Biomedical subjects

M D Sherar

Publications and source records attributed to M D Sherar.

13 recordsLinked to original sources

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↗

PubMed1990

Subsurface ultrasound microscopic imaging of the intact eye.

The authors have developed a method of obtaining images of cross sections of the intact eye at microscopic resolution. High-frequency ultrasound transducers (100 MHz) have been developed and incorporated into imaging devices. These devices are capable of producing images to a depth of 4 mm at an axial and lateral resolution approaching 20 microns. Resolution exceeds that of current combined A- and B-scan imaging devices by a factor of approximately 10. Microscopic images of ocular structures including Schlemm's canal, cornea, iris, ciliary muscles, and retina have been produced in eye bank eyes. These studies show the feasibility of developing an apparatus to be used in the clinical setting for examining anterior structures of the eye not visible by current techniques.

Anterior Chamber↗

PubMed1989

The design and fabrication of high frequency poly(vinylidene fluoride) transducers.

Poly(vinylidene fluoride) (PVDF) transducers are well suited for use in high frequency pulse-echo ultrasound systems because of their high bandwidth. We analyze the design parameters of PVDF transducers operating in the 100 MHz range using the KLM transducer model. The effect of backing layers, electrode configuration, transducer surface area and tuning circuits on the insertion loss and pulse-echo response of the transducers are investigated. Using this design procedure, an experimental PVDF transducer is proposed for applications in the 100 MHz range. The transducer is built into a high frequency SMA electrical connector. Insertion loss and pulse-echo response measurements are compared with theoretical predictions.

Equipment Design↗

PubMed1989

A 100 MHz B-scan ultrasound backscatter microscope.

The construction and operation of a 100 MHz B-mode ultrasound backscatter microscope are described. The powerful B-mode technique is extended into the domain of microscopy allowing the imaging of internal structure in living specimens on a microscopic scale. A frame rate of 5 frames per second is achieved which gives rapid feedback to the operator. Specially designed components of the scanner are described in detail, including the transducer, motion system and scan converter. An f/2 transducer is employed, leading to a scanner resolution of approximately 36 micron in both the lateral and axial directions. The benefits of such high resolution are demonstrated in preliminary images of multicellular spheroids and intact human ocular tissue.

Equipment Design↗

PubMedDate not supplied

Ultrasound backscatter microscopy images the internal structure of living tumour spheroids.

Ultrasound microscopes have the potential for imaging structure at depth in thick specimens, yet this is not possible in biological specimens using conventional ultrasound transmission or reflection methods. But, subsurfacing imaging is possible with ultrasound if a backscatter (pulse-echo) technique, similar to that used in medical imaging, is used. The central problem of extending backscatter imaging to ultrasound microscopy has been the development of high frequency (greater than 100 MHz) transducers with sufficient bandwidth and sensitivity to detect the low levels of backscatter from biological materials. We recently reported the development of such a transducer which we have now incorporated into a new ultrasound backscatter microscope capable of providing tomographic images at depths of up to 4 mm in biological specimens. Here we present the first ultrasound backscatter micrographs of living biological specimens. The benefits of this technique are demonstrated by its application to imaging the internal structures of living tumour spheroids showing striking contrast between the necrotic core and the viable rim of the spheroid.

Cell Aggregation↗

PubMedDate not supplied

Effect of vascular occlusion on tumour temperatures during superficial hyperthermia.

Tumour temperature heterogeneity during hyperthermia has been attributed to irregular tumour vascular perfusion. We have compared temperature distributions in human tumours subjected to superficial hyperthermia under conditions of normal and occluded blood flow. Three patients with recurrent malignant melanoma on the leg were treated with radiation followed by hyperthermia 60-90 min later on days 1, 8 and 22. Heating (15-30 min) with normal blood flow was followed by 15 min of heating with tourniquet occlusion, although the tourniquet had to be intermittently released when the patients complained of discomfort. Hyperthermia was delivered using either a 1.4 MHz ultrasound or 915 MHz microwave applicator. Temperatures were monitored using superficial and interstitial thermometers in tumour and normal tissues. When the tourniquet was applied, the amount of power required to maintain peak temperatures was decreased by a factor of 3-10. With normal blood flow, there was a significant degree of temperature heterogeneity within the treatment volume, both within normal and tumour tissues, which improved with tourniquet application. The T90 and T50 indices increased both in normal tissues and tumour following the tourniquet occlusion, with the temperature increments being greater for normal tissues. Temperatures at depth were increased despite the reduction in applied power and the temperature profiles were smoother when the tourniquet was applied. No cutaneous, vascular or neuromuscular side effects were observed amongst these three subjects either acutely or at 1 month follow-up. These studies demonstrate directly that the temperature heterogeneity which exists in human tumours subjected to external heating can be reduced by occluding the blood supply.

Aged↗

PubMedDate not supplied

A variable microwave array attenuator for use with single-element waveguide applicators.

The effectiveness of hyperthermia treatments is often limited by temperature inhomogeneity that arises in the treatment field due to variable tissue properties and blood flow. Moreover, blood flow can change during a treatment, leading to the formation of hot and cool areas even if the initial temperature distribution is uniform. A variable microwave array attenuator has been constructed, that will enable the field patterns of single element microwave waveguide hyperthermia applicators to be altered during treatment, to improve temperature homogeneity. The coupling bolus was designed with an array of individually controlled elements, each filled with a microwave absorbing saline solution. Additions or withdrawals of saline are made to alter the power deposition in a specific area of the treatment field. Thermographic measurements were made in muscle equivalent phantom materials, with the bolus/waveguide assembly. Results showed that the variable array attenuator was able to significantly alter the heating pattern of a large waveguide applicator.

Biophysical Phenomena↗