RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS, FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS

Raman spectroscopy is a noninvasive, nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations. It does not require sample preparation or pretreatment. However, the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period (a few seconds). In this work, a fast dispersive-type near-infrared (NIR) Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time, noninvasive, in vivo human skin measurements. Spectrograph image aberration was corrected by a parabolic-line fiber array, permitting complete CCD vertical binning, thereby yielding a 16-fold improvement in signal-to-noise ratio. Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second, which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis. Currently, we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection. Intermediate data analysis results are presented. Recently, we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection. Preliminary in vivo results from endoscopic lung Raman measurements are discussed.

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Real-Time in vivo Raman Spectroscopy and Its Clinical Applications in Early Cancer Detection

Chinese Journal of Lasers ◽

10.3788/cjl201845.0207002 ◽

2018 ◽

Vol 45 (2) ◽

pp. 0207002

Author(s):

王爽 Shuang Wang ◽

Haishan Zeng Haishan Zeng

Keyword(s):

Raman Spectroscopy ◽

Real Time ◽

Cancer Detection ◽

Early Cancer ◽

Clinical Applications ◽

Early Cancer Detection ◽

In Vivo Raman Spectroscopy

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Near Infrared Raman Spectroscopy for Cancer Detection in vivo

Biomedical Topical Meeting ◽

10.1364/bio.2002.me4 ◽

2002 ◽

Author(s):

Anita Mahadevan-Jansen ◽

Amy Robichaux ◽

Chad Lieber ◽

Heidi Shappell ◽

Darryl Ellis ◽

...

Keyword(s):

Raman Spectroscopy ◽

Cancer Detection ◽

Near Infrared

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Real-time In Vivo Raman Spectroscopy: Technology Development and Clinical Applications in Early Cancer Detection

Optics in the Life Sciences ◽

10.1364/boda.2013.bm2a.1 ◽

2013 ◽

Author(s):

Haishan Zeng ◽

Jianhua Zhao ◽

Michael Short ◽

David I McLean ◽

Stephen Lam ◽

...

Keyword(s):

Raman Spectroscopy ◽

Real Time ◽

Cancer Detection ◽

Technology Development ◽

Early Cancer ◽

Clinical Applications ◽

Early Cancer Detection ◽

In Vivo Raman Spectroscopy

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Characterization of Raman Spectra Measured in Vivo for the Detection of Cervical Dysplasia

Applied Spectroscopy ◽

10.1366/000370207781746053 ◽

2007 ◽

Vol 61 (9) ◽

pp. 986-993 ◽

Cited By ~ 72

Author(s):

Amy Robichaux-Viehoever ◽

Elizabeth Kanter ◽

Heidi Shappell ◽

Dean Billheimer ◽

Howard Jones ◽

...

Keyword(s):

Raman Spectroscopy ◽

Raman Spectra ◽

Sensitivity And Specificity ◽

Near Infrared ◽

Squamous Metaplasia ◽

Cervical Dysplasia ◽

High Grade Dysplasia ◽

Measured Signal ◽

High Grade

Raman spectroscopy has been shown to have the potential for providing differential diagnosis in the cervix with high sensitivity and specificity in previous studies. The research presented here further evaluates the potential of near-infrared Raman spectroscopy to detect cervical dysplasia in a clinical setting. Using a portable system, Raman spectra were collected from the cervix of 79 patients using clinically feasible integration times (5 seconds on most patients). Multiple Raman measurements were taken from colposcopically normal and abnormal areas prior to the excision of tissue. Data were processed to extract Raman spectra from measured signal, which includes fluorescence and noise. The resulting spectra were correlated with the corresponding histopathologic diagnosis to determine empirical differences between different diagnostic categories. Using histology as the gold standard, logistic regression discrimination algorithms were developed to distinguish between normal ectocervix, squamous metaplasia, and high-grade dysplasia using independent training and validation sets of data. An unbiased estimate of the accuracy of the model indicates that Raman spectroscopy can distinguish between high-grade dysplasia and benign tissue with sensitivity of 89% and specificity of 81%, while colposcopy in expert hands was able to discriminate with a sensitivity and specificity of 87% and 72%.

