Histological evaluation of prostate tissue response to image-guided transurethral thermal therapy after a 48h recovery period

Image-guided transurethral ultrasound thermal therapy shows strong potential for sparing of critical adjacent structures during prostate cancer treatment. Preclinical experiments were conducted to provide further information on the extent of the treatment margin. Four experiments were carried out in a canine model to investigate the pathology of this margin during the early stages of recovery and were compared to previous results obtained immediately posttreatment. Sedated animals were placed in a 1.5T clinical MRI, and the heating device was positioned accurately within the prostatic urethra with image guidance. Using an MRIcompatible system, the ultrasound device was rotated 365° treating a prescribed volume contained within the gland. Quantitative temperature maps were acquired throughout the treatment, providing feedback information for device control. Animals were allowed to recover and, after 48h, an imaging protocol including T2 and contrast enhanced (CE) MRI was repeated before the animals were sacrificed. Prostate sections were stained with H&E. Careful slice alignment methods during histological procedures and image registration were employed to ensure good correspondence between MR images and microscopy. Although T2 MRI revealed no lesion acutely, a hypo-intense region was clearly visible 2 days post-treatment. The lesion volume defined by CE-MRI increased appreciably during this time. Whole-mount H&E sections showed that the margin between coagulated and normal-appearing cells narrowed during recovery, typically to a width of under 1mm compared to 3mm acutely. These results illustrate the high level of precision achievable with transurethral thermal therapy and suggest methods to monitor the physiological response non-invasively.