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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Curr Neurol Neurosci Rep. 2013 Nov;13(11):10.1007/s11910-013-0400-1. doi: 10.1007/s11910-013-0400-1

Table 1.

Summary of recent studies in parkinsonism using dMRI (2012–13)

Authors Hypothesis/Study Intent/Diseases of Interest dMRI Methods* N Regions Studied with dMRI Select dMRI Findings
dMRI in Parkinson’s disease (PD)
Zhan et al. 2012 [20] dMRI as a biomarker in PD; correlations with severity & subtype ROI, TBSS 12 PD
20 NC
Whole brain WM; ROI of cortical white matter, IC, EC, SN, PUT, AN. TBSS- ↓ FA in PD in pre/post central gyri, posterior striatum, frontal WM & projections to SMA, IC, EC, PUT, TH, SN; ROI – confirmed most VBA differences in FA, no differences in MD after correction; SN FA negatively correlated with ↑ UPDRS; spatial correlations b/w sub-regions demonstrated.
Prakash et al. 2012 [84] Investigated asymmetry of SN FA in early PD ROI 11 PD
12 NC
Caudal, middle, & rostral SN No difference in FA & MD b/w PD & NC; asymmetric FA & MD in the rostral SN in both PD & NC; UPDRS positively correlated with FA in L rostral SN.
Planetta et al. 2013 [85] Analysis of specific thalamic tracts in early PD ROI 20 PD
20 NC
6 sub-regions in the TH ↓ FA in WM tracks from the AN, VA, DM; UPDRS negatively correlated with FA in the AN.
dMRI in genetic PD
Agosta et al. 2013 [86] Compared dMRI measures in PD & GBA mutation carriers with PD TBSS, ROI (VBM) 14 PD
15 GBA
16 HC
Whole brain WM, ROI No differences in voxel-wise dMRI between GBA-PD & PD; post-hoc ROI showed ↓ FA in CC, olfactory tracts, cingulum, ECs, L anterior IC; FA in the CC, EC, & olfactory tracts correlated with verbal fluency in patients.
dMRI in PD - Combining neuroimaging methods
Du et al. 2012 [17] Combined dMRI/R2* study of the SN ROI 40 PD
28 NC
6 rostral>caudal SN sub-regions (3 rostral & 3 caudal) ↓ FA in PD SN caudal (early) > rostral (late); ↑ RD in caudal SN in PD; ↑ R2* in rostral & caudal SN in PD; no correlations b/w FA & UPDRS or disease duration; caudal R2* correlated with UPDRS, disease duration, & LEDD.
Sharman et al. 2013 [87] Combined dMRI/resting state fMRI ROI, tractography 36 PD
45 NC
3 cortical & 5 sub-cortical; tractography from these connections. ↓ probability of connectivity in PD in SMC-PUT, SMC-TH, GP-TH, SN-TH; ↓ functional connectivity in GP-PUT, GP-TH, SMC-TH, SN-GP; ↑ functional connectivity in associative-PUT, limbic-TH, PUT-TH. No correlation with UPDRS, disease duration, or H&Y. dMRI & fMRI decreased connectivity overlapped in PD in TH to SMC, GP, & SN.
dMRI in PD – non-motor and specific symptoms
Carlesimo et al. 2012 [88] Multi-modal (dMRI/VBM) examining cognitive performance & MRI ROI & VBA (VBM) 25 PD
25 HC
Hippocampus MD ↑ MD in PD in the hippocampus; ↑ hippocampal MD associated with reduced memory performance in PD patients.
Rae et al. 2012 [89] Compared different two methodologies in the study of cognitive measures TBSS, VBA 14 PD
15 HC
Whole brain WM TBSS - ↓ FA & ↑ MD throughout cerebral WM; ↓ FA in R splenium of CC correlated with UPDRS score; ↓ FA & ↑ MD in anterior CC & prefrontal WM correlated with cognitive scores. VBA – similar WM pattern differences only at more liberal significance threshold.
Deng et al. 2013 [90] dMRI analysis of WM abnormalities & cognitive impairment in PD, PD-MCI, PD-D ROI 64 PD
21 NC
Cortical WM, cingulate bundles, CC, midbrain CST, IC CST, SLF ↓ FA in L frontal, R temporal, bilateral anterior cingulate bundles in PD-MCI & PD-D vs. NC; ↓ FA in the L occipital & L anterior cingulate bundle in cognitively normal PD vs. NC; ↓ FA in the L anterior cingulate bundle in PD-D vs. other groups & in the L occipital WM vs. cognitively normal PD; Some WM abnormalities correlated with cognitive dysfunction; no differences in FA in the CST in any group vs. NC.
Surdhar et al. 2012 [91] Examined dMRI measures in PD +/− depression & NC Tractography (volumetric) 6 PD
6 PD-dep
6NC
CC & bilateral uncinate fasciculus No dMRI differences b/w groups (smaller amygdala volumes in PD-dep vs. NC).
Zheng et al. 2013 [21] Evaluated retrospectively the relationship b/w dMRI measures & cognitive performance ROI, VBA 16 PD 40 ROI encompassing most of cortical & subcortical WM Cognitive performance in distinct domains correlated with dMRI in different areas; dMRI measures correlated with: executive function & language mostly in the frontal WM tracts; attention diffusely in WM; memory in fornix & anterior cingulate; no correlation was found b/w dMRI measures & visuospatial performance. Post-hoc VBA confirmed most correlations.
