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Published on: February 14, 2012
Noninvasive PK11195-PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's
Yeona Kang1, P David Mozley1, Ajay Verma2
1Weill Cornell Medicine, New York, NY.
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 [11 C](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.
Insights
Noninvasive imaging of neuroinflammation using [11C](R)-PK11195 (PK) can distinguish Parkinson's disease (PD) patients from healthy individuals. This method shows potential for tracking drug effects in future Parkinson's disease clinical trials.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Parkinson's Disease
Background:
- Neuroinflammation is a key factor in Parkinson's disease (PD) pathology.
- The radiotracer [11C](R)-PK11195 (PK) uptake serves as a marker for neuroinflammation.
- Noninvasive quantification methods like the Logan graphical method and reference tissue model are used.
Purpose of the Study:
- To determine if noninvasive imaging methods can differentiate PD patients from healthy volunteers (HVs).
- To establish the effect size needed to detect drug-induced changes in longitudinal studies.
Main Methods:
- Utilized [11C](R)-PK11195 (PK) PET imaging in 20 PD patients and 19 HVs.
- Employed Logan graphical analysis with image-derived input functions (IDIFs) and Logan reference tissue model.
- Two independent teams analyzed data to compare results.
Main Results:
- Noninvasive methods successfully identified significantly higher PK uptake in multiple brain regions of PD patients compared to HVs.
- PD patients exhibited lower variability and better repeatability in PK uptake measurements than HVs.
- A 24% difference in substantia nigra PK uptake was observed between PD patients and HVs.
Conclusions:
- Noninvasive imaging analysis methods can effectively discriminate between PD patients and HVs.
- The observed repeatability coefficient of 13% suggests feasibility for longitudinal studies.
- These methods are suitable for assessing neuroprotective drug efficacy in PD clinical trials.
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