[18F]-MFBG Versus [123I]-MIBG and [18F]-PE2I in PD vs. MSA and DLB vs. AD

Difference in diagnostic accuracy between [18F]-MFBG and [I123]-MIBG

Diffirence in diagnostic accuracy ((sensitivity) (prevalence) + (specificity) (1 - prevalence)) of \[18F\]-MFBG versus \[I123\]-MIBG in differentiating PD versus MSA-P and LBD versus AD. The index test is semi-quantitative analysis or visual inspection of the change in myocardial uptake of the tracer. Semi-quantitative analysis will be based on \[18F\]-MFBG myocardial volume of distribution (VT) in L/kg, early and late standardized uptake volume (SUV) in g/ml , heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage. The reference test is the previously established clinical diagnosis.

Effect size

For all subjects, the \[18F\]-MFBG myocardial volume of distribution (VT) in L/kg, early and late standardized uptake volume (SUV) in g/ml , heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage will be calculated. For cardiac \[123I\]-MIBG SPECT, early and late HMR and WR values will be calculated. The effect sizes will be calculated between groups for both tracers through Cohen's d or another relevant effect size measure, depending on the data distribution and scale. Direct comparison of the effect size of the difference in \[18F\]-MFBG and \[123I\]-MIBG myocardial uptake in PD versus healthy controls and MSA-P and DLB versus healthy controls and AD.

Relation to brain DAT

For all subjects, the \[18F\]-MFBG myocardial volume of distribution (VT) in (L/kg), early and late standardized uptake volume (SUV), heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage will be calculated. For the same subjects, the \[18F\]-FE-PE2I binding potential in left and right caudate and putamen, with reference to the occipital neocortex, will be calculated. For each panel (HC and each patient group), the mean and standard deviation for each test and outcome parameter will be calculated and the measurements will be converted to Z scores. The resulting Z scores will be plotted on a scatter plot and the Pearson correlation coefficient or other correlation measures will be calculated to test for a relation between the two tests.

Correlation of myocardial uptake of [18F]-MFBG to autonomic dysfunction

Autonomic dysfunction will be assessed using the SCOPA-AUT scale and by testing for neurogenic orthostatic hypotension. The SCOPA-AUT scale result will be expressed as a single numerical score by assigning a value of 0, 1, 2, 3 to the options and adding up the values for all the questions. A higher score means more symptoms linked to autonomic dysfunction. Myocardial uptake of \[18F\]-MFBG in PD and DLB will be measured and expressed in VT in L/kg or WR as a percentage. The correlation between the SCOPA-AUT scores and \[18F\]-MFBG myocardial uptake will be assessed by calculating Spearman's Rank Correlation Coefficient or another statistical measure. The relationship between measure neurogenic orthostatic hypotension (present/absent) and myocardial uptake of \[18F\]-MFBG will be assessed by Point-Biserial Correlation Coefficient or another statistical measure.

Utility of regional myocardial parameter variation

The myocardial \[18F\]-MFBG uptake will be projected on a polar map of the myocardium comprised of 17 segments. For each segment, scores such as regional wash-out (rWO), and regional myocardial tracer uptake (VT, HRM) will be calculated. These regional values will be compared between groups by two-way ANOVA or another statistical method and post-hoc analysis. The endpoint will be met if different regional segment scores are present between PD/MSA-P or DLB/AD or subtypes of PD.