Disorder strength measured by quantitative phase imaging as intrinsic cancer marker in fixed tissue biopsies

Tissue refractive index provides important information about morphology at the nanoscale. Since the malignant transformation involves both intra- and inter-cellular changes in the refractive index map, the tissue disorder measurement can be used to extract important diagnosis information. Quantitative phase imaging (QPI) provides a practical means of extracting this information as it maps the optical path-length difference (OPD) across a tissue sample with sub-wavelength sensitivity. In this work, we employ QPI to compare the tissue disorder strength between benign and malignant breast tissue histology samples. Our results show that disease progression is marked by a significant increase in the disorder strength. Since our imaging system can be added as an upgrading module to an existing microscope, we anticipate that it can be integrated easily in the pathology work flow.

[1]  M. Plummer,et al.  International agency for research on cancer. , 2020, Archives of pathology.

[2]  Yongkeun Park,et al.  Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum , 2008, Proceedings of the National Academy of Sciences.

[3]  V. Backman,et al.  Partial-wave microscopic spectroscopy detects subwavelength refractive index fluctuations: an application to cancer diagnosis. , 2009, Optics letters.

[4]  Vadim Backman,et al.  Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy. , 2009, Cancer research.

[5]  Vadim Backman,et al.  Role of cytoskeleton in controlling the disorder strength of cellular nanoscale architecture. , 2010, Biophysical journal.

[6]  Silvia Sanduleanu,et al.  In vivo diagnosis and classification of colorectal neoplasia by chromoendoscopy-guided confocal laser endomicroscopy. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[7]  Shikhar Uttam,et al.  Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy. , 2010, Journal of biomedical optics.

[8]  Vadim Backman,et al.  Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening. , 2010, Cancer research.

[9]  Rohit Bhargava,et al.  Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis. , 2010, Optics letters.

[10]  Zhuo Wang,et al.  Optical measurement of cycle-dependent cell growth , 2011, Proceedings of the National Academy of Sciences.

[11]  Vadim Backman,et al.  The influence of chromosome density variations on the increase in nuclear disorder strength in carcinogenesis , 2011, Physical biology.

[12]  Zhuo Wang,et al.  Scattering-phase theorem. , 2011, Optics letters.

[13]  Zhuo Wang,et al.  Measuring the scattering parameters of tissues from quantitative phase imaging of thin slices. , 2011, Optics letters.

[14]  G. Popescu Quantitative Phase Imaging of Cells and Tissues , 2011 .

[15]  Zhuo Wang,et al.  Tissue refractive index as marker of disease. , 2011, Journal of biomedical optics.

[16]  J. Rogers,et al.  Spatial light interference microscopy (SLIM) , 2010, IEEE Photonic Society 24th Annual Meeting.

[17]  Rohit Bhargava,et al.  Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer , 2012, Breast Cancer Research and Treatment.

[18]  Vadim Backman,et al.  Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization. , 2012, Cancer research.

[19]  Vadim Backman,et al.  High-speed spectral nanocytology for early cancer screening , 2013, Journal of biomedical optics.

[20]  Ashish K. Tiwari,et al.  Nano-Architectural Alterations in Mucus Layer Fecal Colonocytes in Field Carcinogenesis: Potential for Screening , 2013, Cancer Prevention Research.

[21]  Vadim Backman,et al.  Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening , 2013, Endoscopy.

[22]  Vadim Backman,et al.  HDAC Up-Regulation in Early Colon Field Carcinogenesis Is Involved in Cell Tumorigenicity through Regulation of Chromatin Structure , 2013, PloS one.

[23]  Yongjin Sung,et al.  Multiple Phases of Chondrocyte Enlargement Underlie Differences in Skeletal Proportions , 2013, Nature.

[24]  Shikhar Uttam,et al.  Investigation of nanoscale structural alterations of cell nucleus as an early sign of cancer , 2014, BMC biophysics.

[25]  Gabriel Popescu,et al.  Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging , 2015, Scientific Reports.

[26]  Vadim Backman,et al.  Nanocytological Field Carcinogenesis Detection to Mitigate Overdiagnosis of Prostate Cancer: A Proof of Concept Study , 2015, PloS one.

[27]  Gabriel Popescu,et al.  Breast cancer diagnosis using spatial light interference microscopy , 2015, Journal of biomedical optics.

[28]  Shikhar Uttam,et al.  Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens. , 2015, Cancer research.

[29]  Liron Pantanowitz,et al.  Quantitative phase imaging to improve the diagnostic accuracy of urine cytology , 2016, Cancer cytopathology.

[30]  Minh N. Do,et al.  Automatic Gleason grading of prostate cancer using quantitative phase imaging and machine learning , 2017, Journal of biomedical optics.

[31]  Gabriel Popescu,et al.  Label-free tissue scanner for colorectal cancer screening , 2017, Journal of biomedical optics.

[32]  Gabriel Popescu,et al.  Quantitative phase imaging for medical diagnosis , 2017, Journal of biophotonics.

[33]  Adam Wax,et al.  Optical Phase Measurements of Disorder Strength Link Microstructure to Cell Stiffness. , 2017, Biophysical journal.

[34]  Gabriel Popescu,et al.  Quantifying collagen fiber orientation in breast cancer using quantitative phase imaging , 2017, Journal of biomedical optics.

[35]  Adam Wax,et al.  Cellular shear stiffness reflects progression of arsenic-induced transformation during G1 , 2017, Carcinogenesis.