Intraoperative detection of insufficient surgical margins in head and neck cancer resection using dual aperture fluorescence ratio imaging

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Improved intraoperative identification of close margins in oral squamous cell carcinoma resections using a dual aperture fluorescence ratio approach:first in-human results

Significance: Surgical excision is the main treatment for solid tumors in oral squamous cell carcinomas, where wide local excision (achieving a healthy tissue margin of &gt;5 mm around the excised tumor) is the goal as it results in reduced local recurrence rates and improved overall survival. Aim: No clinical methods are available to assess the complete surgical margin intraoperatively while the patient is still on the operating table; and while recent intraoperative back-bench fluorescence-guided surgery approaches have shown promise for detecting “positive” inadequate margins (&lt;1 mm), they have had limited success in the detection of “close” inadequate margins (1 to 5 mm). Here, a dual aperture fluorescence ratio (dAFR) approach was evaluated as a means of improving detection of close margins. Approach: The approach was evaluated on surgical specimens from patients who were administered a tumor-specific fluorescent imaging agent (cetuximab-800CW) prior to surgery. The dAFR approach was compared directly against standard widefield fluorescence imaging and pathology measurements of margin thickness in specimens from three patients and a total of 12 margin locations (1 positive, 5 close, and 6 clear margins). Results: The area under the receiver operating characteristic curve, representing the ability to detect close compared to clear margins (&gt;5 mm) was found to be 1.0 and 0.57 for dAFR and sAF, respectively. Improvements in dAFR were found to be statistically significant (p &lt; 0.02). Conclusions: These results provide evidence that the dAFR approach potentially improves detection of close surgical margins.</p

Rapid, variable aperture approach to quantify depth of fluorescence in a heterogenous medium

Post-operative assessment of resected tumor margins is critical to ensure the entirety of malignant tissue has been removed from a patient. Microscopic assessment of tissue post-excision is the current gold standard, however the long wait times for proper specimen evaluation limit a surgeon's ability to be certain they obtained clear margins. To address this need, fluorescence-guided surgery approaches are under development that can yield molecular contrast between healthy and malignant tissues intraoperatively. In head and neck cancer specifically, heterogenous optical properties lead to poor identification in margins greater than 1 mm thick when viewed with single projections. Thus, we demonstrate the use of variable aperture approach to decrease the effects of local optical property variations in the imaged specimen. Here we use Monte Carlo simulations to verify the utility of the idea in a homogenous medium as well in a medium with heterogenous properties. We demonstrate that a ratio metric approach can provide near identical depth discrimination as a single projection in a homogenous medium and is further capable of reducing pixel variability due to local optical properties in a heterogenous medium than a single projection alone.</p