Sodium MRI of the Lumbar Intervertebral Discs of the Human Spine: An Ex Vivo Study.

BACKGROUND: Lower back pain affects 75%-85% of people at some point in their lives. The detection of biochemical changes with sodium (23Na) MRI has potential to enable an earlier and more accurate diagnosis. PURPOSE: To measure 23Na relaxation times and apparent tissue sodium concentration (aTSC) in ex-vivo intervertebral discs (IVDs), and to investigate the relationship between aTSC and histological Thompson grade. STUDY TYPE: Ex-vivo. SPECIMEN: Thirty IVDs from the lumbar spines of 11 human body donors (4 female, 7 male, mean age 86 ± 8 years). FIELD STRENGTH/SEQUENCE: 3 T; density-adapted 3D radial sequence (DA-3D-RAD). ASSESSMENT: IVD 23Na longitudinal (T1), short and long transverse (T2s* and T2l*) relaxation times and the proportion of the short transverse relaxation (ps) were calculated for one IVD per spine sample (11 IVDs). Furthermore, aTSCs were calculated for all IVDs. The degradation of the IVDs was assessed via histological Thompson grading. STATISTICAL TESTS: A Kendall Tau correlation (τ) test was performed between the aTSCs and the Thompson grades. The significance level was set to P < 0.05. RESULTS: Mean 23Na relaxation parameters of a subset of 11 IVDs were T1 = 9.8 ± 1.3 msec, T2s* = 0.7 ± 0.1 msec, T2l* = 7.3 ± 1.1 msec, and ps = 32.7 ± 4.0%. A total of 30 IVDs were examined, of which 3 had Thompson grade 1, 4 had grade 2, 5 had grade 3, 5 had grade 4, and 13 had grade 5. The aTSC decreased with increasing degradation, being 274.6 ± 18.9 mM for Thompson grade 1 and 190.5 ± 29.5 mM for Thompson grade 5. The correlation between whole IVD aTSC and Thompson grade was significant and strongly negative (τ = -0.56). DATA CONCLUSION: This study showed a significant correlation between aTSC and degenerative IVD changes. Consequently, aTSC has potential to be useful as an indicator of degenerative spinal changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Diagnostic performance of a 3D double-echo steady-state sequence at 3 T using radial reformats for detecting and grading rotator cuff tears: a pilot diagnostic accuracy study with magnetic resonance imaging and arthroscopic correlation.

BACKGROUND: In diagnosing rotator cuff tears (RCTs), magnetic resonance imaging (MRI) is the imaging modality of choice, and its accuracy is improving constantly. PURPOSE: To evaluate the diagnostic performance of a high-resolution 3D double-echo steady-state (DESS) sequence with radial and paracoronal 3-T MRI regarding the grading of RCTs in correlation with conventional 2D MRI and arthroscopic findings. MATERIAL AND METHODS: We retrospectively compared arthroscopic findings of RCTs with preoperative MRI, including conventional 2D sequences and radial and paracoronal DESS images in 20 patients. Two observers evaluated supraspinatus (SSP), infraspinatus (ISP), and subscapularis (SSC) tendon tears using a grading system. For statistical analysis, arthroscopy was used as the reference standard. RESULTS: Inter-observer agreement for detecting and grading SSP, ISP, and SSC tendon tears on radial and paracoronal sliced 3D DESS MRI was excellent (intraclass-correlation [ICC] = 0.92-0.98; all P < 0.001). Regarding the detection of SSP lesions, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 93.8%, 50%, 88.2%, and 66.7% for both radial and paracoronal DESS imaging. A sensitivity of 100%, specificity of 61.1%, PPV of 22.2%, and NPV of 100% were noted for detecting ISP tendon tears using radially reformatted DESS images. Regarding detecting SSC tendon tears using radially reformatted DESS images, sensitivity, specificity, PPV, and NPV were 100%, 81.3%, 50%, and 100%, respectively. The results with standard 2D MRI were similar. CONCLUSION: The DESS technique with radially reformatted images provided excellent sensitivity and high inter-observer agreement in detecting RCTs. It showed a moderate to high correlation between MRI and arthroscopy for diagnosing SSP and SSC tendon tears.

