Tissue dynamics spectroscopic imaging: functional imaging of heterogeneous cancer tissue

Abstract. Significance: Tumor heterogeneity poses a challenge for the chemotherapeutic treatment of cancer. Tissue dynamics spectroscopy captures dynamic contrast and can capture the response of living tissue to applied therapeutics, but the current analysis averages over the complicated spatial response of living biopsy samples. Aim: To develop tissue dynamics spectroscopic imaging (TDSI) to map the heterogeneous spatial response of tumor tissue to anticancer drugs. Approach: TDSI is applied to tumor spheroids grown from cell lines and to ex vivo living esophageal biopsy samples. Doppler fluctuation spectroscopy is performed on a voxel basis to extract spatial maps of biodynamic biomarkers. Functional images and bivariate spatial maps are produced using a bivariate color merge to represent the spatial distribution of pairs of signed drug-response biodynamic biomarkers. Results: We have mapped the spatial variability of drug responses within biopsies and have tracked sample-to-sample variability. Sample heterogeneity observed in the biodynamic maps is associated with histological heterogeneity observed using inverted selective-plane illumination microscopy. Conclusion: We have demonstrated the utility of TDSI as a functional imaging method to measure tumor heterogeneity and its potential for use in drug-response profiling.

[1]  E. Cuche,et al.  Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy. , 2005, Optics letters.

[2]  S J Cook,et al.  Mechanisms of acquired resistance to ERK1/2 pathway inhibitors , 2013, Oncogene.

[3]  Russell M Taylor,et al.  Inverse-power-law behavior of cellular motility reveals stromal-epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy. , 2015, Optica.

[4]  E. Cuche,et al.  Digital holography for quantitative phase-contrast imaging. , 1999, Optics letters.

[5]  J. Herman,et al.  Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours , 2002, The Journal of pathology.

[6]  Bihe Hu,et al.  Improved contrast in inverted selective plane illumination microscopy of thick tissues using confocal detection and structured illumination. , 2017, Biomedical optics express.

[7]  Hanchuan Peng,et al.  Extensible visualization and analysis for multidimensional images using Vaa3D , 2014, Nature Protocols.

[8]  Ye Fang,et al.  Label-free cell phenotypic assessment of the molecular mechanism of action of epidermal growth factor receptor inhibitors , 2013 .

[9]  Xian Xu,et al.  Three-dimensional in vitro tumor models for cancer research and drug evaluation. , 2014, Biotechnology advances.

[10]  Leilei Peng,et al.  Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids. , 2004, Applied optics.

[11]  Neil O Carragher,et al.  High-Content Phenotypic Profiling of Drug Response Signatures across Distinct Cancer Cells , 2010, Molecular Cancer Therapeutics.

[12]  Zach DeVito,et al.  Opt , 2017 .

[13]  Tayyaba Hasan,et al.  Diffusive and directional intracellular dynamics measured by field-based dynamic light scattering , 2010, Optics express.

[14]  A. Tomida,et al.  Drug resistance mediated by cellular stress response to the microenvironment of solid tumors. , 1999, Anti-cancer drug design.

[15]  S. Seneviratne,et al.  Bivariate colour maps for visualizing climate data , 2011 .

[16]  Daniel A. Keim,et al.  A survey and task-based quality assessment of static 2D colormaps , 2015, Electronic Imaging.

[17]  David D Nolte,et al.  Biodynamic imaging of live porcine oocytes, zygotes and blastocysts for viability assessment in assisted reproductive technologies. , 2015, Biomedical optics express.

[18]  Michael C. Kolios,et al.  Dynamic light scattering optical coherence tomography to probe motion of subcellular scatterers , 2019, Journal of biomedical optics.

[19]  Tobias Schreck,et al.  Assisted Descriptor Selection Based on Visual Comparative Data Analysis , 2011, Comput. Graph. Forum.

[20]  Kwan Jeong,et al.  Volumetric motility-contrast imaging of tissue response to cytoskeletal anti-cancer drugs. , 2007, Optics express.

