HSE primarily affects the temporal lobe, orbital region of the frontal cortex, cingulate gyrus, and insular cortex.

DWI often shows increased signal intensity, which in some cases is limited to the cortex, though occasionally the white matter is also affected. Apparent Diffusion Coefficient (ADC) maps may reveal decreased values indicating diffusion restriction, which is associated with a poorer prognosis. Conversely, increased ADC values, indicative of vascular edema, generally suggest a better prognosis.

Additionally, the areas affected by the lesions frequently demonstrate cerebral microbleeding.

The inflammatory response to HSE leads to an increase in cerebral blood flow. As a result, Arterial Spin Labeling (ASL) imaging is particularly effective for detecting this augmented blood flow.

Herpes Simplex Encephalitis (HSE) can sometimes progress to brainstem encephalitis, with lesions extending from the pontine tegmentum to the medulla, where the trigeminal nucleus resides. This condition may also involve the middle cerebellar peduncle and trigeminal nerve roots. Typically, the lesions are unilateral, although they can occasionally be bilateral, reflecting the diverse manifestations of HSE within the central nervous system.

In cases of Herpes Simplex Encephalitis (HSE), contrast enhancement in MRI scans can be observed in the affected pia mater, revealing what is known as a PS-pattern meningitis.