Longitudinal changes of cortical microstructure in Parkinson's disease assessed with T1 relaxometry

Background Histological evidence suggests that pathology in Parkinson's disease (PD) goes beyond nigrostriatal degeneration and also affects the cerebral cortex. Quantitative MRI (qMRI) techniques allow the assessment of changes in brain tissue composition. However, the development and pattern of disease-related cortical changes have not yet been demonstrated in PD with qMRI methods. The aim of this study was to investigate longitudinal cortical microstructural changes in PD with quantitative T1 relaxometry. Methods 13 patients with mild to moderate PD and 20 matched healthy subjects underwent high resolution T1 mapping at two time points with an interval of 6.4 years (healthy subjects: 6.5 years). Data from two healthy subjects had to be excluded due to MRI artifacts. Surface-based analysis of cortical T1 values was performed with the FreeSurfer toolbox. Results In PD patients, a widespread decrease of cortical T1 was detected during follow-up which affected large parts of the temporo-parietal and occipital cortices and also frontal areas. In contrast, age-related T1 decrease in the healthy control group was much less pronounced and only found in lateral frontal, parietal and temporal areas. Average cortical T1 values did not differ between the groups at baseline (p = 0.17), but were reduced in patients at follow-up (p = 0.0004). Annualized relative changes of cortical T1 were higher in patients vs. healthy subjects (patients: − 0.72 ± 0.64%/year; healthy subjects: − 0.17 ± 0.41%/year, p = 0.007). Conclusions In patients with PD, the development of widespread changes in cortical microstructure was observed as reflected by a reduction of cortical T1. The pattern of T1 decrease in PD patients exceeded the normal T1 decrease as found in physiological aging and showed considerable overlap with the pattern of cortical thinning demonstrated in previous PD studies. Therefore, cortical T1 might be a promising additional imaging marker for future longitudinal PD studies. The biological mechanisms underlying cortical T1 reductions remain to be further elucidated.

[1]  C. Marsden,et al.  Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia , 1992 .

[2]  G. Halliday,et al.  A comparison of degeneration in motor thalamus and cortex between progressive supranuclear palsy and Parkinson's disease. , 2005, Brain : a journal of neurology.

[3]  Janna H. Neltner,et al.  Is synaptic loss a unique hallmark of Alzheimer's disease? , 2014, Biochemical pharmacology.

[4]  Magnetic resonance relaxometry in Parkinson's disease , 2002, Neurological Sciences.

[5]  R. Deichmann,et al.  Evaluation of brain ageing: a quantitative longitudinal MRI study over 7 years , 2017, European Radiology.

[6]  K. Beyreuther,et al.  Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. , 1993, Dementia.

[7]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[8]  S. Atlas,et al.  Spontaneous remission of a third‐nerve palsy in meningeal lymphoma , 1992, Annals of neurology.

[9]  G. Levy,et al.  The relationship of Parkinson disease with aging. , 2007, Archives of neurology.

[10]  J. Bonny,et al.  Is R2* a New MRI Biomarker for the Progression of Parkinson’s Disease? A Longitudinal Follow-Up , 2013, PloS one.

[11]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[12]  B. Hyman,et al.  Preservation of Neuronal Number Despite Age-Related Cortical Brain Atrophy in Elderly Subjects Without Alzheimer Disease , 2008, Journal of neuropathology and experimental neurology.

[13]  K. Jellinger The morphological basis of mental dysfunction in Parkinson's disease , 2006, Journal of the Neurological Sciences.

[14]  P N Karnauchow,et al.  Accuracy of clinical diagnosis. , 1982, Canadian Medical Association journal.

[15]  R. Ordidge,et al.  Increased iron‐related MRI contrast in the substantia nigra in Parkinson's disease , 1995, Neurology.

[16]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[17]  Rohit Bakshi,et al.  Iron in chronic brain disorders: Imaging and neurotherapeutic implications , 2007, Neurotherapeutics.

[18]  Nadim Joni Shah,et al.  Fully-automated detection of cerebral water content changes: Study of age- and gender-related H2O patterns with quantitative MRI , 2006, NeuroImage.

