Comparison of high-resolution magnetic resonance imaging and micro-computed tomography arthrography for in-vivo assessment of cartilage in non-human primate models.

BACKGROUND: Non-human primate (NHP) could be an interesting model for osteoarthritis (OA) longitudinal studies but standard medical imaging protocols are not able to acquire sufficiently high-resolution images to depict the thinner cartilage (compared to human) in an in vivo context. The aim of this study was thus to develop and validate the acquisition protocols for knee joint examination of NHP using magnetic resonance imaging (MRI) at 1.5 T and X-ray micro-computed tomography arthrography (µCTA). METHODS: The first phase of the study focused on developing dedicated in vivo HR-MRI and µCTA protocols for simultaneous acquisitions of both knee joints on NHP. For MR, a dedicated two-channel receiver array coil and acquisition sequence were developed on a 1.5 T Siemens Sonata system and tuned to respect safety issues and reasonable examination time. For µCTA, an experimental setup was devised so as to fulfill similar requirements. The two imaging protocols were used during a longitudinal study so as to confirm that repeated injections of loxaglic acid (contrast agent used for µCTA) didn't induce any bias in cartilage assessment and to compare segmentation results from the two modalities. Lateral and medial cartilage tibial plateaus were assessed using a common image processing protocol leading to a 3D estimation of the cartilage thickness. RESULTS: From HR-MRI and µCTA images, thickness distributions were extracted allowing for proper evaluation of knee cartilage thickness of the primates. Results obtained in vivo indicated that the µCTA protocol did not induce any bias in the measured cartilage parameters and moreover, segmentation results obtained from the two imaging modalities were consistent. CONCLUSIONS: MR and µCTA are valuable imaging tools for the morphological evaluation of cartilage in NHP models which in turn can be used for OA studies.

A simplified framework to optimize MRI contrast preparation.

PURPOSE: This article proposes a rigorous optimal control framework for the design of preparation schemes that optimize MRI contrast based on relaxation time differences. METHODS: Compared to previous optimal contrast preparation schemes, a drastic reduction of the optimization parameter number is performed. The preparation scheme is defined as a combination of several block pulses whose flip angles, phase terms and inter-pulse delays are optimized to control the magnetization evolution. RESULTS: The proposed approach reduces the computation time of B 0 -robust preparation schemes to around a minute (whereas several hours were required with previous schemes), with negligible performance loss. The chosen parameterization allows to formulate the total preparation duration as a constraint, which improves the overall compromise between contrast performance and preparation time. Simulation, in vitro and in vivo results validate this improvement, illustrate the straightforward applicability of the proposed approach, and point out its flexibility in terms of achievable contrasts. Major improvement is especially achieved for short-T2 enhancement, as shown by the acquisition of a non-trivial contrast on a rat brain, where a short-T2 white matter structure (corpus callosum) is enhanced compared to surrounding gray matter tissues (hippocampus and neocortex). CONCLUSIONS: This approach proposes key advances for the design of optimal contrast preparation sequences, that emphasize their ability to generate non-standard contrasts, their potential benefit in a clinical context, and their straightforward applicability on any MR system.

Constant gradient elastography with optimal control RF pulses.

This article presents a new motion encoding strategy to perform magnetic resonance elastography (MRE). Instead of using standard motion encoding gradients, a tailored RF pulse is designed to simultaneously perform selective excitation and motion encoding in presence of a constant gradient. The RF pulse is designed with a numerical optimal control algorithm, in order to obtain a magnetization phase distribution that depends on the displacement characteristics inside each voxel. As a consequence, no post-excitation encoding gradients are required. This offers numerous advantages, such as reducing eddy current artifacts, and relaxing the constraint on the gradients maximum switch rate. It also allows to perform MRE with ultra-short TE acquisition schemes, which limits T2 decay and optimizes signal-to-noise ratio. The pulse design strategy is developed and analytically analyzed to clarify the encoding mechanism. Finally, simulations, phantom and ex vivo experiments show that phase-to-noise ratios are improved when compared to standard MRE encoding strategies.

Reproducibility of in vivo magnetic resonance imaging T1 rho and T2 relaxation time measurements of hip cartilage at 3.0T in healthy volunteers.

PURPOSE: To assess the T1 ρ and T2 values in the hip cartilage of healthy volunteers and to evaluate the reproducibility of these measurements. MATERIALS AND METHODS: The right hip joint of 30 asymptomatic volunteers was explored with 3T magnetic resonance imaging (MRI). Quantitative 3D T1 ρ- and T2 -maps sequences were repeated twice with a 30-minute delay (immediate reproducibility). The same protocol was repeated 14 days later (short-term reproducibility). Immediate and short-term reproducibility were estimated using coefficients of variation and correlation concordance coefficients (CCC). The precisions of the measurements were estimated by the ratio of the standard deviations. A mixed linear model was used to analyze the effect of patient's characteristics on T1 ρ and T2 values. RESULTS: Immediate reproducibility was significantly better than short-term reproducibility for T1 ρ (CCC of 0.75 versus 0.55; P = 0.007) and T2 (CCC 0.65 versus 0.32; P < 0.001). The precisions of the measurements were estimated between 5.5% and 9.1%. Median T1 ρ values were 6.0 msec higher in women than in men (P = 0.006), with no significant influence of age, body mass index (BMI), or sports activity. Median T2 values were not significantly different between men and women (0.4 msec lower in women; P = 0.76). There was no significant influence of age, BMI, or sports activity. T1 ρ and T2 values were lower in lateral regions than in medial regions (4.9 msec and 2.5 msec lower respectively; P < 0.0001). CONCLUSION: Immediate reproducibility of T1 ρ and T2 values is better than short-term, with limited effect of 30 minutes decubitus. T1 ρ values are significantly higher in women. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1022-1033.

Active control of the spatial MRI phase distribution with optimal control theory.

This paper investigates the use of Optimal Control (OC) theory to design Radio-Frequency (RF) pulses that actively control the spatial distribution of the MRI magnetization phase. The RF pulses are generated through the application of the Pontryagin Maximum Principle and optimized so that the resulting transverse magnetization reproduces various non-trivial and spatial phase patterns. Two different phase patterns are defined and the resulting optimal pulses are tested both numerically with the ODIN MRI simulator and experimentally with an agar gel phantom on a 4.7T small-animal MR scanner. Phase images obtained in simulations and experiments are both consistent with the defined phase patterns. A practical application of phase control with OC-designed pulses is also presented, with the generation of RF pulses adapted for a Magnetic Resonance Elastography experiment. This study demonstrates the possibility to use OC-designed RF pulses to encode information in the magnetization phase and could have applications in MRI sequences using phase images.

Optimal control design of preparation pulses for contrast optimization in MRI.

This work investigates the use of MRI radio-frequency (RF) pulses designed within the framework of optimal control theory for image contrast optimization. The magnetization evolution is modeled with Bloch equations, which defines a dynamic system that can be controlled via the application of the Pontryagin Maximum Principle (PMP). This framework allows the computation of optimal RF pulses that bring the magnetization to a given state to obtain the desired contrast after acquisition. Creating contrast through the optimal manipulation of Bloch equations is a new way of handling contrast in MRI, which can explore the theoretical limits of the system. Simulation experiments carried out on-resonance quantify the contrast improvement when compared to standard T1 or T2 weighting strategies. The use of optimal pulses is also validated for the first time in both in vitro and in vivo experiments on a small-animal 4.7T MR system. Results demonstrate their robustness to static field inhomogeneities as well as the fact that they can be embedded in standard imaging sequences without affecting standard parameters such as slice selection or echo type. In vivo results on rat and mouse brains illustrate the ability of optimal contrast pulses to create non-trivial contrasts on well-studied structures (white matter versus gray matter).

Dose-response of superparamagnetic iron oxide labeling on mesenchymal stem cells chondrogenic differentiation: a multi-scale in vitro study.

AIM: The aim of this work was the development of successful cell therapy techniques for cartilage engineering. This will depend on the ability to monitor non-invasively transplanted cells, especially mesenchymal stem cells (MSCs) that are promising candidates to regenerate damaged tissues. METHODS: MSCs were labeled with superparamagnetic iron oxide particles (SPIO). We examined the effects of long-term labeling, possible toxicological consequences and the possible influence of progressive concentrations of SPIO on chondrogenic differentiation capacity. RESULTS: No influence of various SPIO concentrations was noted on human bone marrow MSC viability or proliferation. We demonstrated long-term (4 weeks) in vitro retention of SPIO by human bone marrow MSCs seeded in collagenic sponges under TGF-ß1 chondrogenic conditions, detectable by Magnetic Resonance Imaging (MRI) and histology. Chondrogenic differentiation was demonstrated by molecular and histological analysis of labeled and unlabeled cells. Chondrogenic gene expression (COL2A2, ACAN, SOX9, COL10, COMP) was significantly altered in a dose-dependent manner in labeled cells, as were GAG and type II collagen staining. As expected, SPIO induced a dramatic decrease of MRI T2 values of sponges at 7T and 3T, even at low concentrations. CONCLUSIONS: This study clearly demonstrates (1) long-term in vitro MSC traceability using SPIO and MRI and (2) a deleterious dose-dependence of SPIO on TGF-ß1 driven chondrogenesis in collagen sponges. Low concentrations (12.5-25 µg Fe/mL) seem the best compromise to optimize both chondrogenesis and MRI labeling.

Low b-value diffusion-weighted cardiac magnetic resonance imaging: initial results in humans using an optimal time-window imaging approach.

OBJECTIVES: Diffusion-weighted imaging (DWI) using low b-values permits imaging of intravoxel incoherent motion in tissues. However, low b-value DWI of the human heart has been considered too challenging because of additional signal loss due to physiological motion, which reduces both signal intensity and the signal-to-noise ratio (SNR). We address these signal loss concerns by analyzing cardiac motion during a heartbeat to determine the time-window during which cardiac bulk motion is minimal. Using this information to optimize the acquisition of DWI data and combining it with a dedicated image processing approach has enabled us to develop a novel low b-value diffusion-weighted cardiac magnetic resonance imaging approach, which significantly reduces intravoxel incoherent motion measurement bias introduced by motion. MATERIALS AND METHODS: Simulations from displacement encoded motion data sets permitted the delineation of an optimal time-window with minimal cardiac motion. A number of single-shot repetitions of low b-value DWI cardiac magnetic resonance imaging data were acquired during this time-window under free-breathing conditions with bulk physiological motion corrected for by using nonrigid registration. Principal component analysis (PCA) was performed on the registered images to improve the SNR, and temporal maximum intensity projection (TMIP) was applied to recover signal intensity from time-fluctuant motion-induced signal loss. This PCATMIP method was validated with experimental data, and its benefits were evaluated in volunteers before being applied to patients. RESULTS: Optimal time-window cardiac DWI in combination with PCATMIP postprocessing yielded significant benefits for signal recovery, contrast-to-noise ratio, and SNR in the presence of bulk motion for both numerical simulations and human volunteer studies. Analysis of mean apparent diffusion coefficient (ADC) maps showed homogeneous values among volunteers and good reproducibility between free-breathing and breath-hold acquisitions. The PCATMIP DWI approach also indicated its potential utility by detecting ADC variations in acute myocardial infarction patients. CONCLUSIONS: Studying cardiac motion may provide an appropriate strategy for minimizing the impact of bulk motion on cardiac DWI. Applying PCATMIP image processing improves low b-value DWI and enables reliable analysis of ADC in the myocardium. The use of a limited number of repetitions in a free-breathing mode also enables easier application in clinical conditions.

New trends in MRI of cartilage: Advances and limitations in small animal studies.

Due to the actual interest for bioengineering in the osteoarthritis (OA) healing context, researchers need accurate qualitative and quantitative methodologies to evaluate in vivo the integration and functionality of their cartilage-like biomaterials. As in clinical diagnostic strategies, advances in Magnetic Resonance Imaging (MRI) seem promising for non-vulnerant assessments of articular cartilage bio-architecture and morphology in small animal models. These experimental models are commonly used to monitor the physiopathology of OA and to evaluate therapeutic responses mediated by chondroprotective drugs or tissue engineering. Nowadays, the application of MR protocols to in vivo small animal cartilage imaging is achievable with the development of high magnetic fields and the adaptation of methodologies to reach the required spatial resolution and contrast. The purpose of this article is to summarize these current MRI strategies used for in vivo small animal articular cartilage assessments.

Transient MR elastography (t-MRE) using ultrasound radiation force: theory, safety, and initial experiments in vitro.

The purpose of our study was to assess the feasibility of using ultrasound radiation force as a safe vibration source for transient MR elastography (t-MRE). We present a theoretical framework to predict the phase shift of the complex MRE signal, the temperature elevation due to ultrasound, and safety indicators (I(SPPA), I(SPTA), MI). Next, we report wave images acquired in porcine liver samples in vitro. MR thermometry was used to estimate the temperature elevation induced by ultrasound. Finally, we discuss the implications of our results with regard to the feasibility of using radiation force for t-MRE in a clinical setting, and a specific echo-planar imaging (EPI) MRE sequence is proposed.

A new EPI-based dynamic field mapping method: application to retrospective geometrical distortion corrections.

PURPOSE: To retrospectively correct for geometrical distortions, a new dynamic field mapping method suitable for dynamic single-shot gradient-echo type echo-planar imaging (GRE-EPI) is proposed. MATERIALS AND METHODS: The method requires a single volume additional acquisition and allows the extraction of a field map from each phase volume, assuming invariance across time of the echo time-independent phase component. Performances of the method are assessed using three sets of experiments: the first tests the prerequisite and the modeling; the second tests the method with time-dependent geometrical distortions; and the third presents a comparison with two other methods. RESULTS: Our results legitimize the modeling procedure and demonstrate that the dynamic method is less sensitive to noise than the other methods. A theoretical explanation for this is proposed in the discussion section. CONCLUSION: Given the minor increase in the acquisition time, this method is well suited for functional magnetic resonance imaging; prospective direction.