NM-MRI validation table tail (Cassidy / Isaias / Ito), Longitudinal NM-MRI in PD (Cristian Salinas 20220625 commentary; Wirth 2022 #2071 Saljas cohort 140+97; vsNMc / disNMc / vsNMs annualized decay rates, UPDRS-III correlation), 79 early PD vs 32 HV cohort with manual SN segmentation, Dopamine Receptor imaging section opener (Booth 2015 #1745 raclopride PET / Bezard 2001 #1748)

Longitudinal

Cristian Salinas (20220625)

I’m assessing the general utility and feasibility of neuromelanin to be considered in the proposed Phib PD study with 341. With respect as to whether should be 3 or 7T, because basically one has to evaluate a neuromelanin volume, a 7T sounds like a better idea but realistically I would prefer to consider the 3T scenario. It will be very difficult to run a large multicenter trial if we impose 7T.

(Wirth, 2022 #2071) Saljas	Cohort	Result
140 patients and 97 controls were included from an UK clinical center, of whom 140 underwent a second scan after 1.5 to 2 years	longitudinal n=46, H&Y 2.0, UPDRS-III 27.3, UPDRS-total 47.1, Disease duration 4.9 y	Serial NM-MRI demonstrated accelerated NM loss in patients compared to controls Annual NM volume loss was estimated to start 5 to 6 years before clinical diagnosis (Fig 3) Voxel-wise signal degeneration was greater in the most affected side, more severe cases (Fig 4) (cross sectional) signal NM volume change correlated with change in motor severity (Fig 4). Figure 4A shows anti-correlations of motor severity (UPDRS-III with vsNMc (r = -0.36, P = 0.001) and vsNMs (r = -0.20, P = 0.02). Similar associations (Fig. 4B) were noted for UPDRS-total scores (vsNMc: r = -0.39, P = 0.0001; vsNMs: r = -0.34, P = 0.0001). Both associations of vsNMs (vs UPDRS-III and UPDRS-total) were better represented by nonlinear curves. No correlations between disNMc and the clinical observation were revealed. [Long]: Individual annualized decay rates were significantly higher in PD for vsNMc (vsNMc retest neuromelanin contrast) (patients: -7.3 ± 19.1% vs controls 0.4 ± 9.1, adjusted P = 0.05; Fig. 3A) and disNMc (patients: 5.3 ± 16.0 vs controls 0.02 ± 7.1, adjusted P = 0.03; Fig. 3A). We also show significantly greater annualized vsNMs loss in PD (i.e. 19.2 + 26.4 % compared to controls -2.2 ± 8.7%, P = 0.0035). Serial changes of these NM measures (vsNMc, disNMc, and vsNMs) were tested against UPDRS-III change rates. We found that only the reduction rate of vsNMc (template-based signal NM volume) was positively correlated with the serial increase rate of UPDRS-III (r = 0.52, P < 0.05).
79 early PD patients, 32 HV, age 64-72y, 30 PD CAVEAT manual segmentation to delineate the SN	Early PD 에서: BAseline 에서 reduced ↓ 1: 30% (vs control) Annual decline rate 1.5 (1.6, 8% based on parameter)) Above samples size is per group: - Correlation with MDS-UPDRS III (Off): Cwd shown mild correlation (r = -0.25), other parameters (volume NMc CNR) show even weaker degree of correlation. (table 4) - average annual rates of changes were – 5.8% for Vol, – 3.6% for Cw, 1.5% for SNR, and 1.9% for CNR; compared with a respectable 0.4% for Vol, 0.3% for Cwd, 0.8% for SNR, and 3.5% for CNR in HV. There were no significant correlations between SN measurements and longitudinal changes in disease severity or time over 2 years.

Dopamine Receptor imaging

study	narrative
(Booth, 2015 #1745)	Postsynaptic striatal neuron density can also be measured with 11C-[((-)-(S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-6-methoxy-salicylamide tartrate; FLA 870(-); A40664] (raclopride) PET showing normal or increased dopamine receptor binding.
(Bezard, 2001 #1748)