Project description:Enthesitis, inflammation at the attachment sites of tendons, ligaments, fascia, and joint capsules to bones plays a critical role in the pathogenesis of spondyloarthritis (SpA), including psoriatic arthritis (PsA). Magnetic resonance imaging (MRI) has aided in a better understanding of pathophysiology, early diagnosis, prognostication, therapeutic outcomes, and follow up of enthesitis. The concept of enthesitis as a focal insertional pathology has transformed over the past decade, with the help of MRI, to a more widespread entity involving both bone and surrounding soft tissues. The utility of MRI in the differential diagnosis of suspected enthesitis has recently been explored. With the emergence of the treat-to-target concept, and a domain-based approach in the management of SpA, objective and sensitive monitoring of response to targeted therapy becomes prudent. Properties like high sensitivity, ability to image intra-osseous pathology along with surrounding structures exemplify the utility of MRI technology. Considering the lack of a comprehensive, validated MRI score the Outcome Measures in Rheumatology (OMERACT) MRI in Arthritis Working Group, informed by a systematic literature review, developed the first international, consensus-based MRI-scoring system, combined with MRI definitions of pathologies for enthesitis in patients with spondyloarthritis (SpA) and PsA. An atlas with representative images of each grade of the scoring system was subsequently developed by the group to aid readers interested in using the heel enthesitis MRI scoring system (HEMRIS). The HEMRIS can find utility in clinical trials targeting enthesitis as the primary outcome. MRI also finds value for global assessment of the total burden of enthesitis. The concept of whole-body MRI (WBMRI), enabling visualization of entheses throughout the body using a single image is relatively new. The MRI whole-body score for inflammation in peripheral joints and entheses (MRI-WIPE) is a promising scoring system, which is undergoing further testing in clinical trials and longitudinal cohorts evaluating global measures of inflammation at entheses. This review discusses the role of MRI in diagnosis and monitoring of enthesitis in SpA and PsA, along with recent advances in the field, based on published literature.
Project description:IntroductionFacioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. Increasing knowledge of the pathophysiology of FSHD has stimulated interest in developing biomarkers of disease severity.MethodsTwo groups of MRI scans were analyzed: whole-body scans from 13 subjects with FSHD; and upper and lower extremity scans from 34 subjects with FSHD who participated in the MYO-029 clinical trial. Muscles were scored for fat infiltration and edema-like changes. Fat infiltration scores were compared with muscle strength and function.ResultsThe analysis revealed a distinctive pattern of both frequent muscle involvement and frequent sparing in FSHD. Averaged fat infiltration scores for muscle groups in the legs correlated with quantitative muscle strength and 10-meter walk times.ConclusionsAdvances in MRI technology allow for acquisition of rapid, high-quality, whole-body imaging in diffuse muscle disease. This technique offers a promising disease biomarker in FSHD and other muscle diseases.
Project description:Enthesitis is a common clinical feature of spondyloarthritis (SpA). For reliable assessment of enthesitis the Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) was developed. The aims of this study were to evaluate changes in HEMRIS over time and to evaluate whether these changes correlated with changes in clinical parameters. This single-center observational study followed patients with SpA and psoriasis, regardless of presence of clinical heel enthesitis, for two years. Clinical evaluation and ankle MRIs were performed annually. Changes in HEMRIS were compared at one-year intervals using the Wilcoxon signed-rank test. The association between changes in the HEMRIS with changes in clinical parameters was evaluated using Spearman's correlation coefficient. In total, 38 patients were included. An increase in the inflammatory and structural HEMRIS was identified in, respectively, 12 (17.9%) and 4 (6.0%) patients in one-year intervals. We found non-significant changes in the HEMRIS during longitudinal follow-up. Changes in the HEMRIS did not correlate with changes in local or general disease activity. Our results show that MRI-findings of enthesitis assessed with HEMRIS changed in a small number of patients in a one-year interval in an observational setting. Changes in HEMRIS were not associated with changes in clinical disease activity.
Project description:Objective: To compare joint inflammation seen by whole-body magnetic resonance imaging (WBMRI), with "whole-body" ultrasound and clinical assessments, in patients with active rheumatoid arthritis (RA) before and during tumor necrosis factor-inhibitor (TNF-I, adalimumab) treatment. Methods: In 18 patients with RA, clinical assessment for joint tenderness and swelling, WBMRI, and ultrasound were obtained at baseline and week 16. Wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP), elbow (except for WBMRI), shoulder, knee, ankle, and metatarsophalangeal joints were examined. Joint inflammation was defined by WBMRI as the presence of synovitis and/or osteitis and by ultrasound as gray-scale synovial hypertrophy grade >2 and/or color Doppler grade >1. On patient level, agreement was assessed by Spearman correlation coefficients (rho) for sum scores for 28 joints (i.e., wrists, MCPs, PIPs, elbows, shoulders, and knees) between clinical examination (DAS28CRP), ultrasound (US28), and WBMRI (WBMRI26; elbows not included). On joint level, agreement on inflammation between WBMRI, ultrasound, and clinical findings was calculated with Cohen's kappa (κ). Results: At patient level, WBMRI26 and US28 sum scores showed good correlation (rho = 0.72; p < 0.01) at baseline, but not at follow-up (rho = 0.25; p = 0.41). At joint level, moderate agreement was seen for hand joints (κ = 0.41-0.44); for other joints κ <0.40. No correlation with DAS28CRP was seen. No statistically significant correlations were observed between changes in WBMRI26, US28, and DAS28CRP during treatment. Conclusions: WBMRI and ultrasound joint inflammation sum scores at patient level showed good agreement in clinically active RA patients before TNF-I initiation, whereas agreement was poorer at joint level, and after treatment.
