MRI in patients with a cerebral aneurysm clip; review of the literature and incident databases and recommendations for the Netherlands.

BACKGROUND: In the past ferromagnetic cerebral aneurysm clips that are contraindicated for Magnetic Resonance Imaging (MRI) have been implanted. However, the specific clip model is often unknown for older clips, which poses a problem for individual patient management in clinical care. METHODS: Literature and incident databases were searched, and a survey was performed in the Netherlands that identified time periods at which ferromagnetic and non-ferromagnetic clip models were implanted. Considering this information in combination with a national expert opinion, we describe an approach for risk assessment prior to MRI examinations in patients with aneurysm clips. The manuscript is limited to MRI at 1.5 T or 3 T whole body MRI systems with a horizontal closed bore superconducting magnet, covering the majority of clinical Magnetic Resonance (MR) systems. RESULTS: From the literature a list of ferromagnetic clip models was obtained. The risk of movement or rotation of the clip due to the main magnetic field in case of a ferromagnetic clip is the main concern. In the incident databases records of four serious incidents due to aneurysm clips in MRI were found. The survey in the Netherlands showed that from 2000 onwards, no ferromagnetic clips were implanted in Dutch hospitals. DISCUSSION: Recommendations are provided to help the MR safety expert assessing the risks when a patient with a cerebral aneurysm clip is referred for MRI, both for known and unknown clip models. This work was part of the development of a guideline by the Dutch Association of Medical Specialists.

Characterizing the Bone Marrow Environment in Advanced-Stage Myelofibrosis during Ruxolitinib Treatment Using PET/CT and MRI: A Pilot Study.

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Early Response Prediction of Multiparametric Functional MRI and 18F-FDG-PET in Patients with Head and Neck Squamous Cell Carcinoma Treated with (Chemo)Radiation.

BACKGROUND: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. METHODS: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). RESULTS: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). CONCLUSIONS: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.

Repeatability of IVIM biomarkers from diffusion-weighted MRI in head and neck: Bayesian probability versus neural network.

PURPOSE: The intravoxel incoherent motion (IVIM) model for DWI might provide useful biomarkers for disease management in head and neck cancer. This study compared the repeatability of three IVIM fitting methods to the conventional nonlinear least-squares regression: Bayesian probability estimation, a recently introduced neural network approach, IVIM-NET, and a version of the neural network modified to increase consistency, IVIM-NETmod . METHODS: Ten healthy volunteers underwent two imaging sessions of the neck, two weeks apart, with two DWI acquisitions per session. Model parameters (ADC, diffusion coefficient Dt , perfusion fraction fp , and pseudo-diffusion coefficient Dp ) from each fit method were determined in the tonsils and in the pterygoid muscles. Within-subject coefficients of variation (wCV) were calculated to assess repeatability. Training of the neural network was repeated 100 times with random initialization to investigate consistency, quantified by the coefficient of variance. RESULTS: The Bayesian and neural network approaches outperformed nonlinear regression in terms of wCV. Intersession wCV of Dt in the tonsils was 23.4% for nonlinear regression, 9.7% for Bayesian estimation, 9.4% for IVIM-NET, and 11.2% for IVIM-NETmod . However, results from repeated training of the neural network on the same data set showed differences in parameter estimates: The coefficient of variances over the 100 repetitions for IVIM-NET were 15% for both Dt and fp , and 94% for Dp ; for IVIM-NETmod , these values improved to 5%, 9%, and 62%, respectively. CONCLUSION: Repeatabilities from the Bayesian and neural network approaches are superior to that of nonlinear regression for estimating IVIM parameters in the head and neck.

Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation.

OBJECTIVES: To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. METHODS: Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. RESULTS: In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). CONCLUSIONS: Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. KEY POINTS: • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

Repeatability of tumor perfusion kinetics from dynamic contrast-enhanced MRI in glioblastoma.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients. METHODS: The Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2-5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland-Altman and percent repeatability coefficient (%RC) analysis. RESULTS: The perfusion parameter with the least RC was the plasma volume fraction (v p ), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (v e ) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (K trans ) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF. CONCLUSIONS: As much as 72% change in K trans (eTM, autoVIF) can be attributable to non-biological changes in the 2-5 days between double-baseline imaging. Poor K trans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck.

BACKGROUND: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF. MATERIALS AND METHODS: We compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (ve, Ktrans, kep) in muscle-located outside the radiation area-were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans. RESULTS: Several parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: ve (0.65, 0.74, 0.58, 0.32), Ktrans (0.30, 0.21, 0.13, 0.06), kep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs. CONCLUSION: Image-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area.

