White matter changes measured by multi-component MR Fingerprinting in multiple sclerosis.

T2-hyperintense lesions are the key imaging marker of multiple sclerosis (MS). Previous studies have shown that the white matter surrounding such lesions is often also affected by MS. Our aim was to develop a new method to visualize and quantify the extent of white matter tissue changes in MS based on relaxometry properties. We applied a fast, multi-parametric quantitative MRI approach and used a multi-component MR Fingerprinting (MC-MRF) analysis. We assessed the differences in the MRF component representing prolongedrelaxation time between patients with MS and controls and studied the relation between this component's volume and structural white matter damage identified on FLAIR MRI scans in patients with MS. A total of 48 MS patients at two different sites and 12 healthy controls were scanned with FLAIR and MRF-EPI MRI scans. MRF scans were analyzed with a joint-sparsity multi-component analysis to obtain magnetization fraction maps of different components, representing tissues such as myelin water, white matter, gray matter and cerebrospinal fluid. In the MS patients, an additional component was identified with increased transverse relaxation times compared to the white matter, likely representing changes in free water content. Patients with MS had a higher volume of the long- component in the white matter of the brain compared to healthy controls (B (95%-CI) = 0.004 (0.0006-0.008), p = 0.02). Furthermore, this MRF component had a moderate correlation (correlation coefficient R 0.47) with visible structural white matter changes on the FLAIR scans. Also, the component was found to be more extensive compared to structural white matter changes in 73% of MS patients. In conclusion, our MRF acquisition and analysis captured white matter tissue changes in MS patients compared to controls. In patients these tissue changes were more extensive compared to visually detectable white matter changes on FLAIR scans. Our method provides a novel way to quantify the extent of white matter changes in MS patients, which is underestimated using only conventional clinical MRI scans.

Sharpness in motion corrected quantitative imaging at 7T.

Sub-millimeter imaging at 7T has opened new possibilities for qualitatively and quantitatively studying brain structure as it evolves throughout the life span. However, subject motion introduces image blurring on the order of magnitude of the spatial resolution and is thus detrimental to image quality. Such motion can be corrected for, but widespread application has not yet been achieved and quantitative evaluation is lacking. This raises a need to quantitatively measure image sharpness throughout the brain. We propose a method to quantify sharpness of brain structures at sub-voxel resolution, and use it to assess to what extent limited motion is related to image sharpness. The method was evaluated in a cohort of 24 healthy volunteers with a wide and uniform age range, aiming to arrive at results that largely generalize to larger populations. Using 3D fat-excited motion navigators, quantitative R1, R2* and Quantitative Susceptibility Maps and T1-weighted images were retrospectively corrected for motion. Sharpness was quantified in all modalities for selected regions of interest (ROI) by fitting the sigmoidally shaped error function to data within locally homogeneous clusters. A strong, almost linear correlation between motion and sharpness improvement was observed, and motion correction significantly improved sharpness. Overall, the Full Width at Half Maximum reduced from 0.88 mm to 0.70 mm after motion correction, equivalent to a 2.0 times smaller voxel volume. Motion and sharpness were not found to correlate with the age of study participants. We conclude that in our data, motion correction using fat navigators is overall able to restore the measured sharpness to the imaging resolution, irrespective of the amount of motion observed during scanning.

An Efficient Method for Multi-Parameter Mapping in Quantitative MRI Using B-Spline Interpolation.

Quantitative MRI methods that estimate multiple physical parameters simultaneously often require the fitting of a computational complex signal model defined through the Bloch equations. Repeated Bloch simulations can be avoided by matching the measured signal with a precomputed signal dictionary on a discrete parameter grid (i.e. lookup table) as used in MR Fingerprinting. However, accurate estimation requires discretizing each parameter with a high resolution and consequently high computational and memory costs for dictionary generation, storage, and matching. Here, we reduce the required parameter resolution by approximating the signal between grid points through B-spline interpolation. The interpolant and its gradient are evaluated efficiently which enables a least-squares fitting method for parameter mapping. The resolution of each parameter was minimized while obtaining a user-specified interpolation accuracy. The method was evaluated by phantom and in-vivo experiments using fully-sampled and undersampled unbalanced (FISP) MR fingerprinting acquisitions. Bloch simulations incorporated relaxation effects (T1,T2) , proton density (PD ) , receiver phase ( φ0 ), transmit field inhomogeneity ( B1+ ), and slice profile. Parameter maps were compared with those obtained from dictionary matching, where the parameter resolution was chosen to obtain similar signal (interpolation) accuracy. For both the phantom and the in-vivo acquisition, the proposed method approximated the parameter maps obtained through dictionary matching while reducing the parameter resolution in each dimension ( T1,T2,B1+ ) by - on average - an order of magnitude. In effect, the applied dictionary was reduced from 1.47GB to 464KB . Furthermore, the proposed method was equally robust against undersampling artifacts as dictionary matching. Dictionary fitting with B-spline interpolation reduces the computational and memory costs of dictionary-based methods and is therefore a promising method for multi-parametric mapping.

