A comprehensive protocol for quantitative magnetic resonance imaging of the brain at 3 Tesla.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism.

Probing muscle recovery following downhill running using precise mapping of MRI T2 relaxation times.

PURPOSE: Postexercise recovery rate is a vital component of designing personalized training protocols and rehabilitation plans. Tracking exercise-induced muscle damage and recovery requires sensitive tools that can probe the muscles' state and composition noninvasively. METHODS: Twenty-four physically active males completed a running protocol consisting of a 60-min downhill run on a treadmill at -10% incline and 65% of maximal heart rate. Quantitative mapping of MRI T2 was performed using the echo-modulation-curve algorithm before exercise, and at two time points: 1 h and 48 h after exercise. RESULTS: T2 values increased by 2%-4% following exercise in the primary mover muscles and exhibited further elevation of 1% after 48 h. For the antagonist muscles, T2 values increased only at the 48-h time point (2%-3%). Statistically significant decrease in the SD of T2 values was found following exercise for all tested muscles after 1 h (16%-21%), indicating a short-term decrease in the heterogeneity of the muscle tissue. CONCLUSION: MRI T2 relaxation time constitutes a useful quantitative marker for microstructural muscle damage, enabling region-specific identification for short-term and long-term systemic processes, and sensitive assessment of muscle recovery following exercise-induced muscle damage. The variability in T2 changes across different muscle groups can be attributed to their different role during downhill running, with immediate T2 elevation occurring in primary movers, followed by delayed elevation in both primary and antagonist muscle groups, presumably due to secondary damage caused by systemic processes.

Estimation of subvoxel fat infiltration in neurodegenerative muscle disorders using quantitative multi-T2 analysis.

MRI's T2 relaxation time is a valuable biomarker for neuromuscular disorders and muscle dystrophies. One of the hallmarks of these pathologies is the infiltration of adipose tissue and a loss of muscle volume. This leads to a mixture of two signal components, from fat and from water, to appear in each imaged voxel, each having a specific T2 relaxation time. In this proof-of-concept work, we present a technique that can separate the signals from water and from fat within each voxel, measure their separate T2 values, and calculate their relative fractions. The echo modulation curve (EMC) algorithm is a dictionary-based technique that offers accurate and reproducible mapping of T2 relaxation times. We present an extension of the EMC algorithm for estimating subvoxel fat and water fractions, alongside the T2 and proton-density values of each component. To facilitate data processing, calf and thigh anatomy were automatically segmented using a fully convolutional neural network and FSLeyes software. The preprocessing included creating two signal dictionaries, for water and for fat, using Bloch simulations of the prospective protocol. Postprocessing included voxelwise fitting for two components, by matching the experimental decay curve to a linear combination of the two simulated dictionaries. Subvoxel fat and water fractions and relaxation times were generated and used to calculate a new quantitative biomarker, termed viable muscle index, and reflecting disease severity. This biomarker indicates the fraction of remaining muscle out of the entire muscle region. The results were compared with those using the conventional Dixon technique, showing high agreement (R = 0.98, p < 0.001). It was concluded that the new extension of the EMC algorithm can be used to quantify abnormal fat infiltration as well as identify early inflammatory processes corresponding to elevation in the T2 value of the water (muscle) component. This new ability may improve the diagnostic accuracy of neuromuscular diseases, help stratification of patients according to disease severity, and offer an efficient tool for tracking disease progression.

Psychophysical Evaluation of Visual vs. Computer-Aided Detection of Brain Lesions on Magnetic Resonance Images.

