Comparative Oncology Chemosensitivity Assay for Personalized Medicine Using Low-coherence Digital Holography of Dynamic Light Scattering from Cancer Biopsies

Overview

Journal Sci Rep

Specialty Science

Date 2024 Feb 9

PMID 38332203

Authors

Zhen Hua

Zhe Li

Dawith Lim

Ali Ajrouch

Ahmad Karkash

Shadia Jalal

Michael Childress

John Turek

David Nolte

Affiliations

Soon will be listed here.

Abstract

Nearly half of cancer patients who receive standard-of-care treatments fail to respond to their first-line chemotherapy, demonstrating the pressing need for improved methods to select personalized cancer therapies. Low-coherence digital holography has the potential to fill this need by performing dynamic contrast OCT on living cancer biopsies treated ex vivo with anti-cancer therapeutics. Fluctuation spectroscopy of dynamic light scattering under conditions of holographic phase stability captures ultra-low Doppler frequency shifts down to 10 mHz caused by light scattering from intracellular motions. In the comparative preclinical/clinical trials presented here, a two-species (human and canine) and two-cancer (esophageal carcinoma and B-cell lymphoma) analysis of spectral phenotypes identifies a set of drug response characteristics that span species and cancer type. Spatial heterogeneity across a centimeter-scale patient biopsy sample is assessed by measuring multiple millimeter-scale sub-samples. Improved predictive performance is achieved for chemoresistance profiling by identifying red-shifted sub-samples that may indicate impaired metabolism and removing them from the prediction analysis. These results show potential for using biodynamic imaging for personalized selection of cancer therapy.

Citing Articles

Evaluating the feasibility and predictive accuracy of biodynamic imaging to platinum-based chemotherapy response in esophageal adenocarcinoma.

Ajrouch A, Krempley B, Karkash A, DeWitt J, Al-Haddad M, Lim D Front Oncol. 2024; 14:1429343.

PMID: 39403334 PMC: 11471442. DOI: 10.3389/fonc.2024.1429343.

References

Jeong K, Turek J, Nolte D . Volumetric motility-contrast imaging of tissue response to cytoskeletal anti-cancer drugs. Opt Express. 2009; 15(21):14057-64. DOI: 10.1364/oe.15.014057. View

Laviana A, Schiftan E, Mashni J, Large M, Kaimakliotis H, Nolte D . Biodynamic prediction of neoadjuvant chemotherapy response: Results from a prospective multicenter study of predictive accuracy among muscle-invasive bladder cancer patients. Urol Oncol. 2022; 41(6):295.e9-295.e17. DOI: 10.1016/j.urolonc.2022.11.017. View

El-Sadek I, Miyazawa A, Shen L, Makita S, Mukherjee P, Lichtenegger A . Three-dimensional dynamics optical coherence tomography for tumor spheroid evaluation. Biomed Opt Express. 2021; 12(11):6844-6863. PMC: 8606131. DOI: 10.1364/BOE.440444. View

Nolte D, An R, Turek J, Jeong K . Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture. Biomed Opt Express. 2012; 3(11):2825-41. PMC: 3493238. DOI: 10.1364/BOE.3.002825. View

Walsh A, Cook R, Rexer B, Arteaga C, Skala M . Optical imaging of metabolism in HER2 overexpressing breast cancer cells. Biomed Opt Express. 2012; 3(1):75-85. PMC: 3255344. DOI: 10.1364/BOE.3.000075. View

Leroux C, Bertillot F, Thouvenin O, Boccara A . Intracellular dynamics measurements with full field optical coherence tomography suggest hindering effect of actomyosin contractility on organelle transport. Biomed Opt Express. 2016; 7(11):4501-4513. PMC: 5119591. DOI: 10.1364/BOE.7.004501. View

Xu H, Nioka S, Glickson J, Chance B, Li L . Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt. 2010; 15(3):036010. PMC: 3188620. DOI: 10.1117/1.3431714. View

Seol H, Suh Y, Ryu Y, Kim H, Chun S, Na D . A patient-derived xenograft mouse model generated from primary cultured cells recapitulates patient tumors phenotypically and genetically. J Cancer Res Clin Oncol. 2013; 139(9):1471-80. DOI: 10.1007/s00432-013-1449-6. View

Cirkel G, Gadellaa-Van Hooijdonk C, Koudijs M, Willems S, Voest E . Tumor heterogeneity and personalized cancer medicine: are we being outnumbered?. Future Oncol. 2014; 10(3):417-28. DOI: 10.2217/fon.13.214. View

10.

Cuche E, Bevilacqua F, Depeursinge C . Digital holography for quantitative phase-contrast imaging. Opt Lett. 2007; 24(5):291-3. DOI: 10.1364/ol.24.000291. View

11.

Mukherjee P, Fukuda S, Lukmanto D, Yamashita T, Okada K, Makita S . Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography. Biomed Opt Express. 2022; 13(7):4071-4086. PMC: 9352293. DOI: 10.1364/BOE.461433. View

12.

Wang Z, Chen W, Zuo L, Xu M, Wu Y, Huang J . The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells. Cancer Commun (Lond). 2022; 42(3):245-265. PMC: 8923131. DOI: 10.1002/cac2.12274. View

13.

Merrill D, An R, Sun H, Yakubov B, Matei D, Turek J . Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts. Sci Rep. 2016; 6:18821. PMC: 4702146. DOI: 10.1038/srep18821. View

14.

Leung H, Wang M, Osman H, Abouei E, MacAulay C, Follen M . Imaging intracellular motion with dynamic micro-optical coherence tomography. Biomed Opt Express. 2020; 11(5):2768-2778. PMC: 7249806. DOI: 10.1364/BOE.390782. View

15.

Li Z, Sun H, Turek J, Jalal S, Childress M, Nolte D . Doppler fluctuation spectroscopy of intracellular dynamics in living tissue. J Opt Soc Am A Opt Image Sci Vis. 2019; 36(4):665-677. PMC: 6791373. DOI: 10.1364/JOSAA.36.000665. View

16.

Munter M, Vom Endt M, Pieper M, Casper M, Ahrens M, Kohlfaerber T . Dynamic contrast in scanning microscopic OCT. Opt Lett. 2020; 45(17):4766-4769. DOI: 10.1364/OL.396134. View

17.

El-Sadek I, Miyazawa A, Shen L, Makita S, Fukuda S, Yamashita T . Optical coherence tomography-based tissue dynamics imaging for longitudinal and drug response evaluation of tumor spheroids. Biomed Opt Express. 2020; 11(11):6231-6248. PMC: 7687946. DOI: 10.1364/BOE.404336. View

18.

Paoloni M, Khanna C . Comparative oncology today. Vet Clin North Am Small Anim Pract. 2007; 37(6):1023-32. PMC: 2174910. DOI: 10.1016/j.cvsm.2007.08.003. View

19.

Gerlinger M, Rowan A, Horswell S, Math M, Larkin J, Endesfelder D . Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366(10):883-892. PMC: 4878653. DOI: 10.1056/NEJMoa1113205. View

20.

Yamaguchi I, Zhang T . Phase-shifting digital holography. Opt Lett. 1997; 22(16):1268-70. DOI: 10.1364/ol.22.001268. View