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Biomedical subjects

E D Wirth

Publications and source records attributed to E D Wirth.

8 recordsLinked to original sources

Visualization of neural tissue water compartments using biexponential diffusion tensor MRI.

The apparent diffusion tensor (ADT) imaging method was extended to account for multiple diffusion components. A biexponential ADT imaging experiment was used to obtain separate images of rapidly and slowly diffusing water fractions in excised rat spinal cord. The fast and slow component tensors were compared and found to exhibit similar gross features, such as fractional anisotropy, in both white and gray matter. However, there were also some important differences, which are consistent with the different structures occupying intracellular and extracellular spaces. Evidence supporting the assignment of the two tensor components to extracellular and intracellular water fractions is provided by an NMR spectroscopic investigation of homogeneous samples of brain tissue. Magn Reson Med 45:580-587, 2001.

Animals↗

Feasibility and safety of neural tissue transplantation in patients with syringomyelia.

Transplantation of fetal spinal cord (FSC) tissue has demonstrated significant potential in animal models for achieving partial anatomical and functional restoration following spinal cord injury (SCI). To determine whether this strategy can eventually be translated to humans with SCI, a pilot safety and feasibility study was initiated in patients with progressive posttraumatic syringomyelia (PPTS). A total of eight patients with PPTS have been enrolled to date, and this report presents findings for the first two patients through 18 months postoperative. The study design included detailed assessments of each subject at multiple pre- and postoperative time points. Outcome data were then compared with each subject's own baseline. The surgical protocol included detethering, cyst drainage, and implantation of 6-9-week postconception human FSC tissue. Immunosuppression with cyclosporine was initiated a few days prior to surgery and continued for 6 months postoperatively. Key outcome measures included: serial magnetic resonance imaging (MRI) exams, standardized measures of neurological impairment and functional disability, detailed pain assessment, and extensive neurophysiological testing. Through 18 months, the first two patients have been stable neurologically and the MRIs have shown evidence of solid tissue at the graft sites, without evidence of donor tissue overgrowth. Although it is still too soon to draw any firm conclusions, the findings from the initial two patients in this study suggest that intraspinal grafting of human FSC tissue is both feasible and safe.

Adult↗

Neurophysiological assessment of the feasibility and safety of neural tissue transplantation in patients with syringomyelia.

The feasibility and safety of a procedure involving fetal spinal cord tissue transplantation in patients with syringomyelia was assessed using a neurophysiological protocol designed to quantitate peripheral nerve function, spinal cord reflex excitability, and spinal cord conduction pathways essential for somatosensory evoked potentials. We report here data obtained before and for 18 months following the transplantation procedure performed on the first two patients in this study. The neurophysiological assessment protocols included measures of cortical and spinal cord evoked potentials, H-reflex excitability, and peripheral nerve conduction. Prior to the procedure, both patients had significant deficits on some of the neurophysiological measures, for example, lower extremity cortical evoked potentials. However, robust measures of intact pathways, such as upper extremity cortical evoked potentials, were also observed preoperatively in both patients. Thus, it was anticipated that conduction in these intact pathways could be at risk either from complications from the transplantation procedure and/or from continued expansion of the syrinx. Following the transplantation procedure, no negative changes were observed in any of the neurophysiological measures in either patient. In addition, patient 1 showed a decrease in the rate potentiation of tibial H-reflexes on the right side and an increase in the response probability of left tibial H-reflexes. The results of this postoperative longitudinal assessment provide a first-level demonstration of the safety of the intraspinal neural tissue transplantation procedure. However, the consideration of safety is currently limited to the grafting procedure itself, since the long-term fates of the donor tissue in these two patients remain to be shown more definitively.

Action Potentials↗

Coordination of a neural tissue transplantation study in patients with posttraumatic syringomyelia.

The need for clinical research coordinators (CRCs) has grown in recent years due to the increasingly rapid translation of scientific advances from preclinical experiments to clinical trials. CRCs perform a number of critical roles in clinical trials, such as ensuring adherence to the research protocol and careful monitoring of the study data. Although many of these duties are now standardized in a general job description, new fields of clinical research may require additional functions of the CRC that are specific to each investigation. This was the case for a pilot clinical study at the University of Florida, which investigated the feasibility and safety of human fetal spinal cord (FSC) tissue allografts in patients with progressive posttraumatic syringomyelia (PTS). The CRC for this study had several essential duties, such as arranging transportation for PTS subjects to the study center from all regions of the United States and coordinating an extensive assessment protocol that required many co-investigators. Given these challenges, successful achievement of the outcome measures required the development of a customized CRC job description that encompassed both standard roles and specific duties for this study. Accordingly, this article will illustrate the role of the CRC in this study and provide a template for similar coordinator roles.

Clinical Nursing Research↗

Diffusion anisotropy in excised normal rat spinal cord measured by NMR microscopy.

A conventional spin-echo NMR imaging pulse sequence was used to obtain high-resolution images of excised normal rat spinal cord at 7 and 14 T. It was observed that the large pulsed-field gradients necessary for high-resolution imaging caused a diffusion weighting that dominated the image contrast and that could be used to infer microscopic structural organization beyond that defined by the resolution of the image matrix (i.e., fiber orientation could be assigned based on diffusion anisotropy). Anisotropic diffusion coefficients were therefore measured using apparent diffusion tensor (ADT) imaging to assess more accurately fiber orientations in the spinal cord; structural anisotropy information is portrayed in the six unique images of the complete ADT. To reduce the dimensionality of the data, a trace image was generated using a separate color scale for each of the three diagonal element images of the ADT. This new image retains much of the invariance of the trace to the relative orientations of laboratory and sample axes (inherent to a greyscale trace image) but provides, by the use of color, contrast reflecting diffusion anisotropy. The colored trace image yields a pseudo-three-dimensional view of the rat spinal cord, from which it is possible to deduce fiber orientations.

