George T. Gillies

Magnetic manipulation instrumentation for medical physics research

The noncontact magnetic manipulation of probe masses within the body is an area of research that has received substantial attention from the medical physics community, especially during the past three decades. The therapeutic and diagnostic possibilities arising from such technology include site‐specific drug delivery within the central nervous system, advancement of techniques for navigation and selective catheterization of vessels within the cardiovascular and cerebrovascular systems, and the nonsurgical exploration of the alimentary and respiratory tracts. In this review, we examine the physical principles underlying in vivo magnetic manipulation systems, and catalog the various types of instrumentation used for such purposes to date. Thereafter, we evaluate the different methods of image‐based localization used to identify the position of the probe within the body. Finally, we appraise an emerging technology known as nonlinear magnetic stereotaxis, a technique that permits minimally invasive access to...

The Newtonian gravitational constant: recent measurements and related studies

Improvements in our knowledge of the absolute value of the Newtonian gravitational constant, G, have come very slowly over the years. Most other constants of nature are known (and some even predictable) to parts per billion, or parts per million at worst. However, G stands mysteriously alone, its history being that of a quantity which is extremely difficult to measure and which remains virtually isolated from the theoretical structure of the rest of physics. Several attempts aimed at changing this situation are now underway, but the most recent experimental results have once again produced conflicting values of G and, in spite of some progress and much interest, there remains to date no universally accepted way of predicting its absolute value. The review will assess the role of G in physics, examine the status of attempts to derive its value and provide an overview of the experimental efforts that are directed at increasing the accuracy of its determination. Regarding the latter, emphasis will be placed on describing the instrumentational aspects of the experimental work. Related topics that are also discussed include the search for temporal variation of G and recent investigations of possible anomalous gravitational effects that lie outside of presently accepted theories.

Nonlinear magnetic stereotaxis : three-dimensional, in vivo remote magnetic manipulation of a small object in canine brain

In a series of in vivo experiments on five adult canines, a small cylindrical permanent magnet (approximately 5-mm diameter x 5 mm long) was magnetically moved under fluoroscopic guidance from an occipital-lobe burr hole to a predetermined destination within the brain and then removed. On three of the animals, dorsal and temporal skull markers were used to establish a coordinate system against which the motions of the seed were referenced. These procedures were sufficiently accurate to permit the guided motion of the seed along nonlinear paths within the brain, including traversal of the midline through the corpus callosum. For removal, the seed could be steered either to a frontal lobe location for extraction through an auxiliary burr hole, or back to the same burr hole through which it had been inserted. This article discusses the way in which stereotactic motions were obtained, the performance limits of the instrumentation and the precision of motion achieved.

Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels

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 infusates 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.

Characteristics of an improved magnetic-implant guidance system

The previous companion paper (see ibid., vol. 42, no. 8, p.793, 1995) 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, the authors 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 Earnshaws theorem governing stability in static magnetic fields. The authors also describe solutions that have been found to the primary difficulties limiting controlled pellet motion in the studies presented in the companion paper.<<ETX>>

Distribution of macromolecular dyes in brain using positive pressure infusion: a model for direct controlled delivery of therapeutic agents

BACKGROUND Direct infusion of therapeutic agents into the brain is a novel technique that has the potential for bypassing the blood-brain barrier and delivering high concentrations of therapeutic agents into the brain parenchyma. We have developed a model to characterize the distribution of Evans Blue (MW 960) and Blue Dextran (MW 2 x 10(6)) in rat brain using a positive pressure infusion system. METHODS Evans Blue and Blue Dextran were infused in volumes of 20, 40, 60, 100, 140, and 180 microL into the caudate putamen of female Fischer rats over a period of 2 h with rates of infusion varying between 0.167 microL and 1.5 microL/min. During the infusions, the pressure generated in the infusion system and intracranial pressure were measured using a fiberoptic pressure monitoring system. After infusions, the volumes of distribution of the dye molecules were measured from 3-mm thick sections using video microscopy and computer image analysis. Histologic changes during the infusion were studied using snap freezing and hematoxylin/eosin staining of cryosections. RESULTS Volumes of distribution for Evans Blue were greater than those for Blue Dextran. There was extensive spread of each dye in the ipsilateral hemisphere and also across the corpus callosum to the opposite hemisphere. Infusion/interstitial pressures peaked during the first 5 min of the infusion period, after which pressures dropped to a plateau value that remained relatively constant during the remainder of the infusion. Histologic findings suggest that this phenomenon is an important transition process that is likely to play a role in the pattern of distribution of macromolecules infused by this technique. No marked changes in intracranial pressure were noted during the infusion procedure. CONCLUSIONS Direct positive pressure infusion into the brain has great potential in the treatment of brain tumors and other central nervous system disorders using both high and low molecular weight compounds (immunotoxins, protein conjugates, pharmacologic agents, oligonucleotides, and viral vectors).

Torsion balances, torsion pendulums, and related devices

The torsion pendulum is not only a mainstay instrument in the world of precision measurement and gravitational physics, but is important in electrical science, biophysics, petrology, metallurgy, and various other fields of endeavor. Whether used in the ‘‘static’’ (deflection) mode, the ‘‘dynamic’’ (oscillating) mode, or in some more complex configuration, instrumentation of this kind enables one to isolate and measure weak effects that would otherwise be difficult if not impossible to observe against the background gravitational field of the earth. In this review, we present a brief history of fiber‐suspended apparatus and assess the fundamental limits of performance of the dumbbell pendulum. We then inventory the different versions of such systems presently used by gravitational physicists and discuss the various interrogation techniques used to monitor the movement of the suspended test mass. Next, we tabulate some of the applications for torsion instruments outside of gravitational physics, and close w...

Neurosurgical Delivery of Chemotherapeutics, Targeted Toxins, Genetic and Viral Therapies in Neuro-Oncology

Local delivery of biologic agents, such as gene and viruses, has been tested preclinically with encouraging success, and in some instances clinical trials have also been performed. In addition, the positive pressure infusion of various therapeutic agents is undergoing human testing and approval has already been granted for routine clinical use of biodegradable implants that diffuse a chemotherapeutic agent into peritumoral regions. Safety in glioma patients has been shown, but anticancer efficacy needs additional refinements in the technologies employed. In this review, we will describe these modalities and provide a perspective on needed improvements that should render them more successful.

Measurement of the force required to move a neurosurgical probe through in vivo human brain tissue

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. The authors 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 /spl ap/0.33 mm s/sup -1/. Penetration forces of (8/spl plusmn/2) grams were found for the spherical probe once it passed 0.5 cm below the cortical surface, and frictional drags of (2.8/spl plusmn/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.

Experimental determination of the force required for insertion of a thermoseed into deep brain tissues.

Our laboratories are developing a new technique for delivering localized hyperthermia to deep-seated brain tumors. In this technique, a spherical thermoseed is stereotactically navigated through the brain and tumor tissues via the noncontact application of an external magnetic force. The force required to produce motion of a 3 mm diameter sphere through in vitro brain tissues was measured to be 0.07 ± 0.03 N. This result was obtained from a series of experiments performed on whole brain specimens extracted from adult canines. Data were also taken with a 3 mm × 3 mm cylinder and a 5 mm sphere. An experimental procedure simulating physiological conditions was developed prior to testing. Evaluations of systematic effects included determinations of the calibration uncertainties, tests of the dependence of the measured force on temperature, and studies of the effects of method of storage of the tissue specimens. The results obtained are compared with (and confirmed by) two different series of experiments performed in vivo on adult canines and with another series of experiments using brain phantom gelatin.