Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI
Harm J van de Haar1,2,3, Jacobus F A Jansen1,3, Cécile R L P N Jeukens1
1Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands.
Purpose:
Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE-MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored.
Methods:
Dual-time resolution DCE-MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki ) and volume fraction of detectable leaking tissue (vL ) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic Ki histograms, mimicking the strong effect of noise and variation in Ki values, were performed to understand the influence of scan time on the estimated leakage.
Results:
The mean Ki was very low (order of 10-4 min-1 ) and highly influenced by noise, causing the Ki to be increasingly overestimated at shorter scan times. In the white matter, the Ki was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, vL proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min.
Conclusions:
Several ways to improve the sensitivity of a DCE-MRI experiment to subtle BBB leakage were presented. We have provided vL as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate Ki . Recommendations on group size and scan time are made based on statistical power calculations to aid future research.
Insights
Detecting subtle blood-brain barrier (BBB) leakage in neurodegenerative diseases requires optimized dynamic contrast-enhanced MRI (DCE-MRI). The new measure, volume fraction of detectable leaking tissue (vL), is more sensitive and time-efficient than leakage rate (Ki) for identifying BBB leakage in Alzheimer's disease patients.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Radiology
Background:
- Dynamic contrast-enhanced MRI (DCE-MRI) is crucial for assessing blood-brain barrier (BBB) leakage.
- Subtle BBB leakage in neurodegenerative disorders like dementia presents significant detection challenges due to noise.
- Optimized DCE-MRI protocols and analysis methods are essential for accurate measurement of BBB integrity.
Purpose of the Study:
- To introduce a novel measure, the volume fraction of detectable leaking tissue (vL), for quantifying the spatial extent of BBB leakage.
- To evaluate the impact of scan time and sample size on the sensitivity of DCE-MRI in detecting subtle BBB leakage.
- To compare the efficacy of vL with the traditional leakage rate (Ki) in identifying BBB abnormalities in early Alzheimer's disease.
Main Methods:
- Dual-time resolution DCE-MRI was conducted on patients with early Alzheimer's disease (AD) and healthy controls.
- Noise-corrected histogram analysis was used to calculate leakage rate (Ki) and vL in cortical and white matter.
- Computer simulations were performed to assess the influence of scan time on Ki estimation, considering noise and Kivalue variations.
Main Results:
- Leakage rate (Ki) was highly sensitive to noise, leading to overestimation at shorter scan times.
- While Ki did not differ in white matter, cortical Ki was significantly higher in AD patients after 14.5 minutes.
- Volume fraction of detectable leaking tissue (vL) showed significantly higher values in AD patients compared to controls in the cortex (8 min) and white matter (15.5 min).
Conclusions:
- The study highlights the challenges of detecting subtle BBB leakage using traditional Ki measurements in DCE-MRI.
- Volume fraction of detectable leaking tissue (vL) is presented as a more sensitive and potentially time-efficient metric for group comparisons in BBB leakage.
- Recommendations for optimal scan times and group sizes are provided to enhance the statistical power of future DCE-MRI studies investigating BBB integrity.
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