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.

Influence of saturation effects on biexponential liver intravoxel incoherent motion.

PURPOSE: Studies on intravoxel incoherent motion (IVIM) imaging in the liver have been carried out with different acquisition protocols. The number of acquired slices and the distances between slices can influence IVIM measurements due to saturation effects, but these effects have often been disregarded. This study investigated differences in biexponential IVIM parameters between two slice settings. METHODS: Fifteen healthy volunteers (21-30 years) were examined at a field strength of 3 T. Diffusion-weighted images of the abdomen were acquired with 16 b values (0-800 s/mm2 ), with four slices for the few slices setting and 24-27 slices for the many slices setting. Regions of interest were manually drawn in the liver. The data were fitted with a monoexponential signal curve and a biexponential IVIM curve, and biexponential IVIM parameters were determined. The dependence on the slice setting was assessed with Student's t test for paired samples (normally distributed IVIM parameters) and the Wilcoxon signed-rank test (non-normally distributed parameters). RESULTS: None of the parameters were significantly different between the settings. For few slices and many slices, respectively, the mean values (SDs) for D $$ D $$ were 1.21 µm 2 / ms $$ 1.21{\upmu \mathrm{m}}^2/\mathrm{ms} $$ ( 0.19 µm 2 / ms $$ 0.19\kern0.3em {\upmu \mathrm{m}}^2/\mathrm{ms} $$ ) and 1.20 µm 2 / ms $$ 1.20{\upmu \mathrm{m}}^2/\mathrm{ms} $$ ( 0.11 µm 2 / ms $$ 0.11\kern0.3em {\upmu \mathrm{m}}^2/\mathrm{ms} $$ ); for f $$ f $$ they were 29.7% (6.2%) and 27.7% (3.6%); and for D * $$ {D}^{\ast } $$ they were 8.76 ⋅ 10 - 2 mm 2 / s $$ 8.76\cdot {10}^{-2}{\mathrm{mm}}^2/\mathrm{s} $$ ( 4.54 ⋅ 10 - 2 mm 2 / s $$ 4.54\cdot {10}^{-2}\kern0.3em {\mathrm{mm}}^2/\mathrm{s} $$ ) and 8.71 ⋅ 10 - 2 mm 2 / s $$ 8.71\cdot {10}^{-2}{\mathrm{mm}}^2/\mathrm{s} $$ ( 4.06 ⋅ 10 - 2 mm 2 / s $$ 4.06\cdot {10}^{-2}\kern0.3em {\mathrm{mm}}^2/\mathrm{s} $$ ). CONCLUSION: Biexponential IVIM parameters in the liver are comparable among IVIM studies that use different slice settings, with mostly negligible saturation effects. However, this may not hold for studies that use much shorter TR.

Reduction of the cardiac pulsation artifact and improvement of lesion conspicuity in flow-compensated diffusion images in the liver-A quantitative evaluation of postprocessing algorithms.

PURPOSE: To enhance image quality of flow-compensated diffusion-weighted liver MRI data by increasing the lesion conspicuity and reducing the cardiac pulsation artifact using postprocessing algorithms. METHODS: Diffusion-weighted image data of 40 patients with liver lesions had been acquired at 1.5 T. These data were postprocessed with 5 different algorithms (weighted averaging, p-mean, percentile, outlier exclusion, and exception set). Four image properties of the postprocessed data were evaluated for optimizing the algorithm parameters. These properties were the lesion to tissue contrast-to-noise ratio (CNR), the reduction of the cardiac pulsation artifact, the data consistency, and the vessel darkness. They were combined into a total quality score ( Q total , $$ {Q}_{\mathrm{total}}, $$ set to 1 for the trace-weighted reference image), which was used to rate the image quality objectively. RESULTS: The weighted averaging algorithm performed best according to the total quality score ( Q total = 1.111 ± 0.067 $$ {Q}_{\mathrm{total}}=1.111\pm 0.067 $$ ). The further ranking was outlier exclusion algorithm ( Q total = 1.086 ± 0.061 $$ {Q}_{\mathrm{total}}=1.086\pm 0.061 $$ ), p-mean algorithm ( Q total = 1.045 ± 0.049 $$ {Q}_{\mathrm{total}}=1.045\pm 0.049 $$ ), percentile algorithm ( Q total = 1.012 ± 0.049 $$ {Q}_{\mathrm{total}}=1.012\pm 0.049 $$ ), and exception set algorithm ( Q total = 0.957 ± 0.027 $$ {Q}_{\mathrm{total}}=0.957\pm 0.027 $$ ). All optimized algorithms except for the exception set algorithm corrected the pulsation artifact and increased the lesion CNR. Changes in Q total $$ {Q}_{\mathrm{total}} $$ were significant for all optimized algorithms except for the percentile algorithm. Liver ADC was significantly reduced (except for the exception set algorithm), particularly in the left lobe. CONCLUSION: Postprocessing algorithms should be used for flow-compensated liver DWI. The proposed weighted averaging algorithm seems to be suited best to increase the image quality of artifact-corrupted flow-compensated diffusion-weighted liver data.

