Joseph H. Battocletti

Directed and enhanced neurite growth with pulsed magnetic field stimulation

Pulsed magnetic field (PMF) stimulation was applied to mammalian neurons in vitro to influence axonal growth and to determine whether induced current would direct and enhance neurite growth in the direction of the current. Two coils were constructed from individual sheets of copper folded into a square coil. Each coil was placed in a separate water-jacketed incubator. One was energized by a waveform generator driving a power amplifier, the other was not energized. Whole dorsal root ganglia (DRG) explant cultures from 15-day Sprague-Dawley rat embryos were established in supplemented media plus nerve growth factor (NGF) at concentrations of 0-100 ng/mL on a collagen-laminin substrate. Dishes were placed at the center of the top and bottom of both coils, so that the DRG were adjacent to the current flowing in the coil. After an initial 12 h allowing DRG attachment to the substrate floor, one coil was energized for 18 h, followed by a postexposure period of 18 h. Total incubation time was 48 h for all DRG cultures. At termination, DRG were histochemically stained for visualization and quantitative analysis of neurite outgrowth. Direction and length of neurite outgrowth were recorded with respect to direction of the current. PMF exposed DRG exhibited asymmetrical growth parallel to the current direction with concomitant enhancement of neurite length. DRG cultures not PMF exposed had a characteristic radial pattern of neurite outgrowth. These results suggest that PMF may offer a noninvasive mechanism to direct and promote nerve regeneration.

Nuclear Magnetic Relaxation in Blood

The nuclear magnetic relaxation time T1 of protons in human blood has been measured as a function of frequency, pH, and hematocrit. For whole blood at 25°C, T1 is approximately 0.1 s at 20 kHz, increasing to approximately 1 s at 50 MHz. T1 of whole blood is analyzed in terms of the exchange of water molecules between plasma and erythrocyte cytoplasm. A cellular residence time of 19 ms provides the best fit to the data. The T1values for plasma and cytoplasm are explained in terms of their protein content, using the well-established theory of nuclear relaxation in macromolecular solutions. The plasma and cytoplasm data are compared with previous T1 results for apotransferrin and hemoglobin solutions, respectively, and qualitative agreement is found. The T1 values increased with decreasing pH, as is expected from existing data on hemoglobin solutions.

The NMR blood flowmeter—theory and history

Research for the application of NMR principles to the noninvasive measurement of blood flow in humans began at the National Heart,Lung, and Blood Institute (NHLBI) in 1956, and has continued to the present at a number of institutions. In addition to NHLBI, contributions for the development of blood flowmeters by the University of California, Berkeley and by the Medical College of Wisconsin are described in this peper. The NMR theory applicable to blood flowmeters is also presented, as well as design criteria of NMR blood flowmeters.

Effects of pulsed magnetic fields on neurite outgrowth from chick embryo dorsal root ganglia

We have previously shown that neurite outgrowth from 6-day chick embryo dorsal root ganglia (DRG) in vitro was stimulated when nerve growth factor (NGF) and pulsed magnetic fields (PMF) are used in combination. 392 DRGs were studied in a field excited by a commercial PMF generator. We have now analyzed an additional 416 DRGs exposed to very similar PMFs produced by an arbitrary wavefrom generator and power amplifier. We reproduced our previous findings that combination of NGF and bursts of asymmetric, 220 microsecond-wide, 4.0 mT-peak pulses induced significantly (p < 0.05) greater outgrowth than NGF alone, that fields without NGF do not significantly alter outgrowth, and that, unlike NGF alone, 4.0 mT fields and NGF can induce asymmetric outgrowth. The asymmetry does not seem to have a preferred orientation with respect to the induced electric field. Analysis of the data for the entire 808 DRGs confirms these findings. Importantly, we find similar results for pulse bursts repeated at 15 or 25 Hz.

Exposure to Pulsed Magnetic Fields Enhances Motor Recovery in Cats After Spinal Cord Injury

Study Design. Animal model study of eight healthy commercial cats was conducted. Objective. To determine whether pulsed electromagnetic field (PMF) stimulation results in improvement of function after contusive spinal cord injury in cats. Summary of Background Data. PMF stimulation has been shown to enhance nerve growth, regeneration, and functional recovery of peripheral nerves. Little research has been performed examining the effects of PMF stimulation on the central nervous system and no studies of PMF effects on in vivo spinal cord injury (SCI) models have been reported. Materials and Methods. PMF stimulation was noninvasively applied for up to 12 weeks to the midthoracic spine of cats with acute contusive spinal cord injury. The injury was produced using a weight-drop apparatus. Motor functions were evaluated with the modified Tarlov assessment scale. Morphologic analyses of the injury sites and somatosensory-evoked potential measurements were conducted to compare results between PMF-stimulated and control groups. Results. There was a significant difference in locomotor recovery between the PMF-stimulated and control groups. Although not statistically significant, PMF-stimulated spinal cords demonstrated greater sparing of peripheral white matter and smaller lesion volumes compared to controls. Somatosensory-evoked potential measurements indicated that the PMF-stimulated group had better recovery of preinjury waveforms than the control group; however, this observation also was not statistically significant because of the small sample size. Conclusions. This preliminary study indicates that pulsed magnetic fields may have beneficial effects on motor function recovery and lesion volume size after acute spinal cord injury.

Measurement of magnetically induced current density in saline in vivo

Magnetically induced current density has been measured in different concentrations of saline solution and in the cerebral cortex of cats in vivo. The results show that the current density decreases with distance from the stimulating coil and with increasing resistivity. The presence of the cranium attenuates the current density in the cortical tissue. The studies show that it is possible to measure directly current densities induced by magnetic fields.<<ETX>>

In Vivo Measurement of Real-Time Aortic Segmental Volume Using the Conductance Catheter

The goal of this investigation was to determine if the conductance catheter technique for chamber volume measurement could be applied in vivo to determine real-time phasic aortic segmental volume. A four-electrode conductance catheter was used to measure time-varying resistance of the descending thoracic aorta in open-chest, anesthetized dogs. Resistance was converted to segmental volume and the slope correction factor (α) and parallel conductance volume (VP) were determined. The results showed excellent linear correlation between conductance and sonomicrometric segmental volume. The correction factors α and VP were found to be empirically related to average vessel diameter. The relatively high values for the slope correction factor (α=4.59±0.17 SEM) were found to be primarily related to low-resistivity shunt paths probably originating in the periadventitial aortic wall and to a lesser extent to changes in flow-induced increases in blood resistivity, hematocrit, catheter position, and other adjacent tissue resistivity. The results demonstrate that correction factors empirically derived from measurements of mean aortic diameter could be used to determine absolute real-time phasic segmental volume, cross-sectional area, or diameter. The conductance technique may possess the same potential for determining aortic mechanical properties which has already been demonstrated for determining ventricular mechanical properties.

Effects of physical parameters on the cylindrical model for volume measurement by conductance

Despite its undisputed utility for determining changes in ventricular pressure-volume relationships, the conductance catheter technique has not been proven reliable for measuring absolute volume. This limitation is due to violations of the assumptions inherent in the cylindrical model on which the method is based (i.e., homogeneous electric field and no leakage current). The purpose of this investigation was to relate cylindrical model correction factors to the physical environment of the catheter and to the cylindrical equation. Physical measurements of saline-filled, nonconductive cylinders using a four-electrode conductance catheter were compared with a three-dimensional finite element model of the physical apparatus. These measurements were incorporated into a parallel conductance model to relate physical parameters to corrections in the cylindrical equation for volume measurement. Excellent agreement between measured and modeled data was found. Results demonstrated a nonlinear relationship between the field nonhomogeneity correction factor (α) and cylinder diameter. The relationship between α and diameter was consistent with a theoretical extrapolation of cylinder diameter toward infinity. An inverse relationship between α and the parallel conductance volume (VP) was also clarified. The parallel conductance model was able to demonstrate opposite effects of the physical presence of the catheter body and electrodes, which tended to cancel out any net effect on measured conductance. Results of this investigation and the developed finite element model clarify the nature of the correction terms in the cylindrical model and may lead to greater application of the conductance technique.

In Vitro and finite-element model investigation of the conductance technique for measurement of aortic segmental volume

This investigation examined the feasibility of applying the conductance catheter technique for measurement of absolute aortic segmental volume. Aortic segment volume was estimated simultaneouslyin vitro by using the conductance catheter technique and sonomicrometer crystals. Experiments were performed in five isolated canine aortas. Vessel diameter and pressure were altered, as were the conductive properties of the surrounding medium. In addition, a three-dimensional finite-element model of the vessel and apparatus was developed to examine the electric field and parallel conductance volume under different experimental conditions. The results indicated that in the absence of parallel conductance volume, the conductance catheter technique predicted absolute changes in segmental volumes and segmental pressure-volume relationships that agreed closely with those determined by sonomicrometry. The introduction of parallel conductance volume added a significant offset error to measurements of volume made with the conductance catheter that were nonlinearly related to the conductive properties of the surrounding medium. The finite-element model was able to predict measured resistance and parallel conductance volume, which correlated strongly with those measuredin vitro. The results imply that absolute segmental volume and distensibility may be determined only if the parallel conductance volume is known. If the offset volume is not known precisely, the conductance catheter technique may still be applied to measure absolute changes in aortic segmental volume and compliance.

The NMR blood flowmeter—design

Two types of crossed-coil nuclear magnetic resonance (NMR) blood flowmeter detectors have been developed for the noninvasive measurement of blood flow. The first is a cylindrical coil configuration suitable for limb blood measurement. A cylindrical flowmeter (12.5 cm internal diam) operating at a nuclear resonance frequency of 3.2 MHz has been applied to measurement of flow in the forearm. The second type is the flat crossed-coil detector, which retains many of the operational advantages of the cylindrical detector, but is suitable for blood flow measurement of almost any surface of the body. Three flat crossed-coil detectors are described, operating at NMR frequencies of 9, 21.4, and 75 MHz. Two types of intermediate frequency signal processors have been used in the NMR receivers, a simple diode type, and a synchronous detector. The synchronous detector is preferred for its ease of operation and superior stability. Modular detection systems containing transmitter, receiver, post-detector signal conditioning, and power supply have been designed for all of the flat crossed-coil detectors. A self-contained synchronous detector module is included in the 21.4 and 75 MHz systems.