Colonoscopic screening and surveillance for colorectal cancer could be made safer and more efficient if endoscopists could predict histology without the need to biopsy and perform histopathology on every polyp. Elastic-scattering spectroscopy (ESS), using fiberoptic probes integrated into standard biopsy tools, can assess, both in vivo and in real time, the scattering and absorption properties of tissue related to its underlying pathology. The objective of this study was to evaluate prospectively the potential of ESS to predict polyp pathology accurately. We obtained ESS measurements from patients undergoing screening/surveillance colonoscopy using an ESS fiberoptic probe integrated into biopsy forceps. The integrated forceps were used for tissue acquisition, following current standards of care, and optical measurement. All measurements were correlated to the index pathology. A machine learning model was then applied to measurements from 367 polyps in 169 patients to prospectively evaluate its predictive performance. The model achieved sensitivity of 0.92, specificity of 0.87, negative predictive value (NPV) of 0.87, and high-confidence rate (HCR) of 0.84 for distinguishing 220 neoplastic polyps from 147 non-neoplastic polyps of all sizes. Among 138 neoplastic and 131 non-neoplastic polyps ≤ 5 mm, the model achieved sensitivity of 0.91, specificity of 0.88, NPV of 0.89, and HCR of 0.83. Results show that ESS is a viable endoscopic platform for real-time polyp histology, particularly for polyps ≤ 5 mm. ESS is a simple, low-cost, clinically friendly, optical biopsy modality that, when interfaced with minimally obtrusive endoscopic tools, offers an attractive platform for in situ polyp assessment.

The universal pathologic features implicated in the progression of chronic kidney disease (CKD) are interstitial fibrosis and tubular atrophy (IFTA). Current methods of estimating IFTA are slow, labor-intensive and fraught with variability and sampling error, and are not quantitative. As such, there is pressing clinical need for a less-invasive and faster method that can quantitatively assess the degree of IFTA. We propose a minimally-invasive optical method to assess the macro-architecture of kidney tissue, as an objective, quantitative assessment of IFTA, as an indicator of the degree of kidney disease. The method of elastic-scattering spectroscopy (ESS) measures backscattered light over the spectral range 320–900 nm and is highly sensitive to micromorphological changes in tissues. Using two discrete mouse models of CKD, we observed spectral trends of increased scattering intensity in the near-UV to short-visible region (350–450 nm), relative to longer wavelengths, for fibrotic kidneys compared to normal kidney, with a quasi-linear correlation between the ESS changes and the histopathology-determined degree of IFTA. These results suggest the potential of ESS as an objective, quantitative and faster assessment of IFTA for the management of CKD patients and in the allocation of organs for kidney transplantation.

Skin cancer is the most prevalent cancer, and its assessment remains a challenge for physicians. This study reports the application of an optical sensing method, elastic scattering spectroscopy ( ESS ), coupled with a classifier that was developed with machine learning, to assist in the discrimination of skin lesions that are concerning for malignancy. The method requires no special skin preparation, is non‐invasive, easy to administer with minimal training, and allows rapid lesion classification. This novel approach was tested for all common forms of skin cancer. ESS spectra from a total of 1307 lesions were analyzed in a multi‐center, non‐randomized clinical trial. The classification algorithm was developed on a 950‐lesion training dataset, and its diagnostic performance was evaluated against a 357‐lesion testing dataset that was independent of the training dataset. The observed sensitivity was 100% (14/14) for melanoma and 94% (105/112) for non‐melanoma skin cancer. The overall observed specificity was 36% (84/231). ESS has potential, as an adjunctive assessment tool, to assist physicians to differentiate between common benign and malignant skin lesions.

Objectives/Hypothesis To evaluate the usefulness of elastic scattering spectroscopy (ESS) as a diagnostic adjunct to frozen section analysis in patients with diagnosed squamous cell carcinoma of the oral cavity. Study Design Prospective analytic study. Methods Subjects for this single institution, institutional review board–approved study were recruited from among patients undergoing surgical resection for squamous cell cancer of the oral cavity. A portable ESS device with a contact fiberoptic probe was used to obtain spectral signals. Four to 10 spectral readings were obtained on each subject from various sites including gross tumor and normal‐appearing mucosa in the surgical margin. Each reading was correlated with the histopathologic findings of biopsies taken from the exact location of the spectral readings. A diagnostic algorithm based on multidimensional pattern recognition/machine learning was developed. Sensitivity and specificity, error rate, and area under the curve were used as performance metrics for tests involving classification between disease and nondisease classes. Results Thirty‐four (34) subjects were enrolled in the study. One hundred seventy‐six spectral data point/biopsy specimen pairs were available for analysis. ESS distinguished normal from abnormal tissue, with a sensitivity ranging from 84% to 100% and specificity ranging from 71% to 89%, depending on how the cutoff between normal and abnormal tissue was defined (i.e., mild, moderate, or severe dysplasia). There were statistically significant differences in malignancy scores between histologically normal tissue and invasive cancer and between noninflamed tissue and inflamed tissue. Conclusions This is the first study to evaluate the effectiveness of ESS in guiding mucosal resection margins in oral cavity cancer. ESS provides fast, real‐time assessment of tissue without the need for pathology expertise. ESS appears to be effective in distinguishing between normal mucosa and invasive cancer and between “normal” tissue (histologically normal and mild dysplasia) and “abnormal” tissue (severe dysplasia and carcinoma in situ) that might require further margin resection. Further studies, however, are needed with a larger sample size to validate these findings and to determine the effectiveness of ESS in distinguishing visibly and histologically normal tissue from visibly normal but histologically abnormal tissue. Level of Evidence NA Laryngoscope , 127:S1–S9, 2017

