Isolated frog hearts were irradiated with pulse modulated microwave energy synchronized with the ECG. No statistically significant or otherwise observable differences were found between the heart rate of irradiated groups and the nonirradiated control group. Experiments were performed to explore the possible effects of currents induced between the recording electrodes. Increases in heart rate occurred when applied current pulses between 20 and 30 mA were synchronized with the ECG during an interval from 200 msec to 300 msec after the peak of the P wave.

Animals↗

PubMedDate not supplied

Inconsistency of fetal trophoblast cells in first trimester maternal peripheral blood prevents non-invasive fetal testing using this cell target.

We have investigated whether maternal peripheral blood from the first trimester of pregnancy is a reliable source of identifiable trophoblast cells. The cells were enriched from 30 ml of venous blood, with multiple antibodies shown previously to enrich trophoblasts and a new cocktail based on known trophoblast surface features. Three different magnetic solid phases were tested to enrich trophoblasts, and both positive and negative cell enrichment strategies were examined. The cells were identified as trophoblast by morphology coupled with immunocytochemistry to co-localize cytokeratin with one of three IGF-II, PAI-1 or hPLH proteins or by in-situ hybridization with a mixture of 50 oligos directed to eight different expressed genes, alpha-HCG, IGF-II, PAI-1, HASH2, hPLH, p57(KIP2), PP5, H-19. While these tools worked beautifully in chorionic villi cell/sprout preparations and tissue sections, we could not detect and identify any trophoblasts in maternal peripheral blood even if the maternal peripheral blood was drawn 5-20 min following termination of pregnancy or from individuals maintaining the pregnancy. Based on our own experience and that of some reports in the literature, trophoblasts do not appear to be a viable candidate for fetal screening using maternal peripheral blood as the source. It is important to note that while trophoblast deportation is a biological phenomenon that has been described repeatable, they do not provide a means to perform prenatal genetic diagnosis.

Antibodies↗

PubMedDate not supplied

Enrichment and identification of fetal trophoblast cells from first trimester maternal cervical lavage and uterine blood specimens.

First trimester prenatal diagnosis of fetal aneuploidies is an active area of research despite years of disappointing data employing maternal peripheral blood samples. To remedy this situation we have investigated other first trimester maternal specimens attempting to find a consistent fetal cell source. Using our previously established positive enrichment procedure along with a commercially available depletion method, fetal trophoblast cells were identified employing immunocytochemistry using an antibody cocktail or by using mRNA in-situ hybridization employing a cocktail of trophoblast specific probes. Fetal origin of positively identified cells was verified using interphase fluorescent in-situ hybridization (FISH) for X and Y-chromosomes. Artificial model systems were established that indicated yields of trophoblast cells and allowed the enrichment procedure to be optimized for minimal losses from maternal specimens. We demonstrate herein that blood drawn from maternal vessels near the placental implantation site to be the most consistent source of fetal cells from any first trimester maternal specimen described to date. In addition, a high yield of multinucleated syncytiotrophoblast cells was obtained using a cell depletion strategy to enrich the target cells. The safety of the procedure or even the clinical utility of blood drawn from maternal vessels near the placental implantation site is yet to be demonstrated.

Cell Separation↗

PubMedDate not supplied

Analysis of temperature responses to diffused ultrasound focal fields produced by a sector-vortex phased array.

The sector-vortex applicator, a disc-shaped ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. Temperature distribution patterns resulting from these acoustic fields have been simulated by solving a steady-state bioheat equation numerically for a wide range of blood perfusion rates. These results suggest that the sector-vortex array will be particularly suitable for heating non-superficial small tumours. The temperature distribution pattern changes due to variations in blood perfusion are interpreted based on spatial frequency domain Fourier analysis of temperature responses to different power deposition patterns. The system behaves like a low-pass spatial frequency filter.

Biophysical Phenomena↗

PubMedDate not supplied

The concentric-ring array for ultrasound hyperthermia: combined mechanical and electrical scanning.

