1991 — 1993 |
Mareci, Thomas H. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mri of Fetal Neural Grafts in Injured Spinal Cords
DESCRIPTION: (Adapted from the application) The goal of the research proposed is to assess the extent of spinal cord damage, and evaluate possible repair following transplantation of fetal spinal cord tissue, by using high-field MR imaging and spectral imaging in vivo. This study will assess on a macroscopic level the survival and development of fetal transplants and their interactions with the host spinal cord in a living animal. The following specific aims will be addressed. Aim 1 is to improve on images currently being obtained with conventional MR imaging methods. The applicants will develop high spatial-resolution images of the injured spinal cord to provide more detailed observations of post-traumatic pathology in vivo. In addition, they will explore whether three-dimensional image reconstructions of spinal lesions can be generated from serial and volume MR slices. Aim 2 will test the ability of H-1 MR spectral imaging to determine the tissue distribution of water and lipid. The focus of this aim will be to relate anatomical and gross chemical changes taking place in both injured cord and transplant tissue. Aim 3 is to study the dynamics of transplant growth and maturation in the acutely- and chronically-injured spinal cord using the methods developed in Aim 1 and Aim 2. Current analyses of fetal CNS transplants and their interactions with host spinal cord have been largely limited to post-mortem histological studies. Examination of spinal cord injury and repair with MR imaging and spectral (MRS) imaging may provide a tool for determining in vivo whether a transplant procedure will be successful.
|
1 |
1991 — 1995 |
Mareci, Thomas H. |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Nmr Imaging and Spectroscopy in Vivo Resource |
1 |
1995 — 1999 |
Mareci, Thomas H. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mr Evaluation of Spinal Cord Injury and Repair
This proposal addresses the development of nuclear magnetic resonance (NMR) spectroscopy and imaging techniques for application to in vivo studies of spinal cord injury (SCI) and functional repair. Three aims are proposed that will test the hypothesis that serial, non-invasive NMR measurements in individual animals can identify tissue parameters that reflect the time-course of lesion stabilization as well as the success of intraspinal grafting methods. The first aim is to develop: (a) diffusion- sensitive NMR imaging; (b) localized 1/H NMR spectroscopy; and (c) implanted radiofrequency (RF) reception coils that can be used to monitor tissue dynamics associated with spinal cord injury and transplantation. These NMR methods will then be used to address specific biological issues pertaining to spinal cord injury and repair with intraspinal fetal grafts. Therefore, the second aim is to obtain reliable, repeated measures of several anatomical (diffusion weighted images, T/1 and T/2 mapping) and neurochemical indices (1/H NMR spectra of lipids, lactate, N-acetyl compounds, and choline) of SCI. This information will be used to: (a) establish the evolution of the lesion; (b) determine the time after injury at which stabilization of spinal cord pathophysiology occurs; and (c) investigate the extent to which various NMR indices of lesion development and biochemical change correlate with functional outcome. The last aim of this project involves studies to: (a) evaluate the maturation, host-graft integration and long-term survival of intraspinal grafts of fetal neural tissue using the NMR approaches outlined in Aim 2; and (b) correlate these NMR parameters with histological assessments of host and graft tissues and measures of locomotor performance.
