Quantitative micro-SPECT/CT for detecting focused ultrasound-induced blood-brain barrier opening in the rat.

Focused ultrasound has been discovered to be able to locally and reversibly increase the permeability of the blood-brain barrier (BBB). The purpose of this study was to investigate the feasibility of micro-single photon emission computed tomography/ computed tomography (micro-SPECT/CT) and 99mTc diethylenetriamine pentaacetate (99mTc-DTPA) for identifying disruption of the BBB induced by focused ultrasound in a rat model. We also assessed the amount of radiotracer that had crossed the BBB using various intensity levels of ultrasound energy. Immediately after sonication, three Sprague-Dawley rats were scanned for 2 h to determine the optimum time for data acquisition. Static SPECT with 1.5-h acquisition time was then performed in 12 rats sonicated with focused ultrasound pressure amplitudes of 0.78-2.45 MPa. Radiotracer and blue dye were used for lesion delineation. SPECT images were evaluated quantitatively and compared to results of histology and autoradiography. Terminal deoxynucleotidyl transferase biotin-desoxyuridine 5'-triphosphate (dUTP) nick end labeling staining was used to examine hemorrhage and tissue damage. The disruption to nondisruption radioactivity ratio showed a gradual increase from dynamic SPECT images, reaching a peak at 1.5 h post injection. The extent and intensity of radioactivity showed a good correlation with autoradiographic distribution and blue dye staining. SPECT measures correlated significantly with quantitative autoradiographic results (r(2)=0.90). According to SPECT findings, high acoustic powers allowed the delivery of larger amounts of radiotracer [0.001+/-0.002%ID (percent injected dose) under 0.78 MPa vs. 0.036+/-0.022%ID under 2.45 MPa]. Brain hemorrhage and tissue damage occurred at pressure amplitudes higher than 1.9 MPa. Our data demonstrate the usefulness of (99m)Tc-DTPA micro-SPECT/CT for detecting focused ultrasound-induced BBB disruption in the rat. This method may be used in vivo in combination with quantitative analysis for evaluating the amount of BBB opening.