Neuroinflammation and PET-CT imaging as a diagnostic tool following spinal cord injury

Neurological examination: Prior to Scan 1 (baseline), the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) physical examination of participants will be conducted by qualified SCI physicians in order to assess the nature and degree of injury and to classify neurological status as part of the formal screening process. This assessment will be used as the baseline neurological score to confirm the participant’s motor, sensory impairment and neurological levels. This neurological examination will be repeated at study completion (6 months following PET-CT; Cohort 1 Only). Neuropathic pain assessment: Participants will be asked to complete the Visual Analogue Scale (VAS), Numerical Pain Rating Scale (Lichert Scale), and The Neuropathic Pain Diagnostic Questionnaire. These examinations will be repeated at study completion (6 months following PET-CT; Cohort 1 only). Biochemical assessment: Blood collection for genotyping will be conducted once, and sampling for biochemical analysis will be conducted once. 35mL of venous blood will be drawn from the cubital fossa using RAH standard care venepuncture and infection control protocols. Blood will be collected into EDTA vacutainer tubes. Blood (25mL) will be cryo-stabilised (8°C) and transported on ice and centrifuged and serum aliquoted into 5mL vacutainer tubes for immediate analysis. Analyses will include CBE – leukocyte counts/percentages, haematocrit (5mL) and, MBA – glucose, cholesterol, LDL, HDL, total protein (5mL) on commercial platforms. Unused serum (15mL) will be stored in 5mL aliquots at -20°C for biochemical analysis. Five (mls) of serum will be stored for 2-years against the contingency of low assay yield. The assay repertoire may be expanded as new studies appear in the literature. Unused serum will be disgorged and destroyed at the end of study. PET-CT assessment: Administration of GEH120714 ([18F]GE-180; 100-270 Megabecquerel (MBq), intravenous administration) in spinal cord injured participants. All participants will be scanned at the Clinical & Research Imaging Centre (Dr. Jones & Partners, SAHMRI) and/or Royal Adelaide Hospital (Nuclear Medicine Department). Cohort 1 participants, PET-CT scans will be performed on 1 occasion: baseline (either 3 months ± 4 weeks, 6 months ± 4 weeks, 9 months ± 4 weeks, or >12 months and <24 ± 4 weeks post injury). For Cohort 2 participants, PET-CT scans will be performed on 1 occasion: >24 months post-injury. Participants will be likely be scheduled in batches of three per visit day over 3 scanners. All data acquisition will occur using one of three, compatible (6-slice CT) PET-CT Scanners (BiographTM, Seimens Healthineers, Australia). On scan days prior to PET scanning, an antecubital venous cannula will be inserted for [18F]GE-180 administration. All participants will receive a maximum dose 270 MBq of [18F]GE-180 by a slow, single bolus intravenous injection (<10mL) over 10 seconds, followed immediately with a normal saline flush (10 mL). Prior to the scan, participants will be transferred to the scanner platform using a pat slide, or electric hoist, as per the clinical treatment plan manual handling requirement. Participants will be positioned and secured in a recumbent position (supine with knees in ~ 30 degrees flexion, hips extended, arms down) on the scanner platform with their head secured in a holding using foam wedges and Velcro straps. Emission data from the head to mid-thigh will be acquired using a whole-body scanner (BiographTM , MCT flow 64 slice cameras) operated by an AHPRA-accredited Nuclear Medicine technologist. Attenuation correction of the images will be performed using a low-dose CT scan to allow standard corrections for tissue scatter and anatomical localisation. Whole Body acquisition will begin at 60 minutes post-injection of the radiotracer. Estimated PET acquisition time is 45 minutes for whole body scan. MRI Assessment: MRI scans will be performed once on all participants. Cohort 1 participants, MRI scans will be performed on 1 occasion: baseline (either 3 months ± 4 weeks, 6 months ± 4 weeks, 9 months ± 4 weeks, or >12 months and <24 ± 4 weeks post injury). For Cohort 2 participants, MRI scans will be performed on 1 occasion: >24 months post-injury. Standard MRI safety screening will be performed (attached) to ensure included participants are safe for MRI. Prior to the scan, participants will be transferred to the scanner platform using a pat slide, or electric hoist, as per the clinical treatment plan manual handling requirement. Participants will be positioned and secured in a recumbent position (supine with knees in ~ 30 degrees flexion, hips extended, arms down) on the scanner platform with their head secured in a holding using foam wedges and Velcro straps. Structural T-weighted, and diffusion-weighted MRI will be performed on each participant. MRI will be performed on a Siemens 3-tesla MAGNETOM Skyra MRI scanner (Siemens, Erlangen, Germany). Co-registration of MRI with PET-CT images will provide additional anatomical information.