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  1. Article ; Online: Improving precision surgery: A review of current intraoperative nerve tissue fluorescence imaging.

    Wang, Lei G / Gibbs, Summer L

    Current opinion in chemical biology

    2023  Volume 76, Page(s) 102361

    Abstract: Iatrogenic nerve injury represents one of the most feared surgical complications and remains a major morbidity across many surgical specialties. Currently, no clinically approved technique can directly enhance intraoperative nerve visualization, where ... ...

    Abstract Iatrogenic nerve injury represents one of the most feared surgical complications and remains a major morbidity across many surgical specialties. Currently, no clinically approved technique can directly enhance intraoperative nerve visualization, where intraoperative nerve identification continues to challenge even experienced surgeons. Fluorescence-guided surgery (FGS) has been successfully integrated into clinical medicine to improve safety and efficacy in the surgical arena. A number of tissue- and disease-specific contrast agents are in the clinical translation pipeline for future FGS integration. Within this context, a diverse repertoire of fluorescent tracers have been developed to improve surgeons' intraoperative vision. This review aims to convey the recent developments for nerve-specific FGS and its potential for clinical translation.
    MeSH term(s) Fluorescent Dyes ; Fluorescence ; Optical Imaging/methods ; Contrast Media ; Surgery, Computer-Assisted/methods ; Nerve Tissue
    Chemical Substances Fluorescent Dyes ; Contrast Media
    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1439176-4
    ISSN 1879-0402 ; 1367-5931
    ISSN (online) 1879-0402
    ISSN 1367-5931
    DOI 10.1016/j.cbpa.2023.102361
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Use of Freshly Amputated Human Limbs for Pre-Clinical Evaluation of Molecular-Targeted Fluorescent Probes.

    Bateman, Logan M / Hebert, Kendra A / Streeter, Samuel S / Nunziata, Jenna A / Barth, Connor W / Wang, Lei G / Gibbs, Summer L / Henderson, Eric R

    Proceedings of SPIE--the International Society for Optical Engineering

    2023  Volume 12361

    Abstract: We have co-developed a first-in-kind model of fluorophore testing in freshly amputated human limbs. ...

    Abstract We have co-developed a first-in-kind model of fluorophore testing in freshly amputated human limbs.
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article
    ISSN 0277-786X
    ISSN 0277-786X
    DOI 10.1117/12.2650356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs.

    Bateman, Logan M / Hebert, Kendra A / Nunziata, Jenna A / Streeter, Samuel S / Barth, Connor W / Wang, Lei G / Gibbs, Summer L / Henderson, Eric R

    Journal of biomedical optics

    2023  Volume 28, Issue 8, Page(s) 82802

    Abstract: Significance: This first-in-kind, perfused, and amputated human limb model allows for the collection of human data in preclinical selection of lead fluorescent agents. The model facilitates more accurate selection and testing of fluorophores with human- ... ...

    Abstract Significance: This first-in-kind, perfused, and amputated human limb model allows for the collection of human data in preclinical selection of lead fluorescent agents. The model facilitates more accurate selection and testing of fluorophores with human-specific physiology, such as differential uptake and signal in fat between animal and human models with zero risk to human patients. Preclinical testing using this approach may also allow for the determination of tissue toxicity, clearance time of fluorophores, and the production of harmful metabolites.
    Aim: This study was conducted to determine the fluorescence intensity values and tissue specificity of a preclinical, nerve tissue targeted fluorophore, as well as the capacity of this first-in-kind model to be used for lead fluorescent agent selection in the future.
    Approach: Freshly amputated human limbs were perfused for 30 min prior to
    Results: In situ
    Conclusions: This model demonstrates an opportunity for preclinical testing, evaluation, and selection of fluorophores for use in clinical trials as well as an opportunity to study peripheral pathologies in a controlled environment.
    MeSH term(s) Animals ; Humans ; Fluorescent Dyes/metabolism ; Muscles ; Extremities ; Optical Imaging/methods ; Amputees
    Chemical Substances Fluorescent Dyes
    Language English
    Publishing date 2023-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1309154-2
    ISSN 1560-2281 ; 1083-3668
    ISSN (online) 1560-2281
    ISSN 1083-3668
    DOI 10.1117/1.JBO.28.8.082802
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.

    Wang, Lei G / Montaño, Antonio R / Combs, Jason R / McMahon, Nathan P / Solanki, Allison / Gomes, Michelle M / Tao, Kai / Bisson, William H / Szafran, Dani A / Samkoe, Kimberley S / Tichauer, Kenneth M / Gibbs, Summer L

    Nature chemistry

    2023  Volume 15, Issue 5, Page(s) 729–739

    Abstract: Non-destructive fluorophore diffusion across cell membranes to provide an unbiased fluorescence intensity readout is critical for quantitative imaging applications in live cells and tissues. Commercially available small-molecule fluorophores have been ... ...

    Abstract Non-destructive fluorophore diffusion across cell membranes to provide an unbiased fluorescence intensity readout is critical for quantitative imaging applications in live cells and tissues. Commercially available small-molecule fluorophores have been engineered for biological compatibility, imparting high water solubility by modifying rhodamine and cyanine dye scaffolds with multiple sulfonate groups. The resulting net negative charge, however, often renders these fluorophores cell-membrane-impermeant. Here we report the design and development of our biologically compatible, water-soluble and cell-membrane-permeable fluorophores, termed OregonFluor (ORFluor). By adapting previously established ratiometric imaging methodology using bio-affinity agents, it is now possible to use small-molecule ORFluor-labelled therapeutic inhibitors to quantitatively visualize their intracellular distribution and protein target-specific binding, providing a chemical toolkit for quantifying drug target availability in live cells and tissues.
    MeSH term(s) Fluorescent Dyes/chemistry ; Rhodamines/chemistry ; Water
    Chemical Substances Fluorescent Dyes ; Rhodamines ; Water (059QF0KO0R)
    Language English
    Publishing date 2023-03-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2464596-5
    ISSN 1755-4349 ; 1755-4330
    ISSN (online) 1755-4349
    ISSN 1755-4330
    DOI 10.1038/s41557-023-01173-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Investigation of Oxazine and Rhodamine Derivatives as Peripheral Nerve Tissue Targeting Contrast Agent for

    Wang, Lei G / Barth, Connor W / Combs, Jason R / Montaño, Antonio R / Gibbs, Summer L

    Proceedings of SPIE--the International Society for Optical Engineering

    2019  Volume 10862

    Abstract: Accidental nerve transection or injury is a significant morbidity associated with many surgical interventions, resulting in persistent postsurgical numbness, chronic pain, and/or paralysis. Nerve-sparing can be a difficult task due to patient-to-patient ... ...

    Abstract Accidental nerve transection or injury is a significant morbidity associated with many surgical interventions, resulting in persistent postsurgical numbness, chronic pain, and/or paralysis. Nerve-sparing can be a difficult task due to patient-to-patient variability and the difficulty of nerve visualization in the operating room. Fluorescence image-guided surgery to aid in the precise visualization of vital nerve structures in real time during surgery could greatly improve patient outcomes. To date, all nerve-specific contrast agents emit in the visible range. Developing a near-infrared (NIR) nerve-specific fluorophore is poised to be a challenging task, as a NIR fluorophore must have enough "double-bonds" to reach the NIR imaging window, contradicting the requirement that a nerve-specific agent must have a relatively low molecular weight to cross the blood-nerve-barrier (BNB). Herein we report our efforts to investigate the molecular characteristics for the nerve-specific oxazine fluorophores, as well as their structurally analogous rhodamine fluorophores. Specifically, optical properties, physicochemical properties and their
    Language English
    Publishing date 2019-03-07
    Publishing country United States
    Document type Journal Article
    ISSN 0277-786X
    ISSN 0277-786X
    DOI 10.1117/12.2507296
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A clinically relevant formulation for direct administration of nerve specific fluorophores to mitigate iatrogenic nerve injury

    Barth, Connor W. / Shah, Vidhi M. / Wang, Lei G. / Masillati, Anas M. / Al-Fatease, Adel / Husain Rizvi, Syed Zaki / Antaris, Alexander L. / Sorger, Jonathan / Rao, Deepa A. / Alani, Adam W.G. / Gibbs, Summer L.

    Biomaterials. 2022 May, v. 284

    2022  

    Abstract: Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. ... ...

    Abstract Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. Fluorescence guided surgery (FGS) offers a potential solution for improved nerve sparing by providing direct visualization of nerve tissue intraoperatively. However, novel probes for FGS face a long regulatory pathway to achieve clinical translation. Herein, we report on the development of a clinically-viable, gel-based formulation that enables direct administration of nerve-specific probes for nerve sparing FGS applications, facilitating clinical translation via the exploratory investigational new drug (eIND) guidance. The developed formulation possesses unique gelling characteristics, allowing it to be easily spread as a liquid followed by rapid gelling for subsequent tissue hold. Optimization of the direct administration protocol with our gel-based formulation enabled a total staining time of 1–2 min for compatibility with surgical procedures and successful clinical translation.
    Keywords biocompatible materials ; drugs ; fluorescence ; fluorescent dyes ; liquids ; nerve tissue ; surgery
    Language English
    Dates of publication 2022-05
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2022.121490
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.

    Barth, Connor W / Rizvi, Syed Zaki Husain / Masillati, Anas M / Chakraborty, Samrat / Wang, Lei G / Montaño, Antonio R / Szafran, Dani A / Greer, William S / van den Berg, Nynke S / Sorger, Jonathan / Rao, Deepa A / Alani, Adam W G / Gibbs, Summer L

    Small (Weinheim an der Bergstrasse, Germany)

    2023  , Page(s) e2300011

    Abstract: Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve-sparing efforts during ... ...

    Abstract Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve-sparing efforts during standard gynecological procedures such as hysterectomy, cystectomy, and colorectal cancer resection difficult, and thus many patients are left with incontinence and sexual dysfunction. Herein, a near-infrared (NIR) fluorescent nerve-specific contrast agent, LGW08-35, that is spectrally compatible with clinical fluorescence guided surgery (FGS) systems is formulated and characterized for rapid implementation for nerve-sparing gynecologic surgeries. The toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) of micelle formulated LGW08-35 are examined, enabling the determination of the optimal imaging doses and time points, blood and tissue uptake parameters, and maximum tolerated dose (MTD). Application of the formulated fluorophore to imaging of female rat and swine pelvic neuroanatomy validates the continued clinical translation and use for real-time identification of important nerves such as the femoral, sciatic, lumbar, iliac, and hypogastric nerves. Further development of LGW08-35 for clinical use will unlock a valuable tool for surgeons in direct visualization of important nerves and contribute to the ongoing characterization of the female pelvic neuroanatomy to eliminate the debilitating side effects of nerve damage during gynecological procedures.
    Language English
    Publishing date 2023-07-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2168935-0
    ISSN 1613-6829 ; 1613-6810
    ISSN (online) 1613-6829
    ISSN 1613-6810
    DOI 10.1002/smll.202300011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Lead Optimization of Nerve-Specific Fluorophores for Image-Guided Nerve Sparing Surgical Procedures.

    Barth, Connor W / Wang, Lei G / Montano, Antonio / Antaris, Alexander L / Klaassen, Alwin / Sorger, Jonathan / Kerr, Darcy A / Henderson, Eric R / Alani, Adam W G / Gibbs, Summer L

    Optical molecular probes, imaging and drug delivery

    2022  Volume 2021

    Abstract: Nerve damage is a major complication of surgery, causing pain and loss of function. We have identified novel near-infrared nerve-specific fluorophores that provide excellent nerve contrast with the ability to identify buried nerve tissue. ...

    Abstract Nerve damage is a major complication of surgery, causing pain and loss of function. We have identified novel near-infrared nerve-specific fluorophores that provide excellent nerve contrast with the ability to identify buried nerve tissue.
    Language English
    Publishing date 2022-09-02
    Publishing country United States
    Document type Journal Article
    DOI 10.1364/OMP.2021.OW3E.3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Publisher Correction: OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.

    Wang, Lei G / Montaño, Antonio R / Combs, Jason R / McMahon, Nathan P / Solanki, Allison / Gomes, Michelle M / Tao, Kai / Bisson, William H / Szafran, Dani A / Samkoe, Kimberley S / Tichauer, Kenneth M / Gibbs, Summer L

    Nature chemistry

    2022  Volume 15, Issue 5, Page(s) 740

    Language English
    Publishing date 2022-03-24
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2464596-5
    ISSN 1755-4349 ; 1755-4330
    ISSN (online) 1755-4349
    ISSN 1755-4330
    DOI 10.1038/s41557-023-01213-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A clinically relevant formulation for direct administration of nerve specific fluorophores to mitigate iatrogenic nerve injury.

    Barth, Connor W / Shah, Vidhi M / Wang, Lei G / Masillati, Anas M / Al-Fatease, Adel / Husain Rizvi, Syed Zaki / Antaris, Alexander L / Sorger, Jonathan / Rao, Deepa A / Alani, Adam W G / Gibbs, Summer L

    Biomaterials

    2022  Volume 284, Page(s) 121490

    Abstract: Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. ... ...

    Abstract Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. Fluorescence guided surgery (FGS) offers a potential solution for improved nerve sparing by providing direct visualization of nerve tissue intraoperatively. However, novel probes for FGS face a long regulatory pathway to achieve clinical translation. Herein, we report on the development of a clinically-viable, gel-based formulation that enables direct administration of nerve-specific probes for nerve sparing FGS applications, facilitating clinical translation via the exploratory investigational new drug (eIND) guidance. The developed formulation possesses unique gelling characteristics, allowing it to be easily spread as a liquid followed by rapid gelling for subsequent tissue hold. Optimization of the direct administration protocol with our gel-based formulation enabled a total staining time of 1-2 min for compatibility with surgical procedures and successful clinical translation.
    MeSH term(s) Fluorescent Dyes ; Gels ; Humans ; Iatrogenic Disease ; Nerve Tissue
    Chemical Substances Fluorescent Dyes ; Gels
    Language English
    Publishing date 2022-03-28
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2022.121490
    Database MEDical Literature Analysis and Retrieval System OnLINE

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