[21]  P. A. Futreal,et al.  Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. , 2012, The New England journal of medicine.

[22]  Bihe Hu,et al.  Enhanced resolution 3D digital cytology and pathology with dual-view inverted selective plane illumination microscopy. , 2019, Biomedical optics express.

[23]  John J. Turek,et al.  Holographic optical coherence imaging of tumor spheroids , 2003 .

[24]  Stephan Saalfeld,et al.  Globally optimal stitching of tiled 3D microscopic image acquisitions , 2009, Bioinform..

[25]  Mina J Bissell,et al.  Tumor reversion: Correction of malignant behavior by microenvironmental cues , 2003, International journal of cancer.

[26]  Hanchuan Peng,et al.  V3D enables real-time 3D visualization and quantitative analysis of large-scale biological image data sets , 2010, Nature Biotechnology.

[27]  Fabrice Harms,et al.  Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis. , 2016, Biomedical optics express.

[28]  Katharine Grieve,et al.  Full-field optical coherence microscopy , 2004, Advanced Laser Technologies.

[29]  Daniel A. Keim,et al.  Explorative analysis of 2D color maps , 2015, WSCG 2015.

[30]  Adrian Mariampillai,et al.  Detecting apoptosis using dynamic light scattering with optical coherence tomography. , 2011, Journal of biomedical optics.

[31]  Stefan M Willems,et al.  Tumor heterogeneity and personalized cancer medicine: are we being outnumbered? , 2014, Future oncology.

[32]  D. Nolte,et al.  Holographic tissue dynamics spectroscopy. , 2011, Journal of biomedical optics.

[33]  Rajendra Bhatia,et al.  A Better Bound on the Variance , 2000, Am. Math. Mon..

[34]  Natan T. Shaked,et al.  Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy , 2010, Biomedical optics express.

[35]  Tejal A Desai,et al.  Optical coherence tomography of cell dynamics in three-dimensional tissue models. , 2006, Optics express.

[36]  Daniel A. Keim,et al.  Visual Analysis of Time‐Series Similarities for Anomaly Detection in Sensor Networks , 2014, Comput. Graph. Forum.

[37]  Joachim Hornegger,et al.  Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence Imaging , 2016, PloS one.

[38]  I. Tannock,et al.  Drug resistance and the solid tumor microenvironment. , 2007, Journal of the National Cancer Institute.

[39]  David D. Nolte,et al.  Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture , 2012, Biomedical optics express.

[40]  Hao Sun,et al.  Dynamic holography in semiconductors and biomedical optics , 2016 .

[41]  John Turek,et al.  Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts , 2016, Scientific Reports.

[42]  David D Nolte,et al.  Doppler fluctuation spectroscopy of intracellular dynamics in living tissue. , 2019, Journal of the Optical Society of America. A, Optics, image science, and vision.

[43]  D. Nolte,et al.  Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study. , 2015, Convergent science physical oncology.

[44]  Eun Kyung Choi,et al.  A patient-derived xenograft mouse model generated from primary cultured cells recapitulates patient tumors phenotypically and genetically , 2013, Journal of Cancer Research and Clinical Oncology.

[45]  John P. Kerekes,et al.  Techniques for Fusion of Multimodal Images: Application to Breast Imaging , 2006, 2006 International Conference on Image Processing.

[46]  Jeff Fingler,et al.  Homodyne en face optical coherence tomography. , 2006, Optics letters.

[47]  Cynthia A. Brewer,et al.  ColorBrewer.org: An Online Tool for Selecting Colour Schemes for Maps , 2003 .

[48]  Jeffrey R. Morgan,et al.  Mammalian Target of Rapamycin Contributes to the Acquired Apoptotic Resistance of Human Mesothelioma Multicellular Spheroids* , 2008, Journal of Biological Chemistry.

[49]  D. Boas,et al.  Dynamic light scattering optical coherence tomography. , 2012, Optics express.

[50]  J. Quincy Brown,et al.  An approach of 3D reconstruction for images by Dual-view Inverted Selective Plane Illumination Microscopy (diSPIM) , 2019, Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP).