Biomedical subjects

Michele Follen

Publications and source records attributed to Michele Follen.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Effect of probe pressure on cervical fluorescence spectroscopy measurements.

Fluorescence spectroscopy is a promising technology for detection of epithelial precancers and cancers. While age and menopausal status influence measurements in the cervix, other variables do not significantly affect the diagnosis. In this study we examine probe pressure as a variable. A fiber optic probe to measure fluorescence spectra at different calibrated levels of pressure was designed and tested. A pilot study was conducted measuring fluorescence excitation emission matrices in 20 patients at light, medium, and firm pressure. Spectroscopic data were pre-processed and analyzed to compare mean peak intensities as a function of pressure. Further statistical analyses tested for differences in intensities at each excitation/emission wavelength pair. Four providers made measurements from 41 sites; 33 yielded good quality spectroscopic data (22 squamous normal, 7 squamous abnormal, 3 columnar normal, 1 transformation zone) from 17 of 20 patients. At all pressure levels, abnormal tissue showed less fluorescence intensity than normal tissue, and post-menopausal patients showed higher fluorescence intensity than premenopausal patients, consistent with previous analyses. A permutation analysis suggests that pressure does not significantly affect fluorescence intensity or lineshape. While other studies are needed to confirm these findings, this study suggests that fluorescence spectroscopy is a robust technology likely not influenced by fiber optic probe pressure.

Adult↗

PubMedDate not supplied

Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer.

Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories.

Algorithms↗

PubMedDate not supplied

Calibration standards for multicenter clinical trials of fluorescence spectroscopy for in vivo diagnosis.

In the context of clinical trials, calibration protocols for optical instruments that ensure measurement accuracy and the ability to carry out meaningful comparisons of data acquired from multiple instruments are required. A series of calibration standards and procedures are presented to assess technical feasibility of optical devices for cervical precancer detection. Measurements of positive and negative standards, and tissue are made with two generations of research grade spectrometers. Calibration accuracy, ability of standards to correct and account for changes in experimental conditions, and device components are analyzed. The relative frequency of measured calibration standards is investigated retrospectively using statistical analysis of trends in instrument performance. Fluorescence measurements of standards and tissue made with completely different spectrometers show good agreement in intensity and lineshape. Frequency of wavelength calibration standards is increased to every 2 h to compensate for thermal drifts in grating mount. Variations in illumination energy detected between standards and patient measurements require probe redesign to allow for simultaneous acquisition of illumination power with every patient measurement. The use of frequent and well-characterized standards enables meaningful comparison of data from multiple devices and unambiguous interpretation of experiments among the biomedical optics community.

Calibration↗

PubMedDate not supplied

Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia.

We present a mathematical model to calculate the relative concentration of light scatterers, light absorbers, and fluorophores in the epithelium and stroma. This mathematical description is iteratively fit to the fluorescence spectra measured in vivo, yielding relative concentrations of each molecule. The mathematical model is applied to a total of 493 fluorescence measurements of normal and dysplastic cervical tissue acquired in vivo from 292 patients. The estimated parameters are compared with histopathologic diagnosis to evaluate their diagnostic potential. The mathematical model is validated using fluorescence spectra simulated with known sets of optical parameters. Subsequent application of the mathematical model to in vivo fluorescence measurements from cervical tissue yields fits that accurately describe measured data. The optical parameters estimated from 493 fluorescence measurements show an increase in epithelial flavin adenine dinucleotide (FAD) fluorescence, a decrease in epithelial keratin fluorescence, an increase in epithelial light scattering, a decrease in stromal collagen fluorescence, and an increase in stromal hemoglobin light absorption in dysplastic tissue compared to normal tissue. These changes likely reflect an increase in the metabolic activity and loss of differentiation of epithelial dysplastic cells, and stromal angiogenesis associated with dysplasia. The model presented here provides a tool to analyze clinical fluorescence spectra yielding quantitative information about molecular changes related to dysplastic transformation.

Computer Simulation↗

PubMedDate not supplied

Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements.

