Generating computational anatomical models of cerebrovascular networks is vital for improving clinical practice and understanding brain oxygen transport. This is achieved by extracting graph-based representations based on pre-mapping of vascular structures. Recent graphing methods can provide smooth vessels trajectories and well-connected vascular topology. However, they require water-tight surface meshes as inputs. Furthermore, adding vessels radii information on their graph compartments restricts their alignment along vascular centerlines. Here, we propose a novel graphing scheme that works with relaxed input requirements and intrinsically captures vessel radii information. The proposed approach is based on deforming geometric graphs constructed within vascular boundaries. Under a laplacian optimization framework, we assign affinity weights on the initial geometry that drives its iterative contraction toward vessels centerlines. We present a mechanism to decimate graph structure at each run and a convergence criterion to stop the process. A refinement technique is then introduced to obtain final vascular models. Our implementation is available on https://github.com/Damseh/VascularGraph. We benchmarked our results with that obtained using other efficient and state-of-the-art graphing schemes, validating on both synthetic and real angiograms acquired with different imaging modalities. The experiments indicate that the proposed scheme produces the lowest geometric and topological error rates on various angiograms. Furthermore, it surpasses other techniques in providing representative models that capture all anatomical aspects of vascular structures.

The Journal of Biomedical Optics (JBO) publishes peer-reviewed papers on the use of novel optical systems and techniques for improved health care and biomedical research.

An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution (25 μm / voxel) 3 × OCT with a high-resolution (1.5 μm / voxel) 40 × OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The 40 × ROIs positions are selected either manually by the microscope operator or using an automated ROI positioning selection algorithm. Additionally, a multimodal and multiresolution registration pipeline is developed in order to align the 2R-SOCT data onto diffusion MRI (dMRI) data acquired in the same ex vivo mouse brains prior to automated histology. Using this imaging system, 3 whole mouse brains are imaged, and 250 high-resolution 40 × three-dimensional ROIs are acquired. The capability of this system to perform multimodal imaging studies is demonstrated by labeling the ROIs using a mouse brain atlas and by categorizing the ROIs based on their associated dMRI measures. This reveals a good correspondence of the tissue microstructure imaged by the high-resolution OCT with various dMRI measures such as fractional anisotropy, number of fiber orientations, apparent fiber density, orientation dispersion, and intracellular volume fraction.

Microvascular stalling, the process occurring when a capillary temporarily loses perfusion, has gained increasing interest in recent years through its demonstrated presence in various neuropathologies. Studying the impact of such stalls on the surrounding brain tissue is of paramount importance to understand their role in such diseases. Despite efforts trying to study the stalling events, investigations are hampered by their elusiveness and scarcity. In an attempt to alleviate these hurdles, we present here a novel methodology enabling transient occlusions of targeted microvascular segments through multiphoton excitation of Rose Bengal, an established photothrombotic agent. With n = 7 mice C57BL/6 J (5 males and 2 females) and 95 photothrombosis trials, we demonstrate the ability of triggering reversible blockages by illuminating a capillary segment during ∼300 s at 1000 nm, using a standard Ti:Sapphire femtosecond laser. Furthermore, we performed concurrent Optical Coherence Microscopy (OCM) angiography imaging of the microvascular network to highlight the specificity of the targeted occlusion and its duration. Through comparison with a control group, we conclude that blood flow cessation is indeed created by the photothrombotic agent via multiphoton excitation and is temporary, followed by a flow recovery in less than 24 h. Moreover, Immunohistology points toward a stalling mechanism driven by adherence of the neutrophil in the vascular lumen. This observation seems to be promoted by the inflammation locally created via multiphoton activation of Rose Bengal.

In recent years, multiple serial histology techniques were developed to enable whole rodent brain imaging in 3-D. The main driving forces behind the emergence of these imaging techniques were the genome-wide atlas of gene expression in the mouse brain, the pursuit of the mouse brain connectome, and the BigBrain project. These projects rely on the use of optical imaging to target neuronal structures with histological stains or fluorescent dyes that are either expressed by transgenic mice or injected at specific locations in the brain. Efforts to adapt the serial histology acquisition scheme to use intrinsic contrast imaging (ICI) were also put forward, thus leveraging the natural contrast of neuronal tissue. This review focuses on these efforts. First, the origin of optical contrast in brain tissue is discussed with emphasis on the various imaging modalities exploiting these contrast mechanisms. Serial blockface histology (SBH) systems using ICI modalities are then reported, followed by a review of some of their applications. These include validation studies and the creation of multimodal brain atlases at a micrometer resolution. The paper concludes with a perspective of future developments, calling for a consolidation of the SBH research and development efforts around the world. The goal would be to offer the neuroscience community a single standardized open-source SBH solution, including optical design, acquisition automation, reconstruction algorithms, and analysis pipelines.

Brain microcirculation is the intricate network of blood vessels encompassing arterioles, capillaries, and venules that delivers oxygen and nutrition and removes waste products necessary for the proper functioning of brain tissue.^1,2 It plays a critical role in maintaining homeostasis associated with metabolic requirements and oxygen distribution to the tissue in the brain. In particular, brain capillaries play a pivotal role in facilitating the exchange of essential nutrients and oxygen to support neurons. However, in the presence of neurological disorders, such as Alzheimer’s disease³ or stroke,^{4 – 6} this microcirculatory system can be disrupted due to capillary stalling.