Noninvasive multimodal fluorescence and magnetic resonance imaging of whole-organ intervertebral discs

Abstract

Low back pain (LBP) is a commonly experienced symptom posing a tremendous healthcare burden to individuals and society at large. The LBP pathology is strongly linked to degeneration of the intervertebral disc (IVD), calling for development of early-stage diagnostic tools for visualizing biomolecular changes in IVD. Multimodal measurements of fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) were performed on IVD whole organ culture model using an in-house built FMT system and a high-field MRI scanner. The resulted multimodal images were systematically validated through epifluorescence imaging of the IVD sections at a microscopic level. Multiple image contrasts were exploited, including fluorescence distribution, anatomical map associated with T1-weighted MRI contrast, and water content related with T2 relaxation time. The developed multimodality imaging approach may thus serve as a new assessment tool for early diagnosis of IVD degeneration and longitudinal monitoring of IVD organ culture status using fluorescence markers.

Neoepitope fragments as biomarkers for different phenotypes of intervertebral disc degeneration

“…Assessment of aggrecan and collagen neoepitopes may be used to evaluate early, severity grade, predict regenerative treatments, and stratify disease phenotypes of IVD degeneration. These, and others not evaluated in this study, neoepitope biomarkers could be used for future diagnostics of IVD disease using specific imaging tools, such as fluorescent molecular tomography 65 and Raman. These advanced imaging techniques, in combination with other conventional tools (e.g., CT, MRI, clinical data, genetic predisposition) and imagine sensible probes, will be instrumental for clinicians to screen patients at risk of IVD degeneration disease and to better define the proper IVD phenotype, leading to a more appropriate treatment.…”

“…Assessment of aggrecan and collagen neoepitopes may be used to evaluate early, severity grade, predict regenerative treatments, and stratify disease phenotypes of IVD degeneration. These, and others not evaluated in this study, neoepitope biomarkers could be used for future diagnostics of IVD disease using specific imaging tools, such as fluorescent molecular tomography65 and Raman. These advanced imaging techniques, in combination with other conventional tools (e.g., CT, MRI, clinical data, genetic predisposition) and imagine sensible probes, will be instrumental for clinicians to screen patients at risk of IVD degeneration disease and to better define the proper IVD phenotype, leading to a more appropriate treatment.AUTHOR CONTRIBUTIONSZhenLi and Mauro Alini designed the study; Shangbin Cui, Wenyue Li, and Graciosa Q. Teixeira performed the experiments; Shangbin Cui analyzed the data; Shangbin Cui drafted the manuscript; Cornelia Neidlinger-Wilke, Hans-Joachim Wilke, Lisbet Haglund, Hongwei Ouyang, R. Geoff Richards, Mauro Alini, Sibylle Grad, and Zhen Li provided critical suggestions and discussions throughout the study and revised the manuscript.…”

Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc

“…Another advantage in terms of imaging organ culture models is the application of molecular imaging to track changes in the biological activity of cells in organ culture over time (e.g., cell metabolism). One example of this is the use of fluorescence molecular tomography (FMT) which is capable of retrieving the 3D bio‐distribution of fluorescent molecular markers noninvasively, thus offering higher molecular sensitivity than microCT or MRI 166 . One key feature of FMT is the use of near‐infrared (NIR) fluorescence probes, which have been shown to be the most effective for deep tissue imaging.…”

“…One example of this is the use of fluorescence molecular tomography (FMT) which is capable of retrieving the 3D bio‐distribution of fluorescent molecular markers noninvasively, thus offering higher molecular sensitivity than microCT or MRI. 166 One key feature of FMT is the use of near‐infrared (NIR) fluorescence probes, which have been shown to be the most effective for deep tissue imaging. In the NIR spectral range, the attenuation of living tissue is minimal, allowing the use of sufficient laser power for fluorescence excitation and detection without causing tissue damage under prolonged illumination.…”

Stochastic reconstruction of dual components facilitates high-fidelity in vivo fluorescence tomographic imaging

“…In comparison to traditional tomographic systems such as positron emission tomography (PET) and magnetic resonance imaging (MRI), FMT benefits from a wide range of applicable fluorescence probes, thus offering a versatile and cost-effective tool for preclinical studies [5,6]. The application of FMT is diverse, including brain imaging [7,8], drug screening [9], tumor detection [10,11], and ex vivo sample monitoring [12][13][14]. More recently, a proof-of-concept study shows that FMT can be further extended to the emerging field of fluorescence-based surgical navigation by achieving 3D fluorescence-enhanced images instead of planar images [15,16].…”