CN-122016708-A - Detection method and system for early Alzheimer disease tissue based on terahertz time-domain spectroscopy

Abstract

The invention discloses a brain tissue detection method and system based on terahertz time-domain spectroscopy, and belongs to the technical fields of biomedical engineering and terahertz spectroscopy detection. The method takes in-vitro brain tissue as a research object, prepares brain tissue slices with preset thickness after fixation and dehydration treatment, acquires time domain signals by using a terahertz time domain spectroscopy system, and extracts refractive index and absorption coefficient by using a fast Fourier transform and parameter inversion model. The identification of the Alzheimer's disease related pathological change is realized by quantitatively analyzing the optical characteristic difference of normal and diseased brain tissues in a specific frequency band. Experiments show that in the effective spectrum range, the refractive index and the absorption coefficient of diseased brain tissues are higher than those of normal brain tissues. The invention has the characteristics of simplicity, no mark, non-ionizing radiation and the like, is highly sensitive to brain tissue microstructure and biochemical composition, and provides a new physical detection means for early auxiliary analysis of Alzheimer's disease.

Inventors

• CUI HONGLIANG
• ZHANG ZIYI
• WEI DONGSHAN
• CHANG TIANYING
• LU XINGXING
• DAI GUANGBIN
• YU MIAO

Assignees

• 中国科学院深圳先进技术研究院

Dates

Publication Date

20260512

Application Date

20260130

Claims (10)

1. 1. The brain tissue detection method based on the terahertz time-domain spectroscopy is characterized by comprising the following steps of: S1, preparing a sample, namely obtaining an isolated brain tissue, and preparing a brain tissue slice with a preset thickness after chemical fixation and dehydration treatment; S2, acquiring a reference signal, namely acquiring a reference terahertz time-domain signal without the brain tissue slice; S3, sample signal acquisition, namely acquiring terahertz time-domain signals of the brain tissue slice samples under the same conditions; S4, frequency domain transformation and complex transmission coefficient calculation, wherein the frequency domain transformation is carried out on the reference signal and the sample signal, and the complex transmission coefficient is obtained through calculation; s5, inverting optical parameters based on an electromagnetic wave propagation model, and inverting the optical parameters of the brain tissue slice from the complex transmission coefficient, wherein the optical parameters comprise a refractive index spectrum and an absorption coefficient spectrum; and S6, judging pathological features, namely comparing the refractive index spectrum, the absorption coefficient spectrum and corresponding normal threshold references in a preset characteristic frequency band, and judging whether the brain tissue slice has the pathological features related to Alzheimer' S disease.
2. 2. The method according to claim 1, wherein in the step S5, the optical parameter is obtained by using an amplitude ratio ρ (ω) and a phase difference corresponding to the complex transmission coefficient Mapping is obtained.
3. 3. The method according to claim 2, wherein in the step S5, a complex refractive index is introduced Based on Fresnel transmission model, obtaining refractive index from inversion of complex transmission coefficient And extinction coefficient And further calculate the absorption coefficient 。
4. 4. The method according to claim 3, wherein the refractive index spectrum and the absorption coefficient spectrum of the brain tissue slice at different frequencies are calculated in the step S5 by using the following relation: Wherein, the In order to achieve the vacuum light velocity, In order to be of an angular frequency, Is the sample thickness.
5. 5. The method according to claim 1, wherein in the step S1, the dehydration treatment is to dehydrate the brain tissue after chemical fixation by immersing the brain tissue in an aqueous solution containing a permeable saccharide or sugar alcohol, wherein the permeable saccharide or sugar alcohol includes one or more of sucrose, mannitol, and sorbitol.
6. 6. The method according to any one of claims 1 to 5, wherein in step S1, the predetermined thickness is 550 μm to 600 μm.
7. 7. The method according to claim 1 to 5, wherein, In the steps S2 and S3, the collection of the reference signal and the sample signal is performed in a sealed environment with a relative humidity not higher than 10%.
8. 8. The method according to any one of claims 1 to 5, wherein in the step S6, the characteristic frequency band is 0.2THz to 0.7THz.
9. 9. The method according to claim 8, wherein, The specific criteria for judging that the brain tissue slice has the relevant pathological characteristics of the Alzheimer disease are as follows: in the range of 0.4THz-0.7THz, the refractive index spectrum is entirely above the normal threshold reference; And in the range of 0.2THz-0.6THz, the absorption coefficient spectrum is significantly higher than the normal threshold reference.
10. 10. A terahertz time-domain spectroscopy-based detection system, comprising: the terahertz generation and detection unit is used for generating terahertz pulses and detecting sample signals; The sealed measurement cavity is used for accommodating the sample and maintaining a preset humidity environment; a host computer for performing the terahertz time-domain spectroscopy-based brain tissue detection method as set forth in any one of claims 1 to 9.

