Diving with terahertz waves into brain mysteries
THz range is between the infrared and microwave frequencies. While THz waves were first discovered at the end of the XIXth century, THz technology was rapidly developed only after 1975, when D. Auston proposed to use photoconductivity effect in semiconductors for the THz-pulse generation and detection. It was found that THz radiation interacts with matter in a unique manner (as compared to other spectral ranges) which pushed its applications in different branches of modern science and technology, including biophotonics, medical spectroscopy and imaging. Indeed, THz waves are strongly absorbed by water molecules, which limits its application for studying hard-to-access tissues and internal organs of human body. At the same time, tissue water simultaneously serves as an endogenous marker of different pathological processes in biological tissues, such as tumors, diabetes mellitus, devitalization and death of tissues.
The authors of this article overviewed applications of THz technology in diagnosis of brain pathologies. Development of novel modalities for neurodiagnosis remains a challenging problem of modern applied physics, biophysics, medical and engineering sciences. As an example, human brain gliomas are among the most common and deadly pathologies of the brain, constituting ≃ 26% of all primary brain tumors and ≃ 81% of malignant primary brain tumors. Gliomas are classified into the WHO Grades I to IV, where Grades I, II and III, IV stand for the low- and high-grade gliomas, respectively. Glioblastoma (glioma of the WHO Grade IV) is the most dangerous tumor of the brain, with the five-year relative survival rate of only ≃ 6.8%. Surgery remains the mainstay of the glial tumors' treatment, the main goal of which is a gross-total resection of a tumor with maximal preservation of surrounding intact tissues. Gliomas usually have unclear margins, that complicate their gross-total resection. In many cases, accurate delineation of glioma margins can be provided only by the ex vivo histopathological examination of the excised tissues, aided by the molecular sensing and genetics. Such examination can be performed either intraoperatively (thus, extending the terms of surgery) or postoperatively (aimed at making a definitive molecular pathological diagnosis). Despite histopathology remains a gold standard in tumor diagnosis, authors notice an increasing demand for novel methods of the rapid intraoperative detection of tumor margins. Most of existing instruments for neurodiagnosis such as MRI, computed tomography, positron emission tomography, and ultrasound suffer from low spatial resolution, while their integration into modern neurosurgical workflows is labor intensive and expensive. Fluorescent-based intraoperative techniques involving exogenous (injected) labels are inexpensive and provide high sensitivity for high-grade gliomas and meningiomas, but their sensitivity drops for the pediatric and low-grade tumors. Optical coherence tomography, Raman spectroscopy and imaging, confocal and polarization-sensitive microscopy, visible and near-IR spectroscopy, as well as photoacoustic imaging are vigorously explored, as tools for the intraoperative brain tissue imaging, but still remain far from clinical practice.
Prospects and challenging problem of THz technology in neurodiagnosis are considered, one of them is THz-wave scattering in tissues of the brain. THz wavelengths are comparable or larger than dimensions of the majority of brain tissue structural elements (Fig.1). That is why nowadays most researchers studying brain tissue in THz range, assuming it to be homogeneous at the THz-wavelength scale, and neglecting the scattering properties of the individual tissue elements. However, modern superresolution THz imaging modalities allow to visualize tissues with an essentially subwavelength resolution, which allows to probe sub-wavelength heterogeneities of intact and pathologically-altered tissues of the brain. On the one side, such heterogeneities can provide additional useful information for the discrimination between healthy tissues and pathology. On the other side, this pose a problem of the development of novel methods for describing the THz wave interactions with such a heterogeneous tissues involving the Mie scattering theory and the radiation transfer theory.
THz technology has a potential in the intraoperative diagnosis of brain tumors, thanks to the high sensitivity of THz waves to the content and state of tissue water. Along with the tissue water, other classes of biomolecules (such as lipids and proteins) play an important role in formation of the tissue dielectric response at THz frequencies. The assessment of all these biochemical compounds makes it possible to differentiate between normal and pathological tissues of the brain, as well as between different stages of a pathological process relying on the THz spectra and images. All these factors, along with the biochemical and structural neuronal and glial features, including microscopic variations of tissue properties, make the brain an exciting subject for study in the THz spectral range. The review paper by N.Chernomyrdin and co-authors describes methods and configurations of THz imaging and spectroscopy applied for studying intact (healthy) brain tissues and different pathologies, such as brain tumors (glioma, meningioma, etc.), degenerative diseases (Alzheimer's disease, demyelinating disease) and traumatic brain injuries.
More information:
Nikita V. Chernomyrdin et al, Terahertz technology in intraoperative neurodiagnostics: A review, Opto-Electronic Advances (2022). DOI: 10.29026/oea.2023.220071
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