Myelitis with flaccid paralysis due to Japanese encephalitis: case report and review of the literature.

BACKGROUND: Japanese encephalitis is an arthropod-borne zoonotic flavivirus infection endemic to tropical and subtropical Asia. A minority of infections leads to a symptomatic course, but affected patients often develop life-threatening encephalitis with severe sequelae. LITERATURE REVIEW: Myelitis with flaccid paralysis is a rare complication of Japanese Encephalitis, which-according to our literature search-was reported in 27 cases, some of which were published as case reports and others as case series. Overall, there is a broad clinical spectrum with typically asymmetric manifestation and partly severe motor sequelae and partly mild courses. Lower limb paralysis appears to be more frequent than upper limb paralysis. An encephalitic component is not apparent in all cases CASE PRESENTATION: We herein add the case of a 29 year-old female who developed encephalitis and myelitis with flaccid paralysis during a long-time stay in Indonesia. Diagnostic workup in Indonesia did not clearly reveal an underlying cause. Upon clinical stabilization, the patient was evacuated to her home country Germany, where further diagnostics confirmed Japanese encephalitis virus as the causative agent. The patient has partly recovered, but still suffers from residual paralysis of the upper limb. CONCLUSION: Flaccid paralysis is a rare, and likely underdiagnosed complication of Japanese encephalitis, which, to the best of our knowledge, has never been diagnosed outside endemic areas before.

Evaluation of Sodium Relaxation Times and Concentrations in the Achilles Tendon Using MRI.

Sodium magnetic resonance imaging (MRI) can be used to evaluate the change in the proteoglycan content in Achilles tendons (ATs) of patients with different AT pathologies by measuring the 23Na signal-to-noise ratio (SNR). As 23Na SNR alone is difficult to compare between different studies, because of the high influence of hardware configurations and sequence settings on the SNR, we further set out to measure the apparent tissue sodium content (aTSC) in the AT as a better comparable parameter. Ten healthy controls and one patient with tendinopathy in the AT were examined using a clinical 3 Tesla (T) MRI scanner in conjunction with a dual tuned 1H/23Na surface coil to measure 23Na SNR and aTSC in their ATs. 23Na T1 and T2* of the AT were also measured for three controls to correct for different relaxation behavior. The results were as follows: 23Na SNR = 11.7 ± 2.2, aTSC = 82.2 ± 13.9 mM, 23Na T1 = 20.4 ± 2.4 ms, 23Na T2s* = 1.4 ± 0.4 ms, and 23Na T2l* = 13.9 ± 0.8 ms for the whole AT of healthy controls with significant regional differences. These are the first reported aTSCs and 23Na relaxation times for the AT using sodium MRI and may serve for future comparability in different studies regarding examinations of diseased ATs with sodium MRI.

Detection of early cartilage degeneration in the tibiotalar joint using 3 T gagCEST imaging: a feasibility study.

OBJECTIVE: To establish and optimize a stable 3 Tesla (T) glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging protocol for assessing the articular cartilage of the tibiotalar joint in healthy volunteers and patients after a sustained injury to the ankle. METHODS: Using Bloch-McConnell simulations, we optimized the sequence protocol for a 3 T MRI scanner for maximum gagCEST effect size within a clinically feasible time frame of less than 07:30 min. This protocol was then used to analyze the gagCEST effect of the articular cartilage of the tibiotalar joint of 17 healthy volunteers and five patients with osteochondral lesions of the talus following ankle trauma. Reproducibility was tested with the intraclass correlation coefficient. RESULTS: The mean magnetization transfer ratio asymmetry (MTRasym), i.e., the gagCEST effect size, was significantly lower in patients than in healthy volunteers (0.34 ± 1.9% vs. 1.49 ± 0.11%; p < 0.001 [linear mixed model]). Intra- and inter-rater reproducibility was excellent with an average measure intraclass correlation coefficient (ICC) of 0.97 and a single measure ICC of 0.91 (p < 0.01). DISCUSSION: In this feasibility study, pre-morphological tibiotalar joint cartilage damage was quantitatively assessable on the basis of the optimized 3 T gagCEST imaging protocol that allowed stable quantification gagCEST effect sizes across a wide range of health and disease in clinically feasible acquisition times.

Differentiating rheumatoid and psoriatic arthritis: a systematic analysis of high-resolution magnetic resonance imaging features-preliminary findings.

BACKGROUND: Because of overlapping phenotypical presentations, the diagnostic differentiation of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) remains challenging. Thus, this study aimed to examine the diagnostic value of distinct imaging features obtained by high-resolution 3-T MRI for the diagnostic differentiation. MATERIALS AND METHODS: Seventeen patients with PsA and 28 patients with RA were imaged at high resolution using 3-T MRI scanners and a dedicated 16-channel hand coil. All images were analyzed according to the outcome measures in rheumatology clinical trials' (OMERACT) RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score) and PsAMRIS (Psoriatic Arthritis Magnetic Resonance Imaging Score) for the presence and intensity of synovitis, flexor tenosynovitis, bone edema, bone erosion, periarticular inflammation, bone proliferation, and joint space narrowing. Next, odds ratios (OR) were calculated to determine the strength of the associations between these imaging features, demographic characteristics, and the outcome RA vs. PsA. RESULTS: PsA could be differentiated from RA by extracapsular inflammatory changes (PsAMRIS sub-score "periarticular inflammation"), with low odds for the presence of RA (OR of 0.06, p < 0.01) at all metacarpophalangeal (MCP) joints. A prediction model informed by the items that were strongest associated with the presence of RA or PsA demonstrated excellent differentiating capability with an area under the curve of 98.1%. CONCLUSION: High-resolution imaging is beneficial for the identification of relevant imaging features that may assist the clinical differentiation of inflammatory conditions of the hand. At the MCP level, extracapsular inflammatory changes were strongly associated with PsA and may consequently allow the imaging differentiation of PsA and RA.

In vitro effects of sex hormones in human meibomian gland epithelial cells.

Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (ß-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -ß (ERα, ERß) and progesterone receptor (PR) in HMGEC. PR, ERα and ERß expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERß. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

Proof-of-Concept Double-Blind Placebo-Controlled Trial Measuring Cartilage Composition in Early Rheumatoid Arthritis under TNF-α-Inhibitor Therapy.

Low levels of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values are indicative of cartilage degeneration. Patients with early rheumatoid arthritis are known to have low dGEMRIC values due to inflammatory activity. The additional effect of biological disease-modifying antirheumatic drug (bDMARD) and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment on cartilage status is still unclear. In this prospective, double-blinded, randomized proof-of-concept clinical trial, patients with early rheumatoid arthritis (disease duration less than 12 months from symptoms onset) were treated with methotrexate + adalimumab (10 patients: 6/4 (f/m)). A control group with methotrexate alone (four patients: 2/2 (f/m)) was used. Cartilage integrity in the metacarpophalangeal joints was compared using dGEMRIC at baseline, 12, and 24 weeks after treatment initiation. A statistically significant increase in dGEMRIC levels was found in the adalimumab group considering the results after 12 and 24 weeks of therapy (p < 0.05) but not in the control group (p: non-significant). After 24 weeks, a tendency towards increased dGEMRIC values under combination therapy was observed, whereas methotrexate alone showed a slight decrease without meeting the criteria of significance (dGEMRIC mean change: +85.8 ms [-156.2-+346.5 ms] vs. 30.75 ms [-273.0-+131.0 ms]; p: non-significant). After 24 weeks of treatment with a combination of methotrexate and adalimumab, a trend indicating improvement in cartilage composition is seen in patients with early rheumatoid arthritis. However, treatment with methotrexate alone showed no change in cartilage composition, as observed in dGEMRIC sequences of metacarpophalangeal joints.

To Contrast or Not to Contrast? On the Role of Contrast Enhancement in Hand MRI Studies of Patients with Rheumatoid Arthritis.

Currently, clinical indications for the application of gadolinium-based contrast agents (GBCA) in magnetic resonance imaging (MRI) are increasingly being questioned. Consequently, this study aimed to evaluate the additional diagnostic value of contrast enhancement in MRI of the hand in patients with rheumatoid arthritis (RA). Thirty-one patients with RA (mean age, 50 ± 14 years (range, 18-72 years)) underwent morphologic MRI scans on a clinical 3 T scanner. MRI studies were analyzed based on (1) the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) and (2) the GBCA-free RAMRIS version, termed RAMRIS Sine-Gadolinium-For-Experts (RAMRIS-SAFE), in which synovitis and tenosynovitis were assessed using the short-tau inversion-recovery sequence instead of the post-contrast T1-weighted sequence. The synovitis subscores in terms of Spearman's ρ, as based on RAMRIS and RAMRIS-SAFE, were almost perfect (ρ = 0.937; p < 0.001), while the tenosynovitis subscores were less strongly correlated (ρ = 0.380 p = 0.035). Correlation between the total RAMRIS and RAMRIS-SAFE was also almost perfect (ρ = 0.976; p < 0.001). Inter-rater reliability in terms of Cohen's κ was high (0.963 ≤ κ ≤ 0.925). In conclusion, RAMRIS-SAFE as the GBCA-free version of the well-established RAMRIS is a patient-friendly and resource-efficient alternative for assessing disease-related joint changes in RA. As patients with RA are subject to repetitive GBCA applications, non-contrast imaging protocols should be considered.

Chemical Exchange Saturation Transfer for Lactate-Weighted Imaging at 3 T MRI: Comprehensive In Silico, In Vitro, In Situ, and In Vivo Evaluations.

Based on in silico, in vitro, in situ, and in vivo evaluations, this study aims to establish and optimize the chemical exchange saturation transfer (CEST) imaging of lactate (Lactate-CEST­LATEST). To this end, we optimized LATEST sequences using Bloch−McConnell simulations for optimal detection of lactate with a clinical 3 T MRI scanner. The optimized sequences were used to image variable lactate concentrations in vitro (using phantom measurements), in situ (using nine human cadaveric lower leg specimens), and in vivo (using four healthy volunteers after exertional exercise) that were then statistically analyzed using the non-parametric Friedman test and Kendall Tau-b rank correlation. Within the simulated Bloch−McConnell equations framework, the magnetization transfer ratio asymmetry (MTRasym) value was quantified as 0.4% in the lactate-specific range of 0.5−1 ppm, both in vitro and in situ, and served as the imaging surrogate of the lactate level. In situ, significant differences (p < 0.001) and strong correlations (τ = 0.67) were observed between the MTRasym values and standardized intra-muscular lactate concentrations. In vivo, a temporary increase in the MTRasym values was detected after exertional exercise. In this bench-to-bedside comprehensive feasibility study, different lactate concentrations were detected using an optimized LATEST imaging protocol in vitro, in situ, and in vivo at 3 T, which prospectively paves the way towards non-invasive quantification and monitoring of lactate levels across a broad spectrum of diseases.

Effects of Anti-Tumor Necrosis Factor Therapy on Osteoblastic Activity at Sites of Inflammatory and Structural Lesions in Radiographic Axial Spondyloarthritis: A Prospective Proof-of-Concept Study Using Positron Emission Tomography/Magnetic Resonance Imaging of the Sacroiliac Joints and Spine.

OBJECTIVE: Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF (18 F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18 F-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18 F-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. RESULTS: Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). 18 F-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18 F-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18 F-NaF uptake, compared with baseline. For VCs, 18 F-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18 F-NaF uptake, compared with baseline. CONCLUSION: Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA.

Adaptive IoU Thresholding for Improving Small Object Detection: A Proof-of-Concept Study of Hand Erosions Classification of Patients with Rheumatic Arthritis on X-ray Images.

In recent years, much research evaluating the radiographic destruction of finger joints in patients with rheumatoid arthritis (RA) using deep learning models was conducted. Unfortunately, most previous models were not clinically applicable due to the small object regions as well as the close spatial relationship. In recent years, a new network structure called RetinaNets, in combination with the focal loss function, proved reliable for detecting even small objects. Therefore, the study aimed to increase the recognition performance to a clinically valuable level by proposing an innovative approach with adaptive changes in intersection over union (IoU) values during training of Retina Networks using the focal loss error function. To this end, the erosion score was determined using the Sharp van der Heijde (SvH) metric on 300 conventional radiographs from 119 patients with RA. Subsequently, a standard RetinaNet with different IoU values as well as adaptively modified IoU values were trained and compared in terms of accuracy, mean average accuracy (mAP), and IoU. With the proposed approach of adaptive IoU values during training, erosion detection accuracy could be improved to 94% and an mAP of 0.81 ± 0.18. In contrast Retina networks with static IoU values achieved only an accuracy of 80% and an mAP of 0.43 ± 0.24. Thus, adaptive adjustment of IoU values during training is a simple and effective method to increase the recognition accuracy of small objects such as finger and wrist joints.

DGEMRIC in the Assessment of Pre-Morphological Cartilage Degeneration in Rheumatic Disease: Rheumatoid Arthritis vs. Psoriatic Arthritis.

BACKGROUND: Even though cartilage loss is a known feature of psoriatic (PsA) and rheumatoid arthritis (RA), research is sparse on its role in the pathogenesis of PsA, its potential use for disease monitoring and for differentiation from RA. We therefore assessed the use of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to evaluate biochemical cartilage changes in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in PsA patients and compared these to RA patients. MATERIALS AND METHODS: A total of 17 patients with active PsA and 20 patients with active RA were evaluated by high-resolution 3 Tesla dGEMRIC using a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices and joint space width (JSW) at MCP and PIP joint levels. RESULTS: No significant differences of dGEMRIC values could be found between both study populations (PsA 472.25 ms, RA 461.11 ms; p = 0.763). In all RA and most PsA patients, PIP joints showed significantly lower dGEMRIC indices than MCP joints (RA: D2: p = 0.009, D3: p = 0.008, D4: p = 0.002, D5: p = 0.002; PsA: D3: p = 0.001, D4: p = 0.004). Most joint spaces had similar widths in both disease entities and no significant differences were found. CONCLUSIONS: As evaluated by dGEMRIC, the molecular composition of the MCP and PIP joint cartilage of PsA patients is similar to that of RA patients, demonstrating the scientific and clinical feasibility of compositional magnetic resonance (MR) imaging in these disease entities. Patterns and severity of compositional cartilage degradation of the finger joints may therefore be assessed beyond mere morphology in PsA and RA patients.

Automated Analysis of Alignment in Long-Leg Radiographs by Using a Fully Automated Support System Based on Artificial Intelligence.