BACKGROUND: Magnetic resonance imaging (MRI) diagnosis is usually performed by analyzing contrast-weighted images, where pathology is detected once it reached a certain visual threshold. Computer-aided diagnosis (CAD) has been proposed as a way for achieving higher sensitivity to early pathology. PURPOSE: To compare conventional (i.e., visual) MRI assessment of artificially generated multiple sclerosis (MS) lesions in the brain's white matter to CAD based on a deep neural network. STUDY TYPE: Prospective. POPULATION: A total of 25 neuroradiologists (15 males, age 39 ± 9, 9 ± 9.8 years of experience) independently assessed all synthetic lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T, T2 -weighted multi-echo spin-echo (MESE) sequence. ASSESSMENT: MS lesions of varying severity levels were artificially generated in healthy volunteer MRI scans by manipulating T2 values. Radiologists and a neural network were tasked with detecting these lesions in a series of 48 MR images. Sixteen images presented healthy anatomy and the rest contained a single lesion at eight increasing severity levels (6%, 9%, 12%, 15%, 18%, 21%, 25%, and 30% elevation in T2 ). True positive (TP) rates, false positive (FP) rates, and odds ratios (ORs) were compared between radiological diagnosis and CAD across the range lesion severity levels. STATISTICAL TESTS: Diagnostic performance of the two approaches was compared using z-tests on TP rates, FP rates, and the logarithm of ORs across severity levels. A P-value <0.05 was considered statistically significant. RESULTS: ORs of identifying pathology were significantly higher for CAD vis-à-vis visual inspection for all lesions' severity levels. For a 6% change in T2 value (lowest severity), radiologists' TP and FP rates were not significantly different (P = 0.12), while the corresponding CAD results remained statistically significant. DATA CONCLUSION: CAD is capable of detecting the presence or absence of more subtle lesions with greater precision than the representative group of 25 radiologists chosen in this study. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Mapping of magnetic resonance imaging's transverse relaxation time at low signal-to-noise ratio using Bloch simulations and principal component analysis image denoising.

High-resolution mapping of magnetic resonance imaging (MRI)'s transverse relaxation time (T2 ) can benefit many clinical applications by offering improved anatomic details, enhancing the ability to probe tissues' microarchitecture, and facilitating the identification of early pathology. Increasing spatial resolutions, however, decreases data's signal-to-noise ratio (SNR), particularly at clinical scan times. This impairs imaging quality, and the accuracy of subsequent radiological interpretation. Recently, principal component analysis (PCA) was employed for denoising diffusion-weighted MR images and was shown to be effective for improving parameter estimation in multiexponential relaxometry. This study combines the Marchenko-Pastur PCA (MP-PCA) signal model with the echo modulation curve (EMC) algorithm for denoising multiecho spin-echo (MESE) MRI data and improving the precision of EMC-generated single T2 relaxation maps. The denoising technique was validated on simulations, phantom scans, and in vivo brain and knee data. MESE scans were performed on a 3-T Siemens scanner. The acquired images were denoised using the MP-PCA algorithm and were then provided as input for the EMC T2 -fitting algorithm. Quantitative analysis of the denoising quality included comparing the standard deviation and coefficient of variation of T2 values, along with gold standard SNR estimation of the phantom scans. The presented denoising technique shows an increase in T2 maps' precision and SNR, while successfully preserving the morphological features of the tissue. Employing MP-PCA denoising as a preprocessing step decreases the noise-related variability of T2 maps produced by the EMC algorithm and thus increases their precision. The proposed method can be useful for a wide range of clinical applications by facilitating earlier detection of pathologies and improving the accuracy of patients' follow-up.

Quantification of Intra-Muscular Adipose Infiltration in Calf/Thigh MRI Using Fully and Weakly Supervised Semantic Segmentation.

