Elastic Light Scattering Spectroscopy Research Articles

Fiber-based visible and near infrared optical coherence tomography (vnOCT) enables quantitative elastic light scattering spectroscopy in human retina.

Elastic light scattering spectroscopy (ELSS) has been proven a powerful method in measuring tissue structures with exquisite nanoscale sensitivity. However, ELSS contrast in the living human retina has been relatively underexplored, primarily due to the lack of imaging tools with a large spectral bandwidth. Here, we report a simple all fiber-based setup to implement dual-channel visible and near infrared (NIR) optical coherence tomography (vnOCT) for human retinal imaging, bridging over a 300nm spectral gap. Remarkably, the fiber components in our vnOCT system support single-mode propagation for both visible and NIR light, both of which maintain excellent interference efficiencies with fringe visibility of 97% and 90%, respectively. The longitudinal chromatic aberration from the eye is corrected by a custom-designed achromatizing lens. The elegant fiber-based design enables simultaneous imaging for both channels and allows comprehensive ELSS analysis on several important anatomical layers, including nerve fiber layer, outer segment of the photoreceptors and retinal pigment epithelium. This vnOCT platform and method of ELSS analysis open new opportunities in understanding structure-function relationship in the human retina and in exploring new biomarkers for retinal diseases.

Preoperative Discrimination of Benign from Malignant Disease in Thyroid Nodules With Indeterminate Cytology Using Elastic Light-Scattering Spectroscopy

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.

Real-time Pathology to Guide Breast Surgery: Seeing Alone Is Not Believing

Tissue diagnostic techniques based on optical spectroscopy, in various incarnations, are approaching clinical reality for intraoperative guidance of surgical procedures. Examination of tissue properties by elastic light-scattering spectroscopy may constitute a preferable alternative to frozen-section pathology or touch imprint cytology for intraoperative assessment of resection margins during breast-conserving surgery.

Elastic light scattering spectroscopy versus standard colposcopy in patients with abnormal cervical cytology

Objective: Elastic light scattering spectroscopy (ELSS) is capable of measuring light scattering in cervical tissues and is being evaluated in the setting of abnormal cervical cytology to determine if it can supplement or replace colposcopy in identifying clinically relevant cervical intraepithelial neoplasia (CIN2/3). The objective of this study is to compare ELSS with clinical impression using colposcopic-directed biopsy histology as the gold standard.

Elastic Light-Scattering Spectroscopy for Discrimination of Benign from Malignant Disease in Thyroid Nodules

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. Under an IRB approved protocol, 36 surgical patients (n = 21 benign thyroid nodules, n = 15 malignant tumors) had collection of ESS data from their fresh ex vivo thyroidectomy specimens. Using surgical pathology as our gold standard, spectral analyses were performed using a training set; these data were used to assess the ESS diagnostic potential using the leave-one-out technique. Our test set was 75% sensitive and 95% specific in differentiating benign from malignant thyroid lesions, with a positive predictive value (PPV) of 0.92 and a negative predictive value (NPV) of 0.83. The ESS can accurately distinguish benign vs malignant thyroid lesions with high PPV and NPV. With further validation ESS could potentially be used as an in situ real-time diagnostic tool or as an adjunct to conventional cytology.

Design, conduct and challenges of a clinical trial utilizing elastic light scattering spectroscopy in the thyroid

