The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology.

Central nervous system (CNS)-resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including multiple sclerosis (MS). Several studies have demonstrated the involvement of pro-inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from patients with MS in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of autoimmune neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a modulator of autoimmune CNS inflammation and potential therapeutic target in MS.

In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI.

Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency, ω $$ \omega $$ , in addition to the diffusion tensor, D $$ \mathbf{D} $$ , and relaxation, R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , correlations. A D ω - R 1 - R 2 $$ \mathbf{D}\left(\omega \right)-{R}_1-{R}_2 $$ clinical imaging protocol was then introduced, with limited brain coverage and 3 mm3 voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse in vivo MD-MRI acquisition protocol providing whole brain coverage at 2 mm3 voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their D ω - R 1 - R 2 $$ \mathbf{D}\left(\omega \right)-{R}_1-{R}_2 $$ distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.

Velocity-compensated intravoxel incoherent motion of the human calf muscle.

PURPOSE: To determine whether intravoxel incoherent motion (IVIM) describes the blood perfusion in muscles better, assuming pseudo diffusion (Bihan Model 1) or ballistic motion (Bihan Model 2). METHODS: IVIM parameters were measured in 18 healthy subjects with three different diffusion gradient time profiles (bipolar with two diffusion times and one with velocity compensation) and 17 b-values (0-600 s/mm2) at rest and after muscle activation. The diffusion coefficient, perfusion fraction, and pseudo-diffusion coefficient were estimated with a segmented fit in the gastrocnemius medialis (GM) and tibialis anterior (TA) muscles. RESULTS: Velocity-compensated gradients resulted in a decreased perfusion fraction (6.9% ± 1.4% vs. 4.4% ± 1.3% in the GM after activation) and pseudo-diffusion coefficient (0.069 ± 0.046 mm2/s vs. 0.014 ± 0.006 in the GM after activation) compared to the bipolar gradients with the longer diffusion encoding time. Increased diffusion coefficients, perfusion fractions, and pseudo-diffusion coefficients were observed in the GM after activation for all gradient profiles. However, the increase was significantly smaller for the velocity-compensated gradients. A diffusion time dependence was found for the pseudo-diffusion coefficient in the activated muscle. CONCLUSION: Velocity-compensated diffusion gradients significantly suppress the IVIM effect in the calf muscle, indicating that the ballistic limit is mostly reached, which is supported by the time dependence of the pseudo-diffusion coefficient.

Smart forecasting of artifacts in contrast-enhanced breast MRI before contrast agent administration.

OBJECTIVES: To evaluate whether artifacts on contrast-enhanced (CE) breast MRI maximum intensity projections (MIPs) might already be forecast before gadolinium-based contrast agent (GBCA) administration during an ongoing examination by analyzing the unenhanced T1-weighted images acquired before the GBCA injection. MATERIALS AND METHODS: This IRB-approved retrospective analysis consisted of n = 2884 breast CE MRI examinations after intravenous administration of GBCA, acquired with n = 4 different MRI devices at different field strengths (1.5 T/3 T) during clinical routine. CE-derived subtraction MIPs were used to conduct a multi-class multi-reader evaluation of the presence and severity of artifacts with three independent readers. An ensemble classifier (EC) of five DenseNet models was used to predict artifacts for the post-contrast subtraction MIPs, giving as the input source only the pre-contrast T1-weighted sequence. Thus, the acquisition directly preceded the GBCA injection. The area under ROC (AuROC) and diagnostics accuracy scores were used to assess the performance of the neural network in an independent holdout test set (n = 285). RESULTS: After majority voting, potentially significant artifacts were detected in 53.6% (n = 1521) of all breast MRI examinations (age 49.6 ± 12.6 years). In the holdout test set (mean age 49.7 ± 11.8 years), at a specificity level of 89%, the EC could forecast around one-third of artifacts (sensitivity 31%) before GBCA administration, with an AuROC = 0.66. CONCLUSION: This study demonstrates the capability of a neural network to forecast the occurrence of artifacts on CE subtraction data before the GBCA administration. If confirmed in larger studies, this might enable a workflow-blended approach to prevent breast MRI artifacts by implementing in-scan personalized predictive algorithms. CLINICAL RELEVANCE STATEMENT: Some artifacts in contrast-enhanced breast MRI maximum intensity projections might be predictable before gadolinium-based contrast agent injection using a neural network. KEY POINTS: • Potentially significant artifacts can be observed in a relevant proportion of breast MRI subtraction sequences after gadolinium-based contrast agent administration (GBCA). • Forecasting the occurrence of such artifacts in subtraction maximum intensity projections before GBCA administration for individual patients was feasible at 89% specificity, which allowed correctly predicting one in three future artifacts. • Further research is necessary to investigate the clinical value of such smart personalized imaging approaches.

