Eighteen consecutive patients with suspected neurodegenerative parkinsonism (i.e., mostly differential diagnosis of PD vs. multiple system atrophy; 14 males; 66.4 ± 8.2 years), which were referred for cardiac MIBG scintigraphy to the Departments of Nuclear Medicine of the University Hospital Freiburg (center a; 6 males, 4 females; 63.6 ± 7.3 years) and University Hospital Würzburg (center b; 8 males; 70.0 ± 8.2 years) were enrolled in this study.
Patient preparation was implemented according to the guidelines of the European Association of Nuclear Medicine [11, 15]. Any drugs with known interference with MIBG uptake (e.g., tricyclic antidepressants) were discontinued for a minimum withdrawal time recommended by the guidelines [11, 15] or (if not specified) for at least 5 plasma half-lives. Potassium perchlorate was used to prevent thyroid uptake of free iodine. MIBG studies were acquired on two dual-headed SPECT/CT systems: Brightview XCT (center a; Philips Medical Systems Inc., Cleveland, OH) and Symbia T2 (center b; Siemens Healthineers, Erlangen, Germany). Brightview XCT was equipped with a 3/8-inch crystal and scans were conducted with LE and ME general-purpose collimators (photopeak window of 159 keV ± 20%). Acquisitions on Symbia T2 (5/8 in. crystal) were performed using LE and ME low penetration collimators (photopeak window of 159 keV ± 15%). Anterior and posterior planar images were obtained twice for 5 min at 4 h after the injection of 183 ± 25 MBq MIBG. The first acquisition was performed with LE, subsequently, the scan was repeated with ME collimator. Scintigrams of one patient were performed in the reversed order. Of note, we did not employ early MIBG scan (i.e., at 15 min after injection) which is inferior to the late MIBG scan according to an earlier meta-analysis . Imaging was performed as part of the clinical work-up. All patients gave written informed consent prior to the investigations for receiving the respective imaging procedures.
MIBG uptake was semi-quantitatively evaluated on the planar anterior images by calculating the H/M ratio using the PMOD image analysis software version 3.7 (PMOD Technologies Ltd, Zurich, Switzerland). First, ME images were automatically co-registered to the LE images and fused. Then, two investigators (JB; CL) defined ROIs of the heart and the mediastinum independently from each other on the fused image data. The center of a circle and one rectangular ROI was manually placed on the heart and the upper mediastinum, respectively. The ROIs were then transferred to the co-registered LE and ME image data and H/M ratios were calculated. Finally, the mean H/M ratio of both raters was calculated for each collimator and each patient by dividing the mean counts per pixel in the cardiac ROI by the mean counts per pixel in the mediastinal ROI.
Statistical analysis was performed with the commercial software package SPSS 25.0 (IBM Corp., Armonk, NY, USA). We explored inter-rater agreement of H/M ratio with the intra-class correlation coefficient (ICC) . Linear regression analyses were employed to describe the association between H/M ratios acquired with LE and ME collimators for both centers individually and pooled together. Analysis of covariance (ANCOVA) was used to test the interaction between center and collimator to evaluate if regression slopes depend upon study center. Finally, we performed a leave-one-out cross-validation (LOOCV) to test the validity of an empiric linear transfer of H/M ratios from ME to LE collimators with an in-house pipeline in MATLAB and Statistics Toolbox Release R2017a (The MathWorks, Inc., Natick, MA, USA). The deviation of the H/M ratio predicted by linear conversion from the actually measured H/M ratio was assessed by calculating the absolute difference (absolute error) and relative absolute difference (relative absolute error; expressed as percentage relative to the measured value).