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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.

Objectives As in-vivo knowledge of training-induced remodeling of intervertebral discs (IVD) is scarce, this study assessed how lumbar IVDs change as a function of long-term training in elite athletes and age-matched controls using compositional Magnetic Resonance Imaging (MRI). Design Prospective case-control study. Methods Prospectively, lumbar spines of 17 elite rowers (ERs) of the German national rowing team (mean age: 23.9 ± 3.3 years) were imaged on a clinical 3.0 T MRI scanner. ERs were imaged twice during the annual training cycle, i.e., at training intensive preseason preparations (t0) and 6 months later during post-competition recovery (t1). Controls (n = 22, mean age: 26.3 ± 1.9 years) were imaged once at corresponding time points (t0: n = 11; t1: n = 11). Segment-wise, the glycosaminoglycan (GAG) content of lumbar IVDs (n = 195) was determined using glycosaminoglycan chemical exchange saturation transfer (gagCEST). Linear mixed models were set up to assess the influence of cohort and other variables on GAG content. Results During preseason, IVD GAG values of ERs were significantly higher than those of controls (ERs(t0): 2.58 ± 0.27% (mean ± standard deviations); controls(t0): 1.43 ± 0.36%; p ≤ 0.001), while during post-competition recovery, such differences were not present anymore (ERs(t1): 2.11 ± 0.18%; controls(t1): 1.89 ± 0.24%; p = 0.362). Conclusions Professional elite-level rowing is transiently associated with significantly higher gagCEST values, which indicate increased lumbar IVD-GAG content and strong remodeling effects in response to training. Beyond professional rowing, core-strengthening full-body exercise may help to enhance the resilience of the lumbar spine as a potential therapeutic target in treating back pain.

To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence. 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. 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. We successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner.

To assess the performance of two point (2-pt) Dixon-based chemical exchange saturation transfer (CEST) imaging for fat suppression in renal transplant patients.The 2-pt Dixon-based CEST MRI was validated in an egg-phantom and in fourteen renal transplant recipients (5 females and 9 males; age range: 23-78 years; mean age: 51 ± 16.8). All CEST experiments were performed on a 3 T clinical MRI scanner using a dual-echo CEST sequence. The 2-pt Dixon technique was applied to generate water-only CEST images at different frequency offsets, which were further used to calculate the z-spectra. The magnetization transfer ratio asymmetry (MTRResults of the in vitro experiments suggest that the 2-pt Dixon technique enables effective fat peak removal and does not introduce additional asymmetries to the z-spectrum. Accordingly, our results in vivo show that the fat-corrected amide proton transfer (APT) effect in the kidney is significantly higher compared to that obtained from the CEST data acquired close to the in-phase condition both in the renal cortex (-0.1 [0.7] vs. -0.7 [1.2], P = 0.029) and medulla (0.3 [0.8] vs. 0.01 [1.3], P = 0.049), indicating that the 2-pt Dixon-based CEST method increases the specificity of the APT contrast by correcting the fat-induced artifacts.Combination of the dual-echo CEST acquisition with Dixon post-processing provides effective water-fat separation, allowing more accurate quantification of the APT CEST effect in the transplanted kidney.

D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.

• 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.

Purpose The present study assessed the influence of the NMDA receptor (R) antagonist amantadine (AMA) on cerebral dopamine D2/3R binding in relation to motor and exploratory activity in the rat. Methods D2/3R binding was determined in anaesthetized animals with small animal SPECT in baseline and after challenge with AMA (10 or 40 mg/kg) using [123I]IBZM as radioligand. Immediately post-challenge and prior to radioligand administration, motor/exploratory behaviors were assessed for 30 min in an open field. Each rat underwent measurements with a dedicated small animal MRI in order to gain anatomical information. Regions of interest were defined on SPECT-MRI overlays. The regional binding potentials in baseline and post-challenge were estimated by computing ratios of the specifically bound compartments to the cerebellar reference region. Results 40 mg/kg AMA reduced D2/3R binding in nucleus accumbens, caudateputamen and thalamus, while 10 mg/kg decreased D2/3R binding in the anterodorsal hippocampus. The higher dose decreased ambulatory activity, rearing and grooming, but elevated sitting and head-shoulder motility relative to both vehicle and the lower dose in the first 15 min post-challenge. Conclusions Results showed reductions of D2/3R binding in regions of the nigrostriatal and mesolimbic system after challenge with AMA, which reflect an increased availability of dopamine. Thereby, an inverse relationship between nigrostriatal and mesolimbic dopamine and motor/exploratory activity can be inferred. Findings may be relevant for the treatment of neurological and psychiatric conditions such as Parkinson's disease, Huntington's disease or schizophrenia, which are characterized by both dopaminergic and glutamatergic dysfunction.

Objective.To assess associations of synovial perfusion, cartilage quality, and outcome in rheumatoid arthritis (RA).Methods.Synovial perfusion and cartilage quality were assessed by dynamic contrast-enhanced magnetic resonance imaging in metacarpophalangeal joints of 28 treatment-naive patients with RA at baseline and at 3 and 6 months after methotrexate. Analysis was by linear mixed modeling.Results.Synovial perfusion variables were associated with remission (p < 0.05) and cartilage quality (p < 0.004). Maximum synovial enhancement was associated to European League Against Rheumatism response (p < 0.05). Synovial perfusion improved in nonresponders over time (p < 0.05).Conclusion.Synovial perfusion relates to remission, response, and cartilage quality in a cohort of therapy-naive patients with early RA.

Objective: To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVDs) in patients with radiculopathy compared with healthy volunteers with glycosaminoglycan chemical exchange saturation transfer (gagCEST). Methods: The lumbar spines of 15 patients with radiculopathy (9 women, 6 men; mean age 45 years; range: 19 - 80 years) and 13 healthy controls (10 women, 3 men; mean age 29 years; range: 19 - 38 years) without lumbar back pain or previous spine surgery were examined at a 3 Tesla (T) magnetic resonance imaging (MRI) scanner in this prospective study. The MRI protocol included standard morphological, sagittal, and transverse T2-weighted (T2w) images of the five lumbar IVDs (L1-S1) to assess Pfirrmann score and to detect disc disorders according to the Combined Task Force classification. To analyze biochemically the lumbar IVDs, a gagCEST sequence was applied to measure the GAG content of the nucleus pulposus (NP) and annulus fibrosus (AF). Results: Patients with radiculopathy indicated significantly lower gagCEST values in NP than healthy volunteers (2.82% ± 3.12% vs. 4.09% ± 2.25%, P = 0.017). The GAG content of AF showed no significant difference between volunteers and patients (2.66% ± 2.01% vs. 1.92% ± 2.56%; P = 0.175). Conclusions. Patients with radiculopathy presented with lower GAG values than healthy volunteers in NP, indicating an association between pain and IVD degeneration. gagCEST of lumbar IVDs is a powerful, non-invasive tool to investigate early disc degeneration, which we could demonstrate in the NP in our study collective.

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.

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.

Background: To compare the effect of Adalimumab (ADA) plus Methotrexate (MTX) versus MTX monotherapy in patients with therapy naïve early rheumatoid arthritis (eRA) on cartilage quality measured by glycosaminoglycan (GAG) content in cartilage using gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). Methods: Prospective double-blinded, randomized clinical trial of cartilage integrity in finger joints of eRA patients according to American College of Rheumatology/ European League Against Rheumatism. Patients were examined therapy-naïve, 12 and 24 weeks after initiation of Adalimumab+MTX or placebo+MTX with 3T-MRI, recording dGEMRIC values of metacarpophalangeal joints of index and middle finger. Results: The study was prematurely terminated due to theoretical safety concerns regarding gadolinium deposition in the brain after MR contrast agent application. Instead of 30 planned patients, 10 patients could be included in the Adalimumab group (ADA+MTX: 6 females, 44.9y, range: 19-65), four in the control group (Placebo+MTX: 2 females, 46.7y, range: 24-64). Between treatment groups, cartilage composition did not change significantly (ADA+MTX: dGEMRIC mean change 85.8ms, range -156.2–346.5ms; Placebo+MTX: mean change-30.75ms, range-273.0–131.0ms; W=27, p=0.37). Neverthless a significant increase of the dGEMRIC values over time was observed in the Adalimumab group (median change 75.88 ms p=0.0117), but not in the placebo group (median change 9.50, p=0.878).Conclusions: In patients with eRA, Adalimumab+MTX leads to a significant dGEMRIC improvement, indicating a possible reduction of cartilage damage in the finger joints. The level of significance for the difference of change in cartilage quality between groups, was not met, potentially due to lower than expected number of patients which could be recruited. Trial registration: The cartilage in early Rheumatoid Arthritis (CAR-ERA)-Study was approved by the local ethics committee of the Heinrich-Heine University of Duesseldorf (reference number: MO-LKP-719) and was registered at clinicaltrials.gov under the number NCT02150473 / CAR-ERA 2013-004604-19 (EudraCT Number).

