Background and purpose: Differentiation of acute and subacute ischemic stroke lesions from acute demyelinating lesions of multiple sclerosis (MS) may not be possible on conventional magnetic resonance imaging (MRI). Both lesion types enhance on T1 with gadolinium (Gd) contrast and both are hyperintense on diffusion-weighted imaging (DWI). This study is an analysis of two quantitative MR indices: (1) calculated apparent diffusion coefficients (ADCs) and (2) T2 relaxation times (T2R) as means toward differentiating acute ischemic lesions from acute demyelinating lesions. Chronic ischemic and demyelinating lesions were evaluated for comparison as well. Methods: The MRI of nine patients with both acute and chronic ischemic lesions and six patients with both acute and chronic demyelinating lesions were analyzed for ADC and T2Rs. The indices were measured by manually placing regions of interest (ROIs) at the anatomic center of the acute lesion. Acute ischemic lesions were chosen by their hyperintensity on DWI and hypointensity on ADC mapping. Acute demyelinating lesions were selected by peripheral contrast enhancement after the administration of Gd. Computation of the ADC involved the diffusion coefficient on a region by region basis as follows: D = -(b0/b1000)ln(Sb1000/Sb0), where Sb1000 is the signal intensity on DWI and Sb0 is the signal intensity on T2 with diffusion sensitivities of b0 and b1000, respectively. Computation of the T2R was made as follows: T2R = (TET2 - TEPD)/(ln SIPD - ln SIT2), where TE is the echo time of the different pulse sequences, SI is signal intensity on the different echo sequences, and PD represents proton density sequence. Results: Twenty-nine acute ischemia, 27 acute demyelination, 28 chronic ischemia, and 43 chronic demyelination image sets were analyzed. The differences between ADCacute infarct (0.760) versus ADCacute plaque (1.106) were significant (p < 0.02). The differences between T2Racute infarct (235.5) versus T2Racute plaque (170.5) were also significant (p < 0.02). Conclusions: ADC in combination with T2R is a useful tool to differentiate acute ischemic from acute demyelinating lesions. The use of these neuroimaging indices along with magnetic resonance spectroscopy metabolite ratios is then demonstrated in elucidating the pathophysiological mechanism for a case of delayed posttraumatic bilateral internuclear ophthalmoplegia.