Transient microstructural brain anomalies and epileptiform discharges in mice defective for epilepsy and language-related NMDA receptor subunit gene Grin2a

Wiley Periodicals, Inc. © 2018 International League Against Epilepsy Objective: The epilepsy-aphasia spectrum (EAS) is a heterogeneous group of age-dependent childhood disorders characterized by sleep-activated discharges associated with infrequent seizures and language, cognitive, and behavioral deficits. Defects in the GRIN2A gene, encoding a subunit of glutamate-gated N-methyl-d-aspartate (NMDA) receptors, represent the most important cause of EAS identified so far. Neocortical or thalamic lesions were detected in a subset of severe EAS disorders, and more subtle anomalies were reported in patients with so-called “benign” phenotypes. However, whether brain structural alterations exist in the context of GRIN2A defects is unknown. Methods: Magnetic resonance diffusion tensor imaging (MR-DTI) was used to perform longitudinal analysis of the brain at 3 developmental timepoints in living mice genetically knocked out (KO) for Grin2a. In addition, electroencephalography (EEG) was recorded using multisite extracellular electrodes to characterize the neocortical activity in vivo. Results: Microstructural alterations were detected in the neocortex, the corpus callosum, the hippocampus, and the thalamus of Grin2a KO mice. Most MR-DTI alterations were detected at a specific developmental stage when mice were aged 30 days, but not at earlier (15 days) or later (2 months) ages. EEG analysis detected epileptiform discharges in Grin2a KO mice in the third postnatal week. Significance: Grin2a KO mice replicated several anomalies found in patients with EAS disorders. Transient structural alterations detected by MR-DTI recalled the age-dependent course of EAS disorders, which in humans start during childhood and show variable outcome at the onset of adolescence. Together with the epileptiform discharges detected in young Grin2a KO mice, our data suggested the existence of early anomalies in the maturation of the neocortical and thalamocortical systems. Whereas the possible relationship of those anomalies with sleep warrants further investigations, our data suggest that Grin2a KO mice may serve as an animal model to study the neuronal mechanisms of EAS disorders and to design new therapeutic strategies

Quantitative analysis of tibial subchondral bone:Texture analysis outperforms conventional trabecular microarchitecture analysis

BACKGROUND: The aim of this study was to compare two different methods of quantitative assessment of tibial subchondral bone in osteoarthritis (OA): statistical texture analysis (sTA) and trabecular microarchitecture analysis (tMA).   METHODS: Asymptomatic controls aged 20-30 (n = 10), patients aged 40-50 with chronic knee pain but without established OA (n = 10) and patients aged 55-85 with advanced OA scheduled for knee replacement (n = 10) underwent knee MR imaging at 3 Tesla with a three-dimensional gradient echo sequence to allow sTA and tMA. tMA and sTA features were calculated using region of interest creation in the medial (MT) and lateral (LT) tibial subchondral bone. Features were compared between groups using one-way analysis of variance. The two most discriminating tMA and sTA features were used to construct exploratory discriminant functions to assess the ability of the two methods to classify participants.   RESULTS: No tMA features were significantly different between groups at either MT or LT. 17/20 and 11/20 sTA features were significantly different between groups at the MT/LT, respectively (P < 0.001). Discriminant functions created using tMA features classified 12/30 participants correctly (40% accuracy; 95% confidence interval [CI], 22-58%) based on MT data and 9/30 correctly (30%,; 95% CI, 14-46) based on LT data. Discriminant functions using sTA features classified 16/30 participants correctly (53%; 95% CI, 35-71) based on MT data and 14/30 correctly (47%; 95% CI, 29-65) based on LT data.   CONCLUSION: sTA features showed more significant differences between the three study groups and improved classification accuracy compared with tMA features. J. Magn. Reson. Imaging 2015

Isotropic three-dimensional T₂ mapping of knee cartilage: Development and validation.

1) To implement a higher-resolution isotropic 3D T &lt;sub&gt;2&lt;/sub&gt; mapping technique that uses sequential T &lt;sub&gt;2&lt;/sub&gt; -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T &lt;sub&gt;2&lt;/sub&gt; estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T &lt;sub&gt;2&lt;/sub&gt; values were compared with those from a clinical standard 2D multislice multiecho (MSME) T &lt;sub&gt;2&lt;/sub&gt; mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R &lt;sup&gt;2&lt;/sup&gt; ≥ 0.99). Repeated measurements of cartilage T &lt;sub&gt;2&lt;/sub&gt; values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T &lt;sub&gt;2&lt;/sub&gt; values (P &lt; 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T &lt;sub&gt;2&lt;/sub&gt; mapping in healthy volunteers, and significantly higher in OA (P = 0.01). This study successfully demonstrated that high-resolution isotropic 3D T &lt;sub&gt;2&lt;/sub&gt; mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T &lt;sub&gt;2&lt;/sub&gt; quantification in any plane of interest. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371

The Founder’s Lecture 2009: advances in imaging of osteoporosis and osteoarthritis

The objective of this review article is to provide an update on new developments in imaging of osteoporosis and osteoarthritis over the past three decades. A literature review is presented that summarizes the highlights in the development of bone mineral density measurements, bone structure imaging, and vertebral fracture assessment in osteoporosis as well as MR-based semiquantitative assessment of osteoarthritis and quantitative cartilage matrix imaging. This review focuses on techniques that have impacted patient management and therapeutic decision making or that potentially will affect patient care in the near future. Results of pertinent studies are presented and used for illustration. In summary, novel developments have significantly impacted imaging of osteoporosis and osteoarthritis over the past three decades

Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon

PURPOSE: To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. MATERIAL AND METHODS: Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. RESULTS: No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p &lt; 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. CONCLUSION: T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience