A handheld device for intra-cavity and ex vivo fluorescence imaging of breast conserving surgery margins with 5-aminolevulinic acid.

Background: Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration.

Customizable optical tissue phantom platform for characterization of fluorescence imaging device sensitivity.

Significance: Optical tissue phantoms serve as inanimate and stable reference materials used to calibrate, characterize, standardize, and test biomedical imaging instruments. Although various types of solid tissue phantoms have been described in the literature, current phantom models are limited in that they do not have a depth feature that can be adjusted in real-time, they cannot be adapted to other applications, and their fabrication can be laborious and costly.

Aim: Our goal was to develop an optical phantom that could assess the imaging performance of fluorescence imaging devices and be customizable for different applications.

Quantitative intravital imaging for real-time monitoring of pancreatic tumor cell hypoxia and stroma in an orthotopic mouse model.

Pancreatic cancer is a lethal disease with few successful treatment options. Recent evidence demonstrates that tumor hypoxia promotes pancreatic tumor invasion, metastasis, and therapy resistance. However, little is known about the complex relationship between hypoxia and the pancreatic tumor microenvironment (TME).

DORA-compliant measures of research quality and impact to assess the performance of researchers in biomedical institutions: Review of published research, international best practice and Delphi survey.

Objective: The San Francisco Declaration on Research Assessment (DORA) advocates for assessing biomedical research quality and impact, yet academic organizations continue to employ traditional measures such as Journal Impact Factor. We aimed to identify and prioritize measures for assessing research quality and impact.

Methods: We conducted a review of published and grey literature to identify measures of research quality and impact, which we included in an online survey.

Assessing the Accuracy of Bioluminescence Image-Guided Stereotactic Body Radiation Therapy of Orthotopic Pancreatic Tumors Using a Small Animal Irradiator.

Stereotactic body radiation therapy (SBRT) has shown promising results in the treatment of pancreatic cancer and other solid tumors. However, wide adoption of SBRT remains limited largely due to uncertainty about the treatment's optimal fractionation schedules to elicit maximal tumor response while limiting the dose to adjacent structures. A small animal irradiator in combination with a clinically relevant oncological animal model could address these questions.

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial.

Background: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells.

New insights into spatio-temporal dynamics of mesenchymal progenitor cell ingress during peri-implant wound healing: Provided by intravital imaging.

Surface topography drives the success of orthopedic and dental implants placed in bone, by directing the biology occurring at the tissue-implant interface. Over the last few decades, striking advancements have been made in the development of novel implant surfaces that enhance bone anchorage to their surfaces through contact osteogenesis: the combination of the two phenomena of recruitment and migration of mesenchymal progenitor cells to the implant surface, and their differentiation into bone-forming cells. While the latter is generally understood, the mechanisms and dynamics underlying the migration and recruitment of such progenitor cells into the wound site have garnered little attention.

Engineering functional microvessels in synthetic polyurethane random-pore scaffolds by harnessing perfusion flow.

Recently reported biomaterial-based approaches toward prevascularizing tissue constructs rely on biologically or structurally complex scaffolds that are complicated to manufacture and sterilize, and challenging to customize for clinical applications. In the current work, a prevascularization method for soft tissue engineering that uses a non-patterned and non-biological scaffold is proposed. Human fibroblasts and HUVECs were seeded on an ionomeric polyurethane-based hydrogel and cultured for 14 days under medium perfusion.

Intravital Imaging for Tracking of Angiogenesis and Cellular Events Around Surgical Bone Implants.

These new experimental methods allow us to image, and quantify, angiogenesis and perivascular cell dynamics in the endosseous healing compartment. As such, the method is capable of providing a new perspective on, and unique information regarding, healing that occurs around orthopedic and dental implants.

Improved detection of clinically relevant wound bacteria using autofluorescence image-guided sampling in diabetic foot ulcers.

