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.

Dynamic assessment of scapholunate ligament status by real-time magnetic resonance imaging: an exploratory clinical study.

OBJECTIVE: Clinical-standard MRI is the imaging modality of choice for the wrist, yet limited to static evaluation, thereby potentially missing dynamic instability patterns. We aimed to investigate the clinical benefit of (dynamic) real-time MRI, complemented by automatic analysis, in patients with complete or partial scapholunate ligament (SLL) tears. MATERIAL AND METHODS: Both wrists of ten patients with unilateral SLL tears (six partial, four complete tears) as diagnosed by clinical-standard MRI were imaged during continuous active radioulnar motion using a 1.5-T MRI scanner in combination with a custom-made motion device. Following automatic segmentation of the wrist, the scapholunate and lunotriquetral joint widths were analyzed across the entire range of motion (ROM). Mixed-effects model analysis of variance (ANOVA) followed by Tukey's posthoc test and two-way ANOVA were used for statistical analysis. RESULTS: With the increasing extent of SLL tear, the scapholunate joint widths in injured wrists were significantly larger over the entire ROM compared to those of the contralateral healthy wrists (p<0.001). Differences between partial and complete tears were most pronounced at 5°-15° ulnar abduction (p<0.001). Motion patterns and trajectories were altered. Complete SLL deficiency resulted in complex alterations of the lunotriquetral joint widths. CONCLUSION: Real-time MRI may improve the functional diagnosis of SLL insufficiency and aid therapeutic decision-making by revealing dynamic forms of dissociative instability within the proximal carpus. Static MRI best differentiates SLL-injured wrists at 5°-15° of ulnar abduction.

calf - Software for CEST Analysis with Lorentzian Fitting.

Analysis of chemical exchange saturation transfer (CEST) MRI data requires sophisticated methods to obtain reliable results about metabolites in the tissue under study. CEST generates z-spectra with multiple components, each originating from individual molecular groups. The individual lines with Lorentzian line shape are mostly overlapping and disturbed by various effects. We present an elaborate method based on an adaptive nonlinear least squares algorithm that provides robust quantification of z-spectra and incorporates prior knowledge in the fitting process. To disseminate CEST to the research community, we developed software as part of this study that runs on the Microsoft Windows operating system and will be made freely available to the community. Special attention has been paid to establish a low entrance threshold and high usability, so that even less experienced users can successfully analyze CEST data.

Lorentzian-Corrected Apparent Exchange-Dependent Relaxation (LAREX) Ω-Plot Analysis-An Adaptation for qCEST in a Multi-Pool System: Comprehensive In Silico, In Situ, and In Vivo Studies.

Based on in silico, in situ, and in vivo studies, this study aims to develop a new method for the quantitative chemical exchange saturation transfer (qCEST) technique considering multi-pool systems. To this end, we extended the state-of-the-art apparent exchange-dependent relaxation (AREX) method with a Lorentzian correction (LAREX). We then validated this new method with in situ and in vivo experiments on human intervertebral discs (IVDs) using the Kendall-Tau correlation coefficient. In the in silico experiments, we observed significant deviations of the AREX method as a function of the underlying exchange rate (kba) and fractional concentration (fb) compared to the ground truth due to the influence of other exchange pools. In comparison to AREX, the LAREX-based Ω-plot approach yielded a substantial improvement. In the subsequent in situ and in vivo experiments on human IVDs, no correlation to the histological reference standard or Pfirrmann classification could be found for the fb (in situ: τ = −0.17 p = 0.51; in vivo: τ = 0.13 p = 0.30) and kba (in situ: τ = 0.042 p = 0.87; in vivo: τ = −0.26 p = 0.04) of Glycosaminoglycan (GAG) with AREX. In contrast, the influence of interfering pools could be corrected by LAREX, and a moderate to strong correlation was observed for the fractional concentration of GAG for both in situ (τ = −0.71 p = 0.005) and in vivo (τ = −0.49 p < 0.001) experiments. The study presented here is the first to introduce a new qCEST method that enables qCEST imaging in systems with multiple proton pools.

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.

Sodium MRI of human articular cartilage of the wrist: a feasibility study on a clinical 3T MRI scanner.

