Research Projects

Multinuclear MRI in Lower Leg Muscles

Magnetic resonance imaging (MRI) provides the unique ability to study both metabolic and microvasculature functions in skeletal muscle using phosphorus (31P) and proton (1H) measurements. However, the low sensitivity of these techniques can make it difficult to capture dynamic muscle activity due to the temporal resolution required for experiments involving kinetic measurements of muscle during and after exercise tasks. Therefore, we constructed a dual-nuclei coil array to enable 1H and 31P MRI of the human lower muscles with high spatial and temporal resolution on a 3 Tesla clinical system. We developed an array with whole-volume coverage of the calf and phosphorus signal-to-noise ratios (SNRs) of more than two times the levels of a volume birdcage coil in the gastrocnemius muscles. The SNR improvement enables us to assess phosphocreatine (PCr) recovery kinetics using an efficient (31P-FLORET) sampling scheme with a 6 s temporal resolution following a plantar flexion exercise.

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(left) Photograph of the developed 31P/1H array with the protective cover removed. (right) Dynamic 31P PCr images acquired using the developed coil array in the calf muscle at different time points during a plantar flexion exercise protocol with the PCr signal time course (bottom) from the segmented gastrocnemius muscle.

Clinical Research in Skeletal Muscle

Diabetes mellitus affects 26 million people in the U.S. Approximately 15% of type 2 diabetes mellitus (T2DM) patients will develop a diabetic foot ulcer (DFU). Despite several therapeutic approaches for wound treatment, approximately 15–20% of all DFUs ultimately require amputation. A major risk factor for the development of DFUs is diabetic peripheral neuropathy (DPN), which affects between 30–50% of all diabetic patients. The underlying mechanisms that cause DPN are not fully understood, and despite encouraging results from clinical trials there are no known therapies to prevent or reverse its progress.

A major obstacle for the development of effective treatments for DPN is the lack of sensitive and objective tests to detect small changes in symptoms and signs seen in clinical studies. In this NIH-funded clinical study we will test the effectiveness of multinuclear (31P and 1H) MRI to early diagnose and stage DPN. If successful, our study will provide new insights into the diverse roles of bioenergetics and microvascular factors responsible for the onset and progression of the disease and could become valuable non-invasive tools for testing the effectiveness of pharmacological agents in reversing DPN symptoms.

Brain Energy Metabolism Assessment using 31P-MR

Phosphorus (31P) magnetic resonance spectroscopy (MRS) is a unique tool for evaluating cerebral metabolism in vivo. It allows direct detection and quantification of cerebral phospholipids, high-energy phosphates such as phosphocreatine (PCr) and adenosine triphosphate (ATP), intracellular pH, and the rate constants of important reactions such as the creatine kinase (CK), and the ATP synthesis hydrolysis cycle (ATPase). 31P-MRS has provided new evidence of underlying bioenergetic abnormalities in many conditions including Alzheimer’s disease, Parkinson’s disease, Bipolar disorder, and Schizophrenia. Unlike other techniques that measure cerebral metabolism such as positron emission tomography (PET) or carbon (13C) MRS, 31P-MRS does not require the injection of labeled precursors and is completely non-invasive.

31P-MRS data typically suffer from low signal-to-noise ratio (SNR) due to the low concentration of 31P containing metabolites in the brain and the low MR sensitivity associated with the 31P nucleus. As a result, undesirable compromises in spatial resolution and coverage have been required to perform 31P-MRS in reasonable acquisition times.

Significant SNR enhancement can also be achieved with improved radiofrequency (RF) coil detectors, which have transitioned from preceding single channel and volume coils to multi-element phased arrays. We recently developed a highly efficient 31P/1H array for brain imaging at 7 T. The array consists of an eight-channel 31P module and separate eight-channel 1H module that embodied the underlying strategy to enhance 31P performance without significantly conceding 31P performance.

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(left) Photograph of the 31P/1H 16-channel array and interface with the protective cover removed. (right) 31P/1H data set: a) anatomical 1H MP-RAGE in the sagittal plane, b) typical 31P-CSI spectrum from a voxel whose location is outlined in (a), spectroscopic images of (c) PCr and (d) γ-ATP in the sagittal plane derived from the 3D-CSI data

We are currently assessing the use of this highly efficient coil to assess brain energy metabolism in metal disorders.