The dependence of diffusion tensor imaging parameters, such as fractional anisotropy (FA), on the diffusion time can probe the scale of alterations in white matter micro-structure. Oscillating gradient spin echo (OGSE) gradient waveforms enable much shorter diffusion times (4 ms) than the typical pulsed gradient spin echo (PGSE, 40 ms) (Figure 1), which gives OGSE sensitivity to water diffusion restriction/hindrance over smaller length scales ^1-3. However, OGSE is challenging to implement on human MRI scanners given the limited gradient strengths; as such there are only two OGSE papers in healthy subjects ^4,5 (only recently in 2014) and one patient study on acute stroke ⁶. The purpose here is to apply OGSE diffusion tensor MRI to study the micro-structural alterations of lesions within the cerebral white matter in patients with multiple sclerosis. Diffusion tensor imaging (DTI) was acquired in 4 MS volunteers (41±14 yr; 3F/1M; 2-RRMS/2-PPMS) on a Varian Inova 4.7 T MRI using OGSE 50 Hz (Δ_eff = 4 ms) and PGSE (Δ_eff = 40 ms). Each OGSE or PGSE DTI protocol took 5 min and used 2D single-shot EPI (4 element receive coil) with: TR = 12.5 s; TE = 110 ms; FOV = 24 cm; 2x2x2.5 mm³; 20 slices over a 5 cm slab centred on the ventricles; 6 averages; R=2 GRAPPA; b = 300 s/mm²; 6 gradient directions 5,6. In addition, a FLAIR using fast spin echo (38 4 mm slices, 1x1 mm² in-plane) was acquired for lesion detection. The diffusion tensor data was processed using ExploreDTI. The OGSE and PGSE scans (b=0 s/mm²) were co-registered to the FLAIR using SPM. The lesions were outlined on the FLAIR and then ROIs transferred to the PGSE and OGSE DTI to measure fractional anisotropy (FA) in all lesions (N=26) and contralateral normal appearing white matter (NAWM). Statistical significance was evaluated using paired t-tests for OGSE relative to PGSE within the NAWM and lesions, and lesions relative to NAWM within either PGSE or OGSE scans. The FLAIR-visible MS lesions showed obvious reductions of FA on the OGSE and PGSE scans, as shown in one SPMS volunteer (Figure 2). Note that the FA maps will appear noisier than expected due to the low b value limitation (b = 300 s/mm²) of OGSE and the need to keep the same b value for PGSE for comparison. The FA values in the lesions and NAWM averaged over the 4 MS volunteers are shown for PGSE and OGSE in Figure 3. There are notable differences of FA between the PGSE and OGSE scans for both normal appearing white matter (NAWM) and lesions. Compared to NAWM, the white matter lesions showed FA reductions on both PGSE (~24%) and OGSE (~23%). Also, the shorter diffusion time of 4 ms in OGSE, relative to the 40 ms in PGSE, yielded a slightly larger FA drop for NAWM (~9%) than in the lesions (~7%).The 9% reduction of FA with shorter diffusion time in NAWM is similar to the 9-12% changes seen in healthy subject white matter with the same diffusion times of 40 ms and 4 ms ⁶, as expected when the water molecules have less time to be hindered by local cell membranes and other micro-structures. The MS lesions showed large reductions of FA relative to the NAWM, but the proportional reductions did not differ between OGSE and PGSE. A cuprizone mouse model of demyelination also showed reduced FA in the corpus callosum using either OGSE or PGSE, but the FA difference between healthy and demyelinated white matter appeared less with OGSE than with PGSE ⁷ – this differs from our results in the MS lesions . Future analysis of this OGSE/PGSE data set will include more MS patients, the need to look at the other diffusion parameters (mean, parallel, and perpendicular diffusivities) and a comparison to controls OGSE vs PGSE in truly normal WM. The use of OGSE DTI permits an investigation of the dependence on diffusion time to infer potential changes in micro-structural scale within MS lesions.