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Research ArticleNeurology

Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography

Carlos A. Sanchez-Catasus, Nicolaas I. Bohnen, Fang-Cheng Yeh, Nicholas D’Cruz, Prabesh Kanel and Martijn L.T.M. Müller
Journal of Nuclear Medicine April 2021, 62 (4) 545-552; DOI: https://doi.org/10.2967/jnumed.120.248500
Carlos A. Sanchez-Catasus
1Division of Nuclear Medicine, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan
2Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
3Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, Michigan
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Nicolaas I. Bohnen
1Division of Nuclear Medicine, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan
3Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, Michigan
4Department of Neurology, University of Michigan Health System, Ann Arbor, Michigan
5Neurology Service and GRECC, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan
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Fang-Cheng Yeh
6Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; and
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Nicholas D’Cruz
7Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium
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Prabesh Kanel
1Division of Nuclear Medicine, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan
3Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, Michigan
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Martijn L.T.M. Müller
1Division of Nuclear Medicine, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan
3Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, Michigan
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Abstract

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. 11C-dihydrotetrabenazine (11C-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by 11C-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on 11C-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 ± 6.2 y; disease duration, 6.4 ± 4.0 y; Hoehn and Yahr stage, 2.1 ± 0.6; Movement Disorder Society [MDS]–revised Unified Parkinson Disease Rating Scale [UPDRS] [I–III] total score, 43.4 ± 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 ± 10.3 y). 11C-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal 11C-DTBZ data using the DSI Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal 11C-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = −0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of early- or even prodromal-stage PD.

  • Parkinson disease
  • dopaminergic nigrostriatal connectivity
  • 11C-DTBZ PET
  • correlational tractography
  • diffusion MRI

Footnotes

  • Published online Aug. 28, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (4)
Journal of Nuclear Medicine
Vol. 62, Issue 4
April 1, 2021
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Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography
Carlos A. Sanchez-Catasus, Nicolaas I. Bohnen, Fang-Cheng Yeh, Nicholas D’Cruz, Prabesh Kanel, Martijn L.T.M. Müller
Journal of Nuclear Medicine Apr 2021, 62 (4) 545-552; DOI: 10.2967/jnumed.120.248500

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Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography
Carlos A. Sanchez-Catasus, Nicolaas I. Bohnen, Fang-Cheng Yeh, Nicholas D’Cruz, Prabesh Kanel, Martijn L.T.M. Müller
Journal of Nuclear Medicine Apr 2021, 62 (4) 545-552; DOI: 10.2967/jnumed.120.248500
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Keywords

  • Parkinson disease
  • dopaminergic nigrostriatal connectivity
  • 11C-DTBZ PET
  • correlational tractography
  • diffusion MRI
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