Engineering next-generation oxygen-generating scaffolds to enhance bone regeneration.

In bone, an adequate oxygen (O) supply is crucial during development, homeostasis, and healing. Oxygen-generating scaffolds (OGS) have demonstrated significant potential to enhance bone regeneration. However, the complexity of O delivery and signaling in vivo makes it challenging to tailor the design of OGS to precisely meet this biological requirement.

BLEscope: A Bluetooth Low Energy (BLE) Microscope for Wireless Multicontrast Functional Imaging.

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.

Development of a High-Fidelity Benchtop Model for Simultaneous Flow, Pressure, and Imaging Assessment of Transarterial Embolization Procedures.

Purpose: 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.

Multimodality imaging reveals angiogenic evolution in vivo during calvarial bone defect healing.

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.

Vascular phenotyping of the invasive front in breast cancer using a 3D angiogenesis atlas.

Objective: Vascular remodeling at the invasive tumor front (ITF) plays a critical role in progression and metastasis of triple negative breast cancer (TNBC). Therefore, there is a crucial need to characterize the vascular phenotype (i.e.

Quantification of Cerebral Vascular Autoregulation Immediately Following Resuscitation from Cardiac Arrest.

Cerebral vascular autoregulation is impaired following resuscitation from cardiac arrest (CA), and its quantification may allow assessing CA-induced brain injury. However, hyperemia occurring immediately post-resuscitation limits the application of most metrics that quantify autoregulation. Therefore, to characterize autoregulation during this critical period, we developed three novel metrics based on how the cerebrovascular resistance (CVR) covaries with changes in cerebral perfusion pressure (CPP): (i) θ, which quantifies the CVR vs CPP gradient, (ii) a CVR-based transfer function analysis, and (iii) CVRx, the correlation coefficient between CPP and CVR.

Vascular-centric mapping of in vivo blood oxygen saturation in preclinical models.

Assessing intravascular blood oxygen saturation (SO) is crucial for characterizing in vivo microenvironmental changes in preclinical models of injury and disease. However, most conventional optical imaging techniques for mapping in vivo SO assume or compute a single value of the optical path-length in tissue. This is especially detrimental when mapping in vivo SO in experimental disease or wound healing models that are characterized by vascular and tissue remodeling.

State-of-the-art techniques for imaging the vascular microenvironment in craniofacial bone tissue engineering applications.

Vascularization is a crucial step during musculoskeletal tissue regeneration via bioengineered constructs or grafts. Functional vasculature provides oxygen and nutrients to the graft microenvironment, facilitates wound healing, enhances graft integration with host tissue, and ensures the long-term survival of regenerating tissue. Therefore, imaging de novo vascularization (i.

In vivo phenotyping of the microvasculature in necrotizing enterocolitis with multicontrast optical imaging.

Objective: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal emergency in premature infants and is characterized by a dysfunctional gut microcirculation. Therefore, there is a dire need for in vivo methods to characterize NEC-induced changes in the structure and function of the gut microcirculation, that is, its vascular phenotype. Since in vivo gut imaging methods are often slow and employ a single-contrast mechanism, we developed a rapid multicontrast imaging technique and a novel analyses pipeline for phenotyping the gut microcirculation.

VascuViz: a multimodality and multiscale imaging and visualization pipeline for vascular systems biology.

Despite advances in imaging, image-based vascular systems biology has remained challenging because blood vessel data are often available only from a single modality or at a given spatial scale, and cross-modality data are difficult to integrate. Therefore, there is an exigent need for a multimodality pipeline that enables ex vivo vascular imaging with magnetic resonance imaging, computed tomography and optical microscopy of the same sample, while permitting imaging with complementary contrast mechanisms from the whole-organ to endothelial cell spatial scales. To achieve this, we developed 'VascuViz'-an easy-to-use method for simultaneous three-dimensional imaging and visualization of the vascular microenvironment using magnetic resonance imaging, computed tomography and optical microscopy in the same intact, unsectioned tissue.

Advances in translational imaging of the microcirculation.

The past few decades have seen an explosion in the development and use of methods for imaging the human microcirculation during health and disease. The confluence of innovative imaging technologies, affordable computing power, and economies of scale have ushered in a new era of "translational" imaging that permit us to peer into blood vessels of various organs in the human body. These imaging techniques include near-infrared spectroscopy (NIRS), positron emission tomography (PET), and magnetic resonance imaging (MRI) that are sensitive to microvascular-derived signals, as well as computed tomography (CT), optical imaging, and ultrasound (US) imaging that are capable of directly acquiring images at, or close to microvascular spatial resolution.

HemoSYS: A Toolkit for Image-based Systems Biology of Tumor Hemodynamics.

Abnormal tumor hemodynamics are a critical determinant of a tumor's microenvironment (TME), and profoundly affect drug delivery, therapeutic efficacy and the emergence of drug and radio-resistance. Since multiple hemodynamic variables can simultaneously exhibit transient and spatiotemporally heterogeneous behavior, there is an exigent need for analysis tools that employ multiple variables to characterize the anomalous hemodynamics within the TME. To address this, we developed a new toolkit called HemoSYS for quantifying the hemodynamic landscape within angiogenic microenvironments.