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.

Echo time dependence of biexponential and triexponential intravoxel incoherent motion parameters in the liver.

PURPOSE: Intravoxel incoherent motion (IVIM) studies are performed with different acquisition protocols. Comparing them requires knowledge of echo time (TE) dependencies. The TE-dependence of the biexponential perfusion fraction f is well-documented, unlike that of its triexponential counterparts f1 and f2 and the biexponential and triexponential pseudodiffusion coefficients D* , D1∗ , and D2∗ . The purpose was to investigate the TE-dependence of these parameters and to check whether the triexponential pseudodiffusion compartments are associated with arterial and venous blood. METHODS: Fifteen healthy volunteers (19-58 y; mean: 24.7 y) underwent diffusion-weighted imaging of the abdomen with 24 b-values (0.2-800 s/mm2 ) at TEs of 45, 60, 75, and 90 ms. Regions of interest (ROIs) were manually drawn in the liver. One set of bi- and triexponential IVIM parameters per volunteer and TE was determined. The TE-dependence was assessed with the Kruskal-Wallis test. RESULTS: TE-dependence was observed for f (P < .001), f1 (P = .001), and f2 (P < .001). Their median values at the four measured TEs were: f: 0.198/0.240/0.274/0.359, f1 : 0.113/0.139/0.146/0.205, f2 : 0.115/0.155/0.182/0.194. D, D* , D1∗ , and D2∗ showed no significant TE-dependence. Their values were: diffusion coefficient D (10-4 mm2 /s): 9.45/9.63/9.75/9.41, biexponential D* (10-2 mm2 /s): 5.26/5.52/6.13/5.82, triexponential D1∗ (10-2 mm2 /s): 1.73/2.91/2.25/2.51, triexponential D2∗ (mm2 /s): 0.478/1.385/0.616/0.846. CONCLUSION: f1 and f2 show similar TE-dependence as f, ie, increase with rising TE; an effect that must be accounted for when comparing different studies. The diffusion and pseudodiffusion coefficients might be compared without TE correction. Because of the similar TE-dependence of f1 and f2 , the triexponential pseudodiffusion compartments are most probably not associated to venous and arterial blood.

Differentiating Benign and Malignant Breast Lesions in Diffusion Kurtosis MRI: Does the Averaging Procedure Matter?

BACKGROUND: Diffusion kurtosis imaging (DKI) is used to differentiate between benign and malignant breast lesions. DKI fits are performed either on voxel-by-voxel basis or using volume-averaged signal. PURPOSE: Investigate and compare DKI parameters' diagnostic performance using voxel-by-voxel and volume-averaged signal fit approach. STUDY TYPE: Retrospective. STUDY POPULATION: A total of 104 patients, aged 24.1-86.4 years. FIELD STRENGTH/SEQUENCE: A 3 T Spin-echo planar diffusion-weighted sequence with b-values: 50 s/mm2 , 750 s/mm2 , and 1500 s/mm2 . Dynamic contrast enhanced (DCE) sequence. ASSESSMENT: Lesions were manually segmented by M.P. under supervision of S.O. (2 and 5 years of experience in breast MRI). DKI fits were performed on voxel-by-voxel basis and with volume-averaged signal. Diagnostic performance of DKI parameters D K (kurtosis corrected diffusion coefficient) and kurtosis K was compared between both approaches. STATISTICAL TESTS: Receiver operating characteristics analysis and area under the curve (AUC) values were computed. Wilcoxon rank sum and Students t-test tested DKI parameters for significant (P <0.05) difference between benign and malignant lesions. DeLong test was used to test the DKI parameter performance for significant fit approach dependency. Correlation between parameters of the two approaches was determined by Pearson correlation coefficient. RESULTS: DKI parameters were significantly different between benign and malignant lesions for both fit approaches. Median benign vs. malignant values for voxel-by-voxel and volume-averaged approach were 2.00 vs. 1.28 ( D K in µm2 /msec), 2.03 vs. 1.26 ( D K in µm2 /msec), 0.54 vs. 0.90 ( K ), 0.55 vs. 0.99 ( K ). AUC for voxel-by-voxel and volume-averaged fit were 0.9494 and 0.9508 ( D K ); 0.9175 and 0.9298 ( K ). For both, AUC did not differ significantly (P = 0.20). Correlation of values between the two approaches was very high (r = 0.99 for D K and r = 0.97 for K ). DATA CONCLUSION: Voxel-by-voxel and volume-averaged signal fit approach are equally well suited for differentiating between benign and malignant breast lesions in DKI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

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.

Nonparametric D-R1-R2 distribution MRI of the living human brain.

