scholarly journals Intravascular Molecular Imaging: Near-Infrared Fluorescence as a New Frontier

2020 ◽  
Vol 7 ◽  
Author(s):  
Haitham Khraishah ◽  
Farouc A. Jaffer
Keyword(s):  
Near Infrared ◽  
Imaging Modality ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Endothelial Permeability ◽  
Intravascular Imaging ◽  
Near Infrared Fluorescence ◽  
New Era ◽  
Nirf Imaging

Despite exciting advances in structural intravascular imaging [intravascular ultrasound (IVUS) and optical coherence tomography (OCT)] that have enabled partial assessment of atheroma burden and high-risk features associated with acute coronary syndromes, structural-based imaging modalities alone do not comprehensively phenotype the complex pathobiology of atherosclerosis. Near-infrared fluorescence (NIRF) is an emerging molecular intravascular imaging modality that allows for in vivo visualization of pathobiological and cellular processes at atheroma plaque level, including inflammation, oxidative stress, and abnormal endothelial permeability. Established intravascular NIRF imaging targets include macrophages, cathepsin protease activity, oxidized low-density lipoprotein and abnormal endothelial permeability. Structural and molecular intravascular imaging provide complementary information about plaque microstructure and biology. For this reason, integrated hybrid catheters that combine NIRF-IVUS or NIRF-OCT have been developed to allow co-registration of morphological and molecular processes with a single pullback, as performed for standalone IVUS or OCT. NIRF imaging is approaching application in clinical practice. This will be accelerated by the use of FDA-approved indocyanine green (ICG), which illuminates lipid- and macrophage-rich zones of permeable atheroma. The ability to comprehensively phenotype coronary pathobiology in patients will enable a deeper understanding of plaque pathobiology, improve local and patient-based risk prediction, and usher in a new era of personalized therapy.

scholarly journals In Vivo Near-Infrared Fluorescence Imaging of Matrix Metalloproteinase Activity after Cerebral Ischemia

2009 ◽  
Vol 29 (7) ◽  
pp. 1284-1292 ◽  
Author(s):  
Jan Klohs ◽  
Nevena Baeva ◽  
Jens Steinbrink ◽  
Riad Bourayou ◽  
Chotima Boettcher ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Near Infrared ◽  
Artery Occlusion ◽  
Substantial Contribution ◽  
Fluorescence Signal ◽  
Sham Operation ◽  
Near Infrared Fluorescence ◽  
Nirf Imaging ◽  
Activatable Probe

Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of cerebral ischemia. In this study, we explored whether MMP activity can be visualized by noninvasive near-infrared fluorescence (NIRF) imaging using an MMP-activatable probe in a mouse model of stroke. C57BI6 mice were subjected to transient middle cerebral artery occlusion (MCAO) or sham operation. Noninvasive NIRF imaging was performed 24 h after probe injection, and target-to-background ratios (TBRs) between the two hemispheres were determined. TBRs were significantly higher in MCAO mice injected with the MMP-activatable probe than in sham-operated mice and in MCAO mice that were injected with the nonactivatable probe as controls. Treatment with an MMP inhibitor resulted in significantly lower TBRs and lesion volumes compared to injection of vehicle. To test the contribution of MMP-9 to the fluorescence signal, MMP9-deficient (MMP9−/-) mice and wild-type controls were subjected to MCAO of different durations to attain comparable lesion volumes. TBRs were significantly lower in MMP9−/- mice, suggesting a substantial contribution of MMP-9 activity to the signal. Our study shows that MMP activity after cerebral ischemia can be imaged noninvasively with NIRF using an MMP-activatable probe, which might be a useful tool to study MMP activity in the pathophysiology of the disease.

