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Effectiveness of surgery as a cancer treatment is reduced when all cancer cells are not detected during surgery, leading to recurrences that negatively impact survival. To maximize cancer cell detection during cancer surgery, we designed an in situ intraoperative, label-free, optical cancer detection system that combines intrinsic fluorescence spectroscopy, diffuse reflectance spectroscopy, and Raman spectroscopy. Using this multimodal optical cancer detection system, we found that brain, lung, colon, and skin cancers could be detected in situ during surgery with an accuracy, sensitivity, and specificity of 97%, 100%, and 93%, respectively. This highly sensitive optical molecular imaging approach can profoundly impact a wide range of surgical and noninvasive interventional oncology procedures by improving cancer detection capabilities, thereby reducing cancer burden and improving survival and quality of life. Cancer Res; 77(14); 3942–50. ©2017 AACR.

Contains a table showing prominent Raman peaks for molecular species; Figures showing pathology images, Raman spectra, and boxplots of Fluorescence & Raman Peaks; Data processing methods for fluorescence and diffuse reflectance.

Effectiveness of surgery as a cancer treatment is reduced when all cancer cells are not detected during surgery, leading to recurrences that negatively impact survival. To maximize cancer cell detection during cancer surgery, we designed an in situ intraoperative, label-free, optical cancer detection system that combines intrinsic fluorescence spectroscopy, diffuse reflectance spectroscopy, and Raman spectroscopy. Using this multimodal optical cancer detection system, we found that brain, lung, colon, and skin cancers could be detected in situ during surgery with an accuracy, sensitivity, and specificity of 97%, 100%, and 93%, respectively. This highly sensitive optical molecular imaging approach can profoundly impact a wide range of surgical and noninvasive interventional oncology procedures by improving cancer detection capabilities, thereby reducing cancer burden and improving survival and quality of life. Cancer Res; 77(14); 3942–50. ©2017 AACR.

Navigation-guided brain biopsies are the standard of care for diagnosis of several brain pathologies. However, imprecise targeting and tissue heterogeneity often hinder obtaining high-quality tissue samples, resulting in poor diagnostic yield. We report the development and first clinical testing of a navigation-guided fiberoptic Raman probe that allows surgeons to interrogate brain tissue in situ at the tip of the biopsy needle prior to tissue removal. The 900 μm diameter probe can detect high spectral quality Raman signals in both the fingerprint and high wavenumber spectral regions with minimal disruption to the neurosurgical workflow. The probe was tested in three brain tumor patients, and the acquired spectra in both normal brain and tumor tissue demonstrated the expected spectral features, indicating the quality of the data. As a proof-of-concept, we also demonstrate the consistency of the acquired Raman signal with different systems and experimental settings. Additional clinical development is planned to further evaluate the performance of the system and develop a statistical model for real-time tissue classification during the biopsy procedure.

Polycaprolactone (PCL) has been widely studied for biological applications. Biodegradable PCL fibrous scaffold can work as an appropriate substrate for tissue regeneration. In this letter, fluorescent nanodiamonds (FNDs) were prepared after surface passivation with octadecylamine. The FNDs were then mixed with PCL polymer and subsequently electrospun into FNDs/PCL fibrous scaffolds. The obtained scaffolds not only exhibited photoluminescence, but also showed reinforced mechanical strength. Toxicity study indicated FNDs/PCL scaffolds were nontoxic. This biocompatible fluorescent composite fibrous scaffold can support in vitro cell growth and also has the potential to act as an optical probe for tissue engineering application in vitro and in vivo.