OBJECTIVE: To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence. MATERIALS AND METHODS: Sodium MRI of human wrists was conducted on a 3T MR system using a dual-tuned 1H/23Na surface coil. We performed two studies with 10 volunteers each investigating either sodium T1 (study 1) or sodium T2* (study 2) relaxation times in the radiocarpal joint (RCJ) and midcarpal joint (MCJ). Sodium concentrations of both regions were determined. RESULTS: No differences for transversal of longitudinal relaxation times were found between RCJ and MCJ (T2,s*(RCJ) = (0.9 ± 0.4) ms; T2,s*(MCJ) = (0.9 ± 0.3) ms; T2,l*(RCJ) = (14.9 ± 0.9) ms; T2,l*(MCJ) = (13.9 ± 1.1) ms; T1(RCJ) = (19.0 ± 2.4) ms; T1(MCJ) = (18.5 ± 2.1) ms). Sodium concentrations were (157.7 ± 28.4) mmol/l for study 1 and (159.8 ± 29.1) mmol/l for study 2 in the RCJ, and (172.7 ± 35.6) mmol/l for study 1 and (163.4 ± 26.3) mmol/l for study 2 in the MCJ. CONCLUSION: We successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner.

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.

Proton exchange in aqueous urea solutions measured by water-exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro.

PURPOSE: To characterize the proton exchange in aqueous urea solutions using a modified version of the WEX II filter at high magnetic field, and to assess the feasibility of performing quantitative urea CEST MRI on a 3T clinical MR system. METHODS: In order to study the dependence of the exchange-rate constant ksw of urea as a function of pH and T, the WEX-spectra were acquired at 600 MHz from urea solutions in a pH range from 6.4 to 8.0 and a temperature range from T=22∘C to 37∘C . The CEST experiments were performed on a 3T MRI scanner by applying a train of 50 Gaussian-shaped pulses, each 100-millisecond long with a spacing of 100 milliseconds, for saturation. Exchange rates of urea were calculated using the (extended) AREX metric. RESULTS: The results showed that proton exchange in aqueous urea solutions is acid and base catalyzed with the rate constants: ka=(9.95±1.1)×106 l/(mol·s) and kb=(6.21±0.21)×106 l/(mol·s), respectively. Since the urea protons undergo a slow exchange with water protons, the CEST effect of urea can be observed efficiently at 3T. However, in neutral solutions the exchange rate of urea is minimal and cannot be estimated using the quantitative CEST approach. CONCLUSIONS: By means of the WEX-spectroscopy, the kinetic parameters of the proton exchange in urea solutions have been determined. It was also possible to estimate the exchange rates of urea in a broad range of pH values using the CEST method at a clinical scanner.

MRI identifies biochemical alterations of intervertebral discs in patients with low back pain and radiculopathy.

KEY POINTS: • Molecular intervertebral disc damage was associated with LBP and radiculopathy.• Patients with radiculopathy and LBP demonstrated a depletion of gagCEST values compared with healthy controls.• GagCEST imaging may be a non-invasive tool for investigation of degeneration processes of lumbar intervertebral discs (IVDs). GagCEST imaging may be an imaging biomarker for biochemical IVD alterations.

Prevention of the progressive biochemical cartilage destruction under methotrexate therapy in early rheumatoid arthritis.

OBJECTIVES: The aim of the study was to investigate biochemical cartilage composition under methotrexate (MTX) therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with early rheumatoid arthritis (eRA). METHODS: dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomised into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore. RESULTS: MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086). CONCLUSIONS: Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients were treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints.

Non-gaussian diffusion evaluation of the human kidney by Padé exponent model.

