Dr. Connor W. Barth Profile

Dr. Connor W. Barth

Senior Research Associate

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Publications (24)

Proceedings Article | 13 March 2024 Presentation

Development of near-infrared fluorophores for improved nerve-sparing surgical procedures

Lei Wang, Connor Barth, Antonio Montaño, Anas Masillati, Dani Szafran, Summer Gibbs

Proceedings Volume PC12862, PC1286205 (2024) https://doi.org/10.1117/12.3003618

KEYWORDS: Nerve, Fluorophores, Near infrared, Visualization, Surgery, Nervous system, Injuries, Imaging systems, Contrast agents, Real time imaging

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Proceedings Article | 13 March 2024 Presentation

Can near infrared nerve-specific imaging assess nerve integrity?

Anas Masillati, Antonio Montaño, Connor Barth, Lei Wang, Summer Gibbs

Proceedings Volume PC12825, PC128250I (2024) https://doi.org/10.1117/12.3004839

KEYWORDS: Nerve, Injuries, Fluorophores, Surgery, Visualization, Near infrared, Fluorescence intensity, Electromyography, Nerve regeneration, Medicine

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SPIE Journal Paper | 18 April 2023 Open Access

Dual probe difference specimen imaging for prostate cancer margin assessment

Marcus J. Kwon, Broderick J. House, Connor W. Barth, Allison Solanki, Jocelyn A. Jones, Scott C. Davis, Summer L. Gibbs

JBO, Vol. 28, Issue 08, 082806, (April 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.8.082806

KEYWORDS: Tumors, Adipose tissue, Prostate cancer, Prostate, Muscles, Tissues, Resection, Antibodies, Fluorescence, Cancer

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SignificancePositive margin status due to incomplete removal of tumor tissue during radical prostatectomy for high-risk localized prostate cancer requires reoperation or adjuvant therapy, which increases morbidity and mortality. Adverse effects of prostate cancer treatments commonly include erectile dysfunction, urinary incontinence, and bowel dysfunction, making successful initial curative prostatectomy imperative.AimCurrent intraoperative tumor margin assessment is largely limited to frozen section analysis, which is a lengthy, labor-intensive process that is obtrusive to the clinical workflow within the operating room (OR). Therefore, a rapid method for prostate cancer margin assessment in the OR could improve outcomes for patients.ApproachDual probe difference specimen imaging (DDSI), which uses paired antibody-based probes that are labeled with spectrally distinct fluorophores, was shown herein for prostate cancer margin assessment. The paired antibody-based probes consisted of a targeted probe to prostate-specific membrane antigen (PSMA) and an untargeted probe, which were used as a cocktail to stain resected murine tissue specimens including prostate tumor, adipose, muscle, and normal prostate. Ratiometric images (i.e., DDSI) of the difference between targeted and untargeted probe uptake were calculated and evaluated for accuracy using receiver operator characteristic curve analysis with area under the curve values used to evaluate the utility of the DDSI method to detect PSMA positive prostate cancer.ResultsTargeted and untargeted probe uptake was similar between the high and low PSMA expressing tumor due to nonspecific probe uptake after topical administration. The ratiometric DDSI approach showed substantial contrast difference between the PSMA positive tumors and their respective normal tissues (prostate, adipose, muscle). Furthermore, DDSI showed substantial contrast difference between the high PSMA expressing tumors and the minimally PSMA expressing tumors due to the ratiometric correction for the nonspecific uptake patterns in resected tissues.ConclusionsPrevious work has shown that ratiometic imaging has strong predictive value for breast cancer margin status using topical administration. Translation of the ratiometric DDSI methodology herein from breast to prostate cancers demonstrates it as a robust, ratiometric technique that provides a molecularly specific imaging modality for intraoperative margin detection. Using the validated DDSI protocol on resected prostate cancers permitted rapid and accurate assessment of PSMA status as a surrogate for prostate cancer margin status. Future studies will further evaluate the utility of this technology to quantitatively characterize prostate margin status using PSMA as a biomarker.

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Proceedings Article | 17 March 2023 Presentation

Two-color imaging of vital nerve structures with applications in fluorescence-guided surgery using near-infrared fluorophores with improved physicochemical properties

Antonio Montaño, Anas Masillati, Lei Wang, Dani Szafran-Reeder, Connor Barth, Nourhan Shams, Summer Gibbs

Proceedings Volume PC12361, PC123610K (2023) https://doi.org/10.1117/12.2648521

KEYWORDS: Nerve, Surgery, Prostate cancer, Cancer, Tumors, Target designation, Proteins, Prostate, Near infrared, Lead

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Proceedings Article | 17 March 2023 Presentation

Utilization of near infrared cranial nerve-specific fluorophores intraoperatively for visualization enhancement

Anas Masillati, Antonio Montaño, Lei Wang, Connor Barth, Dani Szafran-Reeder, Summer Gibbs

Proceedings Volume PC12361, PC123610L (2023) https://doi.org/10.1117/12.2650869

KEYWORDS: Visualization, Near infrared, Nerve, Lead, Tumors, Injuries, Tissues, Surgery, Skull, Sensors

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Proceedings Article | 17 March 2023 Presentation

Clinical translation of near infrared nerve-specific fluorescence contrast agents for enhanced nerve identification during surgery

Connor Barth, Lei Wang, Antonio Montaño, Anas Masillati, Syed Rizvi, Adam Alani, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume PC12361, PC123610J (2023) https://doi.org/10.1117/12.2651327

KEYWORDS: Nerve, Surgery, Near infrared, Luminescence, Visualization, Tissues, Lead, Toxicology, Systems modeling, Safety

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Proceedings Article | 15 March 2023 Presentation + Paper

Use of freshly amputated human limbs for pre-clinical evaluation of molecular-targeted fluorescent probes

Logan Bateman, Kendra Hebert, Samuel Streeter, Jenna Nunziata, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

Proceedings Volume 12361, 1236109 (2023) https://doi.org/10.1117/12.2650356

KEYWORDS: Fluorophores, Animal model studies, Tissues, Nervous system, Nerve, Animals, Lead, Surgery, Performance modeling, Muscles

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Proceedings Article | 15 March 2023 Presentation + Paper

First demonstration of a novel nerve-targeting fluorophore in a cohort of ex vivo human tissues

Kendra Hebert, Logan Bateman, Dylan Parker, Jenna Nunziata, Joseph Paydarfar, Jennifer Hong, Darcy Kerr, George Zanazzi, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

Proceedings Volume 12361, 123610D (2023) https://doi.org/10.1117/12.2650748

KEYWORDS: Fluorophores, Nervous system, Nerve, Adipose tissue, Lead, Biological samples, Surgery, Injuries, Muscles, Visualization

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SPIE Journal Paper | 5 January 2023 Open Access

Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs

Logan Bateman, Kendra Hebert, Jenna Nunziata, Samuel Streeter, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

JBO, Vol. 28, Issue 08, 082802, (January 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.8.082802

KEYWORDS: Fluorophores, Nerve, Nervous system, Animal model studies, Lead, Adipose tissue, Tissues, Imaging systems, Muscles, Fluorescence imaging

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Proceedings Article | 7 March 2022 Presentation

Utilization of near infrared nerve-specific fluorescent contrast agents as an intraoperative assessment methodology for nerve damage

Anas Masillati, Summer Gibbs, Connor Barth, Lei Wang, Nourhan Shams, Antonio Montano

Proceedings Volume PC11943, PC119430C (2022) https://doi.org/10.1117/12.2626009

KEYWORDS: Nerve, Near infrared, Injuries, Tissues, Surgery, Visualization, Molecules, Lead

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Proceedings Article | 4 March 2022 Presentation + Paper

The advantages and disadvantages of novel contrast agent types for fluorescence guided surgery

Connor Barth, Summer Gibbs

Proceedings Volume 11943, 1194309 (2022) https://doi.org/10.1117/12.2613182

KEYWORDS: Drug development, Nano contrast agents, Fluorescent markers, Image-guided intervention, Fluorescent materials, Molecules, Safety, Proteins, Clinical trials, Surgery, Nanoparticles, Tissues, Toxicity, Toxicology

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Proceedings Article | 8 March 2021 Presentation

Development of near-infrared fluorophores for use as nerve-specific contrast agents for fluorescence guided surgery

Lei Wang, Connor Barth, Antonio Montaño, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume 11625, 116250S (2021) https://doi.org/10.1117/12.2583286

KEYWORDS: Nerve, Luminescence, Tissues, Near infrared, Imaging systems, Visualization, Safety, Real time imaging, Molecules, Surgery

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Proceedings Article | 5 March 2021 Presentation + Paper

A method for validating depth-resolved biodistributions in topically-stained specimen with multi-channel fluorescence cryo-imaging

Brook Byrd, Rendall Strawbridge, Wendy Wells, Connor Barth, Summer Gibbs, Scott Davis