Spatial versus angular resolution for tractography-assisted planning of deep brain stimulation.

Given the restricted total scanning time for clinical neuroimaging, it is unclear whether clinical diffusion MRI protocols would benefit more from higher spatial resolution or higher angular resolution. In this work, we investigated the relative benefit of improving spatial or angular resolution in diffusion MRI to separate two parallel running white matter tracts that are targets for deep brain stimulation: the anterior thalamic radiation and the supero-lateral branch of the medial forebrain bundle. Both these tracts are situated in the ventral anterior limb of the internal capsule, and recent studies suggest that targeting a specific tract could improve treatment efficacy. Therefore, we scanned 19 healthy volunteers at 3T and 7T according to three diffusion MRI protocols with respectively standard clinical settings, increased spatial resolution of 1.4 mm, and increased angular resolution (64 additional gradient directions at b = 2200s/mm2). We performed probabilistic tractography for all protocols and quantified the separability of both tracts. The higher spatial resolution protocol improved separability by 41% with respect to the clinical standard, presumably due to decreased partial voluming. The higher angular resolution protocol resulted in increased apparent tract volumes and overlap, which is disadvantageous for application in precise treatment planning. We thus recommend to increase the spatial resolution for deep brain stimulation planning to 1.4 mm while maintaining angular resolution. This recommendation complements the general advice to aim for high angular resolution to resolve crossing fibers, confirming that the specific application and anatomical considerations are leading in clinical diffusion MRI protocol optimization.

White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with Attention-Deficit/Hyperactivity Disorder.

BackgroundMethylphenidate (MPH) is highly effective in treating attention-deficit/hyperactivity disorder (ADHD). However, not much is known about its effect on the development of human brain white matter (WM).PurposeTo determine whether MPH modulates WM microstructure in an age-dependent fashion in a randomized double-blind placebo-controlled trial (Effects of Psychotropic Medication on Brain Development-Methylphenidate, or ePOD-MPH) among ADHD referral centers between October 13, 2011, and June 15, 2015, by using diffusion-tensor imaging (DTI).Materials and MethodsIn this prospective study (NTR3103 and NL34509.000.10), 50 stimulant treatment-naive boys and 49 young adult men diagnosed with ADHD (all types) according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria were randomized to undergo treatment with MPH or placebo for 16 weeks. Before and 1 week after treatment cessation, study participants underwent MRI, including DTI. The outcome measure was change in fractional anisotropy (FA), which was assessed in three regions of interest (ROIs), as well as in a voxel-based analysis in brain WM. Data were analyzed by using intention-to-treat linear mixed models for ROI analysis and a permutation-based method for voxel-based analysis with family-wise error correction.ResultsFifty boys (n = 25 MPH group, n = 25 placebo group; age range, 10-12 years) and 48 men (n = 24 MPH group, n = 24 placebo group; age range, 23-40 years) were included. ROI analysis of FA yielded no main effect of time in any of the conditions. However, voxel-based analysis revealed significant (P < .05) time-by-medication-by-age interaction effects in several association tracts of the left hemisphere, as well as in the lateral aspect of the truncus of the corpus callosum, due to greater increase in FA (standardized effect size, 5.25) in MPH-treated boys. Similar changes were not present in boys receiving a placebo, nor in adult men.ConclusionFour months of treatment with methylphenidate affects specific tracts in brain white matter in boys with attention-deficit/hyperactivity disorder. These effects seem to be age dependent, because they were not observed in adults treated with methylphenidate.© RSNA, 2019Online supplemental material is available for this article.

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.