In vivo pharmacodynamic evaluation of antidepressants based on flux mitochondrial Cys in living mice via near infrared fluorescence imaging

The Analyst ◽  
2020 ◽  
Vol 145 (18) ◽  
pp. 6119-6124
Author(s):  
Xin Wang ◽  
Jiali Zha ◽  
Wei Zhang ◽  
Wen Zhang ◽  
Bo Tang
Keyword(s):  
Fluorescence Imaging ◽  
Mouse Brain ◽  
Near Infrared ◽  
Near Infrared Fluorescence ◽  
Nirf Imaging ◽  
New Strategy ◽  
Near Infrared Fluorescence Imaging

We proposed a new strategy for in vivo evaluation of antidepressants through NIRF imaging for mitochondrial Cys in the mouse brain.

scholarly journals LDL receptor-peptide conjugate as in vivo tool for specific targeting of pancreatic ductal adenocarcinoma

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Angélina Acier ◽  
Magali Godard ◽  
Fanny Gassiot ◽  
Pascal Finetti ◽  
Marion Rubis ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Near Infrared ◽  
Low Density Lipoprotein ◽  
Survival Rates ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Targeting Peptide

AbstractDespite clinical advances in diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains the third leading cause of cancer death, and is still associated with poor prognosis and dismal survival rates. Identifying novel PDAC-targeted tools to tackle these unmet clinical needs is thus an urgent requirement. Here we use a peptide conjugate that specifically targets PDAC through low-density lipoprotein receptor (LDLR). We demonstrate by using near-infrared fluorescence imaging the potential of this conjugate to specifically detect and discriminate primary PDAC from healthy organs including pancreas and from benign mass-forming chronic pancreatitis, as well as detect metastatic pancreatic cancer cells in healthy liver. This work paves the way towards clinical applications in which safe LDLR-targeting peptide conjugate promotes tumor-specific delivery of imaging and/or therapeutic agents, thereby leading to substantial improvements of the PDAC patient’s outcome.

Novel Fluorophores as Building Blocks for Optical Probes for In Vivo Near Infrared Fluorescence (NIRF) Imaging

2010 ◽  
Vol 20 (3) ◽  
pp. 681-693 ◽  
Author(s):  
Jutta Pauli ◽  
Robert Brehm ◽  
Monika Spieles ◽  
Werner A. Kaiser ◽  
Ingrid Hilger ◽  
...  
Keyword(s):  
Near Infrared ◽  
Building Blocks ◽  
Optical Probes ◽  
Near Infrared Fluorescence ◽  
Nirf Imaging

Abstract 647: Induction of Cardiovascular Calcification in Non-transgenic Mice via a Single Injection of Pcsk9 Adeno-associated Viral Vector

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Claudia Goettsch ◽  
Joshua Hutcheson ◽  
Sumihiko Hagita ◽  
Maximillian Rogers ◽  
Jung Choi ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Near Infrared ◽  
Viral Vector ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lesion Size ◽  
Aortic Calcification

Background: Studying atherosclerotic calcification in vivo requires mouse models with genetic deletion of low-density lipoprotein receptor (Ldlr) or apolipoprotein E. A previous study showed a rapid induction of atherosclerosis by proprotein convertase subtilisin/kexin type 9 (PCSK9) in mice. Here, we hypothesize that this method is a useful in vivo tool to study cardiovascular calcification in non-genetically modified C57BL/6 mice. Results: 10 week old C57BL/6 mice received a single tail vein injection of recombinant adeno-associated viral vector (AAV) encoding PCSK9 (rAAV8/D377Y-mPCSK9). Ldlr -/- and saline injected C57BL/6 mice served as controls. Mice consumed a high-fat, high-cholesterol (HF/HC) diet for 15-20 weeks. PCSK9 and total cholesterol serum levels were significantly increased within one week after injection and maintained for 20 weeks (cholesterol: 82 mg/dL to 820 mg/dL, p<0.01; PCSK9: 0.14 μg/ml to 20 μg/ml, p<0.01). Total cholesterol levels remained 20-30% lower than those of of Ldlr -/- mice. Atherosclerotic lesion size was similar between PSCK9 and Ldlr -/- mice. Saline injected mice did not show any lesions. Plaque collagen content was 31.9%±6.6 in PCSK9 mice and 62.9%±16.6 in Ldlr -/- mice at 15 weeks of HF/HC diet (p=0.01). However, by 20 weeks, the PCSK9 mice had 57.9%±18.6 plaque collagen, suggesting a different stage of plaque progression. Fluorescence reflectance imaging of a near infrared calcium tracer in intact arteries detected 0.4%±0.4 aortic calcification in PCSK9 mice and 9.7%±1.6 in Ldlr -/- mice at 15 weeks of HF/HC diet (p=0.01); by 20 weeks, the PCSK9 mice had 5.3%±1.0 aortic calcification. Tissue non-specific alkaline phosphatase activity positive lesion area was 7.9%±4.0 and 8.3%±2.6 in PCSK9 mice and 10.8%±2.5 and 12.7%±1.7in Ldlr -/- mice at 15 and 20 weeks, respectively. Immunofluorescence analysis demonstrated accumulation of CD68 and RUNX2-positive cells in the plaques of PCSK9 mice similar to Ldlr -/- . Conclusion: While injection of recombinant AAV encoding PCSK9 into C57BL/6 mice induces atherosclerotic calcification with slower sclerotic plaque remodeling compared to Ldlr -/- mice, it may serve as a useful tool to study cardiovascular calcification in mice independent of their genetic background.