Purpose: Infiltration of fat into lower limb muscles is one of the key markers for the severity of muscle pathologies. The level of fat infiltration varies in its severity across and within patients, and it is traditionally estimated using visual radiologic inspection. Precise quantification of the severity and spatial distribution of this pathological process requires accurate segmentation of lower limb anatomy into muscle and fat. Methods: Quantitative magnetic resonance imaging (qMRI) of the calf and thigh muscles is one of the most effective techniques for estimating pathological accumulation of intra-muscular adipose tissue (IMAT) in muscular dystrophies. In this work, we present a new deep learning (DL) network tool for automated and robust segmentation of lower limb anatomy that is based on the quantification of MRI's transverse (T2) relaxation time. The network was used to segment calf and thigh anatomies into viable muscle areas and IMAT using a weakly supervised learning process. A new disease biomarker was calculated, reflecting the level of abnormal fat infiltration and disease state. A biomarker was then applied on two patient populations suffering from dysferlinopathy and Charcot-Marie-Tooth (CMT) diseases. Results: Comparison of manual vs. automated segmentation of muscle anatomy, viable muscle areas, and intermuscular adipose tissue (IMAT) produced high Dice similarity coefficients (DSCs) of 96.4%, 91.7%, and 93.3%, respectively. Linear regression between the biomarker value calculated based on the ground truth segmentation and based on automatic segmentation produced high correlation coefficients of 97.7% and 95.9% for the dysferlinopathy and CMT patients, respectively. Conclusions: Using a combination of qMRI and DL-based segmentation, we present a new quantitative biomarker of disease severity. This biomarker is automatically calculated and, most importantly, provides a spatially global indication for the state of the disease across the entire thigh or calf.

Age Differences in Recovery Rate Following an Aerobic-Based Exercise Protocol Inducing Muscle Damage Among Amateur, Male Athletes.

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe. Methods: Twenty-eight Y (n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA (n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at -10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR. Results: During the DHR, HR was lower (p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant (p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated (p < 0.05, r range = -0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant (p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR (r range = -0.62 to (-0.74). Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol.

Correcting for imaging gradients-related bias of T2 relaxation times at high-resolution MRI.

PURPOSE: High-resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T2 relaxation times (qT2 ) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High-resolution T2 mapping, however, suffers from severe underestimation of T2 values due to molecular diffusion. This affects both single-echo and multi-echo spin echo (SSE and MESE), on top of the well-known contamination of MESE signals by stimulated echoes, and especially on high-field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners. METHODS: Diffusion bias due to imaging gradients was analyzed by quantifying the effective b-value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T2 -diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner. RESULTS: Underestimation of T2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T2 values from -33.5 ± 20.5% to -0.1 ± 3.6%. CONCLUSIONS: A new joint T2 -diffusion reconstruction algorithm is able to negate imaging gradient-related underestimation of T2 values, leading to reliable mapping of T2 values at high resolutions.

Determining the internal orientation, degree of ordering, and volume of elongated nanocavities by NMR: Application to studies of plant stem.

This study investigates the fibril nanostructure of fresh celery samples by modeling the anisotropic behavior of the transverse relaxation time (T2) in nuclear magnetic resonance (NMR). Experimental results are interpreted within the framework of a previously developed theory, which was successfully used to model the nanostructures of several biological tissues as a set of water filled nanocavities, hence explaining the anisotropy the T2 relaxation time in vivo. An important feature of this theory is to determine the degree of orientational ordering of the nanocavities, their characteristic volume, and their average direction with respect to the macroscopic sample. Results exhibit good agreement between theory and experimental data, which are, moreover, supported by optical microscopic resolution. The quantitative NMR approach presented herein can be potentially used to determine the internal ordering of biological tissues noninvasively.

Accelerated reconstruction of dictionary-based T2 relaxation maps based on dictionary compression and gradient descent search algorithms.