PURPOSE: To develop and validate a deep learning-based method for automatic quantitative analysis of lower-extremity alignment. MATERIALS AND METHODS: In this retrospective study, bilateral long-leg radiographs (LLRs) from 255 patients that were obtained between January and September of 2018 were included. For training data (n = 109), a U-Net convolutional neural network was trained to segment the femur and tibia versus manual segmentation. For validation data (n = 40), model parameters were optimized. Following identification of anatomic landmarks, anatomic and mechanical axes were identified and used to quantify alignment through the hip-knee-ankle angle (HKAA) and femoral anatomic-mechanical angle (AMA). For testing data (n = 106), algorithm-based angle measurements were compared with reference measurements by two radiologists. Angles and time for 30 random radiographs were compared by using repeated-measures analysis of variance and one-way analysis of variance, whereas correlations were quantified by using Pearson r and intraclass correlation coefficients. RESULTS: Bilateral LLRs of 255 patients (mean age, 26 years ± 23 [standard deviation]; range, 0-88 years; 157 male patients) were included. Mean Sørensen-Dice coefficients for segmentation were 0.97 ± 0.09 for the femur and 0.96 ± 0.11 for the tibia. Mean HKAAs and AMAs as measured by the readers and the algorithm ranged from 0.05° to 0.11° (P = .5) and from 4.82° to 5.43° (P < .001). Interreader correlation coefficients ranged from 0.918 to 0.995 (r range, P < .001), and agreement was almost perfect (intraclass correlation coefficient range, 0.87-0.99). Automatic analysis was faster than the two radiologists' manual measurements (3 vs 36 vs 35 seconds, P < .001). CONCLUSION: Fully automated analysis of LLRs yielded accurate results across a wide range of clinical and pathologic indications and is fast enough to enhance and accelerate clinical workflows.Supplemental material is available for this article.© RSNA, 2020See also commentary by Andreisek in this issue.

Evaluating Lumbar Intervertebral Disc Degeneration on a Compositional Level Using Chemical Exchange Saturation Transfer: Preliminary Results in Patients with Adolescent Idiopathic Scoliosis.

Lumbar intervertebral disc (IVD) degeneration is characterized by structural and compositional changes. This study aimed to assess the glycosaminoglycan (GAG) content of IVDs of patients with adolescent idiopathic scoliosis (AIS) and healthy controls using GAG chemical exchange saturation transfer (gagCEST) imaging. Ten AIS patients (mean age 18.3 ± 8.2 years) and 16 healthy controls (mean age 25.5 ± 1.7 years) were included. Clinical standard morphologic MR images (T1w-, T2w-, and STIR-sequences), to rule out further spinal disorders and assess IVD degeneration using the Pfirrmann score, and compositional gagCEST sequences were acquired on a 3T MRI. In AIS patients, the most distal scoliotic curve was determined on whole-spine conventional radiographs and morphological MRI and IVDs were divided as to whether they were affected by scoliotic deformity, i.e., proximal (affected, aIVDs) or distal (unaffected, uaIVDs) to the stable vertebra of the most distal scoliotic curve. Linear mixed models were used to compare mean gagCEST-values. Over all segments, AIS-patients' IVDs exhibited significantly lower gagCEST-values than the controls: 2.76 [2.32, 3.20]% (AIS), 3.51 [3.16, 3.86]% (Control); p = 0.005. Meanwhile, no significant differences were found for gagCEST values comparing aIVDs with uaIVDs. In conclusion, as a powerful diagnostic adjunct, gagCEST imaging may be prospectively applied to detect early compositional degenerative changes in patients suffering from AIS.

Quantification of Sodium Relaxation Times and Concentrations as Surrogates of Proteoglycan Content of Patellar CARTILAGE at 3T MRI.

Sodium MRI has the potential to depict cartilage health accurately, but synovial fluid can influence the estimation of sodium parameters of cartilage. Therefore, this study aimed to reduce the impact of synovial fluid to render the quantitative compositional analyses of cartilage tissue technically more robust. Two dedicated protocols were applied for determining sodium T1 and T2* relaxation times. For each protocol, data were acquired from 10 healthy volunteers and one patient with patellar cartilage damage. Data recorded with multiple repetition times for T1 measurement and multi-echo data acquired with an additional inversion recovery pulse for T2* measurement were analysed using biexponential models to differentiate longitudinal relaxation components of cartilage (T1,car) and synovial fluid (T1,syn), and short (T2s*) from long (T2l*) transversal relaxation components. Sodium relaxation times and concentration estimates in patellar cartilage were successfully determined: T1,car = 14.5 ± 0.7 ms; T1,syn = 37.9 ± 2.9 ms; c(T1-protocol) = 200 ± 48 mmol/L; T2s* = 0.4 ± 0.1 ms; T2l* = 12.6 ± 0.7 ms; c(T2*-protocol) = 215 ± 44 mmol/L for healthy volunteers. In conclusion, a robust determination of sodium relaxation times is possible at a clinical field strength of 3T to quantify sodium concentrations, which might be a valuable tool to determine cartilage health.

