NON-INVASIVE MEASUREMENT OF DEEP TISSUE TEMPERATURE CHANGES CAUSED BY APOPTOSIS DURING BREAST CANCER NEOADJUVANT CHEMOTHERAPY: A CASE STUDY.

Treatment-induced apoptosis of cancer cells is one goal of cancer therapy. Interestingly, more heat is generated by mitochondria during apoptosis, especially the uncoupled apoptotic state,(1,2) compared to the resting state. In this case study, we explore these thermal effects by longitudinally measuring temperature variations in a breast lesion of a pathological complete responder during neadjuvant chemotherapy (NAC). Diffuse Optical Spectroscopic Imaging (DOSI) was employed to derive absolute deep tissue temperature using subtle spectral features of the water peak at 975 nm.3 A significant temperature increase was observed in time windows during the anthracycline and cyclophosphamide (AC) regimen but in not paclitaxel and bevacizumab regimen. Hemoglobin concentration changes generally did not follow temperature, suggesting that the measured temperature increases were likely due to mitochondrial uncoupling rather than a direct vascular effect. A simultaneous increase of tissue oxygen saturation with temperature was also observed, suggesting that oxidative stress also contributes to apoptosis. Although preliminary, this study indicates that longitudinal DOSI tissue temperature monitoring provides information that can improve our understanding of the mechanisms of tissue response during NAC.

[1]  Scott W. Lowe,et al.  Apoptosis A Link between Cancer Genetics and Chemotherapy , 2002, Cell.

[2]  B. Tromberg,et al.  Non-invasive tissue temperature measurements based on quantitative diffuse optical spectroscopy (DOS) of water , 2010, Physics in medicine and biology.

[3]  R. Estabrook,et al.  Kinetic studies of temperature changes and oxygen uptake concomitant with substrate oxidation by mitochondria: the enthalpy of succinate oxidation during ATP formation by mitochondria. , 1968, Archives of biochemistry and biophysics.

[4]  B Chance,et al.  The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. , 1973, The Biochemical journal.

[5]  Alessandro Torricelli,et al.  Absorption of collagen: effects on the estimate of breast composition and related diagnostic implications. , 2007, Journal of biomedical optics.

[6]  P. Petit,et al.  Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis , 1995, The Journal of cell biology.

[7]  B. Chance,et al.  High and low energy states of cytochromes. I. In mitochondria. , 1966, The Journal of biological chemistry.

[8]  B. Tromberg,et al.  Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods. , 2000, Applied optics.

[9]  A. Yodh,et al.  Diffuse optics for tissue monitoring and tomography , 2010, Reports on progress in physics. Physical Society.

[10]  E Gratton,et al.  Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge. , 1993, Journal of the Optical Society of America. A, Optics and image science.

[11]  L. O. Svaasand,et al.  Properties of photon density waves in multiple-scattering media. , 1993, Applied optics.

[12]  K L WILLIAMS,et al.  Infra-red thermometry in the diagnosis of breast disease. , 1961, Lancet.

[13]  G. Kroemer,et al.  Mitochondrial control of nuclear apoptosis , 1996, The Journal of experimental medicine.

[14]  N. Robert,et al.  Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  F. Sánchez-Jiménez,et al.  Role of reactive oxygen species in apoptosis: implications for cancer therapy. , 2000, The international journal of biochemistry & cell biology.

[16]  A. Cossarizza,et al.  Control of apoptosis by the cellular ATP level , 1996, FEBS letters.

[17]  J. Lerman,et al.  A Practice of Anesthesia for Infants and Children , 2019, A Practice of Anesthesia for Infants and Children.

[18]  M Gautherie,et al.  THERMOPATHOLOGY OF BREAST CANCER: MEASUREMENT AND ANALYSIS OF IN VIVO TEMPERATURE AND BLOOD FLOW , 1980, Annals of the New York Academy of Sciences.

[19]  G. Weissmann,et al.  FATTY ACIDS AND MULTIPLE SCLEROSIS. , 1964, Lancet.

[20]  E. Yu,et al.  Functional infrared imaging of the breast , 2000, IEEE Engineering in Medicine and Biology Magazine.

[21]  L. O. Svaasand,et al.  Boundary conditions for the diffusion equation in radiative transfer. , 1994, Journal of the Optical Society of America. A, Optics, image science, and vision.

[22]  B CHANCE,et al.  The respiratory chain and oxidative phosphorylation. , 1956, Advances in enzymology and related subjects of biochemistry.

[23]  Daniel L. Farkas,et al.  Biomedical Optical Imaging , 2009 .

[24]  David Hsiang,et al.  Diffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study. , 2009, Journal of biomedical optics.

[25]  So Hyun Chung,et al.  Non-Invasive Measurement of Pathological Heterogeneity of Cancer Tissues Using Water State Information from Diffuse Optical Spectroscopic Imaging. , 2009 .

[26]  M. H. Koelink,et al.  Reduced light-scattering properties for mixtures of spherical particles: a simple approximation derived from Mie calculations. , 1992, Applied optics.

[27]  S. Papa,et al.  Reactive oxygen species, mitochondria, apoptosis and aging , 2004, Molecular and Cellular Biochemistry.

[28]  So Hyun Chung,et al.  Non-invasive detection and monitoring of tumor pathological grade during neoadjuvant chemotherapy by measuring tissue water state using diffuse optical spectroscopic imaging. , 2009 .

[29]  G. Kroemer,et al.  Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis , 1996, FEBS letters.

[30]  B. Tromberg,et al.  In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy. , 2006, Journal of biomedical optics.

[31]  R. Estabrook,et al.  Kinetic studies of temperature changes and oxygen uptake in a differential calorimeter: the heat of oxidation of NADH and succinate. , 1967, Archives of biochemistry and biophysics.

[32]  E. Wolvetang,et al.  Mitochondrial respiratory chain inhibitors induce apoptosis , 1994, FEBS letters.

[33]  D. Streiner.  Maintaining Standards: Differences between the Standard Deviation and Standard Error, and When to Use Each , 1996, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[34]  G. Kroemer,et al.  Apoptosis-associated derangement of mitochondrial function in cells lacking mitochondrial DNA. , 1996, Cancer research.

[35]  G Gulsen,et al.  In vivo water state measurements in breast cancer using broadband diffuse optical spectroscopy , 2008, Physics in medicine and biology.

[36]  M. Drouet,et al.  [Oxidative stress and apoptosis]. , 1996, Annales pharmaceutiques francaises.

[37]  R. Youle,et al.  Mitochondrial dynamics and apoptosis. , 2008, Genes & development.

[38]  T. Ozawa,et al.  Oxygen stress induces an apoptotic cell death associated with fragmentation of mitochondrial genome. , 1995, Biochemical and biophysical research communications.