Study the feasibility of aerobic exercise in subjects with mild Relapsing Remitting Multiple Sclerosis (RRMS) and investigate use of ³¹P MR spectroscopic imaging as a biomarker for improvement in tissue metabolism.Exercise has been linked and shown to be effective in slowing aging process and increasing brain neurogenesis^1,2. Our hypothesis is that moderate aerobic exercise will improve the brain health manifested by improved brain metabolism. Human subjects with relapsing-remitting MS were recruited under an IRB approved protocol to study the effect of aerobic exercise. Each subject underwent a series of physiological and cognitive measures (including walking tests, Modified Fatigue Impact Scale (MFIS) and Symbol Digits Modality Test (SDMT)). Subjects were studied on a 7T Siemens Magnetom system (Erlangen, Germany) for MRI and MRS measures. High resolution MPRAGE (0.8 mm isotropic, TR/TI/FA/TAT= 2.3 s/1.05 s/8°/10.8 min) were acquired for tissue segmentation using an 8‑channel proton RF array coil (Rapid Biomedical, Germany)³. Brain ³¹P magnetic resonance spectroscopic imaging was performed using a ³¹P head coil with a ¹Halo coil^3,4 setup. A low-resolution phosphorus B₁ maps were acquired for RF coil inhomogeneity correction. Phosphate metabolite level were also measured following a rest, exercise and recovery protocol in tibialis anterior (TA) of the right leg using a dual-tuned ³¹P/¹H surface coil (4 cm x 9.5 cm oval, with longer axis aligned to the muscle length). Subject’s right leg was positioned in a home-built exercise setup that isolated dorsi-flexion of the ankle against a fixed load. Spectra (TR/TE/FA/NS/SW/NP = 300 ms/0.225 ms/~20°/4/8000 Hz/2048) were acquired continuously during the rest (1.5-3.0 min), exercise (2-3 min) synchronized to a metronome beats of 40 beats/min and recovery period of 4-10 min. A hard pulse of 250 μs was used for excitation centered at PCr resonance frequency. Subjects underwent an aerobic exercise regimen (AER) of 30 minutes at a target heart rate four times per week for eight weeks under supervised training. The above measurements were repeated to measure any post-aerobic exercise regimen changes. Brain phosphorus spectra were fit for phosphocreatine (PCr), adenosine triphosphate (α, β and γ-ATP), phosphoethanolamine (PE), phosphocholine (PC), glycerol-3-phosphoethanolamine (GPE), glycerol‑3‑phosphocholine (GPC) and inorganic phosphate (Pi) peaks using AMARES algorithm^3,5. Spectra from TA muscle were fit for PCr, α, β and γ-ATP, Pi and GPC peaks. Phosphocreatine recovery was modeled as a single exponential⁶ and a non-linear fit was performed using Levenberg-Marquardt algorithm. Measured values were assessed statistically using paired t-test.10 subjects (age = 44.7 ± 9.4 years, EDSS = 3.4 [mean, range: 2.5-4.0] and mean disease duration of 14.6 ± 6.5 years) participated and finished the study. Resting heart rate, fat mass, lean mass and VO₂ max showed a significant improvement (-16.8%, -6.4%, 2.6% and 13.2% respectively, P< 0.05, Table 1). Subjects’ spent significantly more time exercising (21%, P<0.01) and SDMT scores (15%, P<0.05) were improved after post-AER. MFIS cognitive component showed significant improvement (26%, P<0.05). There were no significant changes in brain phosphorus metabolite levels in a volume of interest in superatentorial region (Table 2). Post-aerobic exercise regimen value for PCr recovery constant was significantly improved in TA muscle (Table 3, Figure 1). In addition, ATP/PCr ratio was increased in post-exercise (4.1%, P<0.01, Table 3). While physiological measures of fitness, fatigue and cognition showed an improvement in subjects with MS, brain metabolite levels did not show a significant change after an eight week long aerobic exercise intervention. PCr recovery time decreased post-AER in TA muscle and shows that ³¹P MRS can be used to monitor improvement in muscle health. The small number of subjects and short duration of this pilot study precludes any extensive conclusions about brain metabolism.Aerobic exercise is feasible and beneficial in MS subjects’ fitness and cognitive measures. While ³¹P MRS can be used in leg muscle successfully to monitor improved metabolic function, significant changes in brain metabolite levels were not observed following an 8-week intense aerobic exercise challenge. However, such changes could be apparent following longer duration exercise intervention². Magnetization transfer studies or functional exercise studies that elucidate kinetic parameters of Creatine-Kinase reaction may be a more sensitive measure of tissue metabolism.