Proceedings Volume 11625, 116250X (2021) https://doi.org/10.1117/12.2582542

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Proceedings Article | 5 March 2021 Presentation

Pharmacology of near infrared nerve-specific fluorophores for fluorescence-guided nerve sparing surgical procedures

Connor Barth, Lei Wang, Antonio Montaño, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume 11625, 116250R (2021) https://doi.org/10.1117/12.2583265

KEYWORDS: Nerve, Near infrared, Pharmacology, Visualization, Toxicity, Safety, Animal model studies, Surgery, Luminescence, Imaging systems

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Proceedings Article | 19 February 2020 Presentation + Paper

Fluorescence image-guided surgery: a perspective on contrast agent development

Connor Barth, Summer Gibbs

Proceedings Volume 11222, 112220J (2020) https://doi.org/10.1117/12.2545292

KEYWORDS: Imaging systems, Luminescence, Surgery, Cancer, Multichannel imaging systems, Clinical trials, Tumors, Near infrared, Colorectal cancer, Pancreatic cancer, Image-guided intervention

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Proceedings Article | 19 February 2020 Paper

In vivo nerve-specificity of rhodamines and Si-rhodamines

Antonio Montaño, Lei Wang, Connor Barth, Nourhan Shams, K. A. Sashini Kumarapeli, Summer Gibbs

Proceedings Volume 11222, 112220I (2020) https://doi.org/10.1117/12.2545311

KEYWORDS: Rhodamine, Nerve, Near infrared, In vivo imaging, Surgery

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Proceedings Article | 7 March 2019 Presentation + Paper

Fluorescent nerve identification in resected human tissue specimens

Connor Barth, Christopher Amling, Summer Gibbs

Proceedings Volume 10862, 108620R (2019) https://doi.org/10.1117/12.2510512

KEYWORDS: Nerve, Tissues, Prostate, Luminescence, Imaging systems, Surgery, Image-guided intervention, Robotics, Blood, Biomedical optics and medical imaging, Medical imaging, Medical imaging applications, Molecular imaging, Optical imaging

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Proceedings Article | 7 March 2019 Paper

Investigation of oxazine and rhodamine derivatives as peripheral nerve tissue targeting contrast agent for in vivo fluorescence imaging

Lei Wang, Connor Barth, Jason Combs, Antonio Montaño, Summer Gibbs

Proceedings Volume 10862, 108620H (2019) https://doi.org/10.1117/12.2507296

KEYWORDS: Rhodamine, Nerve, Tissues, In vivo imaging, Absorbance, Near infrared, Image-guided intervention

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Proceedings Article | 7 March 2019 Paper

Diagnostic performance of receptor-specific surgical specimen staining correlate with receptor expression level

Broderick House, Jasmin Schaefer, Connor Barth, Scott Davis, Summer Gibbs

Proceedings Volume 10862, 108620K (2019) https://doi.org/10.1117/12.2510625

KEYWORDS: Tumors, Tissues, Surgery, Cancer, Diagnostics, Breast, Receptors, Breast cancer, Luminescence

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Identification of tumor margins in the operating room in real time is a critical challenge for surgical procedures that serve as cancer cure. Breast conserving surgery (BCS) is particularly affected by this problem, with current reexcision rates above 25%. Due to a lack of clinically available methodologies for detection of involved or close tumor margins, much effort is focused on developing intraoperative margin assessment modalities that can aid in addressing this unmet clinical need. BCS provides a unique opportunity to design contrast-based technologies that are able to assess tumor margins independent from the patient, providing a rapid pathway from bench to bedside at a much lower cost. Since resected tissue is removed from the patient’s blood supply, non-specific contrast agent uptake becomes a challenge due to the lack of clearance. Therefore, a dual probe, ratiometric fluorescence imaging approach was taken in an effort to reduce non-specific signal, and provide a modality that could demonstrate rapid, robust margin assessment on resected patient samples. Termed, dual-stain difference specimen imaging (DDSI), DDSI includes the use of spectrally unique, and fluorescently labeled target-specific, as well as non-specific biomarkers. In the present study, we have applied epidermal growth factor receptor (EGFR) targeted DDSI to tumor xenografts with variable EGFR expression levels using a previously optimized staining protocol, allowing for a quantitative assessment of the predictive power of the technique under biologically relevant conditions. Due to the presence of necrosis in the model tumors, ring analysis was employed to characterize diagnostic accuracy as measured by receiver operator characteristic (ROC) curve analysis. Our findings demonstrate the robust nature of the DDSI technique even in the presence of variable biomarker expression and spatial patterns. These results support the continued development of this technology as a robust diagnostic tool for tumor margin assessment in resected specimens during BCS.

SPIE Journal Paper | 8 February 2019 Open Access

Diagnostic performance of receptor-specific surgical specimen staining correlates with receptor expression level

Jasmin Schaefer, Connor Barth, Scott Davis, Summer Gibbs

JBO, Vol. 24, Issue 02, 026002, (February 2019) https://doi.org/10.1117/12.10.1117/1.JBO.24.2.026002

KEYWORDS: Tumors, Tissues, Diagnostics, Receptors, Luminescence, Surgery, Biological research, Cancer, Flow cytometry, Statistical analysis

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SPIE Journal Paper | 6 July 2018 Open Access

Nile Red derivatives enable improved ratiometric imaging for nerve-specific contrast

Jesse Korber, Connor Barth, Summer Gibbs

JBO, Vol. 23, Issue 07, 076002, (July 2018) https://doi.org/10.1117/12.10.1117/1.JBO.23.7.076002

KEYWORDS: Tissues, Nerve, Luminescence, Magnesium, In vivo imaging, Nitrogen, Quantum efficiency, Surgery, Molecules, Chromatography

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Proceedings Article | 14 March 2018 Presentation

Dual probe difference specimen imaging for rapid identification of margin assessment during breast conserving surgery (Conference Presentation)

Jasmin Schaefer, Connor Barth, Vince Rossi, Kimberley Samkoe, Scott Davis, Summer Gibbs

Proceedings Volume 10478, 104780M (2018) https://doi.org/10.1117/12.2290677

KEYWORDS: Surgery, Breast cancer, Tumors, Luminescence, Breast, Image-guided intervention, Molecules, Tissues

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Proceedings Article | 14 March 2018 Presentation

Topical application of nerve-specific fluorophores for image-guided nerve sparing surgical procedures (Conference Presentation)

Connor Barth, Summer Gibbs, Lei Wang

Proceedings Volume 10478, 104780J (2018) https://doi.org/10.1117/12.2290681

KEYWORDS: Nerve, Luminescence, Image-guided intervention, Surgery, Visualization, Tissues, Near infrared, Oncology, Target designation, Molecular imaging

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Nerve damage plagues surgical outcomes, significantly affecting post-surgical quality of life. Surprisingly, no method exists to enhance direct nerve visualization in the operating room, and nerve detection is completed through a combination of palpation and visualization when possible. Fluorescence image-guided surgery offers a potential means of enhanced nerve identification and preservation, however a clinically approved nerve-specific contrast agent does not yet exist. Several classes of nerve-specific fluorophores have recently been demonstrated including the distyrylbenzenes (DSB), select oxazines (oxazine 4 perchlorate), and certain cyanines (3,3’-diethylthiatricarbocyanine iodine), which could provide intraoperative guidance. The nerve-sparing radical prostatectomy is a surgical procedure that could benefit from fluorescence image-guided nerve identification. Although the nerve-sparing surgical technique was developed over 30 years ago, nerve damage following radical prostatectomy is reported in some form in up to 60% of patients one to two years post-surgery. To facilitate clinical translation of fluorescence image guided surgery to the nerve sparing prostatectomy, a direct administration methodology was developed that allows selective nerve highlighting with a significantly lower fluorophore dose than systemic administration, where large animal studies have confirmed the technique’s translatability. Tissue penetration will be critical for clinical feasibility of the direct administration methodology and novel formulation strategies have been explored to enhance tissue penetration for identifying buried nerves. In addition, several biomolecular targets of Oxazine 4, a promising candidate for nerve-specific fluorophore development into a near-infrared (NIR) agent, have been identified, providing insight into the mechanism of nerve-specificity. Fluorophore development has made progress towards the goal of creating a NIR nerve-specific fluorophore and determining the structure-activity relationship responsible for nerve binding.

Proceedings Article | 4 March 2016 Presentation + Paper

Visualizing Oxazine 4 nerve-specific fluorescence ex vivo in frozen tissue sections

Connor Barth, Summer Gibbs

Proceedings Volume 9696, 96960R (2016) https://doi.org/10.1117/12.2214204

KEYWORDS: Nerve, Visualization, Luminescence, Tissues, Visual analytics, Image-guided intervention, Near infrared, Prostate cancer, Molecules, Surgery, In vivo imaging, Microscopy, Optical filters

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Showing 5 of 24 publications

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