Background Quantitative T2-relaxation-based contrast maps have shown to be highly beneficial for clinical diagnosis and follow-up. The generation of quantitative maps, however, is impaired by long acquisition times, and time-consuming post-processing schemes. The EMC platform is a dictionary-based technique, which involves simulating theoretical signal curves for different physical and experimental values, followed by matching the experimentally acquired signals to the set simulated ones. Purpose Although the EMC technique has shown to produce accurate T2 maps, it involves computationally intensive post-processing procedures. In this work we present an approach for accelerating the reconstruction of T2 relaxation maps. Methods This work presents two alternative post-processing approaches for accelerating the reconstruction of EMC-based T2 relaxation maps. These are (a) Dictionary compression using principal component analysis (PCA) and (b) gradient-descent search algorithm. Additional acceleration was achieved by finding the optimal MATLAB C++ compiler. The utility of the two suggested approaches was examined by calculating the relative error, produced by each technique. Results Gradient descent method was in perfect agreement with the ground truth exhaustive search matching process. PCA based acceleration produced root mean square error (RMSE) of up to 4% compared to exhaustive matching process. Overall acceleration of x16 was achieved using gradient descent in addition to x7 acceleration by choosing the optimal MATLAB C++ compiler. Conclusions Postprocessing of EMC-based T2 relaxation maps can be accelerated without impairing the accuracy of the ensuing T2 values.

Data-driven algorithm for myelin water imaging: Probing subvoxel compartmentation based on identification of spatially global tissue features.

PURPOSE: Multicomponent analysis of MRI T2 relaxation time (mcT2 ) is commonly used for estimating myelin content by separating the signal at each voxel into its underlying distribution of T2 values. This voxel-based approach is challenging due to the large ambiguity in the multi-T2 space and the low SNR of MRI signals. Herein, we present a data-driven mcT2 analysis, which utilizes the statistical strength of identifying spatially global mcT2 motifs in white matter segments before deconvolving the local signal at each voxel. METHODS: Deconvolution is done using a tailored optimization scheme, which incorporates the global mcT2 motifs without additional prior assumptions regarding the number of microscopic components. The end results of this process are voxel-wise myelin water fraction maps. RESULTS: Validations are shown for computer-generated signals, uniquely designed subvoxel mcT2 phantoms, and in vivo human brain. Results demonstrated excellent fitting accuracy, both for the numerical and the physical mcT2 phantoms, exhibiting excellent agreement between calculated myelin water fraction and ground truth. Proof-of-concept in vivo validation is done by calculating myelin water fraction maps for white matter segments of the human brain. Interscan stability of myelin water fraction values was also estimated, showing good correlation between scans. CONCLUSION: We conclude that studying global tissue motifs prior to performing voxel-wise mcT2 analysis stabilizes the optimization scheme and efficiently overcomes the ambiguity in the T2 space. This new approach can improve myelin water imaging and the investigation of microstructural compartmentation in general.

T2 Mapping Values in Postmeniscectomy Knee Articular Cartilage after Running: Early Signs of Osteoarthritis?

Loading on the joints during running may have a deleterious effect on post-partial meniscectomy knee cartilage, leading to osteoarthritis. Utilizing T2-mapping measurements before and after running may enable the observation of changes in the articular cartilage of the postmeniscectomy knees compared with healthy knees. After medial partial meniscectomy, 12 volunteers underwent magnetic resonance imaging (MRI) of the both knees, before and immediately after 30 minutes of running. Quantitative assessment of articular cartilage was performed using a T2-mapping technique. In the medial compartment of the operated knees, significantly lower T2 values were found in anterior tibial plateau (pre- vs. postrun: 33.85 vs. 30.45 ms; p = 0.003) and central tibial plateau (33.33 vs. 30.63 ms; p = 0.007). Similar differences were found in lateral regions of central femur (post- vs. prerun: 35.86 vs. 40.35 ms; p = 0.015), posterior femur (34.89 vs. 37.73 ms; p = 0.001), and anterior tibia (24.66 vs. 28.70 ms, p = 0.0004). In lateral compartment, postrun values were significantly lower in operated compared with healthy knees, in central femur (34.89 vs. 37.59 ms; p = 0.043), posterior femoral (36.88 vs. 39.36 ms; p = 0.017), anterior tibia (24.66 vs. 30.20 ms; p = 0.009), and posterior tibia (28.84 vs. 33.17 ms; p = 0.006). No statistical difference was found while comparing postrun to prerun healthy knees. Lower T2 values were found in operated knees after 30 minutes of running. These changes were seen in medial and lateral compartments. We suspect that running may subject the articular cartilage to excessive loads in the post-partial meniscectomy knee, loads that in healthy knee do not cause any changes.

Post-Run T2 Mapping Changes in Knees of Adolescent Basketball Players.

OBJECTIVE: While articular cartilage defects are common incidental findings among adult athletes, the effect of running on the cartilage of adolescent athletes have rarely been assessed. This study aims to assess the variations in the articular cartilage of the knees in healthy adolescent basketball players using quantitative T2 MRI (magnetic resonance imaging). DESIGN: Fifteen adolescent basketball players were recruited (13.8 ± 0.5 years old). Girls were excluded to avoid potential gender-related confounding effects. Players underwent a pre-run MRI scan of both knees. All participants performed a 30-minute run on a treadmill. Within 15 minutes after completion of their run, players underwent a second, post-run MRI scan. Quantitative T2 maps were generated using the echo modulation curve (EMC) algorithm. Pre-run scans and post-run scans were compared using paired t test. RESULTS: Participants finished their 30-minute run with a mean running distance of 5.77 ± 0.42 km. Pre-run scans analysis found statistically significant (P < 0.05) changes in 3 regions of the knee lateral compartment representing the cartilaginous tissue. No differences were found in the knee medial compartment. Post-run analysis showed lower T2 values in the medial compartment compared to the pre-run scans in several weight-bearing regions: femoral condyle central (pre/post mean values of 33.9/32.2 ms, P = 0.020); femoral condyle posterior (38.1/36.8 ms, P = 0.038); and tibial plateau posterior (34.1/31.0 ms, P < 0.001). The lateral regions did not show any significant changes. CONCLUSIONS: Running leads to microstructural changes in the articular cartilage in several weight-bearing areas of the medial compartment, both in the femoral and the tibial cartilage.

Quantitative platform for accurate and reproducible assessment of transverse (T2 ) relaxation time.

MRI's transverse relaxation time (T2 ) is sensitive to tissues' composition and pathological state. While variations in T2 values can be used as clinical biomarkers, it is challenging to quantify this parameter in vivo due to the complexity of the MRI signal model, differences in protocol implementations, and hardware imperfections. Herein, we provide a detailed analysis of the echo modulation curve (EMC) platform, offering accurate and reproducible mapping of T2 values, from 2D multi-slice multi-echo spin-echo (MESE) protocols. Computer simulations of the full Bloch equations are used to generate an advanced signal model, which accounts for stimulated echoes and transmit field (B1+ ) inhomogeneities. In addition to quantifying T2 values, the EMC platform also provides proton density (PD) maps, and fat-water fraction maps. The algorithm's accuracy, reproducibility, and insensitivity to T1 values are validated on a phantom constructed by the National Institute of Standards and Technology and on in vivo human brains. EMC-derived T2 maps show excellent agreement with ground truth values for both in vitro and in vivo models. Quantitative values are accurate and stable across scan settings and for the physiological range of T2 values, while showing robustness to main field (B0 ) inhomogeneities, to variations in T1 relaxation time, and to magnetization transfer. Extension of the algorithm to two-component fitting yields accurate fat and water T2 maps along with their relative fractions, similar to a reference three-point Dixon technique. Overall, the EMC platform allows to generate accurate and stable T2 maps, with a full brain coverage using a standard MESE protocol and at feasible scan times. The utility of EMC-based T2 maps was demonstrated on several clinical applications, showing robustness to variations in other magnetic properties. The algorithm is available online as a full stand-alone package, including an intuitive graphical user interface.

Tissue Probability Based Registration of Diffusion-Weighted Magnetic Resonance Imaging.

