Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

BACKGROUND: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far. METHODS: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences. We identified a series of potential diagnostic MRI based characteristics useful for the diagnosis of VCP disease and validated them in 1089 MRIs from patients with other genetically confirmed NMDs. RESULTS: Fat replacement of at least one muscle was identified in all symptomatic patients. The most common finding was the existence of patchy areas of fat replacement. Although there was a wide variability of muscles affected, we observed a common pattern characterized by the involvement of periscapular, paraspinal, gluteal and quadriceps muscles. STIR signal was enhanced in 67% of the patients, either in the muscle itself or in the surrounding fascia. We identified 10 diagnostic characteristics based on the pattern identified that allowed us to distinguish VCP disease from other neuromuscular diseases with high accuracy. CONCLUSIONS: Patients with mutations in the VCP gene had common features on muscle MRI that are helpful for diagnosis purposes, including the presence of patchy fat replacement and a prominent involvement of the periscapular, paraspinal, abdominal and thigh muscles.

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

BACKGROUND: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. METHODS: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. RESULTS: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. CONCLUSION: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.

3D CAIPIRINHA SPACE versus standard 2D TSE for routine knee MRI: a large-scale interchangeability study.

OBJECTIVE: To perform a large-scale interchangeability study comparing 3D controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) TSE with standard 2D TSE for knee MRI. METHODS: In this prospective study, 250 patients underwent 3 T knee MRI, including a multicontrast 3D CAIPIRINHA SPACE TSE (9:26 min) and a standard 2D TSE protocol (12:14 min). Thirty-three (13%) patients had previous anterior cruciate ligament and/or meniscus surgery. Two radiologists assessed MRIs for image quality and identified pathologies of menisci, ligaments, and cartilage by using a 4-point Likert scale according to the level of diagnostic confidence. Interchangeability of the protocols was tested under the same-reader scenario using a bootstrap percentile confidence interval. Interreader reliability and intermethod concordance were also evaluated. RESULTS: Despite higher image quality and diagnostic confidence for standard 2D TSE compared to 3D CAIPIRINHA SPACE TSE, the protocols were found interchangeable for diagnosing knee abnormalities, except for patellar (6.8% difference; 95% CI: 4.0, 9.6) and trochlear (3.6% difference; 95% CI: 0.8, 6.6) cartilage defects. The interreader reliability was substantial to almost perfect for 2D and 3D MRI (range κ, 0.785-1 and κ, 0.725-0.964, respectively). Intermethod concordance was almost perfect for all diagnoses (range κ, 0.817-0.986). CONCLUSION: Multicontrast 3D CAIPIRINHA SPACE TSE and standard 2D TSE protocols perform interchangeably for diagnosing knee abnormalities, except for patellofemoral cartilage defects. Despite the radiologist's preference for 2D TSE imaging, a pursuit towards time-saving 3D TSE knee MRI is justified for routine practice. KEY POINTS: • Multicontrast 3D CAIPIRINHA SPACE and standard 2D TSE protocols perform interchangeably for diagnosing knee abnormalities, except for patellofemoral cartilage defects. • Radiologists are more confident in diagnosing knee abnormalities on 2D TSE than on 3D CAIPIRINHA SPACE TSE MRI. • Despite the radiologist's preference for 2D TSE, a pursuit towards accelerated 3D TSE knee MRI is justified for routine practice.

Super-Resolution Magnetic Resonance Imaging of the Knee Using 2-Dimensional Turbo Spin Echo Imaging.

