Jan A. den Hollander - US grants

1H MRSI allows one to obtain metabolic maps of different brain compounds such as N-acetyl aspartate, creatine, choline compounds, lactate, and glutamine. By the implementation of improved acquisition techniques it has been possible to further improve the spatial resolution of these metabolite maps. By using a broad-band water/fat suppressing refocusing pulse in the measuring sequence the SNR (signal-to-noise ratio) has been improved. The use of a shorter recycle delay TR allows one to collect larger data sets, for a improved spatial resolution. With this approach it has been possible to obtain 1H MRSI data sets with a spatial resolution of 0.175 cc. This improved spatial resolution is especially important for the examination of stroke patients, and of temporal lobe epilepsy. Further improvements of the 1H MRSI technique are underway, in particular multislice capabilities to cover a larger part of the brain. [unreadable] The high-contrast T1 weighted 1H MR images obtained at 4.1T allows one to segment the images in gray and white matter. This information has been used to determine the gray/white matter contribution to individual voxels of 1H MRSI measurements, and this information has been used to obtain separate measurements of metabolite ratios and concentrations of gray and white matter, This image segmentation approach has been applied to 31P data sets, to obtain measurements of PCr/ATP, and PCr/Pi for gray and white matter as well The TCA cycle activity can be measured in the human brain, by monitoring the appearance to the 13C label in the brain glutamate pool, following infusion with [1-13C]-glucose. These measurements have been extended, as to obtain separate measurements of the TCA cycling rate of gray and of white matter. Homonuclear editing techniques have been further improved, to uncover hidden resonances in the 1H MRS spectrum of the human brain, in particular to observe GABA, and glutamate. Contributions from macro molecules to the GABA resonance has been reduced, by the use of an improved editing pulse. These techniques are being used to follow GABA levels in epilepsy patients, who are on anti-seizure medication.

DESCRIPTION (Adapted from Applicant's Abstract): Following a myocardial ischemic event, a number of changes take place in the affected part of the myocardium. The center of the ischemic region may be irreversibly damaged, leading to cell death and necrosis. Surrounding this central infarct zone is a region at risk, where the myocardium has been affected by the ischemic event but, with proper intervention, still has the potential for recovery. Information about the extent of the viable region is essential for diagnosis, prognosis, and the planning of appropriate intervention. The applicants proposed to differentiate irreversibly damaged (IR), ischemically insulted but viable (IV), and hibernating (H) myocardium from normal tissue non-involved and without contrast agents using nuclear magnetic resonance (NMR) imaging and spectroscopic techniques. These techniques include: function cine imaging to identify the contractile properties of the myocardium; magnetization transfer contrast imaging to identify IR tissue; T2-weighted turbo spin echo imaging to identify IR and IV tissue; and water-suppressed lipid imaging and 1H spectroscopic imaging to identify IV. Hibernating myocardium is identified by lipid imaging in conjunction with abnormal contraction. Patients who have had recent infarcts or have chronic stable ischemic disease or have ischemic cardiomyopathies have varying degrees of IR, IV, and H. By studying these patients and following up where appropriate, the applicants proposed to confirm the identification of these different tissues. In addition, the MTC effect is little understood in the heart. Using a canine model of ischemia, the applicants proposed to follow the development of the MTC effect and compare it to both ex vivo. images and histology. By using these approaches together with the high quality functional images that can be generated by proton nuclear magnetic resonance cardiac imaging, the type and extent of ischemic damage should be assessable. Once accomplished successfully, such information derived clinically could have an impact on the future of the practice of cardiology.

During myocardial ischemia, oxidative metabolism is reduced and fatty acids and triglycerides accumulate within the myocardial cell. The fatty acids and related substances, such as fatty acylcarnitines, are amphophilic and can lead to cell membrane destruction. Magnetic resonance methods can assess the concentration of lipids (generally triglycerides) within the myocardium. The observation of lipids within the myocardium is postulated to indicate viability. Various pharmacological interventions are used to evaluate their effect on myocardial lipid accumulation in control and during myocardial ischemic insults. Surface coils placed on the epicardium are used to interrogate the myocardial lipid content in a 4.7T Bruker Biospec 40cm bore system in canine models. It is anticipated that in the last years of this RO1, patients with MI, both reperfused and non-reperfused, will be studied in the 4.1T MR system to determine the relationship between myocardial lipid content and high energy phosphate metabolism.