Prospects of terahertz technology in diagnosis of human brain tumors – A review

Guzel R. Musina
Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia

Pavel V. Nikitin
Burdenko Neurosurgery Institute, Moscow, Russia

Nikita V. Chernomyrdin orcid (Login required)
Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia

Irina N. Dolganova
Institute of Solid State Physics of the Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia
Institute for Regenerative Medicine, Sechenov University, Moscow, Russia

Arsenii A. Gavdush
Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia

Gennadiy A. Komandin
Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia

Dmitry S. Ponomarev
V.G. Mokerov Institute of Ultra High Frequency Semiconductor Electronics of the Russian Academy of Sciences, Moscow, Russia

Alexander A. Potapov
Burdenko Neurosurgery Institute, Moscow, Russia

Igor V. Reshetov
Institute for Cluster Oncology, Sechenov University, Moscow, Russia

Valery V. Tuchin
Saratov State University, Russia
Institute of Precision Mechanics and Control of the Russian Academy of Sciences, Saratov, Russia

Kirill I. Zaytsev
Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia
Bauman Moscow State Technical University, Russia

Paper #3375 received 3 Jun 2020; accepted for publication 18 Jun 2020; published online 28 Jun 2020.

DOI: 10.18287/JBPE20.06.020201


Terahertz (THz) waves feature high sensitivity to the content and state of water in biological tissues. Therefore, during the past decades, THz technology has attracted significant attention in biophotonics, including diagnosis of malignant and benign neoplasms with different nosologies and localizations. The pathophysiological features of malignant tumors of the central nervous system determine appearance of several morphological phenomena, such as increased vascularity, edema, necrosis. These phenomena cause water content increase in the studied tissues and, thus, open new ways for the THz technology applications in the intraoperative neurodiagnosis, including delineation of tumor margins. This research area is rather novel and, despite the small amount of accumulated research material, is undoubtedly extremely promising for creation of new diagnostic approaches. In this review, available results in the considered exciting branch of THz technology are summarized, and potential projections of this topic into the future are constructed.


terahertz radiation; terahertz Biophotonics; terahertz spectroscopy; terahertz imaging; brain tumors; glioma; meningioma; neurodiagnostics; neurosurgery

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1. Q. Ostrom, H. Gittleman, G. Truitt, A. Boscia, C. Kruchko, and J. Barnholtz-Sloan, “CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015,” Neuro-Oncology 20(Suppl4), iv1–iv86 (2018).

2. E. F. Chang, A. Clark, R. L. Jensen, M. Bernstein, A. Guha, G. Carrabba, D. Mukhopadhyay, W. Kim, L. M. Liau, S. M. Chang, J. S. Smith, M. S. Berger, and M. W. McDermott, “Multiinstitutional validation of the University of California at San Francisco low-grade glioma prognostic scoring system,” Journal of Neurosurgery 111(2), 203–210 (2009).

3. M. Hefti, H. Mehdorn, I. Albert, and L. Dorner, “Fluorescence-guided surgery for malignant glioma: a review on aminolevulinic acid induced protoporphyrin ix photodynamic diagnostic in brain tumors,” Current Medical Imaging Reviews 6(4), 254–258 (2010).

4. F. N. Obeidat, H. A. Awad, A. T. Mansour, M. H. Hajeer, M. A. Al-Jalabi, and L. E. Abudalu, “Accuracy of Frozen-Section Diagnosis of Brain Tumors: An 11-Year Experience from a Tertiary Care Center,” Turkish Neurosurgery 29(2), 242-246 (2019).

5. W. Stummer, U. Pichlmeier, T. Meinel, O. D. Wiestler, F. Zanella, and H.-J. Reulen, “Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial,” The Lancet Oncology 7(5), 392–401 (2006).

6. M. Jermyn, J. Desroches, J. Mercier, K. St-Arnaud, M.-C. Guiot, F. Leblond, and K. Petrecca, “Raman spectroscopy detects distant invasive brain cancer cells centimeters beyond MRI capability in humans,” Biomedical Optics Express 7(12), 5129–5137 (2016).

7. B. Liang, W. Liu, Q. Zhan, M. Li, M. Zhuang, Q. Huo, and L. J. Yao, “Impacts of the murine skull on high‐frequency transcranial photoacoustic brain imaging,” Journal of Biophotonics 12(7), e201800466 (2019).

8. F. Vase, N. MacKinnon, D. Farkas, and B. Kateb, “Review of the potential of optical technologies for cancer diagnosis in neurosurgery: a step toward intraoperative neurophotonics,” Neurophotonics 4(1), 011010 (2016).

9. I. Dolganova, P. Aleksandrova, S.-I. Beshplav, N. Chernomyrdin, E. Dubyanskaya, S. Goryaynov, V. Kurlov, I. Reshetov, A. Potapov, V. Tuchin, and K. Zaytsev, “Wavelet-domain de-noising of OCT images of human brain malignant glioma,” Proceedings of SPIE 10717, 107171X (2018).

10. Y.-S. Lee, Principles of Terahertz Science and Technology, Springer, 340 (2009).

11. K. Zaytsev, N. Chernomyrdin, K. Kudrin, I. Reshetov, and S. Yurchenko, “Terahertz spectroscopy of pigmentary skin nevi in vivo,” Optics and Spectroscopy 119(3), 404–410 (2015).

12. Y. Sim, J. Park, K.-M. Ahn, C. Park, and J.-H. Son, “Terahertz imaging of excised oral cancer at frozen temperature,” Biomedical Optics Express 4(8), 1413–1421 (2013).

13. C. Reid, A. Fitzgerald, G. Reese, R. Goldin, P. Tekkis, P. O'Kelly, E. Pickwell-MacPherson, A. Gibson, and V. Wallace, “Terahertz pulsed imaging of freshly excised human colonic tissues,” Physics in Medicine & Biology 56(14), 4333–4353 (2011).

14. A. Fitzgerald, V. Wallace, S. Pinder, A. Purushotham, P. O'Kelly, and P. Ashworth, “Classiffication of terahertz-pulsed imaging data from excised breast tissue,” Journal of Biomedical Optics 17(1), 016005 (2012).

15. Y. Ji, C. Park, H. Kim, S.-H. Kim, G. Lee, S. Noh, T.-I. Jeon, J.-H. Son, Y.-M. Huh, S. Haam, S. Oh, S. Lee, and J.-S. Suh, “Feasibility of terahertz reflectometry for discrimination of human early gastric cancers,” Biomedical Optics Express 6(4), 1398–1406 (2015).

16. H. Chen, S.-H. Ma, W.-X. Yan, X.-M. Wu, and X.-Z. Wang, “The diagnosis of human liver cancer by using THz fiber-scanning near-field imaging,” Chinese Physics Letters 30(3), 030702 (2013).

17. A. Gavdush, N. Chernomyrdin, K. Malakhov, S.-I. Beshplav, I. Dolganova, A. Kosyrkova, P. Nikitin, G. Musina, G. Katyba, I. Reshetov, O. Cherkasova, G. Komandin, V. Karasik, A. Potapov, V. Tuchin, and K. Zaytsev, “Terahertz spectroscopy of gelatin-embedded human brain gliomas of different grades: a road toward intraoperative THz diagnosis,” Journal of Biomedical Optics 24(2), 027001 (2019).

18. O. A. Smolyanskaya, N. V. Chernomyrdin, A. A. Konovko, K. I. Zaytsev, I. A. Ozheredov, O. P. Cherkasova, M. M. Nazarov, J.-P. Guillet, S. A. Kozlov, Yu. V. Kistenev, J.-L. Coutaz, P. Mounaix, V. L. Vaks, J.-H. Son, H. Cheon, V. P. Wallace, Yu. Feldman, I. Popov, and V. V. Tuchin, “Terahertz biophotonics as a tool for studies of dielectric and spectral properties of biological tissues and liquids,” Progress in Quantum Electronics 62, 1–77 (2018).

19. K. Cole, R. Cole, “Dispersion and absorption in dielectrics I. Alternating current characteristics,” The Journal of Chemical Physics 9(4), 341–351 (1941).

20. K. Cole, R. Cole, “Dispersion and absorption in dielectrics II. Direct current characteristics,” The Journal of Chemical Physics 10(2), 98–105 (1942).

21. D. Davidson, “Dielectric relaxation in liquids: I. The representation of relaxation behavior,” Canadian Journal of Chemistry 39(3), 571–594 (1961).

22. S. Havriliak, S. Negami, “A complex plane analysis of dispersions in some polymer systems,” Journal of Polymer Science Part C: Polymer Symposia 14(1), 99–117 (1966).

23. E. Pickwell, B. E. Cole, A. J. Fitzgerald, V. P. Wallace, and M. Pepper, “Simulation of terahertz pulse propagation in biological systems,” Applied Physics Letters 84(12), 2190–2192 (2004).

24. E. Pickwell, A. J. Fitzgerald, B. E. Cole, P. F. Taday, R. J. Pye, T. Ha, M. Pepper, and V. P. Wallace, “Simulating the response of terahertz radiation to basal cell carcinoma using ex vivo spectroscopy measurements,” Journal of Biomedical Optics 10(6), 064021 (2005).

25. G. C. Walker, E. Berry, S. W. Smye, N. N. Zinov'ev, A. J. Fitzgerald, R. E. Miles, M. Chamberlain, and M. A. Smith, “Modelling the propagation of terahertz radiation through a tissue simulating phantom,” Physics in Medicine & Biology 49(10), 1853–1864 (2004).

26. A. J. Fitzgerald, E. Pickwell-MacPherson, and V. P. Wallace, “Use of finite difference time domain simulations and Debye theory for modelling the terahertz reflection response of normal and tumour breast tissue,” PLOS ONE 9, e99291 (2014).

27. B. C. Q. Truong, H. D. Tuan, V. P. Wallace, A. J. Fitzgerald, and H. T. Nguyen, “The potential of the double Debye parameters to discriminate between basal cell carcinoma and normal skin,” IEEE Transactions on Terahertz Science & Technology 5(6), 990–998 (2015).

28. E. P. Parrott, S. M. Y. Sy, T. Blu, V. P. Wallace, and E. Pickwell-MacPherson, “Terahertz pulsed imaging in vivo: measurements and processing methods,” Journal of Biomedical Optics 16(10), 106010 (2011).

29. S. J. Oh, S.-H. Kim, Y. B. Ji, K. Jeong, Y. Park, J. Yang, D. W. Park, S. K. Noh, S.-G. Kang, Y.-M. Huh, J.-H. Son, and J.-S. Suh, “Study of freshly excised brain tissues using terahertz imaging,” Biomedical Optics Express 5(8), 2837–2842 (2014).

30. C. S. Joseph, A. N. Yaroslavsky, M. Al-Arashi, T. M. Goyette, J. C. Dickinson, A. J. Gatesman, B. W. Soper, C. M. Forgione, T. M. Horgan, E. J. Ehasz, R. H. Giles, and W. E. Nixon, “Terahertz spectroscopy of intrinsic biomarkers for non-melanoma skin cancer,” Proceedings of SPIE 7215, 72150I (2009).

31. M. Ney, I. Abdulhalim, “Comprehensive Monte-Carlo simulator for optimization of imaging parameters for high sensitivity detection of skin cancer at the THz,” Proceedings of SPIE 9721, 97210W (2016).

32. N. V. Chernomyrdin, A. S. Kucheryavenko, E. N. Rimskaya, I. N. Dolganova, V. A. Zhelnov, P. A. Karalkin, A. A. Gryadunova, I. V. Reshetov, D. V. Lavrukhin, D. S. Ponomarev, V. E. Karasik, and K. I. Zaytsev, “Terahertz microscope based on solid immersion effect for imaging of biological tissues,” Optics & Spectroscopy 126(5), 560–567 (2019).

33. A. Ishimaru, Electromagnetic wave propagation, radiation, and scattering: From fundamentals to applications, Wiley–IEEE Press, Piscataway, NJ, USA (2017).

34. P. Doradla, K. Alavi, C. Joseph, and R. Giles, “Detection of colon cancer by continuous-wave terahertz polarization imaging technique,” Journal of Biomedical Optics 18(9), 090504 (2013).

35. V. Tuchin. Tissue optics: Light scattering methods and instruments for medical diagnostics, Third edition, SPIE Press, Bellingham, Washington, USA (2015).

36. K. I. Zaytsev, I. N. Dolganova, N. V. Chernomyrdin, G. M. Katyba, A. A. Gavdush, O. P. Cherkasova, G. A. Komandin, M. A. Shchedrina, A. N. Khodan, D. S. Ponomarev, I. V. Reshetov, V. E. Karasik, M. Skorobogatiy, V. N. Kurlov, and V. V. Tuchin, “The progress and perspectives of terahertz technology for diagnosis of neoplasms: A review,” Journal of Optics 22(1), 013001 (2020).

37. G. M. Png, R. Flook, B.W.-H. Ng, and D. Abbott, “Terahertz spectroscopy of snap-frozen human brain tissue: an initial study,” Electronics Letters 45(7), 343–345 (2009).

38. L. Shi, P. Shumyatsky, A. Rodríguez-Contreras, and R. Alfano, “Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer’s disease,” Journal of Biomedical Optics 21(1), 015014 (2016).

39. K. Meng, T.-N. Chen, T. Chen, L.-G. Zhu, Q. Liu, Z. Li, F. Li, S.-C. Zhong, Z.-R. Li, H. Feng, and J.-H. Zhao, “Terahertz pulsed spectroscopy of paraffin-embedded brain glioma,” Journal of Biomedical Optics 19(7), 077001 (2014).

40. S. Doblas, T. He, D. Saunders, J. Pearson, J. Hoyle, N. Smith, M. Lerner, and R. A. Towner, “Glioma morphology and tumor‐induced vascular alterations revealed in seven rodent glioma models by in vivo magnetic resonance imaging and angiography,” Journal of Magnetic Resonance Imaging 32(2), 267–275 (2010).

41. Y. Zou, J. Li, Y. Cui, P. Tang, L. Du, T. Chen, K. Meng, Q. Liu, H. Feng, J. Zhao, M. Chen, and L.-G. Zhu, “Terahertz spectroscopic diagnosis of myelin deficit brain in mice and rhesus monkey with chemometric techniques,” Scientific Reports 7, 5176 (2017).

42. S. Yamaguchi, Y. Fukushi, O. Kubota, T. Itsuji, T. Ouchi, and S. Yamamoto, “Brain tumor imaging of rat fresh tissue using terahertz spectroscopy,” Scientific Reports 6, 30124 (2016).

43. Y. B. Ji, S. J. Oh, S.-G. Kang, J. Heo, S.-H. Kim, Y. Choi, S. Song, H. Y. Son, S. H. Kim, J. H. Lee, S. J. Haam, Y. M. Huh, J. H. Chang, C. Joo, and J.-S. Suh, “Terahertz reflectometry imaging for low and high grade gliomas,” Scientific Reports 6, 36040 (2016).

44. N. V. Chernomyrdin, A. A. Gavdush, S.-I. T. Beshplav, K. M. Malakhov, A. S. Kucheryavenko, G. M. Katyba, I. N. Dolganova, S. A. Goryaynov, V. E. Karasik, I. E. Spektor, V. N. Kurlov, S. O. Yurchenko, G. A. Komandin, A. A. Potapov, V. V. Tuchin, and K. I. Zaytsev, “In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study,” Proceedings of SPIE 10716, 107160S (2018).

45. S. Fan, B. Ung, E. P. J. Parrott, and E. Pickwell-MacPherson, “Gelatin embedding: a novel way to preserve biological samples for terahertz imaging and spectroscopy,” Physics in Medicine & Biology 60(7), 2703 (2015).

46. B. M. Fischer, M. Walther, and P. U. Jepsen, “Far-infrared vibrational modes of DNA components studied by terahertz time-domain spectroscopy,” Physics in Medicine & Biology 47(21), 3807–3814 (2002).

47. E. Pickwell-MacPherson, V. P. Wallace, “Terahertz pulsed imaging – A potential medical imaging modality,” Photodiagnosis and Photodynamic Therapy 6(2), 128–134 (2009).

48. M. Tang, M. Zhang, S. Yan, L. Xia, Z. Yang, C. Du, H. L. Cui, and D. Wei, “Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy and microstructures,” PLOS ONE 13(1), e0191515 (2018).

49. P. Wesseling, D. Capper, “WHO 2016 Classification of gliomas,” Neuropathology and Applied Neurobiology 44(2), 139–150 (2018).

50. R. Chen, M. Smith-Cohn, A. L. Cohen, and H. Colman, “Glioma Subclassifications and Their Clinical Significance,” Neurotherapeutics 14(2), 284–297 (2017).

51. X. Chen, C. Pan, P. Zhang, C. Xu, Y. Sun, H. Yu, Y. Wu, Y. Geng, P. Zuo, Z. Wu, J. Zhang, and L. Zhang, “BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas,” Journal of Clinical Neuroscience 46, 50–57 (2017).

52. H. Zhao, Y. Wang, L. Chen, J. Shi, K. Ma, L. Tang, D. Xu, J. Yao, H. Feng, and T. Chen, “High-sensitivity terahertz imaging of traumatic brain injury in a rat model,” Journal of Biomedical Optics 23(3), 036015 (2018).

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