Animals↗

Dynamic assessment of intraspinal neural graft survival using magnetic resonance imaging.

Although previous work has demonstrated the usefulness of magnetic resonance imaging (MRI) for visualizing intraspinal transplants in vivo, the degree to which MRI can differentiate viable fetal neural tissue from evolving spinal cord pathology has not been investigated. Thus, the present study assessed whether MRI performed at earlier postgrafting intervals (0-20 weeks) could document the survival of fetal neural transplants in the injured cat spinal cord. Twelve adult female cats received a hemisection injury at the L1 level, followed immediately by implantation of either embryonic cat spinal cord or neocortex into the cavity. The spinal cords of three control animals were hemisected but received no transplant. Each animal was subsequently imaged at 4 and 8 weeks postoperative. Selected animals from each group were also studied at additional time points ranging from immediately postoperative to 20 weeks. Multislice T2-weighted and intermediate T1-weighted spin-echo images of the lesion or graft site were obtained. Correlative postmortem histological analyses revealed viable donor tissue in 6 of 12 transplant recipients. Spinal cords from the remaining hosts and the control animals all contained cysts at the surgical site that were devoid of donor neural tissue. The graft sites with viable tissue tended to exhibit a slightly hyperintense signal on both intermediate T1-weighted (T1WI) and T2-weighted images (T2WI) throughout the entire experiment. Control cats and cats with failed transplants also were slightly bright on T1WI, but were very hyperintense on T2WI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of an inductively coupled implanted coil with optimized surface coils for in vivo NMR imaging of the spinal cord.

A study was performed to determine whether an implanted, inductively coupled nuclear magnetic resonance (NMR) imaging spine coil could provide a significant gain in signal-to-noise ratio (SNR) on images of the spinal cord relative to the SNR of optimized surface coils. Implanted coils were surgically affixed to the upper lumbar spine (first lumbar through third lumbar vertebrae) in a total of four adult cats. The implanted coil was inductively coupled to an external 12 x 12 cm square surface coil that was mounted on a 14-cm diameter Plexiglas cradle (Townsend Industries, Des Moines, IA). Two similar cradles were prepared with transmit-only 12 x 12 cm surface coils and either a receive-only 6 x 6 cm square surface coil or a receive-only quadrature coil pair (two 4 x 6 cm coils overlapped slightly to minimize their mutual inductance) with the same surface area (6 x 6 cm). A total of five single-slice, T1-weighted spin-echo images (TR = 500 ms, TE = 30 ms, 4-mm slice thickness) were acquired from a 1-liter saline phantom and from the second lumbar spinal level in an adult cat with a normal, uninjured spinal cord. On the spinal cord images, the quadrature coil exhibited a factor of 1.65 increase in SNR relative to the single-turn surface coil, whereas the implanted coil achieved a factor of 2.19 increase in SNR. The improved SNR for the quadrature and implanted coils was observed as a dramatic improvement in the clarity of the images.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo magnetic resonance imaging of fetal cat neural tissue transplants in the adult cat spinal cord.

Magnetic resonance (MR) imaging was evaluated for its possible diagnostic application in determining the survival of fetal central nervous system tissue grafts in the injured spinal cord. Hemisection cavities were made at the T11-L1 level of eight adult female cats. Immediately thereafter, several pieces of tissue, either obtained from the fetal cat brain stem on embryonic Day 37 (E-37), from the fetal neocortex on E-37, or from the fetal spinal cord on E-23, were implanted into the cavities made in seven cats. The eighth cat served as a control for the effect of the lesion only. In another group of four animals, a static-load compression injury was made at the L-2 level. Seven weeks later, the lesion was resected in three cases and fragments of either fetal brain-stem or spinal cord tissue were introduced. A small cyst was observed in a fourth cat in the compression injury group and a suspension of dissociated E-23 brain-stem cells was injected into this region of cavitation without disturbing the surrounding leptomeninges. Five months to 2 years posttransplantation, MR imaging was performed with a 2.0-tesla VIS imaging spectrometer by acquiring multislice spin-echo images (TR 1000 msec, TE 30 msec) in both the transverse and sagittal planes. Collectively, these intermediate-weighted images revealed homogeneous, slightly hyperintense signals at the graft site relative to the neighboring host tissue in seven of the 11 graft recipients. Two of the remaining four cats exhibited signals from the graft site that were approximately isointense with the adjacent host spinal cord, and the final two cats and the lesion-only control presented with very hypointense transplant/resection regions. The hyperintense and isointense images were tentatively interpreted as representing viable graft tissue, whereas the hypointense transplant/resection sites were considered to be indicative of a lack of transplant survival or the absence of tissue in the lesion-only control animal. Postmortem gross inspection of fixed specimens and light microscopy verified the MR findings in the control animal in 10 of the 11 graft recipients by showing either transplants and/or cysts corresponding to the MR images obtained. In one cat in the hemisection group, histological analysis revealed a very small piece of graft tissue that was not detected on the MR images. Therefore, it is suggested that within certain spatial- and contrast-resolution limits, MR imaging can reliably detect the presence of transplanted neural tissue in both the hemisected and compression-injured spinal cord of living animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