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Spatially Offset Raman Spectroscopy toward In Vivo Assessment of the Adipose Tissue in Cardiometabolic Pathologies.

ABSTRACT: Spatially offset Raman spectroscopy (SORS) enhanced the capabilities of Raman spectroscopy for the depth-resolved analysis of biological and diffusely scattering samples. This technique offers selective probing of subsurface layers, providing molecular insights without invasive procedures. While SORS has found application in biomedical research, up to now, studies have focused mainly on the detection of mineralization of bones and tissues. Herein, for the first time, SORS is used to assess the soft, organic tissue beneath the skin's surface. In this study, we demonstrate the diagnostic utility of a hand-held SORS device for evaluating the chemical composition of the adipose tissue. We compared perigonadal white adipose tissue (gWAT) in a murine model of atherosclerosis, heart failure, and high-fat diet (HFD) induced obesity. Our results reveal distinct chemical differences in gWAT between HFD-fed and control mice, showcasing the potential of SORS for intravital adipose tissue phenotype characterization. Furthermore, our findings underscore the effectiveness of SORS as a valuable tool for noninvasive assessment of the adipose tissue composition, holding potential diagnostic significance for metabolic disorders.

SUBMITTER: Stanek E

PROVIDER: S-EPMC11209658 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Spatially Offset Raman Spectroscopy toward In Vivo Assessment of the Adipose Tissue in Cardiometabolic Pathologies.

Stanek Ewa E Majka Zuzanna Z Czamara Krzysztof K Mazurkiewicz Joanna J Kaczor Agnieszka A

Analytical chemistry 20240612 25

Spatially offset Raman spectroscopy (SORS) enhanced the capabilities of Raman spectroscopy for the depth-resolved analysis of biological and diffusely scattering samples. This technique offers selective probing of subsurface layers, providing molecular insights without invasive procedures. While SORS has found application in biomedical research, up to now, studies have focused mainly on the detection of mineralization of bones and tissues. Herein, for the first time, SORS is used to assess the s ...[more]

PMID: 38865715

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Project description:A fundamental question crucial to surface-enhanced spatially offset Raman spectroscopy (SESORS) imaging and implementing it in a clinical setting for in vivo diagnostic purposes is whether a SESORS image can be used to determine the exact location of an object within tissue? To address this question, multiple experimental factors pertaining to the optical setup in imaging experiments using an in-house-built point-collection-based spatially offset Raman spectroscopy (SORS) system were investigated to determine those critical to the three-dimensional (3D) positioning capability of SESORS. Here, we report the effects of the spatial offset magnitude and geometry on locating nanoparticles (NPs) mixed with silica powder as an imaging target through tissue and outline experimental techniques to allow for the correct interpretation of SESORS images to ascertain the correct location of NPs in the two-dimensional x, y-imaging plane at depth. More specifically, the effect of "linear offset-induced image drag" is presented, which refers to a spatial distortion in SESORS images caused by the magnitude and direction of the linear offset and highlight the need for an annular SORS collection geometry during imaging to neutralize these asymmetric effects. Additionally, building on these principles, the concept of "ratiometric SESORS imaging" is introduced for the location of buried inclusions in three dimensions. Together these principles are vital in developing a methodology for the location of surface-enhanced Raman scattering-active inclusions in three dimensions. This approach utilizes the relationship between the magnitude of the spatial offset, the probed depth, and ratiometric analysis of the NP and tissue Raman intensities to ultimately image and spatially discriminate between two distinct NP flavors buried at different depths within a 3D model for the first time. This research demonstrates how to accurately identify multiple objects at depth in tissue and their location using SESORS which addresses a key capability in moving SESORS closer to use in biomedical applications.

Project description:Rationale: The goal of imaging tumors at depth with high sensitivity and specificity represents a significant challenge in the field of biomedical optical imaging. 'Surface enhanced Raman scattering' (SERS) nanoparticles (NPs) have been employed as image contrast agents and can be used to specifically target cells in vivo. By tracking their unique "fingerprint" spectra, it becomes possible to determine their precise location. However, while the detection of SERS NPs is very sensitive and specific, conventional Raman spectroscopy imaging devices are limited in their inability to probe through tissue depths of more than a few millimetres, due to scattering and absorption of photons by biological tissues. Here, we combine the use of "Spatially Offset Raman spectroscopy" (SORS) with that of "surface-enhanced resonance Raman spectroscopy" (SERRS) in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESO(R)RS) to image deep-seated glioblastoma multiforme (GBM) tumors in vivo in mice through the intact skull. Methods: A SORS imaging system was built in-house. Proof of concept SORS imaging was achieved using a PTFE-skull-tissue phantom. Imaging of GBMs in the RCAS-PDGF/N-tva transgenic mouse model was achieved through the use of gold nanostars functionalized with a resonant Raman reporter to create SERRS nanostars. These were then encapsulated in a thin silica shell and functionalized with a cyclic-RGDyK peptide to yield integrin-targeting SERRS nanostars. Non-invasive in vivo SORS image acquisition of the integrin-targeted nanostars was then performed in living mice under general anesthesia. Conventional non-SORS imaging was used as a direct comparison. Results: Using a low power density laser, GBMs were imaged via SESORRS in mice (n = 5) and confirmed using MRI and histopathology. The results demonstrate that via utilization of the SORS approach, it is possible to acquire clear and distinct Raman spectra from deep-seated GBMs in mice in vivo through the skull. SESORRS images generated using classical least squares outlined the tumors with high precision as confirmed via MRI and histology. Unlike SESORRS, conventional Raman imaging of the same areas did not provide a clear delineation of the tumor. Conclusion: To the best of our knowledge this is the first report of in vivo SESO(R)RS imaging. In a relevant brain tumor mouse model we demonstrate that this technique can overcome the limitations of conventional Raman imaging with regards to penetration depth. This work therefore represents a significant step forward in the potential clinical translation of SERRS nanoparticles for high precision cancer imaging.

Project description:In the field of optical imaging, the ability to image tumors at depth with high selectivity and specificity remains a challenge. Surface enhanced resonance Raman scattering (SERRS) nanoparticles (NPs) can be employed as image contrast agents to specifically target cells in vivo; however, this technique typically requires time-intensive point-by-point acquisition of Raman spectra. Here, we combine the use of "spatially offset Raman spectroscopy" (SORS) with that of SERRS in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESORRS) to image deep-seated tumors in vivo. Additionally, by accounting for the laser spot size, we report an experimental approach for detecting both the bulk tumor, subsequent delineation of tumor margins at high speed, and the identification of a deeper secondary region of interest with fewer measurements than are typically applied. To enhance light collection efficiency, four modifications were made to a previously described custom-built SORS system. Specifically, the following parameters were increased: (i) the numerical aperture (NA) of the lens, from 0.2 to 0.34; (ii) the working distance of the probe, from 9 mm to 40 mm; (iii) the NA of the fiber, from 0.2 to 0.34; and (iv) the fiber diameter, from 100 μm to 400 μm. To calculate the sampling frequency, which refers to the number of data point spectra obtained for each image, we considered the laser spot size of the elliptical beam (6 × 4 mm). Using SERRS contrast agents, we performed in vivo SESORRS imaging on a GL261-Luc mouse model of glioblastoma at four distinct sampling frequencies: par-sampling frequency (12 data points collected), and over-frequency sampling by factors of 2 (35 data points collected), 5 (176 data points collected), and 10 (651 data points collected). In comparison to the previously reported SORS system, the modified SORS instrument showed a 300% improvement in signal-to-noise ratios (SNR). The results demonstrate the ability to acquire distinct Raman spectra from deep-seated glioblastomas in mice through the skull using a low power density (6.5 mW/mm2) and 30-times shorter integration times than a previous report (0.5 s versus 15 s). The ability to map the whole head of the mouse and determine a specific region of interest using as few as 12 spectra (6 s total acquisition time) is achieved. Subsequent use of a higher sampling frequency demonstrates it is possible to delineate the tumor margins in the region of interest with greater certainty. In addition, SESORRS images indicate the emergence of a secondary tumor region deeper within the brain in agreement with MRI and H&E staining. In comparison to traditional Raman imaging approaches, this approach enables improvements in the detection of deep-seated tumors in vivo through depths of several millimeters due to improvements in SNR, spectral resolution, and depth acquisition. This approach offers an opportunity to navigate larger areas of tissues in shorter time frames than previously reported, identify regions of interest, and then image the same area with greater resolution using a higher sampling frequency. Moreover, using a SESORRS approach, we demonstrate that it is possible to detect secondary, deeper-seated lesions through the intact skull.

Project description:The fracture resistance of bone arises from the hierarchical arrangement of minerals, collagen fibrils (i.e., cross-linked triple helices of α1 and α2 collagen I chains), non-collagenous proteins, and water. Raman spectroscopy (RS) is not only sensitive to the relative fractions of these constituents, but also to the secondary structure of bone proteins. To assess the ability of RS to detect differences in the protein structure, we quantified the effect of sequentially autoclaving (AC) human cortical bone at 100 °C (∼34.47 kPa) and then at 120 °C (∼117.21 kPa) on the amide I band using a commercial Raman micro-spectroscopy (μRS) instrument and custom spatially offset RS (SORS) instrument in which rings of collection fiber optics are offset from the central excitation fiber optics within a hand-held, cylindrical probe. Being clinically viable, measurements by SORS involved collecting Raman spectra of cadaveric femur mid-shafts (5 male & 5 female donors) through layers of a tissue mimic. Otherwise, μRS and SORS measurements were acquired directly from each bone. AC-related changes in the helical status of collagen I were assessed using amide I sub-peak ratios (intensity, I, at ∼1670 cm-1 relative to intensities at ∼1610 cm-1 and ∼1640 cm-1). The autoclaving manipulation significantly decreased the selected amide I sub-peak ratios as well as shifted peaks at ∼1605 cm-1 (μRS), ∼1636 cm-1 (SORS) and ∼1667 cm-1 in both μRS and SORS. Compared to μRS, SORS detected more significant differences in the amide I sub-peak ratios when the fiber optic probe was directly applied to bone. SORS also detected AC-related decreases in I1670/I1610 and I1670/I1640 when spectra were acquired through layers of the tissue mimic with a thickness ≤2 mm by the 7 mm offset ring, but not with the 5 mm or 6 mm offset ring. Overall, the SORS instrument was more sensitive than the conventional μRS instrument to pressure- and temperature-related changes in the organic matrix that affect the fracture resistance of bone, but SORS analysis of the amide I band is limited to an overlying thickness layer of 2 mm.

Dataset Information

Spatially Offset Raman Spectroscopy toward In Vivo Assessment of the Adipose Tissue in Cardiometabolic Pathologies.

Publications

Spatially Offset Raman Spectroscopy toward In Vivo Assessment of the Adipose Tissue in Cardiometabolic Pathologies.

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