While two-dimensional phased arrays can be electronically focused and steered in three dimensions without physically moving the applicator, they generally require a relatively large number of small transducer elements and, consequently, complex drive electronics. A configuration that does not require a large number of elements is that of a concentric-ring array. The field conjugation method can be used to produce a focal spot (or multiple spots) along the array axis. The resulting focal regions are very small and need to be steered transversely to heat tumours of typical size. However, steering the focused beam away from the array axis results in annular heating patterns which are often associated with undesired secondary foci (hot spots). In this paper, a method based on combining electrical and mechanical scanning using a concentric-ring applicator is presented. Advantages of the new method over the mechanically scanned fixed-focus transducers, currently in use, are pointed out. Computer simulations are conducted to investigate the possibility of heating different size tumours by appropriately combining the two scanning techniques. The bioheat transfer equation is solved numerically and temperature distributions associated with relevant heating patterns are presented and discussed. The simulations demonstrate the possibility of the combined technique to produce useful heating patterns which cannot be produced by either technique separately.

Biomechanical Phenomena↗

PubMedDate not supplied

Optimization of the intensity gain of multiple-focus phased-array heating patterns.

A new technique for enhancing the intensity gain at the focal points in multiple-focus patterns is introduced. The new technique is shown to be effective in reducing the interference typically associated with multiple-focus patterns. This reduction in interference patterns allows multiple-focus scanning to generate highly localized heating. Simulation results indicate that multiple-focus scanning not only provides an alternative to single-focus scanning, but also achieves better localization in the heating pattern. The maximization of intensity gain of multiple-focus heating patterns significantly reduces the pre-focal-depth high-temperature regions that can be caused by single-focus scanning. This is shown by computer simulation of a two-dimensional cylindrical-section array (CSA2D) as a heating applicator. Two series of simulations are presented in which different scan trajectories were used to therapeutically heat a small deep-seated target volume. In every case the heating pattern was generated using single-focus scanning and multiple-focus scanning (with and without intensity gain maximization). Multiple-focus scanning with gain maximization offers the best localization of heating to the target volume of the three methods.

Biophysical Phenomena↗

PubMedDate not supplied

Insonation of fixed porcine kidney by a prototype sector-vortex-phased array applicator.

The sector-vortex applicator, an ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. A perfused tissue phantom, consisting of an alcohol-fixed porcine kidney with thermocouples placed in the cortex, is insonated by a prototype sector-vortex applicator with 16 sectors and two tracks at an ultrasound frequency of 750 kHz. Steady-state temperature distributions are measured for a wide range of perfusion rates. Results demonstrate that the radius of the heated region can be controlled effectively by choosing the focal mode of the applicator as it is predicted by theoretical analysis.

Animals↗

PubMedDate not supplied

Radiant heat-induced hyperthermia in mice: in vivo effects on the immune system.

Whole-body hyperthermia (WBH) in mice was induced by 2-4-h exposure to radiant heat resulting in core body temperatures of 38.5-40.4 degrees C, and correlated directly with the magnitude and duration of heat treatment. Two-hour heat treatments in this temperature range did not consistently affect generation of antibody-forming cells in vivo, while 4-h treatments at temperatures greater than or equal to 40 degrees C significantly suppressed the antibody-forming cell response. The capacity of lymphocytes from similarly heated mice to generate antibody-forming cells in vitro was not affected, suggesting that the observed in vivo suppression may be mediated by circulating factors rather than by some heat-induced alteration in the cells themselves. In vivo treatment did not alter T-cell responsiveness to the mitogen Con-A or delayed-type hypersensitivity responses to sheep red blood cells. Quantitative and flow cytometric assessment of splenic and thymic lymphocyte numbers showed that WBH did not alter absolute numbers of lymphocytes but did temporarily change the proportions of lymphocyte subsets. An immediate increase in splenic L3T4+ cells was observed, followed within 18 h by an overall decrease in Lyt 2+ and Thy 1.2+ T-cells. In the thymus the percentages of mature T cells increased. In general, only minimal effects of heat on the immune responses of normal mice could be demonstrated.

Animals↗

PubMedDate not supplied

Mode scanning: heating pattern synthesis with ultrasound phased arrays.

Modes, the characteristic symmetric focal patterns of an ultrasound phased array, prove especially useful for hyperthermia. Modes cancel the complex pressure fields exactly along the central axis, eliminating axial constructive interference both proximal and distal to the treatment volume. A simple calculation exploits planar or rotational array symmetry and produces the driving signals which generate modal focal patterns. Results show that temporal mode scanning improves heating patterns considerably, expanding the maximum treatable size of the tumour volume.

Body Temperature↗