Subjects: Eight 12 month old mice were included in the study; (wild type controls (strain C57BL/6J, male), 6 double transgenic Alzheimer’s amyloidosis model (APP/PS1) (3 male)). All animal procedures were approved by the National Health Medical Research Council-accredited Curtin Animal Ethics Committee (approval no. 2016-25). The mice were intravenously administered 20 MBq of the amyloid tracer 18F-NAV4694 (NAV) before a 30 minute dynamic acquisition on a Sedecal SuperArgus BioPET/CT (4). Following uptake, each animal was anaesthetized with gaseous isofluorane (2%), eyes were protected with Lacri-Lube gel and placed into the PET scanner bed in a supine position and secured with tape. Respiration was monitored throughout the entire scan.
Co-registration: A T1 weighted MRI-based template (AMBMC)(5) was directly co-registered to a subject CT to allow for PET uptake quantification in various brain VOIs (basal ganglia, hippocampus, cerebellum, and cortex, divided into left and right hemispheres to make 8 VOIs in total). To achieve this inter-modality co-registration, a subject CT is first cropped to include only the skull and converted to a binary mask. The skull cavity is then manually filled in slice by slice in the axial plane using ImageJ(6) software, creating a skull cavity mask. The skull cavity mask, having the same approximate overall shape as the brain, is then used as a co-registration target for the T1 template; which is achieved via an affine transformation using FSL(7) software. This subject is termed the Primary Registration Subject (PRS).
Other subjects in the cohort are then co-registered to the PRS, effectively also co-registering them with the AMBMC template. This intra-modality registration is simpler to implement. Other subjects need only to be cropped to the skull and co-registered to the PRS via affine transformation, which is then applied to their corresponding PET. The result is that the T1 template and all other subjects are transformed into the native space of the PRS. The co-registration process is depicted schematically in Figure 1. Figure 2 shows an example of the AMBMC template co-registration process.
The T1 template is directly co-registered to the PRS. For all other subjects, there are two transformations involved (template to PRS and subject to PRS). This could potentially impact transformation accuracy, and therefore PET counts detected in a given VOI. All possible co-registration permutations, with each subject acting in turn as the PRS, were tested for this cohort to determine if the choice of PRS had an effect on co-registration accuracy or detected PET counts.