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5,767 views
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Review
17 April 2023

The blood-brain barrier (BBB) consists of specialized cells that tightly regulate the in- and outflow of molecules from the blood to brain parenchyma, protecting the brain’s microenvironment. If one of the BBB components starts to fail, its dysfunction can lead to a cascade of neuroinflammatory events leading to neuronal dysfunction and degeneration. Preliminary imaging findings suggest that BBB dysfunction could serve as an early diagnostic and prognostic biomarker for a number of neurological diseases. This review aims to provide clinicians with an overview of the emerging field of BBB imaging in humans by answering three key questions: (1. Disease) In which diseases could BBB imaging be useful? (2. Device) What are currently available imaging methods for evaluating BBB integrity? And (3. Distribution) what is the potential of BBB imaging in different environments, particularly in resource limited settings? We conclude that further advances are needed, such as the validation, standardization and implementation of readily available, low-cost and non-contrast BBB imaging techniques, for BBB imaging to be a useful clinical biomarker in both resource-limited and well-resourced settings.

6,153 views
16 citations
Mini Review
17 March 2023

The blood–brain barrier (BBB) is the neurovascular structure that regulates the passage of cells and molecules to and from the central nervous system (CNS). Alzheimer’s disease (AD) is a neurodegenerative disorder that is associated with gradual breakdown of the BBB, permitting entry of plasma-derived neurotoxins, inflammatory cells, and microbial pathogens into the CNS. BBB permeability can be visualized directly in AD patients using imaging technologies including dynamic contrast-enhanced and arterial spin labeling magnetic resonance imaging, and recent studies employing these techniques have shown that subtle changes in BBB stability occur prior to deposition of the pathological hallmarks of AD, senile plaques, and neurofibrillary tangles. These studies suggest that BBB disruption may be useful as an early diagnostic marker; however, AD is also accompanied by neuroinflammation, which can complicate these analyses. This review will outline the structural and functional changes to the BBB that occur during AD pathogenesis and highlight current imaging technologies that can detect these subtle changes. Advancing these technologies will improve both the diagnosis and treatment of AD and other neurodegenerative diseases.

5,194 views
12 citations
Review
09 February 2023

The blood–brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as β-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer’s disease. Measurements of BBB function are essential toward a better understanding of Alzheimer’s pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer’s disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer’s disease and related dementias. First, we give an overview of the relationship between Alzheimer’s pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer’s disease continuum. Fourth, we introduce a wide range of Alzheimer’s pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer’s disease and related dementias.

5,899 views
16 citations
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