scholarly journals Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jianbo Li ◽  
Baoliang Bao ◽  
Lei Liu ◽  
Xuemei Wang
Keyword(s):  
Near Infrared ◽  
Imaging Modality ◽  
Receptor Expression ◽  
Athymic Mice ◽  
Binding Studies ◽  
Preclinical Research ◽  
Near Infrared Fluorescence ◽  
Tumor Xenografts ◽  
Nirf Imaging ◽  
Ht 29

Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research.

Abstract 656: In Vivo Plaque Inflammation and Endothelial Permeability Independently Predict Atherosclerosis Progression: A Serial Multimodality Imaging Study

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Eric A Osborn ◽  
Giovanni J Ughi ◽  
Johan W Verjans ◽  
Edouard Gerbaud ◽  
Richard A Takx ◽  
...  
Keyword(s):  
Near Infrared ◽  
Ex Vivo ◽  
Multimodality Imaging ◽  
Endothelial Permeability ◽  
Imaging Study ◽  
Plaque Burden ◽  
Plaque Progression ◽  
Nirf Imaging ◽  
Imaging Results

Background: Atheroma inflammation impairs plaque stability and promotes plaque progression and complications. However, it is unknown how measures of plaque biology relate to changes in plaque burden, and whether plaque biology can independently predict plaque progression in coronary-sized arteries. This study evaluated the ability of intravascular near-infrared fluorescence (NIRF) biological imaging to inform experimental atheroma progression in vivo. Methods: Atherosclerosis was induced by balloon-injury in the aorta of 14 cholesterol-fed rabbits. Serial intravascular ultrasound (IVUS) and dual-modality intravascular NIRF - optical coherence tomography (OCT) imaging was performed following injection of a NIRF molecular imaging agent of plaque inflammatory protease activity (ProSense VM110; n=7), or impaired plaque endothelial permeability (indocyanine green (ICG); n=7). Plaque progression was further assessed by IVUS change in plaque burden. Regression analysis was used to evaluate the association of NIRF with plaque progression. In vivo imaging results were corroborated by ex vivo fluorescence reflectance imaging, fluorescence microscopy, and histopathology. Results: Quantitative analysis of 1,811 axial images spanning individual plaques, the change in NIRF plaque biological signals from 8 to 12 weeks strongly correlated with IVUS plaque burden from 8 to 12 weeks (ProSense VM110: r=0.774; ICG: r=0.572; p<0.0001). This finding remained significant on multivariate analysis adjusted for IVUS plaque burden, lumen area, and remodeling index (p<0.001). In additional multivariate analyses, the baseline NIRF signal at 8 weeks further predicted the magnitude of plaque progression even after adjustment for baseline plaque burden (p<0.001 for Prosense VM110; p=0.004 for ICG). Histology demonstrated NIRF agent uptake in inflamed, lipid-rich plaques. Conclusion: Plaque pathobiology and plaque burden progress in concert as assessed by translatable intravascular NIRF imaging technology. The baseline NIRF inflammation and impaired plaque permeability signals independently predict plaque progression. Integrated biological-microstructural imaging may enhance the ability to detect high-risk plaques at risk of progression.

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