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Biomedical subjects

T V Samulski

Publications and source records attributed to T V Samulski.

71 records · Page 4Linked to original sources
PubMedDate not supplied

Characterization of tumour temperature distributions in hyperthermia based on assumed mathematical forms.

Assessing the efficacy of hyperthermia treatments involves three distinct problems: (1) adequately sampling the spatial temperature distribution in a region; (2) defining (a set of) 'descriptors', numerical values which could be used in comparing distinct treatments; (3) testing whether the predictions of prognosis are statistically significant. This paper addresses the first two problems. We use simple assumptions about the tumour geometry and heating pattern to obtain convenient mathematical representations of a temperature distribution, which are then used in defining scalar descriptors such as weighted average temperature TV, and the fraction of tumour volume heated above a given temperature VT/V. Two extreme cases are discussed. In the first, tumour geometry plays the dominant role, and in the second the specific absorption rate (SAR) distribution is assumed to have the greatest influence on the temperature distribution.

Absorption↗
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Comparison of two-dimensional numerical approximation and measurement of SAR in a muscle equivalent phantom exposed to a 915 MHz slab-loaded waveguide.

Computer predictions of the specific absorption rate (SAR) distribution in a uniform muscle-equivalent phantom with an overlying bolus have been compared to those measured experimentally. The microwave source was a 10 cm x 10 cm slab-loaded waveguide applicator operating at 915 MHz. The modelling technique (theory) combines the equivalence principle and a two-dimensional finite element technique to determine the incident and the scattered electric fields separately. The E-field was measured using a small dipole device oriented parallel to the polarized field of the waveguide source. Comparisons of the predicted and measured SAR were made for various bolus properties, and reasonable agreement with theory was found in each case. The results demonstrate the usefulness of numerical modelling in characterizing the fields from microwave applicators used in clinical hyperthermia.

Computer Simulation↗
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Clinical experience with a multi-element ultrasonic hyperthermia system: analysis of treatment temperatures.

A summary of tumour temperature data obtained from 31 patients who underwent 147 hyperthermia treatments with the Sonotherm 1000 ultrasonic system is presented. The treatment goal was to achieve a minimum of 42.0 degrees C in tumour for 60 min duration with normal tissues remaining below 43.0 degrees C. In 83% of treatments at least one measured tumour temperature reached or exceeded 42.0 degrees C at some time during the treatment. Nineteen per cent of these treatments had a time- and spatial-averaged temperature (measured in tumour) greater than or equal to 42.0 degrees C. A variety of anatomical sites were treated and these were grouped into four categories: groin/trunk, axilla, breast/chest wall and head/neck. Measured temperatures in tumours located in the groin and trunk sites were significantly higher (22% greater than or equal to 42 degrees C) than other locations. The head and neck treatment temperatures were significantly lower (8% of measured points greater than or equal to 42 degrees C.

Body Temperature↗
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The use of hydralazine to manipulate tumour temperatures during hyperthermia.

Hydralazine is an antihypertensive drug which theoretically could increase tumour temperatures during hyperthermia via reduction in tumour blood flow from a vascular 'steal' phenomenon. Doses that are therapeutically effective in reducing blood pressure in hypertensive patients would probably cause postural hypotension and other side-effects in normotensive patients beyond the hyperthermia treatment session, however. This study was designed to evaluate whether hydralazine, when administered at a safe dose for normotensive patients (0.125 mg/kg, i.v.) would be effective in increasing tumour temperatures during hyperthermia. The working hypothesis was that hydralazine at a dose of 0.125 mg/kg would be effective in raising tumour temperatures during hyperthermia treatment with minimal change in blood pressure. Fourteen human and five canine subjects were given hydralazine (0.125 mg/kg, i.v.) at the midpoint of a hyperthermia session. Temperatures and blood pressures were monitored before and after drug administration. Although hydralazine resulted in slight reduction in blood pressure, it was ineffective in increasing tumour temperatures in human patients (average maximum rise in median temperature was 0.26 +/- 0.32 degrees C). In canine subjects the same dose of hydralazine was effective in reducing blood pressure in four of five subjects studied (mean maximum drop was 22.7 +/- 4.1 mmHg) and the median temperature rose 0.8 +/- 0.7 degrees C. In the canine subjects the greater the decrease in blood pressure, the greater the increase in temperature. These results suggest that a rise in tumour temperature induced by hydralazine is dependent on creating a drop in blood pressure. Future studies in this laboratory will include tumour blood flow manipulation with antihypertensives which have a shorter half-life and a titratable effect. Using this approach, hypotension, which seems to be required to raise tumour temperature, will be more controllable in terms of magnitude and duration.

