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Real time near-infrared Raman spectroscopy for the diagnosis of nasopharyngeal cancer.

ABSTRACT: Near-infrared (NIR) Raman spectroscopy has been investigated as a tool to differentiate nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue in an ex-vivo setting. Recently, we have miniaturized the fiber-optic Raman probe to investigate its utility in real time in-vivo surveillance of NPC patients. A posterior probability model using partial linear square (PLS) mathematical technique was constructed to verify the sensitivity and specificity of Raman spectroscopy in diagnosing NPC from post-irradiated and normal tissue using a diagnostic algorithm from three significant latent variables. NIR-Raman signals of 135 sites were measured from 79 patients with either newly diagnosed NPC (N = 12), post irradiated nasopharynx (N = 37) and normal nasopharynx (N = 30). The mean Raman spectra peaks identified differences at several Raman peaks at 853 cm-1, 940 cm-1, 1078 cm-1, 1335 cm-1, 1554 cm-1, 2885 cm-1 and 2940 cm-1 in the three different nasopharyngeal conditions. The sensitivity and specificity of distinguishing Raman signatures among normal nasopharynx versus NPC and post-irradiated nasopharynx versus NPC were 91% and 95%; and 77% and 96% respectively. Real time near-infrared Raman spectroscopy has a high specificity in distinguishing malignant from normal nasopharyngeal tissue in vivo, and may be investigated as a novel non-invasive surveillance tool in patients with nasopharyngeal cancer.

SUBMITTER: Ming LC

PROVIDER: S-EPMC5564780 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundCerebral blood flow (CBF) is maintained over a range of blood pressures through cerebral autoregulation (CA). Blood pressure outside the range of CA, or impaired autoregulation, is associated with adverse patient outcomes. Regional oxygen saturation (rSO2) derived from near-infrared spectroscopy (NIRS) can be used as a surrogate CBF for determining CA, but existing methods require a long period of time to calculate CA metrics. We have developed a novel method to determine CA using cotrending of mean arterial pressure (MAP) with rSO2that aims to provide an indication of CA state within 1 minute. We sought to determine the performance of the cotrending method by comparing its CA metrics to data derived from transcranial Doppler (TCD) methods.MethodsRetrospective data collected from 69 patients undergoing cardiac surgery with cardiopulmonary bypass were used to develop a reference lower limit of CA. TCD-MAP data were plotted to determine the reference lower limit of CA. The investigated method to evaluate CA state is based on the assessment of the instantaneous cotrending relationship between MAP and rSO2 signals. The lower limit of autoregulation (LLA) from the cotrending method was compared to the manual reference derived from TCD. Reliability of the cotrending method was assessed as uptime (defined as the percentage of time that the state of autoregulation could be measured) and time to first post.ResultsThe proposed method demonstrated minimal mean bias (0.22 mmHg) when compared to the TCD reference. The corresponding limits of agreement were found to be 10.79 mmHg (95% confidence interval [CI], 10.09-11.49) and -10.35 mmHg (95% CI, -9.65 to -11.05). Mean uptime was 99.40% (95% CI, 99.34-99.46) and the mean time to first post was 63 seconds (95% CI, 58-71).ConclusionsThe reported cotrending method rapidly provides metrics associated with CA state for patients undergoing cardiac surgery. A major strength of the proposed method is its near real-time feedback on patient CA state, thus allowing for prompt corrective action to be taken by the clinician.

Project description:As biospectroscopy techniques continue to be developed for screening or diagnosis within a point-of-care setting, an important development for this field will be high-throughput optimization. For many of these techniques, it is therefore necessary to adapt and develop parameters to generate a robust yet simple approach delivering high-quality spectra from biological samples. Specifically, this is important for surface-enhanced Raman spectroscopy (SERS) wherein there are multiple variables that can be optimised to achieve an enhancement of the Raman signal from a sample. One hypothesis is that "large" diameter (>100 nm) gold nanoparticles provide a greater enhancement at near-infrared (NIR) and infrared (IR) wavelengths than those <100 nm in diameter. Herein, we examine this notion using examples in which SERS spectra were acquired from MCF-7 breast cancer cells incubated with 150 nm gold nanoparticles. It was found that 150 nm gold nanoparticles are an excellent material for NIR/IR SERS. Larger gold nanoparticles may better satisfy the theoretical restraints for SERS enhancement at NIR/IR wavelengths compared to smaller nanoparticles. Also, larger nanoparticles or their aggregates are more readily observed via optical microscopy (and especially electron microscopy) compared to smaller ones. This allows rapid and straightforward identification of target areas containing a high concentration of nanoparticles and facilitating SERS spectral acquisition. To some extent, these observations appear to extend to biofluids such as blood plasma or (especially) serum; SERS spectra of such biological samples often exhibit a low signal-to-noise ratio in the absence of nanoparticles. With protein-rich biofluids such as serum, a dramatic SERS effect can be observed; although this might facilitate improved spectral biomarker identification in the future, it may not always improve classification between control vs. cancer. Thus, use of "large" gold nanoparticles are a good starting point in order to derive informative NIR/IR SERS analysis of biological samples.

Project description:Microbial rhodopsins have become an important tool in the field of optogenetics. However, effective in vivo optogenetics is in many cases severely limited due to the strong absorption and scattering of visible light by biological tissues. Recently, a combination of opsin site-directed mutagenesis and analog retinal substitution has produced variants of proteorhodopsin which absorb maximally in the near-infrared (NIR). In this study, UV-Visible-NIR absorption and resonance Raman spectroscopy were used to study the double mutant, D212N/F234S, of green absorbing proteorhodopsin (GPR) regenerated with MMAR, a retinal analog containing a methylamino modified β-ionone ring. Four distinct subcomponent absorption bands with peak maxima near 560, 620, 710 and 780 nm are detected with the NIR bands dominant at pH <7.3, and the visible bands dominant at pH 9.5. FT-Raman using 1064-nm excitation reveal two strong ethylenic bands at 1482 and 1498 cm-1 corresponding to the NIR subcomponent absorption bands based on an extended linear correlation between λmax and γC = C. This spectrum exhibits two intense bands in the fingerprint and HOOP mode regions that are highly characteristic of the O640 photointermediate from the light-adapted bacteriorhodopsin photocycle. In contrast, 532-nm excitation enhances the 560-nm component, which exhibits bands very similar to light-adapted bacteriorhodopsin and/or the acid-purple form of bacteriorhodopsin. Native GPR and its mutant D97N when regenerated with MMAR also exhibit similar absorption and Raman bands but with weaker contributions from the NIR absorbing components. Based on these results it is proposed that the NIR absorption in GPR-D212N/F234S with MMAR arises from an O-like chromophore, where the Schiff base counterion D97 is protonated and the MMAR adopts an all-trans configuration with a non-planar geometry due to twists in the conjugated polyene segment. This configuration is characterized by extensive charge delocalization, most likely involving nitrogens atoms in the MMAR chromophore.

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Real time near-infrared Raman spectroscopy for the diagnosis of nasopharyngeal cancer.

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