To meet the need for Parkinson's disease biomarkers and evidence for amount and distribution of pathological changes, MRI diffusion tensor imaging (DTI) has been explored in a number of previous studies. However, conflicting results warrant further investigations. As tissue microstructure, particularly of the grey matter, is heterogeneous, a more precise diffusion model may benefit tissue characterization. The purpose of this study was to analyze the diffusion-based imaging technique restriction spectrum imaging (RSI) and DTI, and their ability to detect microstructural changes within brain regions associated with motor function in Parkinson's disease. Diffusion weighted (DW) MR images of a total of 100 individuals, (46 Parkinson's disease patients and 54 healthy controls) were collected using b-values of 0-4000s/mm2. Output diffusion-based maps were estimated based on the RSI-model combining the full set of DW-images (Cellular Index (CI), Neurite Density (ND)) and DTI-model combining b = 0 and b = 1000 s/mm2 (fractional anisotropy (FA), Axial-, Mean- and Radial diffusivity (AD, MD, RD)). All parametric maps were analyzed in a voxel-wise group analysis, with focus on typical brain regions associated with Parkinson's disease pathology. CI, ND and DTI diffusivity metrics (AD, MD, RD) demonstrated the ability to differentiate between groups, with strongest performance within the thalamus, prone to pathology in Parkinson's disease. Our results indicate that RSI may improve the predictive power of diffusion-based MRI, and provide additional information when combined with the standard diffusivity measurements. In the absence of major atrophy, diffusion techniques may reveal microstructural pathology. Our results suggest that protocols for MRI diffusion imaging may be adapted to more sensitive detection of pathology at different sites of the central nervous system.

1st Department of Neurology Medical Faculty Masaryk University and St Anne's University Hospital Brno Czech Republic

Central European Institute of Technology CEITEC Masaryk University Brno Czech Republic

Deparment of Cognitive Sciences University of California San Diego San Diego La Jolla California United States of America

Deparment of Radiology University of California San Diego San Diego La Jolla California United States of America

Department of Neurology Akershus University Hospital Loerenskog Norway

Department of Neurosciences University of California San Diego La Jolla California United States of America

Department of Physics University of Oslo Oslo Norway

Diagnostic Physics Division of Radiology and Nuclear Medicine Oslo University Hospital Rikshospitalet Oslo Norway

Institute of Clinical Medicine Campus Ahus University of Oslo Oslo Norway

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Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery & Psychiatry. 1992;55(3):181–4. PubMed PMC

Dickson DW. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harbor perspectives in medicine. 2012;2(8):a009258 10.1101/cshperspect.a009258 PubMed DOI PMC

Patt S, Gertz H-J, Gerhard L, Cervos-Navarro J. Pathological changes in dendrites of substantia nigra neurons in Parkinson’s disease: a Golgi study. Histol Histopathol. 1991;6(3):373–80. PubMed

Braak H, Del Tredici K, Rüb U, De Vos RA, Steur ENJ, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of aging. 2003;24(2):197–211. PubMed

Kramer ML, Schulz-Schaeffer WJ. Presynaptic α-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. Journal of Neuroscience. 2007;27(6):1405–10. 10.1523/JNEUROSCI.4564-06.2007 PubMed DOI PMC

Schulz-Schaeffer WJ. The synaptic pathology of α-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta neuropathologica. 2010;120(2):131–43. 10.1007/s00401-010-0711-0 PubMed DOI PMC

Burton EJ, McKeith IG, Burn DJ, Williams ED, O’Brien JT. Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain. 2004;127(4):791–800. PubMed

Rektorova I, Biundo R, Marecek R, Weis L, Aarsland D, Antonini A. Grey matter changes in cognitively impaired Parkinson's disease patients. PloS one. 2014;9(1):e85595 10.1371/journal.pone.0085595 PubMed DOI PMC

Selnes P, Stav AL, Johansen KK, Bjørnerud A, Coello C, Auning E, et al. Impaired synaptic function is linked to cognition in Parkinson's disease. Annals of clinical and translational neurology. 2017;4(10):700–13. PubMed PMC

Boska MD, Hasan KM, Kibuule D, Banerjee R, McIntyre E, Nelson JA, et al. Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson’s disease. Neurobiology of disease. 2007;26(3):590–6. 10.1016/j.nbd.2007.02.010 PubMed DOI PMC

Chan L-L, Rumpel H, Yap K, Lee E, Loo H-V, Ho G-L, et al. Case control study of diffusion tensor imaging in Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry. 2007;78(12):1383–6. PubMed PMC

Du G, Lewis MM, Styner M, Shaffer ML, Sen S, Yang QX, et al. Combined R2* and diffusion tensor imaging changes in the substantia nigra in Parkinson's disease. Movement Disorders. 2011;26(9):1627–32. PubMed PMC

