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

Fluorescence mesoscopic imaging of whole lymph nodes for intraoperative sentinel lymph node biopsy procedures

An increasing number of cancer surgery protocols are including sentinel lymph node biopsies on the day of resection to stage for non-palpable spread of cancer through tumor draining lymph nodes. The challenge is that often a tumor-positive node will make it necessary to perform an enhanced resection of the lymphatic network, and if lymph node processing is not completed within the timeframe of surgery, then patients may have to be called back for additional surgery or have to undergo amplified chemo or radiation therapy. Our group is working on a rapid lymph node staining and fluorescence tomography system that we call ADEPT to provide surgeons with lymph node biopsy results within 15 min. The aim is to minimize the number of callback surgery or amplified therapy procedures to minimize stress to patients and reduce health care costs. This work predicts, using Monte Carlo photon propagation modeling simulations, that ADEPT has the potential to yield greater than 95% accuracy in detecting the smallest amount of cancer considered clinically relevant withing 15 min of tissue processing and imaging.</p

Education for the future.

We asked young scientists: Are our schools and universities adequately prepared to educate young people for future challenges? What is the most pressing issue in your field, and what one improvement could your country make to its current education system to prepare students to face it? The responses expressed concerns about the current state of education in countries around the world. Many students lack access to the information they need, and those with access are often constrained by curriculum that emphasizes rote learning and isolated subjects. Our respondents suggested a variety of improvements to prepare the next generation for success