Magnetic Resonance Imaging (Sotak)
Description of the Research
Development of magnetic resonance imaging (MRI) methods for the evaluation of acute stroke and its response to therapy.
Stroke ranks third among the leading causes of death in the US and is the most common cause of adult disability. Of the estimated 500,000 new stroke cases each year, approximately 30% will die and another 20-30% will become severely and permanently disabled. Ischemic stroke results from a local reduction in brain blood supply due to a vascular obstruction (for example, a blood clot) and accounts for 70-80% of all strokes. The characterization of stroke has been greatly facilitated by the availability of diagnostic imaging techniques such as MRI; however, the use of MRI studies for evaluating the effectiveness of therapeutic interventions during early (acute) ischemic stroke is still in its early stages. Since timely detection and treatment of ischemic brain damage significantly improves outcome, the development of new MRI technologies to detect acute stroke, as well as evaluate therapeutic interventions during the acute phase, will play an important role in mitigating this devastating cerebrovascular disease. Fortunately, recent developments in MRI technology make it possible to visualize the brain tissue affected during acute ischemic stroke as well as assess the degree of ischemic brain damage. This new MRI technology also provides powerful tools for evaluating the effectiveness of different cerebroprotective therapies during early stages of the disease, when the chances for a good clinical outcome are the most promising.
Many therapies are being developed to potentially treat acute ischemic stroke. The MRI technologies of diffusion and perfusion imaging provide unique ways to evaluate the effects of anti-ischemic therapy in vivo on ischemic lesion size and brain perfusion. These methods also afford the opportunity to distinguish the contributions of multiple sequential therapies used in combination. It is likely that two or more anti-ischemic therapies directed at different aspects of the pathophysiologic cascade of focal ischemic injury will be more beneficial than a single therapy. In stroke research currently being conducted at WPI, diffusion and perfusion MRI techniques are being used in the pre-clinical evaluation of the individual contributions of multiple therapies and the most effective combination. All of the MRI methodology employed in these studies is directly transferable to human use and these techniques are becoming widely available in the clinical environment. Diffusion and perfusion MRI are currently employed in clinical stroke trials to determine patient eligibility as well as evaluate the effects of treatment based on quantifiable MRI parameters. Such an approach has the potential to hasten clinical stroke drug evaluation if the MRI endpoints can be correlated with standard clinical outcome measures.
Development of fluorine-19 (19F) MRI and magnetic resonance spectroscopy (MRS) methods for measuring tumor oxygenation and evaluating adjuvants for tumor therapy.
The ability to noninvasively monitor the oxygenation state of individual solid tumors would have important implications for planning and evaluation therapy. The presence of hypoxia limits the success of radiotherapy in animal tumors and has been suggested as the cause of therapeutic failure in some human cancers. Hypoxic cells impair the effectiveness of chemotherapeutic agents due to their location in poorly vascularized areas of the tumor and/or because of their cell-cycle kinetics. Residual malignant cells protected from these therapeutic modalities by hypoxia may regrow to cause local recurrence of the disease. Consequently, knowledge of the oxygenation status of clonogenic cells within solid tumors before and during treatment would be extremely valuable in predicting the outcome of therapy.
The objective of this research is to develop novel fluorine-19 (19F) nuclear magnetic resonance (NMR) techniques for noninvasively evaluating the oxygenation state in solid tumors. The NMR spin-lattice relaxation rate, R1 (1/T1), of perfluorocarbon (PFC) emulsions increases linearly with increasing oxygen concentration; providing a potential probe for monitoring oxygen gradients in vivo. Furthermore, it has been shown that intravenously administered PFC emulsions preferentially accumulate in solid tumors and can be detected using 19F NMR spectroscopy and imaging. Consequently, in vivo PFC relaxation rates, measured using 19F NMR spectroscopy and imaging, are a sensitive indicator of tumor oxygen tension and provide a powerful noninvasive method for monitoring tumor hypoxia before and during treatment.
With the advent of these techniques, it is now possible to evaluate the efficacy of chemotherapeutic and radiotherapeutic interventions that depend on particular states of tumor oxygenation. For example, the presence of tumor hypoxia has motivated the development of therapeutic strategies that involve agents that are selectively toxic to hypoxic cells. Compounds of this type exhibit dramatically increased cell kills when used in conjunction with hydralazine; an agent which produces extensive tumor hypoxia. The timeliest administration of this type of therapy, relative to hydralazine, can be evaluated using 19F NMR spectroscopy of PFC's by determining when minimum pO2 levels are attained following hydralazine administration.
