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Purpose: This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging., Procedures: Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS., Results: ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R (1) at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls., Conclusion: These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.

We have synthesized a bimodal lipidic molecule bearing both fluorophore and contrast agent signatures on the same structure in order to create a robust bimodal liposome for both magnetic resonance imaging (MRI) and fluorescence microscopy utility. The dual-modality concept considered in the synthesis of this new paramagnetic and fluorescent lipid is valuable in that anatomical information (MRI) as well as very sensitive localization (ex vivo fluorescence microscopy) of signal, and therefore liposome biodistribution, is obtainable. Bimodal cationic and neutral PEGylated liposomes were formulated using this novel lipid probe and used to label cells in vitro and image human ovarian xenografts in vivo. Tumour signal enhancement was increased by over 6-fold post-administration of the neutral PEGylated liposomes, and was maintained at this level up to the 24 h end-point. Our results showed this lipid to be more effective and sensitive than the single signature paramagnetic lipid Gd.DOTA.DSA at cellular labelling and tumour MRI.

A novel bimodal fluorescent and paramagnetic liposome is described for cellular labeling. In this study, we show the synthesis of a novel gadolinium lipid, Gd.DOTA.DSA, designed for liposomal cell labeling and tumor imaging. Liposome formulations consisting of this lipid were optimized in order to allow for maximum cellular entry, and the optimized formulation was used to label HeLa cells in vitro. The efficiency of this novel bimodal Gd-liposome formulation for cell labeling was demonstrated using both fluorescence microscopy and magnetic resonance imaging (MRI). The uptake of Gd-liposomes into cells induced a marked reduction in their MRI T 1 relaxation times. Fluorescence microscopy provided concomitant proof of uptake and revealed liposome internalization into the cell cytosol. The optimized formulation was also found to exhibit minimal cytotoxicity and was shown to have capacity for plasmid DNA (pDNA) transfection. A further second novel neutral bimodal Gd-liposome is described for the labeling of xenograft tumors in vivo utilizing the enhanced permeation and retention effect (EPR). Balb/c nude mice were inoculated with IGROV-1 cells, and the resulting tumor was imaged by MRI using these in vivo Gd-liposomes formulated with low charge and a poly(ethylene glycol) (PEG) calyx for long systemic circulation. These Gd-liposomes which were less than 100 nm in size were shown to accumulate in tumor tissue by MRI, and this was also verified by fluorescence microscopy of histology samples. Our in vivo tumor imaging results demonstrate the effectiveness of MRI to observe passive targeting of long-term circulating liposomes to tumors in real time, and allow for MRI directed therapy, wherein the delivery of therapeutic genes and drugs to tumor sites can be monitored while therapeutic effects on tumor mass and/or size may be simultaneously observed, quantitated, and correlated.

Abstract: Objectives. To develop and validate a new method of predicting the neutral lumbar spine curve from external (non-invasive electrogoniometer) measurements. Background. Non-invasive techniques for lumbar spine geometry prediction suffer from a lack of a complete geometry description, problems with applicability to field conditions, or both. Methods.The study consisted of three steps. First, utilizing lateral imaging (MRI and X-ray pictures) of the lumbosacral junction, the torso geometry was described using measures of lumbar lordosis via the Cobb method. Second, the relationship between imaging based measurement of lumbar spinal curvature and externally measured torso flexion angle in the sagittal plane using a goniometer was determined. Finally, method validation was performed with an independent set of nine subjects. The predicted lumbar spine curve was determined and the prediction errors were analyzed against the measured curves from digitized lateral X-ray images of the lumbosacral junction. Results.The shape of the lumbar curve was described as function of three externally measured parameters. The lumbar spine Cobb angle, segmental centroid positions (S 1−T 12), and segmental orientations were predicted from the external lumbar motion monitor measurements, with average precisions of 5.8°, 4.4mm, and 3.9°, respectively. Conclusions.The position and orientation of each segment (vertebrae and disc), along with the lumbar spine lordosis, can be predicted in the neutral posture using data from back angular measurements. Relevance The consideration of the spine as a curve is necessary to accurately quantify and describe the forces acting along the (lumbar) vertebral column for any given loading. The method could be a very useful prediction tool for industrial and laboratory experiments, as well as analytical models. [Copyright &y& Elsevier]

BACKGROUND CONTEXT: Accurate anatomical inputs for biomechanical models are necessary for valid estimates of internal loading. The magnitude of the moment arm of the lumbar erector muscle group is known to vary as a function of such variables as gender. Anatomical evidence indicates that the moment arms decrease during torso flexion. However, moment arm estimates in biomechanical models that account for individual variability have been derived from imaging studies from supine postures.PURPOSE: Quantify the sagittal plane moment arms of the lumbar erector muscle group as a function of torso flexion, and identify individual characteristics that are associated with the magnitude of the moment arms as a function of torso flexion.STUDY DESIGN/SETTING: Utilization of a 0.3 Tesla Open magnetic resonance image (MRI) to image and quantify the moment arm of the right erector muscle group as a function of gender and torso flexion.METHODS: Axial MRI images through and parallel to each of the lumbar intervertebral discs at four torso flexion angles were obtained from 12 male and 12 female subjects in a lateral recumbent posture. Multivariate analysis of variance was used to investigate the differences in the moment arms at different torso flexion angles, whereas hierarchical linear regression was used to investigate associations with individual anthropometric characteristics and spinal posture.RESULTS: The largest decrease in the lumbar erector muscle group moment arm from neutral to 45-degree flexion occurred at the L5–S1 level (9.7% and 8.9% for men and women, respectively). Measures of spinal curvature (L1–S1 lordosis), body mass and trunk characteristics (depth or circumference) were associated with the varying moment arm at most lumbar levels.CONCLUSIONS: The sagittal plane moment arms of the lumbar erector muscle mass decrease as the torso flexes forward. The change in moment arms as a function of torso flexion may have an impact on prediction of spinal loading in biomechanical models. [Copyright &y& Elsevier]