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.

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.

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.

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.

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.

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 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.

Reproducibility of DCE-MRI time-intensity curve-shape analysis in patients with knee arthritis: A comparison with qualitative and pharmacokinetic analyses.

PURPOSE: To compare the between-session reproducibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with time-intensity curve (TIC)-shape analysis in arthritis patients, within one scanner and between two different scanners, and to compare this method with qualitative analysis and pharmacokinetic modeling (PKM). MATERIALS AND METHODS: Fifteen knee joint arthritis patients were included and scanned twice on a closed-bore 1.5T scanner (n = 9, group 1), or on a closed-bore 1.5T and on an open-bore 1.0T scanner (n = 6, group 2). DCE-MRI data were postprocessed using in-house developed software ("Dynamo"). Disease activity was assessed. RESULTS: Disease activity was comparable between the two visits. In group 1 qualitative analysis showed the highest reproducibility with intraclass correlation coefficients (ICCs) between 0.78 and 0.98 and root mean square-coefficients of variation (RMS-CoV) of 8.0%-14.9%. TIC-shape analysis showed a slightly lower reproducibility with similar ICCs (0.78-0.97) but higher RMS-CoV (18.3%-42.9%). The PKM analysis showed the lowest reproducibility with ICCs between 0.39 and 0.64 (RMS-CoV 21.5%-51.9%). In group 2 TIC-shape analysis of the two most important TIC-shape types showed the highest reproducibility with ICCs of 0.78 and 0.71 (RMS-CoV 29.8% and 59.4%) and outperformed the reproducibility of the most important qualitative parameter (ICC 0.31, RMS-CoV 45.1%) and the within-scanner reproducibility of PKM analysis. CONCLUSION: TIC-shape analysis is a robust postprocessing method within one scanner, almost as reproducible as the qualitative analysis. Between scanners, the reproducibility of the most important TIC-shapes outperform that of the most important qualitative parameter and the within-scanner reproducibility of PKM analysis.

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.

Evaluation of conventional, dynamic contrast enhanced and diffusion weighted MRI for quantitative Crohn's disease assessment with histopathology of surgical specimens.

OBJECTIVES: To prospectively compare conventional MRI sequences, dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging (DWI) with histopathology of surgical specimens in Crohn's disease. METHODS: 3-T MR enterography was performed in consecutive Crohn's disease patients scheduled for surgery within 4 weeks. One to four sections of interest per patient were chosen for analysis. Evaluated parameters included mural thickness, T1 ratio, T2 ratio; on DCE-MRI maximum enhancement (ME), initial slope of increase (ISI), time-to-peak (TTP); and on DWI apparent diffusion coefficient (ADC). These were compared with location-matched histopathological grading of inflammation (AIS) and fibrosis (FS) using Spearman correlation, Kruskal-Wallis and Chi-squared tests. RESULTS: Twenty patients (mean age 38 years, 12 female) were included and 50 sections (35 terminal ileum, 11 ascending colon, 2 transverse colon, 2 descending colon) were matched to AIS and FS. Mural thickness, T1 ratio, T2 ratio, ME and ISI correlated significantly with AIS, with moderate correlation (r = 0.634, 0.392, 0.485, 0.509, 0.525, respectively; all P < 0.05). Mural thickness, T1 ratio, T2 ratio, ME, ISI and ADC correlated significantly with FS (all P < 0.05). CONCLUSIONS: Quantitative parameters from conventional, DCE-MRI and DWI sequences correlate with histopathological scores of surgical specimens. DCE-MRI and DWI parameters provide additional information. KEY POINTS: • Conventional MR enterography can be used to assess Crohn's disease activity. • Several MRI parameters correlate with inflammation and fibrosis scores from histopathology. • Dynamic contrast enhanced imaging and diffusion weighted imaging give additional information. • Quantitative MRI parameters can be used as biomarkers to evaluate Crohn's disease activity.

Pixel-by-pixel analysis of DCE-MRI curve shape patterns in knees of active and inactive juvenile idiopathic arthritis patients.

OBJECTIVES: To compare DCE-MRI parameters and the relative number of time-intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients. METHODS: DCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (n = 43) and inactive disease (n = 34). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (K(trans)), extravascular space fractional volume (V(e)) and reverse volume transfer constant (k(ep)) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane. RESULTS: Imaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036). CONCLUSIONS: The pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC. KEY POINTS: • The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure.

Accuracy of abdominal ultrasound and MRI for detection of Crohn disease and ulcerative colitis in children.

BACKGROUND: Endoscopy is currently the primary diagnostic technique for inflammatory bowel disease (IBD) in children. OBJECTIVE: To assess the accuracy of US and dynamic contrast-enhanced MRI for diagnosing inflammatory bowel disease and for distinguishing Crohn disease and ulcerative colitis in comparison to a reference standard. MATERIALS AND METHODS: Consecutive children with suspected IBD underwent diagnostic workup including ileocolonoscopy and upper gastrointestinal endoscopy as the reference standard, abdominal US, and MR enterography and colonography at 3 T. The protocol included a dynamic contrast-enhanced 3-D sequence. Sensitivity, specificity and kappa values were calculated for one ultrasonographer and two MRI observers. RESULTS: We included 28 children (15 boys) with mean age 14 years (range 10-17 years). The diagnosis was IBD in 23 children (72%), including 12 with Crohn disease, 10 with ulcerative colitis and 1 with indeterminate colitis. For the diagnosis of inflammatory bowel disease the sensitivity was 55% for US and 57% (both observers) for MR entero- and colonography, and the specificity was 100% for US and 100% (observer 1) and 75% (observer 2) for MR entero- and colonography. Combined MRI and US had sensitivity and specificity of 70% and 100% (observer 1) and 74% and 80% (observer 2), respectively. With the addition of a dynamic contrast-enhanced MR sequence, the sensitivity increased to 83% and 87%. US and MRI could only distinguish between Crohn disease and ulcerative colitis when terminal ileum lesions were present. CONCLUSION: US and MR entero- and colonography have a high accuracy for diagnosing inflammatory bowel disease in children but cannot be used to distinguish Crohn disease and ulcerative colitis.

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.

Dynamic contrast-enhanced MRI in determining disease activity in perianal fistulizing Crohn disease: a pilot study.

OBJECTIVE: The objective of our study was to perform a semiquantitative analysis of dynamic contrast-enhanced MRI for the evaluation of disease activity and therapeutic response in patients with perianal fistulizing Crohn disease. SUBJECTS AND METHODS: Sixteen consecutively registered patients with perianal Crohn disease underwent pelvic MRI. A dynamic contrast-enhanced sequence was performed at 3 T (temporal resolution, 4.2 seconds) during i.v. contrast injection. Maximum enhancement, initial slope of increase, volume transfer constant (K(trans)), and the extravascular space fractional volume (x028B;(e)) were calculated in a region of interest drawn around the fistula. Perianal disease activity index, C-reactive protein concentration, and an MRI-based activity score were calculated as reference standards. Six patients underwent a second MRI examination 6 weeks after starting treatment with anti-tumor necrosis factor α (anti-TNF-α). RESULTS: Perianal disease activity index moderately correlated with maximum enhancement (r = 0.67, p = 0.005), initial slope of increase (r = 0.58, p = 0.018), and volume of enhancing pixels (r = 0.79, p < 0.001) but not with K(trans) or x028B;(e). Volume of enhancing pixels also correlated with C-reactive protein concentration and the MRI-based score (r = 0.52, p = 0.041; r = 0.79, p < 0.001). The K(trans) values had decreased significantly 6 weeks after the start of anti-TNF-α therapy. CONCLUSION: Maximum enhancement and initial slope of increase correlate with disease activity in perianal Crohn disease. K(trans) may be an indicator of the effect of therapy on patients starting anti-TNF-α treatment.

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.

Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging.

The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract-based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H-MRS) in the left centrum semiovale (white matter) showed a reduction of N-acetylasparate/creatine indicative of axonal injury. Voxel-based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H-MRS only in the chemotherapy group. These results converge to suggest that high-dose adjuvant chemotherapy for breast cancer is associated with long-term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment.

Characteristics of synovial inflammation in early arthritis analysed by pixel-by-pixel time-intensity curve shape analysis.

OBJECTIVE: Dynamic contrast-enhanced (DCE-MRI) time-intensity curve (TIC) shape analysis has previously been used in oncology, where fast initial enhancement and early washout are associated with malignancy. As RA synovium has some tumour-like features, we investigated DCE-MRI TIC shape expression in early arthritis in relationship to diagnosis. METHODS: Twenty-eight DMARD-naïve, early arthritis patients (<1 year) with inflammation of at least one knee joint were included. At baseline DCE-MRI of the inflamed knee joint was performed, and the TIC shape type expression, maximal enhancement, maximum slope of increase and total volume of enhancing pixels were calculated. In addition, disease activity parameters were determined. At 2 years of follow-up, patients were classified as RA or non-RA according to established classification criteria. RESULTS: Type 4 TIC shape, characterized by fast initial enhancement followed by a quick washout phase, was significantly higher in patients fulfilling classification criteria for RA after 2 years of follow-up compared with non-RA patients (15.6 and 7.9%, respectively, P = 0.02). All other DCE-MRI parameters showed no differences between the groups, highlighting the specificity of this observation. CONCLUSION: A high expression of aggressive DCE-MRI TIC shape Type 4 is associated with RA. Our results are consistent with the view that increased vascularity plays a key role in the pathogenesis of RA. This study underlines the rationale for further studies investigating the prospect of DCE-MRI TIC shape analysis as a diagnostic tool in early arthritis and the relationship with development of destructive disease.

Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study.

Motoneuron disease is a term encompassing three phenotypes defined largely by the balance of upper versus lower motoneuron involvement, namely amyotrophic lateral sclerosis, primary lateral sclerosis and progressive muscular atrophy. However, neuroradiological and pathological findings in these phenotypes suggest that degeneration may exceed the neuronal system upon which clinical diagnosis is based. To further delineate the phenotypes within the motoneuron disease spectrum, this controlled study assessed the upper- and extra-motoneuron white matter involvement in cohorts of patients with motoneuron disease phenotypes shortly after diagnosis by comparing diffusion tensor imaging data of the different cohorts to those of healthy controls and directly between the motoneuron disease phenotypes (n = 12 for each cohort). Furthermore, we acquired follow-up data 6 months later to evaluate fractional anisotropy changes over time. Combined use of diffusion tensor tractography of the corticospinal tract and whole-brain voxel-based analysis allowed for comparison of the sensitivity of these techniques to detect white matter involvement in motoneuron disease. The voxel-based analysis demonstrated varying extents of white matter involvement in different phenotypes of motoneuron disease, albeit in quite similar anatomical locations. In general, fractional anisotropy reductions were modest in progressive muscular atrophy and most extensive in primary lateral sclerosis. The most extensive patterns of fractional anisotropy reduction were observed over time in the voxel-based analysis, indicating progressive extra-motor white matter degeneration in limb- and bulbar onset amyotrophic lateral sclerosis and in progressive muscular atrophy. The observation of both upper motor and extra-motoneuron involvement in all phenotypes of motoneuron disease shortly after diagnosis suggests that these are all part of a single spectrum of multisystem neurodegenerative disease. Voxel-based analysis was more sensitive to detect longitudinal changes than diffusion tensor tractography of the corticospinal tract. Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time.