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To understand the biological basis of possible mechanisms responsible for increased fractional anisotropy (FA) in different stages of hemorrhage and hemorrhagic brain lesions.A total of 19 patients with cerebral hemorrhage (CH), five patients with hemorrhagic infarct (HI), and nine patients with hemorrhagic brain tumor (HBT) were prospectively evaluated with diffusion tensor imaging (DTI) and the FA and mean diffusivity (MD) was quantified. Ex vivo DTI of blood clot and histology of the blood clot and HBT were performed to interpret the temporal changes in the DTI metrics.High FA (>0.20) with low MD in the acute and early subacute stage and low FA (<0.20) with increased MD in the late subacute and chronic stage of CH and HI were observed. HBT showed high FA with low MD at all stages. In CH and HI, a significant reduction in FA (P < 0.001) with increased MD (P < 0.001) was seen in the late subacute and chronic stages compared to the acute and early subacute stages, normal white matter (NWM), and HBT. In HBT, there was no significant statistical difference in the FA values between different stages. Histology of HBT and ex vivo blood clot showed structural organization of intact red blood cells (RBCs) with fibrin mesh where the FA values were high compared to normal tissue region that is devoid of blood.Intact RBCs entangled within fibrin mesh appear to be responsible for high FA in hemorrhagic brain lesions.