Project description:Objective To determine the distribution and diagnostic value of peripheral enthesitis detected by whole-body MRI (WBMRI) in axial spondyloarthritis (axSpA) diagnosis, and to determine the value of the peripheral enthesitis score in axSpA assessment. Methods Sixty axSpA patients [mean age of 33.2 (24.8–40.6) years] and 50 controls with chronic low back pain (LBP) [mean age of 34.7 (28.3–41.1) years] were enrolled. The gold standard was physician’s comprehensive diagnosis based on current classification criteria and physical examination. All subjects underwent WBMRI, and 47 peripheral entheses were assessed for each patient with scores of 0–188. Results WBMRI identified 155 enthesitis sites in 78.3% (n = 47) patients with axSpA. Meanwhile, 23 enthesitis sites were identified in 32% (n = 16) controls. The pelvis had the maximum number of enthesitis sites (52, 33.5%) in axSpA patients. Pelvic and anterior chest wall enthesitis had the highest sensitivity (51.67%) and specificity (100%) in axSpA diagnosis, respectively. There were different manifestations of enthesitis subtypes between axSpA patients and the control group. Osteitis was more present than soft-tissue inflammation in axSpA patients. The AUC for the number of enthesitis sites was 0.819 (95% CI 0.739–0.899), and that for the enthesitis score was 0.833 (95% CI 0.755–0.910), indicating statistically significant differences (P = 0.025). Based on the Youden index and clinical need, three enthesitis sites (sensitivity of 53.33, specificity of 98, and Youden index of 0.51) and enthesitis score (sensitivity of 58.33, specificity of 98, and Youden index of 0.56) may have the greatest value for axSpA diagnosis. Conclusion The distribution of peripheral enthesitis can be adequately assessed by whole-body MRI, which could help diagnose axial spondyloarthritis. The enthesitis score may provide a more accurate assessment and diagnostic tool in axSpA compared with enthesitis site counting.
Project description:Genome wide DNA methylation profiling of normal and tumour prostate samples. The Illumina Infinium MethylationEPIC Human DNA methylation oligonucleotide beads was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Comparative assessment was carried out.
Project description:ImportanceMagnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.ObjectiveTo determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance.Design, setting, and participantsThis phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up.InterventionsPatients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions.Main outcomes and measuresThe primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes.ResultsBetween May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month.Conclusions and relevanceIn this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist.Trial registrationClinicalTrials.gov Identifier: NCT04384770.
Project description:ObjectiveSince the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement.MethodsEleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4.ResultsPatients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD.ConclusionIn the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.
Project description:Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.
Project description:ObjectiveWe aimed to evaluate the contribution of simultaneous recording of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in the diagnosis of epilepsy syndrome, localization of the epileptogenic zone (EZ), and decision-making regarding surgical treatment.MethodsWe performed a retrospective study to evaluate patients with focal epilepsy who underwent EEG-fMRI. Two evaluators assessed epilepsy syndrome, presumed focus, and surgical candidacy and defined confidence levels. They assessed these clinical characteristics first without EEG-fMRI and then including EEG-fMRI to assess how the results of EEG-fMRI changed the evaluations. We also determined how the clinical evaluation was affected by the concordance level between the blood oxygen level-dependent (BOLD) response and the presumed focus location, and by the confidence level of the BOLD response itself based on the t-value of the primary and secondary clusters.ResultsFifty-one scans from 48 patients were included. The BOLD map affected 66.7% of the evaluations by altering evaluation items (epilepsy syndrome, presumed focus, or surgical candidacy) or their confidence levels. EEG-fMRI results increased the confidence levels of epilepsy syndrome, presumed focus, or surgical candidacy in 47.1% of patients but reduced clinical confidence in these features in 11.8%. More specifically, the confidence levels increased for epilepsy syndrome in 28.5%, identification of presumed focus in 33.9%, and determination of surgical candidacy in 29.4%. The BOLD signal confidence level, whether high or low, did not influence these clinical factors.SignificancePrevious studies have emphasized the utility of EEG-fMRI for the localization of the epileptogenic zone. This study demonstrated the potential of EEG-fMRI to influence clinical confidence when determining epilepsy syndrome, the presumed epileptic focus, and surgical candidacy.