Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson's disease

Rolheiser, Tyler; Fulton, Heather G.; Good, Kimberley P.; Fisk, John D.; McKelvey, J. Roger; Scherfler, Christoph; Khan, Naeem; Leslie, R.A.; Robertson, Harold A.

doi:10.1007/s00415-011-5915-2

Cited by 123 publications

(96 citation statements)

References 23 publications

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“…There is evidence suggesting that neurodegenerative changes occur outside the SN. When combined with olfactory testing, one study 22 found reduced FA of the anterior olfactory structures in patients with PD vs controls, and another study 18 found that patients with PD and anosmia have reduced FA in white matter near the gyrus rectus compared with controls (or patients with PD) with no olfactory dysfunction. Five studies found reductions in the frontal white matter, 4 significant.…”

Section: Resultsmentioning

confidence: 99%

Diffusion tensor imaging in parkinsonian syndromes

2013

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Objectives: We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker. Methods:We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis. Results:Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (20.639, 95% confidence interval 20.860 to 20.417, p , 0.0001).Conclusion: DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers. Differences in natural history and therapy options make early and accurate diagnosis of parkinsonian syndromes important. 1 Emission tomography (SPECT or PET) has a role but it can be expensive, with limited availability, and requires radioactive tracers. 2 There is particular interest in the potential of advanced structural MRI techniques to differentiate among parkinsonian syndromes and to offer candidate biomarkers, facilitating early or premanifest diagnosis and monitoring of disease progression.Diffusion tensor imaging (DTI) is an MRI technique assessing the orientation and integrity of white matter tracts in vivo by measuring the diffusion of water molecules in neural fibers 3 and it also shows promise for studying gray matter areas. It estimates both the degree of directionality using anisotropy (frequently fractional anisotropy [FA]) and the overall movement of molecules (mean diffusivity [MD]; trace; apparent diffusion coefficient [ADC]). These measurements can either be extracted locally in predefined regions using region of interest (ROI) analysis or tractography or, alternatively, globally using voxel-based analysis (VBA) or tract-based spatial statistics (TBSS). Disruptions to microstructural tissue integrity, such as those found in the neurodegeneration of parkinsonian syndromes can be associated with alterations in anisotropy and diffusivity measures. 3 We therefore performed a systematic review of the literature to assess

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Section: Resultsmentioning

confidence: 99%

Diffusion tensor imaging in parkinsonian syndromes

2013

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“…One recent DTI study has demonstrated a decrease in FA also in the anterior olfactory system at an early stage of PD (Rolheiser et al 2011). Of note, two meta-analyses on DTI in PD patients have been published, one claiming that DTI is promising biomarker in Parkinsonian syndromes (Cochrane and Ebmeier 2013) while the other was actually questioning stability and validity of nigral FA changes (Schwarz et al 2013).…”

Section: Introductionmentioning

confidence: 98%

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

et al. 2015

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Evidence suggests that accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between α-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of α-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.

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“…TBSS-based analysis of FA values in central olfactory areas in Parkinson patients confirmed abnormal structural integrity [36]. A recent study found decreased FA values in the anterior central olfactory structures in Parkinson's disease [37]. The same study found Parkinson patients to have a significantly decreased identification function measured with the UPSIT (University of Pennsylvania Smell Identification) test.…”

Section: Discussionmentioning

confidence: 84%