Description

Detection method and system for early Alzheimer disease tissue based on terahertz time-domain spectroscopy Technical Field The invention relates to the technical field of biomedical photonics and terahertz spectrum detection, in particular to a method and a system for measuring and analyzing terahertz optical parameters of an isolated brain tissue slice based on a terahertz time-domain spectroscopy technology so as to realize pathological feature detection and auxiliary analysis of Alzheimer's disease. Background Alzheimer's Disease (AD) is a hidden and progressive neurodegenerative Disease, the earliest pathological feature of which is the abnormal aggregation and deposition of beta-amyloid (Abeta) in the brain, further accompanied by hyperphosphorylation of tau protein and formation of neurofibrillary tangles (NFTs), ultimately leading to synaptic dysfunction, neuronal loss and brain atrophy. Since early pathological changes in AD are subtle and occult, and the occurrence of clinical symptoms is often irreversible, the development of an early, sensitive and label-free diagnostic method is critical for the intervention and treatment of AD. Currently, the clinical diagnostic aids for AD mainly include cerebrospinal fluid biomarker detection, positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI). The cerebrospinal fluid detection has higher biochemical specificity, but the application of large-scale screening is limited by the originality, the PET imaging can visually display amyloid deposition, but has high cost and needs a radioactive tracer, and the conventional MRI technology has relatively limited sensitivity in detecting early microscopic pathological structural changes. Therefore, the search for novel detection technology based on the change of physical characteristics of biological tissues is becoming a research hotspot in the current biomedical engineering field. Terahertz (Terahertz, THz) waves refer to electromagnetic waves with frequencies between 0.1THz and 10THz, and have low photon energy (1 thz=4.1 meV), do not generate ionization damage to biological tissues, and have good safety. Because the skeleton vibration and rotation energy levels of biological macromolecules such as proteins, DNA and the like are positioned in the terahertz wave band, the terahertz spectrum is highly sensitive to the conformational change of the biological molecules and the hydration state in tissues. In the study of nervous system diseases, the biochemical components and microstructures of brain tissues of AD patients are obviously changed, such as Abeta aggregation, tau protein abnormal modification, lipid metabolism disorder and the like, and the changes directly influence the absorption and scattering properties of the brain tissues on THz waves. 2009. In the years Png et al, by using the terahertz time-domain spectroscopy system (THz-TDS), AD tissues rich in protein plaques in the human brain were distinguished from healthy tissues, and a significant difference between the terahertz absorption coefficient of the lesion area and normal tissues was found, which was attributed to the collective response of various abnormal protein accumulation. Similarly, shi et al compared the terahertz spectra of brain tissue of AD transgenic mice with wild-type mice, and observed that AD tissue exhibited absorption peaks associated with tryptophan torsional vibration modes at specific frequencies (e.g., 1.44THz, 1.8THz, 2.11 THz). However, the current AD research based on THz-TDS technology still has the following technical problems that 1, research objects are limited, and the research objects are concentrated on in-vitro dry frozen brain tissues, cell models or simulated peptide fragments, so that systematic spectroscopic analysis on fresh brain slices is deficient. 2. The correlation is not deep, and the change rule of the optical parameters of brain tissues in the pathological process of AD and the inherent correlation between the optical parameters and pathological characteristics are not deep enough. 3. The diagnostic criteria are absent, specific spectral markers and quantitative discrimination criteria which can be used for AD detection are not established yet, and stable quantitative discrimination of normal brain tissues and Alzheimer's brain tissues in a specific terahertz frequency band is difficult to realize. Therefore, it is necessary to provide a detection method and a detection system to realize quantitative distinction between normal brain tissue and Alzheimer's disease in a specific terahertz frequency band, and provide a new physical index for establishing a noninvasive, rapid and early AD early-stage auxiliary diagnosis method. Disclosure of Invention The invention aims to provide an in-vitro brain tissue detection method and system based on a terahertz time-domain spectroscopy technology, and aims to solve the problems that systematic spectroscopic analysis for brain tissue slices is defi