Clinical wound assessment involves microbiological swabbing of wounds to identify and quantify bacterial species, and to determine microbial susceptibility to antibiotics. The Levine swabbing technique may be suboptimal because it samples only the wound bed, missing other diagnostically relevant areas of the wound, which may contain clinically significant bacteria. Thus, there is a clinical need to improve the reliability of microbiological wound sampling.

The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death.

Purpose: Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid near-infrared fluorescence (NIRF) imaging probe, HQ4, which was radiolabeled with Indium-chloride (In-Cl) via the chelate diethylene triamine pentaacetic acid (DTPA), to enable clinical translation.

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model.

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques.

Methods And Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy.

Hybrid Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Modulating Tumor Hypoxia.

Hypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy and contributes to poor prognosis in patients receiving radiotherapy. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO) nanoparticles (MDNP) using biocompatible materials to reoxygenate the TME by reacting with endogenous HO MDNP containing hydrophilic terpolymer-protein-MnO or hydrophobic polymer-lipid-MnO provided different oxygen generation rates in the TME relevant to different clinical settings. In highly hypoxic murine or human xenograft breast tumor models, we found that administering either MDNP formulation before radiotherapy modulated tumor hypoxia and increased radiotherapy efficacy, acting to reduce tumor growth, VEGF expression, and vascular density.

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging.

Purpose: Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT).

Can Imaging Put the "" Back in Advanced Wound Care?

An effective, scientifically validated, diagnostic tool helps clinicians make better, timely, and more objective medical decisions in the care of their patients. Today, the need for such tools is especially urgent in the field of wound care where patient-centric care is the goal, under ever tightening clinical budget constraints. In an era of countless "innovative" treatment options, that is, advanced dressings, negative pressure devices, and various debridement instruments available to the wound care clinical team, one area that has arguably languished in the past decade has been in wound diagnostics.

Emerging Applications for Optically Enabled Intravital Microscopic Imaging in Radiobiology.

Radiation therapy is an effective cancer treatment used in over 50% of cancer patients. Preclinical research in radiobiology plays a major role in influencing the translation of radiotherapy-based treatment strategies into clinical practice. Studies have demonstrated that various components of tumors and their microenvironments, including vasculature, immune and stem cells, and stromal cells, can influence the response of solid tumors to radiation.

Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma.

Standard clinical management of extremity soft tissue sarcomas includes surgery with radiation therapy. Wound complications (WCs) arising from treatment may occur due to bacterial infection and tissue breakdown. The ability to detect changes in these parameters during treatment may lead to earlier interventions that mitigate WCs.

Handheld fluorescence imaging device detects subclinical wound infection in an asymptomatic patient with chronic diabetic foot ulcer: a case report.

Chronic wounds are a significant burden to global patient and health care infrastructures, and there is a need for better methods of early wound diagnosis and treatment. Traditional diagnosis of chronic wound infection by pathogenic bacteria, using clinical signs and symptoms, is based on visual inspection under white light and microbiological sampling (e.g.

Point-of-care autofluorescence imaging for real-time sampling and treatment guidance of bioburden in chronic wounds: first-in-human results.

Background: Traditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds.

Methods And Findings: This was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.

Dual in vivo photoacoustic and fluorescence imaging of HER2 expression in breast tumors for diagnosis, margin assessment, and surgical guidance.

Biomarker-specific imaging probes offer ways to improve molecular diagnosis, intraoperative margin assessment, and tumor resection. Fluorescence and photoacoustic imaging probes are of particular interest for clinical applications because the combination enables deeper tissue penetration for tumor detection while maintaining imaging sensitivity compared to a single optical imaging modality. Here we describe the development of a human epidermal growth factor receptor 2 (HER2)-targeting imaging probe to visualize differential levels of HER2 expression in a breast cancer model.

Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies.

Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be present in asymptomatic patients, leading to missed opportunities for diagnosis and treatment.

Multifunctional albumin-MnO₂ nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response.

Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME.