Biomedical subjects

M D Sherar

Publications and source records attributed to M D Sherar.

At least 37 records · Page 2Linked to original sources

PubMed1999

Optical phantom materials for near infrared laser photocoagulation studies.

BACKGROUND AND OBJECTIVE: Phantoms were developed that simulate tissue with dynamic and static optical properties with which to study the effects of laser irradiation. STUDY DESIGN/MATERIALS AND METHODS: Albumen, agar, and an absorbing dye (Naphthol Green) were combined to form a phantom with heat sensitive optical properties to mimic tissue response. The optical properties of this phantom were measured by using the added absorber technique. A polyacrylamide phantom with static optical properties was designed with the equivalent values of micro(a) and micro'(s) by combining appropriate concentrations of Naphthol Green and Intralipid-10%. RESULTS: The absorption and reduced scattering coefficient of the phantoms were 0. 50 +/- 0.04 cm(-1) and 2.67 +/- 0.07 cm(-1) respectively, in the native state at 805 nm. In the coagulated state, the absorption and scattering coefficient were 0.7 +/- 0.1 cm(-1) and 13.1 +/- 0.5 cm(-1) respectively. CONCLUSION: Two phantoms with dynamic or static optical properties were developed with properties similar to tissue. They may be used in future studies of opto-thermal effects in tissues.

Acrylic Resins↗

PubMed1999

Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo.

A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25- to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients.

Animals↗

PubMed1999

An investigation of the flow dependence of temperature gradients near large vessels during steady state and transient tissue heating.

Temperature distributions measured during thermal therapy are a major prognostic factor of the efficacy and success of the procedure. Thermal models are used to predict the temperature elevation of tissues during heating. Theoretical work has shown that blood flow through large blood vessels plays an important role in determining temperature profiles of heated tissues. In this paper, an experimental investigation of the effects of large vessels on the temperature distribution of heated tissue is performed. The blood flow dependence of steady state and transient temperature profiles created by a cylindrical conductive heat source and an ultrasound transducer were examined using a fixed porcine kidney as a flow model. In the transient experiments, a 20 s pulse of hot water, 30 degrees C above ambient, heated the tissues. Temperatures were measured at selected locations in steps of 0.1 mm. It was observed that vessels could either heat or cool tissues depending on the orientation of the vascular geometry with respect to the heat source and that these effects are a function of flow rate through the vessels. Temperature gradients of 6 degrees C mm(-1) close to large vessels were routinely measured. Furthermore, it was observed that the temperature gradients caused by large vessels depended on whether the heating source was highly localized (i.e. a hot needle) or more distributed (i.e. external ultrasound). The gradients measured near large vessels during localized heating were between two and three times greater than the gradients measured during ultrasound heating at the same location, for comparable flows. Moreover, these gradients were more sensitive to flow variations for the localized needle heating. X-ray computed tomography data of the kidney vasculature were in good spatial agreement with the locations of all of the temperature variations measured. The three dimensional vessel path observed could account for the complex features of the temperature profiles. The flow dependences of the transient temperature profiles near large vessels during the pulsed experiments were consistent with the temperature distributions measured in the steady state experiments and provided unique insights into the process of convective heat transfer in tissues. Finally, it was shown that even for very short treatment times (3-20 s), large vessels had significant effects on the tissue temperature distributions.

Angiography↗

PubMed1998

High-frequency ultrasound properties of multicellular spheroids during heating.

High-frequency ultrasound monitoring is a possible method for real-time imaging of thermal therapy in tissues at microscopic resolution. The objective of this work was to measure changes in the ultrasound properties of V79 spheroids (grown from Chinese Hamster lung fibroblasts) exposed to heating. Spheroids are clonal aggregates of cells that provide a useful model for investigating the ultrasound properties of cells in the absence of connective tissue. Relative echo signal power and attenuation coefficients were measured over the frequency range 30 MHz to 70 MHz, from spheroids heated from 37 degrees C to 50 degrees C or 60 degrees C. Echo signal power from the viable rim decreased during the first 5 min by a factor of 1.08 before the spheroid reached 50 degrees C. For the next 25 min, echo signal power rose to a factor of 1.27 above the initial level, after which it remained relatively constant over the remainder of the 50 degrees C heating period. At 60 degrees C, echo signal from the viable rim remained relatively constant, although it appeared to have possibly decreased slightly over the duration of the heating period. Echo signal power from the necrotic core fell to a factor of 1.4 and 1.54 below the initial level at 50 degrees C and 60 degrees C, respectively. First-order chemical rate analysis applied to the echo signal power results in the viable rim at 50 degrees C revealed a rate constant for the 5-15-min heating interval. Interpretation of the echo signal power results in terms of histological stains indicates that the rise in echo signal power at 50 degrees C was due to a loss of cell cohesion, and the possible drop in echo signal power at 60 degrees C was due to spheroid coagulation. Attenuation coefficients decreased by up to 1.54 dB mm-1 over a 30-min period at 60 degrees C. The appearance of a real-time ultrasound image of lesion formation in cells is discussed.