Animals↗
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Blood perfusion measurements in human tumours: evaluation of laser Doppler methods.

Laser Doppler flowmetry is a simple method of determining, directly and continuously, tissue blood flow. However, its applicability to monitoring tumour blood flow interstitially during hyperthermia treatments is still being evaluated. The purposes of this study were to physically characterize the measurement probes, to evaluate potential sources of artifact with the interstitial use of the probes during hyperthermia treatment, and to obtain measurements in human tumours during hyperthermia sessions. The accuracy of the method in quantifying blood flow, velocity and volume during hyperthermia was found to be unaffected by heating the measurement probe to 42-46 degrees C or by exposing it to various intensities of 915 MHz microwave fields (10-40 W), or 1 MHz ultrasound fields. Catheter insertion methods were developed to place the flow probes interstitially in tumours. Tissue damage was confined to a distance of no greater than 0.12 mm away from the catheter tract, and physical evidence of vascular disruption was within a distance of 0.05 mm as measured in a rat tumour model. This degree of damage/disruption is unlikely to affect LDF measurements which represent blood flow averaged over a 1.0-1.5 mm radius from the probe tip. Concurrently, the device was used to monitor tumour blood flow parameters interstitially in human subjects during hyperthermia treatments given in combination with conventional radiotherapy. Blood-flow data from multiple sites of measurement showed marked heterogeneity within individual tumours (up to 55-fold differences) and between different tumours (greater than 100-fold differences). Measurements made by translating the probe along a tumour radius, beginning at the tumour core and advancing to the tumour edge, were consistent with a two-component tumour perfusion model (shell and core). Data are presented from one patient illustrating a persistent change in perfusion distribution during the hyperthermia treatment course, which occurred concomitantly with increases in thermal data. These results suggest that the technique might be of value in monitoring change in flow between treatments. Responses during hyperthermia treatment sessions were also investigated. Four temporal patterns of flow were observed, ranging from a steady increase in flow to a plateau level to a steady drop in flow during heating. These patterns were not well correlated with average temperature recorded at the site of flow measurement. Further study is needed to determine if this LDF technique is to be useful for evaluation of heat transfer by blood perfusion.

Evaluation Studies as Topic↗
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A comparison of temperatures in canine solid tumours during local and whole-body hyperthermia administered alone and simultaneously.

Temperature measurements were made in canine solid tumours during whole-body hyperthermia (WBH) alone, local hyperthermia alone and local hyperthermia given simultaneously with WBH. During the plateau phase of WBH alone, mean intratumoral temperature ranged from 41.3 +/- 0.2 degrees C to 41.7 +/- 0.1 degrees C and was statistically lower (P = 0.0028) and more variable than rectal temperature, which ranged from 42.0 +/- 0.02 degrees C to 42.1 +/- 0.03 degrees C. The temperature distribution in solid tumours during WBH is more uniform than during local hyperthermia. The simultaneous administration of whole-body and local hyperthermia in five dogs resulted in increased tumour temperatures in comparison to WBH and in more uniformly increased tumour temperatures in comparison to local hyperthermia alone. Median intratumoral temperatures (+/- 95% confidence intervals) resulting from local hyperthermia alone and local hyperthermia given simultaneously with WBH were 39.9 degrees C (39.7-40.1) and 42.9 degrees C (42.6-43.1), respectively, and were statistically different (P = 0.0012). Local applied power requirements to meet predetermined intratumoral temperature limits were decreased by 50% (P = 0.011) in dogs undergoing combined local/whole-body hyperthermia versus local hyperthermia alone. Dogs tolerated the combination of local and WBH without complication.

Animals↗
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Non-invasive thermometry using magnetic resonance diffusion imaging: potential for application in hyperthermic oncology.