OBJECTIVES: The purpose of this study was to assess the technical feasibility of 3-dimensional (3D) super-resolution reconstruction (SRR) of 2D turbo spin echo (TSE) knee magnetic resonance imaging (MRI) and to compare its image quality with conventional 3D TSE sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) MRI. MATERIALS AND METHODS: Super-resolution reconstruction 2D TSE MRI and 3D TSE SPACE images were acquired from a phantom and from the knee of 22 subjects (8 healthy volunteers and 14 patients) using a clinical 3-T scanner. For SRR, 7 anisotropic 2D TSE stacks (voxel size, 0.5 × 0.5 × 2.0 mm; scan time per stack, 1 minute 55 seconds; total scan time, 13 minutes 25 seconds) were acquired with the slice stack rotated around the phase-encoding axis. Super-resolution reconstruction was performed at an isotropic high-resolution grid with a voxel size of 0.5 × 0.5 × 0.5 mm. Direct isotropic 3D image acquisition was performed with the conventional SPACE sequence (voxel size, 0.5 × 0.5 × 0.5 mm; scan time, 12 minutes 42 seconds). For quantitative evaluation, perceptual blur metrics and edge response functions were obtained in the phantom image, and signal-to-noise and contrast-to-noise ratios were measured in the images from the healthy volunteers. Images were qualitatively evaluated by 2 independent radiologists in terms of overall image quality, edge blurring, anatomic visibility, and diagnostic confidence to assess normal and abnormal knee structures. Nonparametric statistical analysis was performed, and significance was defined for P values less than 0.05. RESULTS: In the phantom, perceptual blur metrics and edge response functions demonstrated a clear improvement in spatial resolution for SRR compared with conventional 3D SPACE. In healthy subjects, signal-to-noise and contrast-to-noise ratios in clinically relevant structures were not significantly different between SRR and 3D SPACE. Super-resolution reconstruction provided better overall image quality and less edge blurring than conventional 3D SPACE, yet the perceived image contrast was better for 3D SPACE. Super-resolution reconstruction received significantly better visibility scores for the menisci, whereas the visibility of cartilage was significantly higher for 3D SPACE. Ligaments had high visibility on both SRR and 3D SPACE images. The diagnostic confidence for assessing menisci was significantly higher for SRR than for conventional 3D SPACE, whereas there were no significant differences between SRR and 3D SPACE for cartilage and ligaments. The interreader agreement for assessing menisci was substantial with 3D SPACE and almost perfect with SRR, and the agreement for assessing cartilage was almost perfect with 3D SPACE and moderate with SRR. CONCLUSIONS: We demonstrate the technical feasibility of SRR for high-resolution isotropic knee MRI. Our SRR results show superior image quality in terms of edge blurring, but lower image contrast and fluid brightness when compared with conventional 3D SPACE acquisitions. Further contrast optimization and shortening of the acquisition time with state-of-the-art acceleration techniques are necessary for future clinical validation of SRR knee MRI.

Assessment of Anterolateral Complex Injuries by Magnetic Resonance Imaging in Patients With Acute Rupture of the Anterior Cruciate Ligament.

PURPOSE: To assess anterolateral complex (ALC) injuries in patients with acute anterior cruciate ligament (ACL) rupture on magnetic resonance imaging (MRI). METHODS: Patients with acute ACL rupture who underwent ACL surgery between 2015 and 2017 and underwent MRI within 6 weeks of the initial trauma were included. Two radiologists assessed magnetic resonance images retrospectively for the status of the ALC, including the iliotibial band (ITB), Kaplan fibers, and anterolateral ligament (ALL), as follows: grade 0, normal; grade 1, periligamentous edema; grade 2, partial tear; and grade 3, complete tear. The findings were analyzed using the Friedman test and weighted κ values. RESULTS: Sixty-nine MRI scans were reviewed. Of the 69 patients, 51% had associated injuries to the ITB (grade 1, n = 31; grade 2, n = 4), 33% had associated injuries to the Kaplan fibers (grade 1, n = 21; grade 2, n = 2), and 57% had associated injuries to the ALL (grade 1, n = 12; grade 2, n = 22; grade 3, n = 5). We found a significant difference in the frequency and grading between ITB, Kaplan fiber, and ALL injuries (P ≤ .032). Inter-reader agreement for assessing the ALC on MRI was almost perfect (κ ≥ 0.922). CONCLUSIONS: On the basis of MRI analysis, ALL injuries were found with varying degrees of severity and intensity with noted injuries to associated surrounding fibers in patients with acute ACL rupture. LEVEL OF EVIDENCE: Level IV, case series.

Diffusion tensor imaging of the anterior cruciate ligament graft.

