A Bioorthogonal Probe for Multiscale Imaging by ¹⁹F-MRI and Raman Microscopy: From Whole Body to Single Cells

Abstract

Molecular imaging techniques are essential tools for better investigating biological processes and detecting disease biomarkers with improvement of both diagnosis and therapy monitoring. Often, a single imaging technique is not sufficient to obtain comprehensive information at different levels. Multimodal diagnostic probes are key tools to enable imaging across multiple scales. The direct registration of in vivo imaging markers with ex vivo imaging at the cellular level with a single probe is still challenging. Fluorinated ( 19 F) probes have been increasingly showing promising potentialities for in vivo cell tracking by 19 F-MRI. Here we present the unique features of a bioorthogonal 19 F-probe that enables direct signal correlation of MRI with Raman imaging. In particular, we reveal the ability of PERFECTA, a superfluorinated molecule, to exhibit a remarkable intense Raman signal distinct from cell and tissue fingerprints. Therefore, PERFECTA combines in a single molecule excellent characteristics for both macroscopic in vivo 19 F-MRI, across the whole body, and microscopic imaging at tissue and cellular levels by Raman imaging.

Image-guided Raman spectroscopy navigation system to improve transperineal prostate cancer detection. Part 2: in-vivo tumor-targeting using a classification model combining spectral and MRI-radiomics features

“…As multimodal information provides significant advantages for navigation, different characterization modalities are also advantageous for classification purposes. 43 One of the models that combined optical and image-based properties exhibited the best performance: . The complementary information of mesoscopic and macroscopic characterization allowed to outperform the models that only used a single modality (FP or Rad) on all metrics.…”

“…Multimodal and multiscale characterization is advantageous for tissue characterization purposes given the complementary information it provides, as single modalities may not capture all critical elements of the interrogated sample. 24 , 38 , 43 , 44 …”

“…41,42 Multimodal and multiscale characterization is advantageous for tissue characterization purposes given the complementary information it provides, as single modalities may not capture all critical elements of the interrogated sample. 24,38,43,44 This pilot clinical study aims to evaluate the feasibility of a multimodal and multiscale characterization approach for in-vivo PCa classification during clinical procedures. We combined real-time mesoscopic characterization provided by RS and macroscopic characterization from preoperative mpMRI, co-localized with multimodal image registration and EM tracking, as input for a support vector machine (SVM), for assessing the classification potential of such characterization.…”

Hydrophobin‐Coated Solid Fluorinated Nanoparticles for 19F‐MRI

“…The protocol for cell labelling and isolating the cell pellets were adapted from an optimized protocol. [ 6a,26 ] The cellular uptake of 19 F from the HFBII‐FNP were evaluated performing 19 F‐NMR measurements on the suspension of cellular pellets obtained after incubating the cells for different time points (4, 6, 8 h). The uptake at different time points was also checked by 19 F‐MRI.…”

19F MRI Probes for Multimodal Imaging**

“…The minimal concentration of PERFECTA for Raman modality was approximately 0.2 mM. There is considerable potential for this combination of modalities, especially in multicolor imaging, with various derivatives of PERFECTA showing distinct Raman bands and 19 F NMR chemical shifts [69] …”