Achilles tendon ste-RS-EPI DTI can non-invasively detect the tendinopathy-induced changes to microstructural integrity, consistent with the disruption of collagen arrangement and increased cellularity. This study demonstrated the robustness and sensitivity of the proposed protocol in Achilles tendinopathy.

The growth of axons is an intricately regulated process involving intracellular signaling cascades and gene transcription. We had previously shown that the stimulus-dependent transcription factor, serum response factor (SRF), plays a critical role in regulating axon growth in the mammalian brain. However, the molecular mechanisms underlying SRF-dependent axon growth remains unknown. Here we report that SRF is phosphorylated and activated by GSK-3 to promote axon outgrowth in mouse hippocampal neurons. GSK-3 binds to and directly phosphorylates SRF on a highly conserved serine residue. This serine phosphorylation is necessary for SRF activity and for its interaction with MKL-family cofactors, MKL1 and MKL2, but not with TCF-family cofactor, ELK-1. Axonal growth deficits caused by GSK-3 inhibition could be rescued by expression of a constitutively active SRF. The SRF target gene and actin-binding protein, vinculin, is sufficient to overcome the axonal growth deficits of SRF-deficient and GSK-3-inhibited neurons. Furthermore, short hairpin RNAmediated knockdown of vinculin also attenuated axonal growth. Thus, our findings reveal a novel phosphorylation and activation of SRF by GSK-3 that is critical for SRF-dependent axon growth in mammalian central neurons.

ObjectivesThe aim of this study was to determine the feasibility and performance of a deep learning system used to create synthetic artificial intelligence‐based fat-suppressed magnetic resonance imaging (AFSMRI) scans of the knee.Materials and MethodsThis single-center study was approved by the institutional review board. Artificial intelligence‐based FS MRI scans were created from non-FS images using a deep learning system with a modified convolutional neural network–based U-Net that used a training set of 25,920 images and validation set of 16,416 images. Three musculoskeletal radiologists reviewed 88 knee MR studies in 2 sessions, the original (proton density [PD] + FSPD) and the synthetic (PD + AFSMRI). Readers recorded AFSMRI quality (diagnostic/nondiagnostic) and the presence or absence of meniscal, ligament, and tendon tears; cartilage defects; and bone marrow abnormalities. Contrast-to-noise rate measurements were made among subcutaneous fat, fluid, bone marrow, cartilage, and muscle. The original MRI sequences were used as the reference standard to determine the diagnostic performance of AFSMRI (combined with the original PD sequence). This is a fully balanced study design, where all readers read all images the same number of times, which allowed the determination of the interchangeability of the original and synthetic protocols. Descriptive statistics, intermethod agreement, interobserver concordance, and interchangeability tests were applied. A P value less than 0.01 was considered statistically significant for the likelihood ratio testing, and P value less than 0.05 for all other statistical analyses.ResultsArtificial intelligence‐based FS MRI quality was rated as diagnostic (98.9% [87/88] to 100% [88/88], all readers). Diagnostic performance (sensitivity/specificity) of the synthetic protocol was high, for tears of the menisci (91% [71/78], 86% [84/98]), cruciate ligaments (92% [12/13], 98% [160/163]), collateral ligaments (80% [16/20], 100% [156/156]), and tendons (90% [9/10], 100% [166/166]). For cartilage defects and bone marrow abnormalities, the synthetic protocol offered an overall sensitivity/specificity of 77% (170/221)/93% (287/307) and 76% (95/125)/90% (443/491), respectively. Intermethod agreement ranged from moderate to substantial for almost all evaluated structures (menisci, cruciate ligaments, collateral ligaments, and bone marrow abnormalities). No significant difference was observed between methods for all structural abnormalities by all readers (P > 0.05), except for cartilage assessment. Interobserver agreement ranged from moderate to substantial for almost all evaluated structures. Original and synthetic protocols were interchangeable for the diagnosis of all evaluated structures. There was no significant difference for the common exact match proportions for all combinations (P > 0.01). The conspicuity of all tissues assessed through contrast-to-noise rate was higher on AFSMRI than on original FSPD images (P < 0.05).ConclusionsArtificial intelligence‐based FS MRI (3D AFSMRI) is fe...

