Magnetic Resonance Spectroscopy

Ever since the discovery of Magnetic Resonance Imaging (MRI), the field of MR has diverged into MRI and Magnetic Resonance Spectroscopy (MRS). Whereas MRI typically observes a water signal, MRS detects all chemicals above a minimum concentration threshold. The members of the Yale MRS group have been pioneers in many of the applications of MRS to the study of metabolism in vivo. The detection of glycogen has been a breakthrough in the non-invasive study of liver and muscle function. The development of 13C MRS methods to study dynamic metabolic fluxes provides unique insights into metabolism that can not be obtained by any other technique. Combining MRS methods with other modalities, like electrophysiology, enhances the understanding of the relation between metabolism and function. And while the current applications of MRS are already many and diverse, the future holds even more promise with the exploration of other nuclei and improved hardware.

The Yale Magnetic Resonance Spectroscopy (MRS) group was founded in 1986 under the leadership of Robert Shulman. Recognizing the potential of MRS to study metabolism and function non-invasively in vivo, the group quickly evolved the MRS studies from cells to animals and ultimately to humans. Among the numerous contributions of the Yale group to the field of in vivo MRS are the development of 13C MR methods to study metabolic fluxes in vivo, the use of multi-modal MR methods to study brain function, and the implementation of sophisticated hardware to address specific MRS problems. Under the leadership of Douglas Rothman, the MRS group has expanded to a large roster of several faculty, staff and postdoctoral associates and students, using three animal (4, 9.4 and 11.7 T) and two human (4 and 7 T) MR systems.

The research performed in the Yale MRS group is as diverse as its faculty. The long and rich history of the Yale MRS group with the study of metabolism using heteronuclear (¹³C, ¹⁵N, ³¹P) MRS techniques still remains a prime focus point today. Among the many collaborations, ¹³C MRS is applied to study metabolism in diabetes (Douglas Rothman) and psychiatric disorders (Graeme Mason). Fahmeed Hyder is studying cerebral metabolism in relation to neuronal activity and function with a wide range of techniques, whereas Kevin Behar is studying cerebral metabolism under a variety of conditions, like hypoxia. The research of Robin de Graaf focuses on the further development of MR methods and hardware to enhance the MRS information content and reliability.

Dr. Robin deGraaf’s current research encompasses three primary areas. Central to the technological innovation of this research is the development of methods to achieve magnetic field uniformity throughout the human and animal brain. The problem of magnetic field inhomogeneity is tackled through dynamic shimming and the use of electrical coil and passive shim element arrays. Methods for ¹³C NMR have been pioneered at YSM, and part of the research involves extending these methods to achieve 3D coverage, higher sensitivity (through 1H detection), and higher specificity (e.g., GABA turnover detection). Additionally, the field of ¹⁷O NMR appears promising for fast and sensitive mapping of various metabolic fluxes. This research includes the synthesis of ¹⁷O-labeled compounds, the development of novel ¹⁷O MR methods, and the in vivo detection of ¹⁷O label turnover.

Dr. Fahmeed Hyder's laboratory focuses on several specific ongoing research topics. These include high spatiotemporal resolution fMRI at ultra-high fields to study sensory columns at extremely high resolution, and investigating the electrophysiological basis of the BOLD signal by examining excitatory and inhibitory neural events underlying the response. Additionally, the lab explores the rheological basis of the BOLD signal, considering the contributions of blood plasma and erythrocytes on the BOLD response. The energetics of neuronal populations are studied through fMRI to understand subcortical mechanisms underlying cortical activations for unisensory and multisensory stimuli. Furthermore, the lab is involved in translating smart contrast agents for tumor characterization by MR, aiming to synthesize and translate agents for improved biosensing of pH and temperature.

Dr. Graeme Mason's research integrates quantitative approaches to measure functional brain chemistry and the study of neuropsychiatric disorders. The primary methods employed are ¹H and ¹³C magnetic resonance spectroscopy and mathematical assessment of metabolism. Current research areas include depression, manic-depressive disorder, alcoholism, panic disorder, premenstrual syndrome, and post-partum depression. His primary interests lie in the effects of alcohol and nicotine dependence on the brain. Dr. Mason's research program evaluates both the acute and chronic effects of alcohol and nicotine on the brain, from perspectives of neurotransmission, metabolism, adaptation, and vulnerability to dependence.