Background Determining mechanisms of secondary stroke injury related to cerebral blood flow and the severity of microvascular injury contributing to edema and blood-brain barrier breakdown will be critical for the development of adjuvant therapies for revascularization treatment. Aim To characterize the heterogeneity of the ischemic lesion using quantitative T2 imaging along with diffusion-weighted magnetic resonance imaging (DWI) within five hours of treatment. Methods Quantitative T2 magnetic resonance imaging was acquired within 5 h (baseline) and at 24 h (follow-up) of stroke treatment in 29 patients. Dynamic contrast enhanced permeability imaging was performed at baseline in a subgroup of patients. Absolute volume change and lesion percent change was determined for the quantitative T2, DWI, and absolute volume change sequences. A Gaussian process with RRELIEFF feature selection algorithm was used for prediction of relative quantitative T2 and DWI lesion growth, baseline and follow-up quantitative T2/DWI lesion ratios, and also NIHSS at 24 h and change in NIHSS from admission to 24 h. Results In n = 27 patients, median (interquartile range) lesion percent change was 114.8% (48.9%, 259.1%) for quantitative T2, 48.2% (−12.6%, 179.6%) for absolute volume change, and 62.7% (26.3%, 230.9%) for DWI, respectively. Our model, consisting of baseline NIHSS, CT ASPECTS, and systolic blood pressure, showed a strong correlation with quantitative T2 percent change (cross correlation R² = 0.80). There was a strong predictive ability for quantitative T2/DWI lesion ratio at 24 h using baseline NIHSS and last seen normal to 24 h magnetic resonance imaging time (cross correlation R² = 0.93). Baseline dynamic contrast enhanced permeability was moderately correlated to the baseline quantitative T2 values (rho = 0.38). Conclusion Quantitative T2 imaging provides critical information for development of therapeutic approaches that could ameliorate microvascular damage during ischemia reperfusion.