Background Existing ultrashort echo time magnetic resonance imaging (UTE MRI) methods require prohibitively long acquisition times (~ 20–40 min) to quantitatively assess the clinically relevant fast decay T2* component in ligaments and tendons. The purpose of this study was to evaluate the feasibility and clinical translatability of a novel abbreviated quantitative UTE MRI paradigm for monitoring graft remodeling after anterior cruciate ligament (ACL) reconstruction. Methods Eight patients who had Graftlink™ hamstring autograft reconstruction were recruited for this prospective study. A 3D double-echo UTE sequence at 3.0 Tesla was performed at 3- and 6-months post-surgery. An abbreviated UTE MRI paradigm was established based on numerical simulations and in vivo validation from healthy knees. This proposed approach was used to assess the T2* for fast decay component ($$ {T}_{2s}^{\ast } $$ T 2 s ∗ ) and bound water signal fraction (fbw) of ACL graft in regions of interest drawn by a radiologist. Results Compared to the conventional bi-exponential model, the abbreviated UTE MRI paradigm achieved low relative estimation bias for $$ {T}_{2s}^{\ast } $$ T 2 s ∗ and fbw over a range of clinically relevant values for ACL grafts. A decrease in $$ {T}_{2s}^{\ast } $$ T 2 s ∗ of the intra-articular graft was observed in 7 of the 8 ACL reconstruction patients from 3- to 6-months (− 0.11 ± 0.16 ms, P = 0.10). Increases in $$ {T}_{2s}^{\ast } $$ T 2 s ∗ and fbw from 3- to 6-months were observed in the tibial intra-bone graft ($$ {\varDelta T}_{2s}^{\ast } $$ ΔT 2 s ∗ : 0.19 ± 0.18 ms, P < 0.05; Δfbw: 4% ± 4%, P < 0.05). Lower $$ {T}_{2s}^{\ast } $$ T 2 s ∗ (− 0.09 ± 0.11 ms, P < 0.05) was observed at 3-months when comparing the intra-bone graft to the graft/bone interface in the femoral tunnel. The same comparisons at the 6-months also yielded relatively lower $$ {T}_{2s}^{\ast } $$ T 2 s ∗ (− 0.09 ± 0.12 ms, P < 0.05). Conclusion The proposed abbreviated 3D UTE MRI paradigm is capable of assessing the ACL graft remodeling process in a clinically translatable acquisition time. Longitudinal changes in $$ {T}_{2s}^{\ast } $$ T 2 s ∗ and fbw of the ACL graft were observed.

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1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1690-1699.

Background Patellar tendon (PT) microstructure integrity and microcirculation status play a crucial role in the progression of tendinopathy and tendon repair. Purpose To assess the feasibility and robustness of stimulated‐echo based diffusion‐weighted MRI with readout‐segmented echo‐planar imaging (ste‐RS‐EPI) for noninvasive assessment of microstructure and microcirculation of human PT. Study Type Prospective. Subjects Fifteen healthy volunteers. Field Strength/Sequence PT diffusion tensor imaging (DTI) and intravoxel incoherent motion (IVIM) were acquired with an ste‐RS‐EPI protocol on a 3T MRI scanner. Assessment Subjects were positioned with their PT at the magic angle. DTI‐derived parameters including axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) were estimated with b‐values of 0 and 800 s/mm2 and 12 diffusion directions. IVIM‐derived parameters, f p, D* × f p, V b, and D* × V b were assessed in the central‐third and the outer‐two thirds of the PT with b‐values of 0, 20, 30, 60, 80, 120, 200, 400, and 600 s/mm2 in three orthogonal directions. Statistical Tests Paired t‐tests were used to evaluate differences in IVIM parameters between the central‐third and outer‐two thirds regions of the patellar tendon. Paired t‐tests and within‐subject coefficient of variation were used to assess the intra‐ and intersession reproducibility of PT DTI and IVIM parameters. Results DTI parameters for healthy PT were 1.54 ± 0.09 × 10‐3 mm2/s, 1.01 ± 0.05 × 10‐3 mm2/s, 1.18 ± 0.06 × 10‐3 mm2/s, and 0.30 ± 0.04 for AD, RD, MD, and FA, respectively. Significantly higher (P < 0.05) IVIM parameters f p and D* × f p were observed in the outer‐two thirds (6.1% ± 2.4% and 95.2 ± 49.6, respectively) compared with the central‐third (3.8% ± 2.3% and 48.6 ± 35.2, respectively) of the PT. Data Conclusion Diffusion MRI of PT with an ste‐RS‐EPI protocol is clinically feasible. Both DTI‐ and IVIM‐derived parameters of the PT demonstrated good test–retest reproducibility and interrater reliability. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:780–790.

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