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

Introduction 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. Methods 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. Results 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. Conclusions 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.