We present Monte Carlo modeling studies to provide a quantitative understanding of contrast observed in spatially resolved reflectance spectra of normal and highly dysplastic cervical tissue. Simulations have been carried out to analyze the sensitivity of spectral measurements to a range of changes in epithelial and stromal optical properties that are reported to occur as dysplasia develops and to predict reflectance spectra of normal and highly dysplastic tissue at six different source-detector separations. Simulation results provide important insights into specific contributions of different optical parameters to the overall spectral response. Predictions from simulations agree well with in vivo measurements from cervical tissue and successfully describe spectral differences observed in reflectance measurements from normal and precancerous tissue sites. Penetration depth statistics of photons detected at the six source-detector separations are also presented to reveal the sampling depth profile of the fiber-optic probe geometry simulated. The modeling studies presented provide a framework to meaningfully interpret optical signals obtained from epithelial tissues and to optimize design of optical sensors for in vivo reflectance measurements for precancer detection. Results from this study can facilitate development of analytical photon propagation models that enable inverse estimation of diagnostically relevant optical parameters from in vivo reflectance measurements.

Biomarkers, Tumor↗

PubMedDate not supplied

Natural history of cervical intraepithelial neoplasia: a meta-analysis.

OBJECTIVE: To determine the probabilities of transition of stages in the cervical cancer by conducting a meta-studies on the topic. STUDY DESIGN: We identified health states of interest in the natural history of cervical precancer, identified all possible papers that could meet selection criteria, developed relevance and acceptability criteria for inclusion, then thoroughly reviewed the selected studies. To determine the transition probability data we used a random effects model. We determined probabilities for 4 health state transitions. The 6-month mean predictive transition probability (95% confidence intervals with "prediction interval" in parentheses) for high grade squamous intraepithelial lesions (HSIL) to cancer was 0.0037 (0.00004, 0.03386), for low grade squamous intraepithelial lesions (LSIL) to HSIL was 0.0362 (0.00055, 0.23220), for HSIL to LSIL was 0.0282 (0.00027, 0.35782), and for LSIL to normal was 0.0740 (0.00119, 0.42672). CONCLUSION: The transition probabilities between cervical cancer health states for 6-month intervals are small; however, the cumulative risk of cervical cancer is significant. Markers to identify the cervical precursors that will lead to the transition to cervical cancer are needed.

Confidence Intervals↗

PubMedDate not supplied

Collecting direct non-health care and time cost data: application to screening and diagnosis of cervical cancer.

BACKGROUND: Data on direct non-health care and time costs are rarely collected, though the incorporation of such data is essential for performing cost-effectiveness analyses according to established guidelines. OBJECTIVES: To explore the challenges involved in collecting and analyzing these data from patients enrolled in a clinical trial. METHODS: Through the use of a pilot study, the authors designed a questionnaire to collect these costs. They used this questionnaire in a clinical trial conducted at a comprehensive cancer center and a public community hospital. Patients in the trial were undergoing screening or diagnostic procedures through a clinical protocol designed to measure the effectiveness of fluorescence and reflectance spectroscopy for detecting cervical precancers. Direct non-health care costs were adjusted to 2003 constant dollars. RESULTS: The authors successfully collected direct non-health care and time cost data, thus demonstrating the feasibility of acquiring such data. Compared to patients receiving diagnostic services for cervical cancer, those receiving screening services for the same condition in both settings incurred lower direct non-health care costs and time costs, as defined in the questionnaire. Compared to patients receiving either service at the comprehensive cancer center, those seeking either service at the public community hospital incurred lower direct non-health care costs and time costs. When outliers were removed, total direct non-health care costs and time costs substantially decreased for diagnostic patients in the comprehensive cancer center; total direct non-health care costs and time costs for other subgroups remained essentially unchanged. CONCLUSIONS: Direct non-health care and time cost data can be collected within a large-scale clinical trial. The setting (community v. specialty hospital) and population (patients receiving screening v. diagnostic examination) makes a difference regarding the cost totals. The order of magnitude of the final result depends on the context in which the non-health care and time cost data will be used.

Adult↗