Table.

Neuroimaging Biomarkers of Disease State and Parkinson Disease (PD) Progression

Imaging modality	Disease-state biomarker	Progression biomarker	Clinical application and potential limitations
T1-weighted structural MRI	Potential disease-state biomarker in preclinical, prodromal, early-stage, and moderate to late-stage PD	Potential progression biomarker in early-stage and moderate to late-stage PD (detected >18 mo)	PD-specific progression effects require long follow-up periods
Dopaminergic PET/SPECT	Potential disease-state marker in preclinical and prodromal PD, and established disease-state marker in early-stage and moderate to late-stage PD	Potential progression biomarker in preclinical and prodromal PD, and established marker in early-stage PD (<2 y postdiagnosis; detected over 1 y)	SPECT imaging has limited spatial resolution, and there are significant treatment effects of various drugs for dopaminergic PET/SPECT. There is a poor relationship between change in DA imaging and change in clinical outcome. Does not differentiate other parkinsonian syndromes.
Nondopaminergic PET	Potential disease-state biomarker in preclinical, prodromal, early-stage, and moderate to late-stage PD	NA	Still limited in clinical application for tracking progression and differentiating atypical parkinsonisms
Metabolic and network imaging	Established disease-state biomarker in preclinical, prodromal, early-stage, and moderate to late-stage PD	Potential progression biomarker in preclinical, prodromal, and early-stage PD, and established progression marker in moderate to late-stage PD (detected over 2 y)	Significant acute treatment effects with levodopa and dopamine agonists as well as other therapies, such as deep brain stimulation
Iron-sensitive MRI	Potential disease-state biomarker in preclinical, prodromal, and early-stage PD, and established marker in moderate to late-stage PD	Potential progression biomarker in moderate to late-stage PD (detected >18 mo)	Still unclear if useful in differentiating atypical parkinsonisms
Free-water imaging	Potential disease-state marker in preclinical and prodromal PD, and established marker in early-stage and moderate to late-stage PD	Established progression biomarker in early-stage PD (detected over 1 y), and potential progression in moderate to late-stage PD	Newer automated methods make these advanced analyses feasible for clinical application
Neuromelanin-sensitive MRI	Potential disease-state marker in preclinical and prodromal PD, and established marker in early-stage and moderate to late-stage PD	Potential progression biomarker in early-stage and moderate PD (detected over 2 y)	Only moderately distinguishes atypical parkinsonisms

Abbreviations: DA, dopaminergic; MRI, magnetic resonance imaging; NA, not applicable; PET, positron emission tomography; SPECT, single photon emission computed tomography.