Table 5. . Most promising imaging biomarkers.

Imaging	Total n	Direction	Study (year)	Ref.
DatScan SPECT	56 85 50	Decline in [123I]β-CIT striatal uptake in PD β -CIT binding reduced in PD & APS, normal in ET; declined over 1 year in PD short duration and APS, not significant in PD long duration and ET decreased [123I]β-CIT over 1 year in PD	Marek et al. (2001) Pirker et al. (2002) Winogrodzka et al. (2003)	[47] [48] [49]
DMRI	(1722) 37 44 72 59 28	DTI may be promising for differential diagnosis in parkinsonian symptoms Lower FA in PD in neuromelanin SN ROI, not T2 ROI FW values higher in PD pos SN, FW increased in PD over 1 year FW values higher in ant & pos SN of PD, MSA, PSP Increase in nigral MD in PD FA reduced in SN in PD	Cochrane & Ebmeier (2013) Langley et al. (2016) Ofori et al. (2015) Planetta et al. (2016) Schwarz et al. (2013) Vaillancourt et al. Neurology, (2009)	[50] [51] [52] [53] [54] [55]
MRI	140 110	Reduced gyrification overall in PD; accelerated loss of gyrification in mid-stage PD Midbrain/putaminal vol & cerebellar gray matter constructed prediction model has 97.4% diagnostic accuracy for PD vs MSA/PSP	Sterling et al. (2016) Scherfler et al. (2016)	[56] [57]
fMRI	42 60 112 24 80 42 42	Altered FC resting-state fMRI in distinguishing PD from controls PD & PSP show hypoactivity using BOLD measures PSC from task-based fMRI shows deterioration in motor cortex and putamen in PD over 1 year Dopaminergic modulation of resting-state connectivity predicted dyskinesias with spec 100% and sens 91% ALFF shows decreased activity in PD, deficit increases with H&Y stage Increased PSC in ET, correlates w/3–8 Hz force oscillations Reduced activation in motor control areas in MSAp and PD	Bowman et al. (2016) Burciu et al. (2015) Burciu et al. (2016) Herz et al. (2016) Luo et al. (2015) Neely et al. (2015) Planetta et al. Human Brain Mapping (2015)	[58] [59] [60] [61] [62] [63] [64]
Metabolic PET	15 66 47 70	Increased activity of PDRP over time; increased expression of PDCP over time; increased putamen metabolic activity; decreased precuneus metabolic activity Decreased prefrontal and parietal metabolism and increased brainstem/cerebellar metabolism in MD-MCI; increased PDCP expression with worsening cognitive impairment Correlation between PDCP and memory performance, visuospatial function and perceptual motor speed Correlation between MSA, PSP and abnormal pattern expression of regional metabolic activity	Tang et al. (2010) Huang et al. (2008) Huang et al. (2007) Eckert et al. (2008)	[65] [66] [67] [68]
Cholinergic PET	149 143 143 157	Decreased thalamic cholinergic innervation in PD FoG more common with diminished neocortical cholinergic innervation and increased neocortical β-amyloid deposition in PD Increased caudate nucleus dopaminergic denervation and cortical cholinergic denervation in PD with more severe cognitive impairments Significant slower gait speed in the low cholinergic PD subgroup	Muller et al. (2013) Bohnen et al. (2014) Bohnen et al. (2015) Bohnen et al. (2013)	[69] [70] [71] [72]
SWI MRI	68 161 210	R2* increased in SN of PD Loss of DNH in iRBD patients, similar to patients with PD 88.8% sensitive and 83.6% specific for identifying parkinsonism, concordance to DatScan 86.2%	Du et al. (2012) De Marzi et al. (2016) Bae et al. (2016)	[73] [74] [75]

Select candidate imaging markers were prioritized by the authors for inclusion in this table. This list is incomplete due to space limitations; it does not presume to represent the entire literature.

ALFF: Amplitude of low frequency fluctuation; APS: Atypical parkinsonian syndrome; BOLD: Blood oxygen level dependent; DaTScan: Dopamine transporting imaging using [¹²³I]β-CIT; dMRI: Diffusion magnetic resonance imaging; DNH: Dorsolateral hyperintensity; ET: Essential tremor; FA: Fractional anisotropy; FC: Functional connectivity; FoG: Freezing of gait; FW: Free water; iRBD: Idiopathic rapid eye movement behavior disorder; MD: Mean diffusivity; MRI: Magnetic resonance imaging; MSA: Multiple system atrophy; PD: Parkinson's disease; PDCP: PD cognitive pattern; PDRP: PD-related pattern; PSC: Percent signal change; PSP: Progressive supranuclear palsy; SN: Substantia nigra; SPECT: Single photon emission computed tomography; SWI: Susceptibility weighted imaging.