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Investigation of single beam ultrasound sensitivity as a monitoring tool for local hyperthermia treatment in breast cancer

Abstract

Local Hyperthermia treatment (LHT) holds great promise as an adjuvant method in combating breast cancer. In LHT treatment, cancerous tissue is exposed to supraphysiological temperature in order to destroy the tissue directly or improve their susceptibility to other treatment regimes. To observe the progression of tissue necrosis during LHT treatment, a temperature elevation monitoring system is important. Single beam ultrasound (SBUS) is a convenient, non-invasive, and radiation free method that is relatively simple compared to other imaging modalities. Therefore, this study investigates the sensitivity of SBUS towards microstructural tissue changes during LHT treatment. Ex-vivo experiments are conducted on both normal and pathological breast tissues harvested from carcinogenic induced animal models. These tissue samples are exposed to high temperatures ranging from 37oC to 55oC. Different sets of samples were used for each temperature range. For each temperature group, 11 samples were used and tested. Protein concentrations in all the samples are then quantitatively measured for in-depth correlation and sensitivity analysis. Microscopic histological analysis and comparison with B-Mode ultrasound are also carried out for verification purposes. Result shows that there is a significant correlation between attenuation level and total protein concentration in pathological tissues with an observed value of 0.617 and p-value of 0.0001. Histological analysis indicates that cellular-level damage seen in pathological tissue samples is much more significant compared to normal tissues. Comparison with B-Mode ultrasound shows consistent mean grey scale and attenuation trends during LHT treatment, which supported the findings obtained using the SBUS method.

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References

  1. Abolhassani MD, Norouzy A, Takavar A, Ghanaati H (2007) Noninvasive temperature estimation using sonographic digital images. J Ultrasound Med 26:215–222

    Google Scholar 

  2. Al-Zhoughbi W, Huang J, Paramasivan GS, Till H et al (2014) Tumor macroenvironment and metabolism. Semin Oncol 41:281–295

    Google Scholar 

  3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular Biology of the cell, 4th ed. Garland Science, New York

  4. Anbar M (1994) Hyperthermia of the cancerous breast: Analysis of mechanism. Cancer Lett 84:23–29

    Google Scholar 

  5. Arthur RM, Straube WL, Starman JD, Moros EG (2003) Noninvasive temperature estimation based on the energy of backscattered ultrasound. Med Phys 30:1021–1029

    Google Scholar 

  6. Bazán I, Vazquez M, Ramos A, Vera A, Leija L (2009) A performance analysis of echographic ultrasonic techniques for non-invasive temperature estimation in hyperthermia range using phantoms with scatterers. Ultrasonics 49:358–376

    Google Scholar 

  7. Bettaieb A, Wrzal PK, Averill-bates DA (2013) Hyperthermia: Cancer treatment and beyond. Cancer Treat Innov Approaches B 2:257–283

  8. Borrelli MJ, Wong RSL, Dewey WC (1986) A direct correlation between hyperthermia-induced membrane blebbing and survival in synchronous G1 CHO cells. J Cell Physiol 126:181–190

    Google Scholar 

  9. Borrelli MJ, Thompson LL, Cain CA, Dewey WC (1990) Time-temperature analysis of cell killing of BHK cells heated at temperatures in the range of 43.5oC to 57.0oC. Int J Radiat Oncol Biol Phys 19:389–399

    Google Scholar 

  10. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Google Scholar 

  11. Bunnell TM, Burbach BJ, Shimizu Y, Ervasti JM (2011) β-Actin specifically controls cell growth, migration, and the G-actin pool. Mol Biol Cell 22:4047–4058

    Google Scholar 

  12. Chanda S, Nagani K (2013) In vitro and in vivo methods for anticancer activity evaluation and some indian medicinal plants possessing anticancer properties: an overview. IC J Pharmacogn Phytochem 8192(2):2668735–5. https://doi.org/10.1007/s13197-011-0276-5