In vivo high-resolution diffusion tensor imaging of the developing neonatal rat cortex and its relationship to glial and dendritic maturation.

Diffusion tensor imaging (DTI) is increasingly utilized as a sensitive tool for studying brain maturation and injuries during the neonatal period. In this study, we acquired high resolution in vivo DTI data from neonatal rat brains from postnatal day 2 (P2) to P10 and correlated temporal changes in DTI derived markers with microstructural organization of glia, axons, and dendrites during this critical period of brain development. Group average images showed dramatic temporal changes in brain morphology, fractional anisotropy (FA) and mean diffusivity (MD).

Tumor Ensemble-Based Modeling and Visualization of Emergent Angiogenic Heterogeneity in Breast Cancer.

There is a critical need for new tools to investigate the spatio-temporal heterogeneity and phenotypic alterations that arise in the tumor microenvironment. However, computational investigations of emergent inter- and intra-tumor angiogenic heterogeneity necessitate 3D microvascular data from 'whole-tumors' as well as "ensembles" of tumors. Until recently, technical limitations such as 3D imaging capabilities, computational power and cost precluded the incorporation of whole-tumor microvascular data in computational models.

A miniature multi-contrast microscope for functional imaging in freely behaving animals.

Neurovascular coupling, cerebrovascular remodeling and hemodynamic changes are critical to brain function, and dysregulated in neuropathologies such as brain tumors. Interrogating these phenomena in freely behaving animals requires a portable microscope with multiple optical contrast mechanisms. Therefore, we developed a miniaturized microscope with: a fluorescence (FL) channel for imaging neural activity (e.

Phenotyping the Microvasculature in Critical-Sized Calvarial Defects via Multimodal Optical Imaging.

Tissue-engineered scaffolds are a powerful means of healing craniofacial bone defects arising from trauma or disease. Murine models of critical-sized bone defects are especially useful in understanding the role of microenvironmental factors such as vascularization on bone regeneration. Here, we demonstrate the capability of a novel multimodality imaging platform capable of acquiring in vivo images of microvascular architecture, microvascular blood flow, and tracer/cell tracking via intrinsic optical signaling (IOS), laser speckle contrast (LSC), and fluorescence (FL) imaging, respectively, in a critical-sized calvarial defect model.

Brain tumors disrupt the resting-state connectome.

Brain tumor patients often experience functional deficits that extend beyond the tumor site. While resting-state functional MRI (rsfMRI) has been used to map such functional connectivity changes in brain tumor patients, the interplay between abnormal tumor vasculature and the rsfMRI signal is still not well understood. Therefore, there is an exigent need for new tools to elucidate how the blood‑oxygenation-level-dependent (BOLD) rsfMRI signal is modulated in brain cancer.

Implications of neurovascular uncoupling in functional magnetic resonance imaging (fMRI) of brain tumors.

Functional magnetic resonance imaging (fMRI) serves as a critical tool for presurgical mapping of eloquent cortex and changes in neurological function in patients diagnosed with brain tumors. However, the blood-oxygen-level-dependent (BOLD) contrast mechanism underlying fMRI assumes that neurovascular coupling remains intact during brain tumor progression, and that measured changes in cerebral blood flow (CBF) are correlated with neuronal function. Recent preclinical and clinical studies have demonstrated that even low-grade brain tumors can exhibit neurovascular uncoupling (NVU), which can confound interpretation of fMRI data.

Quantification and tracking of genetically engineered dendritic cells for studying immunotherapy.

Purpose: Genetically encoded reporters can assist in visualizing biological processes in live organisms and have been proposed for longitudinal and noninvasive tracking of therapeutic cells in deep tissue. Cells can be labeled in situ or ex vivo and followed in live subjects over time. Nevertheless, a major challenge for reporter systems is to identify the cell population that actually expresses an active reporter.

Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts.

Cyclooxygenase-2 (COX-2) is a critically important mediator of inflammation that significantly influences tumor angiogenesis, invasion, and metastasis. We investigated the role of COX-2 expressed by triple negative breast cancer cells in altering the structure and function of the extracellular matrix (ECM). COX-2 downregulation effects on ECM structure and function were investigated using magnetic resonance imaging (MRI) and second harmonic generation (SHG) microscopy of tumors derived from triple negative MDA-MB-231 breast cancer cells, and a derived clone stably expressing a short hairpin (shRNA) molecule downregulating COX-2.

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development.

Structure and Function of a Prostate Cancer Dissemination-Permissive Extracellular Matrix.

The poor prognosis of metastatic prostate cancer continues to present a major challenge in prostate cancer treatment. The tumor extracellular matrix (ECM) plays an important role in facilitating metastasis. Here, we investigated the structure and function of an ECM that facilitates prostate cancer metastasis by comparing orthotopic tumors that frequently metastasize to poorly metastatic subcutaneous tumors.

Intracellular Expression of PAI-1 Specific Aptamers Alters Breast Cancer Cell Migration, Invasion and Angiogenesis.

Plasminogen activator inhibitor-1 (PAI-1) is elevated in various cancers, where it has been shown to effect cell migration and invasion and angiogenesis. While, PAI-1 is a secreted protein, its intercellular levels are increased in cancer cells. Consequently, intracellular PAI-1 could contribute to cancer progression.