A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery

Warram, Jason M.; Boer, Esther de; Moore, Lindsay; Schmalbach, Cecelia E.; Withrow, Kirk; Carroll, William R.; Richman, Joshua S.; Morlandt, Anthony B.; Brandwein-Gensler, Margaret; Rosenthal, Eben L.

doi:10.1002/jso.23946

Cited by 25 publications

(27 citation statements)

References 17 publications

(28 reference statements)

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“…Here we show that development of tumor-specific fluorescence imaging has further ameliorated current deficits in oncologic surgery by extending tumor detection as it disseminates into regional lymph nodes. Interim results from a recent clinical trial (#NCT01987375) demonstrated that cetuximab-IRDye800CW could be safely administered as a tumor-specific contrast agent for use during surgical navigation to aid in the identification of subclinical disease with high sensitivity and specificity(21). It was determined that high levels of fluorescence, as measured by tumor-to-background ratio (TBR), correlated with primary HNSCC and may further represent a tumor-specific method for accurate detection of sentinel lymph node disease.…”

Section: Introductionmentioning

confidence: 99%

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Rosenthal

Moore

Tipirneni

et al. 2017

Clinical Cancer Research

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111

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Purpose Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer. Experimental Design Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients (n=12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3–7days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence-imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1mm) into their respective blocks, metastatic cancer was found in 8.1% of the re-cut nodal specimens, which altered staging in two of those cases. Conclusions Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning.

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Section: Introductionmentioning

confidence: 99%

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Rosenthal

Moore

Tipirneni

et al. 2017

Clinical Cancer Research

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111

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“…The default method for identifying residual tumor using intraoperative imagers has been physician identification from an image. Efforts to define a common quantification metric for imaging tools have centered around the signal-to-background ratio (SBR) 8,9 . Implicit in this metric is a tumor signal significantly above background -true for larger tumor foci, but not necessarily for microscopic disease, which is often just above background contributed by non-specific binding, autofluorescence, and other optical and electronic sources.…”

Section: Introductionmentioning

confidence: 99%

Signal to Noise Ratio as a Cross-Platform Metric for Intraoperative Fluorescence Imaging

Gharia

Papageorgiou

Giverts

et al. 2019

Preprint

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AbstractReal-time molecular imaging to guide curative cancer surgeries is critical to ensure removal of all tumor cells, however visualization of microscopic tumor foci remains challenging. Wide variation in both imager instrumentation and molecular labeling agents demands a common metric conveying the ability of a system to identify tumor cells. Microscopic disease, comprised of a small number of tumor cells, has a signal on par with the background, making the use of signal (or tumor) to background ratio inapplicable in this critical regime. Therefore, a metric that incorporates the ability to subtract out background, evaluating the signal itself relative to the sources of uncertainty, or noise is required. Here we introduce the signal-to-noise ratio (SNR) to characterize the ultimate sensitivity of an imaging system, and optimize factors such as pixel size. Variation in the background (noise) are due to electronic sources, optical sources, and spatial sources (heterogeneity in tumor marker expression, fluorophore binding, diffusion). Here we investigate the impact of these noise sources and ways to limit its effect on SNR. We use empirical tumor and noise measurements to procedurally generate tumor images and run a monte carlo simulation of microscopic disease imaging to optimize parameters such as pixel size.

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“…In addition, histological processing can take time [9], which is labor intensive and prolongs surgery time. Fluorescence imaging guided cancer resection has been shown to improve the number of complete resections [10-16]. However, fluorescence-based approaches require the injection of a fluorescence imaging agent during surgery and the agent needs to be approved by the U.S. Food and Drug Administration.…”

Section: Introductionmentioning

confidence: 99%

Label-free hyperspectral imaging and quantification methods for surgical margin assessment of tissue specimens of cancer patients

Fei

Halicek

et al. 2017

2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

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Hyperspectral imaging (HSI) is a relatively new modality in medicine and can have many potential applications. In this study, we developed label-free hyperspectral imaging for tumor margin assessment. HSI data, hypercube (x,y,λ), consists of a series of images of the same field of view that are acquired at different wavelengths. Every pixel in the hypercube has an optical spectrum. We collected surgical tissue specimens from 16 human subjects who underwent head and neck (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and fluorescence images with 2-NBDG and proflavine from the specimens. Digitized histologic slides were examined by an H&N pathologist. We developed image preprocessing and classification methods for HSI data and differentiate cancer from benign tissue. The hyperspectral imaging and classification method was able to distinguish between cancer and normal tissue from oral cavity with an average accuracy of 90±8%, sensitivity of 89±9%, and specificity of 91±6%. This study suggests that label-free hyperspectral imaging has great potential for surgical margin assessment in tissue specimens of H&N cancer patients. Further development of the imaging technology and quantification methods is warranted for its application in image-guided surgery.

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A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery

Cited by 25 publications

References 17 publications

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Signal to Noise Ratio as a Cross-Platform Metric for Intraoperative Fluorescence Imaging

Label-free hyperspectral imaging and quantification methods for surgical margin assessment of tissue specimens of cancer patients

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