Animals↗

PubMed1998

Ultrasound imaging of thermal therapy in in vitro liver.

The objective of this work was to image liver tissue heated to temperatures below the vaporization threshold as a function of time, to test the feasibility of real-time ultrasound monitoring to control lesion size during minimally invasive thermal therapy (MITT). Two experiments were devised. In one experiment, a thermal gradient was established in a rectangular volume of tissue to correlate changes in ultrasound image echogenicity (B-mode image brightness) with tissue temperature. In the other, a thermal lesion was produced in a rectangular volume of tissue by an interstitial microwave antenna, and the progression of the lesion was monitored by ultrasound. In both experiments, the echogenicity of the tissue increased slightly for tissue temperatures up to 40 degrees C, but became lower than that of unheated tissue for temperatures above 40 degrees C. In the second experiment, images of the lesion were compared with a photograph of the lesion taken after the experiment was complete. The final lesion was composed of two concentric regions--an inner region of heavily coagulated tissue and an outer region of less-damaged tissue. These two damaged regions indicated that increased ultrasound attenuation was largely responsible for the decreased echogenicity observed in the ultrasound images, and the increase in echogenicity of tissue heated to temperatures up to 40 degrees C is thought to be due to decreased ultrasound attenuation at these temperatures.

Animals↗

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↗

PubMed1998

A theoretical comparison of energy sources--microwave, ultrasound and laser--for interstitial thermal therapy.

A number of heating sources are available for minimally invasive thermal therapy of tumours. The purpose of this work was to compare, theoretically, the heating characteristics of interstitial microwave, laser and ultrasound sources in three tissue sites: breast, brain and liver. Using a numerical method, the heating patterns, temperature profiles and expected volumes of thermal damage were calculated during standard treatment times with the condition that tissue temperatures were not permitted to rise above 100 degrees C (to ensure tissue vaporization did not occur). Ideal spherical and cylindrical applicators (200 microm and 800 microm radii respectively) were modelled for each energy source to demonstrate the relative importance of geometry and energy attenuation in determining heating and thermal damage profiles. The theoretical model included the effects of the collapse of perfusion due to heating. Heating patterns were less dependent on the energy source when small spherical applicators were modelled than for larger cylindrical applicators due to the very rapid geometrical decrease in energy with distance for the spherical applicators. For larger cylindrical applicators, the energy source was of greater importance. In this case, the energy source with the lowest attenuation coefficient was predicted to produce the largest volume of thermally coagulated tissue, in each tissue site.

Brain↗

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

Ultrasound properties of liver tissue during heating.

The objective of this work was to determine changes in the ultrasound properties of heated tissues, with potential application to monitoring of minimally invasive thermal therapy (MITT). Changes in backscatter coefficients and frequency-dependent attenuation coefficients were measured over the frequency range 2.5 MHz to 5 MHz from heated samples of store-bought fresh bovine liver, which was used as a tissue model. Individual liver samples were heated from 37 degrees C to either 50 degrees C, 55 degrees C, 60 degrees C, 65 degrees C or 70 degrees C by warm water. The backscatter coefficient increased during the first 3 min by a factor of 1.09 and 1.11 before the tissue reached 50 degrees C and 55 degrees C, respectively. A decrease in backscatter coefficient followed at 50 degrees C by a factor of 1.12 below the initial level and, at 55 degrees C, the backscatter coefficient dropped below the initial level by a factor of 1.19. The backscatter coefficient decreased within the first 2 min by a factor of 1.22 before the tissue reached 60 degrees C, then increased gradually to a factor of 1.05 below the initial level. At 65 degrees C and 70 degrees C, the changes in backscatter coefficient were highly variable, which may have been due to production of gas microbubbles in the heated tissues. The ultrasound attenuation coefficient increased by as much as 1.48 dB cm-1 over a 30-min period at 70 degrees C. First-order rate parameters derived from the attenuation results revealed one rate process at 50 degrees C and 55 degrees C and two rate processes at 60 degrees C, 65 degrees C and 70 degrees C. An activation energy of 1.00 x 10(4) cal mol-1 was derived from the second rate constants at 60 degrees C, 65 degrees C and 70 degrees C, which indicates that changes in attenuation may be due to protein denaturation. In conclusion, ultrasound image monitoring of thermal therapy treatment in liver may be feasible; however, the backscatter coefficient changes during heating are small and are of the same order as the variation in these changes from point to point in the tissue.

Animals↗

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↗

PubMed1996

The relationship between intracellular pH and heat sensitivity in a thermoresistant cell line.

