Abstract
Fourier transform infrared (FT-IR) microscopy coupled with machine learning approaches has been demonstrated to be a powerful technique for identifying abnormalities in human tissue. The ability to objectively identify the prediseased state and diagnose cancer with high levels of accuracy has the potential to revolutionize current histopathological practice. Despite recent technological advances in FT-IR microscopy, sample throughput and speed of acquisition are key barriers to clinical translation. Wide-field quantum cascade laser (QCL) infrared imaging systems with large focal plane array detectors utilizing discrete frequency imaging have demonstrated that large tissue microarrays (TMA) can be imaged in a matter of minutes. However, this ground breaking technology is still in its infancy, and its applicability for routine disease diagnosis is, as yet, unproven. In light of this, we report on a large study utilizing a breast cancer TMA comprised of 207 different patients. We show that by using QCL imaging with continuous spectra acquired between 912 and 1800 cm-1, we can accurately differentiate between 4 different histological classes. We demonstrate that we can discriminate between malignant and nonmalignant stroma spectra with high sensitivity (93.56%) and specificity (85.64%) for an independent test set. Finally, we classify each core in the TMA and achieve high diagnostic accuracy on a patient basis with 100% sensitivity and 86.67% specificity. The absence of false negatives reported here opens up the possibility of utilizing high throughput chemical imaging for cancer screening, thereby reducing pathologist workload and improving patient care.
Highlights
Fourier transform infrared (FT-IR) microscopy coupled with machine learning approaches has been demonstrated to be a powerful technique for identifying abnormalities in human tissue
We showed that focal plane array (FPA)-based quantum cascade laser (QCL) imaging using continuous frequency spectra enables highly accurate discrimination between malignant and nonmalignant stroma
We further showed that we can use high throughput automated histopathology to accurately diagnose biopsy cores on a patient basis
Summary
Fourier transform infrared (FT-IR) microscopy coupled with machine learning approaches has been demonstrated to be a powerful technique for identifying abnormalities in human tissue. Wide-field quantum cascade laser (QCL) infrared imaging systems with large focal plane array detectors utilizing discrete frequency imaging have demonstrated that large tissue microarrays (TMA) can be imaged in a matter of minutes This ground breaking technology is still in its infancy, and its applicability for routine disease diagnosis is, as yet, unproven. In principle, increased throughput can be achieved using lower magnification optics such as a 4× magnification objective, enabling a 2.4 × 2.4 mm field of view and a corresponding pixel size of ≈19 μm Utilizing this approach for imaging large areas of laryngeal carcinoma, Beleites[11] demonstrated that acquisition times could be reduced by an order of magnitude compared to using a standard 15× objective. The trade-off between spatial resolution and throughput means that, at present, chemical images with acceptable spatial resolution are extremely difficult to acquire with an FTIR instrument on a clinically relevant time scale
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