BACKGROUND: Current registration methods for diffusion-MRI (dMRI) data mostly focus on white matter (WM) areas. Recently, dMRI has been employed for the characterization of gray matter (GM) microstructure, emphasizing the need for registration methods that consider all tissue types. PURPOSE: To develop a dMRI registration method based on GM, WM, and cerebrospinal fluid (CSF) tissue probability maps (TPMs). STUDY TYPE: Retrospective longitudinal study. POPULATION: Thirty-two healthy participants were scanned twice (legacy data), divided into a training-set (n = 16) and a test-set (n = 16), and 35 randomly-selected participants from the Human Connectome Project. FIELD STRENGTH/SEQUENCE: 3.0T, diffusion-weighted spin-echo echo-planar sequence; T1-weighted spoiled gradient-recalled echo (SPGR) sequence. ASSESSMENT: A joint segmentation-registration approach was implemented: Diffusion tensor imaging (DTI) maps were classified into TPMs using machine-learning approaches. The resulting GM, WM, and CSF probability maps were employed as features for image alignment. Validation was performed on the test dataset and the HCP dataset. Registration performance was compared with current mainstream registration tools. STATISTICAL TESTS: Classifiers used for segmentation were evaluated using leave-one-out cross-validation and scored using Dice-index. Registration success was evaluated by voxel-wise variance, normalized cross-correlation of registered DTI maps, intra- and inter-subject similarity of the registered TPMs, and region-based intra-subject similarity using an anatomical atlas. One-way ANOVAs were performed to compare between our method and other registration tools. RESULTS: The proposed method outperformed mainstream registration tools as indicated by lower voxel-wise variance of registered DTI maps (SD decrease of 10%) and higher similarity between registered TPMs within and across participants, for all tissue types (Dice increase of 0.1-0.2; P < 0.05). DATA CONCLUSION: A joint segmentation-registration approach based on diffusion-driven TPMs provides a more accurate registration of dMRI data, outperforming other registration tools. Our method offers a "translation" of diffusion data into structural information in the form of TPMs, allowing to directly align diffusion and structural images. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1.

A New Method for Cartilage Evaluation in Femoroacetabular Impingement Using Quantitative T2 Magnetic Resonance Imaging: Preliminary Validation against Arthroscopic Findings.

OBJECTIVE: The outcome of arthroscopic treatment for femoroacetabular impingement (FAI) depends on the preoperative status of the hip cartilage. Quantitative T2 can detect early biochemical cartilage changes, but its routine implementation is challenging. Furthermore, intrinsic T2 variability between patients makes it difficult to define a threshold to identify cartilage lesions. To address this, we propose a normalized T2-index as a new method to evaluate cartilage in FAI. DESIGN: We retrospectively analyzed magnetic resonance imaging (MRI) data of 18 FAI patients with arthroscopically confirmed cartilage defects. Cartilage T2 maps were reconstructed from multi-spin-echo 3-T data using the echo-modulation-curve (EMC) model-based technique. The central femoral cartilage, assumed healthy in early-stage FAI, was used as the normalization reference to define a T2-index. We investigated the ability of the T2-index to detect surgically confirmed cartilage lesions. RESULTS: The average T2-index was 1.14 ± 0.1 and 1.13 ± 0.1 for 2 separated segmentations. Using T2-index >1 as the threshold for damaged cartilage, accuracy was 88% and 100% for the 2 segmentations. We found moderate intraobserver repeatability, although separate segmentations yielded comparable accuracy. Damaged cartilage could not be identified using nonnormalized average T2 values. CONCLUSIONS: This preliminary study confirms the importance of normalizing T2 values to account for interpatient variability and suggests that the T2-index is a promising biomarker for the detection of cartilage lesions in FAI. Future work is needed to confirm that combining T2-index with morphologic MRI and other quantitative biomarkers could improve cartilage assessment in FAI.

