Quantitative comparison of MR imaged focused ultrasound lesions and cell death zones in the in vivo rabbit brain

The purpose of this study is to evaluate cell viability in MR imaged focused ultrasound (FUS) lesions using cell viability staining with Triphenyl Tetrazolium Chloride (TTC) combined with light and electron microscopy. Ten paired ultrasonic lesions were created in 5 rabbit brains in vivo. T2-weighted fast spin echo (FSE) MRI was performed to detect the FUS lesions in the brain 4 hours after treatment, after which the animals were immediately sacrificed. Lesion sizes were measured on TTC stained specimens, histological sections stained with hematoxlin and eosin (H&E), and T2-weighted MR images. The results showed that the lesion sizes measured from MRI correlated well with those measured from H&E sections (r=0.90). The measurements of the lesion from MRI slightly overestimated lesion sizes on TTC stained wet tissues by approximately one MRI pixel (0.3 mm). The differences between the lesion diameters measured with the three techniques were within the range of 0.1-0.7 mm. Electron microscopy demonstrated nuclear and cytoplasmic ultrastructural damage within the grey-white, non-TTC staining lesion zone, whereas the TTC positively staining, normal tissue, showed preservation of neuronal ultrastructure. Therefore, MR imaged lesions represent a cell death zone in rabbit brain 4 hours after FUS ablation, with slight overestimation by approximately one MRI pixel.