Discriminating benign from malignant thyroid nodules in real-time using a novel probe with an integrated elastic scattering spectroscopy biopsy syringe

Thesis (M.A.)--Boston UniversityBackground. Thyroid cancer is the most common endocrine malignancy. The current standard of diagnosis, fine needle aspiration biopsy (FNAB) yields indeterminate results for approximately 10–25% of biopsies, necessitating thyroidectomy for diagnosis. Elastic scattering spectroscopy (ESS) is a minimally invasive optical biopsy technique that is sensitive to cellular and subcellular morphological features. We hypothesized that it was feasible to use ESS in vivo to improve our ability to preoperatively differentiate benign from malignant thyroid nodules. Methods. Under an IRB approved protocol, we collected ESS data from patients undergoing thyroid FNAB using our miniaturized integrated ESS/biopsy probe. Spectral findings were compared to cytology. Results. 108 patients enrolled, 5 patients were excluded due to procedural and mechanical issues. Data from 103 patients was submitted for analysis. Initial evaluation of spectra data demonstrates adequacy and comparability of the miniaturized probe to the prior full-size ESS fiber construct. Conclusion. Performing a clinical trial using a miniaturized integrated ESS/biopsy probe in vivo is feasible and acceptable to patients. Both spectral data and cytologic material are adequate in the majority of patients. With further accrual and analysis, this ESS device may provide cost-effective, real-time, and operator independent assessment of thyroid nodules

In vivo and ex vivo techniques using elastic scattering spectroscopy for diagnosis of malignancy in the thyroid gland

Thesis (M.A.)--Boston University, 2011.OBJECTIVE: Thyroid cancer is the most common endocrine malignancy and patients presenting with thyroid nodules often undergo surgery solely for diagnostic purposes. The goal of our study was to examine the accuracy of Elastic Scattering Spectroscopy (ESS) in distinguishing between benign and malignant thyroid nodules in fresh ex vivo specimens and to design an in vivo ESS probe and device, manufacture it and conduct a clinical trial. METHODS: Patients already undergoing thyroidectomy surgery were consented for the ex vivo study. ESS data was obtained from ex vivo specimens by recording 5 readings per nodule with five repetitive readings per each site. Final pathology reports were used to confirm the diagnosis. The spectra were analyzed using principal component analysis, linear discriminant analysis and leave one out technique. The in vivo ESS study was conceptually designed and IRB approval from Boston Medical Campus was obtained. RESULTS: The ex vivo study showed that ESS could predict the difference between benign and malignant tumors with a sensitivity of 74%, specificity of 90%, positive predictive value of 82% and negative predictive value of 85%. 193 spectra were analyzed from 64 patients, 120 spectra were from benign nodules and 73 from malignant nodules. Subanalysis examined only indeterminate nodules showed sensitivity of 65%, specificity of 79%, PPV 77% and NPV 67%. The in vivo ESS probe was designed and 12 identical instruments were manufactured. Initial experimental readings were taken and parameters were adjusted for the in vivo tissue environment. The clinical trial is underway. CONCLUSIONS: ESS is a practical tool that can accurately identify malignancy in ex vivo thyroid specimens with high specificity and sensitivity. Initial in vivo experimental trials have been conducted and show promise for similar results

Initial experience of intraoperative identification of parathyroid glands with elastic scattering spectroscopy