PURPOSE: To evaluate the feasibility of renal diffusion quantification using the Padé exponent model (PEM) in healthy subjects. MATERIALS AND METHODS: Diffusion measurements were completed in 10 healthy subjects (mean age, 32.4 ± 8.9 years) on a 3T MRI scanner (Magnetom Trio, Siemens AG, Germany). A respiratory-triggered echo planar imaging sequence (15 slices with 6 mm thickness; 16 b-values [0-750 s/mm2 ]; three diffusion directions; field of view: 400 × 375 mm; Matrix 192 × 192; repetition time/echo time: 3000/74 ms) was acquired in the coronal direction. Parameter maps were calculated for the monoexponential, biexponential, kurtosis models, and the PEM. A regression analysis using an R2 -test and corrected Akaike information criterion (AICc) was performed to identify the best mathematical fitting to the measured diffusion-weighted imaging signal decay. RESULTS: The mathematical accuracy of the PEM was significantly higher than for the other three-parameter and the monoexponential model (P < 0.05), which enables more precise information about the deviation of the Gaussian behavior of the diffusion signal by the PEM. The biexponential model showed better fitting to the diffusion signal (medullar Rbi2 0.989 ± 0.008, AICcbi 113.3 ± 6.6; cortical Rbi2 0.992 ± 0.006, AICcbi 113.3 ± 5.2) than the three-parameter models (medullar RPadé2 0.965 ± 0.016, AICcPadé 122.6 ± 6.4, RK2 0.954 ± 0.019, AICcK 128.5 ± 6.0; cortical RPadé2 0.989 ± 0.005, AICcPadé 116.3 ± 4.4, RK2 0.985 ± 0.007, AICcK 120.4 ± 4.8). The monoexponential model fits least to the diffusion signal in the kidney (medullar Rmono2 0.898 ± 0.039, AICcmono 141.4 ± 5.6; cortical Rmono2 0.961 ± 0.013, AICcmono 135.4 ± 4.8). CONCLUSION: The PEM is a novel promising approach to quantify diffusion properties in the human kidney and might further improve functional renal MR imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:160-167.

Cartilage Imaging: Techniques and Developments.

Cartilage degeneration is one of the most common chronic age-related joint disorders leading to pain and reduced joint motion. The increasing prevalence of osteoarthritis requires accurate cartilage imaging, both clinically and in research. Detailed cartilage imaging is also necessary for traumatic cartilage lesions and for pre- and postoperative assessment of cartilage repair procedures. Although still widely used, conventional radiography bears significant limitations because it assesses cartilage indirectly by joint space width. Magnetic resonance imaging (MRI) enables direct visualization of cartilage damage along with other concomitantly affected joint tissues. Several semiquantitative grading systems and volumetric analysis methods exist to assess cartilage damage and cartilage repair on MRI. Quantification of hyaline and fibrocartilage biochemical composition is possible with novel MRI methods such as T2- and T1ρ-mapping, delayed gadolinium-enhanced MRI of cartilage, glycosaminoglycan chemical exchange saturation transfer, and sodium imaging, along with quantitative computed tomography arthrography. These techniques provide promising quantitative imaging biomarkers that can detect early cartilage changes before morphological alterations occur.

Comparison of B0 versus B0 and B1 field inhomogeneity correction for glycosaminoglycan chemical exchange saturation transfer imaging.

PURPOSE: The study compares glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging of intervertebral discs corrected for solely B0 inhomogeneities or both B0 and B1 inhomogeneities. METHODS: Lumbar intervertebral discs of 20 volunteers were examined with T2-weighted and gagCEST imaging. Field inhomogeneity correction was performed with B0 correction only and with correction of both B0 and B1. GagCEST effects measured by the asymmetric magnetization transfer ratio (MTRasym) and signal-to-noise ratio (SNR) were compared between both methods. RESULTS: Significant higher MTRasym and SNR values were obtained in the nucleus pulposus using B0 and B1 correction compared with B0-corrected gagCEST. The GagCEST effect was significantly different in the nucleus pulposus compared with the annulus fibrosus for both methods. CONCLUSION: The B0 and B1 field inhomogeneity correction method leads to an improved quality of gagCEST imaging in IVDs compared with only B0 correction.

Comparison of glycosaminoglycan chemical exchange saturation transfer using Gaussian-shaped and off-resonant spin-lock radiofrequency pulses in intervertebral disks.

PURPOSE: To investigate, if a train of spin-lock pulses (chemical exchange saturation transfer with spin-lock pulses = CESL) improves biochemical glycosaminoglycan imaging compared with conventional chemical exchange saturation transfer with Gaussian-shaped pulses (CEST) in lumbar intervertebral discs. METHODS: T2 , CEST, and CESL imaging was performed in lumbar intervertebral discs of 15 healthy volunteers at 3 Tesla. Mean and standard deviation of the asymmetric magnetization transfer ratio (MTRasym ), the asymmetric spin-lock ratio (SLRasym ) and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF). Wilcoxon test was used to analyze differences between MTRasym and SLRasym . Pearson correlation was used to determine the relationship between MTRasym , SLRasym and T2 . RESULTS: Data showed no significant difference between MTRasym and SLRasym (NP: P = 0.35; AF: P = 0.34). MTRasym and SLRasym values differed significantly between NP and AF (MTRasym : P = 0.014, SLRasym : P = 0.005). T2 values correlated significantly with MTRasym (NP: ρ = 0.76, P < 0.001; AF: ρ = 0.60, P < 0.001) and SLRasym (NP: ρ = 0.73, P < 0.001; AF: ρ = 0.47, P < 0.001). CONCLUSION: CESL does not improve the chemical exchange asymmetry effect compared with conventional CEST, but leads to comparable results. Magn Reson Med 78:280-284, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Quantitative pulsed CEST-MRI at a clinical 3T MRI system.

