Biomedical subjects

J W Hunt

Publications and source records attributed to J W Hunt.

At least 19 recordsLinked to original sources

PubMed1998

Experimental evaluation of two simple thermal models using transient temperature analysis.

Thermal models are used to predict temperature distributions of heated tissues during thermal therapies. Recent interest in short duration high temperature therapeutic procedures necessitates the accurate modelling of transient temperature profiles in heated tissues. Blood flow plays an important role in tissue heat transfer and the resultant temperature distribution. This work examines the transient predictions of two simple mathematical models of heat transfer by blood flow (the bioheat transfer equation model and the effective thermal conductivity equation model) and compares their predictions to measured transient temperature data. Large differences between the two models are predicted in the tissue temperature distribution as a function of blood flow for a short heat pulse. In the experiments a hot water needle, approximately 30 degrees C above ambient, delivered a 20 s heating pulse to an excised fixed porcine kidney that was used as a flow model. Temperature profiles of a thermocouple that primarily traversed the kidney cortex were examined. Kidney locations with large vessels were avoided in the temperature profile analysis by examination of the vessel geometry using high resolution computed tomography angiography and the detection of the characteristic large vessel localized cooling or heating patterns in steady-state temperature profiles. It was found that for regions without large vessels, predictions of the Pennes bioheat transfer equation were in much better agreement with the experimental data when compared to predictions of the scalar effective thermal conductivity equation model. For example, at a location r approximately 2 mm away from the source, the measured delay time was 10.6 +/- 0.5 s compared to predictions of 9.4 s and 5.4 s of the BHTE and ETCE models, respectively. However, for the majority of measured locations, localized cooling and heating effects were detected close to large vessels when the kidney was perfused. Finally, it is shown that increasing flow in regions without large vessels minimally perturbs temperature profiles for short exposure times; regions with large vessels still have a significant effect.

Angiography↗

PubMed1997

Mechanism of ultrasound enhanced porphyrin cytotoxicity. Part I: A search for free radical effects.

Intense ultrasound beams may have the potential to treat malignant tumours when combined with sensitizers, often called sonodynamic agents. Some of these agents, e.g., the porphyrins, are currently used for photodynamic therapy. However, the experimental evidence for ultrasound activation of sensitizers is inconsistent. This paper attempts to discover whether they yield of free radicals such as .OH and .H, which are produced by transient cavitation, could explain the killing of Chinese hamster ovary (CHO) cells in vitro with and without sonodynamic agents. CHO cells were irradiated with ultrasound beams in phosphate-buffered saline or in growth medium, and the immediate cell lysis and loss of cell colony forming ability were measured. Under our specific conditions, in which the standing wave patterns were minimized, a general correlation was observed between the transient cavitation, free radical production, and cytotoxicity. However, the yield of free radicals was much too small to explain the cell killing observed. We conclude that cytotoxicity is not linked to attack from free radicals formed outside the cells. In our experiments, immediate cell lysis is closely linked to the transient cavitation, which is known to produce shear forces that disrupt cellular membranes. We hypothesize that the loss of cell colony forming ability is also linked to damage of cellular membranes.

Animals↗

PubMed1997

Ultrasonic biomicroscopy of viable, dead and apoptotic cells.

Ultrasonic imaging is frequently used in medical diagnosis to differentiate normal and tumour tissues. Here we investigate if distinct types of cell death can be discriminated through the use of ultrasound biomicroscopy. By using a well-controlled system in vitro, we demonstrate that this imaging modality can be used to differentiate living cells, dead cells and cells that have died by programmed cell death or apoptosis. The results indicate a greater than twofold ultrasound backscatter signal from apoptotic cells in comparison to viable cells, whereas heat-killed cells exhibit an intermediate level of ultrasound backscatter. The results have potential implications in the study of disease-related biological processes involving apoptosis.

Antineoplastic Agents↗

PubMed1997

Magnetic resonance imaging of temperature changes during interstitial microwave heating: a phantom study.

Changes in magnetic resonance (MR) signals during interstitial microwave heating are reported, and correlated with simultaneously acquired temperature readings from three fiber-optic probes implanted in a polyacrylamide gel phantom. The heating by a MR-compatible microwave antenna did not interfere with simultaneous MR image data acquisition. MR phase-difference images were obtained using a fast two-dimensional-gradient echo sequence. From these images the temperature-sensitive resonant frequency of the 1H nuclei was found to decrease approximately by 0.008 ppm/ degree C. The method and results presented here demonstrate that noninvasive MR-temperature imaging can be performed simultaneously with interstitial microwave thermal treatment.

Biophysical Phenomena↗

PubMed1996

Blood flow cooling and ultrasonic lesion formation.

This article examines lesion formation using focused ultrasound and demonstrates how blood flow may affect lesion dimensions using a theoretical model. The effects of blood flow on temperature distributions during ultrasonic lesioning are examined for both regional cooling by the microvasculature and localized cooling due to thermally significant vessels. Regional cooling was critically assessed using two models: the Pennes bioheat transfer equation and the scalar effective thermal conductivity equation. Localized cooling was modeled by adding an advective term in the heat diffusion equation in regions enclosed by thermally significant vessels. A finite difference approach was used to solve the basic equations of heat transfer in perfused tissues in cylindrical coordinates. The extent of the lesioned tissue was determined by the accumulated thermal dose at each location. The size of the lesion was then calculated from the boundaries of the thermal isodose curves generated by the simulations. The results were compared to published in vivo lesion data in rat liver. It was shown that even for short ultrasound exposure times (approximately 8 s), blood flow may play an important role in the thermal dose distribution.

Algorithms↗

PubMed1995

Influence of salinity on copper and azide toxicity to larval topsmelt Atherinops affinis (Ayres).

Performance of a 7-d growth and survival toxicity test protocol using larval topsmelt, Atherinops affinis (Ayres), was evaluated for copper chloride and sodium azide at representative estuarine salinities. Results showed that topsmelt are amenable to toxicity testing at estuarine salinities ranging from 5 to 34/1000 since control survival was 100% in all toxicity tests. Sensitivity to both toxicants increased at lower salinities, with the LC50s for copper ranging from 205 micrograms/L at 34/1000 to 44 micrograms/L at 10/1000, and those for sodium azide ranging from 54 mg/L at 34/1000 to 7 mg/L at 5/1000. Larval tissue osmolality decreased with increasing copper concentration relative to control fish. Copper uptake was not affected by changes in salinity. This suggests that increased sensitivity to copper was due, in part, to the increasing physiological challenge of osmoregulation. It is also possible that cupric ion concentration increased at lower salinities, resulting in reduced larval survival. It is hypothesized that increased sensitivity to azide at lower salinity was due to the interaction between azide toxicity and increasing osmotic challenge. A second experiment with azide showed that larval acclimation time did not affect the interaction between salinity and azide toxicity.

Analysis of Variance↗

PubMed1995

The subtleties of ultrasound images of an ensemble of cells: simulation from regular and more random distributions of scatterers.

Significant differences in the backscatter amplitudes which are correlated with different tissue morphology have been observed in ultrasound images of tissue. While many factors could be linked to subtle changes in the images, the purpose of this paper is to explore the possibility that backscatter signals are linked to the organization of the spatial distribution of individual cells that produce an ensemble of scattering sources. Simple one- and two-dimensional simulations of backscatter signals produced by weak scatters separated by << lambda to < lambda in regular, random, and pseudo-random distributions in a "sample" are performed. Both regular and pseudo-random distributions produce large boundary signals, and in the central regions of the sample, the square root of the backscatter power is directly related to the amount of randomization, R, over a large range. Large changes in backscattering intensities are predicted for the same density of scatterers with differing R in different regions of the same sample. Thus, the subtle differences in the scattering distribution should show significant changes in the backscatter images.

Animals↗

PubMed1995

The effect of refraction and assumed speeds of sound in tissue and blood on Doppler ultrasound blood velocity measurements.