Comparison of contrast-enhanced and diffusion-weighted MRI in assessment of the terminal ileum in Crohn's disease patients.

PURPOSE: The purpose of the study was to compare the performance of contrast-enhanced (CE)-MRI and diffusion-weighted imaging (DW)-MRI in grading Crohn's disease activity of the terminal ileum. METHODS: Three readers evaluated CE-MRI, DW-MRI, and their combinations (CE/DW-MRI and DW/CE-MRI, depending on which protocol was used at the start of evaluation). Disease severity grading scores were correlated to the Crohn's Disease Endoscopic Index of Severity (CDEIS). Diagnostic accuracy, severity grading, and levels of confidence were compared between imaging protocols and interobserver agreement was calculated. RESULTS: Sixty-one patients were included (30 female, median age 36). Diagnostic accuracy for active disease for CE-MRI, DW-MRI, CE/DW-MRI, and DW/CE-MRI ranged between 0.82 and 0.85, 0.75 and 0.83, 0.79 and 0.84, and 0.74 and 0.82, respectively. Severity grading correlation to CDEIS ranged between 0.70 and 0.74, 0.66 and 0.70, 0.69 and 0.75, and 0.67 and 0.74, respectively. For each reader, CE-MRI values were consistently higher than DW-MRI, albeit not significantly. Confidence levels for all readers were significantly higher for CE-MRI compared to DW-MRI (P < 0.001). Further increased confidence was seen when using combined imaging protocols. CONCLUSIONS: There was no significant difference of CE-MRI and DW-MRI in determining disease activity, but the higher confidence levels may favor CE-MRI. DW-MRI is a good alternative in cases with relative contraindications for the use of intravenous contrast medium.

Comparison of MRI Activity Scoring Systems and Features for the Terminal Ileum in Patients With Crohn Disease.

OBJECTIVE: The purpose of this study was to evaluate four previously validated MRI activity scoring systems for diagnosis and grading of Crohn disease (CD) in the terminal ileum against an endoscopic and histopathologic reference standard. SUBJECTS AND METHODS: Ethics approval and written informed consent were obtained. Subjects with known or suspected CD were prospectively recruited between December 2011 and August 2014. Each patient underwent MRI and ileocolonoscopy with terminal ileum biopsies. Four MRI scoring systems (Magnetic Resonance Index of Activity [MaRIA], Clermont score, London score, and Crohn disease MRI Index) and component features were applied by two observers and correlated to the Crohn disease endoscopic index of severity (CDEIS, 0-44) and histopathologic endoscopic acute inflammation score (0-6). Interobserver agreement (weighted kappa and intraclass correlation coefficient [ICC]) and diagnostic accuracy for active and ulcerating endoscopic or histopathologic disease were evaluated. RESULTS: Ninety-eight patients (median age, 32 years old; 55 women, 43 men) were included. All four scoring systems showed good interobserver agreement (ICC = 0.70-0.78), moderate-to-strong correlation to CDEIS (r = 0.57-0.67) and weak-to-moderate correlation to endoscopic acute inflammation score (r = 0.38-0.49). Scoring systems' diagnostic accuracy for active and ulcerating endoscopic disease ranged from 73% to 78% and 71% to 76%, respectively, whereas for active histopathologic disease accuracy ranged from 65% to 72%. Between the scoring systems, no significant differences were found for both observers regarding interobserver agreement, correlation coefficients, and diagnostic accuracy. CONCLUSION: All scoring systems were comparable in terms of interobserver agreement, correlation to the endoscopic and histopathologic reference standard, and diagnostic accuracy. The London score, MaRIA, and Clermont score have the additional benefit of having validated cutoff values for both active and ulcerating endoscopic disease.

Three-Dimensional Registration of Freehand-Tracked Ultrasound to CT Images of the Talocrural Joint.

