Search PubMed⌕ Search

Biomedical subjects

D M Prescott

Publications and source records attributed to D M Prescott.

150 records · Page 9Linked to original sources
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Estimation of cell survival in tumours heated to nonuniform temperature distributions.

UNLABELLED: A stochastic model describing the probability of cell survival as a function of thermal exposure was developed and fit to data arising from studies of CHO cell survival under hyperthermic conditions. This model characterizes the separate risks of temperature-induced cell death and induction of thermotolerance during heating. Tumour cells are assumed to be affected independently of each other by hyperthermia. Tumour geometry, perfusion and power deposition affect hyperthermia-induced temperature distributions in tumours, producing nonuniform temperatures. Two tumours may respond to hyperthermia slightly differently because of differences in tumour geometry, perfusion, power deposition, or by chance alone and the approach presented here incorporates chance and these other factors explicitly. THE RESULTS: (1) the time-temperature history is important for estimating tumour cell survival; (2) tumour temperature heterogeneity leaves more surviving cells at a given T90 temperature than would be expected if the entire tumour were uniformly heated to that same temperature; and (3) changes in the shape of the temperature distribution because of tumour geometry and perfusion distribution greatly influence cell survival between tumours, even when the standard temperature descriptors, such as T90, are fixed. The simulations also showed a modest effect on cell kill attributable to varying the lengths of the warm-up and the cool-down periods. These simulations indicate that these types of sensitivity studies can be used to investigate relationships between various modifiers of temperature distributions achieved when treating tumours with hyperthermia and to assess their potential therapeutic impact in clinical trials.

Animals↗
PubMedDate not supplied

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↗