Péran P, Cherubini A, Assogna F, Piras F, Quattrocchi C, Peppe A, et al. Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain. 2010;133(11):3423–33. 10.1093/brain/awq212 PubMed DOI

Vaillancourt D, Spraker M, Prodoehl J, Abraham I, Corcos D, Zhou X, et al. High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology. 2009;72(16):1378–84. 10.1212/01.wnl.0000340982.01727.6e PubMed DOI PMC

Zhan W, Kang GA, Glass GA, Zhang Y, Shirley C, Millin R, et al. Regional alterations of brain microstructure in Parkinson's disease using diffusion tensor imaging. Movement disorders. 2012;27(1):90–7. PubMed PMC

Zhang G, Zhang Y, Zhang C, Wang Y, Ma G, Nie K, et al. Diffusion kurtosis imaging of substantia nigra is a sensitive method for early diagnosis and disease evaluation in Parkinson’s disease. Parkinson’s disease. 2015;2015. PubMed PMC

Prakash BD, Sitoh Y-Y, Tan LC, Au WL. Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson's disease. Parkinsonism & related disorders. 2012;18(9):1029–33. PubMed

Lenfeldt N, Larsson A, Nyberg L, Birgander R, Forsgren L. Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture. European journal of neurology. 2015;22(10):1408–14. PubMed

Van Camp N, Blockx I, Verhoye M, Casteels C, Coun F, Leemans A, et al. Diffusion tensor imaging in a rat model of Parkinson's disease after lesioning of the nigrostriatal tract. NMR in Biomedicine. 2009;22(7):697–706. PubMed

Wang J-J, Lin W-Y, Lu C-S, Weng Y-H, Ng S-H, Wang C-H, et al. Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology. 2011;261(1):210–7. 10.1148/radiol.11102277 PubMed DOI

Hikishima K, Ando K, Komaki Y, Kawai K, Yano R, Inoue T, et al. Voxel-based morphometry of the marmoset brain: In vivo detection of volume loss in the substantia nigra of the MPTP-treated Parkinson’s disease model. Neuroscience. 2015;300:585–92. 10.1016/j.neuroscience.2015.05.041 PubMed DOI

Menke RA, Jbabdi S, Miller KL, Matthews PM, Zarei M. Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson's disease. Neuroimage. 2010;52(4):1175–80. 10.1016/j.neuroimage.2010.05.086 PubMed DOI

Schuff N, Wu IW, Buckley S, Foster ED, Coffey CS, Gitelman DR, et al. Diffusion imaging of nigral alterations in early Parkinson's disease with dopaminergic deficits. Movement Disorders. 2015;30(14):1885–92. PubMed

Schwarz ST, Abaei M, Gontu V, Morgan PS, Bajaj N, Auer DP. Diffusion tensor imaging of nigral degeneration in Parkinson's disease: a region-of-interest and voxel-based study at 3T and systematic review with meta-analysis. NeuroImage: Clinical. 2013;3:481–8. PubMed PMC

Auning E, Kjærvik VK, Selnes P, Aarsland D, Haram A, Bjørnerud A, et al. White matter integrity and cognition in Parkinson’s disease: a cross-sectional study. BMJ open. 2014;4(1):e003976 10.1136/bmjopen-2013-003976 PubMed DOI PMC

Al-Radaideh AM, Rababah EM. The role of magnetic resonance imaging in the diagnosis of Parkinson's disease: a review. Clinical imaging. 2016;40(5):987–96. 10.1016/j.clinimag.2016.05.006 PubMed DOI

Modrego PJ, Fayed N, Artal J, Olmos S. Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease. Academic radiology. 2011;18(2):235–41. 10.1016/j.acra.2010.09.022 PubMed DOI

Planetta PJ, Schulze ET, Geary EK, Corcos DM, Goldman JG, Little DM, et al. Thalamic projection fiber integrity in de novo Parkinson disease. American Journal of Neuroradiology. 2013;34(1):74–9. 10.3174/ajnr.A3178 PubMed DOI PMC

Jensen JH, Helpern JA, Ramani A, Lu H, Kaczynski K. Diffusional kurtosis imaging: The quantification of non‐gaussian water diffusion by means of magnetic resonance imaging. Magnetic Resonance in Medicine. 2005;53(6):1432–40. PubMed

Khairnar A, Latta P, Drazanova E, Ruda-Kucerova J, Szabó N, Arab A, et al. Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of α-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study. Neurotoxicity research. 2015;28(4):281–9. 10.1007/s12640-015-9537-9 PubMed DOI

Khairnar A, Ruda-Kucerova J, Szabó N, Drazanova E, Arab A, Hutter-Paier B, et al. Early and progressive microstructural brain changes in mice overexpressing human α-Synuclein detected by diffusion kurtosis imaging. Brain, behavior, and immunity. 2017;61:197–208. 10.1016/j.bbi.2016.11.027 PubMed DOI

