Remote whole-brain functional microscopy of the vascular system: a paradigm shift for the monitoring and treatment of small vessel diseases

Introduction

Obtaining functional information on living organs non-invasively across different size scales is a tremendous challenge in medical imaging research, as diseases start locally at the cellular level deep into organs before expressing large-scale and observable symptoms.

Challenges in Neuroimaging

The unique complexity of the human brain adds another level of difficulty for neuroimaging. The cerebrovascular system consists of a multiscale network of blood vessels. Interaction between neurons and this vascular system, the so-called neurovascular coupling, is a major foundation of brain function leading to constant adaptation of the local cerebral blood flow to local metabolic demand. Its alteration is intimately linked to cerebral dysfunction.

Limitations of Current Modalities

Current brain imaging modalities are essential for evaluating cerebrovascular diseases in patients but are restricted to millimetric resolution and fail to capture most of the blood flow dynamics.

Proposed Solution: fULM

Here, we propose to revolutionize the field of neuroimaging by introducing a groundbreaking technology called functional Ultrasound Localization Microscopy (fULM) capable of monitoring transcranially the whole human brain vasculature and function down to microscopic resolution.

Advantages of fULM

Beyond opening a complete paradigm shift in brain angiography (at least two orders of magnitude increase in spatial resolution), fULM will also be able to:

1. Map the functional brain response during task-evoked and spontaneous activity at microscopic levels.
2. Address major technical challenges of ultrasound imaging.
3. Develop advanced neurocomputational analysis methods.
4. Validate our methods in preclinical models of cerebrovascular diseases.
5. Perform a First-In-Human study.

Expected Outcomes

Fundamental understanding of brain hemodynamics and neurovascular coupling, as well as early clinical diagnosis of neurovascular abnormalities and evaluation of drug efficacy, would tremendously benefit from such capabilities revealing both the brain vasculature and neurofunctional activity down to microscopic resolutions.