A rigid surface⁻volume registration scheme is presented in this study to register computed tomography (CT) and free-hand tracked ultrasound (US) images of the talocrural joint. Prior to registration, bone surfaces expected to be visible in US are extracted from the CT volume and bone contours in 2D US data are enhanced based on monogenic signal representation of 2D US images. A 3D monogenic signal data is reconstructed from the 2D data using the position of the US probe recorded with an optical tracking system. When registering the surface extracted from the CT scan to the monogenic signal feature volume, six transformation parameters are estimated so as to optimize the sum of monogenic signal features over the transformed surface. The robustness of the registration algorithm was tested on a dataset collected from 12 cadaveric ankles. The proposed method was used in a clinical case study to investigate the potential of US imaging for pre-operative planning of arthroscopic access to talar (osteo)chondral defects (OCDs). The results suggest that registrations with a registration error of 2 mm and less is achievable, and US has the potential to be used in assessment of an OCD' arthroscopic accessibility, given the fact that 51% of the talar surface could be visualized.

Relationship between MRI quantified small bowel motility and abdominal symptoms in Crohn's disease patients-a validation study.

OBJECTIVE: Previous single-centre MRI data suggests an inverse correlation between normal small bowel motility variance and abdominal symptoms in Crohn's disease (CD) patients. The current work prospectively assesses this observation in a larger, two-centre study. METHODS: MR enterography datasets were analysed from 82 patients (38 male, aged 16-68), who completed a contemporaneous Harvey-Bradshaw index (HBI) questionnaire. Dynamic "cine motility" breath-hold balanced steady-state free precession sequences were acquired through the whole small bowel (SB) volume. Regions of interest (ROIs) were manually applied to encompass all morphologically normal SB (i.e. excluding Crohn's affected bowel) and a validated registration technique used to produce motility maps. Mean and variance motility metrics were correlated with HBI and symptom components (well-being, pain and diarrhoea) using Spearman's correlation statistics. RESULTS: Overall, motility variance was non-significantly negatively correlated with the total HBI score, (r = -0.17, p = 0.12), but for subjects with a HBI score over 10, the negative correlation was significant (r = -0.633, p = 0.027). Motility variance was negatively correlated with diarrhoea (r = -0.29, p < 0.01). No significant correlation was found between mean motility and HBI (r = -0.02, p = 0.84). CONCLUSION: An inverse association between morphologically normal small bowel motility variance and patient symptoms has been prospectively confirmed in patients with HBI scores above 10. This association is particularly apparent for the symptom of diarrhoea. Advances in knowledge: This study builds on preliminary work by confirming in a large, well-controlled prospective multicentre study a relationship between normal bowel motility variance and patient reported symptoms which may have implications for drug development and clinical management.

Comparison of Multi-Tensor Diffusion Models' Performance for White Matter Integrity Estimation in Chronic Stroke.

Better insight into white matter (WM) alterations after stroke onset could help to understand the underlying recovery mechanisms and improve future interventions. MR diffusion imaging enables to assess such changes. Our goal was to investigate the relation of WM diffusion characteristics derived from diffusion models of increasing complexity with the motor function of the upper limb. Moreover, we aimed to evaluate the variation of such characteristics across different WM structures of chronic stroke patients in comparison to healthy subjects. Subjects were scanned with a two b-value diffusion-weighted MRI protocol to exploit multiple diffusion models: single tensor, single tensor with isotropic compartment, bi-tensor model, bi-tensor with isotropic compartment. From each model we derived the mean tract fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivities outside the lesion site based on a WM tracts atlas. Asymmetry of these measures was correlated with the Fugl-Meyer upper extremity assessment (FMA) score and compared between patient and control groups. Eighteen chronic stroke patients and eight age-matched healthy individuals participated in the study. Significant correlation of the outcome measures with the clinical scores of stroke recovery was found. The lowest correlation of the corticospinal tract FAasymmetry and FMA was with the single tensor model (r = -0.3, p = 0.2) whereas the other models reported results in the range of r = -0.79 ÷ -0.81 and p = 4E-5 ÷ 8E-5. The corticospinal tract and superior longitudinal fasciculus showed most alterations in our patient group relative to controls. Multiple compartment models yielded superior correlation of the diffusion measures and FMA compared to the single tensor model.

Semiautomatic Assessment of the Terminal Ileum and Colon in Patients with Crohn Disease Using MRI (the VIGOR++ Project).

RATIONALE AND OBJECTIVES: The objective of this study was to develop and validate a predictive magnetic resonance imaging (MRI) activity score for ileocolonic Crohn disease activity based on both subjective and semiautomatic MRI features. MATERIALS AND METHODS: An MRI activity score (the "virtual gastrointestinal tract [VIGOR]" score) was developed from 27 validated magnetic resonance enterography datasets, including subjective radiologist observation of mural T2 signal and semiautomatic measurements of bowel wall thickness, excess volume, and dynamic contrast enhancement (initial slope of increase). A second subjective score was developed based on only radiologist observations. For validation, two observers applied both scores and three existing scores to a prospective dataset of 106 patients (59 women, median age 33) with known Crohn disease, using the endoscopic Crohn's Disease Endoscopic Index of Severity (CDEIS) as a reference standard. RESULTS: The VIGOR score (17.1 × initial slope of increase + 0.2 × excess volume + 2.3 × mural T2) and other activity scores all had comparable correlation to the CDEIS scores (observer 1: r = 0.58 and 0.59, and observer 2: r = 0.34-0.40 and 0.43-0.51, respectively). The VIGOR score, however, improved interobserver agreement compared to the other activity scores (intraclass correlation coefficient = 0.81 vs 0.44-0.59). A diagnostic accuracy of 80%-81% was seen for the VIGOR score, similar to the other scores. CONCLUSIONS: The VIGOR score achieves comparable accuracy to conventional MRI activity scores, but with significantly improved reproducibility, favoring its use for disease monitoring and therapy evaluation.

A hybrid optimization strategy for registering images with large local deformations and intensity variations.

PURPOSE: To develop a method for intra-patient registration of pre- and post-contrast abdominal MR images with large local deformations and large intensity variations. METHOD: A hybrid method is proposed to deal with this problem. It consists of two coupled techniques: (1) descriptor matching (DM) at the original resolution using a discrete optimization strategy to avoid getting trapped in a local minimum; (2) continuous optimization to refine the registration outcome based on autocorrelation of local image structure (ALOST). Our method-called DM-ALOST-has become insensitive to the local uptake of contrast agent by exploiting the mean phase and the phase congruency extracted from the multi-scale monogenic signal. The method was extensively tested on abdominal MR data of 30 patients with Crohn's disease. RESULTS: DM-ALOST produced significantly larger mean Dice coefficients than two state-of-the-art methods [Formula: see text]. CONCLUSION: Both qualitative and quantitative tests demonstrated improved registration using the proposed method compared to the state-of-the-art. The DM-ALOST method facilitates measurement of corresponding features from different abdominal MR images, which can aid to assess certain diseases, particularly Crohn's disease.

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.

Semi-automatic bowel wall thickness measurements on MR enterography in patients with Crohn's disease.

OBJECTIVE: To evaluate a semi-automatic method for delineation of the bowel wall and measurement of the wall thickness in patients with Crohn's disease. METHODS: 53 patients with suspected or proven Crohn's disease were selected. Two radiologists independently supervised the delineation of regions with active Crohn's disease on MRI, yielding manual annotations (Ano1, Ano2). Three observers manually measured the maximal bowel wall thickness of each annotated segment. An active contour segmentation approach semi-automatically delineated the bowel wall. For each active region, two segmentations (Seg1, Seg2) were obtained by independent observers, in which the maximum wall thickness was automatically determined. The overlap between (Seg1, Seg2) was compared with the overlap of (Ano1, Ano2) using Wilcoxon's signed rank test. The corresponding variances were compared using the Brown-Forsythe test. The variance of the semi-automatic thickness measurements was compared with the overall variance of manual measurements through an F-test. Furthermore, the intraclass correlation coefficient (ICC) of semi-automatic thickness measurements was compared with the ICC of manual measurements through a likelihood-ratio test. RESULTS: Patient demographics: median age, 30 years; interquartile range, 25-38 years; 33 females. The median overlap of the semi-automatic segmentations (Seg1 vs Seg2: 0.89) was significantly larger than the median overlap of the manual annotations (Ano1 vs Ano2: 0.72); p = 1.4 × 10-5. The variance in overlap of the semi-automatic segmentations was significantly smaller than the variance in overlap of the manual annotations (p = 1.1 × 10-9). The variance of the semi-automated measurements (0.46 mm2) was significantly smaller than the variance of the manual measurements (2.90 mm2, p = 1.1 × 10-7). The ICC of semi-automatic measurement (0.88) was significantly higher than the ICC of manual measurement (0.45); p = 0.005. CONCLUSION: The semi-automatic technique facilitates reproducible delineation of regions with active Crohn's disease. The semi-automatic thickness measurement sustains significantly improved interobserver agreement. Advances in knowledge: Automation of bowel wall thickness measurements strongly increases reproducibility of these measurements, which are commonly used in MRI scoring systems of Crohn's disease activity.

Simulation of scanner- and patient-specific low-dose CT imaging from existing CT images.

PURPOSE: Simulating low-dose Computed Tomography (CT) facilitates in-silico studies into the required dose for a diagnostic task. Conventionally, low-dose CT images are created by adding noise to the projection data. However, in practice the raw data is often simply not available. This paper presents a new method for simulating patient-specific, low-dose CT images without the need of the original projection data. METHODS: The low-dose CT simulation method included the following: (1) computation of a virtual sinogram from a high dose CT image through a radon transform; (2) simulation of a 'reduced'-dose sinogram with appropriate amounts of noise; (3) subtraction of the high-dose virtual sinogram from the reduced-dose sinogram; (4) reconstruction of a noise volume via filtered back-projection; (5) addition of the noise image to the original high-dose image. The required scanner-specific parameters, such as the apodization window, bowtie filter, the X-ray tube output parameter (reflecting the photon flux) and the detector read-out noise, were retrieved from calibration images of a water cylinder. The low-dose simulation method was evaluated by comparing the noise characteristics in simulated images with experimentally acquired data. RESULTS: The models used to recover the scanner-specific parameters fitted accurately to the calibration data, and the values of the parameters were comparable to values reported in literature. Finally, the simulated low-dose images accurately reproduced the noise characteristics in experimentally acquired low-dose-volumes. CONCLUSION: The developed methods truthfully simulate low-dose CT imaging for a specific scanner and reconstruction using filtered backprojection. The scanner-specific parameters can be estimated from calibration data.

Reliable Dual Tensor Model Estimation in Single and Crossing Fibers Based on Jeffreys Prior.

PURPOSE: This paper presents and studies a framework for reliable modeling of diffusion MRI using a data-acquisition adaptive prior. METHODS: Automated relevance determination estimates the mean of the posterior distribution of a rank-2 dual tensor model exploiting Jeffreys prior (JARD). This data-acquisition prior is based on the Fisher information matrix and enables the assessment whether two tensors are mandatory to describe the data. The method is compared to Maximum Likelihood Estimation (MLE) of the dual tensor model and to FSL's ball-and-stick approach. RESULTS: Monte Carlo experiments demonstrated that JARD's volume fractions correlated well with the ground truth for single and crossing fiber configurations. In single fiber configurations JARD automatically reduced the volume fraction of one compartment to (almost) zero. The variance in fractional anisotropy (FA) of the main tensor component was thereby reduced compared to MLE. JARD and MLE gave a comparable outcome in data simulating crossing fibers. On brain data, JARD yielded a smaller spread in FA along the corpus callosum compared to MLE. Tract-based spatial statistics demonstrated a higher sensitivity in detecting age-related white matter atrophy using JARD compared to both MLE and the ball-and-stick approach. CONCLUSIONS: The proposed framework offers accurate and precise estimation of diffusion properties in single and dual fiber regions.

White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment.

OBJECTIVE: Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment. DESIGN: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. METHODS: We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. RESULTS: HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/µl, but not with HIV-associated cognitive deficits. CONCLUSION: Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits. VIDEO ABSTRACT: .

Image Registration Based on Autocorrelation of Local Structure.

Registration of images in the presence of intra-image signal fluctuations is a challenging task. The definition of an appropriate objective function measuring the similarity between the images is crucial for accurate registration. This paper introduces an objective function that embeds local phase features derived from the monogenic signal in the modality independent neighborhood descriptor (MIND). The image similarity relies on the autocorrelation of local structure (ALOST) which has two important properties: 1) low sensitivity to space-variant intensity distortions (e.g., differences in contrast enhancement in MRI); 2) high distinctiveness for 'salient' image features such as edges. The ALOST method is quantitatively compared to the MIND approach based on three different datasets: thoracic CT images, synthetic and real abdominal MR images. The proposed method outperformed the NMI and MIND similarity measures on these three datasets. The registration of dynamic contrast enhanced and post-contrast MR images of patients with Crohn's disease led to relative contrast enhancement measures with the highest correlation (r=0.56) to the Crohn's disease endoscopic index of severity.