Khairnar A, Ruda‐Kucerova J, Drazanova E, Szabó N, Latta P, Arab A, et al. Late‐stage α‐synuclein accumulation in TNWT‐61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging. Journal of neurochemistry. 2016;136(6):1259–69. PubMed

White NS, Leergaard TB, D'Arceuil H, Bjaalie JG, Dale AM. Probing tissue microstructure with restriction spectrum imaging: Histological and theoretical validation. Hum Brain Mapp. 2013;34(2):327–46. PubMed PMC

Brunsing RL, Schenker‐Ahmed NM, White NS, Parsons JK, Kane C, Kuperman J, et al. Restriction spectrum imaging: an evolving imaging biomarker in prostate MRI. Journal of Magnetic Resonance Imaging. 2017;45(2):323–36. PubMed PMC

Carper RA, Treiber JM, White NS, Kohli JS, Müller R-A. Restriction spectrum imaging as a potential measure of cortical neurite density in autism. Frontiers in neuroscience. 2017;10:610 10.3389/fnins.2016.00610 PubMed DOI PMC

Sowa P, Harbo HF, White NS, Celius EG, Bartsch H, Berg-Hansen P, et al. Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis. Multiple Sclerosis Journal. 2018;0(0):1352458518765671. 10.1177/1352458518765671 PubMed DOI

Anderkova L, Barton M, Rektorova I. Striato‐cortical connections in Parkinson's and Alzheimer's diseases: Relation to cognition. Movement Disorders. 2017. PubMed

Anderkova L, Eliasova I, Marecek R, Janousova E, Rektorova I. Distinct pattern of gray matter atrophy in mild Alzheimer’s disease impacts on cognitive outcomes of noninvasive brain stimulation. Journal of Alzheimer's Disease. 2015;48(1):251–60. 10.3233/JAD-150067 PubMed DOI

Holland D, Kuperman JM, Dale AM. Efficient correction of inhomogeneous static magnetic field-induced distortion in Echo Planar Imaging. Neuroimage. 2010;50(1):175–83. 10.1016/j.neuroimage.2009.11.044. PubMed DOI PMC

Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23:S208–S19. 10.1016/j.neuroimage.2004.07.051 PubMed DOI

Behrens TE, Woolrich MW, Jenkinson M, Johansen‐Berg H, Nunes RG, Clare S, et al. Characterization and propagation of uncertainty in diffusion‐weighted MR imaging. Magnetic resonance in medicine. 2003;50(5):1077–88. PubMed

Andersson JL, Jenkinson M, Smith S. Non-linear registration, aka Spatial normalisation FMRIB technical report TR07JA2. FMRIB Analysis Group of the University of Oxford. 2007;2.

Douaud G, Smith S, Jenkinson M, Behrens T, Johansen-Berg H, Vickers J, et al. Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. Brain. 2007;130(9):2375–86. PubMed

Stav AL, Johansen KK, Auning E, Kalheim LF, Selnes P, Bjørnerud A, et al. Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinson's disease: a cross-sectional study. NPJ Parkinson's Disease. 2016;2:15030 10.1038/npjparkd.2015.30 PubMed DOI PMC

Lanskey JH, McColgan P, Schrag AE, Morris HR, Acosta-Cabronero J, Rees G, et al. Can neuroimaging predict dementia in Parkinson’s disease? Brain. 2018;141(9):2545–60. 10.1093/brain/awy211 PubMed DOI PMC

Syková E, Nicholson C. Diffusion in brain extracellular space. Physiol Rev 2008;88(4):1277–340. 10.1152/physrev.00027.2007 PubMed DOI PMC

Song S-K, Sun S-W, Ramsbottom MJ, Chang C, Russell J, Cross AH. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage. 2002;17(3):1429–36. PubMed

Aung WY, Mar S, Benzinger TL. Diffusion tensor MRI as a biomarker in axonal and myelin damage. Imaging in medicine. 2013;5(5):427–40. . PubMed PMC

Sexton CE, Kalu UG, Filippini N, Mackay CE, Ebmeier KP. A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease. Neurobiology of aging. 2011;32(12):2322.e5–.e18. PubMed

Assaf Y, Cohen Y. Non-mono-exponential attenuation of water andn-acetyl aspartate signals due to diffusion in brain tissue. Journal of Magnetic Resonance. 1998;131(1):69–85. 10.1006/jmre.1997.1313 PubMed DOI

Doorn KJ, Moors T, Drukarch B, van de Berg WD, Lucassen PJ, van Dam A-M. Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients. Acta neuropathologica communications. 2014;2(1):90 10.1186/s40478-014-0090-1 PubMed DOI PMC

Halliday GM. Thalamic changes in Parkinson's disease. Parkinsonism & Related Disorders. 2009;15:S152–S5. 10.1016/S1353-8020(09)70804-1. PubMed DOI

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension