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Daniel C Fernandez

Publications and source records attributed to Daniel C Fernandez.

2 recordsLinked to original sources

High throughput assessment of cells and tissues: Bayesian classification of spectral metrics from infrared vibrational spectroscopic imaging data.

Vibrational spectroscopy allows a visualization of tissue constituents based on intrinsic chemical composition and provides a potential route to obtaining diagnostic markers of diseases. Characterizations utilizing infrared vibrational spectroscopy, in particular, are conventionally low throughput in data acquisition, generally lacking in spatial resolution with the resulting data requiring intensive numerical computations to extract information. These factors impair the ability of infrared spectroscopic measurements to represent accurately the spatial heterogeneity in tissue, to incorporate robustly the diversity introduced by patient cohorts or preparative artifacts and to validate developed protocols in large population studies. In this manuscript, we demonstrate a combination of Fourier transform infrared (FTIR) spectroscopic imaging, tissue microarrays (TMAs) and fast numerical analysis as a paradigm for the rapid analysis, development and validation of high throughput spectroscopic characterization protocols. We provide an extended description of the data treatment algorithm and a discussion of various factors that may influence decision-making using this approach. Finally, a number of prostate tissue biopsies, arranged in an array modality, are employed to examine the efficacy of this approach in histologic recognition of epithelial cell polarization in patients displaying a variety of normal, malignant and hyperplastic conditions. An index of epithelial cell polarization, derived from a combined spectral and morphological analysis, is determined to be a potentially useful diagnostic marker.

Bayes Theorem↗

Infrared spectroscopic imaging for histopathologic recognition.

The process of histopathology, comprising tissue staining and morphological pattern recognition, has remained largely unchanged for over 140 years. Although it is integral to clinical and research activities, histopathologic recognition remains a time-consuming, subjective process to which only limited statistical confidence can be assigned because of inherent operator variability. Although immunohistochemical approaches allow limited molecular detection, significant challenges remain in using them for quantitative, automated pathology. Vibrational spectroscopic approaches, by contrast, directly provide nonperturbing molecular descriptors, but a practical spectroscopic protocol for histopathology is lacking. Here we couple high-throughput Fourier transform infrared (FTIR) spectroscopic imaging of tissue microarrays with statistical pattern recognition of spectra indicative of endogenous molecular composition and demonstrate histopathologic characterization of prostatic tissue. This automated histologic segmentation is applied to routine archival tissue samples, incorporates well-defined tests of statistical significance and eliminates any requirement for dyes or molecular probes. Finally, we differentiate benign from malignant prostatic epithelium by spectroscopic analyses.

Diagnosis, Differential↗