Imaging subtle leaks in the blood –brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions

AbstractRecent studies using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium-based contrast agents (GBCA) have demonstrated subtle blood –brain barrier (BBB) leaks in the human brain during normal aging, in individuals with age-related cognitive dysfunction, genetic risk for Alzheimer’s disease (AD), mild cognitive impairment, early AD, cerebral small vessel disease (SVD), and other neurodegenerative disorders. In these neurologi cal conditions, the BBB leaks, quantified by the unidirectional BBB GBCA tracer’s constantKtrans maps, are typically orders of magnitude lower than in brain tumors, after stroke and/or during relapsing episodes of multiple sclerosis. This puts extra challenges for the DCE-MRI technique by pushing calculations towards its lower limits of detectability. In addition, presently, there are no standardized multivendor protocols or evidence of repeatability and reproducibility. Nevertheless, subtle BBB leaks may critically contribute to the pathophysiology of cognitive impairment and dementia associated with AD or SVD, and therefore, efforts to improve sensitivity of detection, reliability, and reproducibility are warranted. A larger number of participants scanned by different MR scanners at different clinical sites are sometimes required to detect differences in BBB integrity between control and at-risk groups, which impose additional challenges. Here, we focus on these new challenges and propose some approaches to norm...
Source: AGE - Category: Geriatrics Source Type: research