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We have designed, built, and tested an early prototype of a novel subxiphoid access system intended to facilitate epicardial electrophysiology, but with possible applications elsewhere in the body. The present version of the system consists of a commercially available insertion needle, a miniature pressure sensor and interconnect tubing, read-out electronics to monitor the pressures measured during the access procedure, and a host computer with user-interface software. The nominal resolution of the system is Index Terms--Epicardial ablation, epicardial access, pericardium, physiological measurements, thoracic pressure.

We have used agarose gel to develop a robust model of the intraparenchymal brain tissues for the purpose of simulating positive-pressure infusion of therapeutic agents directly into the brain. In parallel with that effort, we have synthesized a mathematical description of the infusion process on the basis of a poroelastic theory for the swelling of the tissues under the influence of the infusate's penetration into the interstitial space. Infusion line pressure measurements and video microscopy determinations of infusate volume of distribution within the gel demonstrate a good match between theory and experiment over a wide range of flow rates (0.5-10.0 microliters/min) and have clinical relevance for the convection-enhanced delivery of drugs into the brain without hindrance by the blood-brain barrier. We have put the brain phantom gel and the infusion measurement system into routine use in determining performance characteristics of novel types of neurosurgical catheters. This approach simplifies the catheter design process and helps to avoid some of the costs of in vivo testing. It also will allow validation of the elementary aspects of treatment planning systems that predict infusion distribution volumes on the basis of theoretical descriptions such as those derived from the poroelastic model. Index Terms--Intraparenchymal drug delivery, poroelasticity, positive-pressure infusion.

The advent of high-precision magnetic and robotic computer-controlled neurosurgery systems makes it necessary to determine the range of forces that will be encountered by the probes of such devices as they are guided through the brain tissues to intraparenchymal targets. We have measured the penetration forces on 2.5-mm spheres and the drag forces on 3.0-mm ventricular shunt catheters advanced 2.0-3.5 cm deep into in vivo human brain tissues (in patients about to have those tissues resected during epilepsy surgery) at rates of [approximately equal to]0.33 mm [s.sup.-1]. Penetration forces of (8 [+ or -] 2) grams were found for the spherical probe once it passed 0.5 cm below the cortical surface, and frictional drags of 12.8 [+ or -] 0.3) grams [cm.sup.-1] were exerted on the catheters. The variable nature of these forces is discussed and the results are compared with earlier studies on experimental animal tissues and brain phantom gelatins. The implications of these results for magnetic and robotic surgery systems are considered. Index Terms - Bulk brain tissue, friction, magnetic stereotaxis, penetration force, robotic stereotaxis.

As part of our studies on the magnetic stereotaxis system (MSS), a means of delivering therapies to the bulk brain, we have measured the frictional forces on a thin, straight tube used to simulate a catheter. Experiments were done with a spring-loaded, stainless steel tube of 1.9-mm diameter which was passed through 5.5 cm of gelatin phantom or, alternatively, through in vitro calf brain. The dynamic response of the tube to sudden displacement of the outer end of the spring yields estimates of the tube's friction per unit length. Twenty-three runs in the two media were analyzed for the static and dynamic frictional forces exhibited. In these series the static frictional forces were found to be (0.0132 [+ or -] 0.0012) N [cm.sup.-1] [(1.32 [+ or -] 0.12) g [cm.sup.-1]] of length in the gelatin phantom and (0.0079 [+ or -] 0.0008) N [cm.sup.-1] [(0.79 [+ or -] 0.08) g [cm.sup.-1]] of length in brain. The kinetic friction coefficient, b, was found to be (8.4 [+ or -] 2.1) N s [m.sup.-1]/cm length of catheter in brain and (16.3 [+ or -] 7.6) N s [m.sup.-1]/cm length of catheter in the phantom material. based on these figures, the MSS will be capable of moving straight catheters of similar friction that are 20-cm long at rates of displacement of 0.02 to 0.05 cm [s.sup.-1] in the white and grey matter of the brain. Future studies will evaluate the forces arising from curved paths. Unanswered questions remain as to the mechanical difference between in vivo and in vitro brain, between animal and human brain, and the involvement of sulci in practical paths of motion. Index Terms - Brain phantoms, brain properties, catheter friction, magnetic stereotaxis, tissue drag force.

