Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents

Sevick‐Muraca, Eva M.; Houston, Jessica P.; Gurfinkel, Michael

doi:10.1016/s1367-5931(02)00356-3

Cited by 320 publications

(226 citation statements)

References 40 publications

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“…Recent advances in optical tomography suggest that depth penetration up to 4 cm may someday be possible. 22,23 A second limitation of this method is its inability to measure the functional metabolic response to cardioplegia delivery; in essence, adequate flow of cardioplegia does not always correlate with protection from myocardial ischemia. Nevertheless, without the technology we describe in this study, there is no simple way to even assess cardioplegia distribution prior to cardiac arrest.…”

Section: Discussionmentioning

confidence: 99%

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Soltesz¹,

Laurence²,

Grand³

et al. 2007

The Heart Surgery Forum

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Objectives-Homogenous distribution of cardioplegia delivered to the myocardium has been identified as an important predictor of post-cardiopulmonary bypass ventricular recovery and function. Presently, a method to determine adequate distribution of cardioplegia in patients during cardiac surgery does not exist. The goal of this study was to evaluate the feasibility of quantifying cardioplegia delivery using a novel, non-invasive optical method. Such a system would permit instantaneous imaging of jeopardized myocardium and allow immediate, intraoperative corrective measures.Methods-We have previously developed a portable, intraoperative near-infrared (NIR) fluorescence imaging system for use in large animal cardiac surgery, which simultaneously displays color video and NIR fluorescent images of the surgical field. By introducing exogenous, non-isotopic NIR fluorophores, specific cardiac functions can be visualized in real-time.Results-In a cardiopulmonary bypass porcine model, we demonstrate that the FDA-approved intravascular fluorophore indocyanine green (ICG) permits real-time assessment of cardioplegia delivery. ICG was injected into an aortic root and/or transatrial coronary sinus catheter during delivery of cold crystalloid cardioplegia solution. Segmental distribution was immediately noted at the time of injection. In a subset of animals, simulated coronary occlusions resulted in imaging defects consistent with poor cardioplegia delivery and jeopardized myocardium. Videodensitometric analysis was performed on-line to quantify right and left ventricular (RV, LV) distribution.Conclusions-We report the development of a novel, non-invasive, intraoperative technique which can easily and safely provide a visual assessment of cardioplegia delivery (antegrade and/or retrograde) and which offers the potential to quantify the relative segmental distribution during cardiac surgical procedures.ULTRAMINI ABSTRACT-Intraoperative near-infrared fluorescence imaging is a novel, noninvasive technique that can safely and easily visualize and quantify cardioplegia distribution during cardiac surgery. This system should permit surgeons to identify regions of poor myocardial protection, and guide interventions, intraoperatively and in real-time.

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Section: Discussionmentioning

confidence: 99%

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Soltesz¹,

Laurence²,

Grand³

et al. 2007

The Heart Surgery Forum

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“…Dimeric RGD peptide, E[c(RGDyK)] 2 , was prepared according to the literature method (37). The tetrameric RGD peptide E{E[c(RGDyK)] 2 } 2 was obtained by coupling Boc-protected glutamic acid activated ester Boc-E(OSu) 2 with RGD dimer E[c(RGDyK)] 2 in the presence of diiso-propylethylamine (DIPEA) (pH = 8.5-9) followed by semipreparative HPLC purification (46).…”

Section: Peptide Synthesismentioning

confidence: 99%

Near-Infrared Fluorescent RGD Peptides for Optical Imaging of Integrin α_vβ₃ Expression in Living Mice