7 tricks for 7 T CEST: Improving the reproducibility of multipool evaluation provides insights into the effects of age and the early stages of Parkinson's disease.

The objective of the current study was to optimize the postprocessing pipeline of 7 T chemical exchange saturation transfer (CEST) imaging for reproducibility and to prove this optimization for the detection of age differences and differences between patients with Parkinson's disease versus normal subjects. The following 7 T CEST MRI experiments were analyzed: repeated measurements of a healthy subject, subjects of two age cohorts (14 older, seven younger subjects), and measurements of 12 patients with Parkinson's disease. A slab-selective, B 1 + -homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, B 0 -correction, normalization, denoising, B 1 + -correction and Lorentzian fitting, was optimized regarding the intrasubject and intersubject coefficient of variation (CoV) of the amplitudes of the amide pool and the aliphatic relayed nuclear Overhauser effect (rNOE) pool within the brain. Seven "tricks" for postprocessing accomplished an improvement of the mean voxel CoV of the amide pool and the aliphatic rNOE pool amplitudes of less than 5% and 3%, respectively. These postprocessing steps are: motion correction with interpolation of the motion of low-signal offsets (1) using the amide pool frequency offset image as reference (2), normalization of the Z-spectrum using the outermost saturated measurements (3), B 0 correction of the Z-spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), B 1 + correction using a linear fit (6) and Lorentzian fitting using the five-pool fit model (7). With the optimized postprocessing pipeline, a significant age effect in the amide pool can be detected. Additionally, for the first time, an aliphatic rNOE contrast between subjects with Parkinson's disease and age-matched healthy controls in the substantia nigra is detected. We propose an optimized postprocessing pipeline for CEST multipool evaluation. It is shown that by the use of these seven "tricks", the reproducibility and, thus, the statistical power of a CEST measurement, can be greatly improved and subtle changes can be detected.

Linear projection-based chemical exchange saturation transfer parameter estimation.

Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.

Prevalence and influencing factors for artifact development in breast MRI-derived maximum intensity projections.

BACKGROUND: Magnetic resonance imaging (MRI) provides high diagnostic sensitivity for breast cancer. However, MRI artifacts may impede the diagnostic assessment. This is particularly important when evaluating maximum intensity projections (MIPs), such as in abbreviated MRI (AB-MRI) protocols, because high image quality is desired as a result of fewer sequences being available to compensate for problems. PURPOSE: To describe the prevalence of artifacts on dynamic contrast enhanced (DCE) MRI-derived MIPs and to investigate potentially associated attributes. MATERIAL AND METHODS: For this institutional review board approved retrospective analysis, MIPs were generated from subtraction series and cropped to represent the left and right breasts as regions of interest. These images were labeled by three independent raters regarding the presence of MRI artifacts. MRI artifact prevalence and associations with patient characteristics and technical attributes were analyzed using descriptive statistics and generalized linear models (GLMMs). RESULTS: The study included 2524 examinations from 1794 patients (median age 50 years), performed on 1.5 and 3.0 Tesla MRI systems. Overall inter-rater agreement was kappa = 0.54. Prevalence of significant unilateral artifacts was 29.2% (736/2524), whereas bilateral artifacts were present in 37.8% (953/2524) of all examinations. According to the GLMM, artifacts were significantly positive associated with age (odds ratio [OR] = 1.52) and magnetic field strength (OR = 1.55), whereas a negative effect could be shown for body mass index (OR = 0.95). CONCLUSION: MRI artifacts on DCE subtraction MIPs of the breast, as used in AB-MRI, are a relevant topic. Our results show that, besides the magnetic field strength, further associated attributes are patient age and body mass index, which can provide possible targets for artifact reduction.

