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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.

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.

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 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).

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.

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

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.

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 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 assess the glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in healthy volunteers with facet tropism (FT) and sagittal facet joint (FJ) orientation using glycosaminoglycan chemical exchange saturation transfer imaging (gagCEST).Seventy-five lumbar IVDs of twenty-five young, healthy volunteers without any history of lumbar spine pathologies (13 female; 12 male; mean age: 28.0 ± 4.4 years; range: 21-35 years) were examined with a 3T MRI scanner. Orientation of FT and FJ were assessed for L3/4, L4/5 and L5/S1 using standard T2 weighted images. Biochemical gagCEST imaging was used to determine the GAG content of each nucleus pulposus (NP) and annulus fibrosus (AF).Significantly higher gagCEST values of NP were found in volunteers without FT and normal FJ orientation compared to volunteers with FT and sagittal FJ orientation45° (P 0.0001). GagCEST values were significantly higher in volunteers without FT compared to volunteers with moderate or severe FT (moderate FT: P 0.0001; severe FT: P = 0.0033). Volunteers with normal FJ orientation showed significantly higher gagCEST values compared to those with sagittal FJ orientation45° (P 0.001). We found a significant, negative correlation between gagCEST values and higher angels in sagittal FJ orientation (rho = -0.459; P 0.0001).GagCEST analysis indicated lower GAG values of NP in young volunteers with FT and sagittal orientated FJ, indicating that FT and sagittal orientation of the FJ represent risk factors for the development of early biochemical alterations of lumbar IVDs.

Methods Cohorts and Acquisition: 41 volunteers (HV, 25 ± 5 y.), 14 STEMI (63 ± 7 y.), 12 DCM (54 ± 17 y.), and 5 DCM+LBBB (47 ± 8 y.) patients were investigated. Acquisition parameters were: Philips Achieva 3 T, 32 channel cardiac coil, velocity encoded (Tissue Phase Mapping, TPM) segmented black-blood gradient echo with VENC = 30 cm/s, TR/TE = 6.1/4.6 ms, FOV adapted to patient size, resolution = 2x8 mm, 3 k-lines/segment, SENSE = 2, phase interval = 30 ms, and nominal scan time = 5:51 min:sec for 3 short axis slices. Parameters (see [1]): a) velocity-based: Standard Deviation of Times to Peak [SD(TTP)], Asynchrony Correlation Coefficient [ACC], Temporal Uniformity of Velocity [TUV], and Velocity Ranges (difference: maximum-minimum velocity). b) strain-based: Base Apex Rotation Correlation [BARC], Temporal Uniformity of Strain [TUS], Standard Deviation of Onset/Peak Time [SD(T)], Coefficient of Variation [CV], Difference between Septal and Lateral Peak Circumferential Strain [DiffSLpeakCS], Onset/Peak Of Shortening Delay [Delay], Regional Variance of Strain [RVS], and Regional Variance Vector of Strain [RVVPS]. Analysis: The significance of resulting differences between the different groups was assessed via non-parametric Kruskal-WallisTest.

Introduction Synovial inflammation and joint destruction in rheumatoid arthritis (RA) may progress despite clinical remission. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to detect synovial inflammation in RA. Although small joints such as metacarpophalangeal (MCP) joints are mainly affected by RA, MRI findings have never been directly compared to histological synovitis in MCP synovial tissue. The objective of the current study was therefore to analyse if DCE-MRI relates to histological signs of synovitis small RA joints. Methods In 9 RA patients, DCE-MRI (3 Tesla, dynamic 2D T1 weighted turbo-flash sequence) of the hand was performed prior to arthroscopically-guided synovial biopsies from the second MCP of the imaged hand. Maximum enhancement (ME), rate of early enhancement, and maximum rate of enhancement were assessed in the MCP. Synovial biopsies were stained for determination of sublining CD68 and the Synovitis Score. Correlations between MRI and histological data were calculated according to Spearman. Results ME of the MCP significantly correlated to sublining CD68 staining (r = 0.750, P = 0.02), the Synovitis Score (r = 0.743, P = 0.02), and the subscores for lining layer hypertrophy (r = 0.789, P = 0.01) and cellular density (r = 0.842; P = 0.004). Conclusions Perfusion imaging of synovial tissue in RA finger joints employing DCE-MRI reflects histological synovial inflammation. According to our study, ME is the most closely associated parameter amongst the measures considered.