Gallagher et al. 2013 [92] Investigated relationship b/w dMRI & cognition (especially executive function) TBSS 15 PD
15 NC
Frontal subcortical WM ↓ FA in PD vs. NC in portions of the anterior limb of IC & anterior CR, body of CC, inferior ILF & inferior fronto-occipital fasciculus, uncinate fasciculus, deep cerebellar WM. ↑ MD in PD patients present in portions of most tracts. FA correlated with executive function in PD but not NC. Both ↓ FA & ↑ MD correlated with increased susceptibility to interference in Stroop task.
Kamagata et al. 2013 [93] Examined the relationship b/w dMRI measures & cognitive performance TBSS/tractography 20 PD
20 PD-D
20 NC
Whole brain WM/genu of CC No difference b/w PD & NC in FA & MD; ↓ FA & ↑ MD in major WM tracts of PD-D vs. NC; ↓ FA & ↑ MD in WM adjacent to prefrontal area & genu of CC in PD-D vs. PD; FA correlated with MMSE in combined but not separate PD groups; no correlation b/w dMRI & disease duration, H&Y, or levodopa dose.
Ford et al. 2013 [94] Evaluated dMRI measures in PD +/− RBD by questionnaire TBSS (VBM) 124 PD Whole brain WM No difference in FA or MD when adjusted for multiple comparisons based on presence of RBD
dMRI in the differential diagnosis of parkinsonian syndromes
Tsukamoto et al. 2012 [95] MSA-C&P, PSP, PD, NC (retrospective) ROI 5 MSA-P
20 MSA-C
20 PSP
17 PD
18 NC
CN, TH, PUT, GP, midbrain, pons, SCP, MCP, DEN, cerebellar WM In MSA: ↑ MD in the pons, MCP, cerebellar WM, & DEN vs. to PSP, PD, NC; ↑ MD in the posterior PUT vs. PSP, NC. MD in MSA-P > MSA-C in PUT, GP, CN; MD in MSA-C > MSA-P in pons, MCP, cerebellar WM. In PSP: ↑ MD in GP & midbrain vs. MSA, PD, NC; ↑ MD in CN & SCP vs. MSA & NC. In PD: no difference in any region vs. NC
Agosta et al. 2012 [96] PSP-RS, PSP-P, NC (retrospective) TBSS, ROI, (VBM) 21 PSP-RS
16 PSP-P
42 NC
Whole brain WM (TBSS), infra- & supra-tentorial WM, TH (ROI) No corrected difference b/w PSP-P & PSP-RS.
Haller et al. 2012 [97] PD & AP (Retrospective) TBSS 17 PD
23 AP
Whole brain WM ↑FA & ↓RD & MD in multiple brain areas (especially R frontal WM) on TBSS; correctly classified PD & AP up to 97%.
Prodoehl et al. [19] PD, MSA-P, PSP, ET, NC ROI 15 PD
14 MSA-P
12 PSP
14 ET
17 NC
CN, PUT, GP, SN, RN, SCP, MCP, ICP, DN AUC & sensitivity/specificity in distinguishing: PD vs. AP - 0.99 (sensitivity = 90%; specificity = 100%); PD vs. ET - 0.96 (sensitivity = 92%; specificity = 87%); PD vs. MSA-P – 0.99 (sensitivity = 94%; specificity = 100%); PD vs. PSP - 0.96 (sensitivity = 87%; specificity = 100%); PSP vs. MSA-P - 0.97 (sensitivity = 90%; specificity = 100%)
Nair et al. 2013 [98] Decision tree analysis using conventional/volumetric & dMRI in PD & MSA ROI, (volumetric) 26 PD
13 MSA
PUT, SN, pons, MCP, CBM Significant dMRI measures (included in decision tree): rostral SN compacta FA, MCP FA, cerebellar FA, MCP MD. Decision tree diagnostic accuracy: Sensitivity 92 %; specificity 96 %; PPV 0.92; NPV 0.96.
dMRI in Progressive supranuclear palsy (PSP)
Whitwell et al. 2012 [99] Examined the association b/w clinical scale & MRI ROI, (linear & volumetric) 22 PSP SCP SCP FA correlated with clinical scores; No correlations between rates of change in dMRI measures & clinical scores
Saini et al. 2012 [100] Evaluated dMRI measures in PSP-RS & PSP-P TBSS (VBM) 13 PSP-RS
11 PSP-P
26 NC
Whole brain WM ↓ FA, ↑ MD, ↑ AD, & ↑ RD in various WM areas in PSP vs. NC; ↓ FA in bilateral frontal WM & CC in PSP-RS vs. PSP-P; ↓ AD in R frontal region in PSP-RS vs. PSP-P. No correlation between dMRI & UPDRS.
dMRI in Multiple system atrophy (MSA)
Lu et al. 2013 [101] Combined Network analysis & dMRI in MSA-C Tractography 19 MSA-C
19 NC
Whole brain fiber tracking Small-world architecture/network strength/efficiency (more pronounced in cerebellar vs. cerebral network) was reduced in WM networks of MSA-C vs. controls, with abnormalities correlating with clinical scores.
dMRI in other parkinsonian syndromes
Wang et al. 2012 [102] Investigated dMRI measures in VP Global analysis, VBA, tractography 12 VP
12 NC
Whole brain WM Global ↓ FA & ↑ MD in VP vs. NC; ↓ FA on VBA in L TH, R frontal subcortical WM, L anterior IC vs. NC; ↑ MD on VBA in frontal subcortical WM in VP vs. NC; FA & MD in regions above correlated with PIGD clinical scores in VP patients; FA in fiber tracts in anterior IC negatively correlated with PIGD clinical scores; MD in fiber tracts in anterior CC correlated with PIGD clinical scores.
*

( ) indicate non-dMRI methods.

AD = axial diffusivity; AL = ansa lenticularis; AN = anterior nucleus; AP = atypical parkinsonism; BG = basal ganglia; b/w = between; CBT = corticobulbar tract; CC = corpus callosum; CMB = cerebellum; CN = caudate nucleus; CR = corona radiata; CST = corticospinal tract; DaT = brain 123I ioflupane SPECT (DaTSCAN); DM = dorsomedial nucleus; DEN = cerebellar dentate nucleus; Dys = dystonia; EC= external capsule; ET = essential tremor; FA = fractional anisotropy; FCMTE = familial cortical myoclonic tremor with epilepsy; fMRI = functional magnetic resonance imaging; GP = globus pallidus; HARDI = High-angular resolution diffusion-weighted imaging; HD = Huntington’s disease; H&Y = Hohn & Yahr scale score; IC= internal capsule; ICP = inferior cerebellar peduncle; ILF = inferior longitudinal fasciculus; L = left; LEDD = levodopa-equivalent daily dose; MCP = Middle cerebellar peduncle; MD = mean diffusivity (ADC); M-D = myoclonus dystonia; MIBG = 123I-metaiodobenzylguanidine; MMSE = Mini-mental status exam; MRPI = magnetic resonance parkinsonism index; MSA = Multiple system atrophy; MSA-C = Multiple system atrophy - cerebellar subtype; MSA-P = Multiple system atrophy - parkinsonism subtype; NC = normal control; PC-HD – pre-clinical Huntington’s disease; PD-D = Parkinson’s disease with dementia; PD-dep = Parkinson’s disease with depression; PD-MCI = Parkinson’s disease with mild cognitive impairment; PIGD = modified postural instability gait difficulty subscore of UPDRS; PPN = pedunculopontine nucleus; PSP = Progressive supranuclear palsy; PSP-P = Progressive supranuclear palsy - parkinsonism subtype; PSP-RS = Progressive supranuclear palsy - Richardson syndrome subtype; PU = pulvinar; PUT= putamen; Q-BI = Q-ball imaging; Quin = rats infused with quinolinic acid; R = right; R2* = 1/T2* relaxation rate; RBD = REM sleep behavior disorder; RD = radial diffusivity; RN = red nucleus; ROI = region of interest; SCP = Superior cerebellar peduncle; SLF = superior longitudinal fasciculus; SMC = sensorimotor cortex; SN= substantial nigra; TBSS = tract-based spatial statistics; TH = Thalamus; UPDRS = Unified Parkinson’s Disease Rating Scale; VA = ventral anterior nucleus; VBA = voxel-based analysis; VBM = voxel-based morphometry; VL = ventral lateral nucleus; VP = vascular parkinsonism; VPL = ventral posterior lateral nucleus; VPM = ventral posterior medial nucleus; WM= white matter.