OBJECTIVES: The goal of this study was to quantify CEST related parameters such as chemical exchange rate and fractional concentration of exchanging protons at a clinical 3T scanner. For this purpose, two CEST quantification approaches-the AREX metric (for 'apparent exchange dependent relaxation'), and the AREX-based Ω-plot method were used. In addition, two different pulsed RF irradiation schemes, using Gaussian-shaped and spin-lock pulses, were compared. MATERIALS AND METHODS: Numerical simulations as well as MRI measurements in phantoms were performed. For simulations, the Bloch-McConnell equations were solved using a two-pool exchange model. MR experiments were performed on a clinical 3T MRI scanner using a cylindrical phantom filled with creatine solution at different pH values and different concentrations. RESULTS: The validity of the Ω-plot method and the AREX approach using spin-lock preparation for determination of the quantitative CEST parameters was demonstrated. Especially promising results were achieved for the Ω-plot method when the spin-lock preparation was employed. CONCLUSION: Pulsed CEST at 3T could be used to quantify parameters such as exchange rate constants and concentrations of protons exchanging with free water. In the future this technique might be used to estimate the exchange rates and concentrations of biochemical substances in human tissues in vivo.

Glycosaminoglycan chemical exchange saturation transfer at 3T MRI in asymptomatic knee joints.

BACKGROUND: Biochemical alterations such as glycosaminoglycan (GAG) depletion occur early in the course of osteoarthritis, but cannot be detected with standard magnetic resonance techniques. With glycosaminoglycan chemical exchange saturation transfer (gagCEST), a biochemical imaging technique, it is feasible to detect biochemical components in knee joint cartilage. PURPOSE: To establish baseline values for gagCEST magnetic resonance imaging (MRI) in knee joint cartilage at 3 Tesla (T). MATERIAL AND METHODS: Twenty volunteers (8 women, 12 men; mean age, 24.55 ± 2.35 years;age range, 21-29 years) with no history or clinical findings indicative of knee joint pathologies underwent MRI at 3T. The imaging protocol included three-dimensional (3D) double-echo steady-state sequence for morphological cartilage assessment and a prototype 3D CEST pulse sequence to evaluate the CEST effects in six cartilage regions of the knee joint: (i) lateral femoral condyle; (ii) medial femoral condyle; (iii) lateral tibial plateau; (iv) medial tibial plateau; (v) patella; and (vi) trochlea. We used the asymmetry of the magnetization transfer ratio (MTRasym) parameter to quantify the gagCEST effects in these regions. RESULTS: Regional differences revealed high MTRasym values in the patellar (1.62% ± 1.19%) and the trochlear (1.17% ± 1.29%) cartilages, and low MTRasym values in the medial femoral condyle (0.41% ± 0.58%) and the lateral tibial plateau (0.52% ± 0.53%) cartilages. CONCLUSION: Regional differences in the gagCEST values must be considered when conducting gagCEST imaging of knee joint cartilage. In the future gagCEST imaging may be an additional feature in the evaluation of the biochemical composition of knee joint cartilage.

Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results.

OBJECTIVE: To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. MATERIALS AND METHODS: Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 ± 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). RESULTS: GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17% ± 1.03% vs. 0.79% ± 1.75%; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76% ± 0.92% vs. 0.52% ± 1.17%; p < 0.001). CONCLUSION: Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging.

Age-dependency of glycosaminoglycan content in lumbar discs: A 3t gagcEST study.