The proposition to use non-invasive thermometry based on magnetic resonance diffusion imaging for applications in therapeutic hyperthermia is examined. The measurement of proton motion predominantly associated with the self-diffusion of water can be characterized by a Boltzmann temperature dependence (i.e. e-Ea/kT). The activation energy (Ea) is on the order of 0.2 eV and, for a restricted range (approximately 30 degrees) at a base temperature of approximately 300 K, the relationship between the effective diffusion coefficient and temperature is approximately linear. This response has been empirically demonstrated in water-based gel phantoms using magnetic resonance imaging (MRI). Additionally, it is feasible to have compatibility between radiofrequency (RF) heating devices and MRI equipment. An MRI-compatible heating applicator that includes a hexagonal array of coherently phased dipoles was assembled. This heating array easily fits into a standard 1.5 T head imaging coil (diameter 28 cm). The RF fields associated with heating (130 MHz) and imaging (64 MHz) were decoupled using bandpass filters providing isolation in excess of 100 dB. This isolation was sufficient to allow simultaneous imaging and RF heating without deterioration of the image signal-to-noise ratio. In this report temperature, spatial and time resolution achieved in phantom are examined in order to assess the potential for using this non-invasive temperature measurement in applications of hyperthermic oncology. Using this system and conventional multi-slice imaging techniques, 0.5 degrees C resolution in a voxel size of less than 1 cm3 has been achieved using an acquisition time of 4.15 min.

Diffusion↗
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On the accuracy of noninvasive thermometry using molecular diffusion magnetic resonance imaging.

Temperature measurement using magnetic resonance imaging (MRI) of water self-diffusion is investigated. Diffusion images and derived temperatures are obtained in polyacrylamide gel phantom. The temperatures measured from MRI are compared with those from temperature probes to verify their accuracy. In general, the difference between temperatures determined from MRI diffusion images over 0.3 cm3 regions of interest and from temperature probes were 0.2 degrees C. It is concluded that current MRI technology allows noninvasive temperature tomography that is comparable with invasive thermometry with respect to temperature accuracy, has spatial and time resolutions that would be useful in hyperthermic oncology.

Body Temperature↗
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Serious toxicity associated with annular microwave array induction of whole-body hyperthermia in normal dogs.

Using a regional annular microwave array it was possible to produce a systemic temperature of 42 degrees C in approximately 80 min with applied net power levels of approximately 150 W. Resulting temperature distributions were non-uniform. Sites within the array were above systemic temperature during heating but approximated systemic temperature during the plateau phase. Sites outside of the array were lower than systemic temperature during heating and plateau phases. Dogs allowed to recover from the procedure experienced severe toxicity consisting of lumbar muscle haemorrhage, pain and swelling, and pelvic limb paralysis. Histologically, there was severe myopathy and haemorrhage and oedema in neural tissue in the caudal lumbar spine. Acute necrosis of lymphoid tissue was observed in all dogs. Temperatures in muscle reached 43-46 degrees C and were higher than at other measured sites. Spinal canal temperatures were essentially equal to rectal temperature, approximating 42-43 degrees C during heating and plateau phases. These data suggest regionally induced whole-body hyperthermia may result in: (1) power deposition non-uniformity leading to muscle and spinal canal temperatures which exceed systemic temperature and which are sufficient to cause serious toxicity; (2) systemic temperature non-uniformity which is undesirable for systemic thermochemotherapy; and (3) possible immunological dysfunction associated with lymphoid necrosis. Extreme caution must be exercised in administering energy to localized regions of human patients with the intent of elevating systemic temperature.

Animals↗
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Application of new technology in clinical hyperthermia.

Two areas of technical progress related to hyperthermic oncology are presented: (1) numerical modelling of absorbed power and temperature distributions; and (2) non-invasive thermometry using magnetic resonance imaging. The results represent achievements made during the past 5 years at Duke University Medical Center's Departments of Radiation Oncology and Radiology. They represent examples of progress in the technology of hyperthermia that have potential for greatly improving the delivery, monitoring and assessment of clinical hyperthermia.

Body Temperature↗
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Temperature dependence of canine brain tissue diffusion coefficient measured in vivo with magnetic resonance echo-planar imaging.