  13. Chaudary SS, Mishra RK, Swarup A, Thomas JM (1984) Dielectric properties of normal and malignant human breast tissue at microwave and radiowave frequencies. Indian J Biochem Biophys 21:76–79

    Google Scholar 

  14. Chicheł A, Skowronek J, Kubaszewska M, Kanikowski M (2007) Hyperthermia - Description of a method and a review of clinical applications. Rep Pract Oncol Radiother 12:267–275

    Google Scholar 

  15. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103

    Google Scholar 

  16. Clarke RL, Bush NL, Haar GR (2003) The changes in acoustic attenuation due to in vitro heating. Ultrasound Med Biol 29:127–135

    Google Scholar 

  17. Coss RA, Linnemans WAM (1996) The effects of hyperthermia on the cytoskeleton: a review. Int J Hyperth 12:173–196

    Google Scholar 

  18. Desouza M, Gunning PW, Stehn JR (2012) The actin cytoskeleton as a sensor and mediator of apoptosis. Bioarchitecture 2:75–87

    Google Scholar 

  19. Dibbyan M, Ram MV, Debasish R, Rajan K (2018) A remote temperature sensor for an ultrasound hyperthermia system using the acoustic signal derived from the heating signals. Int J Hyperth 34(1):122–131. https://doi.org/10.1080/02656736.2017.1324178

    Article  Google Scholar 

  20. Dmitrii IL, Anastasiya VP, Valeria VM, Olga PN (2008) Thermal unfolding and aggregation of actin Stabilization and destabilization of actin filaments. FEBS J 275:4280–4295

    Google Scholar 

  21. Doyle TE, Factor RE, Ellefson CL, Sorensen KM et al (2011) High-frequency ultrasound for intraoperative margin assessments in breast conservation surgery: a feasibility study. BMC Cancer 11:444

    Google Scholar 

  22. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Google Scholar 

  23. Falk MH, Issels RD (2001) Hyperthermia in oncology. Int J Hyperth 17:1–18

    Google Scholar 

  24. Ferrara FJ (2015) Spatial and temporal control of hyperthermia using real time ultrasonic thermal strain imaging with motion compensation, phantom study. PLoS ONE 10(8):e0134938. https://doi.org/10.1371/journal.pone.0134938

    Article  Google Scholar 

  25. Gang Liu WM, Grant D, Persky VM, Latham RH Jr, Singer, Condeelis Paul J, Matsudaira T (2002) Interactions of elongation factor 1α with F-Actin and β-Actin mRNA: implications for anchoring mRNA in cell protrusions. Mol Biol Cell 13(2):579–592

    Google Scholar 

  26. Ghoshal G, Luchies AC, Blue JP, Oelze ML (2011) Temperature dependent ultrasonic characterization of biological media. J Acoust Soc Am 130:2203

    Google Scholar 

  27. Graham SJ, Chen L, Leitch M, Peters RD et al (1999) Quantifying tissue damage due to focused ultrasound heating observed by MRI. Magn Reson Med 41:321–328

    Google Scholar 

  28. Hendee WR, Ritenour ER (2002) Medical Imaging Physics, 4th edn. Wiley Liss, New York

    Google Scholar 

  29. James RM, Brian JS (2007) MR Imaging in Hyperthermia. Radiographics 27(6):1809–1181

    Google Scholar 

  30. Jockusch BM, Schoenenberger CA, Stetefeld J, Aebi U (2006) Tracking down the different forms of nuclear actin. Trends Cell Biol 16:391–396

    Google Scholar 

  31. Khan VR, Brown IR (2002) The effect of hyperthermia on the induction of cell death in brain, testis, and thymus of the adult and developing rat. Cell Stress Chaperones 7:73–90

    Google Scholar 

  32. Kemmerer JP, Oelze ML (2012) Ultrasonic assessment of thermal therapy in rat liver. Ultrasound Med Biol 38:2130–2137

    Google Scholar 

  33. Kennedy JE (2005) High-intensity focused ultrasound in the treatment of solid tumours. Nat Rev Cancer 5:321–327

  34. Kim JH, Hahn EW, Ahmed SA (1982) Combination hyperthermia and radiation therapy for malignant melanoma. Cancer 50:478–482

