Dataset Information

In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy.

ABSTRACT: Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi-parameter molecular imaging technologies have been established to date. Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS). Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS. Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries. Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes. Conclusion: This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.

SUBMITTER: Noonan J

PROVIDER: S-EPMC6299693 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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<i>In vivo</i> multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy.

Noonan Jonathan J Asiala Steven M SM Grassia Gianluca G MacRitchie Neil N Gracie Kirsten K Carson Jake J Moores Matthew M Girolami Mark M Bradshaw Angela C AC Guzik Tomasz J TJ Meehan Gavin R GR Scales Hannah E HE Brewer James M JM McInnes Iain B IB Sattar Naveed N Faulds Karen K Garside Paul P Graham Duncan D Maffia Pasquale P

Theranostics 20181129 22

Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis. The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi-parameter molecular imaging technologies have been established to date. Here, we report the targeted <i>in vivo</i> imaging of multiple vascular biomarkers using antibody-functionalized nan ...[more]

PMID: 30613292

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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: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.

Dataset Information

In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy.

Publications

<i>In vivo</i> multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy.

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