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Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transrnantle pressure differences between lateral ventricles and SASs (~ 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (~ 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity. [ABSTRACT FROM AUTHOR]

The lateral bending test is routinely used by clinicians for the preoperative assessment of spinal mobility. The evaluation of bending motion is usually based on the qualitative analysis of a two-dimensional (2-D) antero-posterior X-ray image. The aim of this paper is to introduce a novel three-dimensional (3-D) reconstruction technique that is a prerequisite for the quantitative 3-D analysis of lateral bending motion. An algorithm was developed for the 3-D reconstruction of the spine from a single X-ray image. The X-ray is calibrate using a small calibration object and an explicit calibration algorithm. The information contained in the single X-ray is completed by registering a priori 3LD geometric models of individual vertebrae. Part of the error yielded by the 3-D12-D registration is corrected by a vertebral alignment constraint that aims to minimize intervertebral dislocations. Three-di- mensional models of 15 different scoliosis patients, obtained from a standard stereo-radiographic 3-D reconstruction, were used in simulation and validation experiments. Experimental results show that the new method is robust and accurate. With pessimistic levels of simulated noise, the average root mean square reconstruction error is 2.89 mm, which is appropriate for common clinical applications. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) is the most difficult target for drug delivery therapies. Despite datasets available describing physiological, biochemical, cellular, and metabolic properties of the CNS, the development of infusion therapies still faces major delivery challenges. There is a need for the integration of data obtained from different experimental modalities to design molecular therapies. In this paper, we propose a novel mathematical method for the integration of datasets to generate useful dosing criteria for infusion therapies. A case study is used to demonstrate the design of gene silencing therapies to down regulate NMDA receptors in the spinal cord for chronic pain management. Based on experimentally derived kinetics for short interfering RNA (siRNA) and magnetic resonance images, the biodistribution and pharmacokinetics of siRNAs were predicted for different infusion modes. This adaptable, multiscale computational platform enables the prediction of dose–response on an organ-wide level. The quantitative integration of valuable datasets with engineering precision is expected to accelerate the clinical implementation of novel therapeutics. [ABSTRACT FROM PUBLISHER]

This paper examines how electrical stimulation of the spinal cord can modulate the output of the central pattern generator (CPG) for locomotion. Application of discrete current pulses to a single spinal segment was shown to affect multiple parameters of an ongoing locomotor pattern in an in vitro spinal cord. For any given stimulus, the effects on frequency, duration, and symmetry of locomotor output were strongly dependent on the phase at which stimulation was applied within the CPG cycle. Additionally, most stimuli had an immediate impact and evinced no effects on subsequent cycles. The most dramatic changes were seen when stimulation was applied during motor bursting: stimuli applied to the ipsilateral spinal hemicord increased the burst length, while stimuli applied to the contralateral spinal hemicord decreased the burst length. Smaller changes were observed when stimulating during delays between motor bursts. Thus, phasic stimulation was shown to influence the behavior of the CPG and spinal locomotion circuits on a cycle-by-cycle basis. This work represents the first step toward our ultimate goal of developing a neuroprosthetic device to restore locomotion after a severe spinal cord injury. [ABSTRACT FROM AUTHOR]

The effects of spinal cord injuries are likely to be ameliorated with the help of functional electrical stimulation of the spinal cord, a technique that may benefit from a new style of electrode: the cylindrical multielectrode. This paper describes the specifications for, fabrication techniques for, and in vitro evaluation of cylindrical multielectrodes. Four tip shapes were tested to determine which shape required the lowest peak force and would, therefore, be expected to minimize dimpling during implantation. The impedance of the electrode interface was monitored for changes due to insertion as well as repetitive delivery of current pulses. The charge delivery capacity was determined by testing with safe (≤ 0.6 mC/cm²) and damaging levels (≥ 0.8 mC/cm²) of charge density. The results of these tests suggest that this electrode design could be used to stimulate neurons in the ventral horn of the spinal cord. [ABSTRACT FROM AUTHOR]

A cylindrical multielectrode system specifically designed for intraspinal microstimulation was mechanically and electrically evaluated in the ventral horn of the feline lumbo-sacral spinal cord. Electrode insertions proved to be straight as evaluated from radiographs. Impedances were measured in situ and force recruitment curves from quadriceps muscles were collected over a wide range of stimulus parameters. For a given charge, higher current amplitudes produced greater forces than proportionally longer pulse durations, indicating that charge is not the sole indicator of evoked force in applications utilizing electrical stimulation. Overlap measurements for calculating current-distance constants were collected at a variety of current amplitudes, electrode pair separations, and pair orientations in the spinal grey matter. Forces obtained in the majority of these trials demonstrated an order effect, presumably due to asymmetric neuronal connectivity within the spinal cord. In the cases showing no order effect, the dorso-ventral electrode pair orientation yielded a higher average current-distance constant (278 μA/mm²) than either the medio-lateral or rostro-caudal electrode pair orientations (197 μA/mm²). Specifications of an array of cylindrical multielectrodes for use in future intraspinal microstimulation prostheses were updated. [ABSTRACT FROM AUTHOR]

After a short review of the nervous system and its constituents, recent data on microwave bioeffects are reviewed and evaluated, in particular, the effects on the brain and the spinal cord and under low-level irradiation. Special attention is paid to new results on the effects of modulated and pulsed waves with respect to both continuous wave (CW) irradiation, and, in particular, to the frequency of the modulation. The last section is devoted to modeling and simulation of the nervous system and nervous fibers, where significant progress has been made during the last years. Except for some tutorial aspects, the reviewed literature essentially covers the 1990-1995 period. [ABSTRACT FROM AUTHOR]