are 1.4 +/- 0.3 times greater, that produced by the multisensor Teflon-sheathed probe is 2.1 +/- 0.3 times greater, and that produced by the Teflon-sheathed thermocouple without a catheter is 2.3 +/- 0.4 times greater. The results in the beef phantom indicate that the needle microprobe and polyurethane-sheathed thermocouple both produce artifacts of 0.7 +/- 0.1 degree in tissue at an SAR of 100 W/kg.
The thermal clearance method utilizes the rate of temperature decay after the applied power is turned off to estimate the local blood flow. A limitation of this method has been its inability to account for the contribution of thermal conduction to the rate of temperature decay. As a result, the blood flow is generally overestimated. A modification of the thermal clearance method is described in this paper which enables the conduction component to be determined. Profiles of the tissue temperature are obtained in three mutually orthogonal directions about the point where thermal clearance is measured. The Laplacian of the temperature is evaluated from these profiles by the method of finite differences. The tissue thermal conductivity is estimated from literature values. The greatest source of error is the uncertainty in the location of the washout point in each catheter. Strict thermometry requirements must be adopted to reduce the localization error to +/- 0.25 cm. The thermometry catheters should be orthogonal to within +/- 10 degrees and all three catheters should be in contact at the washout point. The methodology was tested in a phantom, studied by use of a computer model, and implemented in the clinic. The experimental error in the conduction component is typically 50%. The resulting error in the blood flow depends on the relative rates of energy removal by blood flow and thermal conduction. When perfusion is the dominant mode of energy removal, the resulting uncertainty in the blood flow is typically in the range 20-30%.
In a prospective study CT scanning was used to evaluate the precision of thermometry catheter placement in tumours in the head and neck or on the chest wall in 30 consecutive patients prior to hyperthermia treatment. Patients had variable-sized tumours from several primary sites. Thermometry catheter placement was guided by palpation with or without a prior CT scan. Catheter placement was confirmed by CT. All lesions were less than 8 x 8 x 6 cm (L x W x D) in size. A mean of 4.2 +/- 0.2 (+/- 1 SEM, range 2-7) closed-end polyurethane catheters were inserted orthogonally by the same experienced radiation oncologist. Horizontal thermometry catheters were intended to traverse the centre and base of the tumour mass, and a vertical catheter was often inserted to intersect a horizontal catheter. After catheter placement, wire cables with 1 cm spacings were inserted into the catheters and positions determined using orthogonal films and CT scans. The success of catheter placement was judged on the following criteria: (1) catheter distribution factor (CDF = proportion of tumour CT slices transected by at least one catheter); (2) catheter hit ratio (CHR = average number of catheters in tumour per CT slice); (3) catheter miss factor (CMF = average number of catheters out of tumour per CT slice); (4) catheter placement index, CPI = [(CHR)(CDF)]-CMF; and (5) distance of nearest catheter from the visually estimated centre of tumour in the most central tumour CT scan. In the first seven lesions with 3-6 cm depth catheter insertion was guided by palpation only. In the next 23 lesions catheter insertion was guided by a prior CT scan. In the latter group, 15 lesions had depth 3-6 cm while eight lesions had depth < or = 3 cm. Catheter placement by palpation only, without the benefit of CT scan, was much less accurate in terms of the nearest catheter to the centre of the tumour (p = .001), the proportion of CT slices with catheter in tumour (CDF, p = 0.04) and the probability of a catheter being outside the tumour (CMF, p = 0.01). The catheter placement index (CPI) was a good measure of the accuracy and adequacy of catheter placement in large tumours (p = 0.04). Displacement of normal tissue structures by tumour precluded accurate catheter placement and led to a low CPI. It was difficult to accurately instrument lesions < or = 3 cm depth even with the benefit of a prior CT scan.(ABSTRACT TRUNCATED AT 400 WORDS)
An error in temperature measurement, commonly referred to as a temperature artifact, frequently occurs during ultrasound hyperthermia as a result of viscous and absorption heating of the thermometer probe. At the present time there is no convenient method for correcting the clinical data for this error, which can be 0.5 degrees C, or greater. A technique is described by which the artifact can be estimated from a 10-s interruption in ultrasonic power. This technique is based on the observation that thermal decay recorded by a probe can be represented by the summation of two exponential decay rates, one of which represents the decay of tissue temperature and other decay of the artifact. Temperature drop during the first 10 s arises primarily from decay of the artifact because its time constant is approximately 7 s whereas that of the tissue generally ranges from 100 to 1000 s. A relationship between artifact and temperature drop derived from clinical data shows that the artifact is directly proportional to temperature drop. This relationship can be used to estimate the artifact during therapy if power is interrupted for 10 s. Because the interruption in power is brief, it is feasible to sample the artifact periodically during therapy and to make an on-line correction for the temperature artifact.