et al. 2005

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Near-infrared fluorescence optical imaging is a powerful technique for studying diseases at the molecular level in preclinical models. We recently reported that monomeric RGD peptide c(RGDyK) conjugated to the NIR fluorescent dye specifically targets integrin receptor both in cell culture and in living subjects. In this report, Cy5.5-conjugated mono-, di-, and tetrameric RGD peptides were evaluated in a subcutaneous U87MG glioblastoma xenograft model in order to investigate the effect of multimerization of RGD peptide on integrin avidity and tumor targeting efficacy. The binding affinities of Cy5.5-conjugated RGD monomer, dimer, and tetramer for α v β 3 integrin expressed on U87MG cell surface were determined to be 42.9 ± 1.2, 27.5 ± 1.2, and 12.1 ± 1.3 nmol/L, respectively. All three peptide-dye conjugates had integrin specific uptake both in vitro and in vivo. The subcutaneous U87MG tumor can be clearly visualized with each of these three fluorescent probes. Among them, tetramer displayed highest tumor uptake and tumor-tonormal tissue ratio from 0.5 to 4 h postinjection. Tumor-to-normal tissue ratio for Cy5.5-conjugated RGD monomer, dimer, and tetramer were found to be 3.18 ± 0.16, 2.98 ± 0.05, and 3.63 ± 0.09, respectively, at 4 h postinjection. These results suggest that Cy5.5-conjugated monomeric, dimeric, and tetrameric RGD peptides are all suitable for integrin expression imaging. The multmerization of RGD peptide results in moderate improvement of imaging characteristics of the tetramer, compared to that of the monomer and dimeric counterparts.

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“…The reaction was quenched with water, diluted with CHCl 3 , and washed three times with aq. NH 4 Cl. The organic layer was collected, dried with Na 2 SO 4 , filtered, and evaporated.…”

Section: Introductionmentioning

confidence: 99%

Controlling Bulk Optical Properties of Emissive Polymersomes through Intramembranous Polymer−Fluorophore Interactions

Ghoroghchian

Frail

et al. 2007

Chem. Mater.

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Interdisciplinary investigation at the interface of chemistry, engineering, and medicine has enabled the development of self-assembled nanomaterials with novel biochemical and electro-optical properties. We have recently shown that emissive polymersomes, polymer vesicles incorporating porphyrin-based fluorophores, feature large integrated-emission oscillator strengths and narrow emission bands; these nanoscale assemblies can be further engineered to fluoresce at discrete wavelengths throughout the visible and near-infrared (NIR) spectral domains. As such, emissive polymersomes effectively define an organic-based family of soft-matter quantum-dot analogs that possess not only impressive optical properties, but also tunable physical and biomaterial characteristics relative to inorganic fluorescent nanoparticles.Here, we expand upon our initial studies on poly(ethyleneoxide)-block-poly(butadiene)-based vesicles to examine fluorophore membrane-loading in other polymersome systems. Through modulation of fluorophore ancilliary group substituents and choice of polymer chain chemistries, we are able to predictably control intramembranous polymer-fluorophore interactions; these phenomena, in turn, influence the nature of fluorophore solvation, local dielectric environment, and emission quantum yield within emissive polymersome assemblies. By utilizing different classes of vesiclegenerating diblock copolymers, including bioresorbable poly(ethyleneoxide)-block-poly(ε-caprolactone) (PEO-b-PCL) and poly(ethyleneoxide)-block-poly(γ-methyl-ε-caprolactone) (PEO-b-PMCL), we ascertain general principles important for engineering nanoscale optical vesicles. Further, this work heralds the first generation of fully-biodegradable fluorescent nanoparticles suitable for deep-tissue in vivo imaging.

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Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents

Cited by 320 publications

References 40 publications

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Near-Infrared Fluorescent RGD Peptides for Optical Imaging of Integrin α_vβ₃ Expression in Living Mice

Controlling Bulk Optical Properties of Emissive Polymersomes through Intramembranous Polymer−Fluorophore Interactions

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Fluorescence-enhanced, near infrared diagnostic imaging with contrast agents

Cited by 320 publications

References 40 publications

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Image-Guided Quantification of Cardioplegia Delivery during Cardiac Surgery

Near-Infrared Fluorescent RGD Peptides for Optical Imaging of Integrin αvβ3 Expression in Living Mice

Controlling Bulk Optical Properties of Emissive Polymersomes through Intramembranous Polymer−Fluorophore Interactions

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Near-Infrared Fluorescent RGD Peptides for Optical Imaging of Integrin α_vβ₃ Expression in Living Mice