Deciphering the internal complexity of living cells with quantitative phase microscopy: a multiscale approach

Abstract. The distribution of refractive indices (RIs) of a living cell contributes in a nonintuitive manner to its optical phase image and quite rarely can be inverted to recover its internal structure. The interpretation of the quantitative phase images of living cells remains a difficult task because (1) we still have very little knowledge on the impact of its internal macromolecular complexes on the local RI and (2) phase changes produced by light propagation through the sample are mixed with diffraction effects by the internal cell bodies. We propose to implement a two-dimensional wavelet-based contour chain detection method to distinguish internal boundaries based on their greatest optical path difference gradients. These contour chains correspond to the highest image phase contrast and follow the local RI inhomogeneities linked to the intracellular structural intricacy. Their statistics and spatial distribution are the morphological indicators suited for comparing cells of different origins and/or to follow their transformation in pathologic situations. We use this method to compare nonadherent blood cells from primary and laboratory culture origins and to assess the internal transformation of hematopoietic stem cells by the transduction of the BCR-ABL oncogene responsible for the chronic myelogenous leukemia.

[1]  Jingang Zhong,et al.  Phase retrieval of optical fringe patterns from the ridge of a wavelet transform. , 2005, Optics letters.

[2]  Wolfgang Wiechert,et al.  Single-cell microfluidics: opportunity for bioprocess development. , 2014, Current opinion in biotechnology.

[3]  Andreas Stemmer,et al.  Simplified approach to diffraction tomography in optical microscopy. , 2009, Optics express.

[4]  Daniele Zink,et al.  Nuclear structure in cancer cells , 2004, Nature Reviews Cancer.

[5]  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.

[6]  B. Lee,et al.  Full-field optical coherence microscopy for identifying live cancer cells by quantitative measurement of refractive index distribution. , 2010, Optics express.

[7]  T. Voeltzel,et al.  Primitive CML cell expansion relies on abnormal levels of BMPs provided by the niche and on BMPRIb overexpression. , 2013, Blood.

[8]  A. Roggan,et al.  Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm. , 1999, Journal of biomedical optics.

[9]  Stéphane Mallat,et al.  Singularity detection and processing with wavelets , 1992, IEEE Trans. Inf. Theory.

[10]  John F. Canny,et al.  A Computational Approach to Edge Detection , 1986, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[11]  Serge Monneret,et al.  Modeling quantitative phase image formation under tilted illuminations. , 2012, Optics letters.

[12]  L. Gerace,et al.  The size-wise nucleus: nuclear volume control in eukaryotes , 2007, The Journal of cell biology.

[13]  YoungJu Jo,et al.  Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications , 2013, Sensors.

[14]  Xianyu Su,et al.  Wavelet ridge techniques in optical fringe pattern analysis. , 2010, Journal of the Optical Society of America. A, Optics, image science, and vision.

[15]  A. Thaer.  The refractive index and dry mass distribution of mammalian erythrocytes , 1969, Journal of microscopy.

[16]  W. Pear,et al.  BCR/ABL induces multiple abnormalities of cytoskeletal function. , 1997, The Journal of clinical investigation.

[17]  M. Greaves,et al.  Detection of refractive index changes in individual living cells by means of surface plasmon resonance imaging. , 2010, Biosensors & bioelectronics.

[18]  R. Barer.  Refractometry and interferometry of living cells. , 1957, Journal of the Optical Society of America.

[19]  YongKeun Park,et al.  Active illumination using a digital micromirror device for quantitative phase imaging. , 2015, Optics letters.

[20]  J. Wang,et al.  An actin‐binding function contributes to transformation by the Bcr‐Abl oncoprotein of Philadelphia chromosome‐positive human leukemias. , 1993, The EMBO journal.

[21]  Sophia Mã ¶ ller,et al.  Biomechanics — Mechanical properties of living tissue , 1982 .

[22]  C. Hammond.  A symmetrical representation of the geometrical optics of the light microscope , 1998 .

[23]  Françoise Argoul,et al.  Diffraction phase microscopy: retrieving phase contours on living cells with a wavelet-based space-scale analysis , 2014, Journal of biomedical optics.

[24]  S. Shapshay,et al.  Detection of preinvasive cancer cells , 2000, Nature.

[25]  Gabriel Popescu,et al.  Hilbert phase microscopy for investigating fast dynamics in transparent systems. , 2005, Optics letters.

[26]  Shouyu Wang,et al.  Three-dimensional refractive index reconstruction of red blood cells with one-dimensional moving based on local plane wave approximation , 2012 .

[27]  R. Dasari,et al.  Diffraction phase microscopy for quantifying cell structure and dynamics. , 2006, Optics letters.

