Noninvasive PK11195‐PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease
ABSTRACT BACKGROUND AND PURPOSE Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11C](R)‐PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quanti...
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| Published in | Journal of neuroimaging Vol. 28; no. 5; pp. 496 - 505 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.09.2018
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| Subjects | |
| Online Access | Get full text |
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| Summary: | ABSTRACT
BACKGROUND AND PURPOSE
Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11C](R)‐PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image‐derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug‐induced changes from system variance in longitudinal trials.
METHODS
The sample consisted of 20 participants with PD and 19 HVs. Two independent teams analyzed the data to compare the volume of distribution calculated using image‐derived input functions (IDIFs), and binding potentials calculated using the Logan reference region model.
RESULTS
With all methods, the higher signal‐to‐background in patients resulted in lower variability and better repeatability than in controls. We were able to use noninvasive techniques showing significantly increased uptake of PK in multiple brain regions of participants with PD compared to HVs.
CONCLUSION
Although not necessarily reflecting absolute values, these noninvasive image analysis methods can discriminate between PD patients and HVs. We see a difference of 24% in the substantia nigra between PD and HV with a repeatability coefficient of 13%, showing that it will be possible to estimate responses in longitudinal, within subject trials of novel neuroprotective drugs. |
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| Bibliography: | Acknowledgments and Disclosure This study was designed in collaboration with its sponsor, Biogen Idec, Inc., a pharmaceutical company that has no market in imaging per se, but sometimes uses imaging to make decisions about new drug development. The authors declare that they have no conflicts‐of‐interests. The authors are grateful to Robert B. Innis of NIMH, who provided guidance on the design and execution of the study throughout its development. The authors also want to acknowledge the guidance by Gary S. Dorfman, who shepherded the study and actively edited the protocol, its derivative documents, and this manuscript. Elizabeth Monohan ran the FreeSurfer analyses that delivered the regions of interest. Nancy Obuchowski of the Cleveland Clinic guided the application of the repeatability coefficient as a primary study deliverable and helped make it consistent with the endpoints calculated by the Quantitative Imaging Biomarker Alliance of the Radiological Society of North America. Linda M. Gerber and Gulce Askin of Weill Cornell Medicine reviewed the other statistical analyses. This study was conducted by the professional staff at the Citigroup Biomedical Imaging Center of Weill Cornell Medical College, including, in alphabetical order, John W. Babich, Jonathan Dyke, Simon Morim, Amelia Ng, and Nelsie Pastrano‐Redula. |
| ISSN: | 1051-2284 1552-6569 |
| DOI: | 10.1111/jon.12519 |