Participants
Ten healthy male volunteers (mean age, 34.6 years; range 22–45 years) were recruited through our institute’s website participated in this study. All the participants were right-handed except one, non-smokers (past and present), and did not have psychiatric or neurologic disorders or a history of head trauma. MRI of each participant was performed on the same day as the PET scans to confirm the absence of abnormal findings on 3D-T1 weighted MR images (T1WI), T2WI, FLAIR, or MRA using 3-T tomography (Verio, Siemens Healthcare GmbH, Erlangen, Germany). This prospective study was performed in accordance with the Declaration of Helsinki and approved by the institutional review board of our institute’s hospital (CRB3180004). Informed consent was obtained from all the participants.
FDG-PET protocol
All participants fasted for at least 6 h prior to receiving their FDG injection and were confirmed to have a blood glucose level below 100 mg/dL. Each patient was administered 4.1 ± 0.5 MBq/kg (range 241.7–323.4 MBq) of FDG after resting for 5 min in the supine position on the bed of the whole-body PET in a quiet environment while closing their eyes and wearing an eye mask. Each participant maintained this resting status until the first PET scan was completed, which was started 30 min after the injection, using a representative current clinical whole-body PET/CT system (Discovery MI; GE Healthcare, Milwaukee, WI, USA) for 10 min. CT (120 kV, 200 mA) images were acquired immediately before the PET scan. Next, the patients were moved to another room on the same floor to undergo a Vrain scan, which was started 45 min after FDG injection and lasted 10 min. These two 10-min brain scans were performed with the participant’s head and chin fixed to the scanner’s headrest using dedicated bands. Vrain was approved by the Pharmaceuticals and Medical Devices Agency in Japan and was commercialised by ATOX Co., Ltd. (Minato-ku, Japan). Figure 1 shows one participant undergoing a brain PET scan with the whole-body PET system and with Vrain. In Vrain, the participants underwent the PET scan in the sitting position with the backrest of the chair reclined by 45°. The gantry of the Vrain can tilt to cover the head such that the angle of the Vrain’s field of view and the head are the same as whole-body PET.
The Vrain consists of 54 block detectors, 45 of which are arranged to form a hemisphere, whereas the other nine are placed to form a half-ring behind the neck. The inner ring diameter was 279 mm at the bottom ring, and the axial field of view (FOV) was 224 mm from the top detector to the bottom of the neck detectors. The detector block was composed of lutetium fine silicate crystals and a silicon photomultiplier with one-to-one coupling [11]. There were a total of 7,776 crystals. The dimensions of each crystal were 4.14 × 4.14 × 10 mm3. The spatial resolution was 3.1-mm at full width at half maximum (FWHM) at 1 cm, 3.6 mm at 10 cm from the centre of the FOV, and 3.0-mm FWHM at 1 cm from the centre at the base of the hemisphere. These spatial resolutions were calculated based on the data of 22Na point source images reconstructed by filtered back projection (FBP) according to the NEMA NU 2–2018 standards. The TOF resolution was 245 ps. Brain PET images were reconstructed using ordered-subset expectation–maximization (OSEM), including the TOF information, with four iterations and eight subsets, and were smoothed using a 3D Gaussian filter of 4 mm FWHM. The matrix size was 140 × 140 × 112 with a voxel size of 2.0 × 2.0 × 2.0 mm3. Attenuation correction was performed using CT images acquired with whole-body PET/CT by co-registering the PET and CT images for each participant.
Whole-body PET/CT (Discovery MI) consists of five 744-mm-diameter block detector rings and has an axial FOV of 250 mm [6]. There were a total of 24,480 crystals made of lutetium yttrium orthosilicate. The dimensions of each crystal were 3.95 × 5.3 × 25 mm3. The FBP FWHM spatial resolution was 4.3 mm at 1 cm from the centre of the FOV. The TOF resolution was reported as 381.7 ps [13]. PET images were reconstructed using OSEM, including TOF information with four iterations and 16 subsets, and were smoothed with a 3D Gaussian filter of 4 mm in FWHM. The matrix size was 192 × 192 × 89, and the voxel size was 2.73 × 2.73 × 2.78 mm3.
Image evaluation
The voxel values of all PET images were converted to SUVs using the patient’s weight and FDG dose. For visual evaluation, the whole-body PET and Vrain images were anatomically co-registered to each subject’s MRI T1WI using an automatic procedure that maximises mutual information and re-sliced with a voxel size of 0.8 × 0.8 × 0.8 mm3 with trilinear interpolation equipped in PMOD (PMOD version 3.7; PMOD Technologies Ltd., Zurich, Switzerland). Visual inspection was then performed using the PMOD viewer. When the small nuclei were identified, a 4-mm-diameter spherical volume-of-interest (VOI) were manually placed to include the highest FDG accumulation of the structure, or two 4-mm-diameter spherical VOIs were placed continuously if the structure was larger than 4 mm diameter. The average SUV of these right- and left-side values was calculated and compared with the participants’ age.
Next, all PET images were anatomically normalised using transformation parameters, which were obtained through MRI normalization of each subject to the anatomical standard template provided by the PMOD. Then, an automated anatomical labelling atlas [14], which is a template VOI consisting of 116 VOIs, was applied to the anatomically normalised PET images. The SUVs of the following representative areas were selected and compared between whole-body PET and Vrain images: frontal lobe, mesial temporal lobe, lateral temporal lobe, medial parietal (posterior cingulate and precuneus) lobe, lateral parietal lobe, occipital lobe, and striatum.
Statistics
Correlations between the SUVs of each region and the participants’ ages were tested using Spearman's rank correlation coefficient test. Comparisons of the SUVs of each region between whole-body PET and Vrain were performed using the Mann–Whitney U test. Statistical significance was set at two-tailed p < 0.05. SUVs of each region are represented as the average ± 2SD.