Quantum Cascade Laser Spectral Histopathology: Breast Cancer Diagnostics Using High Throughput Chemical Imaging

• Published in: Analytical chemistry (Washington) Vol. 89; no. 14; pp. 7348 - 7355
• Main Authors: Pilling, Michael J, Henderson, Alex, Gardner, Peter
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.07.2017
• Subjects: Abnormalities; artificial intelligence; Breast cancer; breast neoplasms; Breast Neoplasms - diagnostic imaging; Cancer; Cancer screening; Chemistry; Continuous spectra; Detectors; Diagnostic systems; diagnostic techniques; disease diagnosis; Female; Focal plane devices; Fourier transform infrared spectroscopy; Fourier transforms; High-Throughput Screening Assays; histology; Histopathology; Human performance; Humans; image analysis; Imaging; Infrared imaging; Infrared lasers; Infrared spectroscopy; Lasers; Lasers, Semiconductor; Learning algorithms; Machine learning; microarray technology; Microscopy; Optical Imaging; patient care; patients; Quantum cascade lasers; Quantum physics; screening; Spectral sensitivity; Spectrum analysis; Stroma
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/acs.analchem.7b00426

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.