Hypoxic cells in solid tumors are also generally considered to be the major impediment to successful treatment by radiotherapy. Fortunately, previously hypoxic tumor cells frequently "reoxygenate" following irradiation, due to the death of well-oxygenated cells that reside between the hypoxic cells and the capillaries supplying oxygen and nutrients. This phenomenon has prompted the routine use of a fractionated course of radiotherapy, a regimen that kills a progressively increasing number of reoxygenated hypoxic cells during subsequent treatments. Although most animal tumors reoxygenate, the rate and degree of reoxygenation varies widely among individual tumor lines. Therefore, if the time course of reoxygenation can be established for a particular tumor type, via changes in tumor pO2 measured by 19F NMR of PFC's, then the fractionated treatments can be administered at the most efficacious time. In addition, agents known to sensitize hypoxic tumor cells to radiotherapy, such as nicotinamide, can be evaluated using 19F NMR of PFC's to determine the most timely administration of the compound relative to irradiation.
Characterization of structural information in fluid-saturated porous media using diffusion-weighted magnetic resonance imaging (MRI) and spectroscopy (MRS).
Recent developments in diffusion-weighted MRI and MRS have shown that the time dependence of the apparent diffusion coefficient in fluid-saturated porous media contains structural information about the system under study. At short diffusion times, the pore surface-area-to-volume ratio can be determined. At long diffusion times, information about the interpore connectivity or tortuosity is obtained. New methods have been developed for accurately measuring the diffusion coefficient of water in the presence of restrictions and large background magnetic field gradients. These techniques have been applied to diffusion measurements in porous media (such as rock cores) and have recently been extended to biological model systems to explain the diffusion behavior of water in the cellular milieu. In particular, the application of these techniques to the study of cerebral ischemia, solid tumors, and soft tissue (e.g., Achilles tendon) have provided new insights into the structural properties of tissues and how these properties change as a function of disease or under the influence of mechanical perturbations.
Description of Space, Resources, and Specialty Equipment Used
The WPI Magnetic Resonance Imaging (MRI) research facility is attached to the Central Massachusetts Magnetic Imaging Center (CMMIC) at 367 Plantation Street (adjacent to the University of Massachusetts Medical School). This facility was established in 1987 as part of the Conjoint Research Program in Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) between the WPI Biomedical Engineering Department and the Department of Radiology at UMASS Memorial Health Care. This 1630 sq. ft. research facility houses a General Electric (GE)/Bruker CSI-II 2.0 Tesla/45 cm research MRI system that operates at 85.56 MHz for protons (1H). The facility also contains a chemistry/electronics laboratory (for sample preparation and radiofrequency coil research) and staff offices with a local-area network of PC's (also connected to the MRI instrument) for data analysis. MRI data from the WPI MRI research facility can also be transferred to the main WPI campus via the internet. In addition to the WPI MRI research facility, CMMIC has an 8500 sq. ft. clinical MRI facility that houses two GE 1.5 T clinical MRI instruments. In addition to routine clinical MRI studies, these instruments are available for suitable MRI research projects.
The WPI MRI research program also has laboratory space on the main WPI campus; located in Salisbury Laboratory (SL 327). The laboratory houses a home-built 15.04 MHz (for 1H) benchtop NMR instrument that was developed for educational purposes. The laboratory also contains student offices as well as data-analysis facilities for off-line processing of research or clinical MRI data obtained from CMMIC.
Pictures from WPI MRI Research Laboratory CMMIC (Central Massachusetts Magnetic Imaging Center)
General Electric/Bruker CSI-II 2.0 Tesla/45 cm research MRI system that operates at 85.56 MHz for protons (1H).
Pictures from WPI MRI Research Laboratory Facilities in Salisbury Laboratory (SL 327) at WPI
Spin-echo detection (on digital oscilloscope) on 15.04 MHz (for 1H) benchtop NMR system (frequency synthesizer on right-hand side of picture).
From left-to-right appears the free-induction decay (FID) following the 90° radiofrequency pulse, a smaller FID arising from imperfections in the 180° radiofrequency pulse, and finally the spin-echo NMR signal at the echo time (TE).
op view of 3500 Gauss magnet (inside a Faraday cage) associated with 15.04 MHz benchtop NMR system. The radiofrequency coil and sample tube (with red cap) can be observed between the pole faces of the magnet.
Last modified: September 20, 2006 14:39:19