|
1 |
1996 — 2000 |
Mareci, Thomas H. |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Magnetic Resonance Imaging Facility
The primary mission of the magnetic resonance imaging (MRI) Core is to provide a detailed view of in vivo anatomy that is essential for the fulfillment of the objectives of the three Subprojects of this Program Project. Each MRI time point has been carefully selected to obtain specific information that will help to a) determine the severity of spinal cord injury, b) guide the transplant or vehicle injections, and c) determine transplant viability at key points (e.g., immediately prior to Cyclosporine A withdrawal). In addition, we will investigate the potential of MR microscopy for providing detailed 3-dimensional images of the injury or transplant site in selected postmortem spinal cord specimens. Since these data can be acquired in a time-efficient and cost-effective manner, we will assess the accuracy and reliability of MR microscopy for measuring important morphological parameters (e.g., lesion volume). Accordingly, the specific aims of this core are: (i) to provide in vivo anatomical views of the spinal cord at key time points during the injury and transplantation protocols, and (ii) to determine the ability of MR microscopy to provide reliable measures of several gross morphological parameters relevant to spinal cord injury and fetal tissue grafting. The MR images in Aim 1 will (a) provide an early evaluation of lesion severity by demonstrating hemorrhage and edema, (b) show lesion volume when locomotor function has stabilized, (c) show the lesion location and volume 1 week prior to delayed transplantation, which will assist greatly in determining the volume of the injection material, and (d) determine whether a viable graft is present 1 week prior to withdrawal of Cyclosporine A. Aim 2 will determine how accurately MR microscopy can illustrate lesion volume, transplant volume, and host- graft apposition, as well as white matter sparing in the adjacent host spinal cord. In addition, the noninvasive nature of the in vivo MRI studies underscores the clinical relevance of this Program Project, and the data obtained herein will be invaluable to any future cellular grafting approaches aimed at repair of human spinal cord injury.
|
1 |
2009 — 2010 |
Mareci, Thomas H. |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Selective Wirelessly-Adjustable Multiple-Frequency Probe (Swamp) Coil For Mri/S
DESCRIPTION (provided by applicant): In this project described in this revised proposal, a selective wirelessly-adjustable multiple-frequency probe (SWAMP) will be developed for non-invasive measurement of nuclear magnetic resonance (NMR) in vivo from a range of biologically important nuclei within implanted tissue constructs. This device will be instrumental in guiding the development of these tissue-engineered constructs by providing a method to monitor the viability and efficacy of these constructs in living subjects. But the same technology can be used to study a range of other significant biological systems, such as the spinal cord and other deep organ-systems, which require remote monitoring. Most importantly for our study, this device can non-invasively monitor the function of an implanted bioartificial-pancreas tissue construct. Therefore, the long-term objective of this project is to provide a clinical device that can be used in any magnet system to non-invasively examine the viability and function of a bioengineered tissue construct within a patient. The SWAMP system will use an NMR coil, implanted with the tissue construct, which is inductively coupled to an external coil. The development of this system will be accomplished by completing three specific aims: 1) Develop a microchip system to selectively tune an implanted NMR coil remotely to the frequency (nucleus) of interest and also develop an external-coil circuit, which will automatically impedance match the system. 2) Integrate these two components into the inductively coupled coil system and develop radio frequency pulse programs to automatically control the device. 3) Test the device performance by examining the functional status of a bioartificial pancreas tissue construct in gel phantoms during a longitudinal study of construct viability. This device is a major advance in NMR technology for monitoring implanted tissue or organs deep within the body. Current NMR implanted coil technology cannot be used to measure a full range of biologically important nuclei from implanted tissue without a severe loss of sensitivity for some nuclei. Therefore NMR measurements are not possible for this important range of nuclei without sacrificing significant biochemical information. The proposed SWAMP system overcomes this limitation through the innovative use of micro- fabrication technology to produce a single device that has optimum performance at all nuclei of interest and can be tuned remotely. Because of these significant performance improvements and ease of use, the SWAMP system can be used to obtain NMR data from a complete range of nuclei and provide critical information about the biochemical status of an implanted tissue construct. PUBLIC HEALTH RELEVANCE: Tissue constructs are a potential treatment of a range of diseases, such as diabetes using a bioartificial pancreas, which can replace the function of failed tissue, e.g. pancreas tissues. However artificial tissue constructs must be monitored to assure that they are functioning properly and to predict if they might fail, e.g. for diabetes, well in advance of changes in blood glucose levels. The proposed selective wirelessly-adjustable multiple-frequency probe for nuclear magnetic resonance can monitor an implanted tissue construct, such as a bioartificial pancreas, non-invasively by remotely selecting key nuclei to examine with optimum sensitivity.
|
1 |