[28]  Gabriel Popescu,et al.  Measurement of red blood cell mechanics during morphological changes , 2010, Proceedings of the National Academy of Sciences.

[29]  P. H. Yap,et al.  Determining refractive index of single living cell using an integrated microchip , 2007 .

[30]  D. Polyzos,et al.  Scattering of he-ne laser light by an average-sized red blood cell. , 1999, Applied optics.

[31]  V. Lauer.  New approach to optical diffraction tomography yielding a vector equation of diffraction tomography and a novel tomographic microscope , 2002, Journal of microscopy.

[32]  Gabriel Popescu,et al.  Diffraction phase and fluorescence microscopy. , 2006, Optics express.

[33]  C. Fang-Yen,et al.  Optical diffraction tomography for high resolution live cell imaging. , 2009, Optics express.

[34]  C. Fang-Yen,et al.  Tomographic phase microscopy , 2008, Nature Methods.

[35]  E. Cuche,et al.  Measurement of the integral refractive index and dynamic cell morphometry of living cells with digital holographic microscopy. , 2005, Optics express.

[36]  A. Arneodo,et al.  Chromosome territories have a highly nonspherical morphology and nonrandom positioning , 2007, Chromosome Research.

[37]  A. Gotoh,et al.  Hematopoietic colony formation from human growth factor-dependent TF1 cells and human cord blood myeloid progenitor cells depends on SHP2 phosphatase function. , 2013, Stem cells and development.

[38]  K. Badizadegan,et al.  Live cell refractometry using microfluidic devices. , 2006, Optics letters.

[39]  N. Decoster,et al.  A wavelet-based method for multifractal image analysis. II. Applications to synthetic multifractal rough surfaces , 2000 .

[40]  Osman Kalender,et al.  Automatic segmentation, counting, size determination and classification of white blood cells , 2014 .

[41]  Axel Niendorf,et al.  Passive and active single-cell biomechanics: a new perspective in cancer diagnosis , 2009 .

[42]  Gabriel Popescu,et al.  Real Time Blood Testing Using Quantitative Phase Imaging , 2013, PloS one.

[43]  H. Pham,et al.  Diffraction phase microscopy with white light. , 2012, Optics letters.

[44]  Syed Twareque Ali,et al.  Two-Dimensional Wavelets and their Relatives , 2004 .

[45]  Christian Depeursinge,et al.  Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium. , 2008, Optics letters.

[46]  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.

[47]  K. Nugent,et al.  Refractive index measurement in viable cells using quantitative phase‐amplitude microscopy and confocal microscopy , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[48]  Alexander V Kretushev,et al.  Dissecting eukaryotic cells by coherent phase microscopy: quantitative analysis of quiescent and activated T lymphocytes. , 2012, Journal of biomedical optics.

[49]  Y C Fung,et al.  Theory of the sphering of red blood cells. , 1968, Biophysical journal.

[50]  M. Monsur Ali,et al.  Droplet microfluidics for single-molecule and single-cell analysis in cancer research, diagnosis and therapy , 2014 .

[51]  P. So,et al.  Diffraction optical tomography using a quantitative phase imaging unit. , 2014, Optics letters.

[52]  Alain Arneodo,et al.  A wavelet-based method for multifractal image analysis: From theoretical concepts to experimental applications , 2003 .

[53]  Jun Ma,et al.  Two-dimensional continuous wavelet transform for phase determination of complex interferograms. , 2011, Applied optics.

[54]  Takahiro Shibata,et al.  Detection of swelling of single isolated mitochondrion with optical microscopy. , 2014, Biomedical optics express.

[55]  A. Arneodo,et al.  A wavelet-based method for multifractal image analysis. I. Methodology and test applications on isotropic and anisotropic random rough surfaces , 2000 .

[56]  Stéphane Mallat,et al.  Characterization of Signals from Multiscale Edges , 2011, IEEE Trans. Pattern Anal. Mach. Intell..

[57]  M. Miwa,et al.  Low-coherent quantitative phase microscope for nanometer-scale measurement of living cells morphology. , 2008, Optics express.

[58]  Barry R. Masters,et al.  Quantitative Phase Imaging of Cells and Tissues , 2012 .

[59]  Yuhki Yanase,et al.  Evaluation of peripheral blood basophil activation by means of surface plasmon resonance imaging. , 2012, Biosensors & bioelectronics.

[60]  Huanfeng Ma,et al.  Advanced continuous wavelet transform algorithm for digital interferogram analysis and processing , 2006 .

[61]  Yongjin Sung,et al.  Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy , 2012, PloS one.

[62]  J. Wang,et al.  Activation of tyrosinase kinase and microfilament-binding functions of c-abl by bcr sequences in bcr/abl fusion proteins , 1991, Molecular and cellular biology.