A helmet with a roughly cubic array of six superconducting coils is used to apply force on a small permanent magnet pellet in brain or in brain phantom material. This apparatus, called the Magnetic Stereotaxis System, will be used to deliver drugs and other therapies directly into deep brain tissues, under control of a computer and fluoroscopic imaging system. This paper considers only the force application aspects of the instrument. The primary design features of the helmet and power supply controls are presented, along with field plot data and single-axis motion results. The field plot data show that agreement with the finite-element iron-free field calculations is sufficiently high (>1%) for the instrument. These preliminary motion data indicate accuracy better than 2 mm for the impulsive pellet motion, even though the visual position observations had significantly greater error than the completed imaging system will have. The companion paper will take up analysis of the control aspects of the motion, and our recent solutions to difficulties found in the experimental work described here.

The previous companion paper described the motivation, design, and early experiments of a Magnetic Stereotaxis System. The part of the system considered in these papers is a helmet with a roughly cubic array of six superconducting coils used to apply force on small permanent magnet pellets in brain and in brain phantom material. This apparatus will be used to deliver drugs and other therapies directly into deep brain tissues, under control of a computer and fluoroscopic imaging system. Here, we analyze the general stability problems of controlling the currents in the coils for impulsive stepwise motion of the pellet, subject to quench avoidance in the superconducting coils, and in the face of Earnshaw's theorem governing stability in static magnetic fields. We also describe solutions that have been found to the primary difficulties limiting controlled pellet motion in the studies presented in the companion paper.

We compared quantitative experimental results on the diffusion of [sup.35]S-labeled phosphorothioate oligonucleotide (PS-ODN) after intraparenchymal infusion in rat brain, with the distributions predicted by Fick's second law of diffusion. Fischer 344 rats underwent identical intracerebral infusions of [sup.35]S-PS-ODN. After 0, 5, 11, 23, and 47 h, groups of animals were sacrificed and sequential brain cryosections subjected to autoradiography. The resulting experimental data were compared to the predicted distributions, for estimation of the apparent free diffusion coefficient, D*. Volumes of distribution and total content of [sup.35]S-PS-ODN in the parenchyma were also computed, to monitor loss of total material. The values for D* were within the expected range for the 21-mer PS-ODN used, but a progressive decrease in D* over time was noted. The model requires D* to remain constant and, thus, does not adequately explain the spread of [sup.35]S-PS-ODN following infusion. The progressive slowing of spread over time suggests that at later time points, [sup.35]S-PS-ODN may be fixed by tissue binding or cellular uptake in the brain. Loss of material via vascular and CSF clearance may also contribute to the lack of fit. Our results highlight issues to be addressed in the modeling and experimental design of the intraparenchymal infusion process. Index Terms--Antisense oligodeoxynucleotide, Fick's second law, high-flow microinfusion, mathematical diffusion modeling, three-dimensional diffusion.

The measurement of tumor volumes is a practical and objective method of assessing the efficacy of a therapeutic agent. However, the relative accuracy of different methods of assessing tumor volume has been unclear. Using [T.sub.1]-weighted, gadolinium-enhanced magnetic resonance Imaging ([T.sub.1]-MRI), Evans Blue infusion and histology we measured intracranial tumor volumes in a rodent brain tumor model (RT2) at days 10, 16 and 18 after implantation of cells in the caudate putamen. There is a good correlation between tumor volumes comparing [T.sub.1]-MRI and Evans Blue ([r.sup.2] = 0.99), [T.sub.1]-MRI and Histology (r2 = 0.98) and histology and Evans Blue ([r.sup.2] = 0.93). Each of these methods is reliable in estimating tumor volumes in laboratory animals. There was significant uptake of gadolinium and Evans Blue in the tumor suggesting a wide disruption of the blood-brain barrier. Index Terms--Blood-brain barrier, Evans Blue, magnetic resonance imaging (MRI), tumor volumes.

Background: It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Purpose: Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Methods: Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Results: Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. Conclusion: To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS. [ABSTRACT FROM AUTHOR]

Discovery, Pursuit, and Justification in Modern Physics. ALLAN FRANKLIN. American Institute if Physics, New York, 1993. vii, 141 pp., illus. $29.95 or 25£. 'In the case of news, we should [...]

In Query 17 of Notes on the State of Virginia, Thomas Jefferson, in his own remarkable style, wrote, 'The Newtonian principle of gravitation is now more firmly established, on the [...]

Focuses on a study which used an agrose gel to develop a robust model of the intraparenchymal brain tissue for the purpose of simulating positive-pressure infusion of therapeutic agents directly into the brain. Types of catheter designs used; Pore fraction at long times as a function of radial distance for various flow rates; Infusion pressure as a function of time.