Brain cancer diagnosis requires histological, molecular, and genomic tumor analyses. Since conventional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) don’t provide molecular characterisation, tumor sampling is often achieved using a targeted needle biopsy approach. Targeting errors and cancer heterogeneity are important limitations of this technique, causing inaccurate sampling resulting in non-diagnostic or poor quality samples leading and the need for repeated biopsies, which poses an elevated patient risk because of infections and potential hemorrhages. Previously, we presented the design of an optically-guided brain biopsy needle using high wavenumber Raman spectroscopy (RS) to characterize tissue prior to sample collection with demonstrated efficacy in a live animal. Using an intraoperative probe we further demonstrated in vivo high wavenumber or fingerprint RS can distinguish cancer and normal brain tissue with >90% accuracy. Here we report on the design, development, and validation of a new intraoperative cancer detection optical needle system based on the combination of fingerprint and high wavenumber RS for highly accurate brain biopsy targeting based on molecular tissue features. This optical cancer detection device was engineered into the internal cannula of a widely used commercially available biopsy needle allowing tumor analysis prior to tissue harvesting with minimal workflow disruption. First in-human results are presented setting the stage for the clinical translation of this optical molecular imaging method for high yield and safe targeted brain biopsy.

Modern cancer diagnosis requires histological, molecular, and genomic tumor analyses. Tumor sampling is often achieved using a targeted needle biopsy approach. Targeting errors and cancer heterogeneity causing inaccurate sampling are important limitations of this blind technique leading to non-diagnostic or poor quality samples, and the need for repeated biopsies pose elevated patient risk. An optical technology that can analyze the molecular nature of the tissue prior to harvesting could improve cancer targeting and mitigate patient risk. Here we report on the design, development, and validation of an in situ intraoperative, label-free, cancer detection system based on high wavenumber Raman spectroscopy. This optical detection device was engineered into a commercially available biopsy system allowing tumor analysis prior to tissue harvesting without disrupting workflow. Using a dual validation approach we show that high wavenumber Raman spectroscopy can detect human dense cancer with >60% cancer cells in situ during surgery with a sensitivity and specificity of 80% and 90%, respectively. We also demonstrate for the first time the use of this system in a swine brain biopsy model. These studies set the stage for the clinical translation of this optical molecular imaging method for high yield and safe targeted biopsy.

In this contribution we present a dual modality fiber optic probe combining fluorescence lifetime imaging (FLIm) and Raman spectroscopy for in vivo endoscopic applications. The presented multi-spectroscopy probe enables efficient excitation and collection of fluorescence lifetime signals for FLIm in the UV/visible wavelength region, as well as of Raman spectra in the near-IR for simultaneous Raman/FLIm imaging. The probe was characterized in terms of its lateral resolution and distance dependency of the Raman and FLIm signals. In addition, the feasibility of the probe for in vivo FLIm and Raman spectral characterization of tissue was demonstrated. Graphical Abstract An image comparison between FLIm and Raman spectroscopy acquired with the bimodal probe onseveral tissue samples.

Effectiveness of surgery as a cancer treatment is reduced when all cancer cells are not detected during surgery, leading to recurrences that negatively impact survival. To maximize cancer cell detection during cancer surgery, we designed an

Raman spectroscopy has been proven to have tremendous potential as biomedical analytical tool for spectroscopic disease diagnostics. The use of fiberoptic coupled Raman spectroscopy systems can enable in-vivo characterization of suspicious lesions. However, Raman spectroscopy has the drawback of rather long acquisition times of several hundreds of milliseconds which makes scanning of larger regions quite challenging. By combining Raman spectroscopy with a fast imaging technique this problem can be alleviate in part. Fluorescence lifetime imaging (FLIm) offers a great potential for such a combination. FLIm can allow for fast tissue area pre-segmentation and location of the points for Raman spectra acquisition. Here, we introduce an optical fiber probe combining FLIm and Raman spectroscopy with an outer diameter of 2 mm. Fluorescence is generated via excitation with a fiber laser at 355 nm. The fluorescence emission is spectrally resolved using a custom-made wavelength-selection module (WSM). The Raman excitation power at 785 nm was set to 50 mW for the in-vivo measurements to prevent sample drying. The lateral probe resolution was determined to be

A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%.