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Biomedical subjects

M D Sherar

Publications and source records attributed to M D Sherar.

50 records · Page 3Linked to original sources
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

The use of CT perfusion to monitor the effect of hypocapnia during laser thermal therapy in a rabbit model.

One of the limiting factors in the thermal therapy of tumours is the dissipation of heat by blood flow. The current study investigates the use of hyperventilation (hypocapnia) to decrease tumour blood flow during laser thermal therapy. Rabbits with implanted VX2 thigh tumours were treated using a diode laser (805 nm) as the heating source. One group of rabbits (n = 8) was treated with the new hypocapnia protocol and another group (n = 8) with the conventional (normocapnia) protocol. The mean tumour volume and blood flow were the same for the two groups prior to treatment. The laser power temporal profile (3.0-1.5 W) and the duration of treatment (60 min) were also the same for both treatment protocols. Blood flow maps were calculated from a series of contrast-enhanced CT images. The average change in thermal lesion area at 60 min post-laser thermal therapy from pre-treatment normalized to the pre-treatment tumour area was significantly different between the two treatment protocols: 0.52+/-0.13 (hypocapnia) vs 0.33+/-0.12 (normocapnia) (p < 0.001). Similarly, the average fractional decrease in global tumour blood flow 60 min post-treatment from pre-treatment was also significantly different between the two protocols: 0.64+/-0.10 (hypocapnia) vs 0.41+/-0.14 (normocapnia) (p < 0.001). The hypocapnia protocol produced larger thermal lesion area and greater decrease in tumour blood flow post-treatment than the normocapnia protocol. These results support the further investigation of the use of hypocapnia to increase the therapeutic effect of laser thermal therapy.

Animals↗
PubMedDate not supplied

An edge-element based finite element model of microwave heating in hyperthermia: method and verification.

Hyperthermia has been shown to improve local tumour control of superficial and deep seated lesions when combined with radiotherapy. There remains difficulty in heating larger tumours with conventional applicators, but this is being addressed by several new applicator designs. This paper presents a new numerical model of microwave heating which is designed to aid in the development of new applicators for superficial heating. The model is based on a finite element method which utilises vector valued basis functions instead of the more conventional scalar valued basis functions. These basis functions were chosen since they are inherently suited for the solution of Maxwell's equations due to their vector nature. The model was successfully verified against an analytic solution to the Mie scattering problem as well as against previously published measurements of heating from a modified water bolus attached to a conventional waveguide applicator. An accompanying paper describes an application of this model to the design optimization of this modified bolus.

Biophysical Phenomena↗
PubMedDate not supplied

An edge-element based finite element model of microwave heating in hyperthermia: application to a bolus design.

Heating of superficial tumours with microwave waveguide applicators has been shown in phase III trials to significantly improve the local control of small lesions when combined with radiation therapy. This success has not yet translated to the treatment of larger tumours, due to difficulty in adequately heating the entire tumour region. Several modifications to the water bolus used with external waveguide applicators have been made in the past in order to increase the heating area. One such modification consisted of a large, microwave-absorbing patch placed inside the bolus, which flattens out the beam profile produced by the applicator. Using this bolus instead of a conventional one resulted in a 30% increase in the effective heating volume produced by the BSD MA120 applicator. This paper describes an optimization procedure for this bolus design which utilises a new finite element model of microwave heating described in an accompanying paper. The optimization procedure resulted in a further 28% increase in the effective heating volume.

Adipose Tissue↗
PubMedDate not supplied

Edge-element based finite element analysis of microwave hyperthermia treatments for superficial tumours on the chest wall.

Several three-dimensional hyperthermia treatment planning systems for deep regional hyperthermia have been successfully utilized for improving the performance of applicators such as the BSD Sigma 60. Treatment planning systems for superficial heating in contrast have been less utilized. This paper presents a study of the applicability of the finite element method that has been developed for modelling hyperthermia treatments of recurrent chest wall cancer using a patient geometry. The patient model was created by reconstructing the tissue geometry of a patient using a series of axial CT scans. Tetrahedral grids were generated from this geometry for use in finite element simulations of the SAR profile using edge-elements and in finite element simulations of the steady-state temperature profile using scalar elements. The predicted temperature profile was well correlated with thermometry readings taken after 30 min of heating during a hyperthermia treatment. The model predicted the presence of hot-spots in regions that were not monitored. Simulations also showed that the hot-spots can be manipulated by rotating the applicator by 90 degrees. This study demonstrates the ability of the model to provide detailed and accurate heating profiles in a patient specific model for superficial microwave hyperthermia of the chest wall.

