ABSTRACT
Recently, a clear association has been found between the progression of motor neurodegenerative disorders (MNDs) and carotid atherosclerosis. Significant vascular abnormalities with arterial hypertension were shown to be in patients with familial antecedents of MNDs. The main scope of this work is to explore the feasibility of recently developed integrated nano-based imaging modalities for the assessment of early diagnosis of the inflammatory processes associated with the neurological disorder syndromes, with the implication of recently developed nanopharmaceutical therapeutic interventions.
ABSTRACT
OBJECTIVE: Noninvasive imaging of atherosclerosis remains challenging in clinical applications. Here, we applied noninvasive molecular imaging to detect vascular cell adhesion molecule-1 in early and advanced atherosclerotic lesions of apolipoprotein E-deficient mice. METHODS AND RESULTS: Ultrasmall superparamagnetic iron oxide particles functionalized with (P03011) or without (P3007) vascular cell adhesion molecule-1-binding peptide were visualized by ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a marked signal loss in the aortic root of apolipoprotein E-deficient mice fed a Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection measurements, P3007-injected mice, and P03011- or P3007-injected age-matched C57BL/6 controls. Histological analyses revealed iron accumulations in the intima, in colocalization with vascular cell adhesion molecule-1-expressing macrophages and endothelial cells. Coherent anti-Stokes Raman scattering microscopy demonstrated iron signals in the intima and media of the aortic root in the P03011-injected but not untreated apolipoprotein E-deficient mice, localized to macrophages, luminal endothelial-like cells, and medial regions containing smooth muscle cells. Electron microscopy confirmed iron particles enclosed in endothelial cells and in the vicinity of smooth muscle cells. CONCLUSIONS: Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying P03011 as a contrast agent for imaging of atherosclerosis.
Subject(s)
Atherosclerosis/metabolism , Atherosclerosis/pathology , Ferric Compounds/metabolism , Nanoparticles , Vascular Cell Adhesion Molecule-1/metabolism , Vasculitis/metabolism , Vasculitis/pathology , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Atherosclerosis/genetics , Disease Models, Animal , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Macrophages/metabolism , Macrophages/pathology , Magnetic Resonance Imaging/methods , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron, Transmission , Spectrum Analysis, Raman , Tunica Intima/metabolism , Tunica Intima/pathologyABSTRACT
The scope of this study highlights application of an emerging hybrid vibrational nanoimaging techniques based on surface enhanced nanoimaging microscopy in investigating the inflammatory process in the vascular system and neurodegenerative disorder. The experiments were performed on transgenic rat and ApoE knockout mice model, intravenously injected with USPIO based MR contrast agent. Marked signal enhancement were observed in contrast treated specimens in specific pathological regions, which is known to be infiltrated by helper T cells. The findings were subsequently correlated with the results from MR imaging and immunohistochemistry. The focus of this work encompasses the latest innovation of nanoimaging technology in monitoring the inflammatory process in neurodegenerative diseases, and implementing the first observation of intracellular iron uptakes in the endothelial and medial smooth muscle cells based on Coherent anti-Stokes Raman Scattering (SECARS) Microscopy.
Subject(s)
Brain/metabolism , Brain/pathology , Inflammation/diagnosis , Nanotechnology/methods , Neurodegenerative Diseases/diagnosis , Animals , Apolipoproteins E/deficiency , Contrast Media , Disease Models, Animal , Humans , Inflammation/etiology , Inflammation/genetics , Magnetic Resonance Imaging , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Mutation/genetics , Neurodegenerative Diseases/complications , Neurodegenerative Diseases/genetics , Rats , Rats, Sprague-Dawley , Spectrum Analysis, Raman/methods , Superoxide Dismutase/genetics , Superoxide Dismutase-1ABSTRACT
We report a novel application to demonstrate and visualize the selective binding of lipids in cells of the reticuloendothelial system to super paramagnetic iron oxide (SPIO) nanoparticles. Ten New Zealand White rabbits that were experimentally injected intravenously with SPIO and five controls were investigated with vibrational microspectroscopy based on surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy. Marked cellular intensity enhancements in hepatic Kupffer cells and melanomacrophages of spleen have been observed in the range of 2850-2875 cm-1 in SPIO-injected animals but not in controls. The enhancements are related to the selective association of lipid molecules in cells of the reticuloendothelial system to uptaken SPIO, which can uniquely be visualized with SECARS microscopy.
