PMID- 33071729
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201022
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 14
DP  - 2020
TI  - Molecular Imaging of Striatal Dopaminergic Neuronal Loss and the Neurovascular 
      Unit in Parkinson Disease.
PG  - 528809
LID - 10.3389/fnins.2020.528809 [doi]
LID - 528809
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder, 
      characterized by loss of nigrostriatal dopaminergic neurons. Impairment of the 
      neurovascular unit (NVU) has been hypothesized to play a critical role in early 
      PD pathophysiology, and to precede neurodegenerative mechanisms. [C-11]-PE2I 
      (N-(3-iodoprop-2E-enyl)-2b-carbomethoxy-3b-(4-methyl-phenyl)nortropane) (PE2I) is 
      a PET radiotracer targeting neuronal dopamine transporters (DaT) with high 
      specificity, allowing for highly accurate and specific DaT quantification. We 
      investigated NVU integrity using arterial spin labeling (ASL) MRI in a 
      prospective cohort of 26 patients with PD, and correlated our findings with 
      analysis of striatal DaT density using PE2I PET in a subcohort of 17 patients. 
      Analysis was performed in FreeSurfer to obtain rCBF and mean standardized 
      regional PET avidity. Pearson correlations and Mann-Whitney tests were performed. 
      Significantly lower mean normalized striatal PE2I SUV values were seen in 
      multiple regions in patients with greater disease duration (p < 0.05). PET uptake 
      in the putamen correlated with disease duration independent of patient age. 
      Stratifying patients based on Montreal Cognitive Assessment (MoCA) scores 
      (stratified into >/= 27 vs. < 27), there was statistically significantly lower PE2I 
      PET avidity in the higher MoCA score group in both more and less affected sides 
      of the caudate, putamen and pallidum (p < 0.05). A moderate negative correlation 
      between MDS-UPDRS part 3 (motor) "off" and rCBF values was also seen in the L and 
      R cerebellum WM (r = -0.43 and -0.47, p < 0.05). A statistically significant 
      negative correlation was found between dominant hand pegboard test results and 
      rCBF in the less affected pallidum (r = -0.41; p = 0.046). A statistically 
      significant negative correlation of ASL MRI with [11C]-PE2I PET was also found (r 
      = -0.53 to -0.58; p-value 0.017-0.033) between left cerebral WM rCBF and more and 
      less affected striatal PET regions. Our ROI-based analyses suggest that longer 
      disease duration is associated with lower rCBF and lower PE2I mean SUV, implying 
      greater NVU dysfunction and dopaminergic neuronal loss, respectively. Combined 
      ASL MRI and PE2I PET imaging could inform future prospective clinical trials 
      providing an improved mechanistic understanding of the disease, laying the 
      foundation for the development of early disease biomarkers and potential 
      therapeutic targets.
CI  - Copyright (c) 2020 Ivanidze, Skafida, Pandya, Patel, Osborne, Raj, Gupta, 
      Henchcliffe and Dyke.
FAU - Ivanidze, Jana
AU  - Ivanidze J
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Skafida, Myrto
AU  - Skafida M
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Pandya, Sneha
AU  - Pandya S
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Patel, Dylon
AU  - Patel D
AD  - Department of Neurology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Osborne, Joseph R
AU  - Osborne JR
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Raj, Ashish
AU  - Raj A
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Gupta, Ajay
AU  - Gupta A
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Henchcliffe, Claire
AU  - Henchcliffe C
AD  - Department of Neurology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
FAU - Dyke, Jonathan P
AU  - Dyke JP
AD  - Department of Radiology, Weill Cornell Medicine, Cornell University, New York, 
      NY, United States.
LA  - eng
PT  - Journal Article
DEP - 20200918
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC7530280
OTO - NOTNLM
OT  - ASL "arterial spin labeling"
OT  - PE2I PET
OT  - Parkinson disease
OT  - molecular imaging
OT  - neurovascular unit
EDAT- 2020/10/20 06:00
MHDA- 2020/10/20 06:01
PMCR- 2020/01/01
CRDT- 2020/10/19 05:54
PHST- 2020/01/21 00:00 [received]
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/10/19 05:54 [entrez]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2020/10/20 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2020.528809 [doi]
PST - epublish
SO  - Front Neurosci. 2020 Sep 18;14:528809. doi: 10.3389/fnins.2020.528809. 
      eCollection 2020.