Visible Resonance Raman Spectroscopy in Human Brain Tissues

J. Innov. Opt. Health Sci.

Liu

et al. 2019

Self Cite

The purpose of this study is to examine optical spatial frequency spectroscopy analysis (SFSA) combined with visible resonance Raman (VRR) spectroscopic method, for the first time, to discriminate human brain metastases of lung cancers adenocarcinoma (ADC) and squamous cell carcinoma (SCC) from normal tissues. A total of 31 label-free micrographic images of three types of brain tissues were obtained using a confocal micro-Raman spectroscopic system. VRR spectra of the corresponding samples were synchronously collected using excitation wavelength of 532[Formula: see text]nm from the same sites of the tissues. Using SFSA method, the difference in the randomness of spatial frequency structures in the micrograph images was analyzed using Gaussian function fitting. The standard deviations, [Formula: see text] calculated from the spatial frequencies of the micrograph images were then analyzed using support vector machine (SVM) classifier. The key VRR biomolecular fingerprints of carotenoids, tryptophan, amide II, lipids and proteins (methylene/methyl groups) were also analyzed using SVM classifier. All three types of brain tissues were identified with high accuracy in the two approaches with high correlation. The results show that SFSA–VRR can potentially be a dual-modal method to provide new criteria for identifying the three types of human brain tissues, which are on-site, real-time and label-free and may improve the accuracy of brain biopsy.

Section: Resultsmentioning

confidence: 99%

Combined spatial frequency spectroscopy analysis with visible resonance Raman for optical biopsy of human brain metastases of lung cancers

J. Innov. Opt. Health Sci.

Liu

et al. 2019

Self Cite

“…More details about the study can be found in Ref. 99. The results may be used to develop a new fiber optic navigator for in vivo diagnosis of brain cancers and cancer margins that combines all VRR molecular spectral biomarkers.…”

mentioning

confidence: 99%

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy

Liu

et al. 2019

J. Biomed. Opt.

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Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins.

“…1222-1293cm -1 range contains amide III formation of β-sheet secondary structure and αhelix secondary structure as well as the conformation of amide I secondary structure. These prove the unique advantages of VRR spectroscopy using 532nm wavelength excitation for biological materials with the resonance enhancement of vibrational modes of chemical bonds from cells and tissues [18,[21][22][23][24][25] if compared with conventional NIR Raman methods [26]. The Raman vibration bands around 441-483cm -1 and 1430-1457cm -1 observed in Aβ protein corresponds to δ(CC) bending vibration of aromatic residues and δ(CH2), bending vibration of aromatic residues, respectively [11,13,27].…”

Section: Resultsmentioning

confidence: 77%

“…VRR spectral bands of Aβ-(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) protein in the region of 400 -4000cm -1 The animal tissue samples were prepared following the guideline of animal care and required procedures approved by the local Institutional Animal Care and Use Committee (IACUC) of the City College of New York (CCNY). The VRR spectra of AD and control specimens and Aβ and Tau proteins were recorded and analyzed using two Raman systems including WITec alpha 300R Confocal Raman Microscope and VRR-LRR TM Raman analyzer systems[18][19] ex vivo.…”

mentioning

confidence: 99%

Amyloid beta and tau protein metabolic changes detected by visible resonance Raman scattering microscopy in Alzheimer's disease mouse model

Shi¹,

Optical Biopsy XXI: Toward Real-Time Spectroscopic Imaging and Diagnosis

Wu³

et al. 2023

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Alzheimer's disease (AD) pathogenesis is widely believed to be associated with the production and deposition of the βamyloid peptide (Aβ) and neurofibrillary tangles (NFTs) which are composed of a highly-phosphorylated form of the microtubule-associated protein tau. Based on the above hypothesis, there are currently no sufficiently effective technologies and drugs for early detection and treatment of AD. Even the most promising new drug Lecanemab that is based on an anti-amyloid monoclonal antibody therapy, has only partially slowed down the cognitive performance of patients with mild impairment caused by Alzheimer's disease. The main symptoms of AD brain tissue lesions in patients are the deposition of β-amyloid peptide and the hyperphosphorylation of tau protein, which aggregates the microtubule structure of neurons. Therefore, Aβ deposition and hyperphosphorylation of Tau are important pathological biomarkers of Alzheimer's disease. Therefore, the main targets of research for AD prevention, detection and pharmaceuticals are still Aβ and Tau protein. The aim of this study was to detect the changes of Aβ and Tau proteins in the mouse brain tissue with AD and control samples using Visible Resonance Raman (VRR) spectroscopic technology. An attempt was made to develop criteria for the detection of early AD lesions by optical spectroscopy technology. The VRR spectra of AD, the control mouse brain tissues, and Aβ and Tau proteins were recorded and analyzed. The AD and the control mouse brain tissue samples were selected from the thalamus, frontal lobe cortex and hippocampus brain areas. VRR technology with high spatial resolution and the resonance-enhanced features of certain protein molecules is first used in this study to detect and characterize the changes of Aβ and Tau proteins in AD mouse brain model. The optical spectroscopy biomarkers of AD and Control brain tissue were identified in fingerprint and the high-wavenumber regions. The Raman spectra of the secondary structure of protein in amide (I-II-III-B-A) are detected and analyzed. The results indicate that the intensity of Amide I decreased at the 1666 cm -1 corresponding to the β-sheet structure, and the intensity of the amide III bands (1220-1320 cm-1) increased in all AD brain tissues. It was also observed that the Raman peaks of 1448 and 980 cm -1 related to the abundance of proline, serine, and threonine at tau phosphorylation sites were significantly enhanced in the frontal lobe cortex and hippocampus of AD brain tissues. The intensity ratio biomarker of high phosphorylation in the high wavenumber range from 2898 to 2932 cm -1 increased in all AD brain tissues. Changes of protein secondary conformation and abnormally phosphorylated tau or tauopathies were observed. In summary, VRR is a sensitive tool for characterizing protein structural changes and monitoring the tau phosphorylation. It may potentially be used for early detection of AD.