Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications.

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355-1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.

Frameworks of wavelength selection in diffuse reflectance spectroscopy for tissue differentiation in orthopedic surgery.

Significance: Wavelength selection from a large diffuse reflectance spectroscopy (DRS) dataset enables removal of spectral multicollinearity and thus leads to improved understanding of the feature domain. Feature selection (FS) frameworks are essential to discover the optimal wavelengths for tissue differentiation in DRS-based measurements, which can facilitate the development of compact multispectral optical systems with suitable illumination wavelengths for clinical translation. Aim: The aim was to develop an FS methodology to determine wavelengths with optimal discriminative power for orthopedic applications, while providing the frameworks for adaptation to other clinical scenarios. Approach: An ensemble framework for FS was developed, validated, and compared with frameworks incorporating conventional algorithms, including principal component analysis (PCA), linear discriminant analysis (LDA), and backward interval partial least squares (biPLS). Results: Via the one-versus-rest binary classification approach, a feature subset of 10 wavelengths was selected from each framework yielding comparable balanced accuracy scores (PCA: 94.8±3.47%, LDA: 98.2±2.02%, biPLS: 95.8±3.04%, and ensemble: 95.8±3.16%) to those of using all features (100%) for cortical bone versus the rest class labels. One hundred percent balanced accuracy scores were generated for bone cement versus the rest. Different feature subsets achieving similar outcomes could be identified due to spectral multicollinearity. Conclusions: Wavelength selection frameworks provide a means to explore domain knowledge and discover important contributors to classification in spectroscopy. The ensemble framework generated a model with improved interpretability and preserved physical interpretation, which serves as the basis to determine illumination wavelengths in optical instrumentation design.

Mobile multi-configuration clinical translational Raman system for oral cancer application.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

Label-Free Optical Spectroscopy for Early Detection of Oral Cancer.

Oral cancer is the 16th most common cancer worldwide. It commonly arises from painless white or red plaques within the oral cavity. Clinical outcome is highly related to the stage when diagnosed. However, early diagnosis is complex owing to the impracticality of biopsying every potentially premalignant intraoral lesion. Therefore, there is a need to develop a non-invasive cost-effective diagnostic technique to differentiate non-malignant and early-stage malignant lesions. Optical spectroscopy may provide an appropriate solution to facilitate early detection of these lesions. It has many advantages over traditional approaches including cost, speed, objectivity, sensitivity, painlessness, and ease-of use in clinical setting for real-time diagnosis. This review consists of a comprehensive overview of optical spectroscopy for oral cancer diagnosis, epidemiology, and recent improvements in this field for diagnostic purposes. It summarizes major developments in label-free optical spectroscopy, including Raman, fluorescence, and diffuse reflectance spectroscopy during recent years. Among the wide range of optical techniques available, we chose these three for this review because they have the ability to provide biochemical information and show great potential for real-time deep-tissue point-based in vivo analysis. This review also highlights the importance of saliva-based potential biomarkers for non-invasive early-stage diagnosis. It concludes with the discussion on the scope of development and future demands from a clinical point of view.

Silicon Photomultiplier-A High Dynamic Range, High Sensitivity Sensor for Bio-Photonics Applications.

This work is an overview of silicon photomultipliers (SiPMs) with a view to defining their importance for bio-photonic and clinical applications. SiPMs are benchmarked against other common photodetectors, namely, PIN diodes and avalanche photodetectors (APDs) and are compared with respect to important circuit design parameters. It will be shown that careful selection of the design bias voltage, overvoltage, gain defining components and device integration to micro-optics can allow SiPM detectors to achieve considerable sensitivity for auto-fluorescence (AF) detection and a wide dynamic range at low optical powers (~1 pW to ~4 µW). The SiPM has a manageable bias voltage (~25 V to ~30 V DC) for systems integration, and with optimised sensitivity it will enhance bio-photonic research in the area of AF to detect intraoperatively, for example, brain tumour margins.

Perspective on the integration of optical sensing into orthopedic surgical devices.

SIGNIFICANCE: Orthopedic surgery currently comprises over 1.5 million cases annually in the United States alone and is growing rapidly with aging populations. Emerging optical sensing techniques promise fewer side effects with new, more effective approaches aimed at improving patient outcomes following orthopedic surgery. AIM: The aim of this perspective paper is to outline potential applications where fiberoptic-based approaches can complement ongoing development of minimally invasive surgical procedures for use in orthopedic applications. APPROACH: Several procedures involving orthopedic and spinal surgery, along with the clinical challenge associated with each, are considered. The current and potential applications of optical sensing within these procedures are discussed and future opportunities, challenges, and competing technologies are presented for each surgical application. RESULTS: Strong research efforts involving sensor miniaturization and integration of optics into existing surgical devices, including K-wires and cranial perforators, provided the impetus for this perspective analysis. These advances have made it possible to envision a next-generation set of devices that can be rigorously evaluated in controlled clinical trials to become routine tools for orthopedic surgery. CONCLUSIONS: Integration of optical devices into surgical drills and burrs to discern bone/tissue interfaces could be used to reduce complication rates across a spectrum of orthopedic surgery procedures or to aid less-experienced surgeons in complex techniques, such as laminoplasty or osteotomy. These developments present both opportunities and challenges for the biomedical optics community.