Non-Specific Low Back Pain and Lumbar Radiculopathy: Comparison of Morphologic and Compositional MRI as Assessed by gagCEST Imaging at 3T.

Using glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) magnetic resonance imaging (MRI), this study comparatively evaluated the GAG contents of lumbar intervertebral disks (IVDs) of patients with non-specific low back pain (nsLBP), radiculopathy, and asymptomatic volunteers to elucidate the association of clinical manifestation and compositional correlate. A total of 18 patients (mean age 57.5 ± 22.5 years) with radiculopathy, 16 age-matched patients with chronic nsLBP and 20 age-matched volunteers underwent standard morphologic and compositional gagCEST MRI on a 3T scanner. In all cohorts, GAG contents of lumbar IVDs were determined using gagCEST MRI. An assessment of morphologic IVD degeneration based on the Pfirrmann classification and T2-weighted sequences served as a reference. A linear mixed model adjusted for multiple confounders was used for statistical evaluation. IVDs of patients with nsLBP showed lower gagCEST values than those of volunteers (nsLBP: 1.3% [99% confidence intervals (CI): 1.0; 1.6] vs. volunteers: 1.9% [99% CI: 1.6; 2.2]). Yet, IVDs of patients with radiculopathy (1.8% [99% CI: 1.4; 2.1]) were not different from patients with nsLBP or volunteers. In patients with radiculopathy, IVDs directly adjacent to IVD extrusions demonstrated lower gagCEST values than distant IVDs (adjacent: 0.9% [99% CI: 0.3; 1.5], distant: 2.1% [99% CI: 1.7; 2.5]). Advanced GAG depletion in nsLBP and directly adjacent to IVD extrusions in radiculopathy indicates close interrelatedness of clinical pathology and compositional degeneration.

Introduction of a Simplified Psoriatic Arthritis Magnetic Resonance Imaging Score (sPsAMRIS): A Potential Tool for Treatment Monitoring in Peripheral Psoriatic Arthritis.

BACKGROUND: To evaluate whether a simplified (s) version of the psoriatic arthritis magnetic resonance imaging score (PsAMRIS), sPsAMRIS, is a potential tool for therapy monitoring in psoriatic arthritis (PsA). METHODS: Seventeen patients with active psoriatic arthritis (PsA) underwent magnetic resonance imaging (MRI) at 3 T of the clinically dominant hand at baseline and after 6 months. Scoring was performed by two musculoskeletal radiologists in terms of the PsAMRIS and sPsAMRIS, which is a simplified version with reduced item numbers based on prior evaluation of responsiveness to change by standardized response means (SRMs). Both scores were compared by calculation of overall and each sub-score's SRMs and relative efficacy (RE) after bootstrapping. RESULTS: PsAMRIS sub-scores of MCP joints 3 and 4, and proximal interphalangeal (PIP) joint 4 had the highest SRM (-0.07 each), indicating highest responsiveness to change, and were, therefore, included in sPsAMRIS. Compared to PsAMRIS, sPsAMRIS was characterized by higher SRMs (sPsAMRIS: -0.13 vs. PsAMRIS: -0.02) and higher RE (29.46). sPsAMRIS and PsAMRIS were highly correlated at baseline (r = 0.75, p < 0.01 (Pearson's correlation)) and at 6-month follow-up (r = 0.64, p = 0.01). Mean time burden for completion of scoring per MRI study was significantly reduced when using PsAMRIS (469 ± 87.03 s) as compared to sPsAMRIS (140.1 ± 21.25 s) (p < 0.001). CONCLUSION: Due to its similar responsiveness to change compared to standard PsAMRIS, and time efficiency, sPsAMRIS might be a potential diagnostic tool to quantitatively assess and monitor therapy in PsA.