To explore further the relationship between intracellular pH (pHi) and thermosensitivity, we compared survival and pHi levels in RIF-1 cells and a thermoresistant variant, TR-4 cells, while heating under different conditions of acid or neutral extracellular pH (pHe). We also added 5-(N-ethyl-N-isopropyl) amiloride (EIPA), a potent inhibitor of one of the major membrane regulators of pHi, the Na+/H+ antiport, and/or removed NaHCO3 to inactivate the alternate membrane regulator of pHi, the HCO3-/Cl- exchanger. At pHe 7.3 with NaHCO3, EIPA (15 microM) did not enhance the cytotoxicity of heat in either cell line. At pHe 6.8 with NaHCO3, EIPA enhanced thermal cytotoxicity for RIF-1 cells only, but without NaHCO3, at pHe 6.8 or 6.5, EIPA treatment during heating resulted in a significant decrease in survival of TR-4 cells also. Measurements of pHi levels immediately after heating correlated with the survival data, demonstrating a linear relationship between pHi and log surviving fraction for both cell lines. This relationship, however, is different between the two cell lines in that the TR-4 cells are more resistant to reduction in pHi with heating, and for any given pHi level to demonstrate a higher correlation is different for the two cell lines, suggesting a difference in the relationship between pHi and log surviving fraction between the TR-4 and RIF-1 cells.

Amiloride↗

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↗

PubMed1994

A model for characterizing residential ground current and magnetic field fluctuations.

The current through the residential grounding circuit is an important source for magnetic fields; field variations near the grounding circuit accurately track fluctuations in this ground current. In this paper, a model is presented which permits calculation of the range of these fluctuations. A discrete network model is used to simulate a local distribution system for a single street, and a statistical model to simulate unbalanced currents in the system. Simulations of three-house and ten-house networks show that random appliance operation leads to ground current fluctuations which can be quite large, on the order of 600%. This is consistent with measured fluctuations in an actual house.

Electricity↗

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↗

PubMed1992

Use of a high frequency ultrasound microscope to image the action of 2-nitroimidazoles in multicellular spheroids.

A system was designed to allow imaging of control and drug treated multicellular spheroids with a high frequency backscatter ultrasound microscope. It allowed imaging of individual spheroids under good growth conditions. Since little data were available on cellular toxicity of ultrasound at these high frequencies (80 MHz), studies were undertaken to evaluate effects on cell survival, using a colony forming assay. No toxicity was observed on cell monolayers subjected to pulsed ultrasound at the intensities used for imaging experiments. Spheroids were also subjected to pulsed ultrasound and no growth delay was observed when exposed spheroids were compared with mock-exposed spheroids. Imaging studies were performed and pictures of untreated spheroids were obtained in which the necrotic and viable regions are clearly distinguishable. When the hypoxic cell cytotoxin 1-methyl-2-nitroimidazole (INO2) was added to the spheroid, dramatic changes were observed in the backscatter signal. The interior viable cells of the spheroid were selectively affected. Changes in the backscatter signal were also observed when the reduction product 1-methyl-2-nitrosoimidazole (INO) was added to spheroids. With INO however, the changes were located at the periphery of the spheroid, presumably due to the high reactivity of INO which limits diffusion of the drug into the spheroid. The present work demonstrates the potential usefulness of ultrasound backscatter microscopy in following the action of selected drugs in this in vitro tumour model.

Animals↗

PubMed1991

Clinical use of ultrasound biomicroscopy.

The authors have developed a method of obtaining images of cross-sections of the intact anterior globe at microscopic resolution. High-frequency ultrasound transducers (50-100 MHz) have been developed and incorporated into a clinical B-scan device capable of producing images in the living human eye to a depth of approximately 4 mm at an axial and lateral resolution approaching 20 microns. Clinical use of this instrument is no more difficult than conventional immersion ultrasonography. The authors' results in a series of 14 clinical cases have shown that this method can provide information unavailable from any other imaging technique. Anterior segment tumors difficult to define with conventional ultrasound can be measured and the extent of invasion determined. Differentiation of tissue on the basis of internal acoustic characteristics is aided by the very fine backscatter speckle patterns at these frequencies. Pathology behind anterior segment opacities can be imaged in detail and the ability to image angle structures in cross-section allows a new quantitative method of gonioscopy. The ability to define the relationship of the iris, posterior chamber, zonules, ciliary body, and lens is potentially helpful in understanding mechanisms of glaucoma. Ocular structures can be measured with increased accuracy. Clinical ultrasound biomicroscopy (UBM) has shown significant potential as an aid in diagnoses of ocular disease.

Anterior Eye Segment↗

PubMed1990

A simple model for calculating residential 60-Hz magnetic fields.

A model is presented that permits the calculation of densities of 60-Hz magnetic fields throughout a residence from only a few measurements. We assume that residential magnetic fields are produced by sources external to the house and by the residential grounding circuit. The field from external sources is measured with a single probe. The field produced by the grounding circuit is calculated from the current flowing in the circuit and its geometry. The two fields are combined to give a prediction of the total field at any point in the house. A data-acquisition system was built to record the magnitude and phase of the grounding current and the field from external sources. The model's predictions were compared with measurements of the total magnetic field at a single location in 23 houses; a correlation coefficient of .87 was obtained, indicating that the model has good predictive capability. A more detailed study that was carried out in one house permitted comparisons of measurements with the model's predictions at locations throughout the house. Again, quite reasonable agreement was found. We also investigated the temporal variability of field readings in this house. Daily magnetic field averages were found to be considerably more stable than hourly averages. Finally, we demonstrate the use of the model in creating a profile of the magnetic fields in a home.

Electromagnetic Fields↗