6,543 research outputs found

    Using Fluorescence – Polarization Endoscopy in Detection of Precancerous and Cancerous Lesions in Colon and Pancreatic Cancer

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    Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real time detection of these lesions. Utilizing a new thermoresponsive sol-gel formulation with targeted molecular probe allowed topical application and detection of precancerous and cancerous lesions during endoscopy. Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy served as a validation strategy prior to obtaining biopsies. In order to reduce repeat surgeries arising from incomplete tumor resection, we demonstrated the efficacy of the targeted molecular probe towards margins of sporadic colorectal cancer (SCC). Fluorescence-polarization microscopy using circular polarized (CP) light served as a rapid, supplementary tool for assessment and validation of excised tissue to ensure complete tumor resection for examining tumor margins prior to H&E-based pathological diagnosis. We extended our platform towards non-invasive directed detection of pancreatic cancer utilizing fluorescence molecular tomography (FMT) and NIR laparoscopy using identified targeted molecular probe. We were able to non-invasively distinguished between pancreatitis and pancreatic cancer and guide pancreatic tumor resection using NIR laparoscopy

    Changing landscape of optical imaging in skeletal metastases

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    Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics

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    Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.\ud \u

    In vivo imaging of protease activity by Probody therapeutic activation.

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    Probodyâ„¢ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment

    Broadband hyperspectral imaging for breast tumor detection using spectral and spatial information

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    Complete tumor removal during breast-conserving surgery remains challenging due to the lack of optimal intraoperative margin assessment techniques. Here, we use hyperspectral imaging for tumor detection in fresh breast tissue. We evaluated different wavelength ranges and two classification algorithms; a pixel-wise classification algorithm and a convolutional neural network that combines spectral and spatial information. The highest classification performance was obtained using the full wavelength range (450-1650nm). Adding spatial information mainly improved the differentiation of tissue classes within the malignant and healthy classes. High sensitivity and specificity were accomplished, which offers potential for hyperspectral imaging as a margin assessment technique to improve surgical outcome. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

    Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues

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    The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits

    Human serum albumin nanoparticles loaded with phthalocyanine dyes for potential use in photodynamic therapy of atherosclerotic plaques

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    Diseases caused by obstruction or rupture of vulnerable plaques in the arterial walls such as cardiovascular infarction or stroke are the leading cause of death in the world. In the present work, we developed human serum albuminnanoparticles loaded by physisorption with zinc phthalocyanine, TT1, mainly used for industrial application as near-infrared photosensitizer and compared these to HSA NPsloaded with the well-known silicone phthalocyanine (Pc4). The use of NIR light allows for better tissue penetration, while the use of nanoparticles permitshigh local concentrations. The particles were characterized and tested for toxicity and stability as well as for their potential use as a contrast agent and NIR photosensitizer for photodynamic therapy in cardiovascular disease. We focused on the distribution of the nanoparticles in RAW264.7macrophage cells and atherosclerotic mice. The nanoparticles had an average size of 120 nm according todynamic light scattering, good loading capacity for zinc phthalocyanine,and satisfying stability in 50% (v/v) fetal bovine serum for 8 hours and in an aqueous environment at 4°C for 4–6 weeks. Under light irradiation we found a high production of singlet oxygen and the products showed no dark toxicity in vitro with macrophages(the target cells in vulnerable plaques),but at a low μg/mL nanoparticleconcentration killed efficiently the macrophagesupon LED illumination. Injection of the contrast agentin atherosclerotic mice led to a visible fluorescence signal of zinc phthalocyaninein the atherosclerotic plaque at 30 minutes and in the lungs with afast clearance of the nanoparticles. Zinc phthalocyanine loaded human serum albumin nanoparticles present an interesting candidate for the visualization and potentially photodynamictreatment of macrophages in atherosclerotic plaquesThe research leading to these results has received funding from FP7-NMP CosmoPHOS-Nano under grant agreement No. 310337. Additional funding was received by the Spanish groups from MINECO (CTQ2017-85393-P) and ERA-NET/MINECO EuroNanoMed2017-191 / PCIN-2017-04

    In Vivo Fluorescence Imaging of E-Selectin: Quantitative Detection of Endothelial Activation in Arthritis

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    Rheumatoid arthritis (RA) is a chronic progressive systemic inflammatory disease, characterized by synovial inflammation and localized destruction of cartilage and bone. Heterogeneity in the clinical presentation of RA and uncertainty about which patients will respond to treatment makes diagnosis and management challenging. Fluorescent imaging in the near infrared (NIR) spectrum significantly decreases tissue autofluorescence offering unique potential to detect specific molecular targets in vivo. E-selectin or endothelial adhesion molecule-1 (ELAM-1), a 115kDa glycoprotein induced on endothelial cells in response to pro-inflammatory cytokines involved in RA, such as interleukin (IL)-1 beta and tumour necrosis factor alpha (TNF alpha). E-selectin has been well validated as a potential biomarker of disease activity. My study aimed to investigate whether E-selectin targeted optical imaging in vivo could be developed as a sensitive, specific and quantifiable preclinical molecular imaging technique, and also whether this approach could be used to delineate the molecular effects of novel therapies. I utilised anti-E-selectin antibody labelled with NIR fluorophore in a mouse model of paw swelling induced by intra-plantar injection of TNF alpha, and in acute collagen-induced arthritis (CIA) in DBA/1 mice, a widely used model of RA. E-selectin generated signal, localised to points of maximal clinical inflammation in the inflamed mouse paw in both models with significant differences to control antibody. Binding of anti-E-selectin antibody was also demonstrated by immunohistochemistry in both models. The ability of E-selectin targeted imaging to detect sub-clinical endothelial activation was also investigated, demonstrating that E-selectin may be an excellent way of determining subclinical vascular activation in CIA. Finally the effect of novel targeted therapy – RB200 which blocks epidermal growth factor (EGF) signalling was investigated. This demonstrated that E-selectin targeted signal could be absolutely abrogated to a level seen in unimmunised healthy control animals, following combination treatment with RB200 and the TNF alpha inhibitor etanercept. E-selectin targeted optical imaging is a viable in vivo imaging technique that can also be applied to quantify disease and investigate the effects of novel molecular therapies. It holds significant promise as a molecular imaging technique for future translation into the clinic for patients with rheumatoid arthritis and other inflammatory diseases
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