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H D I N S I G H T S HD Research Around the World: France By: Isaac M. Adanyeguh Imaging Brain Metabolic Markers at the Institut du Cerveau et de la Moelle Épinière (ICM), Paris In addition to the well-known neurological phenotype, HD presents with non-neurological symptoms that suggest hyper-catabolism in the early stage of the disease, leading to significant weight loss1. Metabolic dysfunction is therefore a major focus of HD research and may be easily amenable to therapeutic intervention2. Our team has shown that dietary anaplerotic therapy can improve peripheral energy metabolism in HD patients3. We also emphasized the potential of non-invasive 31phosphorus magnetic resonance spectroscopy (31P MRS) in biomarker identification3. However, a sensitive biomarker of brain energy metabolism in HD patients has yet to be identified. Our team at ICM, Hôpital PitiéSalpêtrière in Paris, led by Prof. Alexandra Durr and Dr. Fanny Mochel, is therefore interested in identifying biomarkers that reflect brain energy metabolism that could be used in therapeutic trials in HD patients. To identify sensitive brain metabolic markers based on the results obtained in muscle3, we recruited 15 HD patients in the early stage of HD, but who were without significant cognitive impairment, and 15 age- and sex-matched controls, as subjects for brain 31P MRS on a 3T Siemens Magnetom Trio system. We targeted the visual cortex for the single-voxel functional MRS because it is easily stimulated and has high energy metabolism (Figure 1a). It is also very close to the scalp, giving an increased sensitivity to the small surface coils. A 6 cm 31P transmit/receive surface coil (Figure 1b) was used to detect signals (free induction decays – FIDs) from the visual cortex for 4 minutes at rest (baseline), 8 minutes during visual activation, and 8 minutes after visual stimulation (recovery), while limiting signals from other brain regions. A small sphere 10 mm in diameter filled with water and placed below the coil along the coil axis helped to verify and adjust the position of the 31P coil on T1 images (Figure 1a). Visual stimulation was performed with 6 Hz red and black checkerboard flashes (Figure 1c) generated in MATLAB and projected by a video projector onto a screen at the beginning of 8 minutes of stimulation. Subjects were able to focus on the flashes with a nonmagnetic mirror mounted above their eyes. (continued on Page 9...) Figure 1: a) T1-weighted image with highlighted visual cortex showing the position of the sphere filled with water. The black square shows the region used for localized 1H shimming. The dashed white line indicates the sensitive volume of the coil encompassing most of the visual cortex. b) The 6 cm 31P transmit/receive coil in a holder with mounted mirror used in the lab. c) Red and black checkerboard used for visual stimulation. If you are interested in contributing a piece that highlights research in your part of the world, please contact us at editor@hdinsights.org. 8 Copyright © Huntington Study Group 2013. All rights reserved. HD Insights, Vol. 6