    Google Scholar 

  35. Kim Y, Gelehrter SK, Fifer CG, Lu JC et al (2011) Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: Feasibility study in a fetal sheep model. Ultrasound Obstet Gynecol 37:450–457

    Google Scholar 

  36. Kok HP, Wust P, Stauffer PR, Bardati F et al (2015) Current state of the art of regional hyperthermia treatment planning: a review. Radiat Oncol 10:19

    Google Scholar 

  37. Lambotte L (1986) Cellular swelling and anoxic injury of the liver. Eur Surg Res 18:224–229

    Google Scholar 

  38. Landini L, Sarnelli R (1986) Evaluation of the attenuation coefficients in normal and pathological breast tissue. Med Biol Eng Comput 24:243–247

    Google Scholar 

  39. Lewis MA, Staruch RM, Chopra R (2015) Thermometry and ablation monitoring with ultrasound. Int J Hyperth 31:163–181

    Google Scholar 

  40. Luchetti F, Mannello F, Canonico B, Battistelli M, Burattini S, Falcieri E, Papa S (2004) Integrin and cytoskeleton behaviour in human neuroblastoma cells during hyperthermia-related apoptosis. Apoptosis 9:635-648

  41. Manaf NA, Aziz MNC, Ridzuan DF, Salim MIM, Wahab AA, Lai KW, Hum YC (2016) Feasibility of A-mode ultrasound attenuation as a monitoring method of local hyperthermia treatment. Med Biol Eng Comput 54(6):967–981

    Google Scholar 

  42. McDannold N (2005) Quantitative MRI-based temperature mapping based on the proton resonant frequency shift: review of validation studies. Int J Hyperth 21:533–546

    Google Scholar 

  43. Mokhtari-Dizaji M, Gorji-Ara T, Ghanaeati H, Kalbasi M (2007) Ultrasound monitoring of temperature change during interstitial laser thermotherapy of liver: an in vitro study. Annu Int Conf IEEE Eng Med Biol - Proc 15:2130–2133

  44. Mortensen CL, Edmonds PD, Gorfu Y, Hill JR et al (1996) Ultrasound tissue characterization of breast biopsy specimens: expanded study. Ultrason Imaging 18:215–230

    Google Scholar 

  45. Oleson JR, Samulski TV, Leopold KA, Clegg ST, Dewhirst MW, Dodge RK, George SL (1993) Sensitivity of hyperthermia trial outcomes to temperature and time—implications for thermal goals of treatment. Int J Radiat Oncol Biol Phys 25:289–297

    Google Scholar 

  46. Parmar N, Kolios MC (2006) An investigation of the use of transmission ultrasound to measure acoustic attenuation changes in thermal therapy. Med Biol Eng Comput 44:583–591

    Google Scholar 

  47. Pasternak MM, Strohm EM, Berndl ESL, Kolios MC (2015) Properties of cells through life and death - an acoustic microscopy investigation. Cell Cycle 14:2891–2898

    Google Scholar 

  48. Pousek L, Jelinek M, Storkova B, Novak P (2006) Noninvasive temperature monitoring using ultrasound tissue characterization method. Inf Technol Interfaces Conf, 219–224

  49. Rufang Z, Deyu Y, Chanjuan Z, Ke C, Zhao L, Liang C, Liang F, Peng X (2012) β-actin as a loading control for plasma-based Western blot analysis of major depressive disorder patients. Anal Biochem 427(2):116-20

  50. Russo IH, Russo J (1978) Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz(a)anthracene. J Natl Cancer Inst 61:1439–1442

    Google Scholar 

  51. Salim MIM, Ahmmad SNZ, Rosidi B, Ariffin I, Ahmad AH, Supriyanto E, S.N.Z (2010) Measurements of Ultrasound Attenuation for normal and pathological mice breast tissue Using 10 MHz Ultrasound Wave. Proceeding of The 3rd WSEAS International Conference on Visualization Imaging and Simulation, 118-122