One test for thermotolerance development in a clinical situation is to evaluate the effects of altering the hyperthermia fractionation interval on tumour response to thermoradiotherapy. Between 1983 and 1990 44 evaluable advanced superficial tumours of miscellaneous origin in 41 patients were randomized to receive either once-weekly or twice-weekly external microwave hyperthermia treatments combined with radiation therapy. The mean age of patients was 62 years, and 85% had failed previous therapy. All lesions were less than 8 x 8 x 4 cm (L x W x D) and were heated by external 915 MHz microwaves. The mean radiation dose was 44 +/- 3 Gy (mean +/- SE) in the once-weekly group and 46 +/- 3 Gy in the twice-weekly group (p = 0.64). The mean volume of the lesions heated once weekly was 17 +/- 6 versus 23 +/- 5 cm3 for those heated twice weekly (p = 0.45). Hyperthermia was administered once weekly for 4.6 +/- 0.2 sessions (range 3-7) or twice weekly for 8.1 +/- 0.3 sessions (range 4-10). Thermometry was performed using 3.4 +/- 0.2 catheters and 5.1 +/- 0.6 thermal sensors per tumour in the once-weekly group, and 2.7 +/- 0.2 catheters and 5.8 +/- 0.3 thermal sensors per tumour in the twice-weekly group. Of the 44 evaluable randomized lesions a complete response (CR) at 2 months post-treatment was observed in 59% (13/22) heated once weekly and 55% (12/22) in those heated twice weekly. The prognostic factors predictive of tumour complete response were found by logistic regression analysis to be radiation dose and tumour volume, while the prognostic factors predictive of duration of response (Cox proportional hazards analysis) were median minimum tumour temperature (Tmin), minimum tumour temperature during the first heat treatment (Tmin1) and tumour volume. The duration of local control in lesions with Tmin < or = 39.5 degrees C was 11.7 +/- 1.9 months while for lesions with Tmin > 39.5 degrees C it was 23.0 +/- 4.2 months (p = 0.01). The ED50 was calculated by logistic regression to be 40 Gy (95% CI = 22-54 Gy) for once- and twice-weekly heated lesions. There was not a significant difference in tumour response or duration of response between populations randomized to receive once- versus twice-weekly hyperthermia treatments. There was also no difference in skin reaction rates between once- and twice-weekly hyperthermia treatments, nor could a correlation be found between any thermal parameter and skin reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
Advanced tumours in the head and neck 3-6 cm depth are too deep to be completely heated by external 915 MHz microwaves. A preliminary study was performed using interstitial plus external hyperthermia combined with external beam radiation therapy to heat tumours to depths > or = 3 cm. Nine advanced metastatic lesions of squamous cell carcinoma located in the head and neck were treated between 1987 and 1990 with the combined hyperthermia technique and radiation doses of 38-60 Gy (mean of 49 +/- 3 Gy). The mean tumour volume was 58 +/- 9 (SE) cm3 (range 24-94 cm3) with a mean tumour depth of 3.9 +/- 0.3 cm (range 3-5.5 cm). The deeper aspects of the tumour were heated by interstitial 915 MHz microwave antennas and the superficial aspects heated by external 915 MHz applicators. A single plane of polyurethane closed-end catheters, 16 Ga, were inserted under local anaesthesia approximately 1.5-2 cm apart in parallel arrays at the base of a lesion behind the sternomastoid muscle, or an equivalent site in a dissected neck, extending forward and angled deeply no more than 15 degrees. Hyperthermia was administered twice weekly immediately after radiation therapy in a mean of 5.3 +/- 0.7 external heat sessions (range 3-7) and a mean of 3.5 +/- 0.6 interstitial heat sessions (range of 1-6). Interstitial hyperthermia was usually administered in alternating sessions with external hyperthermia, but in some patients all of the sessions of one modality were administered followed by all of the sessions of the other modality. In no case were both interstitial and external heatings performed on the same day. Surface thermometers were used to monitor skin temperature during external hyperthermia sessions. Results showed that by 8 weeks after completion of treatment, six lesions exhibited a complete response (67%) and three a partial response (33%). One of the partial responses continued to regress and became a complete response (78% complete response). The recurrence rate in complete responders was 14% (1/7) with time to recurrence of 7.7 months. Six lesions were recurrence-free at last follow-up of 21.3 +/- 8.8 months. Skin reactions were absent in four fields (44%), erythema was noted in five (56%) and thermal blistering in one (11%). Ulceration occurred only in association with tumour breakdown when the skin was infiltrated by tumour (three patients, 33%).(ABSTRACT TRUNCATED AT 400 WORDS)
Tumour deposits in the head and neck region were treated with hyperthermia using 915 MHz external microwave applicators and radiation therapy between 1986 and 1990. The mean (+/- SE) radiation dose was 47 +/- 2 Gy (range 21-77 Gy). All but four patients had failed previous therapy. Mean tumour volume was 40 +/- 10 cm3 (range 0.3-276 cm3). Hyperthermia was administered biweekly in 80% of the patients in 6.0 +/- 0.4 sessions (range 1-10); thermometry involved 3.6 +/- 0.4 catheters (range 1-9) and 5.7 +/- 0.4 sensors (range 1-12) per tumour. Of the 50 lesions evaluable for response, 29 had a complete response (58%), and 20 had a partial response (40%). Lesions were stratified by depth. In tumours considered potentially heatable (i.e. depth < or = 3 cm and lateral dimensions at least 2 cm less than boundary of applicator), the complete response rate was 81% (26/32, 47 +/- 2 Gy, 15 +/- 3 cm3); whereas for patients with tumours deeper than 3 cm, the complete response rate was 17% (3/18, 48 +/- 3 Gy, 110 +/- 21 cm3), p = 0.0001. Among lesions < or = 3 cm depth that exhibited a complete response, six recurred (24%, 5.8 +/- 1.8 months) while 20 lesions were recurrence free at last follow-up of 11.9 +/- 1.2 months). The overall survival of patients with lesions < or = 3 cm depth was 11.5 +/- 1.3 months (range 2.4-32.3 months) while for patients with lesions > 3 cm depth survival was 6.7 +/- 0.9 months (range 2.1-18.6 months), p = 0.01. In superficial lesions with depth < or = 3 cm, multivariate logistic regression analysis indicated that the model best correlating with complete response included radiation dose (p = 0.08) and tumour volume (p = 0.08, model p = 0.004). Multivariate proportional hazard analysis indicated that the model best correlating with duration of local control included tumour depth (p = 0.03) and previous radiation therapy (p = 0.08, model p = 0.006). Twenty-two fields were treated without any skin reactions (39%), 23 evidenced erythema (40%) and eight thermal blistering (14%). Ulceration occurred in 11 treatment fields but in all but one of these cases the ulceration may have been due to tumour breakdown as there was direct invasion of the skin by tumour prior to the initiation of treatment. The maximal skin temperature was the best predictor of morbidity although the correlation was not statistically significant (p = 0.19).
Extensive recurrences on the chest wall of advanced carcinoma of the breast in 20 patients were treated with multiple field patchwork hyperthermia combined with radiation therapy between 1987-1991. The objective of the study was to evaluate the feasibility, tumour response and complications of treating extensive lesions with multiple, overlapping fields of hyperthermia. All lesions were diffuse encompassing up to 2900 cm2 in area with or without multiple nodules < or = 3 cm deep. All lesions had failed previous therapy with all but three failing previous radiotherapy. Hyperthermia consisted of 282 hyperthermia applicator fields and 357 hyperthermia treatments with external 915 MHz microwaves using commercially available applicators. Hyperthermia applicator fields were defined by the surface 50% SAR distribution of a particular applicator, and hyperthermia fields were abutted to cover the entire tumour bearing area. Radiation therapy consisted of 81 fields to a mean dose of 40 +/- 1 Gy (SE), 88% of fields received between 30 and 50 Gy. The equivalent dose was 42 +/- 1 Gy, based on the linear-quadratic model and alpha/beta = 25 (Fowler 1989). Overlapping hyperthermia fields were separated by an interval of at least three days. Up to four heat sessions per week were required to cover the entire tumour in a rotating fashion. The hyperthermia treatment time was 60 min. Hyperthermia treatments were continued for the duration of radiation therapy. Each hyperthermia applicator field was heated at least once. Patients were exposed to a mean of 14 +/- 3 hyperthermia applicator fields (range of 3-46 fields) and a mean of 18 +/- 3 hyperthermia treatments (range of 6-61) delivered over a mean of 7.5 +/- 0.9 weeks (range of 3-17 weeks). Each field was heated an average of 1.3 times. The tumour complete response rate was 95% with a recurrence rate of 5%. Nevertheless, the mean survival of patients with a complete response was only 10.8 +/- 1.7 months (range of 2-28 months) because of the systemic tumour burden existing outside of the treated fields in these patients. Neither complete response, local control nor survival after thermoradiotherapy correlated with the disease free interval between initial mastectomy and recurrence. There was no evidence of increased thermal damage to skin nor evidence of tumour recurrence at junctions of hyperthermia field overlap. It is concluded that recurrent advanced carcinoma of the breast presenting as extensive, diffuse lesions on the chest wall can be treated as effectively with multiple field patchwork thermoradiotherapy as can nodular lesions treated with single hyperthermia fields.
RTOG thermometry guidelines for clinical trials of hyperthermia using planar ultrasound recommended that temperatures be mapped in polyurethane catheters by use of single-junction copper-constantan thermocouples. These guidelines were based on an assumption that the error in temperature measurement due to thermal conduction would generally not exceed +/- 0.3 degrees C. The validity of this assumption was tested with a commercially available single-junction copper-constantan thermocouple. The width of the point spread function, an indicator of the relative magnitude of the conduction error, was five times greater than expected. As a result, the conduction error is projected to exceed 0.3 degrees C in a temperature gradient of only 1.5 degrees C/cm. This projection was confirmed by mapping a thermal peak which simulates a typical clinical temperature profile. This peak had an amplitude of 6 degrees C, a full-width at half-maximum of 3.5 cm, and a maximum gradient of approximately 3 degrees C/cm. Temperatures measured at 0.5-cm intervals over the span of this peak were in error by a mean of +/- 0.6 degrees C. It is strongly recommended that the RTOG guidelines be revised to replace copper-constantan thermocouples with manganin-constantan single- or multi-junction thermocouples which will assure that the conduction error will be < +/- 0.3 degrees C.
Commercial ultrasound hyperthermia systems typically include thermometry units designed for copper-constantan thermocouples. Replacing these copper-constantan thermocouples with manganin-constantan thermocouples is advantageous in reducing the measurement error caused by the conduction of heat along the copper wire, but their performance in these thermometry units is uncertain. The accuracy of manganin-constantan thermocouples in the Labthermics LT-100, Clini-Therm TS1200/TM100, and Physitemp TM-12 thermometry units was investigated using a temperature controlled circulating water bath monitored by a mercury thermometer having a calibration traceable to NIST. The results demonstrate that an accuracy of +/- 0.2 degrees C can be achieved with manganin-constantan thermocouples over the range 35-55 degrees C without hardware modification provided specific calibration procedures are followed. With the Labthermics LT-100, a double point calibration should be carried out at 35 and 55 degrees C. With the Clini-Therm TS1200/TM100, a self-calibration of the unit using its internal calibration well plus a single point calibration using an external temperature standard provides sufficient accuracy. The Physitemp TM-12 requires an external computer for read out and the user must provide additional software to correct for the error by either a single or multiple point calibration.