To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence.Sodium MRI of human wrists was conducted on a 3T MR system using a dual-tunedNo differences for transversal of longitudinal relaxation times were found between RCJ and MCJ (TWe successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner.

In this review, a series of experiments is presented, in which γ-amino butyric acid (GABA)ergic and glutamatergic effects on dopamine function in the rat nigrostriatal and mesolimbic system was systematically assessed after pharmacological challenge with GABAA receptor (R) and and N-methyl d-aspartate (NMDA)R agonists and antagonists. In these studies, [123I]iodobenzamide binding to the D2/3R was mesured in nucleus accumbens (NAC), caudateputamen (CP), substantia nigra/ventral tegmental area (SN/VTA), frontal (FC), motor (MC) and parietal cortex (PC) as well as anterior (aHIPP) and posterior hippocampus (pHIPP) with small animal SPECT in baseline and after injection of either the GABAAR agonist muscimol (1 mg/kg), the GABAAR antagonist bicuculline (1 mg/kg), the NMDAR agonist d-cycloserine (20 mg/kg) or the NMDAR antagonist amantadine (40 mg/kg). Muscimol reduced D2/3R binding in NAC, CP, SN/VTA, THAL and pHIPP, while, after amantadine, decreases were confined to NAC, CP and THAL. In contrast, d-cycloserine elevated D2/3R binding in NAC, SN/VTA, THAL, frontal cortex, motor cortex, PC, aHIPP and pHIPP, while, after bicuculline, increases were confined to CP and THAL. Taken together, similar actions on regional dopamine levels were exterted by the GABAAR agonist and the NMDAR antagonist on the one side and by the GABAAR antagonist and the NMDAR agonist on the other, with agonistic action, however, affecting more brain regions. Thereby, network analysis suggests different roles of GABAARs and NMDARs in the mediation of nigrostriatal, nigrothalamocortical and mesolimbocortical dopamine function.

Purpose Reproducibility of quantitative perfusion analysis of DCE requires a standardized AIF acquisition. However, there are many different approaches for AIF assessment so that the absolute values of perfusion parameters may vary depending on the used method. This study analyzes the influence of the method of AIF determination on quantitative DCE-MRI. Methods In this retrospective, single-center, cohort study three different methods of AIF determination in 50 consecutive patients with multiparametric MRI of the prostate were conducted. As a reference, AIF was selected manually by defining a region of interest in an artery manually (AIFm). The second method (AIFa), based on an automated algorithm and the third, population-derived AIFp where then compared. Primary endpoint were differences in the performance of the perfusion parameters Ktrans, ve and kep regarding the AIF acquisition methods, secondary endpoints consisted of the evaluation of differences in the peripheral and transition zone of the prostate (PZ, TZ). Results In all three methods, Ktrans, ve, and kep were significantly higher in PZ than in TZ with Ktrans showing least overlapping. There were no significant differences for Ktrans determined with AIFm and AIFa (0.3 ± 0.2 min−1 for PZ for both and 0.5 ± 0.3 min−1 for TZ in AIFm and 0.4 ± 0.3 min−1 in AIFa), while there were great differences between AIFa and AIFp and AIFm and AIFp (0.1 ± 0.03 min−1 for TZ and PZ in AIFp). Spearman test demonstrated good correlation of values for Ktrans and kep in all 3 methods (ρ ≥ 0.76). AIFa showed a success rate of 98% in finding the artery. Conclusion AIFa is a recommendable user-independent automatical method to determine quantitative perfusion parameters allowing an objective measurement and saving interactive time for the radiologist. AIFp may be applied as second alternative method.

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.

Purpose To evaluate the feasibility of renal diffusion quantification using the Pade 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

D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.

The study was performed to preoperatively assess the cartilage integrity of cervical intervertebral discs (IVDs) using Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC). Therefore, fifty-three cervical intervertebral discs of nine preoperative patients with neck and shoulder/arm pain scheduled for discectomy (5 females, 4 males; mean age: 47.1 ± 8.4 years; range: 36 - 58 years) were included for biochemical analysis in this retrospective study. The patients underwent 3T magnetic resonance imaging (MRI) including biochemical imaging with dGEMRIC and morphological, sagittal T2 weighted (T2w) imaging. Cervical IVDs were rated using an MRI based grading system for cervical IVDs on T2w images. Region-of-interest measurements were performed in the nucleus pulposus (NP) and annulus fibrosus (AF) and a dGEMRIC index was calculated. Our results demonstrated that IVDs scheduled for discectomy showed significantly lower dGEMRIC index compared to IVDs that did not require surgical intervention in NP and AF (NP: 898.4 ms ± 191.9 ms vs. 1150.3 ms ± 320.7, p = 0.008; AF: 738.7 ms ± 183.8 ms vs. 984.6 ms ± 178.9, p = 0.008). For Miyazaki score 3, the dGEMRIC indices were significantly lower in IVDs scheduled for surgery compared to non-operated discs for NP (p = 0.043) and AF (p = 0.018). In conclusion we could demonstrate that biochemical imaging with dGEMRIC is feasible in cervical IVDs. Significantly lower dGEMRIC index suggested GAG depletion in degenerated cervical IVD, scheduled for discectomy. This article is protected by copyright. All rights reserved

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

Purpose To optimize B 0 -field inhomogeneity correction for chemical exchange saturation transfer (CEST) imaging by investigating different water saturation shift referencing (WASSR) Z-spectrum shapes and different frequency correction techniques. Methods WASSR Z-spectra were simulated for different B 1 -fields and pulse durations (PD). Two parameter settings were used for further simulations and experiments (WASSR1: B 1 = 0.1 μT, PD = 50 ms; WASSR2: B 1 = 0.3 μT, PD = 40 ms). Four frequency correction techniques were investigated: 1) MinW: Minimum of the spline-interpolated WASSR-spectrum; 2) MSCF: maximum symmetry center frequency algorithm; 3) PMSCF: further development of MSCF algorithm; 4) BFit: fit with Bloch equations. Performance of frequency correction was assessed with Monte-Carlo simulations and in-vivo MR examinations in the brain and intervertebral disks. Results Different shapes of WASSR-Z-spectra were obtained by changing B 1 and PD including spectra with one (1-Peak) or two (2-Peak) minima. WASSR1 resulted in 1-Peak WASSR-spectrum, whereas WASSR2 resulted in 2-Peak WASSR-spectrum. Both Monte-Carlo simulations and in-vivo MR examinations revealed highest accuracy of field-inhomogeneity correction with WASSR1 combined with PMSCF or BFit. Conclusion Using a WASSR sequence, which results in a Z-spectrum with a single absorption peak, in combination with advanced postprocessing algorithms enables improved B 0 -field inhomogeneity correction for CEST imaging.

Background: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.Objectives:Is local perfusion in PsA patients measured by dynamic MRI associated to local cartilage loss?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 significant association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.Figure 1.dGEMRIC maps (third digit) and perfusion maps (peak parameter) of MCP, PIP, and DIP joints in 26-year-old male (A and B) and a 59-year-old female (C and D) with PsA. Lower dGEMRIC values are illustrated in D, indicating more proteoglycan loss than in A. Higher peak values are depicted in C, indicating a higher severity of synovitis than in B. Peak parameter is illustrated in mM/l per second, dGEMRIC indices in ms.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Anja Müller-Lutz: None declared, Miriam Frenken: None declared, Karl Ludger Radke: None declared, Stefan Vordenbäumen: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared

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.

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 k sw 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: k a = ( 9.95 ± 1.1 ) × 10 6 l/(mol·s) and k b = ( 6.21 ± 0.21 ) × 10 6 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.

Object To assess changes diffusion properties of renal cortex over the entire cardiac cycle using electrocardiogram-gated respiratory-triggered dynamic diffusion-weighted imaging (DWI). Materials and methods 20 healthy volunteers were investigated on a 1.5 T MR scanner. Blood flow velocity within the renal arteries was determined by electrocardiogram-gated phase-contrast measurements. For dynamic renal DWI, an electrocardiogram-gated respiratory-triggered coronal single-slice EPI sequence was acquired at 14 times at 20, 70, 120, 170, …, 570, 620, 720 ms after the R-wave over the cardiac cycle. ROI measurements were performed by two authors in the renal cortex on apparent diffusion coefficient (ADC) maps. A pulsatility index was calculated for ADC as maximal percentage change. Five subjects were measured twice to assess scan-rescan reproducibility. Results Flow measurements exhibited a minimum velocity of 15.7 ± 4.3 cm/s during the R-wave and a maximum of 43.2 ± 10.4 cm/s at 182.5 ± 48.3 ms after the R-wave. A minimal mean ADC of 2.19 ± 0.09 × 10−3 mm2/s was observed during the R-wave. A maximum mean ADC of 2.85 ± 0.20 × 10−3 mm2/s was measured 193 ± 57 ms after the R-wave. The mean ADC pulsatility index in the renal cortex was 29.9 ± 5.8%. ADC variation exhibited a significant correlation with pulsatile blood flow velocity. The scan-rescan reproducibility in this study had a low deviation of 0.3 ± 0.1%. The inter-reader reproducibility was 2.9 ± 0.6%. Conclusion Renal ADCs exhibit pulsatile characteristics. Due to the significant difference of systolic and diastolic ADCs, the pulsatility index can be calculated.

Background Can methotrexate (MTX) stop cartilage loss measured by Delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) in patients with early rheumatoid arthritis (eRA)? Objectives Objective of the study was to investigate biochemical cartilage composition under MTX therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with 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 dichotomized 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 are 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. Acknowledgements: Funding The ArthroMark project was founded by the Bundesministerium fur Bildung und Forschung(BMBF) grant number FKZ 01EC1009A Disclosure of Interest None declared

Purpose: The present study assessed the effects of the GABAA receptor (R) agonist muscimol (MUS), and the GABAAR antagonist bicuculline (BIC) on neocortical and subcortical radioligand binding to dopamine D2/3Rs in relation to motor and exploratory behaviors in the rat. Methods: D2/3R binding was measured with small animal SPECT in baseline and after challenge with either 1 mg/kg MUS or 1 mg/kg BIC, using [123I]IBZM as radioligand. Motor/exploratory behaviors were assessed for 30 min in an open field prior to radioligand administration. Anatomical information was gained with a dedicated small animal MRI tomograph. Based on the Paxinos rat brain atlas, regions of interest were defined on SPECT-MRI overlays. Estimations of the binding potentials in baseline and after challenges were obtained by computing ratios of the specifically bound compartments to the cerebellar reference region. Results: After MUS, D2/3R binding was significantly reduced in caudateputamen, nucleus accumbens, thalamus, substania nigra/ventral tegmental area, and posterior hippocampus relative to baseline (0.005 ≤ p ≤ 0.012). In all these areas, except for the thalamus, D2/3R binding was negatively correlated with grooming in the first half and positively correlated with various motor/exploratory behaviors in the second half of the testing session. After BIC, D2/3R binding was significantly elevated in caudateputamen (p = 0.022) and thalamus (p = 0.047) relative to baseline. D2/3R binding in caudateputamen and thalamus was correlated negatively with sitting duration and sitting frequency and positively with motor/exploratory behaviors in the first half of the testing time. Conclusions: Findings indicate direct GABAergic control over nigrostriatal and mesolimbic dopamine levels in relation to behavioral action. This may be of relevance for neuropsychiatric conditions such as anxiety disorder and schizophrenia, which are characterized by both dopaminergic and GABAergic dysfunction.

The study compares glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging of intervertebral discs corrected for solely BLumbar intervertebral discs of 20 volunteers were examined with TSignificant higher MTRThe B

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).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.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).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.

To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. 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). 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

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.

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

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 (T2w) 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