Neuromelanin pigment biochemistry (Zecca review caption: NM-pigment biosynthesis & NM-containing organelle formation in human SN), Function (chelate iron / pigmented neurons vs TH correlation, Mor 2008 #1643), Rodent vs NHP, Neuromelanin-MRI section opener (Principle Sulzer 2018 #1597 / Iron in non-pigmented cells / SN pars reticulata, globus pallidus, caudate nucleus), METHODS (T1-weighted FSE / voxelwise NM-MRI / test-retest), Cassidy 2019 #1595 validation studies opener (NM-MRI vs neuromelanin tissue concentration / dopamine release / neural activity / clinical severity)

Function

Directly bind to (Chelate) and sequester iron in the cytosol of neurons, thus protects neurons.
Correlation: Neuromelanin pigment vs TH:
- (Mor, 2008 #1643) TH-negative pigmented neurons (no TH × Neuromelanin O) are present in the SN and LC of patients with PD (10-20%), but no normal controls (8). It is still uncertain whether these are dying neurons or not.
- (Mor, 2008 #1643) no correlation between the degree of pigmentation & TH immunoreactivity
CF) pigmented neurons 표준화 AB(아 이건 그만 그만 ?)

Rodent: no neuromelanin existing → less vulnerable to neurodegeneration

NHP: neuromelanin exist (n=at least macaques)

(Sulzer, 2018 #1597) Neuromelanin-iron complex is specific to NM neurons.

	NM-iron complex	Iron in non-pigmented cells
	NM-iron complexes are paramagnetic (i.e. possessing at least one unpaired electron, the chelating groups are catechols bearing a stable free radical)	Because most iron storage proteins (e.g. ferritin) is constructed of paramagnetic chelating groups are amino acids... but ferritin is the case of ferritin Fe-O. The N-MRI signal arises from a NM-iron complex.
SN pars reticulata, globus pallidus, and caudate nucleus	are bound to neurons and less NM-iron complex

usually performed using T1-weighted fast spin echo sequence
voxelwise method of NM-MRI analysis is now fully automated and can be run without requiring expertise or staff time.
high test-retest reproducibility of NM-MRI techniques makes longitudinal studies of NM possible
L-DOPA should increase NM (not fully examine since)

Objective: Relationship between NM-MRI signal and	(n=7)	result
Neuromelanin tissue concentration (biochemical method)	SN section (n=7), 41 healthy human Postmortem (i.e interindividual variability), Pectroscopiometric analysis of neuromelanin	linear model 굵은 회: ρ=-0.45, t(33)=-2.13, P=0.030, a 19% increase in NM-MRI CNR (contrast-to-noise ratio) corresponds with an estimated increase of 0.10 µg of NM per mg of tissue.
Validation of voxelwise approach (i.e. to establish whether regional differences in NMMRI signal capture biologically meaningful variation in neuromelanin content within the substantia nigra)	9 (HC) & 9 schizophrenia patients, [11C] raclopride] (baseline & dextroamphetamine administration)	higher NM-MRI signal had greater dopamine-release capacity (Spearman p = 0.64, 95% CI = 0.26-0.87, P = 0.013)
Relationship of NM-MRI signal to neural activity in fMRI (ASL-MRI) to measure regional cerebral blood flow (CBF)
Relationship of NM-MRI signal to clinical severity	PANSS

study	cohort		Correlation with Neuromelanin MRI	Correlation with DAT imaging	Correlation with dopamine synthesis rate (1-dopa PET)
(Isaias, 2016 #1065)	Cross sectional	SN volume: 70% of control 로서 DATScan 보다 덜 차이남 (SD는 30% 정도로 유사)
(Ito, 2017 #1668)	Cross sectional, HV			r=-0.24	r=-0.47