Brain Bioenergetics

We combine our efficient multi-channel coil array and time-efficient pulse sequences with the enhanced signal strength available in a 7 Tesla magnet to provide volumetric phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single metabolite phosphorus whole-brain imaging with 2.7mL voxels in 15 minutes. This approach could provide new insights into the underlying energy metabolism impairment in neuro-degenerative conditions such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia.

 

Skeletal Muscle Metabolism and Microvasculature Function

MRI provides the unique ability to study metabolic and microvasculature functions in skeletal muscle using phosphorus and proton measurements. We developed a coil array with full calf coverage and a phosphorus signal-to-noise ratio of more than double that of a standard volume coil in the gastrocnemius muscles. This enabled the local assessment of phosphocreatine recovery kinetics following a plantar flexion exercise with a 6 second temporal resolution. The integrated proton array demonstrated image quality on par with that of a clinical state-of-the-art knee coil, which we use for fat quantification and dynamic blood oxygen level-dependent measurements that reflect microvasculature function.

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 multi-nuclear (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.