Safety evaluation and post-FUS susceptibility effects
Vasogenic edema, hyperintensity, edema, myelin loss, hemorrhage, volume loss
GLIOSIS, EDEMA, HEMORRHAGE, ADVERSE EVENT, CORTEX
Signal changes manifested on blood-sensitive sequences at targeted brain regions following FUS (Fig. No serious adverse event was encountered by any trial participant. No hemorrhage or susceptibility effects were detected at any site remote from FUS-targeted brain volumes. No evidence of acute or chronic tissue injury, including ADC signal dropout to suggest cytotoxic edema, persistent parenchymal T2-FLAIR hyperintensity to suggest gliosis, or parenchymal volume loss was detected including at the regions of susceptibility effects and along sites of perivenous enhancement. Vasogenic edema occurred in the hippocampus of two subjects who received a higher hippocampal FUS cavitation dose, and was associated with local sulcal effacement in one patient, however these findings resolved completely without any residual parenchymal signal abnormality. No edema was detected in the frontal or parietal lobes of any individual. Quantitative segmentation analysis revealed no significant differences in volume of treated brain cortical regions (hippocampus, entorhinal cortex, and precuneus) at 60 days or 1 year following FUS, compared to baseline (ps > 0.3). T1 signal intensity returned to baseline at all treatment sites, without findings of parenchymal or extraparenchymal gadolinium retention or myelin loss. Study participants did not show any acute cognitive decline and formal neurologic and neuropsychological follow-up examinations have shown no unexpected clinical deterioration, after up to 48 months, compared to age-matched controls [