Table 1.
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.