Morse, S. V. | Search bioRxiv

bioRxiv2026

Cerebrovascular Structure-Flow Gradients Revealed by Volumetric Ultrasound Localization Microscopy

Characterizing the joint organization of microscale cerebrovascular structure and flow in vivo is challenging. Volumetric ultrasound localization microscopy (ULM) provides spatially resolved measures of microvascular structure and flow from the same acquisition, but how these features are jointly organized across brain networks remains unclear. Here, we characterized local vascular phenotypes from transcranial volumetric ULM in mice and examined whether they contained reproducible low-dimensional organization. Local measures of vascular structure and flow dynamics were summarized within corresponding brain regions across mice. Subject-specific vascular phenotype similarity matrices were combined into a group-consensus graph and analyzed using diffusion embedding. Two leading gradients, showing distinct spatial distributions across brain networks, were reproducibly recovered across subject and spatial scales. The principal gradient was associated with local vascular density and flow complexity, defining a vascular structure-related axis. The secondary gradient was associated with flow speed and acceleration, defining a flow-dynamics-related axis. These gradients provide a low-dimensional representation of the cerebrovascular structure and flow and provide a reference for studying coordinated vascular changes across disease, aging, and intervention.

neuroscience↗

bioRxiv2023

Microbubble dynamics in brain microvessels

BackgroundFocused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in cerebral capillaries have never been previously recorded. The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue. MethodsMicrobubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue(R) and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2-1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second. ResultsWe observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma, refuting a previous assumption that microbubbles are confined to vessels. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index [≥] 0.6. ConclusionsThese observations provide important insight into microbubble dynamics in microvessels, and are critical leads into ultimately identifying the microbubble activities that lead to both safe drug delivery and into activities we seek to avoid, such as petechiae and other bioeffects.

bioengineering↗