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Applications of Vibrational Spectroscopy for Analysis of Connective Tissues

Molecules ◽

10.3390/molecules26040922 ◽

2021 ◽

Vol 26 (4) ◽

pp. 922

Author(s):

William Querido ◽

Shital Kandel ◽

Nancy Pleshko

Keyword(s):

Raman Spectroscopy ◽

Vibrational Spectroscopy ◽

Near Infrared ◽

Ex Vivo ◽

Biological Tissues ◽

Label Free ◽

Connective Tissues ◽

Bone Properties ◽

Composition And Structure

Advances in vibrational spectroscopy have propelled new insights into the molecular composition and structure of biological tissues. In this review, we discuss common modalities and techniques of vibrational spectroscopy, and present key examples to illustrate how they have been applied to enrich the assessment of connective tissues. In particular, we focus on applications of Fourier transform infrared (FTIR), near infrared (NIR) and Raman spectroscopy to assess cartilage and bone properties. We present strengths and limitations of each approach and discuss how the combination of spectrometers with microscopes (hyperspectral imaging) and fiber optic probes have greatly advanced their biomedical applications. We show how these modalities may be used to evaluate virtually any type of sample (ex vivo, in situ or in vivo) and how “spectral fingerprints” can be interpreted to quantify outcomes related to tissue composition and quality. We highlight the unparalleled advantage of vibrational spectroscopy as a label-free and often nondestructive approach to assess properties of the extracellular matrix (ECM) associated with normal, developing, aging, pathological and treated tissues. We believe this review will assist readers not only in better understanding applications of FTIR, NIR and Raman spectroscopy, but also in implementing these approaches for their own research projects.

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In vivo detection of cervical dysplasia with near-infrared Raman spectroscopy

10.1117/12.460793 ◽

2002 ◽

Cited By ~ 2

Author(s):

Amy Robichaux ◽

Chad A. Lieber ◽

Heidi Shappell ◽

Beth Huff ◽

Howard Jones III ◽

...

Keyword(s):

Raman Spectroscopy ◽

Near Infrared ◽

Cervical Dysplasia

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Potential of Near-Infrared Fourier Transform Raman Spectroscopy in Food Analysis

Applied Spectroscopy ◽

10.1366/000370292789619368 ◽

1992 ◽

Vol 46 (10) ◽

pp. 1503-1507 ◽

Cited By ~ 118

Author(s):

Y. Ozaki ◽

R. Cho ◽

K. Ikegaya ◽

S. Muraishi ◽

K. Kawauchi

Keyword(s):

Raman Spectroscopy ◽

Fourier Transform ◽

Fatty Acid ◽

Raman Spectra ◽

Food Analysis ◽

Near Infrared ◽

Egg White ◽

Ft Raman Spectroscopy ◽

Ft Raman

The 1064-nm excited Fourier transform (FT) Raman spectra have been measured in situ for various foods in order to investigate the potential of near-infrared (NIR) FT-Raman spectroscopy in food analysis. It is demonstrated here that NIR FT-Raman spectroscopy is a very powerful technique for (1) detecting selectively the trace components in foodstuffs, (2) estimating the degree of unsaturation of fatty acids included in foods, (3) investigating the structure of food components, and (4) monitoring changes in the quality of foods. Carotenoids included in foods give two intense bands near 1530 and 1160 cm−1 via the pre-resonance Raman effect in the NIR FT-Raman spectra, and therefore, the NIR FT-Raman technique can be employed to detect them nondestructively. Foods consisting largely of lipids such as oils, tallow, and butter show bands near 1658 and 1443 cm−1 due to C=C stretching modes of cis unsaturated fatty acid parts and CH2 scissoring modes of saturated fatty acid parts, respectively. It has been found that there is a linear correlation for various kinds of lipid-containing foods between the iodine value (number) and the intensity ratio of two bands at 1658 and 1443 cm−1 ( I1658/ I1443), indicating that the ratio can be used as a practical indicator for estimating the unsaturation level of a wide range of lipid-containing foods. A comparison of the Raman spectra of raw and boiled egg white shows that the amide I band shifts from 1666 to 1677 cm−1 and the intensity of the amide III band at 1275 cm−1 decreases upon boiling. These observations indicate that most α-helix structure changes into unordered structure in the proteins constituting egg white upon boiling. The NIR FT-Raman spectrum of old-leaf (about one year old) Japanese tea has been compared with that of its new leaf. The intensity ratio of two bands at 1529 and 1446 cm−1 ( I1529/ I1446), assignable to carotenoid and proteins, respectively, is considerably smaller in the former than in the latter, indicating that the ratio is useful for monitoring the changes in the quality of Japanese tea.

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