Cartilage Degradation in Psoriatic Arthritis Is Associated With Increased Synovial Perfusion as Detected by Magnetic Resonance Imaging.

Objective: Even though cartilage loss is a known feature of psoriatic arthritis (PsA), research is sparse on its role in the pathogenesis of PsA and its potential use for disease detection and monitoring. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and dynamic contrast-enhanced MRI (DCE MRI), research has shown that early cartilage loss is strongly associated with synovial inflammation in rheumatoid arthritis (RA). The aim of this study was to determine if acute inflammation is associated with early cartilage loss in small finger joints of patients with PsA. Methods: Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution 3 Tesla dGEMRIC and DCE MRI using a dedicated 16-channel hand coil. Semi-quantitative and quantitative perfusion parameters were calculated. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), total cartilage thickness (TCT), and joint space width (JSW). Results: We found significant negative correlations between perfusion parameters (except Kep) and dGEMRIC indices, with the highest value at the MCP joints (KTrans: τ = -0.54, p = 0.01; Kep: τ = -0.02, p = 0.90; IAUC: τ = -0.51, p = 0.015; Initial Slope: τ = -0.54, p = 0.01; Peak: τ = -0.67, p = 0.002). Heterogeneous correlations were detected between perfusion parameters and both, total PsAMRIS and PsAMRIS synovitis sub-scores. No significant correlation was seen between any perfusion parameter and JSW and/or TCT. Conclusion: As examined by DCE MRI and dGEMRIC, there is a potential association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.

Functional MR imaging beyond structure and inflammation-radiographic axial spondyloarthritis is associated with proteoglycan depletion of the lumbar spine.

BACKGROUND: To compare the glycosaminoglycan (GAG) content of lumbar intervertebral disks (IVDs) of patients with ankylosing spondylitis (AS) and healthy volunteers and to investigate the association of GAG depletion and disease-related clinical and imaging features. METHODS: Lumbar spines of 50 AS patients (mean age 50 ± 10.5 years) and 30 age-matched volunteers were studied with 3-T magnetic resonance imaging (MRI) and conventional radiographs (CR). The MRI protocol included high-resolution morphological sequences and the compositional GAG chemical exchange saturation transfer imaging technique (gagCEST). Morphological images were analyzed by three raters for inflammatory activity, fat deposition, disk degeneration, and structural changes on CR. Clinical and serological measures included the Bath AS Disease Activity (BASDAI) and Bath AS Function (BASFI) Indices and C-reactive protein (CRP) levels. GagCEST values of both groups were compared using a linear mixed model. Kendall-Tau correlation analyses were performed. RESULTS: GagCEST values were significantly lower in AS patients (2.0 ± 1.7%) vs. healthy volunteers (2.4 ± 1.8%), p = 0.001. Small, yet significant correlations were found between gagCEST values and CRP levels (τ = - 0.14, p = 0.007), BASFI (τ = - 0.18, p < 0.001) and presence of syndesmophytes (τ = - 0.17, p = 0.001). No significant correlations were found with BASDAI, inflammation, and fat deposition MRI scores. CONCLUSIONS: Lumbar spines of r-AS patients undergo significant GAG depletion, independently associated with syndesmophyte formation, functional disability, and increased serological inflammation markers. Beyond establishing a pathophysiological role of the cartilage in AS, these findings suggest that gagCEST imaging may have an adjunct confirmatory role in the assessment of disease-related pathological MRI findings in axial spondyloarthritis. TRIAL REGISTRATION: 3980 ( https://studienregister.med.uni-duesseldorf.de ).