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This article is from PLoS ONE , volume 8 . Abstract Background and Purpose: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI) may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI) may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI) to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. Materials and Methods: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54) and infectious (n = 46) lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium) was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV) values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. Results: Neoplastic lesions had higher rCBV values (4.28±2.11) than infectious lesions (0.63±0.49) (p