High resolution μSPECT for brain activation analysis in small animals

A stimulus on/off imaging study is often used to evaluate the brain´s response to a presented visual, electrical or chemical trigger. Clinical software and human templates already exist but given the recent advent of ultrahigh resolution μSPECT and μPET, a larger need rises for a post processing platform to perform these subtraction molecular imaging studies also in small animals. We have designed such a multimodal framework to perform μSPECT activation studies in rats thereby making use of μCT and MRI for anatomical land marking. Our software solution is a combination of Amide, MRIcroN and a custom made Matlab implementation. We have studied the performance of different deep brain stimulations for which 6 rats were implanted with a multi-polar stimulation electrode in the right hippocampus. Each animal underwent a 99mTc-HMPAO μSPECT with the Milabs U-SPECT-II and a μCT scan with the GMI X-O CT before and after stimulation. Two line markers in oblique positions filled with low activity of 125I are used to register the μSPECT and μCT images. Afterwards the animals were sacrificed, their electrode was removed and a MRI scan was performed using the wrist coil of a Siemens Trio 3T. A semi-automated five step procedure delivers the activation map: (i) first the stimulus-on μCT and the MRI are registered to the stimulus-off μCT followed by (ii) the fusion of the off/on μSPECT scans with their off/on μCT counterparts. From the MRI, (iii) the rat brain is extracted, which is used as a mask for the calculation. Afterwards, (iv) both off/on μSPECT scans are normalized and subtracted within this MRI brain mask. Finally, (v) the Z-score, representing the activation map, is achieved by dividing the result with the standard deviation of the masked stimulus-off μSPECT. This semi-automated approach allows the experimental neu-roscientist to draw conclusions- - on the location, spatial extent and intensity of the small animal brains response to the stimulus.