title: Quantitative micro-SPECT/CT for detecting focused ultrasound-induced blood-brain barrier opening in the rat.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, 333 Taoyuan, Taiwan;.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Po-Hong
authors.initials: PH
authors.lastname: Hsu
authors.forename: Yi-Hsiu
authors.initials: YH
authors.lastname: Chung
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Jin-Chung
authors.initials: JC
authors.lastname: Chen
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Ing-Tsung
authors.initials: IT
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D005240:Feasibility Studies; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D016284:Technetium Tc 99m Pentetate; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
chemical_list: D004396:Coloring Agents; D016284:Technetium Tc 99m Pentetate