Arvind P. Pathak

Objective: Reconstruction of vascular topology from imperfect 3D imaging data is essential for accurate hemodynamic simulations. Therefore, we developed a “gap‐filling” method predicated on vascular biology and empirical patterns to restore incomplete vessels, independent of the imaging modality and spatial resolution employed. Methods: Our gap‐filling algorithm reconstructs a vascular network based on distributions of its extant morphological features and employs different rules for healthy and tumor tissue. Algorithm performance was evaluated on (i) incomplete synthetic vascular trees with simulated CT noise, (ii) micro‐CT‐acquired brain tumor vasculature, (iii) micro‐MRI‐derived vasculature from a healthy mouse brain, and (iv) vasculature from the murine hippocampus imaged with light‐sheet microscopy (LSM). Results: For synthetic vascular trees, our algorithm restored more gaps when the volume fraction was between 80% and 95%. Peak vessel segment recovery occurred for intermediate volume fractions (86%–89%). Gap‐filling performance was impacted when image noise was introduced. Across CT, MRI, and LSM, our method successfully reconnected missing vessel segments while preserving the overall features of the vascular network. Gap‐filling of tumor vasculature, with its abnormal topology, was better when tumor‐specific reconstruction rules were employed. Conclusions: Our method showed efficient restoration of vascular network connectivity for 3D data derived from common imaging modalities at different resolutions. We also demonstrated the significance of applying distinct biologically‐informed rules when reconstructing healthy and tumor vascular networks.

Miniaturized microscopes or ‘miniscopes’ for neuroimaging in freely behaving animals mostly operate over short durations (24 h) imaging, remote operation and simultaneous characterization of multiple neurophysiological variables such as neuronal activity, blood flow, blood volume, oxygenation and cellular dynamics (a capability that we call ‘neurosurveillance’). Thus, we developed the ‘CloudScope’, a cloud-based multicontrast miniscope for autonomous neurosurveillance in freely behaving animals. Its cloud-based architecture enables global remote operation and continuous acquisition of multicontrast images over CNS disease model life cycles. We demonstrate CloudScope’s neurosurveillance capabilities in predicting behavior from 24-h neuroimaging data with deep learning (DL), characterizing neurovascular changes during natural behavior, seizure-induced neurovascular disruptions, and in vivo cellular and microvascular phenotyping of brain tumor microenvironments. Finally, CloudScope’s architecture enables ‘time-shared’ imaging, which potentially reduces animal use. Collectively, CloudScope’s neurosurveillance capabilities in conjunction with CNS disease models establish a new paradigm for characterizing their etiology and evolution.

The bone marrow niche (BMN) plays a central role in regulating hematopoietic stem-cell (HSC) maintenance, lineage commitment, and immune homeostasis, while also supporting osteogenesis and maintaining skeletal integrity. Once considered static, the BMN is now recognized as a dynamic and responsive microenvironment that integrates local signals and systemic cues to meet physiological demands and respond to stress. Aging causes profound and progressive changes to this niche, leading to functional decline across both hematopoietic and stromal compartments. Recent advances in high-resolution imaging, single-cell and spatial transcriptomics, and in vivo lineage tracing have revealed remarkable heterogeneity and plasticity within the vascular and mesenchymal elements of this niche. Yet, key questions remain unresolved, including the identity and hierarchy of mesenchymal and osteolineage cells, the specialization of subsets of endothelial cells, the integration of systemic regulation, and whether the aging bone marrow acts as a driver or a passenger in malignancy and chronic inflammation. This review revisits current models of the BMN, with a focus on the reciprocal interactions between osteogenic cells and specialized vasculature, and how their disruption during aging impairs hematopoietic output and skeletal remodeling. We also examine how systemic factors such as neural input, metabolic status, and inflammatory signaling influence the aging of the BMN. Finally, we highlight emerging translational platforms, including iPSC-derived bone marrow organoids, engineered niches/hydrogels, and vascularized organ-on-chip systems, that enable mechanistic testing of rejuvenation strategies. Together, these insights have the potential to pave the way toward targeted interventions that restore the function of the BMN and promote healthy aging of the bone and blood systems.