The intensity of conventional spin-echo diffusion-weighted magnetic resonance (MR) images is approximately linearly dependent on temperature over a restricted range using conventional diffusion-weighted spin-echo magnetic resonance imaging (MRI). However, conventional diffusion-weighted MRI is too motion sensitive for in vivo thermometry. The present work evaluated rapid diffusion-weighted echo-planar imaging (EPI), which is less sensitive to motion, for application to non-invasive thermometry in acrylamide gel materials and in vivo in canine brain tissue for applications in therapeutic hyperthermia. The rapidly switched, strong gradients needed for EPI were achieved using a 'local' z-axis gradient coil. Gel materials were heated with a small (10 cm diameter) spiral surface microwave (MW) applicator at 433 MHz, while in vivo heating was accomplished with whole body RF hyperthermia using an annular phased array (130 MHz). The MW or RF fields associated with heating and imaging (64 MHz) were decoupled using bandpass filters providing isolation in excess of 100 dB. This isolation was sufficient to allow simultaneous imaging and MW or RF heating without deterioration of the image signal-to-noise ratio. Using this system in a gel, temperature sensitivity of the diffusion coefficient was observed to be (3.04 +/- 0.03)%/degrees C which allowed temperature changes of 0.55 degrees C to be resolved for a 1.8 cm3 region in < 10 s of data acquisition. In vivo, cardiac gating of the pulse sequence was necessary to minimize motion artifacts in the brain. The temperature sensitivity of brain tissue was (1.9 +/- 0.1)%/degrees C allowing temperature changes of 0.9 degrees C to be resolved in a 0.9 cm3 volume in < 10 s of data acquisition. We conclude that with further optimization of the data acquisition conditions it will be possible to determine 0.5 degrees C temperature changes in 1 cm3 volumes in < 10 s using this technique.

Animals↗
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Verification of a hyperthermia model method using MR thermometry.

Simulation of hyperthermia induced power and temperature distributions is becoming generally accepted and finding its way into clinical hyperthermia treatments. Such simulations provide a means for understanding the complete three-dimensional temperature distribution. However, the results of the simulation studies should be regarded with caution since modelling errors will result in differences between the actual and simulated temperature distribution. This study uses a diffusion weighted magnetic resonance (MR) based technique to measure hyperthermia induced temperature distributions in a three-dimensional space in a non-perfused phantom. The measured data are used to verify the accuracy of numerical simulations of the same three-dimensional temperature distributions. The simulation algorithm is a finite element based method that first computes the electromagnetic induced power deposition then the temperature distribution. Two non-perfused phantom studies were performed and qualitatively the MR and simulated distributions agreed for steady-state. However, due to the long MR sampling time (approximately 4 min), poor agreement between the simulations and MR measurements were obtained for thermal transients. Good agreement between the simulations and fibreoptic thermometry measurements were obtained. The fiberoptic measurements differed from the simulations by 0.11 +/- 0.59 degrees C and -0.17 +/- 0.29 degrees C (mean +/- standard deviation for the two studies).

Algorithms↗
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Simulation of electromagnetically induced hyperthermia: a finite element gridding method.

A finite element gridding method for simulating electromagnetically (EM) induced hyperthermia is presented. The method uses patient CT data as its primary input, with critical structures manually outlined (on a graphics workstation) for explicit demarcation. The paper outlines the various stages involved in mesh creation, including procedures for conforming the finite element representation of critical structures to their smooth boundaries, modelling of heating equipment, and modelling of the outer boundaries. The procedure for generating the finite element model is illustrated for an example treatment. Additionally, the results of computing the SAR in six patients are compared to measured values. The comparison reveals agreement between the model prediction and actual treatment within the limits of measurement error.

Combined Modality Therapy↗
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A phase I/II study to evaluate radiation therapy and hyperthermia for deep-seated tumours: a report of RTOG 89-08.