Deep learning-based quantitative susceptibility mapping (QSM) in the presence of fat using synthetically generated multi-echo phase training data.

PURPOSE: To enable a fast and automatic deep learning-based QSM reconstruction of tissues with diverse chemical shifts, relevant to most regions outside the brain. METHODS: A UNET was trained to reconstruct susceptibility maps using synthetically generated, unwrapped, multi-echo phase data as input. The RMS error with respect to synthetic validation data was computed. The method was tested on two in vivo knee and two pelvis data sets. Comparisons were made to a conventional fat-water separation pipeline by applying a commonly used graph-cut algorithm, both without and with an extended mask for background field removal (FWS-CONV-QSM and FWS-MASK-CONV-QSM, respectively). Several regions of interest were segmented and compared. Furthermore, the approach was tested on a prostate cancer patient receiving low-dose-rate brachytherapy, to detect and localize the seeds by MRI. RESULTS: The RMS error was 0.292 ppm with FWS-CONV-QSM and 0.123 ppm for the UNET approach. Susceptibility maps were reconstructed much faster (< 10 s) and completely automatically (no background masking needed) by the UNET compared with the other applied techniques (5 min 51 s and 22 min 44 s for CONV-QSM and FWS-MASK-CONV-QSM, respectively. Background artifacts, fat-water swaps, and hypointense artifacts between I-125 seeds of a patient receiving low-dose brachytherapy in the prostate were largely reduced in the UNET approach. CONCLUSIONS: Deep learning-based QSM reconstruction, trained solely with synthetic data, is well-suited to rapidly reconstructing high-quality susceptibility maps in the presence of fat without needing masking for background field removal.

Automated artifact detection in abbreviated dynamic contrast-enhanced (DCE) MRI-derived maximum intensity projections (MIPs) of the breast.

OBJECTIVES: To automatically detect MRI artifacts on dynamic contrast-enhanced (DCE) maximum intensity projections (MIPs) of the breast using deep learning. METHODS: Women who underwent clinically indicated breast MRI between October 2015 and December 2019 were included in this IRB-approved retrospective study. We employed two convolutional neural network architectures (ResNet and DenseNet) to detect the presence of artifacts on DCE MIPs of the left and right breasts. Networks were trained on images acquired up to and including the year 2018 using a 5-fold cross-validation (CV). Ensemble classifiers were built with the resulting CV models and applied to an independent holdout test dataset, which was formed by images acquired in 2019. RESULTS: Our study sample contained 2265 examinations from 1794 patients (median age at first acquisition: 50 years [IQR: 17 years]), corresponding to 1827 examinations of 1378 individuals in the training dataset and 438 examinations of 416 individuals in the holdout test dataset with a prevalence of image-level artifacts of 53% (1951/3654 images) and 43% (381/876 images), respectively. On the holdout test dataset, the ResNet and DenseNet ensembles demonstrated an area under the ROC curve of 0.92 and 0.94, respectively. CONCLUSION: Neural networks are able to reliably detect artifacts that may impede the diagnostic assessment of MIPs derived from DCE subtraction series in breast MRI. Future studies need to further explore the potential of such neural networks to complement quality assurance and improve the application of DCE MIPs in a clinical setting, such as abbreviated protocols. KEY POINTS: • Deep learning classifiers are able to reliably detect MRI artifacts in dynamic contrast-enhanced protocol-derived maximum intensity projections of the breast. • Automated quality assurance of maximum intensity projections of the breast may be of special relevance for abbreviated breast MRI, e.g., in high-throughput settings, such as cancer screening programs.

The traveling heads 2.0: Multicenter reproducibility of quantitative imaging methods at 7 Tesla.

OBJECT: This study evaluates inter-site and intra-site reproducibility at ten different 7 T sites for quantitative brain imaging. MATERIAL AND METHODS: Two subjects - termed the "traveling heads" - were imaged at ten different 7 T sites with a harmonized quantitative brain MR imaging protocol. In conjunction with the system calibration, MP2RAGE, QSM, CEST and multi-parametric mapping/relaxometry were examined. RESULTS: Quantitative measurements with MP2RAGE showed very high reproducibility across sites and subjects, and errors were in concordance with previous results and other field strengths. QSM had high inter-site reproducibility for relevant subcortical volumes. CEST imaging revealed systematic differences between the sites, but reproducibility was comparable to results in the literature. Relaxometry had also very high agreement between sites, but due to the high sensitivity, differences caused by different applications of the B1 calibration of the two RF coil types used were observed. CONCLUSION: Our results show that quantitative brain imaging can be performed with high reproducibility at 7 T and with similar reliability as found at 3 T for multicenter studies of the supratentorial brain.

