Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin.
Ontology highlight
ABSTRACT:
SUBMITTER: Saif M
PROVIDER: S-EPMC8310386 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.
| S-EPMC5924901 | biostudies-other
Project description:Advances in fluorescence imaging coupled with the generation of near infrared probes have significantly improved the capabilities of non-invasive, real-time imaging in whole animals. In this study we were able to overcome a limitation of in vivo fluorescence imaging and have established a dual cell tracking method where two different cell types can be monitored according to the spectral signature of the cell labelling fluorophore. Using a mouse model of acute liver injury, we have characterised the in vivo migration patterns of wild type and transgenic neutrophils with impaired chemotaxis. Here, we were able to demonstrate that IVIS provides a sensitive multiplexing technology to differentiate two different cell populations based on the spectral signature of the cell labelling fluorophores. This spectral unmixing methodology has the potential to uncover multidimensional cellular interactions involved in many diseases such as fibrosis and cancer. In vivo spectral un-mixing provides a useful tool for monitoring multiple biological process in real-time in the same animal.
| S-EPMC7809207 | biostudies-literature
Project description:BACKGROUND:Fundus autofluorescence is a non-invasive imaging technique in ophthalmology. Conventionally, short-wavelength autofluorescence (SW-AF) is used for detection of lipofuscin, a byproduct of the visual cycle which accumulates with age or disease in the retinal pigment epithelium (RPE). Furthermore, near-infrared autofluorescence (NIR-AF) is used as a marker for RPE and choroidal melanin, but contribution of lipofuscin to the NIR-AF signal is unclear. METHODS:We employed fluorescence microscopy to investigate NIR-AF properties of melanosomes, lipofuscin and melanolipofuscin granules in histologic sections of wildtype and Abca4-/- mouse eyes, the latter having increased lipofuscin, as well as aged human donor eyes. Differentiation between these pigments was verified by analytical electron microscopy. To investigate the influence of oxidative and photic stress we used an in vitro model with isolated ocular melanosomes and an in vivo phototoxicity mouse model. FINDINGS:We show that NIR-AF is not an intrinsic property of melanin, but rather increases with age and after photic or oxidative stress in mice and isolated melanosomes. Furthermore, when lipofuscin levels are high, lipofuscin granules also show NIR-AF, as confirmed by correlative fluorescence and electron microscopy in human tissue. However, lipofuscin in albino Abca4-/- mice lacks NIR-AF signals. INTERPRETATION:We suggest that NIR-AF is derived from melanin degradation products that accumulate with time in lipofuscin granules. These findings can help to improve the interpretation of patient fundus autofluorescence data. FUNDING:This work was supported by Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft and Chinese Scholarship Council. Major instrumentation used in this work was supported by Deutsche Forschungsgemeinschaft, the European Fund for Regional Development and the state of Baden-Württemberg.
| S-EPMC6838394 | biostudies-literature
Project description:The use of visible/NIR-emitting gold nanoclusters (Au NCs), previously proposed for in vivo imaging, has been limited to some extent by low quantum yields (QYs) and the limited penetration of visible light in tissue. Here we report short wavelength infrared (SWIR, ? = 1-2 ?m) emitting Au NCs with a good photoluminescence QY for this wavelength range (0.6% to 3.8% for ?em = 1000 to 900 nm) and excellent stability under physiological conditions. We show that surface ligand chemistry is critical to achieving these properties. We demonstrate the potential of these SWIR-emitting Au NCs for in vivo imaging in mice. The Au NCs have a hydrodynamic diameter that is small (?5 nm) enough that they exhibit a rapid renal clearance, and images taken in the SWIR region show better resolution of the blood vessels than in the NIR region.
| S-EPMC5902176 | biostudies-literature
Project description:Developing chemical tools to detect and influence biological processes is a cornerstone of chemical biology. Here we combine two tools which rely on orthogonality- perfluorocarbons and multiplexed shortwave infrared (SWIR) fluorescence imaging- to visualize nanoemulsions in real time in living mice. Drawing inspiration from fluorous and SWIR fluorophore development, we prepared two SWIR-emissive, fluorous-soluble chromenylium polymethine dyes. These are the most red-shifted fluorous fluorophores- "fluorofluorophores"-to date. After characterizing the dyes, their utility was demonstrated by tracking perfluorocarbon nanoemulsion biodistribution in vivo. Using an excitation-multiplexed approach to image two variables simultaneously, we gained insight into the importance of size and surfactant identity on biodistribution.
| S-EPMC9892283 | biostudies-literature
Project description:Autotaxin (ATX), an autocrine motility factor that is highly upregulated in metastatic cancer, is a lysophospholipase D enzyme that produces the lipid second messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Dysregulation of the lysolipid signaling pathway is central to the pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has emerged as an important source of biomarkers and therapeutic targets. Herein we describe development and validation of a fluorogenic analog of LPC (AR-2) that enables visualization of ATX activity in vivo. AR-2 exhibits minimal fluorescence until it is activated by ATX, which substantially increases fluorescence in the near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In mice with orthotopic ATX-expressing breast cancer tumors, ATX activated AR-2 fluorescence. Administration of AR-2 to tumor-bearing mice showed high fluorescence in the tumor and low fluorescence in most healthy tissues with tumor fluorescence correlated with ATX levels. Pretreatment of mice with an ATX inhibitor selectively decreased fluorescence in the tumor. Together these data suggest that fluorescence directly correlates with ATX activity and its tissue expression. The data show that AR-2 is a non-invasive and selective tool that enables visualization and quantitation of ATX-expressing tumors and monitoring ATX activity in vivo.
| S-EPMC3835791 | biostudies-literature
Project description:Fluorescent organic dyes that absorb and emit in the near-infrared (NIR, 700-1000 nm) and shortwave infrared (SWIR, 1000-1700 nm) regions have the potential to produce noninvasive high-contrast biological images and videos. BODIPY dyes are well known for their high quantum yields in the visible energy region. To tune these chromophores to the NIR region, fused nitrogen-based heterocyclic indolizine donors were added to a BODIPY scaffold. The indolizine BODIPY dyes were synthesized via microwave-assisted Knoevenagel condensation with indolizine aldehydes. The non-protonated dyes showed NIR absorption and emission at longer wavelengths than an aniline benchmark. Protonation of the dyes produced a dramatic 0.35 eV bathochromic shift (230 nm shift from 797 nm to 1027 nm) to give a SWIR absorption and emission (λmaxemis = 1061 nm). Deprotonation demonstrates that material emission is reversibly switchable between the NIR and SWIR.
| S-EPMC9919721 | biostudies-literature
Project description:Therapeutic drug monitoring (TDM) in cancer, while imperative, has been challenging due to inter-patient variability in drug pharmacokinetics. Additionally, most pharmacokinetic monitoring is done by assessments of the drugs in plasma, which is not an accurate gauge for drug concentrations in target tumor tissue. There exists a critical need for therapy monitoring tools that can provide real-time feedback on drug efficacy at target site to enable alteration in treatment regimens early during cancer therapy. Here, we report on theranostic optical imaging probes based on shortwave infrared (SWIR)-emitting rare earth-doped nanoparticles encapsulated with human serum albumin (abbreviated as ReANCs) that have demonstrated superior surveillance capability for detecting micro-lesions at depths of 1 cm in a mouse model of breast cancer metastasis. Most notably, ReANCs previously deployed for detection of multi-organ metastases resolved bone lesions earlier than contrast-enhanced magnetic resonance imaging (MRI). We engineered tumor-targeted ReANCs carrying a therapeutic payload as a potential theranostic for evaluating drug efficacy at the tumor site. In vitro results demonstrated efficacy of ReANCs carrying doxorubicin (Dox), providing sustained release of Dox while maintaining cytotoxic effects comparable to free Dox. Significantly, in a murine model of breast cancer lung metastasis, we demonstrated the ability for therapy monitoring based on measurements of SWIR fluorescence from tumor-targeted ReANCs. These findings correlated with a reduction in lung metastatic burden as quantified via MRI-based volumetric analysis over the course of four weeks. Future studies will address the potential of this novel class of theranostics as a preclinical pharmacological screening tool.
| S-EPMC7575924 | biostudies-literature
Project description:Cell-based tissue engineering strategies have been widely established. However, the contributions of the transplanted cells within the tissue-engineered scaffolds to the process of tissue regeneration remain poorly understood. Near-infrared (NIR) fluorescence imaging systems have great potential to non-invasively monitor the transplanted cell-based tissue constructs. In this study, labeling mesenchymal stem cells (MSCs) using a lipophilic pentamethine indocyanine (CTNF127, emission at 700 nm) as a NIR fluorophore was optimized, and the CTNF127-labeled MSCs (NIR-MSCs) were printed embedding in gelatin methacryloyl bioink. The NIR-MSCs-loaded bioink showed excellent printability. In addition, NIR-MSCs in the 3D constructs showed high cell viability and signal stability for an extended period in vitro. Finally, we were able to non-invasively monitor the NIR-MSCs in constructs after implantation in a rat calvarial bone defect model, and the transplanted cells contributed to tissue formation without specific staining. This NIR-based imaging system for non-invasive cell monitoring in vivo could play an active role in validating the cell fate in cell-based tissue engineering applications.
| S-EPMC8126817 | biostudies-literature
Project description:BackgroundComplete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial, we evaluated the efficacy of near-infrared (NIR) intraoperative imaging using second window indocyanine green during metastasectomy to identify known metastases and to detect occult nodules.MethodsThirty patients with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All patients received intravenous indocyanine green (5 mg/kg) 24 hours before metastasectomy. Patients 1 through 10 (cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within cohort 1, patients 11 through 30 (cohort 2) underwent video-assisted thoracic surgery metastasectomy with NIR imaging.ResultsIn cohort 1, 14 out of 16 preoperatively identified pulmonary metastases (87.5%) displayed tumor fluorescence. Nonfluorescent metastases were deeper than fluorescent metastases (2.1 cm vs 1.3 cm; P = .03). Five out of 5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In cohort 2, 33 out of 37 known pulmonary metastases (89.1%) displayed fluorescence. Nonfluorescent tumors were deeper than 2.0 cm (P = .007). NIR imaging identified 24 additional occult lesions. Of 24 occult lesions, 21 (87.5%) were confirmed metastases and the remaining 3 nodules were lymphoid aggregates.ConclusionsNIR intraoperative imaging with indocyanine green (5 mg/kg and 24 hours before surgery) localizes known sarcoma pulmonary metastases and identifies otherwise occult lesions. This approach may be a useful intraoperative adjunct to improve metastasectomy.
| S-EPMC6625353 | biostudies-literature