Project description:Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon.The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training.The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate.The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.
Project description:Fluorescence-guided surgery has emerged as a promising imaging technique for real-time intraoperative tumour delineation and visualisation of submillimetre tumour masses in cytoreductive surgery for epithelial ovarian cancer (EOC). Researchers have developed several EOC-targeted fluorescent probes, most of which are currently in the preclinical stage. Interestingly, imaging devices designed for open surgery are proof of concept. This review summarises the recent advances in EOC-targeted fluorescent probes and open-field fluorescence imaging strategies and discusses the challenges and potential solutions for clinical translation.
Project description:SignificanceNear-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important.AimConventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff.ApproachIn this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer.ResultsWe demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making.ConclusionsThese results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.
Project description:SignificanceBreast-conserving surgery (BCS) is limited by high rates of positive margins and re-operative interventions. Fluorescence-guided surgery seeks to detect the entire lesion in real time, thus guiding the surgeons to remove all the tumor at the index procedure.AimOur aim was to identify the optimal combination of a camera system and fluorophore for fluorescence-guided BCS.ApproachA systematic review of medical databases using the terms "fluorescence," "breast cancer," "surgery," and "fluorescence imaging" was performed. Cameras were compared using the ratio between the fluorescent signal from the tumor compared to background fluorescence, as well as diagnostic accuracy measures, such as sensitivity, specificity, and positive predictive value.ResultsTwenty-one studies identified 14 camera systems using nine different fluorophores. Twelve cameras worked in the infrared spectrum. Ten studies reported on the difference in strength of the fluorescence signal between cancer and normal tissue, with results ranging from 1.72 to 4.7. In addition, nine studies reported on whether any tumor remained in the resection cavity (5.4% to 32.5%). To date, only three studies used the fluorescent signal for guidance during real BCS. Diagnostic accuracy ranged from 63% to 98% sensitivity, 32% to 97% specificity, and 75% to 100% positive predictive value.ConclusionIn this systematic review, all the studies reported a clinically significant difference in signal between the tumor and normal tissue using various camera/fluorophore combinations. However, given the heterogeneity in protocols, including camera setup, fluorophore studied, data acquisition, and reporting structure, it was impossible to determine the optimal camera and fluorophore combination for use in BCS. It would be beneficial to develop a standardized reporting structure using similar metrics to provide necessary data for a comparison between camera systems.
Project description:BackgroundAlthough therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).MethodsmAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging.ResultsIn vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.ConclusionsWe showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.
Project description:The purpose of this study was to assess the potential of U.S. Food and Drug Administration-cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery.MethodsConsenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed preoperatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio characterized fluorescence contrast.ResultsIn the preoperative clinic, the open-field device demonstrated potential to guide preoperative mapping of tumor borders, optimize the day of surgery, and identify occult lesions. Intraoperatively, the device demonstrated robust potential to guide surgical resections, as all peak tumor-to-background ratios were greater than 2 (range, 2.2-14.1). Postresection wound bed fluorescence was significantly less than preresection tumor fluorescence (P < 0.001). The repurposed device also successfully identified positive margins.ConclusionThe open-field imaging device was successfully repurposed to distinguish cancer from normal tissue in the preoperative clinic and throughout surgical resection. This study illuminated the potential for existing open-field optical imaging devices with overlapping excitation and emission spectra to be used for fluorescence-guided surgery.
Project description:BackgroundDespite significant improvements in preoperative workup and surgical planning, surgeons often rely on their eyes and hands during surgery. Although this can be sufficient in some patients, intraoperative guidance is highly desirable. Near-infrared fluorescence has been advocated as a potential technique to guide surgeons during surgery.MethodsA literature search was conducted to identify relevant articles for fluorescence-guided surgery. The literature search was performed using Medical Subject Headings on PubMed for articles in English until November 2022 and a narrative review undertaken.ResultsThe use of invisible light, enabling real-time imaging, superior penetration depth, and the possibility to use targeted imaging agents, makes this optical imaging technique increasingly popular. Four main indications are described in this review: tissue perfusion, lymph node assessment, anatomy of vital structures, and tumour tissue imaging. Furthermore, this review provides an overview of future opportunities in the field of fluorescence-guided surgery.ConclusionFluorescence-guided surgery has proven to be a widely innovative technique applicable in many fields of surgery. The potential indications for its use are diverse and can be combined. The big challenge for the future will be in bringing experimental fluorophores and conjugates through trials and into clinical practice, as well as validation of computer visualization with large data sets. This will require collaborative surgical groups focusing on utility, efficacy, and outcomes for these techniques.
Project description:BackgroundIndocyanine green (ICG) imaging has been increasingly used for intraoperative guidance in colorectal surgery over the past decade. The aim of this study was to review and organize, according to different type of use, all available literature on ICG guided colorectal surgery and highlight areas in need of further research and discuss future perspectives.MethodsPubMed, Scopus, and Google Scholar databases were searched systematically through November 2022 for all available studies on fluorescence-guided surgery in colorectal surgery.ResultsAvailable studies described ICG use in colorectal surgery for perfusion assessment, ureteral and urethral assessment, lymphatic mapping, and hepatic and peritoneal metastases assessment. Although the level of evidence is low, results are promising, especially in the role of ICG in reducing anastomotic leaks.ConclusionsICG imaging is a safe and relatively cheap imaging modality in colorectal surgery, especially for perfusion assessment. Work is underway regarding its use in lymphatic mapping, ureter identification, and the assessment of intraperitoneal metastatic disease.
Project description:The use of indocyanine green (ICG) fluorescence near-infrared (NIR) imaging during gastrointestinal surgery has surged in recent years. Its use in esophageal surgery is actively being studied both in the clinical setting and in the lab. NIR imaging has several important applications in esophageal surgery including assessing perfusion of the gastrointestinal-esophageal anastomosis, lymphatic drainage and tracheal blood flow after mediastinal dissection. This is a review of the modern literature summarizing the current knowledge on fluorescence-guided surgery of the esophagus.
Project description:ObjectiveAlthough fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type.BackgroundFor many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye.MethodsWe performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016.Inclusion criteriafluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases.Exclusion criteriafluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence.ResultsInitial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision.ConclusionsThe use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.