A pharmacokinetic model including arrival time for two inputs and compensating for varying applied flip-angle in dynamic gadoxetic acid-enhanced MR imaging.

PURPOSE: Pharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration. METHODS: We propose an improved pharmacokinetic model for the liver that (1) analytically models the arrival-time of the contrast agent for both inputs separately; (2) implicitly compensates for signal fluctuations that can be modeled by varying applied flip-angle e.g. due to B1-inhomogeneity. Orton's AIF model is used to analytically represent the vascular input functions. The inputs are independently embedded into the Sourbron model. B1-inhomogeneity-driven variations of flip-angles are accounted for to justify the voxel's displacement with respect to a pre-contrast image. RESULTS: The new model was shown to yield lower root mean square error (RMSE) after fitting the model to all but a minority of voxels compared to Sourbron's approach. Furthermore, it outperformed this existing model in the majority of voxels according to three model-selection criteria. CONCLUSION: Our work primarily targeted to improve pharmacokinetic modeling for DCE-MRI of the liver. However, other types of pharmacokinetic models may also benefit from our approaches, since the techniques are generally applicable.

Prolonged time between intravenous contrast administration and image acquisition results in increased synovial thickness at magnetic resonance imaging in patients with juvenile idiopathic arthritis.

BACKGROUND: Post-contrast synovial thickness measurement is necessary for scoring disease activity in juvenile idiopathic arthritis (JIA). However, the timing of post-contrast sequences varies widely among institutions. This variation in timing could influence thickness measurements. OBJECTIVE: To measure thickness of the synovial membrane on early and late post-contrast knee magnetic resonance (MR) images of patients with JIA. MATERIALS AND METHODS: Dynamic contrast-enhanced T1-weighted knee MR images of 53 children with JIA with current or past knee arthritis were used to study synovial thickness at time point 1 (about 1 min) and time point 2 (about 5 min after contrast administration). Two experienced readers, who were blinded for the time point, independently measured synovial thickness at a predefined, marked location in the patellofemoral compartment on randomized images. Synovial thickness at the two time points was compared using the Wilcoxon signed rank test. Repeatibility of the synovial thickness measurements was studied using intraclass correlation coefficients and Bland-Altman plots. RESULTS: Median synovial thickness of the 53 patients (median age: 13.5 years, 59% female) increased with prolonged post-contrast interval with a synovial thickness of 1.4 mm at time point 1 and a synovial thickness of 1.5 mm at time point 2 (P<0.001). Repeated synovial thickness measurements showed an intraclass correlation coefficient (ICC) of 0.75, P<0.05 for time point 1 and an ICC of 0.91, P<0.05 for time point 2. CONCLUSION: Post-contrast synovial membrane thickness measurements are time-dependent. Therefore, standardization of post-contrast image acquisition timing is important to achieve consistent grading of synovial inflammation.

Correction to: Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents.

The original version of this article, published on 12 June 2017, unfortunately contained a mistake.

Evaluation of Dispersion MRI for Improved Prostate Cancer Diagnosis in a Multicenter Study.

OBJECTIVE: The purpose of this study is to compare dispersion MRI and Tofts model (TM) for analysis of quantitative dynamic contrast-enhanced (DCE) MRI (DCE-MRI) for localization of prostate cancer and to assess the correlation between quantitative DCE-MRI parameters and tumor grade. MATERIALS AND METHODS: This retrospective multicenter study included 80 patients with biopsy-proven prostate cancer who underwent DCE-MRI followed by radical prostatectomy. DCE-MRI parameters were extracted from dispersion MRI analysis (the dispersion parameter [kd], the flux rate [kep], and the intravascular mean transit time) and TM analysis (the forward volume transfer constant [Ktrans], kep, and the extravascular extracellular volume fraction [ve]). ROIs representing benign and malignant tissue were drawn on each DCE-MRI slice according to the histopathologic findings, and the diagnostic performance of the estimated parameters for the diagnosis of prostate cancer was evaluated using fivefold cross-validation and ROC curve analysis. Further analysis was conducted for the two most relevant parameters (i.e., kd [for dispersion MRI] and kep [for TM]), to investigate the correlation between DCE-MRI parameters and tumor grade. RESULTS: DCE-MRI parameters were significantly different between benign and malignant prostate tissue (p < 0.0001). The dispersion MRI parameter kd outperformed all other DCE-MRI parameters for prostate cancer diagnosis, showing the highest area under the ROC curve value (p < 0.0001). Only a weak linear correlation (Pearson r = 0.18; p < 0.05) was found between the dispersion parameter and the Gleason grade group. CONCLUSION: Dispersion MRI outperformed TM analysis, improving the diagnostic performance of quantitative DCE-MRI for prostate cancer localization. Of the DCE-MRI parameters, kd (for dispersion MRI) and kep (for TM) provided only poor characterization of tumor grade.

Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (I): Theory, method, and phantom experiments.

BACKGROUND: The arterial input function (AIF) represents the time-dependent arterial contrast agent (CA) concentration that is used in pharmacokinetic modeling. PURPOSE: To develop a novel method for estimating the AIF from dynamic contrast-enhanced (DCE-) MRI data, while compensating for flow enhancement. STUDY TYPE: Signal simulation and phantom measurements. PHANTOM MODEL: Time-intensity curves (TICs) were simulated for different numbers of excitation pulses modeling flow effects. A phantom experiment was performed in which a solution (without CA) was passed through a straight tube, at constant flow velocity. FIELD STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGRs) at 3T MRI, both in the simulations and in the phantom experiment. TICs were generated for a duration of 373 seconds and sampled at intervals of 1.247 seconds (300 timepoints). ASSESSMENT: The proposed method first estimates the number of pulses that spins have received, and then uses this knowledge to accurately estimate the CA concentration. STATISTICAL TESTS: The difference between the median of the estimated number of pulses and the true value was determined, as well as the interquartile range (IQR) of the estimations. The estimated CA concentrations were evaluated in the same way. The estimated number of pulses was also used to calculate flow velocity. RESULTS: The difference between the median estimated and reference number of pulses varied from -0.005 to -1.371 (corresponding IQRs: 0.853 and 48.377) at true values of 10 and 180 pulses, respectively. The difference between the median estimated CA concentration and the reference value varied from -0.00015 to 0.00306 mmol/L (corresponding IQRs: 0.01989 and 1.51013 mmol/L) at true values of 0.5 and 8.0 mmol/l, respectively, at an intermediate value of 100 pulses. The estimated flow velocities in the phantom were within 10% of the reference value. DATA CONCLUSION: The proposed method accurately corrects the MRI signal affected by the inflow effect. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1190-1196.

Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (II): Applications in spine diagnostics and assessment of crohn's disease.

BACKGROUND: Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. PURPOSE/HYPOTHESIS: To evaluate a novel method for subject-specific AIF estimation that takes inflow effects into account. STUDY TYPE: Retrospective study. SUBJECTS: Thirteen clinical patients referred for spine-related complaints; 21 patients from a study into luminal Crohn's disease with known Crohn's Disease Endoscopic Index of Severity (CDEIS). FIELD STRENGTH/SEQUENCE: Dynamic fast spoiled gradient echo (FSPGR) at 3T. ASSESSMENT: A population-averaged AIF, AIFs derived from distally placed regions of interest (ROIs), and the new AIF method were applied. Tofts' PK model parameters (including vp and Ktrans ) obtained with the three AIFs were compared. In the Crohn's patients Ktrans was correlated to CDEIS. STATISTICAL TESTS: The median values of the PK model parameters from the three methods were compared using a Mann-Whitney U-test. The associated variances were statistically assessed by the Brown-Forsythe test. Spearman's rank correlation coefficient was computed to test the correlation of Ktrans to CDEIS. RESULTS: The median vp was significantly larger when using the distal ROI approach, compared to the two other methods (P < 0.05 for both comparisons, in both applications). Also, the variances in vp were significantly larger with the ROI approach (P < 0.05 for all comparisons). In the Crohn's disease study, the estimated Ktrans parameter correlated better with the CDEIS (r = 0.733, P < 0.001) when the proposed AIF was used, compared to AIFs from the distal ROI method (r = 0.429, P = 0.067) or the population-averaged AIF (r = 0.567, P = 0.011). DATA CONCLUSION: The proposed method yielded realistic PK model parameters and improved the correlation of the Ktrans parameter with CDEIS, compared to existing approaches. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2018;47:1197-1204.

MRI protocol optimization for quantitative DCE-MRI of the spine.

PURPOSE: In this study we systematically investigated different Dynamic Contrast Enhancement (DCE)-MRI protocols in the spine, with the goal of finding an optimal protocol that provides data suitable for quantitative pharmacokinetic modelling (PKM). MATERIALS AND METHODS: In 13 patients referred for MRI of the spine, DCE-MRI of the spine was performed with 2D and 3D MRI protocols on a 3T Philips Ingenuity MR system. A standard bolus of contrast agent (Dotarem - 0.2ml/kg body weight) was injected intravenously at a speed of 3ml/s. Different techniques for acceleration and motion compensation were tested: parallel imaging, partial-Fourier imaging and flow compensation. The quality of the DCE MRI images was scored on the basis of SNR, motion artefacts due to flow and respiration, signal enhancement, quality of the T1 map and of the arterial input function, and quality of pharmacokinetic model fitting to the extended Tofts model. RESULTS: Sagittal 3D sequences are to be preferred for PKM of the spine. Acceleration techniques were unsuccessful due to increased flow or motion artefacts. Motion compensating gradients failed to improve the DCE scans due to the longer echo time and the T2* decay which becomes more dominant and leads to signal loss, especially in the aorta. The quality scoring revealed that the best method was a conventional 3D gradient-echo acquisition without any acceleration or motion compensation technique. The priority in the choice of sequence parameters should be given to reducing echo time and keeping the dynamic temporal resolution below 5s. Increasing the number of acquisition, when possible, helps towards reducing flow artefacts. In our setting we achieved this with a sagittal 3D slab with 5 slices with a thickness of 4.5mm and two acquisitions. CONCLUSION: The proposed DCE protocol, encompassing the spine and the descending aorta, produces a realistic arterial input function and dynamic data suitable for PKM.

Construct validity of pixel-by-pixel DCE-MRI: Correlation with conventional MRI scores in juvenile idiopathic arthritis.

OBJECTIVES: To assess the capability of the pixel-by-pixel DCE-MRI time intensity curve (TIC)-shape analysis method in the evaluation of juvenile idiopathic arthritis (JIA) disease activity by correlating DCE-MRI parameters with semi-quantitative conventional-MRI scores of synovitis. METHODS: Clinical, laboratory, and (DCE)-MRI datasets of 85 JIA patients were prospectively obtained. TIC-shapes of each voxel were classified into one of seven predefined color-coded TIC shape categories. Spatial information on the relative amount of TIC-shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV) was calculated of the synovial membrane. The grade of synovitis was scored on conventional MR images by two readers using the validated JAMRIS system. The Bonferroni method was used to correct for multiple testing, therefore, a P value of <0.0056 is considered significant (0.05/9=0.0056). RESULTS: The semi-quantitative JAMRIS synovitis score correlated substantially with the ME, EV, and iAUC (Rs=0.658, P<0.001; Rs=0.618, P<0.001; Rs=0.639, P<0.001), and moderately with MIS (Rs=0.453, P<0.001). A poor correlation was observed between the relative number of TIC-shapes 2-5 and the JAMRIS synovitis score (Rs=0.209, P=0.054; Rs=0.328, P=0.002; Rs=0.241, P=0.023; Rs=-0.241, P=0.026). CONCLUSION: In this explorative study, both TIC shape and semi-quantitative DCE-MRI analysis methods showed moderate to substantial correlations with conventional MRI scores of disease activity, indicating that this methods are feasible. Further research is warranted whether DCE-MRI holds potential to become an objective and quantitative method for the evaluation of disease activity in JIA.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents.

OBJECTIVES: To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA). METHODS: Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI. RESULTS: Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10-3mm2/s in MRI-active and 1.25 × 10-3mm2/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10-3mm2/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05). CONCLUSIONS: Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI. KEY POINTS: • MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis • Both DWI and DCE can differentiate active from inactive JIA • The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA • DWI is non-invasive and thus safer and more patient-friendly • DWI is a potentially powerful and non-invasive imaging biomarker for JIA.

Dynamic contrast-enhanced magnetic resonance imaging can play a role in predicting flare in juvenile idiopathic arthritis.

PURPOSE: The study was performed to determine whether conventional and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters of a previously affected target joint in patients with clinically inactive juvenile idiopathic arthritis (JIA) have prognostic meaning for a flare of joint inflammation during follow-up. MATERIAL AND METHODS: Thirty-two JIA patients with clinically inactive disease at the time of MRI of the knee were prospectively included. DCE-MRI provided both descriptive measures and time-intensity-curve shapes, representing functional properties of the synovium. Conventional MRI outcome measures included validated scores for synovial hypertrophy, bone marrow edema, cartilage lesions and bone erosions. During a 2-year period the patients were monitored by their pediatric rheumatologist and clinical flares were registered. RESULTS: MRI analysis revealed synovial hypertrophy in 13 (39.4%) of the clinically inactive patients. Twelve patients (37.5%) had at least one flare during 2-year clinical follow-up. Persistently inactive and flaring patients differed significantly in the maximum enhancement of the synovium on the DCE-MRI (p<0.05), whereas no difference was found between these two groups in any of the baseline scores of conventional MRI. CONCLUSIONS: Our prospective clinical follow-up study indicates that the assessment of 'maximum enhancement' upon DCE-MRI may be able to predict a clinical flare within 2 years in inactive JIA patients.

Dynamic contrast-enhanced magnetic resonance imaging of the wrist in children with juvenile idiopathic arthritis.

BACKGROUND: Dynamic contrast-enhanced MRI provides information on the heterogeneity of the synovium, the primary target of disease in children with juvenile idiopathic arthritis (JIA). OBJECTIVE: To evaluate the feasibility of dynamic contrast-enhanced MRI in the wrist of children with JIA using conventional descriptive measures and time-intensity-curve shape analysis. To explore the association between enhancement characteristics and clinical disease status. MATERIALS AND METHODS: Thirty-two children with JIA and wrist involvement underwent dynamic contrast-enhanced MRI with movement-registration and were classified using validated criteria as clinically active (n = 27) or inactive (n = 5). Outcome measures included descriptive parameters and the classification into time-intensity-curve shapes, which represent the patterns of signal intensity change over time. Differences in dynamic contrast-enhanced MRI outcome measures between clinically active and clinically inactive disease were analyzed and correlation with the Juvenile Arthritis Disease Activity Score was determined. RESULTS: Comprehensive evaluation of disease status was technically feasible and the quality of the dynamic dataset was improved by movement registration. The conventional descriptive measure maximum enhancement differed significantly between clinically active and inactive disease (P = 0.019), whereas time-intensity-curve shape analysis showed no differences. Juvenile Arthritis Disease Activity Score correlated moderately with enhancing volume (P = 0.484). CONCLUSION: Dynamic contrast-enhanced MRI is a promising biomarker for evaluating disease status in children with JIA and wrist involvement. Conventional descriptive dynamic contrast-enhanced MRI measures are better associated with clinically active disease than time-intensity-curve shape analysis.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Pharmacokinetic Modeling: Initial Experience in Patients With Early Arthritis.

OBJECTIVE: Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs). METHODS: Forty-seven patients with early arthritis (arthritis duration <1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs. RESULTS: The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve ). CONCLUSION: These results suggest that the K(trans) , kep , and ve can be used to detect synovial inflammation in patients with early arthritis, and these PKM parameters may be helpful in differential diagnosis. This approach may also be useful in translational research analyzing tissue microcirculation and angiogenesis.

Feasibility of diffusion-weighted magnetic resonance imaging in patients with juvenile idiopathic arthritis on 1.0-T open-bore MRI.

OBJECTIVE: To evaluate the feasibility of non-invasive diffusion-weighted imaging (DWI) of the knee of children with juvenile idiopathic arthritis (JIA) and, further, to analyze the apparent diffusion coefficient (ADC) levels to distinguish synovium from effusion. MATERIALS AND METHODS: Standard magnetic resonance imaging of the knee including post-contrast imaging was obtained in eight patients (mean age, 12 years 8 months, five females) using an open-bore magnetic resonance imaging system (1.0 T). In addition, axially acquired echo-planar DWI datasets (b-values 0, 50, and 600) were prospectively obtained and the diffusion images were post-processed into ADC50-600 maps. Two independent observers selected a region of interest (ROI) for both synovium and effusion using aligned post-contrast images as landmarks. Mann-Whitney U test was performed to compare ADC synovium and ADC effusion. RESULTS: DWI was successfully obtained in all patients. When data of both observers was combined, ADC synovium was lower than ADC effusion in the ROI in seven out of eight patients (median, 1.92 × 10(-3) mm(2)/s vs. 2.40 × 10(-3) mm(2)/s, p = 0.006, respectively). Similar results were obtained when the two observers were analyzed separately (observer 1: p = 0.006, observer 2: p = 0.04). CONCLUSIONS: In this pilot study, on a patient-friendly 1.0-T open-bore MRI, we demonstrated that DWI may potentially be a feasible non-invasive imaging technique in children with JIA. We could differentiate synovium from effusion in seven out of eight patients based on the ADC of synovium and effusion. However, to select synovium and effusion on DWI, post-contrast images were still a necessity.