BACKGROUND: Postoperative hypoparathyroidism due to damage to the parathyroid glands during a thyroidectomy is a well-known surgical complication. The current gold standard intraoperative method for identifying parathyroid glands is surgical judgment; other methods are limited in both their sensitivity and convenience. There is a clear need for an objective diagnostic tool that is effective in its identification of the parathyroid glands and of their viability. We hypothesized that an intraoperative tool using Elastic Scattering Spectroscopy (ESS) has the potential to differentiate optical signatures of the parathyroid gland from surrounding tissues in real-time. METHODS: ESS optical signatures were collected intraoperatively from perfused parathyroid, thyroid, fat, muscle, and nerve tissue during thyroidectomy. The ESS data was collected using a portable, handheld, noninvasive, "cold" fiber optic probe able to detect spectra in a non-ionizing, broadband spectrum of light (320 to 920 nm). Five measurements were collected at each tissue site over a total of 1.2 seconds. Visual analysis of tissue was analyzed and compared to pathology, and spectral measurements attained with ESS. RESULTS: No complications resulted from the use of the ESS probe. Of the 10 parathyroid glands evaluated to be at risk in the study, the optical probe utilizing ESS was able to detect unique spectral features associated with the parathyroid gland. All 10 parathyroid glands are optically differentiable from surrounding tissues with ESS. CONCLUSIONS: Utilizing spectroscopy in the form of a hand-held probe is feasible for intraoperative differentiation between tissue types. Preliminary results of this spectral technique warrant further investigation. If successful, implementation of a portable ESS probe to identify the parathyroid tissue during endocrine surgical procedures could reduce surgical complications and improve patient safety

Raman Microspectroscopy for the Discrimination of Thyroid and Lung Cancer Subtypes for Application in Clinical Cytopathology

The branch of cytology known as cytopathology, studies and diagnoses diseases at a cellular level, and is a useful method for detecting cancer. The procedures used to attain cytological samples for diagnostic purposes, such as aspiration and exfoliative methods are safe, accurate and cost-effective. Histochemical and immunohistochemical (IHC) techniques are commonly applied to cytological samples to aid cancer diagnosis, however multiple limitations occur using these methods for the diagnosis of thyroid cancer (TC) and non-small cell lung cancer (NSCLC). Fine needle aspiration cytology (FNAC) is the prominent diagnostic method used for the initial investigation of thyroid nodules but is limited by the inability to accurately diagnose malignancy in follicular-patterned lesion. As a result, more than 20% of cases under investigation for TC are classified as cytologically “indeterminate”, requiring surgical resection for accurate diagnosis. In the case of NSCLC, with the advent of targeted therapies, it is imperative to accurately differentiate (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques are increasingly part of the diagnostic work-up of NSCLC patients however due to the limitation of small sample size, overlapping morphological features and molecular characterisation, differential diagnosis of NSCLC still proves challenging. Raman spectroscopy has shown promising results for the detection of a variety of cancers, however to date there has been no evaluation of Raman spectroscopy on cytology bronchoscopy samples or thyroid FNAC samples, which may eliminate the limitations of current methods. This thesis explores the use of Raman spectroscopy as an alternative or adjunct tool for the diagnosis of TC and NSCLC using cytological specimens

Towards minimally-invasive, quantitative assessment of chronic kidney disease using optical spectroscopy

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.T32 HL007224 - NHLBI NIH HHS; R01 CA175382 - NCI NIH HHS; T32 GM086308 - NIGMS NIH HHS; R01 HL132325 - NHLBI NIH HHS; UL1 TR001430 - NCATS NIH HHSAccepted manuscriptPublished versio

The Boston University Photonics Center annual report 2013-2014

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2013-2014 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This annual report summarizes activities of the Boston University Photonics Center in the 2013–2014 academic year.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $14.5M in new research grants and contracts this year. Faculty and staff also expanded their efforts in education and training, through National Science Foundation–sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Innovations at the Intersections of Micro/Nanofabrication Technology, Biology, and Biomedicine at our annual Future of Light Symposium. We took a leadership role in running national workshops on emerging photonic fields, including an OSA Incubator on Controlled Light Propagation through Complex Media, and an NSF Workshop on Noninvasive Imaging of Brain Function. Highlights of our research achievements for the year include a distinctive Presidential Early Career Award for Scientists and Engineers (PECASE) for Assistant Professor Xue Han, an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, launch of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Cathy Klapperich, and successful completion of the ambitious IARPA-funded contract for Next Generation Solid Immersion Microscopy for Fault Isolation in Back-Side Circuit Analysis led by Professor Bennett Goldberg. These three programs, which represent more than$20M in research funding for the University, are indicative of the breadth of Photonics Center research interests: from fundamental modeling of optoelectronic materials to practical development of cancer diagnostics, from exciting new discoveries in optogenetics for understanding brain function to the achievement of world-record resolution in semiconductor circuit microscopy. Our community welcomed an auspicious cohort of new faculty members, including a newly hired assistant professor and a newly hired professor (and Chair of the Mechanical Engineering Department). The Industry/University Cooperative Research Center—the centerpiece of our translational biophotonics program—continues to focus on advancing the health care and medical device industries, and has entered its fourth year of operation with a strong record of achievement and with the support of an enthusiastic industrial membership base