The purpose of this paper is to evaluate the safety and efficacy of deep hyperthermia in conjunction with radiation therapy. This study employed 'second generation' electromagnetic devices which were felt to be better able to confine heating and spare normal tissue than the devices evaluated in a previous study (RTOG 84-01). Sixty six patients at six institutions were enrolled on a prospective Phase I/II study. Eligible deep seated tumours were treated with a combination of external hyperthermia and radiation therapy. Radiation consisted of 1.7-2 Gy per fraction, 4-5 fractions per week, to > 20 Gy (previously irradiated lesions) or > 50 Gy (no previous radiation). Deep hyperthermia was delivered with electromagnetic devices: BSD 2000 for 92% of cases, Thermotron for 5% of cases, other low frequency electromagnetic for 4% of cases. Hyperthermia was delivered < or = twice weekly. Overall complete and partial response rates were 34% and 16% respectively. Response was not correlated with maximum tumour temperature or disease site. There was, however, a strong association with radiation dose: 54% CR with > or = 45 Gy versus 7% with < 45 Gy (p < 0.0001). The achieved temperatures were less than ideal. Although the average maximum tumor temperature was 41.9 degrees C (range 35.7 degrees C-46.7 degrees C), the minimum tumour temperatures were low. The average minimum tumour temperature was 38.5 degrees C and was never > 41.8 degrees C. Treatment was well tolerated with no fatalities. There were four acute grade 3 or 4 toxicities (6% of patients). Patient discomfort resulted in interruption or discontinuation of sessions in 30% of the sessions. In 12 cases (18% of patients) the planned course of hyperthermia was discontinued due to acute discomfort. The devices used in this study were better tolerated than the devices used in the previous Phase I/II deep hyperthermia trial (RTOG 84-01) with less patient discomfort and no problems with severe systemic cardiovascular stress. In the previous study 68% of the hyperthermia courses were prematurely terminated primarily due to patient discomfort and toxicity; in the present study 18% were prematurely terminated. However, as indicated by the low minimum tumour temperature, fundamental problems with achieving acceptable temperature distributions remain.

Adult↗
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Hyperthermia treatment planning and temperature distribution reconstruction: a case study.

While a great deal of effort has been applied toward solving the technical problems associated with modelling clinical hyperthermia treatments, much of that effort has focused on only estimating the power deposition. Little effort has been applied toward using the modelled power depositions (either electromagnetic (EM) or ultrasonic) as inputs to estimate the hyperthermia induced three-dimensional temperature distributions. This paper presents a case report of a patient treated with hyperthermia at the Duke University Medical Center where numerical modelling of the EM power deposition was used to prospectively plan the treatment. Additionally, the modelled power was used as input to retrospectively reconstruct the transient three-dimensional temperature distribution. The modelled power deposition indicated the existence of an undesirable region of high power in the normal tissue. Based upon this result, amplitudes and phases for driving the hyperthermia applicator were determined that eliminated the region of high power and subsequent measurements confirmed this. The steady-state and transient three-dimensional temperature distributions were reconstructed for four out of the seven treatments. The reconstructed steady-state temperatures agreed with the measured temperatures; root-mean-square error ranged from 0.45 to 1.21 degrees C. The transient three-dimensional tumour temperature was estimated assuming that the perfusion was constant throughout the treatment. Using the computed three-dimensional transient temperature distribution, the hyperthermia thermal dose was computed. The equivalent minutes at 43 degrees C achieved by 50% (T50Eq43) of the tumour volume was computed from the measured data and the three-dimensional reconstructed distribution yielding T50Eq43 = 40.6 and 19.8 min respectively.

Arm↗
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Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs.

BACKGROUND: Nitric oxide synthase (NOS) inhibitors have been investigated as potential cytotoxic agents to treat tumors lacking p53 function. Furthermore, their ability to reduce tumor blood flow can be combined with drugs that are specifically designed to kill cells that are hypoxic or to improve temperatures during local heat (hyperthermia) treatment of tumors. This paper reports the unexpected development of acute pancreatitis in two tumor-bearing pet dogs that were treated with the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during administration of local hyperthermia. METHODS: Prior to the use of L-NAME in tumor-bearing dogs, purpose-bred beagles were studied. Following induction of inhalation anesthesia, local hyperthermia was applied to either normal thigh muscle (beagles) or tumors (tumor-bearing dogs). Once a thermal steady state was achieved, L-NAME was administered and temperature monitoring continued. Animals were observed after treatment for evidence of toxicity. RESULTS: The beagles tolerated the treatment well, with no side effects noted either clinically or by routine CBC or blood chemistry analyses. In contrast, the first two tumor-bearing dogs accrued onto the phase I study developed acute pancreatitis in the immediate post-treatment period which necessitated hospitalization and intensive care. The trial was stopped. Both dogs had intercurrent risk factors which predisposed them to development of pancreatitis, although neither had a history of symptoms of pancreatitis at the time the hyperthermia + L-NAME treatment was given. CONCLUSIONS: We conclude that caution should be exercised when considering NOS inhibition for cancer treatment. Careful evaluation of history and health status as well as recognition of potential risk factors may be key in avoiding potentially fatal complications. This study demonstrates the value of performing potentially harmful treatments in tumor-bearing dogs prior to introduction into the human clinic.

Acute Disease↗