Novel multimodal molecular imaging of Vitamin H (Biotin) transporter activity in the murine placenta.

Vitamin H (biotin) is delivered to the fetus transplacentally by an active biotin-transport mechanism and is critical for fetal development. Our objective was to develop a comprehensive MRI technique for mapping biotin transporter activity in the murine placenta. Visualization of transporter activity can employ MRI's unique T2*-dependent signal 'off-switch', which is triggered by transporter mediated aggregation of biotinylated contrast agent (b-BSA-Gd-DTPA). MRI data were collected from pregnant mice after administration of b-BSA-Gd-DTPA and analyzed using a new sub-voxel biophysical signal model. Validation experiments included competition with native biotin, comparative tests using PET, histology, and ICPMS. MRI signal was governed by binding, aggregation, and clearance of biotin (confirmed by histology). Signal dynamics reflected the placenta's perfusion pattern modulated by biotin transporter activity and trophoblast mediated retention, and were in congruence with a three-compartment sub-voxel model. Pre-saturation of the transporters with free biotin suppressed b-BSA-Gd-DTPA uptake. The results were confirmed by PET, histology and ICPMS. The presented MRI-based platform allows to track activity of essential molecular transporters in the placenta, reflecting a transporter-mediated uptake, followed by retention and aggregation, and recycling associated with the large b-BSA-Gd-DTPA conjugate. The presented DCE-MRI technique can furthermore be used to map and characterize microstructural compartmentation and transporter activity without exposing the fetus to contrast media.

Analysis of magnetization transfer (MT) influence on quantitative mapping of T2 relaxation time.

PURPOSE: Multi-echo spin-echo (MESE) protocol is the most effective tool for mapping T2 relaxation in vivo. Still, MESE extensive use of radiofrequency pulses causes magnetization transfer (MT)-related bias of the water signal, instigated by the presence of macromolecules (MMP). Here, we analyze the effects of MT on MESE signal, alongside their impact on quantitative T2 measurements. METHODS: Study used 3 models: in vitro urea phantom, ex vivo horse brain, and in vivo human brain. MT ratio (MTR) was measured between single-SE and MESE protocols under different scan settings including varying echo train lengths, number of slices, and inter-slice gap. MTR and T2 values were extracted for each model and protocol. RESULTS: MT interactions biased MESE signals, and in certain settings, the corresponding T2 values. T2 underestimation of up to 4.3% was found versus single-SE values in vitro and up to 13.8% ex vivo, correlating with the MMP content. T2 bias originated from intra-slice saturation of the MMP, rather than from indirect saturation in multi-slice acquisitions. MT-related signal attenuation was caused by slice crosstalk and/or partial T1 recovery, whereas smaller contribution was caused by MMP interactions. Inter-slice gap had a similar effect on in vivo MTR (21.2%), in comparison to increasing the number of slices (18.9%). CONCLUSIONS: MT influences MESE protocols either by uniformly attenuating the entire echo train or by cumulatively attenuating the signal along the train. Although both processes depend on scan settings and MMP content, only the latter will cause underestimation of T2 .

New rapid, accurate T2 quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients.

INTRODUCTION: Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). METHODS: The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2 values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation. RESULTS: Compared to conventional exponential T2 modeling, EMC fitting provided more accurate estimations of T2 with less variance across scans, MRI systems, and healthy individuals. Thalamic T2 was increased 8.5% in RRMS subjects (p < 0.001) and could be used to discriminate RRMS from healthy controls well (AUC = 0.913). Manual segmentation detected both statistically significant increases (corpus callosum & temporal stem) and decreases (posterior limb internal capsule) in T2 associated with RRMS diagnosis (all p < 0.05). In healthy controls, we also observed statistically significant T2 differences for different white and gray matter structures. CONCLUSIONS: The EMC algorithm precisely characterizes T2 values, and is able to detect subtle T2 changes in normal-appearing brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2 variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.