Sample size estimation: Current practice and considerations for original investigations in MRI technical development studies.

PURPOSE: To investigate and to provide guidance for sample size selection based on the current practice in MR technical development studies in which healthy volunteers are examined. METHODS: All original articles published in Magnetic Resonance in Medicine between 2017 and 2019 were investigated and categorized according to technique, anatomical region, and magnetic field strength. The number of examined healthy volunteers (ie, the sample size) was collected and evaluated, whereas the number of patients was not considered. Papers solely measuring patients, animals, phantoms, specimens, or studies using existing data, for example, from an open databank, or consisting only of theoretical work or simulations were excluded. RESULTS: The median sample size of the 882 included studies was 6. There were some peaks in the sample size distribution (eg, 1, 5, and 10). In 49.9%, 82.1%, and 95.6% of the studies, the sample size was smaller or equal to 5, 10, and 20, respectively. CONCLUSION: We observed a large variance in sample sizes reflecting the variety of studies published in Magnetic Resonance in Medicine. Therefore, it can be concluded that it is current practice to balance the need for statistical power with the demand to minimize experiments involving healthy humans, often by choosing small sample sizes between 1 and 10. Naturally, this observation does not release an investigator from ensuring that sufficient data are acquired to reach statistical conclusions.

Optimal acquisition scheme for flow-compensated intravoxel incoherent motion diffusion-weighted imaging in the abdomen: An accurate and precise clinically feasible protocol.

PURPOSE: Flow-compensated (FC) diffusion-weighted MRI (DWI) for intravoxel-incoherent motion (IVIM) modeling allows for a more detailed description of tissue microvasculature than conventional IVIM. The long acquisition time of current FC-IVIM protocols, however, has prohibited clinical application. Therefore, we developed an optimized abdominal FC-IVIM acquisition with a clinically feasible scan time. METHODS: Precision and accuracy of the FC-IVIM parameters were assessed by fitting the FC-IVIM model to signal decay curves, simulated for different acquisition schemes. Diffusion-weighted acquisitions were added subsequently to the protocol, where we chose the combination of b-value, diffusion time and gradient profile (FC or bipolar) that resulted in the largest improvement to its accuracy and precision. The resulting two optimized FC-IVIM protocols with 25 and 50 acquisitions (FC-IVIMopt25 and FC-IVIMopt50 ), together with a complementary acquisition consisting of 50 diffusion-weighting (FC-IVIMcomp ), were acquired in repeated abdominal free-breathing FC-IVIM imaging of seven healthy volunteers. Intersession and intrasession within-subject coefficient of variation of the FC-IVIM parameters were compared for the liver, spleen, and kidneys. RESULTS: Simulations showed that the performance of FC-IVIM improved in tissue with larger perfusion fraction and signal-to-noise ratio. The scan time of the FC-IVIMopt25 and FC-IVIMopt50 protocols were 8 and 16 min. The best in vivo performance was seen in FC-IVIMopt50 . The intersession within-subject coefficients of variation of FC-IVIMopt50 were 11.6%, 16.3%, 65.5%, and 36.0% for FC-IVIM model parameters diffusivity, perfusion fraction, characteristic time and blood flow velocity, respectively. CONCLUSIONS: We have optimized the FC-IVIM protocol, allowing for clinically feasible scan times (8-16 min).

MRI Brain Signal Intensity and Relaxation Times in Individuals with Prior Exposure to Gadobutrol.

