Absolute quantitation of regional cerebral blood flow in mouse using 123I-iodoamphetamine and pinhole SPECT

Background and aims: Pre-clinical study using small animals is essential for evaluation of new therapy. Regional cerebral blood flow (rCBF) as physiological parameter is one of indexes to evaluate the effect of therapy for cerebral infarction. For imaging distribution of radioisotope in mouse, imaging modality with high-spatial resolution (<1 mm) is required. Unlike autoradiography (ARG), pinhole SPECT allows to obtain 3D distribution of radioisotope without cutting specimen into thin slices. This study was aimed at evaluating feasibility of absolute quantitation of rCBF in mouse using 123I-iodoamphetamine (IMP) and our pinhole SPECT system. Methods: The pinhole SPECT system consists of an object rotating stage, a conventional gamma camera (Toshiba GCA-7200A) and a pinhole collimator. The pinhole of 1 mm was used. The spatial resolution was 0.9 mm. This study was performed on six mice of cerebral infarction model. The MCA-infarction was created on 9 days before SPECT experiments. The anesthetized mice were sacrificed 13-23 min after administration of IMP (0.44-0.47 mCi), and then brains were extracted and placed on the rotating stage with holder. Immediately before sacrifice, arterial blood in heart chamber was sampled to calibrate population-based input function which was determined separately on five mice by frequent blood sampling. Each brain was scanned for one hour. The images were reconstructed by pinhole 3D-OSEM method and CBF values were calculated using a two-compartment model (2CM) with distribution volume of 45 ml/ml as proposed previously (Iida et al. JNM 1994). CBF images were generated on a pixel-by-pixel basis. T2 weighted images of brain in all mice were obtained by MRI (GE Signa 3T) scans the day before the SPECT study, which has been used for identification of region-of-interest (ROI). SPECT images were superimposed on MR images through X-ray CT images. Two ROIs were set on infarction region including penumbra and the symmetrical region in unaffected side. Results: SPECT images could be obtained and successfully superimposed on MRI images (Fig. 1). CBF images showed significant defect in infarction regions, and demonstrated significantly decreased CBF values in infarct side as compared with unaffected side, namely 0.68+/-0.20 versus 0.88+/-0.25 ml/g/min, respectively. The CBF values in normal regions were within a range measured previously by 14C-iodoantipyrine and autoradiography (Maeda et al. JCBFM 2000). Conclusions: This result suggested feasibility of absolute quantitation of rCBF in mouse using IMP and our pinhole SEPCT system.