PURPOSE: A great need exists for objective biomarkers to assess graft healing following ACL reconstruction to guide the time of return to sports. The purpose of this study was to evaluate the feasibility and reliability of diffusion tensor imaging (DTI) to delineate the anterior cruciate ligament (ACL) graft and to investigate its diffusion properties using a clinical 3T scanner. MATERIALS AND METHODS: DTI of the knee (b = 0, 400, and 800 s/mm2 , 10 diffusion directions, repeated 16 times for a total of 336 diffusion-weighted volumes) was performed at 3T in 17 patients between 3 and 7 months (mean, 4 months) following ACL reconstruction. Tractography was performed by two independent observers to delineate the ACL graft. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated within the graft. Interrater reliability was assessed using the intraclass correlation coefficient (ICC) and the scan-rescan reproducibility was evaluated based on the percentage coefficient of variance (%CV) across 20 repetition bootknife samples. RESULTS: In all subjects, tractography of the ACL graft was feasible. Quantitative evaluation of the diffusion properties of the ACL graft yielded the following mean ± SD values: FA = 0.23 ± 0.04; MD = 1.30 ± 0.11 × 10-3 mm2 /s; AD = 1.61 ± 0.12 × 10-3 mm2 /s, and RD = 1.15 ± 0.11 × 10-3 mm2 /s. Interrater reliability for the DTI parameters was excellent (ICC = 0.91-0.98). Mean %CVs for FA, MD, AD, and RD were 4.6%, 3.5%, 3.7%, and 4.4%, respectively. CONCLUSION: We demonstrated the feasibility and reliability of DTI for the visualization and quantitative evaluation of the ACL graft at 3T. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1423-1432.

The Anterolateral Ligament of the Knee: What the Radiologist Needs to Know.

The anterolateral ligament (ALL) was recently identified as a distinct component of the anterolateral capsule of the human knee joint with consistent origin and insertion sites. Biomechanical studies revealed that the current association between the pivot shift and an injured anterior cruciate ligament (ACL) should be loosened and that the rotational component of the pivot shift is significantly affected by the ALL. This may change the clinical approach toward ACL-injured patients presenting with anterolateral rotatory instability (ALRI), the most common instability pattern after ACL rupture. Radiologists should be aware of the importance of the ALL to ACL injuries. They should not overlook pathology of the anterolateral knee structures, including the ALL, when reviewing MR images of the ACL-deficient knee. In this article, the current knowledge regarding the anatomy, biomechanical function, and imaging appearance of the ALL of the knee is discussed with emphasis on the clinical implications of these findings.

Imaging of the Postoperative Anterior Cruciate Ligament: Emphasis on New Surgical and Imaging Methods.

The aim of anterior cruciate ligament (ACL) reconstruction is to restore normal function of the knee, but unfortunately abnormal kinematics and a predisposition to knee osteoarthritis occur in a significant percentage of patients. So there is an ongoing need to improve treatment options and long-term outcome of patients with a ruptured ACL. With the recent advancements in the field of ACL tissue engineering, the focus of treatment for ACL injuries is changing from resection and reconstruction toward repair and regeneration. Several new ACL repair methods were recently introduced as an alternative to traditional ACL reconstructive procedures. Radiologists must become familiar with these new surgical methods to interpret their appearance correctly on postoperative imaging studies. This article provides an overview of the latest advancements in ACL surgical methods and discusses the role of imaging to assess the postoperative ACL including both standard and advanced imaging methods.

Anterolateral ligament abnormalities in patients with acute anterior cruciate ligament rupture are associated with lateral meniscal and osseous injuries.

OBJECTIVE: To determine the frequency of anterolateral ligament (ALL) injury in patients with acute anterior cruciate ligament (ACL) rupture and to analyse its associated injury patterns. METHODS: Ninety patients with acute ACL rupture for which MRI was obtained within 8 weeks after the initial trauma were retrospectively identified. Two radiologists assessed the status of the ALL on MRI by consensus. The presence or absence of an ALL abnormality was compared with the existence of medial and lateral meniscal tears diagnosed during arthroscopy. Associated collateral ligament and osseous injuries were documented with MRI. RESULTS: Forty-one of 90 knees (46 %) demonstrated ALL abnormalities on MRI. Of 49 knees with intact ALL, 15 (31 %) had a torn lateral meniscus as compared to 25 torn lateral menisci in 41 knees (61 %) with abnormal ALL (p = 0.008). Collateral ligament (p ≤ 0.05) and osseous injuries (p = 0.0037) were more frequent and severe in ALL-injured as compared with ALL-intact knees. CONCLUSION: ALL injuries are fairly common in patients with acute ACL rupture and are statistically significantly associated with lateral meniscal, collateral ligament and osseous injuries. KEY POINTS: • ALL injuries are fairly common in patients with acute ACL rupture. • ALL injuries are highly associated with lateral meniscal and osseous injuries. • MRI assessment of ACL-injured knees should include evaluation of the ALL.

