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Published on: April 6, 2014
Reference tissue models and blood-brain barrier disruption: lessons from (R)-[11C]PK11195 in traumatic brain injury
Hedy Folkersma1, Ronald Boellaard, W Peter Vandertop
1Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. hedy.folkersma@vumc.nl
Unlabelled:
(R)-[(11)C]PK11195 is a tracer for activated microglia. The purpose of this study was to assess the validity of the simplified reference tissue model for analyzing (R)-[(11)C]PK11195 studies in traumatic brain injury (TBI), where blood-brain barrier disruptions are likely.
Methods:
Dynamic (R)-[(11)C]PK11195 scans were acquired at 3 time points after TBI. Plasma input-derived binding potential (BP(ND)(PI)), volume of distribution (V(T)) and K(1)/k(2), and simplified reference tissue model-derived binding potential (BP(ND)(SRTM)) were obtained. Simulations were performed to assess the effect of varying K(1)/k(2).
Results:
Early after TBI, an increase in V(T), but not in BP(ND)(PI), was found. Early K(1)/k(2) correlated with V(T) and BP(ND)(SRTM) but not with BP(ND)(PI). One and 6 mo after TBI, BP(ND)(SRTM) correlated with BP(ND)(PI).
Conclusion:
Early after TBI, (R)-[(11)C]PK11195 studies should be analyzed using plasma input models.
Insights
The simplified reference tissue model is not ideal for early traumatic brain injury (TBI) studies using (R)-[(11)C]PK11195. Plasma input models are recommended for accurate analysis in the acute phase post-TBI.
Area of Science:
- Neuroimaging
- Radiochemistry
- Traumatic Brain Injury Research
Background:
- Activated microglia play a role in TBI pathogenesis.
- (R)-[(11)C]PK11195 is a positron emission tomography (PET) tracer used to image activated microglia.
- Traumatic brain injury (TBI) can disrupt the blood-brain barrier, potentially affecting tracer kinetics.
Purpose of the Study:
- To evaluate the accuracy of the simplified reference tissue model (SRTM) for analyzing (R)-[(11)C]PK11195 PET data in TBI.
- To compare SRTM-derived binding potential with plasma input-derived measures in the context of TBI.
- To determine the optimal analysis method for (R)-[(11)C]PK11195 PET studies following TBI.
Main Methods:
- Dynamic (R)-[(11)C]PK11195 PET scans were acquired at three time points post-TBI.
- Analysis included plasma input-derived binding potential (BP(ND)(PI)) and simplified reference tissue model-derived binding potential (BP(ND)(SRTM)).
- Simulations were conducted to assess the impact of varying kinetic parameters (K(1)/k(2)) on model performance.
Main Results:
- Early after TBI, increased volume of distribution (V(T)) was observed, but not BP(ND)(PI).
- Early K(1)/k(2) values correlated with V(T) and BP(ND)(SRTM), but not BP(ND)(PI).
- At 1 and 6 months post-TBI, BP(ND)(SRTM) showed correlation with BP(ND)(PI).
Conclusions:
- The simplified reference tissue model (SRTM) is less reliable for analyzing (R)-[(11)C]PK11195 PET data in the acute phase after TBI.
- Plasma input models are recommended for accurate quantification of microglial activation using (R)-[(11)C]PK11195 in the early stages of TBI.
- Longer-term after TBI, SRTM may provide valid results, but plasma input methods are preferred for early assessment.