Recent advances in low-power wireless-capable system-on-chips (SoCs) have accelerated diverse Internet of Things (IoT) applications, encompassing wearables, asset monitoring, and more. Concurrently, the field of neuroimaging has experienced escalating demand for lightweight, untethered, low-power systems capable of imaging in small animals. This article explores the feasibility of using a low-power asset monitoring system as the basis of a new architecture for fluorescence and hemodynamic contrast-based wireless functional imaging. The core system architecture hinges on the fusion of a Bluetooth Low Energy (BLE) 5.2 SoC and a low-power 560 × 560, 8-bit monochrome CMOS image sensor module. Successful integration of a multicontrast optical front-end consisting of a fluorescence channel (FL) and an intrinsic optical signal (IOS) channel resulted in the creation of a wireless microscope called ‘BLEscope’. Next, we developed a wireless (i.e., BLE) protocol to remotely operate the BLEscope via a laptop and acquire in vivo images at 1 frame per second (fps). We then conducted a comprehensive characterization of the BLEscope to assess its optical capabilities and power consumption. We report a new benchmark for continuous wireless imaging of ∼1.5 hours with a 100 mAh battery. Via the FL channel of the BLEscope, we successfully tracked the kinetics of an intravenously injected fluorescent tracer and acquired images of fluorescent brain tumor cells in vivo. Via the IOS channel, we characterized the differential response of normal and tumor-associated blood vessels to a carbogen gas inhalation challenge. When miniaturized, the BLEscope will result in a new class of low-power, implantable or wireless microscopes that could transform preclinical and clinical neuroimaging applications.

The development of new endovascular technologies for transarterial embolization has relied on animal studies to validate efficacy before clinical trials are undertaken. Because embolizations in animals and patients are primarily conducted with fluoroscopy alone, local hemodynamic changes are not assessed during testing. However, such hemodynamic metrics could be important indicators of procedure efficacy that could support improved patient outcomes, such as via the determination of procedural endpoints. The purpose of this study is to create a high-fidelity benchtop system for multiparametric (i.e., hemodynamic and imaging) assessment of transarterial embolization procedures. The benchtop system consists of a 3D printed, anatomically accurate vascular phantom; a flow loop with a cardiac output simulator; a high-speed video camera; and pressure transducers and flow meters. This system enabled us to vary the heart rate and blood pressure and to simulate clinically relevant hemodynamic states, such as healthy adult, aortic regurgitation, and hypovolemic shock. With our radiation-free angiography-mimetic imaging system, we could simultaneously assess gauge pressure and flow values during transarterial embolization. We demonstrated the feasibility of recapitulating the digital subtraction angiography workflow. Finally, we highlighted the utility of this system by characterizing the relationship between an imaging-based metric of procedural endpoint and intravascular flow. We also characterized hemodynamic changes associated with particle embolization within a branch of the hepatic artery and found them to be within reported patient data. Our benchtop vascular system was low-cost and reproduced transarterial embolization-related hemodynamic phenomena with high fidelity. We believe that this novel platform enables the characterization of patient physiology, novel catheterization devices, and techniques.

The healing of calvarial bone defects is a pressing clinical problem that involves the dynamic interplay between angiogenesis and osteogenesis within the osteogenic niche. Although structural and functional vascular remodeling (i.e., angiogenic evolution) in the osteogenic niche is a crucial modulator of oxygenation, inflammatory and bone precursor cells, most clinical and pre-clinical investigations have been limited to characterizing structural changes in the vasculature and bone. Therefore, we developed a new multimodality imaging approach that for the first time enabled the longitudinal (i.e., over four weeks) and dynamic characterization of multiple in vivo functional parameters in the remodeled vasculature and its effects on de novo osteogenesis, in a preclinical calvarial defect model. We employed multi-wavelength intrinsic optical signal (IOS) imaging to assess microvascular remodeling, intravascular oxygenation (SO₂), and osteogenesis; laser speckle contrast (LSC) imaging to assess concomitant changes in blood flow and vascular maturity; and micro-computed tomography (μCT) to validate volumetric changes in calvarial bone. We found that angiogenic evolution was tightly coupled with calvarial bone regeneration and corresponded to distinct phases of bone healing, such as injury, hematoma formation, revascularization, and remodeling. The first three phases occurred during the initial two weeks of bone healing and were characterized by significant in vivo changes in vascular morphology, blood flow, oxygenation, and maturity. Overall, angiogenic evolution preceded osteogenesis, which only plateaued toward the end of bone healing (i.e., four weeks). Collectively, these data indicate the crucial role of angiogenic evolution in osteogenesis. We believe that such multimodality imaging approaches have the potential to inform the design of more efficacious tissue-engineering calvarial defect treatments.