PURPOSE: To analyze age-dependency of glycosaminoglycan content using gagCEST (glycosaminoglycan chemical exchange saturation transfer) imaging in lumbar intervertebral discs of healthy volunteers. MATERIALS AND METHODS: In all, 70 volunteers without low back pain (mean age 44 ± 14 years, range: 21-69 years) were examined with T2 -weighted and gagCEST imaging with a 3T MR scanner, with approval of the local Ethics Committee after written informed consent was obtained. Pfirrmann grading and classification into discs without bulging and herniation, discs with bulging, and discs with herniation were performed. Only intervertebral discs without bulging and herniation were analyzed. A region-of-interest-based gagCEST analysis of nucleus pulposus (NP) and annulus fibrosus (AF) was performed. Correlation between age and gagCEST was tested within groups of equal Pfirrmann score. RESULTS: GagCEST effects decreased significantly from 3.09 ± 1.12% in 20-29 years old volunteers to -0.24 ± 1.36% in 50-59 years old volunteers (P < 0.001). In the case of Pfirrmann scores 2 and 3, a significant correlation was observed between gagCEST effect and age (Pfirrmann score 2, NP: ρ = -0.558, P < 0.001; Pfirrmann score 3, NP: ρ = -0.337, P = 0.048). For Pfirrmann scores 1 and 4, no significant correlation was obtained (Pfirrmann score 1, NP: ρ = -0.046, P = 0.824; Pfirrmann score 4, NP: ρ = -0.316, P = 0.188). CONCLUSION: We show a decreased gagCEST effect likely corresponding to decreasing glycosaminoglycans with aging. Hence, age-matched analysis of gagCEST imaging may be necessary in future studies.

Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis.

PURPOSE: To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with spondyloarthritis (SpA) using glycosaminoglycan chemical exchange saturation transfer (gagCEST). MATERIALS AND METHODS: Ninety lumbar intervertebral discs of nine patients with SpA and nine age-matched healthy controls (eight patients with ankylosing spondylitis; one patient with spondylitis related to inflammatory bowel disease; mean age: 44.1 ± 14.0 years; range: 27-72 years) were examined with a 3T magnetic resonance imaging (MRI) scanner in this prospective study. The MRI protocol included standard morphological, sagittal T2 -weighted (T2 w) images to assess Pfirrmann score of the five lumbar IVDs (L1 to S1) and biochemical imaging with gagCEST to calculate a region of interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). Prior to statistical testing of gagCEST effects (MTRasym values in percent) in patients and controls, IVDs were classified according to the Pfirrmann score. RESULTS: Significantly lower gagCEST values of NP and AF were found in SpA patients compared with healthy volunteers (NP: 1.41% ± 0.41%, P = 0.001; 95% confidence interval, CI [0.600%-2.226%]; AF: 1.19% ± 0.32%, P < 0.001; CI [0.560%-1.822%]) by comparing the differences of the means. Pooled nondegenerative IVDs (Pfirrmann 1 and 2) had significantly lower gagCEST effects in patients suffering from SpA compared with healthy controls in NP (P < 0.001; CI [1.176%-2.337%]) and AF (P < 0.001; CI [0.858%-1.779%]). No significant difference of MTRasym values was found in degenerative IVDs between patients and controls in NP (P = 0.204; CI [-0.504%-2.170%]). CONCLUSION: GagCEST analysis of morphologically nondegenerative IVDs (Pfirrmann score 1 and 2) in T2 w images demonstrated significantly lower GAG values in patients with spondyloarthritis in NP and AF, possibly representing a depletion of GAG in spondyloarthritis in the absence of morphologic degeneration.

Comparison of quantitative and semiquantitative dynamic contrast-enhanced MRI with respect to their correlation to delayed gadolinium-enhanced MRI of the cartilage in patients with early rheumatoid arthritis.

OBJECTIVE: The objective of this study was to investigate the correlation between semiquantitative and quantitative dynamic contrast-enhanced (DCE) parameters with delayed gadolinium-enhanced magnetic resonance imaging (MRI) of the cartilage (dGEMRIC). METHODS: Fifteen patients with early rheumatoid arthritis (RA) from the ArthroMark cohort were investigated at a 3-T MRI scanner. The metacarpophalangeal (MCP) joint of the index finger was examined with DCE-MRI and dGEMRIC. Semiquantitative and quantitative DCE perfusion parameters were calculated. The RA MRI score of the second MCP joint and the joint space width were measured. RESULTS: Significant correlations were noted between both semiquantitative and quantitative DCE parameters and the RA MRI score of the second MCP joint. There was a significant negative correlation between DCE parameters and dGEMRIC. No association between joint space width and DCE parameters was observed. CONCLUSIONS: Semiquantitative and quantitative analyses of perfusion are applicable to show that cartilage damage correlates with the inflammation activity despite the absence of joint space narrowing.