Subjects
This was a retrospective study that evaluated the diagnostic value of 123I-FP-CIT SPECT for differentiating PSP, including stereotype and subtypes, and PD patients. This study used data obtained at a single medical center, and was approved by our Institutional Review Board (IRB). The retrospective nature of this study made it difficult to acquire informed consent from all patients. Therefore, with the permission of IRB, we provided an opportunity for these patients to opt out. The privacy of all patients was completely protected.
Patient backgrounds were standardized by applying the following inclusion criteria: (1) diagnoses of PSP and PD at the Department of Neurology and (2) the acquisition of both 123I-FP-CIT SPECT and 123I-MIBG scintigraphy within a short interval (less than two weeks for most patients). The diagnosis of PSP including typical cases (Richardson's syndrome; PSP-RS) and other subtypes (PSP-variants; PSP-V) was based on the current diagnostic criteria [1, 17, 18, 19]. PD patients were diagnosed on the basis of the criteria set by the United Kingdom Parkinson’s Disease Society Brain Bank [20]. Exclusion criteria were insufficient quality of the 123I-FP-CIT SPECT images and failure of image analyses due to the presence of significantly abnormal findings (e.g., large cerebral infarctions or hemorrhages). All patients were evaluated clinically, tested for L-dopa responses, and examined with SPECT between April 2014 and March 2017. Thirty-nine PSP (mean age, 73 ± 7 years; 28 men and 11 women) and 42 PD (mean age, 75 ± 7 years; 19 men and 23 women) patients were enrolled.
123 I-FP-CIT SPECT imaging and volume of interest analysis
SPECT imaging was performed four hours after an intravenous injection of 167 MBq 123I-FP-CIT (DaTSCAN®; Nihon Medi-Physics, Tokyo, Japan) on a dual-head gamma camera system PRISM-AXIS (SHIMADZU. Co., Kyoto, Japan), equipped with low-energy, high-resolution, and parallel-hole collimators. Energy windows were set at 140 keV ± 20%, and 90 views were obtained throughout 360 degrees of rotation (128 × 128 matrix, 3.0 mm/pixel). Data processing was performed on an ODYSSEY FX PRISM-AXIS (SHIMADZU. Co., Kyoto, Japan). All images were reconstructed using OSEM (iteration 3, subset 15) and then 3D smoothed with a Butterworth filter (order 8, cut-off 0.3 cycles/pixel). The brain volume was resliced after reorienting the axial planes along the anterior-posterior commissural line, and axial sections of 3.0 mm in thickness were produced.
To perform the volume of interest (VOI) analyses, image processing was performed with Statistical Parametric Mapping (SPM) 8 (Welcome Department of Cognitive Neurology, University College, London, UK) implemented in MATLAB version R2010a (The MathWorks, Inc., Natick, MA). 123I-FP-CIT SPECT images of all PSP and PD patients were spatially normalized onto this in-house-made 123I-FP-CIT SPECT template, as described previously, in the Montreal Neurological Institute (MNI) space [21]. The final image format was 16-bit, with a size of 79 × 95 × 68 and voxel size of 2 × 2 × 2 mm.
To evaluate the striatal binding, bilateral striatal VOIs were created using an in-house-made 123I-FP-CIT SPECT template and MRIcron (https://www.nitrc.org/projects/mricron). Considering previous studies that reported posterior dominant binding reduction in PD and uniform binding reduction in PSP, bilateral striatal VOIs were divided into anterior and posterior VOIs [22]. According to studies that reported lower SERT midbrain binding in PSP patients, the midbrain VOI was obtained with WFU PickAtlas tool in SPM8 [8, 9, 23]. Additionally, the bilateral occipital lobes were selected as a reference region. After spatial normalization and VOI placement, the presence of misregistration was visually evaluated. Specific–to–nonspecific binding ratios (SBR) in the targeting region (i.e., striatum and midbrain) were defined as (mean counts of targeting region – mean counts of occipital lobe)/(mean counts of occipital lobe) [24]. Additionally, the anterior-to-posterior striatal ratio (StAP), which represented anterior striatal counts/posterior striatal counts, and asymmetry striatal ratio (StAS), which represented the less affected side striatal counts/more affected side striatal counts, were also calculated to evaluate the anteroposterior and asymmetry indices of the striatum according to the previously reported method.
123 I-MIBG myocardial scintigraphy and region of interest analysis
Early and delayed static images with a 128 × 128 matrix were obtained at 20 minutes and 4 hours after intravenous injection of 111 MBq of 123I-MIBG, respectively. Planar images were obtained using the same dual-head gamma camera system, equipped with low-energy, general-purpose, and parallel-hole collimators. Regions of interest (ROI) were drawn manually around the whole heart and mediastinum. According to the standard method described previously, the heart-to-mediastinum (H/M) ratio was calculated from the average counts per pixel in the heart and mediastinum [25]. The washout rate (WR), which is an index of the rate at which MIBG is washed out between the early and delayed images, was also calculated according to the following formula: WR = [(early heart counts – early mediastinal counts) – (delayed heart counts – delayed mediastinal counts)]/(early heart counts – early mediastinal counts) x 100. For the comparison study, early and delayed H/M ratios and WR were used for analysis.