Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

[1]  Gianmario Sambuceti,et al.  Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study , 2009, Movement disorders : official journal of the Movement Disorder Society.

[2]  Fabrice Crivello,et al.  Age- and sex-related effects on the neuroanatomy of healthy elderly , 2005, NeuroImage.

[3]  V. Dhawan,et al.  Changes in network activity with the progression of Parkinson's disease. , 2007, Brain : a journal of neurology.

[4]  M. Kenward,et al.  An Introduction to the Bootstrap , 2007 .

[5]  H. Shill,et al.  Defining mild cognitive impairment in Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[6]  G. C. Román,et al.  Vascular dementia , 1993, Neurology.

[7]  M. Turk,et al.  Eigenfaces for Recognition , 1991, Journal of Cognitive Neuroscience.

[8]  David Eidelberg,et al.  Metabolic brain networks associated with cognitive function in Parkinson's disease , 2007, NeuroImage.

[9]  David Eidelberg,et al.  Differential diagnosis of parkinsonian syndromes using PCA-based functional imaging features , 2009, NeuroImage.

[10]  V. Dhawan,et al.  Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[12]  Albert Gjedde,et al.  Subcortical elevation of metabolism in Parkinson's disease — A critical reappraisal in the context of global mean normalization , 2009, NeuroImage.

[13]  R. Barker,et al.  Mild cognitive impairment in Parkinson disease , 2010, Neurology.

[14]  Y. Itoyama,et al.  Distinct patterns of regional cerebral glucose metabolism in Parkinson's disease with and without mild cognitive impairment , 2009, Movement disorders : official journal of the Movement Disorder Society.

[15]  Ashutosh Kumar Singh,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction , 2010 .

[16]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[17]  A Z Snyder,et al.  Long term treatment and disease severity change brain responses to levodopa in Parkinson’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[18]  Yaakov Stern,et al.  Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance , 2004, NeuroImage.

[19]  T. Anderson,et al.  The MoCA , 2010, Neurology.

[20]  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.

[21]  Y. Fukuuchi,et al.  Levodopa-induced local cerebral blood flow changes in Parkinson's disease and related disorders , 1995, Journal of the Neurological Sciences.

[22]  D. Alsop,et al.  Continuous flow‐driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields , 2008, Magnetic resonance in medicine.

[23]  A. Bonnet,et al.  [The Unified Parkinson's Disease Rating Scale]. , 2000, Revue neurologique.

[24]  Abu-Bakr Al-Mehdi,et al.  Increased Depth of Cellular Imaging in the Intact Lung Using Far-Red and Near-Infrared Fluorescent Probes , 2006, Int. J. Biomed. Imaging.

[25]  David Eidelberg,et al.  Dissociation of Metabolic and Neurovascular Responses to Levodopa in the Treatment of Parkinson's Disease , 2008, The Journal of Neuroscience.

[26]  J. Detre,et al.  Assessment of cerebral blood flow in Alzheimer's disease by spin‐labeled magnetic resonance imaging , 2000, Annals of neurology.

[27]  David Eidelberg,et al.  Assessment of the progression of Parkinson's disease: a metabolic network approach , 2007, The Lancet Neurology.

[28]  D. Molloy,et al.  A Guide to the Standardized Mini-Mental State Examination , 1997, International Psychogeriatrics.

[29]  D. Alsop,et al.  Parkinson's Disease Spatial Covariance Pattern: Noninvasive Quantification with Perfusion MRI , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  W. Mali,et al.  Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults. , 1998, Radiology.

[31]  Yoshinori Doi,et al.  Three‐dimensional stereotactic surface projection SPECT analysis in Parkinson's disease with and without dementia , 2005, Movement disorders : official journal of the Movement Disorder Society.

[32]  G. Alexander,et al.  Application of the scaled subprofile model to functional imaging in neuropsychiatric disorders: A principal component approach to modeling brain function in disease , 1994 .

[33]  V J Cunningham,et al.  Cortical dysfunction in non-demented Parkinson's disease patients: a combined (31)P-MRS and (18)FDG-PET study. , 2000, Brain : a journal of neurology.

[34]  R. Albin,et al.  Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[35]  Christian G. Habeck,et al.  Reciprocal Benefits of Mass-Univariate and Multivariate Modeling in Brain Mapping: Applications to Event-Related Functional MRI, H2 15O-, and FDG-PET , 2006, Int. J. Biomed. Imaging.

[36]  M. J Firbank,et al.  Regional cerebral blood flow in Parkinson's disease with and without dementia , 2003, NeuroImage.

[37]  Albert Gjedde,et al.  Cortical hypometabolism and hypoperfusion in Parkinson’s disease is extensive: probably even at early disease stages , 2010, Brain Structure and Function.

[38]  M Samii,et al.  Resting regional cerebral glucose metabolism in advanced Parkinson's disease studied in the off and on conditions with [18F]FDG‐PET , 2001, Movement disorders : official journal of the Movement Disorder Society.

[39]  David Eidelberg,et al.  Relationships among the metabolic patterns that correlate with mnemonic, visuospatial, and mood symptoms in Parkinson's disease. , 2002, The American journal of psychiatry.

[40]  David Eidelberg,et al.  Network biomarkers for the diagnosis and treatment of movement disorders , 2009, Neurobiology of Disease.

[41]  N. Yanagisawa,et al.  [Cognitive impairment in Parkinson's disease]. , 1991, No to shinkei = Brain and nerve.

[42]  Albert Gjedde,et al.  Artefactual subcortical hyperperfusion in PET studies normalized to global mean: Lessons from Parkinson’s disease , 2009, NeuroImage.

[43]  D. Eidelberg Metabolic brain networks in neurodegenerative disorders: a functional imaging approach , 2009, Trends in Neurosciences.

[44]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[45]  Kazuto Yoshida,et al.  Brain 3D-SSP SPECT analysis in dementia with Lewy bodies, Parkinson's disease with and without dementia, and Alzheimer's disease , 2005, Clinical Neurology and Neurosurgery.

[46]  Yaakov Stern,et al.  Multivariate and Univariate Analysis of Continuous Arterial Spin Labeling Perfusion MRI in Alzheimer's Disease , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  E. Tolosa,et al.  Diagnostic procedures for Parkinson's disease dementia: Recommendations from the movement disorder society task force , 2007, Movement disorders : official journal of the Movement Disorder Society.

[48]  Hisao Tachibana,et al.  Cerebral Blood Flow in Parkinson’s Disease, Dementia with Lewy Bodies, and Alzheimer’s Disease according to Three-Dimensional Stereotactic Surface Projection Imaging , 2005, Dementia and Geriatric Cognitive Disorders.

[49]  T. Jung,et al.  Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[50]  E. Melamed,et al.  Regional cerebral blood flow in patients with Parkinson's disease under chronic levodopa therapy: measurements during "on" and "off" response fluctuations. , 1986, Journal of neurology, neurosurgery, and psychiatry.

[51]  D. Berg,et al.  Cortical hypometabolism assessed by a metabolic ratio in Parkinson's disease primarily reflects cognitive deterioration—[18F]FDG‐PET , 2009, Movement disorders : official journal of the Movement Disorder Society.

[52]  C. Marsden,et al.  Recent Developments in Parkinson's Disease , 1986 .

[53]  W Fernandez,et al.  Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine , 1992, Annals of neurology.

[54]  Albert Gjedde,et al.  Normalization in PET group comparison studies—The importance of a valid reference region , 2008, NeuroImage.