  52. Siegel R, Miller K, Jemal A (2015) Cancer statistics. CA Cancer J Clin 65(1):29. https://doi.org/10.3322/caac.21254

    Article  Google Scholar 

  53. Simon C, VanBaren P, Ebbini ES (1998) Two-dimensional temperature estimation using diagnostic ultrasound. Ultrason Ferroelectr Freq Control IEEE Trans 45:1088–1099

    Google Scholar 

  54. Spencer VA, Costes S, Inman JL, Xu R, Chen J, Hendzel MJ, Bissell MJ (2011) Depletion of nuclear actin is a key mediator of quiescence in epithelial cells. J Cell Sci 124:123–132

    Google Scholar 

  55. Surowiec AJ, Stuchly SS, Barr JB, Swarup A (1988) Dielectric properties of Breast Carcinoma and the Surrounding tissue. IEEE Trans Biomed Eng 35:257–263

    Google Scholar 

  56. Techavipoo U, Varghese T, Chen Q, Stiles T et al (2004) Temperature dependence of ultrasonic propagation speed and attenuation in excised canine liver tissue measured using transmitted and reflected pulses. J Acoust Soc Am 115:2859–2865

    Google Scholar 

  57. The Global Cancer Observatory, International Agency for Research on Cancer (2021)World Health Organization. https://gco.iarc.fr/today/home. Accessed 1 July 2021

  58. Tina MB, Brandon JB, Yoji S, James ME (2011) β-Actin specifically controls cell growth, migration, and the G-actin pool. Mol Biol Cell 22:21

    Google Scholar 

  59. Tinoco G, Warsch S, Avancha K, Montero AJ (2013) Treating breast cancer in the 21st century: Emerging biological therapies. J Cancer 4:117–132

    Google Scholar 

  60. van Dongen KW, a, Verweij MD (2011) A feasibility study for non-invasive thermometry using non-linear ultrasound. Int J Hyperth 27:612–624

    Google Scholar 

  61. World health Organization (2021) Breast Cancer. https://www.who.int/news-room/fact-sheets/detail/breast-cancer. Accessed 1 July 2021

  62. Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag PM (2002) Hyperthermia in combined treatment of cancer. Lancet Oncol 3(8):487–497

    Google Scholar 

  63. Yang C, Zhu H, Wu S, Bai Y, Gao H (2010) Correlations between B-mode ultrasonic image texture features and tissue temperature in microwave ablation. J Ultrasound Med 29:1787–1799

    Google Scholar 

  64. Yilmaz IA, Akçay T, Çakatay U, Telci A et al (2003) Relation between bladder cancer and protein oxidation. Int Urol Nephrol 35:345–350

    Google Scholar 

  65. Zagar TM, Oleson JR, Vujaskovic Z, Dewhirst MW et al (2010) Hyperthermia for locally advanced breast cancer. Int J Hyperth 26:618–624

    Google Scholar 

  66. Zhaleh B, Zahra J, Behnaz K, Nazila E, Reza ZA (2016) Hyperthermia: How can it be used. Oman Med J 31(2):89–97

    Google Scholar 

  67. Zhou Y-F, Arbab S, Xu A (2011) High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol 2:8–27

    Google Scholar 

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Acknowledgements

The authors would like to express gratitude to the Ministry of Higher Education of Malaysia (MOHE), Universiti Malaya RU Grant (ST014-2019) and UTM for supporting this research under Vot 15J83 and 04G47.

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Correspondence to Khin Wee Lai.

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Manaf, N.A., Wahab, A.A., Rasheed, H.A. et al. Investigation of single beam ultrasound sensitivity as a monitoring tool for local hyperthermia treatment in breast cancer. Multimed Tools Appl (2022). https://doi.org/10.1007/s11042-021-11845-5

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  • DOI: https://doi.org/10.1007/s11042-021-11845-5

Keywords

  • Local hyperthermia
  • Single beam
  • Ultrasound
  • Monitoring system