Combined autofluorescence and diffuse reflectance for brain tumour surgical guidance: initial ex vivo study results.

This ex vivo study was conducted to assess the potential of using a fibre optic probe system based on autofluorescence and diffuse reflectance for tissue differentiation in the brain. A total of 180 optical measurements were acquired from 28 brain specimens (five patients) with eight excitation and emission wavelengths spanning from 300 to 700 nm. Partial least square-linear discriminant analysis (PLS-LDA) was used for tissue discrimination. Leave-one-out cross validation (LOOCV) was then used to evaluate the performance of the classification model. Grey matter was differentiated from tumour tissue with sensitivity of 89.3% and specificity of 92.5%. The variable importance in projection (VIP) derived from the PLS regression was applied to wavelengths selection, and identified the biochemical sources of the detected signals. The initial results of the study were promising and point the way towards a cost-effective, miniaturized hand-held probe for real time and label-free surgical guidance.

Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus.

OBJECTIVES: We sought to determine rates and factors associated with screening for type 2 diabetes mellitus (DM) in women with a history of gestational diabetes mellitus. METHODS: We retrospectively studied women with diagnosed gestational diabetes mellitus who delivered at a university-affiliated hospital (n=570). Data sources included medical and administrative record review. Main outcome measures were the frequency of any type of glucose testing at least 6 weeks after delivery and the frequency of recommended glucose testing. We assessed demographic data, past medical history, and prenatal and postpartum care characteristics. RESULTS: Rates of glucose testing after delivery were low. Any type of glucose testing was performed at least once after 38% of deliveries, and recommended glucose testing was performed at least once after 23% of deliveries. Among women with at least 1 visit to the health care system after delivery (n=447), 42% received any type of glucose test at least once, and 35% received a recommended glucose test at least once. Factors associated with testing were being married, having a visit with an endocrinologist after delivery, and having more visits after delivery. CONCLUSIONS: These findings suggest that most women with gestational diabetes mellitus are not screened for type 2 DM after delivery. Opportunities for DM prevention and early treatment are being missed.

Opportunistic screening for diabetes in routine clinical practice.

OBJECTIVE: Since 1997, the American Diabetes Association has recommended that nondiabetic individuals >/=45 years of age be screened for diabetes at least every 3 years. We sought to characterize the frequency, methods, and results of diabetes screening in routine clinical practice. RESEARCH DESIGN AND METHODS: We studied opportunistic screening in nondiabetic members of a health maintenance organization >/=45 years of age who were assigned to a large, integrated, academic health care delivery system. Screening was defined as the first glucose, HbA(1c), or oral glucose tolerance test (OGTT) performed between 1 January 1998 and 31 December 2000. Chart review was performed to determine the prevalence of diabetes risk factors and to describe follow-up. RESULTS: Of 8,286 nondiabetic patients >/=45 years of age, 69% (n = 5,752) were screened. The frequency of screening was greater in patients with one or more primary care visits and increased with age. Women were more likely to be screened than men, and patients with at least one diabetes risk factor were more likely to be screened than those without risk factors. Random plasma glucose was the most common screening test (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n = 77) of those with abnormal results received appropriate follow-up, and 17% (n = 35) were diagnosed with diabetes within 6 months of screening. The yield of screening was very low (0.6%, 35 of 5,752). CONCLUSIONS: Despite frequent screening and appropriate targeting of high-risk patients, follow-up of patients with abnormal results is uncommon and the yield of screening is low. Interventions are needed to help physicians recognize and provide appropriate follow-up for patients with potentially abnormal random glucose levels.

Improving diabetes processes of care in managed care.

OBJECTIVE: To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices. RESEARCH DESIGN AND METHODS: Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA(1c), blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models. RESULTS: Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes. CONCLUSIONS: The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.

Community-based screening for diabetes in Michigan.

OBJECTIVE: To describe and evaluate a community-based diabetes screening program supported by the Michigan Department of Community Health. RESEARCH DESIGN AND METHODS: Between 1 June 1999 and 31 December 1999, community screening for diabetes was conducted by voluntary organizations using a standard protocol, American Diabetes Association (ADA) questionnaires, and ADA capillary plasma glucose criteria. RESULTS: A total of 3506 individuals were screened, 14% of whom did not meet criteria for screening. Of the 3031 individuals appropriately screened, 57% were classified as being at high risk based on the ADA questionnaire and 5% had positive screening tests based on ADA capillary plasma glucose criteria. Despite systematic follow-up, the screening program's yield of individuals with undiagnosed diabetes was <1%. CONCLUSIONS: Community screening for diabetes conducted according to ADA recommendations was extremely inefficient at identifying individuals with undiagnosed diabetes. The ADA diabetes screening questionnaire resulted in many false positive tests, and the ADA criteria for positive plasma glucose tests likely missed a substantial portion of individuals with undiagnosed diabetes. Relying on biochemical tests such as random plasma glucose, changing the criteria for a positive plasma glucose test, targeting racial and ethnic minority groups, and targeting medically underserved individuals might improve the yield of community-based diabetes screening.