Fig. 1. Structural features of brain tissues (neurofibrils, neurons, glial cells, etc.) as well as meninges and blood vessels at the THz-wavelength scale.The horizontal axis depicts the ratio between the typical size of the structural elements d and the typical free-space wavelength λ₀= 300 μm (ν₀≈ 1.0 THz), while the vertical solid red line shows the λ/2-Abbe diffraction limit. Courtesy of G.R. Musina.

Fig. 2. Scheme of the THz pulsed spectrometer. (a) Transmission-mode measurements. (b) Reflection-mode measurements. (c) ATR configuration. A pair of photoconductive antennas (that rely on photoconductivity/photoswitching effect), nonlinear optical crystals (that rely on optical rectification and electrooptical effects, respectively), or other principles can be used as an emitter and a detector of THz pulses. Here, BS is a beam splitter; OAPM is an off-axis parabolic mirror. Courtesy of G.R. Musina.

Fig. 3. Scheme of representative THz imaging systems operating in transmission mode. Courtesy of G.R. Musina.

Fig. 4. THz measurements data of intact brain ex vivo. (a–d) 3.43 THz quantum cascade laser-based images (left column) and visible morphological pictures (right column) of the frontal sections of the dehydrated rat brain ex vivo. (e) Water content in different freshy-excised (hydrated) tissues from rats ex vivo estimated based on the TPS data and tissue weighting (mass). Figure reproduced with permission from: (a) ref.⁸¹, Optical Society of America; (b) ref.⁵⁸, under the OSA Open Access Publishing Agreement.

Fig. 5. THz measurements data of the Alzheimer's and demyelinating diseases. (a–c) THz absorption coefficient α of the intact and Alzheimer's disease-altered tissues of the human brain ex vivo obtained at cryogenic temperatures using TPS, where CG, IFG, and SFG stand for the cingulate gyrus, inferior frontal gyrus, and superior frontal gyrus of the brain, respectively. (d–i) THz refractive index distributions n(r) measured by TPI (left) and Thioflavin S-stained fluorescence images (right) of the wild-type and APP/PS1 Alzheimer’s disease models depending on age. (j, k) Averaged THz absorption coefficient α of a liquid buffer with β-amyloid aggregates-containing nanodroplets, as well as the sketch of a single nanodroplet with a β-amyloid aggregate. (l) THz refractive index n and absorption coefficient α obtained from the myelin deficit (Rheb1 KO) and normal mice brains ex vivo. Figure reproduced with permission from: (a–c) ref.⁵⁹, IET; (d–i) ref.¹⁴⁰, (j, k) ref.⁶² Elsevier; (l) ref.⁶⁸, under a Creative Commons Attribution 4.0 International License.

Fig. 6. THz imaging of brain glioma models from laboratory animals ex vivo. (a–i) Visible, THz, and MRI images of orthotopic glioma model from rats, where the THz image dimensions and resolution are 4 cm×3 cm and 250 μm, respectively. (j–o) Visual image, H&E-stained histology and temperature-dependent 2.52 THz CW ATR images of orthotopic glioma model from miceex vivo, where the sample temperature varies in the range from −20 to 35 °C. In (k–o), the blue boarder marks the boundary between background and a sample; while in (k), boxes 1 and 2 point areas of healthy and tumorous tissues. Figure reproduced with permission from: (a–i) ref.³⁵, Optical Society of America; (j–o) ref.⁸⁹, under the Optica Open Access Publishing Agreement.

Fig. 7. Spectra of the THz refractive index n and absorption coefficient α (by field), as well as H&E-stained histology of intact tissues, edematous tissues, and gelatin-embedded human brain gliomasex vivo of the different WHO Grades. (a–c) Grade I. (d–f) Grade II. (g–i) Grade III. (j–l) Grade IV. THz optical properties of gliomas are compared with equal data for intact and edematous tissues, where the error bars represent a ±2.0σ confidential interval of measurements (σ is a standard deviation). Figure reproduced with permission from ref.⁶⁴, under a Creative Commons Attribution 4.0 Unported License.

Fig. 8. Water content in healthy and pathological tissues of the brain measured using different experimental techniques. (a) Intact tissues, edema, and WHO Grade I–IV gliomas (GI–GIV) of the human brain ex vivo measured by TPS in ref.⁶⁵. (b) Intact tissues and C6 glioma model from rat brain ex vivo measured by TPS in ref.⁶⁷. (c) Healthy human brain tissues and tumoral edema in vivo measured by MRI in refs.^162–164, where WM and GM stand for white matter and gray matter, respectively. (d) Healthy rat brain tissues ex vivo measured by pycnometry in ref.¹⁶⁵. Here, error bars represent fluctuations of water content within the considered set of tissue specimens. Figure reproduced with permission from ref.⁶⁵, under the OSA Open Access Publishing Agreement.

Fig. 9. THz optical properties of IDH1 wild-type sample and IDH1 mutant positive sample. (a) Refractive index n. (b) Absorption coefficient α. Figure reproduced with permission from ref.⁶⁹, under the Optica Open Access Publishing Agreement.

Fig. 10. The data of TPS measurements and quantitative superresolution CW THz solid immersion microscopy (at ν = 0.6 THz or λ ≈ 500 µm) of the freshly-excised intact brain and glioma model 101.8 from rats ex vivo. (a–c) Effective THz refractive index n and absorption coefficient α (by field) of intact tissues and a tumor, measured by TPS and verified by H&E-stained histology. (d–i) Visible photo, THz image I (r), refractive index distribution n (r), absorption coefficient (by power) distribution α (r), water content distribution C (r), and H&E-stained histology, respectively, for the intact tissues. Here,r is a radius vector at the imaging plane; markers I, II point the gray matter (cortex) and white matter, respectively. (j–o) Equal data set for a tumor, where markers III, IV indicate the tumor cells accumulation and the necroses zone. Figure reproduced with permission from: (a–c) ref.¹¹⁶, (d–o) ref.⁴¹, under the OSA Open Access Publishing Agreement.

Fig. 11. Results of the THz measurements ex vivo of the freshly-excised intact rat brain and those with TBI models of the different degrees. (a–l) Visible, THz, and MRI images of freshly-excised intact rat brain and TBI models of the mild, moderate, and severe degrees. (m) Spectra of the absorption coefficient α of the paraffin-embedded brain samples from intact rat brain and TBIs. Figure reproduced with permission from ref.⁸³, SPIE.