Purpose To perform follow-up brain MRI in volunteer participants who had previously received multiple doses of gadobutrol and to assess for changes in signal intensities and relaxation times. Materials and Methods This prospective study included 160 participants who received gadobutrol only between 2007 and 2017. The participants were separated into two groups, including participants with at least five contrast agent-enhanced examinations and normal kidney function (group 1) or at least one examination and impaired renal function (group 2). Control groups with normal and impaired renal function (groups 3 and 4) without history of contrast agent exposure were included for comparison. Unenhanced brain MRI was performed in 220 participants (76, 84, 25, and 35 participants in groups 1-4, respectively) with T1-weighted spin-echo and T1 and T2 mapping to determine visual signal intensity changes, signal intensity ratios (globus pallidus-to-thalamus and dentate nucleus-to-pons ratios), and T1 and T2 relaxation times. Results In groups 1 and 2, neither visual signal alterations nor differences in signal intensity ratio or T2 mapping were found. T1 mapping showed no changes for dentate nucleus, pons, and thalamus. However, shorter T1 relaxation times in the globus pallidus were found in group 1 compared with group 3 (difference of -26.2 msec; P = .002), which correlated with the number of previous gadobutrol doses in this group (P = .001). Conclusion In study participants who had previously received gadobutrol, brain MRI showed no differences relative to healthy control participants without gadobutrol exposure. However, quantitative T1 measurements might indicate gadolinium retention in the globus pallidus. © RSNA, 2018 Online supplemental material is available for this article.

Multiple interleaved mode saturation (MIMOSA) for B1+ inhomogeneity mitigation in chemical exchange saturation transfer.

PURPOSE: To mitigate B1+ inhomogeneity in quantitative CEST MRI at ultra-high magnetic field strengths (B0 ≥ 7 Tesla) using a parallel transmit system. METHODS: Multiple interleaved mode saturation employs interleaving of 2 complementary phase sets during the saturation pulse train. Phase differences of 45° (first mode) and 90° (second mode) between 2 adjacent transmitter coil channels are used. The influence of the new saturation scheme on the CEST contrast was analyzed using Bloch-McConnell simulations. The presented method was verified in phantom and in vivo measurements of the healthy human brain. The relayed nuclear Overhauser effect was evaluated, and the inverse magnetic transfer ratio metric was calculated. Results were compared to a published B1+ correction method. All measurements were conducted on a whole-body 7 Tesla MRI system using an 8 transmitter and 32 receiver channel head coil. RESULTS: Simulations showed that the inverse magnetic transfer ratio metric contrast of relayed nuclear Overhauser effect shows a smaller dependency on the relative amplitudes of the 2 different modes than the contrasts of Cr and amide proton transfer. Measurements of an egg white phantom showed markedly improved homogeneity compared to the uncorrected inverse magnetic transfer ratio metric (relayed nuclear Overhauser effect) images and slightly improved results compared to B1+ corrected images. In vivo multiple interleaved mode saturation images showed similar contrast compared to B1+ corrected images. CONCLUSION: Multiple interleaved mode saturation can be used as a simple method to mitigate B1+ inhomogeneity effects in CEST MRI at ultra-high magnetic field strengths. Compared to previous B1+ correction methods, acquisition time can be reduced because an additional scan, usually required for B1+ correction, can be omitted.

23 Na MRI depicts early changes in ion homeostasis in skeletal muscle tissue of patients with duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disease leading to progressive muscle wasting. Since there is a need for MRI variables that serve as early sensitive indicators of response to treatment, several quantitative MRI methods have been suggested for disease monitoring. PURPOSE: To evaluate the potential of sodium (23 Na) and proton (1 H) MRI methods to assess early pathological changes in skeletal muscle of DMD. STUDY TYPE: Prospective clinical study. POPULATION: 23 Na and 1 H MRI of the right leg were performed in 13 patients with DMD (age 7.8 ± 2.4) and 14 healthy boys (age 9.5 ± 2.2). FIELD STRENGTH/SEQUENCE: 3 T including a multiecho-spin-echo sequence, diffusion-weighted sequences, 1 H spectroscopy, 3-pt Dixon, and 23 Na ultrashort echo time sequences. ASSESSMENT: We obtained water T2 maps, fat fraction (FF), pH, and diffusion properties of the skeletal muscle tissue. Moreover, total tissue sodium concentration (TSC) was calculated from the 23 Na sequence. Intracellular-weighted 23 Na signal (ICwS) was derived from 23 Na inversion-recovery imaging. STATISTICAL TESTS: Results from DMD patients and controls were compared using Wilcoxon rank-sum tests and repeated analysis of variance (ANOVA). Spearman-rank correlations and area under the curve (AUC) were calculated to assess the performance of the different MRI methods to distinguish dystrophic from healthy muscle tissue. RESULTS: FF, water T2 , and pH were higher in DMD patients (0.07 ± 0.03, 39.4 ± 0.8 msec, 7.06 ± 0.03, all P < 0.05) than in controls (0.02 ± 0.01, 36.0 ± 0.4 msec, 7.03 ± 0.02). No difference was observed in diffusion properties. TSC (26.0 ± 1.3 mM, P < 0.05) and ICwS (0.69 ± 0.05 a.u., P < 0.05) were elevated in DMD (controls: 16.5 ± 1.3 mM and 0.47 ± 0.04 a.u.). The ICwS was frequently abnormal in DMD even when water T2 , FF, and pH were in the normal range. 23 Na MRI showed higher AUC values in comparison to the 1 H methods. DATA CONCLUSION: Sodium anomalies were regularly observed in patients with DMD compared with controls, and were present even in absence of fatty degenerative changes and water T2 increases. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1103-1113.

Suitable reference tissues for quantitative susceptibility mapping of the brain.

PURPOSE: Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease. METHODS: To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease. RESULTS: Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csfpost ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csfpost and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease. CONCLUSION: The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Prediction of malignancy by a radiomic signature from contrast agent-free diffusion MRI in suspicious breast lesions found on screening mammography.

PURPOSE: To assess radiomics as a tool to determine how well lesions found suspicious on breast cancer screening X-ray mammography can be categorized into malignant and benign with unenhanced magnetic resonance (MR) mammography with diffusion-weighted imaging and T2 -weighted sequences. MATERIALS AND METHODS: From an asymptomatic screening cohort, 50 women with mammographically suspicious findings were examined with contrast-enhanced breast MRI (ceMRI) at 1.5T. Out of this protocol an unenhanced, abbreviated diffusion-weighted imaging protocol (ueMRI) including T2 -weighted, (T2 w), diffusion-weighted imaging (DWI), and DWI with background suppression (DWIBS) sequences and corresponding apparent diffusion coefficient (ADC) maps were extracted. From ueMRI-derived radiomic features, three Lasso-supervised machine-learning classifiers were constructed and compared with the clinical performance of a highly experienced radiologist: 1) univariate mean ADC model, 2) unconstrained radiomic model, 3) constrained radiomic model with mandatory inclusion of mean ADC. RESULTS: The unconstrained and constrained radiomic classifiers consisted of 11 parameters each and achieved differentiation of malignant from benign lesions with a .632 + bootstrap receiver operating characteristics (ROC) area under the curve (AUC) of 84.2%/85.1%, compared to 77.4% for mean ADC and 95.9%/95.9% for the experienced radiologist using ceMRI/ueMRI. CONCLUSION: In this pilot study we identified two ueMRI radiomics classifiers that performed well in the differentiation of malignant from benign lesions and achieved higher performance than the mean ADC parameter alone. Classification was lower than the almost perfect performance of a highly experienced breast radiologist. The potential of radiomics to provide a training-independent diagnostic decision tool is indicated. A performance reaching the human expert would be highly desirable and based on our results is considered possible when the concept is extended in larger cohorts with further development and validation of the technique. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:604-616.

Potential of quantitative susceptibility mapping for detection of prostatic calcifications.

PURPOSE: To evaluate whether quantitative susceptibility (QSM) may be used as an alternative to computed tomography (CT) to detect calcification in prostate cancer patients. MATERIALS AND METHODS: Susceptibility map calculation was performed using 3D gradient echo magnetic resonance imaging (MRI) data from 26 patients measured at 3T who previously received a planning CT of the prostate. Phase images were unwrapped using Laplacian-based phase unwrapping, the background field was removed with the V-SHARP method, and susceptibility maps were calculated with the iLSQR method. Two blinded readers were asked to identify peri- and intraprostatic calcifications. RESULTS: Average mean and minimum susceptibility values (referenced to iliopsoas muscle) of calcifications were -0.249 ± 0.179 ppm and -0.551 ± 0.323 ppm, and average mean and maximum intensities in CT images were 319 ± 164 HU and 679 ± 392 HU. Twenty-one and 17 out of 22 prostatic calcifications were identified using susceptibility maps and magnitude images, respectively, as well as more than half of periprostatic phleboliths depicted by CT. Calcifications in the prostate and its periphery were quantitatively differentiable from noncalcified prostate tissue in CT (mean values for calcifications / for noncalcified tissue: 71 to 649 / -1 to 83 HU) and in QSM (mean values for calcifications / for noncalcified tissue: -0.641 to 0.063 / -0.046 to 0.181 ppm). Moreover, there was a significant correlation between susceptibility values and CT image intensities for calcifications (P < 0.004). CONCLUSION: Prostatic calcifications could be well identified with QSM. Susceptibility maps can be easily obtained from clinical prostate MR protocols that include a 3D gradient echo sequence, rendering it a promising technique for detection and quantification of intraprostatic calcifications. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:889-898.