Traumatic myelopathy: current concepts in imaging.

Traumatic myelopathy is a frequent complication after spinal trauma. The prognosis is often very poor, and the condition has important socioeconomic consequences. Knowledge of the epidemiology and imaging features is mandatory to ensure correct diagnosis and timely intervention. Imaging studies play an increasing role in the diagnosis and follow-up of this condition. Computed tomography remains the first-line investigation whenever spinal cord injury is suspected. It may indicate the presence of spinal cord lesions by visualizing vertebral lesions, but it cannot assess the spinal cord itself. Magnetic resonance imaging (MRI) can depict possible spinal cord edema, hemorrhage, or transection, and it is essential in diagnosing and predicting the outcome of spinal cord injury. Follow-up should also be performed with MRI to evaluate long-term intramedullary changes. Diffusion-weighted imaging and diffusion tensor imaging are promising new techniques that allow very early detection of spinal cord injury by measuring the diffusion within the spinal cord, thereby providing information on white matter integrity. However, technical limitations of these new techniques prompt further investigation to improve specificity.

Diagnostic performance of 3D SPACE for comprehensive knee joint assessment at 3 T.

OBJECTIVE: To assess the diagnostic performance of 3D sampling perfection with application-optimised contrasts using variable flip-angle evolution (SPACE) turbo spin-echo (TSE) sequences compared to 2D TSE for comprehensive knee assessment at 3 T. METHODS: From January to July 2011, isotropic 3D SPACE was added to a 2D knee protocol at 3 T. Forty patients underwent subsequent arthroscopy. Three readers independently assessed MR images for meniscus, anterior cruciate ligament (ACL) and cartilage lesions. Readers 1 and 2 evaluated 3D and 2D data at separate sittings; reader 3 interpreted the complete exam including 3D and 2D sequences. Accuracies were calculated using arthroscopy as reference standard. McNemar's test (p < 0.05) was used to compare 3D and 2D techniques. RESULTS: The highest diagnostic yield was obtained by reader 3 (accuracies ≥88 %). For the medial meniscus, readers performed better with the 2D technique than with 3D SPACE (accuracies 85-88 % vs. 78-80 %, respectively) (p > 0.05). For the lateral meniscus and ACL, 3D and 2D techniques had similar performance (accuracies ≥93 %). For cartilage lesions, 3D SPACE had significantly lower specificity (p = 0.0156) than the 2D protocol for one reader. CONCLUSION: The conventional 2D TSE acquisition is more reliable than 3D SPACE for comprehensive assessment of the knee at 3.0 T. MAIN MESSAGES: • 3D SPACE is a valuable component of a knee MR protocol at 3 T. • 3D SPACE cannot be used as a single sequence in the MR evaluation of the knee at 3 T. • Knee MR protocols at 3 T should include both 2D and 3D TSE sequences.

Partial tear of the anterior cruciate ligament of the knee: injury patterns on MR imaging.

PURPOSE: To describe rupture patterns of partial anterior cruciate ligament (ACL) tears on magnetic resonance (MR) imaging. METHODS: MR images of 51 patients with a surgically confirmed partial ACL tear were retrospectively and independently interpreted by 2 experienced, blinded radiologists. Using previously described MR criteria, ACLs were categorized as follows: complete tear, partial tear, isolated anteromedial or posterolateral bundle tear, mucoid degeneration or normal ACL. MR interpretations were compared with the arthroscopic results as the standard of reference. Inter- and intraobserver agreements were determined using kappa (к) coefficients. RESULTS: On MR imaging, ACL injuries were categorized as complete tears (16-23%), partial tears (20-47%), mucoid degeneration (12-27%) or normal ACLs (18-23%). Isolated ACL bundle tears were diagnosed on MR in 6% of our patients. Accuracy of MR for the diagnosis of partial ACL tears was 25-53%. Interobserver agreement was moderate (к = 0.48-0.56). Intraobserver agreement was good (к = 0.72-0.76). CONCLUSION: MR diagnosis of a partial ACL tear is difficult because various tear patterns may be seen. Many partial tears demonstrate MR features that are indistinguishable from complete ACL tear, mucoid ACL degeneration or normal ACL. An isolated ACL bundle tear is infrequently detected on MR images.