The combined effect of three assumptions relating to refraction, the speed of sound in tissue and the speed of sound in blood on the accuracy of Doppler ultrasound blood velocity measurements has been investigated. A theoretical relationship giving the net velocity measurement error introduced by these three assumptions has derived using a model in which tissue and blood layers are separated by straight, parallel boundaries. This net error is dependent on the assumed and actual speed of sound in tissue, the assumed speed of sound in blood and the Doppler angle, but is effectively independent of the actual speed of sound in blood. For clinical blood velocity measurements, the net error is estimated to be as much as an 8% overestimation of the actual velocity, higher than previously predicted for any of the factors individually. The relationship also predicts a net velocity measurement error in experimental flow systems and string phantoms which is dependent on the speed of sound in the liquid bath. A water bath at room temperature will give an overestimation of approximately 2%. Experimental investigations using conventional and modified string phantoms and a 5-MHz linear phased array system support these conclusions. The effect of perturbing the layers from their parallel orientation has also been considered theoretically and has provided additional support for the above conclusions. These results may help more accurate Doppler velocity measurements in both experimental and clinical settings.

Blood↗

PubMed1995

Large blood vessel cooling in heated tissues: a numerical study.

Large blood vessels can produce steep temperature gradients in heated tissues leading to inadequate tissue temperatures during hyperthermia. This paper utilizes a finite difference scheme to solve the basic equations of heat transfer and fluid flow to model blood vessel cooling. Unlike previous formulations, heat transfer coefficients were not used to calculate heat transfer to large blood vessels. Instead, the conservation form of the finite difference equations implicitly modelled this process. Temperature profiles of heated tissues near thermally significant vessels were calculated. Microvascular heat transfer was modelled either as an effective conductivity or a heat sink. An increase in perfusion in both microvascular models results in a reduction of the cooling effects of large vessels. For equivalent perfusion values, the effective conductivity model predicted more effective heating of the blood and adjacent tissue. Furthermore, it was found that optimal vessel heating strategies depend on the microvascular heat transfer model adopted; localized deposition of heat near vessels could produce higher temperature profiles when microvascular heat transfer was modelled according to the bioheat transfer equation (BHTE) but not the effective thermal conductivity equation (ETCE). Reduction of the blood flow through thermally significant vessels was found to be the most effective way of reducing localized cooling.

Animals↗

PubMed1995

Optimizing ultrasound focus distributions for hyperthermia.

A method is described for generating ultrasound focus patterns for ultrasound hyperthermia treatment planning for steady state and transient hyperthermia. The solution for placement and intensity of ultrasound focus points is based on two types of temperature constraints: 1) equality constraints on the tumor boundary (temperature is held at maximum safe level) and 2) inequality constraints in the tumor interior (in a therapeutic range of temperatures). The method employs a simplex algorithm to solve a series of linear equations which approximate the heating distribution in tissue. Examples are given for field conjugate acoustic lens applicators capable of generating multiple foci simultaneously.

Humans↗

PubMed1995

Dimethylformamide as an enhancer of cavitation-induced cell lysis in vitro.

Polar solvents, including dimethylformamide (DMF), have been investigated as anticancer drugs, but their potential usefulness is constrained by hepatotoxic side effects. The ability to enhance drug cytotoxicity with ultrasound would be valuable in creating locally intense chemotherapy while minimizing effects peripheral to the treatment site. The effects of continuous wave ultrasound (US) (985 kHz; 0.5-2.5 W/cm2) were evaluated on cultured HL-60 human promyelocytic leukemia cells alone and with a noncytotoxic DMF dose (0.11 M). The cells were insonified in a configuration that created no cell lysis without the introduction of albumin-stabilized microbubbles into the exposure chamber. When microbubbles were introduced, US with bubbles induced cell lysis, and the presence of DMF significantly increased the lysis induced by ultrasound with bubbles. The necessary presence of microbubbles for the DMF-US synergism to occur suggests that a likely mechanism is acoustic cavitation, initiated by the presence of microbubbles as nuclei. Detection of subharmonics confirmed the presence of cavitation, and cell lysis was well correlated with the subharmonic amplitude. The results show that albumin-stabilized microbubbles, similar to those currently used as US contrast agents, may provide a significant source of nuclei and improve prospects for cancer therapy using acoustic cavitation. The evidence presented supports the hypothesis that cell damage is due to a sonochemical rather than to a sonomechanical process.

Cell Membrane↗

PubMed1993

Beam shaping for microwave waveguide hyperthermia applicators.

PURPOSE: Hyperthermia treatments commonly use single element microwave waveguide applicators. The microwave beam patterns produced by these applicators are often non-uniform. As a result, hot spots are formed in the heated tissue and therapeutic temperatures are reached in only small areas of the treatment field. We have constructed new coupling boluses that improve the heating patterns of external microwave applicators. METHODS: The microwave beam transmitted through the bolus is modified by microwave absorbing saline/gelatin pads. The pads can be designed to result in a uniform heating pattern over a large area or alternatively, complex heating patterns can be generated for specific clinical applications. An analysis of the effect of bolus design parameters on microwave absorption patterns is presented. The heating patterns of the MA-100 and MA-120 microwave waveguide applicators have been measured in muscle and fat phantom materials with both the manufacturer's boluses and the new boluses. RESULTS: In the case of the MA-100, the area above the 70% heating level measured in a muscle phantom was increased by a factor of 2.3 by an absorbing pad bolus. Similarly, the heating area of the MA-120 was increased by a factor of 2.6 by an absorbing pad bolus. The boluses were tested in a clinical setting by measuring tissue temperature profiles in patients under different bolus arrangements. The area over which therapeutic temperature was achieved was increased considerably when the absorbing bolus was used. A second bolus was designed for the MA-120 to produce a ring heating pattern for the treatment of a breast cancer patient who had developed recurrences at the periphery of a skin graft. The heating pattern produced in a muscle phantom is compared with tissue temperature profiles measured during the hyperthermia treatment of this patient. CONCLUSIONS: Microwave absorbing filters using saline pads significantly improve the heating patterns of microwave waveguide hyperthermia applicators. This improvement was confirmed in clinical application where much greater areas of homogeneous heating were observed. The technology was extended to produce complex heating patterns for special clinical applications.

Breast Neoplasms↗

PubMed1993

In vitro evaluation of gallstone dissolution with methyl-tert-butyl ether and ultrasound energy.

Given the large number of cholecystectomies performed annually, a nonsurgical approach to gallstone therapy is of great interest. A laboratory ultrasound system has been developed to study enhancement of methyl-tert-butyl ether (MTBE) dissolution of human gallstones in vitro. A mathematical model that quantitatively characterizes the dissolution process via a rate constant has been developed. Using this model, the kinetics of 15 gallstones from a single patient were evaluated for three dissolution methods: 1) unstirred MTBE, 2) aspirated MTBE, and 3) ultrasonically enhanced MTBE. The results showed excellent fits between the model and measured dissolution rates. 195 kHz continuous-wave (CW) ultrasonically enhanced dissolution rates exhibited a 6.2 fold gain over the manually aspirated MTBE and a 49.5 fold gain over static MTBE dissolution. Investigation of 50% duty cycle pulsed mode ultrasound revealed that total power appears to be the determinant of the observed dissolution rates. Gallstone calcification showed a strong correlation with dissolution rates measured by the model.

Cholelithiasis↗

PubMed1993

Radiofrequency capacitive heaters: the effect of coupling medium resistivity on power absorption along a mouse leg.

A capacitive radiofrequency source in conjunction with a temperature-controlled electromagnetic coupling medium has the potential of delivering uniform heating distributions in a mouse leg for experimental studies to investigate the use of hyperthermia as a treatment for cancer. The system has been adopted by a number of groups who have confirmed that uniform temperatures can be achieved in the presence of blood flow along a one-dimensional line which extends between the plates across the leg. In this paper, a simple mathematical model is presented and verified experimentally to demonstrate that parallel-plate capacitive radiofrequency heaters produce an inherent absorbed power distribution along the leg which is determined by the impedances across the loads. Hence, the thicker or thinner regions of the leg can be preferentially heated by using a coupling medium with lower or higher salinity, respectively. Uniform power absorption along the mouse leg required that the coupling medium had equivalent electrical properties to those of tissue.

Animals↗

PubMed1992

A method for computer simulation of ultrasound Doppler color flow images--I. Theory and numerical method.

Ultrasound imaging systems utilizing the pulsed Doppler principle are capable of providing images of blood flow in real time. We present a useful method for simulating flow images on a computer. Our method assumes that blood and surrounding tissue consist of many point-like scatters positioned randomly in three dimensions. The position-dependent acoustic response of each scatterer is calculated using the acoustic impulse response method. This method takes into account the spatial effects of the transducer geometry on both the amplitude and temporal response of point-scattering. Details of theory, assumptions made in the simulation, and numerical methods are described fully for a spherically focused transducer, as well as a discussion of signal processing for generation of the flow image. Motion of a single scatterer is investigated to test the performance of the simulation algorithm. This simulation method could potentially be beneficial for detailed study of current and future flow imaging systems.

Blood Flow Velocity↗

PubMed1992

A method for computer simulation of ultrasound Doppler color flow images--II. Simulation results.

A computational method of simulating Doppler color flow images has been developed. It is based on a point-scattering model of moving blood and surrounding tissue and is capable of treating the entire flow image generation process. Simulated images of parabolic flow dynamics in a cylindrical vessel are presented to show the statistical nature of the map of velocity estimates and to demonstrate the effects of wall filters and different display schemes. Quantitative results of extracted velocity profiles are included and indicate the usefulness of the simulation method for studying the quantitative capabilities of flow imaging.

Blood Flow Velocity↗

PubMed1992

In vitro high resolution intravascular imaging in muscular and elastic arteries.

High resolution (125-microns lateral, 55-microns axial) images of 16 muscular (femoral) and 15 elastic (common carotid) human arteries were made in vitro with use of a prototype 45-MHz intravascular imaging system. Four distinct regions of scattering, excluding plaque, were identified in the ultrasound images corresponding histologically to the adventitia, media, thickened intima and elastic laminae, both internal and external. Arterial samples imaged under pressure and in a collapsed state underwent dimensional changes but exhibited similar levels of backscatter amplitude. All the elastic arteries displayed a prominent echogenic media, whereas all the muscular arteries displayed an echolucent media. Scattering from the internal elastic lamina in muscular arteries provided an excellent landmark for defining the location and extent of intimal thickening or plaque. In elastic arteries the internal elastic lamina could not be distinguished from the echogenic media; consequently, the boundary between the media and intimal layer was indistinct. Differences in the relative concentration and organization of collagen and elastin were found to provide a consistent explanation for the differences in scattering that were observed between individual layers within an artery as well as between muscular and elastic arteries.

Arteriosclerosis↗

PubMed1992

Accelerated gallstone dissolution in methyl tert-butyl ether by sonication. An in vitro study.

OBJECTIVES: The authors tested the effect of 195 KHz therapeutic ultrasound energy on gallstone dissolution in concert with methyl tert-butyl ether (MTBE) in vitro. METHODS: Sixteen sets of three gallstones matched for weight and appearance were selected from 16 surgically resected human gallbladders. One stone from each set was analyzed for its density pattern by computed tomography (CT) and biochemically for cholesterol content. Based on CT appearance, the stones were classified into eight noncalcified, four partially calcified, and four heavily calcified sets. The three stones were subjected to dissolution with MTBE: one with simultaneous sonication via an experimental ultrasound unit, one with manual stirring, and one acted as control without added treatment. RESULTS: Sonication reduced the dissolution time of noncalcified stones by 96% (range, 94%-98%; standard deviation [SD], 2%) relative to controls, and it was three to four times more effective than manual stirring. It was similarly effective in helping to dissolve partially calcified stones, but not heavily calcified stones. CONCLUSIONS: This study demonstrates the positive effect of sonication in accelerating gallstone dissolution with MTBE in vitro for stones without heavy calcification.

Cholelithiasis↗