Walter S. Friauf

Effects of coil design on delivery of focal magnetic stimulation. Technical considerations

The localization of effects from magnetic coil stimulation is not immediately obvious. We measured the magnetic fields produced by several different coils and compared the results with theoretical calculations. Magnetic stimuli were delivered from a Cadwell MES-10 magnetic stimulator using 3 circular coils (one 9 cm in diameter; two with an angulated extension, 5 and 9 cm in diameter) and twin oval coils arranged in a butterfly shape (each coil approximately 4 cm in diameter) and from a Novametrix Magstim 200 using two circular flat-spiral coils (6.7 and 14 cm in diameter). Peak-induced strength of the magnetic field was recorded with a measuring loop (1 cm in diameter) at different distances from the center of the coil. When the measuring loop was moved in the same plane laterally from the center of the coil, for all coils except the butterfly-shaped coil, the field was highest in the center and fell off near the circumference of the coil. The field dropped progressively when measurements were made more distant from the plane of the coils. The electric field induced from the magnetic coil could be calculated from the coil geometry. For all coils except the butterfly-shaped coil, the largest electric field was at the circumference of the coils. The 6.7 cm flat-spiral coil induced currents similar to those induced by the larger coils but more focally. The butterfly-shaped coil induced the largest currents under its center, where the circumferences of the two component coils come together. The component of the electric field parallel to the wire in the center of this coil was the largest and most localized.

Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors

PURPOSE Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors. METHODS AND MATERIALS Patients received dihematoporphyrin ethers (DHE) 1.5-2.5 mg/kg by i.v. injection prior to surgery. Patients resected to < or = 5 mm of residual disease underwent laser light delivery to all peritoneal surfaces. RESULTS Fifty-four patients entered the study. Thirty-nine underwent resection and light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8-3.0 J/cm2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10-15 J/cm2 red light or 5-7.5 J/cm2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7-9 days, while one had a gastric perforation. At potential follow-up times of 3.8-43.1 months (median 22.1 months), 30/39 patients are alive and 9/39 are free of disease. CONCLUSION The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0-7.5 J/cm2 of 514 nm green light or 10-15 J/cm2 of 630 nm red light to sites of gross disease encountered at surgery.

Intrapleural Photodynamic Therapy: Results of a Phase I Trial

AbstractBackground: The management of pleural neoplasms, specifically mesothelioma, remains difficult. We performed a phase I trial in 54 patients with isolated hemithorax pleural malignancy to determine (a) the feasibility of intraoperative, intrapleural photodynamic therapy after debulking surgery; (b) the influence of light dose/sensitizer interval on postoperative morbidity in order to define the photodynamic therapy (PDT) maximal tolerated dose (MTD); and (c) whether first order dosimetry could be applied to this complex geometry. Methods: Cohorts of three patients were given escalating intraoperative light doses of 15–35 J/cm2 48 h after i.v. delivery of 2.0 mg/kg Photofrin II (Quadra Logic Technologies, Vancouver, British Columbia, Canada), and then escalating light doses of 30–32.5 J/cm2 after a 24-h sensitizer/operation interval. Twelve patients could not be debulked to the prerequisite 5 mm residual tumor thickness. The remaining 42 patients underwent 19 modified pleuropneumonectomies, five lobectomy-pleurectomies, and 18 pleurectomies. Intrapleural PDT was delivered using 630 nm light from two argon pump-dye lasers, and real-time and cumulative light doses were monitored using seven uniquely designed, computer-interfaced photodiodes. Results: There was one 30-day mortality from intraoperative hemorrhage. In the 48-h sensitizer/operation group (n=33), possible PDT-related complications included an empyema with late hemorrhage in one of three patients at 17.5 J/cm2 and a bronchopleural fistula at 35 J/cm2. At each of these light doses, three additional patients were treated without complication. Two patients subjected to 24-h sensitizer dosing and 32.5 J/cm2 developed esophageal perforations after pleuropneumonectomy at identical sites. The MTD was declared as 30 J/cm2 light with a 24-h dosing interval when none of the six patients (three original, three repeat) at that level developed toxicity. Conclusions: These data demonstrate that resection and intrapleural PDT can be performed safely with currently available sensitizers and lasers. Phase II and III trials are now warranted at this MTD in a homogeneous population of patients with pleural malignancies.

Design Considerations for Positron Emission Tomography

The surge of interest in medical research with positron-emitting nuclides has been accompanied by improvements in the design of positron emission tomographs (scanners). Bismuth germanate has emerged as the scintillation material of choice for high resolution scanners, as its detection efficiency with small crystals is higher than that of NaI. Other detector materials, such as CsF, may be useful when timing accuracy is of great importance, as in high count rate studies or time-of-flight measurements. Circular detector arrays are now generally preferred because they provide the best sensitivity and uniformity of coverage. Multiple rings are used to increase the axial coverage. Other design parameters, such as detector and collimator dimensions, are surveyed and their effect on scanner performance is discussed.

High Speed Optical Stopped‐Flow Apparatus

A stopped flow apparatus for the study of fast reactions in solution is described. The measured dead time was 270 μsec with an uncertainty in the measurement of 50 μsec. At 410 mμ and an optical density of about 0.09 a change of 0.0044 optical density units could be observed at a flow velocity of 30 m/sec through a 3.0 mm observation tube. Ten milliliters of each of the two reagents are required to fill the system, and less than 1.0 ml of each needs to be expended per experiment.

Phase I trial of photo dynamic therapy in the treatment of recurrent superficial transitional cell carcinoma of the bladder

Abstract Objectives A Phase I trial of photodynamic therapy (PDT) in the treatment of superficial transitional cell carcinoma (TCC) of the bladder was performed. Methods Twenty patients with recurrent superficial TCC of the bladder after receiving a mean of 2.6 (range 1 to 6) courses of intravesical therapy were treated with PDT. The photosensitizer Photofrin II dose was 1.5 or 2.0 mg/kg. A 630-nm intravesical red laser was used to activate the photosensitizer 2 days after administration of Photofrin II. A 0.01 % intralipid solution was used as a bladder-filling medium to scatter light and achieve more homogeneous light distribution. Light doses from 5.1 to 25.6 J/cm 2 (total dosage 1500 to 5032 J) were used to illuminate the bladder. Results Twenty patients underwent 21 treatments with PDT. Complications included asymptomatic reflux in 4 patients. One other patient, treated at the highest total light dose, experienced bladder contraction and fibrosis. Nine patients (45%) had no tumor evident at cystoscopy, on random biopsies, or in urinary cytology at the 3-month evaluation after treatment. Four patients remained without recurrent disease for 23 to 56 months. Sixteen of 20 (80%) patients experienced recurrence, and 8 of the 16 underwent cystectomy. Conclusions An intravenous photosensitizer dose of 1.5 mg/kg Photofrin II followed by light energy in the range of 13 J/cm 2 (total light dose 2500 to 3250 J) was defined as a safe treatment parameter and resulted in tumor responses. With present technologies, administration of PDT requires careful dosimetry.

An optimized differential heat conduction solution microcalorimeter for thermal kinetic measurements

Heat conduction calorimeters are widely used in the biological sciences, but baseline instability, low resolution, electrical noise and motion artifacts have limited their utility. Two main sources of noise, baseline fluctuation or drift and a motion artifact, were traced to amplifier drift, a small (0.015 degrees C) gradient within the constant temperature cylinder, and the method of installing the thermopiles. The addition of heaters to the top and bottom of the cylinder reduced the gradient to approximately 0.003 degrees C and greatly reduced the slow component of the motion artifact. The drift error was reduced by proper mounting of the amplifier and its external components and the enclosure of the calorimeter in a temperature-controlled box. An R-C model of the heat flow in the calorimeter was developed which was employed to discover several means of increasing sensitivity without increasing the rise-time of the calorimeter. Analysis, also based on the model, showed that variations in the air gap between the cell and cell holder can be a major source of error when the calorimeter is used to investigate the kinetics of a chemical reaction. This analysis also showed that the time for the heat to flow through the solution in the cell can be the dominant factor in determining the rise-time of the instrument. The heat conduction calorimeter described here has improved characteristics: a baseline stability of 200 nJ x s-1 (peak-to-peak) over a 48 h period; a resolution of 200 nJ x s-1; a sensitivity of 6.504 +/- 0.045 J x V-1 x s-1 referred to the sensor output; and a rise-time of 122 s for the 10-90% response.

Instrumentation and procedures for real time measurements of proton motive force, membrane potential, ΔpH, proton extrusion, and oxygen uptake in respiring cells and vesicles

The construction and use of two polyvinyl chloride, solid‐state membrane ion‐selective electrodes, one selective to tetraphenylphosphonium (TPP+) [to measure membrane potential (ΔΨ)] and the other selective to salicylate ion [to measure the pH gradient (ΔpH)], are described. A reaction vessel is fitted with these two electrodes plus a pH and an oxygen electrode. The signals from all four electrodes pass through an electronic interface to a microcomputer which filters out noise, corrects for relaxation time delay of electrodes as needed, converts the raw readings to real time kinetic values for rate of oxygen uptake, rate of proton extrusion, ratio of protons extruded per atom of oxygen consumed, membrane potential, the pH gradient across the membrane and the proton motive force. These values are continuously updated every 90 ms and passed to a multipen recorder for observation.

A method of recording single cell discharges in the cerebral cortex of man

Abstract A method of using a field effect transistor to record single cell discharges through a closed system from the cerebral cortex of human patients is described. There have been no complications encountered in six patients under investigation.

Subdural electrode as a dipole source for magnetoencephalography

A subdural electrode was designed and constructed with 3 pairs of contacts to make 3 dipoles. The dipoles well approximate the expected magnetic behavior for a current dipole and can be used clinically to test localization capabilities of magnetoencephalography.