The Boston University Photonics Center annual report 2013-2014

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2013-2014 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This annual report summarizes activities of the Boston University Photonics Center in the 2013–2014 academic year.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $14.5M in new research grants and contracts this year. Faculty and staff also expanded their efforts in education and training, through National Science Foundation–sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Innovations at the Intersections of Micro/Nanofabrication Technology, Biology, and Biomedicine at our annual Future of Light Symposium. We took a leadership role in running national workshops on emerging photonic fields, including an OSA Incubator on Controlled Light Propagation through Complex Media, and an NSF Workshop on Noninvasive Imaging of Brain Function. Highlights of our research achievements for the year include a distinctive Presidential Early Career Award for Scientists and Engineers (PECASE) for Assistant Professor Xue Han, an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, launch of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Cathy Klapperich, and successful completion of the ambitious IARPA-funded contract for Next Generation Solid Immersion Microscopy for Fault Isolation in Back-Side Circuit Analysis led by Professor Bennett Goldberg. These three programs, which represent more than$20M in research funding for the University, are indicative of the breadth of Photonics Center research interests: from fundamental modeling of optoelectronic materials to practical development of cancer diagnostics, from exciting new discoveries in optogenetics for understanding brain function to the achievement of world-record resolution in semiconductor circuit microscopy. Our community welcomed an auspicious cohort of new faculty members, including a newly hired assistant professor and a newly hired professor (and Chair of the Mechanical Engineering Department). The Industry/University Cooperative Research Center—the centerpiece of our translational biophotonics program—continues to focus on advancing the health care and medical device industries, and has entered its fourth year of operation with a strong record of achievement and with the support of an enthusiastic industrial membership base

A combined microwave and optical sensor system with application in cancer detection

Cancer remains a significant health problem, despite great scientific advances in recent years. Biomedical imaging procedures are commonly used to facilitate the diagnosis and treatment of different types of cancer. However, there are still many limitations to these diagnostic techniques. To overcome some of these issues, new approaches are urgently needed. This study aims to establish potential new techniques to improve disease staging diagnosis through more accurate detection and allow real-time monitoring of sample characteristics to help the surgeons reduce the number of biopsies for making a diagnosis. An optical probe has been fabricated in our laboratory with specific characteristics resulting from modelling and experimental exploration. This probe produced encouraging results from a tissue phantom with an ability to distinguish between different particle sizes 2, 0.8 and 0.413 μm with various polystyrene spheres in suspension (PS) concentrations. A Microwave cavity resonator showed the ability to distinguish between different saline dilutions for two types of preparation and different PS concentrations with some limitations. Many correction techniques were developed to enhance the quality of the data obtained. A novel T- Structure and capacitive coupling technique enabled a more robust S21 measurement to be made utilising a resonant coaxial probe at microwave frequencies between around 0.1 GHz and 6 GHz. This structure was modelled and used in experimental scenarios leading to the ability to distinguish between various saline dilutions and different concentrations of PS. Additional correction techniques showed a significant improvement in PS detection limits. Some difficulties have been overcome, relating to settling the PS particles in suspension, corrosion of the microwave probe, and signal processing. All of this has led to a novel system design by combined the optical and microwave sensor system to facilitate effective and efficient tumour detection. This novelty demonstrated that this new system could distinguish between different particles sizes by optical detection and dielectric properties by microwave characterisation. The concluding section of this thesis presents the simultaneous detection of PS samples of different concentrations optically and with the microwave probe. This represents the first time such simultaneous measurements have been carried out using a combined probe such as that described here

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted