RESEARCH

ARTICLE

Diffusion Tensor Imaging of the Nigrostriatal Fibers in Parkinson’s Disease Yu Zhang, MD,1,2* I-Wei Wu, BS,1,2 Shannon Buckley, BA,1,2 Christopher S. Coffey, PhD,3 Eric Foster, PhD,3 Susan Mendick, MPH,4 John Seibyl, MD,4 and Norbert Schuff, PhD1,2 1

Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, CA, USA 2 Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA 3 Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA 4 Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging, LLC (MNI), New Haven CT, USA

ABSTRACT: Background: Parkinson’s disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios.

Methods: Diffusion tensor tractography was performed on 50 drug-na€ıve PD patients and 27 healthy control subjects from the international multicenter Parkinson’s Progression Marker Initiative. Results: Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Conclusion: Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging C 2015 International Parkinson and Moveof early PD. V ment Disorder Society

Key Words: Parkinson’s disease; MRI; diffusion tensor imaging; diffusion tensor tractography; nigrostriatal pathway

------------------------------------------------------------------------------------------------------------------------------

*Correspondence to: Dr. Yu Zhang, MD, Center for Imaging of Neurodegenerative Diseases, VA Medical Center, 4150 Clement Street, Mail Stop 114M, San Francisco, CA 94121; e-mail: [email protected]

Relevant conflicts of interest/financial disclosures: Dr. Yu Zhang has no disclosures to report. Ms. I-Wei Wu has no disclosures to report. Mr. Shannon Buckley has no disclosures to report. Dr. Christopher S. Coffey has no disclosure to report. Dr. Eric Foster has no disclosures to report. Ms. Susan Mendick has no disclosures to report. Dr. John Seibyl has received research funding from Michael J. Fox Foundation for Parkinson’s Research, consulting fees from GE Healthcare, Navidea Biopharmaceuticals, and Piramal Imaging. He has equity interest in Molecular Neuroimaging, LLC. Dr. Norbert Schuff receives research funding from Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health, Department of Defense, and consulting honoraria from Eli Lilly. Funding agencies: The study was supported by the funding partners of the Parkinson’s Progression Marker Initiative (PPMI) group. PPMI is sponsored by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbot, Avid Radiopharmaceuticals, Biogen Idec, BristolMyers Squibb, Covance, Elan Corporation, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Pfizer and UCB. The study was also supported by an NIH grant (P41 EB015904). Full financial disclosures and author roles may be found in the online version of this article. The statistical analysis was conducted by Dr. Norbert Schuff, PhD.1,2 Received: 18 December 2014; Revised: 14 March 2015; Accepted: 23 March 2015 Published online 29 April 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26251

Movement Disorders, Vol. 30, No. 9, 2015

1229

Z H A N G

E T

A L

Parkinson’s disease (PD) is histopathologically characterized by loss of dopamine neurons in the substantia nigra (SN) pars compacta (SNc). The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, a bundle of nerve fibers that links the SN to the striatum, causing a dysregulation in striatal activity that ultimately leads to lack of movement control.1,2 Assessing the nigrostriatal pathway is therefore useful for aiding the diagnosis and treatment interventions of PD. Previous studies in PD using diffusion tensor imaging (DTI)3 by evaluating the nigral fractional anisotropy (FA)4 have reported mixed results,5 although a recent study—attempting the separation between free and tissue water diffusion using a bi-tensor model— found a prominent free water increase in PD.6 Diffusion tensor imaging tractography7 of the nigrostriatal pathway has been demonstrated in healthy subjects,8 although this tract was termed “striatomesencephalic fiber.” Studies analyzing the nigrostriatal tract in PD patients are rare, presumably because of the difficulties in reliably identifying this small tract in the presence of crossing or joining fibers.9 Two recent studies10,11 have analyzed the connectivity profile, which was defined as the number of the most probable fibers that connect SN and putamen using probabilistic tractography. One study10 reported a significant reduction in this connectivity, whereas the other11 found no significant abnormality in PD. To our knowledge, no previous study reports variations in DTI measures of the nigrostriatal tract in PD. In this study, DTI measures were used for assessing the integrity of the nigrostriatal fibers based on data from the Parkinson’s Progression Marker Initiative (PPMI),12 an international multicenter study. The main goals were to 1) demonstrate that tractography of the nigrostriatal tract can reliably be performed in PD patients and healthy control (HC) subjects; 2) test whether DTI measures along the nigrostriatal tract differ between PD patients and HC subjects; and 3) determine the degree to which DTI variations along the nigrostriatal tract in PD are associated with the severity of motor symptoms and striatal dopaminergic deficits.

