Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study

Ofori, Edward; Krismer, Florian; Burciu, Roxana G.; Pasternak, Ofer; McCracken, Johanna; Lewis, Mechelle M.; Du, Guangwei; McFarland, Nikolaus R.; Okun, Michael S.; Poewe, Werner; Mueller, Christoph; Gizewski, Elke R.; Schocke, Michael; Kremser, Christian; Li, Hong; Huang, Xuemei; Seppi, Klaus; Vaillancourt, David E.

doi:10.1002/mds.27100

Cited by 69 publications

(69 citation statements)

References 42 publications

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“…However, the separate categorization performances of the FA decrease and MD increase in these structures were low. In future studies, it would be interesting to more specifically investigate changes in the internal and external segments of the globus pallidus and subregions of the putamen and calculate other promising metrics, such as diffusion‐based free water, that have proven to be more effective than the DTI metrics in the SN . Although pathologically the STN was previously shown to be one of the most affected structures in PSP, no structural changes or Lewy pathologies have been reported in the STN .…”

Section: Discussionmentioning

confidence: 99%

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

et al. 2019

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Background Progressive supranuclear palsy (PSP) is a neurodegenerative clinically heterogeneous disorder, formal diagnosis being based on postmortem histological brain examination. Objective We aimed to perform a precise in vivo staging of neurodegeneration in PSP using quantitative multimodal MRI. The ability of MRI biomarkers to differentiate PSP from PD was also evaluated. Methods Eleven PSP patients were compared to 26 age‐matched healthy controls and 51 PD patients. Images were acquired at 3 Tesla (three‐dimensional T1‐weighted, diffusion tensor, and neuromelanin‐sensitive images) and 7 Tesla (three‐dimensional‐T2* images). Regions of interest included the cortical areas, hippocampus, amygdala, basal ganglia, basal forebrain, brainstem nuclei, dentate nucleus, and cerebellum. Volumes, mean diffusivity, and fractional anisotropy were measured. In each region, a threshold value for group categorization was calculated, and four grades of change (0–3) were determined. Results PSP patients showed extensive volume decreases and diffusion changes in the midbrain, SN, STN, globus pallidus, basal forebrain, locus coeruleus, pedunculopontine nucleus, and dentate nucleus, in close agreement with the degrees of impairment in histological analyses. The predictive factors for the separation of PSP and healthy controls were, in descending order, the neuromelanin‐based SN volume; midbrain fractional anisotropy; volumes of the midbrain, globus pallidus, and putamen; and fractional anisotropy in the locus coeruleus. The best predictors for separating PSP from PD were the neuromelanin‐based volume in the SN, fractional anisotropy in the pons, volumes of the midbrain and globus pallidus, and fractional anisotropy in the basal forebrain. Conclusions These results suggest that it is possible to evaluate brain neurodegeneration in PSP noninvasively, even in small brainstem nuclei, in close agreement with previously published histological data. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 99%

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

et al. 2019

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“…Interestingly, a prospective study showed progressive abnormalities of the diffusivity of the putamen over time, thus allowing the possibility of using DWI imaging as a marker of disease progression and an outcome measure in clinical trials for MSA (Pellecchia et al, 2011). Diffusion tensor imaging (DTI), a similar technique to DWI which analyzes the three-dimensional shape of the diffusion and produces 3-D neural tract images (Huisman, 2010), is being increasingly used to distinguish MSA from PD and PSP (Du et al, 2017; Ofori et al, 2017; Planetta et al, 2016; Prodoehl et al, 2013; Worker et al, 2014). …”

Section: Brain and Cardiac Neuroimagingmentioning

confidence: 99%

Diagnosis of multiple system atrophy

Palma

Norcliffe‐Kaufmann

Kaufmann

2018

Autonomic Neuroscience

126

114

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Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs.

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“…In comparison, conventional single‐tensor diffusion imaging outcomes, such as fractional anisotropy, model the combined effects of multiple microstructures within a voxel. Prior work has compared a single‐tensor diffusion approach to the two‐compartment free‐water (FW) analysis model, and the two‐compartment model had increased effect sizes for the substantia nigra (Ofori et al, ). The NODDI model has not yet been implemented to compare between different subtypes of Parkinsonism.…”

Section: Introductionmentioning

confidence: 99%

“…All three present with similar motor symptoms in early stages and have nigrostriatal degeneration (Dickson, ). However, MSAp and PSP have more widespread pathological changes characterized by distinct gray and white matter neurodegeneration throughout the basal ganglia, midbrain, thalamus, cerebellum, and corpus callosum (Ahmed, Josephs, Gonzalez, DelleDonne, & Dickson, ; Cykowski et al, ; Halliday, Macdonald, & Henderson, ; Ofori et al, ; Planetta et al, ; Salvesen et al, ; Tsuboi et al, ; Wenning, Tison, Ben Shlomo, Daniel, & Quinn, ). Moreover, differential diagnosis of these syndromes has important implications for good prognosis and selection for inclusion in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Neurite orientation dispersion and density imaging (NODDI) and free‐water imaging in Parkinsonism

Mitchell

Archer

Chu

et al. 2019

Human Brain Mapping

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Neurite orientation dispersion and density imaging (NODDI) uses a three‐compartment model to probe brain tissue microstructure, whereas free‐water (FW) imaging models two‐compartments. It is unknown if NODDI detects more disease‐specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi‐ and single‐shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi‐shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single‐shell; FW; free‐water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.

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Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study

Cited by 69 publications

References 42 publications

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy

Diagnosis of multiple system atrophy

Neurite orientation dispersion and density imaging (NODDI) and free‐water imaging in Parkinsonism

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