Diffusion tensor MRI (DTI), using single-shot 2D diffusion weighted-EPI (2D ss-DWEPI), is limited to intracranial (i.c.) applications far from the sinuses and bony structures, due to the severe geometric distortions caused by significant magnetic field inhomogeneities at or near the tissue-air or tissue-bone interfaces. Reducing these distortions in single-shot EPI by shortening the readout period generally requires a reduced field of view (and the potential of wraparound artifact) in the phase-encoding direction and/or reduced spatial resolution. To resolve the problem, a novel 2D reduced FOV single-shot diffusion-weighted EPI (2D ss-rFOV-DWEPI) pulse sequence applicable for high resolution diffusion-weighted MRI of local anatomic regions, such as brainstem, cervical spinal cord, and optic nerve, has been developed. In the proposed technique, time-efficient interleaved acquisition of multiple slices with a limited FOV was achieved by applying an even number of refocusing 180 degrees pulses with the slice-selection gradient applied in the phase-encoding direction. The two refocusing pulses used for each slice acquisition were separated by a short time interval (typically less than 45 ms) required for the 2D EPI echotrain acquisition. The new technique can be useful for high resolution DTI of various anatomies, such as localized brain structures, cervical spinal cord, optic nerve, heart, or other extra-cerebral organ, where conventional 2D ss-DWEPI is limited in usage due to the severity of image distortions.