Biology subjects

Kleninfeld, D.

Publications and source records attributed to Kleninfeld, D..

5 recordsLinked to original sources

bioRxiv2026

Cortical vasodynamics exhibit multiscale propagation structure in the awake mouse

Spontaneous vasomotor rhythms and fluctuations are recognized contributors to functional MRI (fMRI) signals. Yet the spatial evolution of vasomotor contributions, which bear on the interpretation of fMRI signals in terms of functionally connected brain regions, remains unresolved. To clarify this issue, we analyze the 0.01 - 0.20 Hz space-frequency modes of 14T cerebral blood volume (CBV)-weighted fMRI across the awake mouse cortex. High-resolution CBV-fMRI identified single-vessel-aligned, frequency-specific modes of vasodynamic propagation, and ultra-fast CBV-fMRI enabled mapping of phase-gradients along tangential and radial axes. Tangential gradients extended maps of vasomotor traveling waves across the entire cortical mantle, with a median speed of 0.9 - 1.3 mm/s. Radial gradients revealed approximately three-fold slower changes in timing that support lamina-dependent regulation of perfusion. Region-specific differences in propagation speed and direction occur across cortical areas and between mice. These findings reframe vascular fluctuations as a feature of brain-wide physiology, as opposed to residual noise.

neuroscience↗

bioRxiv2025

Fast and accessible morphology-free functional fluorescence imaging analysis

Optical calcium imaging is a powerful tool for recording neural activity across a wide range of spatial scales, from dendrites and spines to whole-brain imaging through two-photon and widefield microscopy. Traditional methods for analyzing functional calcium imaging data rely heavily on spatial features, such as the compact shapes of somas, to extract regions of interest and their associated temporal traces. This spatial dependency can introduce biases in time trace estimation and limit the applicability of these methods across different neuronal morphologies and imaging scales. To address these limitations, the Graph Filtered Temporal Dictionary Learning (GraFT) uses a graph-based approach to identify neural components based on shared temporal activity rather than spatial proximity, enhancing generalizability across diverse datasets. Here we present significant advancements to the GraFT algorithm, including the integration of a more efficient solver for the L1 least absolute shrinkage and selection operator (LASSO) problem and the application of compressive sensing techniques to reduce computational complexity. By employing random projections to reduce data dimensionality, we achieve substantial speedups while maintaining analytical accuracy. These advancements significantly accelerate the GraFT algorithm, making it more scalable for larger and more complex datasets. Moreover, to increase accessibility, we developed a graphical user interface to facilitate running and analyzing the outputs of GraFT. Finally, we demonstrate the utility of GraFT to imaging data beyond meso-scale imaging, including vascular and axonal imaging.

bioinformatics↗

bioRxiv2023

Guide to the construction and use of an adaptive optics two-photon microscope with direct wavefront sensing

Two-photon microscopy, combined with appropriate optical labeling, has enabled the study of structure and function throughout nervous systems. This methodology enables, for example, the measurement and tracking of sub-micrometer structures within brain cells, the spatio-temporal mapping of spikes in individual neurons, and the spatio-temporal mapping of transmitter release in individual synapses. Yet the spatial resolution of two-photon microscopy rapidly degrades as imaging is attempted at depths more than a few scattering lengths into tissue, i.e., below the superficial layers that constitute the top 300 to 400 {micro}m of neocortex. To obviate this limitation, we measure the wavefront at the focus of the excitation beam and utilize adaptive optics that alters the incident wavefront to achieve an improved focal volume. We describe the constructions, calibration, and operation of a two-photon microscopy that incorporates adaptive optics to restore diffraction-limited resolution throughout the nearly 900 {micro}m depth of mouse cortex. Our realization utilizes a guide star formed by excitation of red-shifted dye within the blood serum to directly measure the wavefront. We incorporate predominantly commercial optical, optomechanical, mechanical, and electronic components; computer aided design models of the exceptional custom components are supplied. The design is modular and allows for expanded imaging and optical excitation capabilities. We demonstrate our methodology in mouse neocortex by imaging the morphology of somatostatin-expressing neurons at 700 {micro}m beneath the pia, calcium dynamics of layer 5b projection neurons, and glutamate transmission to L4 neurons.

neuroscience↗

bioRxiv2022

A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled conditions. We present an approach to model luminal vessel thrombo-inflammation using amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium. Vessel disruption in conjunction with transient hyperglycemia from a single injection of metabolically active D-glucose results in real-time responses to venule damage that include rapid serum extravasation, platelet aggregation, and neutrophil recruitment, in normal mice. In contrast, vessel thrombo-inflammation following laser-induced vessel disruption is significantly reduced in mice injected with metabolically inert L-glucose. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, or by a nitric oxide donor. For comparison, in diabetic mice injured vessel thrombo-inflammatory responses are also reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies of transient metabolic and physical vascular perturbations and reveals new aspects of brain pathophysiology.

neuroscience↗

bioRxiv2020

Single-vessel cerebral blood flow fMRI to map blood velocity by phase-contrast imaging

Current approaches to high-field fMRI provide two means to map hemodynamics at the level of single vessels in the brain. One is through changes in deoxyhemoglobin in venules, i.e., blood oxygenation level-dependent (BOLD) fMRI, while the second is through changes in arteriole diameter, i.e., cerebral blood volume (CBV) fMRI. Here we introduce cerebral blood flow (CBF)-fMRI, which uses high-resolution phase-contrast MRI to form velocity measurements of flow and demonstrate CBF-fMRI in single penetrating microvessels across rat parietal cortex. In contrast to the venule-dominated BOLD and arteriole-dominated CBV fMRI signal, the phase-contrast -based CBF signal changes are highly comparable from both arterioles and venules. Thus, we have developed a single-vessel fMRI platform to map the BOLD, CBV, and CBF from penetrating microvessels throughout the cortex. This high-resolution single-vessel fMRI mapping scheme not only enables the vessel-specific hemodynamic mapping in diseased animal models but also presents a translational potential to map vascular dementia in diseased or injured human brains with ultra-high field fMRI. SummaryWe established a high-resolution PC-based single-vessel velocity mapping method using the high field MRI. This PC-based micro-vessel velocity measurement enables the development of the single-vessel CBF-fMRI method. In particular, in contrast to the arteriole-dominated CBV and venule-dominated BOLD responses, the CBF-fMRI shows similar velocity changes in penetrating arterioles and venules in activated brain regions. Thus, we have built a noninvasive single-vessel fMRI mapping scheme for BOLD, CBV, and CBF hemodynamic parameter measurements in animals.

neuroscience↗