Methods Population The data were obtained through the PPMI study,12 which has been approved by the respective Institutional Review Boards of all participating sites, and all subjects provided written informed consent. After initial screening, the subjects were fully assessed at the baseline visit for clinical (motor, neuropsychological, and cognitive) performance by the site investigators. Specifically, motor function was assessed using Part III of the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale

1230

Movement Disorders, Vol. 30, No. 9, 2015

TABLE 1. Group demographics and clinical characteristics

Number of tractography Age (y) Sex (M/F) Handedness (L:R:M)a Side of symptom onset (L:R:S)b Total UPDRS (I-IV)c UPDRS IIId Hoehn & Yahre MoCAf Putaminal DAT (minimum side)

HC

PD

Group Difference (P)

27 56.8 6 10.7 21/6 23: 4: 0 —

50 59.7 6 9.2 32/18 44: 4: 2 27: 22: 1

— NS NS — —

5.8 6 2.5 0.4 6 0.8 0 28.1 6 1.1 1.25 6 0.4

38.8 6 13.3 21.9 6 7.8 1.6 6 0.5 28.0 6 1.7 0.58 6 0.2

Diffusion tensor imaging of the nigrostriatal fibers in Parkinson's disease.

Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of ...
586KB Sizes 5 Downloads 31 Views

Recommend Documents


Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor.
Parkinson's disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity

Deep Into the Fibers! Postmortem Diffusion Tensor Imaging in Forensic Radiology.
In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy

Novel diffusion tensor imaging findings in Krabbe disease.
Krabbe disease is a lysosomal disorder that primarily affects myelin. Diffusion tensor imaging (DTI) provides quantitative information about the white matter organization and integrity. Radial diffusivity (RD) reflects myelin injury selectively.

Brain MR diffusion tensor imaging in Kennedy's disease.
Kennedy's disease (KD) is a progressive degenerative disorder affecting lower motor neurons. We investigated the correlation between disease severity and whole brain white matter microstructure, including upper motor neuron tracts, by using diffusion

3T magnetic resonance diffusion tensor imaging in chronic kidney disease.
To investigate the relationship of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with renal function on 3T diffusion tensor imaging (DTI) in chronic kidney disease.

Comparison of twice refocused spin echo versus stimulated echo diffusion tensor imaging for tracking muscle fibers.
To compare the precision of measuring the pennation angle and fiber length in the vastus lateralis (VL) using two distinctly different diffusion tensor imaging (DTI) sequences.

Anisotropic fractional diffusion tensor imaging.
Traditional diffusion tensor imaging (DTI) maps brain structure by fitting a diffusion model to the magnitude of the electrical signal acquired in magnetic resonance imaging (MRI). Fractional DTI employs anomalous diffusion models to obtain a better

Longitudinal diffusion tensor imaging in frontotemporal dementia.
Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of W

Diffusion tensor imaging in hemorrhagic stroke.
Diffusion tensor imaging (DTI) has evolved considerably over the last decade to now be knocking on the doors of wider clinical applications. There have been several efforts over the last decade to seek valuable and reliable application of DTI in diff

Diffusion tensor imaging in musculoskeletal disorders.
Diffusion tensor (DT) imaging is an emerging magnetic resonance (MR) imaging technique for evaluating the microstructure of well-organized biologic tissues such as muscles and nerves. DT imaging provides information about tissue microstructure by pro