All procedures performed in studies involving human participants were in accordance with the ethical standards of the Academic Medical Center medical ethical committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Subjects were scheduled for a routine DAT SPECT scan on the NeuroFocus for clinical evaluation of possible neurodegenerative parkinsonism or participated in a research project on heroin addiction (n = 2; these participants had a 2-week heroin- and methadone-free period between the end of detoxification and the SPECT scan. All subjects were required to have a negative urine drug screen for opioids, cocaine, and amphetamine on the day of the SPECT scan) in which the striatal DAT binding was examined . A total of 24 subjects agreed to participate. They were injected with ~ 111 MBq 123I-ioflupane ([123I]FP-CIT; GE Healthcare) and scanned on the NeuroFocus 3-h post-injection . Patients were scanned directly after finalization of the NeuroFocus scan, on the InSPira system (~ 4-h post-injection). Subjects did not use any medication known to influence [123I]FP-CIT binding. Data from seven subjects was excluded because of early termination of the scan on the InSPira system because of fatigue of the subjects due to the antecedent scan obtained on the NeuroFocus. In addition, for two patients, technical problems during the scan on the InSPira resulted in inability to reconstruct the data. For one patient, technical problems on the NeuroFocus resulted in insufficient quality for quantification, and the patient was therefore excluded. Consequently, complete data sets for 14 subjects were available for analysis.
The striatal phantom (RS-901T, Radiology Support Devices Inc., CA, USA) consists of left and right caudate nucleus, left and right putamen, and the rest of the brain. Striatal compartments were filled with 30/40 kBq/mL iodine-123 (123I) (left/right), and the rest of the brain with a range of activity concentrations, 5, 10, and 15 kBq/mL 123I, as earlier described .
NeuroFocus scan procedure
For details on the NeuroFocus system, see [5, 6]. In short, the NeuroFocus system has 12 individual crystals equipped with a focusing collimator (resulting in sensitivity being higher in the central focal point), and a spatial resolution of approximately 6.5 mm FWHM throughout the 20-cm FOV. With a bore diameter of 28.6 cm. Axial slices were acquired, parallel and upward from the orbitomeatal line at least covering the entire striatum. For the phantom scans, a slice time of 180 s and a slice spacing of 4 mm was used. The energy window was set at 159 keV, with 20% lower and upper boundaries (resulting in an energy window of 143–175 keV). For subjects, slice thickness of 10 mm, slice spacing of 5 mm, and slice timing of 150 s were applied (slice timing of 180 s was applied for subjects that were part of the research project) . A proprietary iterative reconstruction algorithm was used to reconstruct the data (with a fixed, unknown, number of iterations). Attenuation correction for patient data was performed using a spherical volume (with a uniform attenuation coefficient of 0.0105/mm) that was manually aligned using a rigid transformation.
InSPira scan procedure
For details on the InSPira system, see [1, 2]. In short, high-resolution imaging is achieved by the unique design of the detector ring of the InSPira HD. The detector ring consists of two clamshells, each containing 12 (focusing) fanbeam collimators, creating a 29.0-cm diameter bore. At start position, the two clams touch and the collimators are focused at the center of the ring, achieving a focal point of 3 mm in diameter. During acquisition, the gantry rotates and simultaneously the two clams are moved outward leading the two focal points of the clam’s collimators to follow spiral trajectories over the field of view (FOV). A proprietary iterative reconstruction algorithm (with 60 iterations) tailored to this unique method of spatial sampling is used to reconstruct the data into 3D images. This iterative reconstruction algorithm is based on a maximum a posteriori (MAP) estimation. It includes a point spread function (PSF), which is defined as the detector response to an impulse activity source point placed in the scanner FOV . For positioning see section “NeuroFocus scan procedure”. For phantom studies, the same scan parameters were applied as on the NeuroFocus. A CT-scan of the phantom was used for attenuation correction. For subjects, slice timing ranged from 120 to 240 s, slice thickness from 3.125–6 mm. The energy window was set at 159 keV, with 20% lower and upper boundaries (resulting in an energy window of 143–175 keV). An adult head CT template was manually aligned and used for attenuation correction.
All scans were visually evaluated by an experienced reader (JB), who was blinded to clinical data and scanner. Striatal binding was rated as normal when bilateral caudate nucleus and putamen showed high and symmetric [123I]FP-CIT binding . If the loss of DAT binding was more pronounced in the putamen than in the caudate nucleus on one or both sides, the scan was rated as abnormal supporting the clinical diagnosis of PD.
The Brain Registration & Analysis Software Suite (BRASS™, HERMES Medical, Sweden) was used for phantom and patient data analysis to quantify striatal DAT binding, as earlier described . BRASS automatically registers the patient data to a template containing a number of VOIs and calculates bilateral caudate nucleus, putamen, and whole striatal binding ratios. This was done by subtracting counts in the VOIs with counts in the reference region (occipital cortex) and finally dividing by counts in the reference region (i.e., specific striatal to non-specific binding ratios, which reflects the binding potential). The ENC-DAT control database  as implemented in BRASS was used as a reference template and for region definition. An independent sample of healthy subjects scanned on the InSPira was used to assess if patient’s striatal ratios fell within the normal range (only available for InSPira data) .
Pearson correlations were calculated to assess associations between striatal ratios of the two systems (the average of left and right striatal ratios). In order to obtain more detailed insight into the agreement between the two systems, Bland-Altman plots were examined. Limits of agreement were set at ± 1.96 standard deviation from the mean difference.