Computer Simulation↗
PubMedDate not supplied

Measurement of the thermal conductivity of polyacrylamide tissue-equivalent material.

The purpose of this work was to measure the thermal conductivity of polyacrylamide (PAG) and compare it with previously reported values. Polyacrylamide phantoms play an important role in the development of hyperthermia and high-temperature thermal therapies based on electromagnetic (EM) radiation by providing a material that mimics the electrical and thermal properties of human tissue. The thermal properties of PAG have, up until now, not been thoroughly investigated and at least two significantly different values have been published. In this study, the thermal conductivity of polyacrylamide was measured from the steady state temperature drop across samples exposed to a known heat flux. The measured conductivity was 0.56 +/- 0.047 W m(-1) degrees C(-1). To validate the correct set of thermal properties for polyacrylamide, simple heating experiments were performed in a PAG phantom and then simulated using a finite element numerical model that incorporated the measured thermal conductivity along with literature values for specific heat and density. Temperature predictions from the model agreed with average temperatures measured in the phantom to within 1 SD of the measured temperatures.

Acrylic Resins↗
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↗
PubMedDate not supplied

The potential role of HSP70 as an indicator of response to radiation and hyperthermia treatments for recurrent breast cancer.

Twenty-three patients with recurrent breast cancer participating in a Phase III trial evaluating radiotherapy (XRT) with or without hyperthermia (HT) were included in a parallel study of heat shock protein (hsp) expression. The patients had core biopsies and/or fine needle aspirates (FNA) performed on their tumours, before and after treatment. These were analysed for hsp content using immunohistochemical staining with a monoclonal antibody to the inducible form of hsp 70. The proportion of samples containing identifiable cancer cells was greater for the core biopsy specimens (80%) than with FNA (60%). Staining intensity was analysed using either the majority score, i.e. the staining intensity (on a relative scale from 0 to 3) for the largest proportion of tumour cells, or the arithmetic score, which is the sum of the product of percentage of tumour cells and their staining intensity. The staining intensity for hsp's after treatment correlated inversely with the probability of attaining a complete response (CR). Specifically, the median and maximum scores for the biopsy specimens were significantly inversely related to the probability of attaining CR. The results suggest that this technique may be useful in predicting for thermotolerance development, though more data is needed to confirm the utility of the technique. Results from this study corroborate data from other clinical studies which suggest that tumours with elevated hsp levels may demonstrate resistant biologic behaviour.

Biopsy↗
PubMedDate not supplied

Effect of simultaneous pulsed hyperthermia and pulsed radiation treatment on survival of SiHa cells.

Relatively mild temperatures (40-41.5 degrees C) can sensitize human cells to radiation without the development of thermal tolerance to radiosensitization. Therefore there may be a therapeutic benefit to adding mild hyperthermia to brachytherapy regimens for the treatment of cancer. However, the required heating times are long (approximately 48 h) which renders this approach somewhat impractical. A novel alternative is to combine pulsed brachytherapy with pulsed hyperthermia to enable the total radiation dose to be given at an elevated temperature while the total heating time is kept short. A treatment schedule in which 1 Gy radiation pulses were given once per hour during 5-min heating pulses also delivered once per hour, was investigated in vitro in the human cervical carcinoma line, SiHa. The degree of cytotoxicity and thermoradiosensitization of the cells were assessed by cell survival using the colony forming assay. Cells were exposed to pulsed hyperthermia alone (5 min at 45 degrees C, delivered once per hour), acute hyperthermia alone (45 degrees C), pulsed radiation alone (1 Gy per hour), acute radiation alone, and simultaneous pulsed hyperthermia and pulsed radiation. Pulsed heating alone caused little cytotoxicity. However when pulsed heating was added to pulsed radiation, the level of cytotoxicity was greater than for pulsed radiation alone or acute radiation alone. The effect was also greater than would be predicted from a simple additive effect of pulsed radiation and pulsed heating. In conclusion, pulsed heating at 45 degrees C sensitized cells to pulsed radiation without the development of thermal tolerance.

Cell Survival↗