[19]  I. Ferrer,et al.  Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease , 2011, Journal of Neural Transmission.

[20]  S. Aoki,et al.  Magnetic resonance , 2012, International Journal of Computer Assisted Radiology and Surgery.

[21]  B. Hallgren,et al.  THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN , 1958, Journal of neurochemistry.

[22]  Alexander Hammers,et al.  In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease , 2006, Neurobiology of Disease.

[23]  John F Schenck,et al.  Magnetic resonance imaging of brain iron , 2003, Journal of the Neurological Sciences.

[24]  Patrick R Hof,et al.  Changes in the structural complexity of the aged brain , 2007, Aging cell.

[25]  Vasily L Yarnykh,et al.  Actual flip‐angle imaging in the pulsed steady state: A method for rapid three‐dimensional mapping of the transmitted radiofrequency field , 2007, Magnetic resonance in medicine.

[26]  Brian A. Nosek,et al.  Power failure: why small sample size undermines the reliability of neuroscience , 2013, Nature Reviews Neuroscience.

[27]  K. Jellinger,et al.  Formation and development of Lewy pathology: a critical update , 2009, Journal of Neurology.

[28]  G. Halliday,et al.  Neuropathology of α‐synuclein propagation and braak hypothesis , 2016, Movement disorders : official journal of the Movement Disorder Society.

[29]  J. Trojanowski,et al.  Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies , 2013, Nature Reviews Neuroscience.

[30]  R A Brooks,et al.  Relaxometry and magnetometry of ferritin , 1998, Magnetic resonance in medicine.

[31]  T. Peters,et al.  High‐resolution T1 and T2 mapping of the brain in a clinically acceptable time with DESPOT1 and DESPOT2 , 2005, Magnetic resonance in medicine.

[32]  C D Marsden,et al.  Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. , 1991, Brain : a journal of neurology.

[33]  N. Toschi,et al.  Progression of brain atrophy in the early stages of Parkinson's disease: A longitudinal tensor‐based morphometry study in de novo patients without cognitive impairment , 2014, Human brain mapping.

[34]  C. Olanow,et al.  The pathogenesis of cell death in Parkinson's disease , 2006, Neurology.

[35]  O. Hornykiewicz,et al.  The discovery of dopamine deficiency in the parkinsonian brain. , 2006, Journal of neural transmission. Supplementum.

[36]  Guy B. Williams,et al.  Baseline and longitudinal grey matter changes in newly diagnosed Parkinson’s disease: ICICLE-PD study , 2015, Brain : a journal of neurology.

[37]  O. Kano,et al.  Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease , 2013, Neurology.

[38]  Mojtaba Zarei,et al.  Cortical thinning is associated with disease stages and dementia in Parkinson's disease , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[39]  Marguerite Wieler,et al.  Midbrain iron content in early Parkinson disease , 2008, Neurology.

[40]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[41]  Martin Styner,et al.  Combined R2* and Diffusion Tensor Imaging Changes in the Substantia Nigra in Parkinson's Disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[42]  R. Barker,et al.  Mild cognitive impairment and Parkinson's disease--something to remember. , 2015, Journal of Parkinson's disease.

[43]  Paul M. Matthews,et al.  Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson's disease , 2010, NeuroImage.

[44]  B. Pakkenberg,et al.  Aging and the human neocortex , 2003, Experimental Gerontology.

[45]  C. Olanow,et al.  The pathogenesis of cell death in Parkinson's disease – 2007 , 2007, Movement disorders : official journal of the Movement Disorder Society.

[46]  K. Uğurbil,et al.  Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo , 2007, Magnetic resonance in medicine.

[47]  M. Maier Quantitative MRI of the brain—measuring changes caused by disease , 2004 .

[48]  E. Tolosa,et al.  Progression of cortical thinning in early Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[49]  P P Fatouros,et al.  In Vivo Brain Water Determination by T1 Measurements: Effect of Total Water Content, Hydration Fraction, and Field Strength , 1991, Magnetic resonance in medicine.

[50]  J. Connor,et al.  Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions , 1995, Journal of neurochemistry.

[51]  D Wang,et al.  Longitudinal Study of Gray Matter Changes in Parkinson Disease , 2015, American Journal of Neuroradiology.

[52]  O. Monchi,et al.  Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson's disease longitudinally. , 2014, Brain : a journal of neurology.

[53]  F. Valldeoriola,et al.  Patterns of cortical thinning in nondemented Parkinson's disease patients , 2016, Movement disorders : official journal of the Movement Disorder Society.

[54]  Bruce Fischl,et al.  Within-subject template estimation for unbiased longitudinal image analysis , 2012, NeuroImage.

[55]  Takashi Kato,et al.  Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing , 2003, Journal of neurology, neurosurgery, and psychiatry.

[56]  D E Kuhl,et al.  Motor correlates of occipital glucose hypometabolism in Parkinson’s disease without dementia , 1999, Neurology.

[57]  Sean C L Deoni,et al.  Quantitative Relaxometry of the Brain , 2010, Topics in magnetic resonance imaging : TMRI.

[58]  C. Marsden,et al.  Increased Nigral Iron Content and Alterations in Other Metal Ions Occurring in Brain in Parkinson's Disease , 1989, Journal of neurochemistry.

[59]  John F. Schenck,et al.  Imaging of brain iron by magnetic resonance: T2 relaxation at different field strengths , 1995, Journal of the Neurological Sciences.

[60]  Isidre Ferrer,et al.  Early involvement of the cerebral cortex in Parkinson's disease: Convergence of multiple metabolic defects , 2009, Progress in Neurobiology.

[61]  Ralf Deichmann,et al.  Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson's disease , 2010, NeuroImage.

[62]  Peng Lei,et al.  A delicate balance: Iron metabolism and diseases of the brain , 2013, Front. Aging Neurosci..

[63]  A. Jackson Quantitative MRI of the brain: measuring changes caused by disease. By P Tofts, pp. xvi+633, 2003 (John Wiley & Sons Ltd, Chichester, UK) £175.00 ISBN 0-470-84721-2 , 2005 .

[64]  G. Chiro,et al.  T1 and t2 of ferritin at different field strengths: effect on mri , 1992, Magnetic resonance in medicine.

[65]  Vladimir N Uversky,et al.  Biophysics of Parkinson's disease: structure and aggregation of alpha-synuclein. , 2009, Current protein & peptide science.

[66]  Vladimir V. Frolkis,et al.  Neurobiology of Aging , 2019, Psychobiology of Behaviour.

[67]  M. Styner,et al.  Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds” , 2016, Neurology.

[68]  P. Mcgeer,et al.  Glial reactions in Parkinson's disease , 2008, Movement disorders : official journal of the Movement Disorder Society.

[69]  G. Halliday,et al.  Selective loss of pyramidal neurons in the pre‐supplementary motor cortex in Parkinson's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[70]  C. Marsden,et al.  Decreased Ferritin Levels in Brain in Parkinson's Disease , 1990, Journal of neurochemistry.

[71]  Karl J. Friston Ten ironic rules for non-statistical reviewers , 2012, NeuroImage.

[72]  N. Gelman,et al.  Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: Relation to estimated iron and water contents , 2001, Magnetic resonance in medicine.

[73]  R. Deichmann,et al.  Influence of RF spoiling on the stability and accuracy of T1 mapping based on spoiled FLASH with varying flip angles , 2009, Magnetic resonance in medicine.

[74]  Stephen M. Smith,et al.  A Bayesian model of shape and appearance for subcortical brain segmentation , 2011, NeuroImage.

[75]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[76]  Nikolaus Weiskopf,et al.  Using high-resolution quantitative mapping of R1 as an index of cortical myelination , 2014, NeuroImage.

[77]  R. Brooks,et al.  T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. , 1999, Radiology.

[78]  N. Raz,et al.  Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods , 2015, Neuropsychology Review.