Fast and Noninvasive Characterization of Suspicious Lesions Detected at Breast Cancer X-Ray Screening: Capability of Diffusion-weighted MR Imaging with MIPs.

PURPOSE: To evaluate the ability of a diagnostic abbreviated magnetic resonance (MR) imaging protocol consisting of maximum intensity projections (MIPs) from diffusion-weighted imaging with background suppression (DWIBS) and unenhanced morphologic sequences to help predict the likelihood of malignancy on suspicious screening x-ray mammograms, as compared with an abbreviated contrast material-enhanced MR imaging protocol and a full diagnostic breast MR imaging protocol. MATERIALS AND METHODS: This prospective institutional review board-approved study included 50 women (mean age, 57.1 years; range, 50-69 years), who gave informed consent and who had suspicious screening mammograms and an indication for biopsy, from September 2014 to January 2015. Before biopsy, full diagnostic contrast-enhanced MR imaging was performed that included DWIBS (b = 1500 sec/mm(2)). Two abbreviated protocols (APs) based on MIPs were evaluated regarding the potential to exclude malignancy: DWIBS (AP1) and subtraction images from the first postcontrast and the unenhanced series (AP2). Diagnostic indexes of both methods were examined by using the McNemar test and were compared with those of the full diagnostic protocol and histopathologic findings. RESULTS: Twenty-four of 50 participants had a breast carcinoma. With AP1 (DWIBS), the sensitivity was 0.92 (95% confidence interval [CI]: 0.73, 0.98), the specificity was 0.94 (95% CI: 0.77, 0.99), the negative predictive value (NPV) was 0.92 (95% CI: 0.75, 0.99), and the positive predictive value (PPV) was 0.93 (95% CI: 0.75, 0.99). The mean reading time was 29.7 seconds (range, 4.9-110.0 seconds) and was less than 3 seconds (range, 1.2-7.6 seconds) in the absence of suspicious findings on the DWIBS MIPs. With the AP2 protocol, the sensitivity was 0.85 (95% CI: 0.78, 0.95), the specificity was 0.90 (95% CI: 0.72, 0.97), the NPV was 0.87 (95% CI: 0.69, 0.95), the PPV was 0.89 (95% CI: 0.69, 0.97), and the mean reading time was 29.6 seconds (range, 6.0-100.0 seconds). CONCLUSION: Unenhanced diagnostic MR imaging (DWIBS mammography), with an NPV of 0.92 and an acquisition time of less than 7 minutes, could help exclude malignancy in women with suspicious x-ray screening mammograms. The method has the potential to reduce unnecessary invasive procedures and emotional distress for breast cancer screening participants if it is used as a complement after the regular screening clarification procedure.

On contrast mechanisms in p-space imaging.

PURPOSE: The effects of microstructure on susceptibility mapping have recently received increasing attention. In this work, the capability of p-space imaging to resolve subvoxel structure and susceptibility is assessed. METHODS: In a simulation study, the p-space contrast of axon bundles comprised of hollow cylinders is investigated. Various axon and susceptibility distributions are considered and compared with the corresponding case of a voxel with homogeneous substructure of the order of the voxel size. RESULTS: MR signal behavior for p-space imaging of a voxel containing axon bundles and a voxel containing homogeneous substructure are nearly identical. CONCLUSION: p-Space imaging resolves subvoxel structure of the order of the voxel size. Due to dephasing effects, strong susceptibility variations alter p-space contrast. However, p-space contrast is not directly linked to the susceptibility of the axon compartment. Magn Reson Med 75:2526-2533, 2016. © 2015 Wiley Periodicals, Inc.