Thyroid cancer is the most common endocrine malignancy. The standard of care in the management of a patient with a thyroid nodule is fine-needle aspiration biopsy (FNA) with cytological evaluation. While 5-10% of nodules are malignant, 10-25% of FNAs are indeterminate. Consequently, about twice as many patients undergo surgery for a suspicious lesion that turns out to be benign as undergo surgery for a known malignant lesion. A more accurate molecular and ultrastructural based algorithm would be useful to improve diagnostic accuracy. Noninvasive optical tissue diagnosis mediated by fiber-optic probes can be used to perform non-invasive, or minimally-invasive, real-time assessment of tissue pathology in-situ. Elastic light-scattering spectroscopy (ESS) is a point spectroscopic measurement technique, which is sensitive to cellular and subcellular morphological features. Normal and abnormal tissues can generate different spectral signatures as a result of changes in nuclear size, density, and other sub-cellular features, the optical-spectroscopy equivalent of histopathological readings. ESS is optimal for use in the small-volume area as found in thyroid FNA. An important advantage of ESS is that it provides an objective and quantitative assessment of tissue pathology that may not require on-site special expertise and subjective image interpretation as in conventional histopathology. Here we will describe our experience in the clinical application of elastic scattering spectroscopy in the thyroid.

Characterization of Malignant Brain Tumor Using Elastic Light Scattering Spectroscopy

We report a pilot study designed to test elastic light-scattering (ELS) spectroscopy for characterizing normal, tumor, and tumor-infiltrated brain tissues. ELS spectra were measured from 393 sites on 36 ex vivo tissue specimen obtained from 29 patients. We employed and compared the performances of three methods of spectral classification for tissue characterization, including spectral slope analysis, principle component analysis (PCA), and artificial neural network (ANN) classification. The ANN classifier yielded the best correlation between spectral pattern and histopathological diagnosis, with a typical sensitivity of 80% and specificity of 93% for differentiating tumor from normal brain tissues. We also demonstrate that all three classification methods discriminate between tumor and normal tissue and have the potential to identify and quantitatively characterize tumor-infiltrated brain tissues.

Assessment of the relative contribution of cellular components to the acetowhitening effect in cell cultures and suspensions using elastic light-scattering spectroscopy

We aim to investigate the mechanism of acetowhitening upon which the colposcopic diagnosis of cervical cancer is based. The changes in light scattering induced by acetic acid in intact cervical cancer cells and cellular components were studied using elastic light-scattering spectroscopy. After adding acetic acid to intact cancer cell culture samples (cell suspensions and attached monolayer cell cultures), a slight decrease in small-angle forward scattering was observed, while the large-angle scattering increased by a factor of 5-9, indicating that acetowhitening signals are mainly contributed from small-sized intracellular scattering structures. The cellular components of different sizes and masses were isolated to investigate their individual contribution to the changes of light scattering induced by acetic acid. The study provided the evidence that the cellular components of diameter smaller than 0.2 microm in the cytoplasm are the major contributors to the acetowhitening effect in whole cells, while the light scattering from the mitochondria are not sensitive to the acetic acid.

Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy

We report the feasibility of monitoring both hemoglobin oxygen saturation and hemoglobin concentration in the superficial layer of tissue using polarization-gated elastic light-scattering spectroscopy. We detail our analysis technique, the experimental validation of our analysis, and the detection of an early increase in blood supply to the superficial layer of colon tissue in human patients with colonic adenomas as well as in an animal model of colon carcinogenesis. To the best of our knowledge, this study represents the first evidence that polarization gating can be used as a spectroscopic tool to quantify hemoglobin concentration as well as oxygen saturation in the uppermost tissue layer.

Extensive Measurements on Soot Particles in Laminar Premixed Flames by Quasi Elastic Light Scattering Spectroscopy

Abstract The data obtained by Quasi-Elastic Light-Scattering Spectroscopy on twenty five alkane-oxygen sooting flames are presented. This optical method, based on the interaction between particles and their surrounding, allows the granulometric study of the soot aerosol evolution accounting for the specific aerosol regime existing in the considered flame. Diffusion Broadening and/or Photon Correlation Spectroscopy adapted to a Brownian aerosol in a flowing high temperature medium are used for the simultaneous measurements of soot diameter and number density or diameter and polydispersity. The data reduction method employed permits easy analysis including the transit time and the polydispersity aspects of the scatterers. Soot coagulation growth rates are also determined for these flames.