Abstract Thyroid cancer is the most common endocrine tumor. The gold standard, fine-needle aspiration biopsy, yields 10-25% indeterminate results necessitating diagnostic surgery. Using the real-time imaging technique of elastic scattering spectroscopy (ESS), a pair of fiber optics are inserted through the lumen of a biopsy needle and placed in contact with the thyroid nodule moments before cell collection occurs. Our research focuses on utilizing this optical-biopsy technique to measure tissue in vivo with broadband light during biopsy. In this study we demonstrate the potential our novel ESS-integrated optical biopsy syringe can have on cancer diagnostics. Spectra from 148 patients were collected. Additional time during biopsy to perform ESS measurements was less than 20 seconds. Cytology results for enrolled patients were as follows: 37 indeterminate, 6 insufficient, 5 malignant and 100 benign. Correlating ESS measurements with cytology, we identified changes in spectra when fiber optics were placed in contact with malignant versus benign tissue. From our enrolled benign and malignant patients, we trained an algorithm to diagnose indeterminate nodules based off of ESS spectra and compared to pathology. Preliminary analysis of spectra show ESS has a NPV of 0.99, a sensitivity of 0.92 and a specificity of 0.85. This data suggests that elastic scattering spectroscopy may improve the reliability, speed, and cost of cancer diagnostics. Citation Format: Jennifer E. Rosen, Nicholas J. Giordano, Eladio Rodriguez-Diaz, Ousama M. A'Amar, Irving J. Bigio, Stephanie L. Lee. Addressing the limitations of thyroid biopsies: Using elastic scattering spectroscopy to improve the assessment of indeterminate nodules. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4294. doi:10.1158/1538-7445.AM2014-4294

Thyroid nodules are a frequent clinical finding and the most common endocrine malignancy is thyroid cancer. The standard of care in the management of a patient with a thyroid nodule is to perform a preoperative fine needle aspiration (FNA) biopsy of the suspect nodule under ultrasound imaging guidance. In a significant percentage of the cases, cytological assessment of the biopsy material yields indeterminate results, the consequence of which is diagnostic thyroidectomy. Unfortunately, 75–80% of diagnostic thyroidectomies following indeterminate cytology result in benign designation by post-surgery histopathology, indicating potentially unnecessary surgeries. Clearly, the potential exists for the improvement in patient care and the reduction of overall procedure costs if an improved preoperative diagnostic technique was developed. Elastic scattering spectroscopy (ESS) is an optical biopsy technique that is mediated by optical fiber probes and has been shown to be effective in differentiating benign from malignant thyroid tissue in ex vivo surgical tissue samples. The goal of the current research was to integrate the ESS fiber optic probes into a device that can also collect cells for cytological assessment and, thus, enable concurrent spectroscopic interrogation and biopsy of a suspect nodule with a single needle penetration. The primary challenges to designing the device included miniaturizing the standard ESS fiber optic probe to fit within an FNA needle and maintaining the needle’s aspiration functionality. We demonstrate the value of the fabricated prototype devices by assessing their preliminary performance in an on-going clinical study with >120 patients. The devices have proven to be clinically friendly, collecting both aspirated cells and optical data from the same location in thyroid nodules and with minimal disruption of clinical procedure. In the future, such integrated devices could be used to complement FNA-based cytological results and have the potential to both reduce the number of diagnostic thyroidectomies on benign nodules and improve the surgical approach for patients with thyroid malignancies, thereby, decreasing healthcare costs and improving patient outcomes.

Thyroid nodules are common and often require fine needle aspiration biopsy (FNAB) to determine the presence of malignancy to direct therapy. Unfortunately, approximately 15-30% of thyroid nodules evaluated by FNAB are not clearly benign or malignant by cytology alone. These patients require surgery for the purpose of diagnosis alone; most of these nodules ultimately prove to be benign. Elastic light scattering spectroscopy (ESS) that measures the spectral differences between benign and malignant thyroid nodules has shown promise in improving preoperative determination of benign status of thyroid nodules. We describe the results of a large, prospective, blinded study validating the ESS algorithm in patients with thyroid nodules. An ESS system was used to acquire spectra from human thyroid tissue. Spectroscopic results were compared to the histopathology of the biopsy samples. Sensitivity and specificity of the ESS system in the differentiation of benign from malignant thyroid nodules are 74% and 90% respectively, with a negative predictive value of 97%. These data suggest that ESS has the potential for use in real time diagnosis of thyroid nodules as an adjunct to FNAB cytology.

Introduction: Thyroid cancer is the most common endocrine malignancy. The current gold standard for diagnosis, fine-needle aspiration (FNA) biopsy, yields 10-25% of indeterminate cytology results, leading to patients undergoing thyroidectomy for diagnosis. We assessed the technical potential of a miniaturized in vivo ESS (elastic light scattering spectroscopy) probe, built into an FNA needle assembly, to differentiate benign from malignant thyroid nodules. Methods: Under IRB approval, 15 patients in the endocrine clinic undergoing FNAB of a thyroid nodule had collection of ESS data using our novel miniaturized FNA probe. Using final surgical pathology as our gold standard, data post processing and visual inspection was completed. Results: 225 spectra were grouped and analyzed (120 benign, 30 malignant and 75 from indeterminate cytology). ESS probes demonstrated excellent reproducibility in use. Initial analysis of these preliminary data is promising, indicating distinction of spectral ESS features between malignant and benign conditions. Conclusion(s): An in vivo trial of an invasive miniaturized integrated ESS biopsy probe is acceptable to patients, and collection of ESS data is feasible and reliable. With development of a disease-specific algorithm, ESS could potentially be used as an in-situ real time intra-operative diagnostic tool or as a minimally invasive adjunct to conventional FNA cytology.

The false-negative rate of ultrasound-guided sextant prostate biopsy has been estimated to be as high as 35 %. A significant percentage (10–35 %) of these prostate cancers diagnosed at a second or later attempt are high grade and, therefore, potentially lethal. We discuss the feasibility for performing optically guided biopsy using elastic scattering spectroscopy (ESS) to reduce sampling errors and improve sensitivity. ESS measurements were performed on 42 prostate glands ex vivo and correlated with standard histopathological assessment. Sliced glands were examined with wavelength ranges of 330–760 nm. The ESS portable system used a new fiber-optic probe with integrated cutting tool, designed specifically for ex vivo pathology applications. ESS spectra were grouped by diagnosis from standard histopathological procedure and then classified using linear support vector machine. Preliminary data are encouraging. ESS data showed strong spectral trends correlating with the histopathological assignments. The classification results showed a sensitivity of 0.83 and specificity of 0.87 for distinguishing dysplastic prostatic tissue from benign prostatic tissue. Similar results were obtained for distinguishing dysplastic prostatic tissue from prostatitis with a sensitivity and specificity of 0.80 and 0.88, respectively. The negative predictive values obtained with ESS are better than those obtained with transrectal ultrasound (TRUS)-guided core-needle biopsy.

Thyroid cancer is the most common endocrine malignancy. The current standard of diagnosis, fine-needle aspiration biopsy, yields approximately 10–25% of indeterminate results leading to twice as many thyroidectomies for further diagnosis. Elastic scattering spectroscopy (ESS) is a new, minimally invasive optical-biopsy technique mediated by fiber-optic probes that is sensitive to cellular and subcellular morphological features. We assessed the diagnostic potential of ESS in the thyroid to differentiate benign from malignant thyroid nodules as determined by histology.

Mie theory has been used to describe the reduced scattering coefficient from a model that extracts optical properties from a reflectance spectrum. Preliminary results are presented from normal and inflamed colon mucosa.

Spectral reflectance measurements of biological tissues have been studied for early diagnoses of several pathologies such as cancer. These measurements are often performed with a fiber optic probe in contact with the tissue surface. We report a study in which reflectance measurements are obtained in vivo from mouse thigh muscle while varying the contact pressure of the fiber optic probe. It is determined that the probe pressure is a variable that affects the local optical properties of the tissue. The reflectance spectra are analyzed with an analytical model that extracts the tissue optical properties and facilitates the understanding of underlying physiological changes induced by the probe pressure.

A system to measure light scattering from individual cells excited by an acoustic wave was designed, and tests were performed on live Jurkat cells. Cells passing in a laminar stream within a water bath were excited by a focused ultrasound pulse, while the scattered light from a laser beam was monitored at various scattering angles. The cells were modeled as viscoelastic liquid drops, which return to equilibrium via shape oscillations after an acoustically-induced deformation. The Fast Fourier Transform of the scattered light signal was used to extract information about the highly-damped resonant frequencies of the cells, and the detected frequencies are consistent with theoretical predictions.

Monte Carlo simulations and experiments in tissue phantoms were used to empirically develop an analytical model that characterizes the reflectance spectrum in a turbid medium. The model extracts the optical properties (scattering and absorption coefficients) of the medium at small source-detector separations, for which the diffusion approximation is not valid. The accuracy of the model and the inversion algorithm were investigated and validated. Four fiber probe configurations were tested for which both the source and the detector fibers were tilted at a predetermined angle, with the fibers parallel to each other. This parallel-fiber geometry facilitates clinical endoscopic applications and ease of fabrication. Accurate extraction of tissue optical properties from in vivo spectral measurements could have potential applications in detecting, noninvasively and in real time, epithelial (pre)cancers.