Three-dimensional ultrashort echo time (3D UTE) MRI of Achilles tendon at 4.7T MRI with comparison to conventional sequences in an experimental murine model of spondyloarthropathy.

BACKGROUND: Due to the very short T2 of its components, the normal anatomy of Achilles enthesis is impossible to define with "conventional" long echo time (TE) T2 sequences. However, this is a common site affected by rheumatologic disease. Early abnormalities related to inflammatory processes are impossible to detect in this location. PURPOSE: To assess the feasibility of a 3D-UTE (ultrashort echo time) sequence to evaluate normal and pathological Achilles entheses, determining both anterior fibrocartilaginous and posterior collagenic portions at 4.7T, in a rat model of spondyloarthropathy (SpA) with histological correlation. To assess whether this sequence detects SpA enthesopathy prior to long TE T2 sequences, enabling disease monitoring. STUDY TYPE: Prospective case-control study. ANIMAL MODEL: Twelve immunocompetent Wistar male rats imaged before (controls); the model was induced in eight rats (16 tendons) imaged at day 6, day 13, and day 21 with regular sacrifice for ex vivo imaging and histological correlation. FIELD STRENGTH: 4.7T Bruker Biospec Systems. 3D balanced steady-state free precession (bSSFP) and 3D-UTE sequences, performed at baseline (day 0, n = 12 animals / 24 tendons), day 6 (n = 8/16), 13 (n = 4/8), and day 21 (n = 2/4). ASSESSMENT: Visual analysis and signal intensity measurements (signal to noise ratio, SNR) of both bSSFP and UTE images were performed by two independent musculoskeletal radiologists at different locations of the Achilles enthesis and preinsertional area. STATISTICAL TESTS: Normal and pathological rat values were compared by Wilcoxon signed-rank tests, as well as interobserver differences. MRI findings were compared against histological data. RESULTS: The 3D-UTE sequence identified the anterior fibrocartilage and posterior collagenic areas of Achilles entheses in all cases. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at days 6 and 13 (P = 0.002 and P = 0.006, respectively). Neither the normal anatomy of the enthesis nor its pathological pattern could be identified on T2 bSSFP sequences. DATA CONCLUSION: Unlike bSSFP T2 sequences, 3D-UTE sequences enable visualization of normal enthesis anatomy and early detection of abnormalities in pathological conditions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:127-135.

Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering.

For bone tissue engineering, human Adipose Derived Stem Cells (hADSCs) are proposed to be associated with a scaffold for promoting bone regeneration. After implantation, cellularised scaffolds require a non-invasive method for monitoring their fate in vivo. The purpose of this study was to use Magnetic Resonance Imaging (MRI)-based tracking of these cells, labelled with magnetic agents for in vivo longitudinal assessment. hADSCs were isolated from adipose tissue and labelled with USPIO-rhodamine (Ultrasmall SuperParamagnetic Iron Oxide). USPIO internalisation, absence of toxicity towards hADSCs, and osteogenic differentiation of the labelled cells were evaluated in standard culture conditions. Labelled cells were then seeded within a 3D porous polysaccharide-based scaffold and imaged in vitro using fluorescence microscopy and MRI. Cellularised scaffolds were implanted subcutaneously in nude mice and MRI analyses were performed from 1 to 28 d after implantation. In vitro, no effect of USPIO labelling on cell viability and osteogenic differentiation was found. USPIO were efficiently internalised by hADSCs and generated a high T2* contrast. In vivo MRI revealed that hADSCs remain detectable until 28 d after implantation and could migrate from the scaffold and colonise the area around it. These data suggested that this scaffold might behave as a cell carrier capable of both holding a cell fraction and delivering cells to the site of implantation. In addition, the present findings evidenced that MRI is a reliable technique to validate cell-seeding procedures in 3D porous scaffolds, and to assess the fate of hADSCs transplanted in vivo.

Optimizing 4D abdominal MRI: image denoising using an iterative back-projection approach.

4D-MRI is a promising tool for organ exploration, target delineation and treatment planning. Intra-scan motion artifacts may be greatly reduced by increasing the imaging frame rate. However, poor signal-to-noise ratios (SNR) are observed when increasing spatial and/or frame number per physiological cycle, in particular in the abdomen. In the current work, the proposed 4D-MRI method favored spatial resolution, frame number, isotropic voxels and large field-of-view (FOV) during MR-acquisition. The consequential SNR penalty in the reconstructed data is addressed retrospectively using an iterative back-projection (IBP) algorithm. Practically, after computing individual spatial 3D deformations present in the images using a deformable image registration (DIR) algorithm, each 3D image is individually enhanced by fusing several successive frames in its local temporal neighborood, these latter being likely to cover common independent informations. A tuning parameter allows one to freely readjust the balance between temporal resolution and precision of the 4D-MRI. The benefit of the method was quantitatively evaluated on the thorax of 6 mice under free breathing using a clinically acceptable duration. Improved 4D cardiac imaging was also shown in the heart of 1 mice. Obtained results are compared to theoretical expectations and discussed. The proposed implementation is easily parallelizable and optimized 4D-MRI could thereby be obtained with a clinically acceptable duration.

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy.

Microglia are phagocytic cells that are chemoattracted by brain tumors and can represent up to 70% of the tumor cell population. To get insight into gene therapy against glioma, we decided to take advantage of those microglia properties and to use those cells as vehicles to transport simultaneously a suicide gene (under the control of a heat-sensitive promoter) and contrast agents to localize them by magnetic resonance imaging before applying any therapeutic treatment. Thymidine kinase (TK) expression and its functionality after gancyclovir administration were investigated. After the heat shock (44 degrees C and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir treatment, 90% of the cells died by apoptosis, showing an important bystander effect. Then, the cells were incubated with new lanthanide contrast agents to check both their potential toxicity and their MR properties. Results indicate that the nanoparticles did not induce any cell toxicity and yield a hypersignal on MR images at 4.7 T. These in vitro experiments indicate that microglia are good candidates as vectors in gene therapy against brain tumors. Finally, microglia containing gadolinium-grafted nanoparticles were injected in the close vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo images as well as its retention time show the potential of the novel contrast agents for cellular imaging.

Gadolinium-enhanced small-animal TOF magnetic resonance angiography.

So far, magnetic resonance angiography (MRA) of rodents has only been performed by using time-of-flight (TOF) MRI techniques. This is because applications of first-passage contrast agents as in humans are hampered by pronounced physiologic differences (blood volume and heart beat rate). Here we describe the use of low-dose Gd-DOTA to enhance the performance of TOF MRA in rat brain. While no improvement in contrast was achieved, the measuring time could be reduced by almost a factor of three. This decrease in total acquisition time has been used to study the impact of a model of ligatured common carotid on the upper part of the blood system of the rat.