Diffusion-relaxation correlation NMR can simultaneously characterize both the microstructure and the local chemical composition of complex samples that contain multiple populations of water. Recent developments on tensor-valued diffusion encoding and Monte Carlo inversion algorithms have made it possible to transfer diffusion-relaxation correlation NMR from small-bore scanners to clinical MRI systems. Initial studies on clinical MRI systems employed 5D D-R1 and D-R2 correlation to characterize healthy brain in vivo. However, these methods are subject to an inherent bias that originates from not including R2 or R1 in the analysis, respectively. This drawback can be remedied by extending the concept to 6D D-R1-R2 correlation. In this work, we present a sparse acquisition protocol that records all data necessary for in vivo 6D D-R1-R2 correlation MRI across 633 individual measurements within 25 min-a time frame comparable to previous lower-dimensional acquisition protocols. The data were processed with a Monte Carlo inversion algorithm to obtain nonparametric 6D D-R1-R2 distributions. We validated the reproducibility of the method in repeated measurements of healthy volunteers. For a post-therapy glioblastoma case featuring cysts, edema, and partially necrotic remains of tumor, we present representative single-voxel 6D distributions, parameter maps, and artificial contrasts over a wide range of diffusion-, R1-, and R2-weightings based on the rich information contained in the D-R1-R2 distributions.

Brain tissues have single-voxel signatures in multi-spectral MRI.

Since the seminal works by Brodmann and contemporaries, it is well-known that different brain regions exhibit unique cytoarchitectonic and myeloarchitectonic features. Transferring the approach of classifying brain tissues - and other tissues - based on their intrinsic features to the realm of magnetic resonance (MR) is a longstanding endeavor. In the 1990s, atlas-based segmentation replaced earlier multi-spectral classification approaches because of the large overlap between the class distributions. Here, we explored the feasibility of performing global brain classification based on intrinsic MR features, and used several technological advances: ultra-high field MRI, q-space trajectory diffusion imaging revealing voxel-intrinsic diffusion properties, chemical exchange saturation transfer and semi-solid magnetization transfer imaging as a marker of myelination and neurochemistry, and current neural network architectures to analyze the data. In particular, we used the raw image data as well to increase the number of input features. We found that a global brain classification of roughly 97 brain regions was feasible with gross classification accuracy of 60%; and that mapping from voxel-intrinsic MR data to the brain region to which the data belongs is possible. This indicates the presence of unique MR signals of different brain regions, similar to their cytoarchitectonic and myeloarchitectonic fingerprints.

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.

Apparent exchange rate imaging: On its applicability and the connection to the real exchange rate.

PURPOSE: Water exchange between the intracellular and extracellular space can be measured using apparent exchange rate (AXR) imaging. The aim of this study was to investigate the relationship between the measured AXR and the geometry of diffusion restrictions, membrane permeability, and the real exchange rate, as well as to explore the applicability of AXR for typical human measurement settings. METHODS: The AXR measurements and the underlying exchange rates were simulated using the Monte Carlo method with different geometries, size distributions, packing densities, and a broad range of membrane permeabilities. Furthermore, the influence of SNR and sequence parameters was analyzed. RESULTS: The estimated AXR values correspond to the simulated values and show the expected proportionality to membrane permeability, except for fast exchange (ie, AXR>20-30s-1 ) and small packing densities. Moreover, it was found that the duration of the filter gradient must be shorter than 2·AXR-1 . In cell size and permeability distributions, AXR depends on the average surface-to-volume ratio, permeability, and the packing density. Finally, AXR can be reliably determined in the presence of orientation dispersion in axon-like structures with sufficient gradient sampling (ie, 30 gradient directions). CONCLUSION: Currently used experimental settings for in vivo human measurements are well suited for determining AXR, with the exception of single-voxel analysis, due to limited SNR. The detection of changes in membrane permeability in diseased tissue is nonetheless challenging because of the AXR dependence on further factors, such as packing density and geometry, which cannot be disentangled without further knowledge of the underlying cell structure.

An optimized b-value distribution for triexponential intravoxel incoherent motion (IVIM) in the liver.

PURPOSE: To find an optimized b-value distribution for reproducible triexponential intravoxel incoherent motion (IVIM) exams in the liver. METHODS: A numeric optimization of b-value distributions was performed using the triexponential IVIM equation and 27 different IVIM parameter sets. Starting with an initially optimized distribution of 6 b-values, the number of b-values was increased stepwise. Each new b-value was chosen from a set of 64 predefined b-values based on the computed summed relative mean error of the fitted triexponential IVIM parameters. This process was repeated for up to 100 b-values. In simulations and in vivo measurements, optimized b-value distributions were compared to 4 representative distributions found in literature. RESULTS: The first 16 optimized b-values were 0, 0.3, 0.3, 70, 200, 800, 70, 1, 3.5, 5, 70, 1.2, 6, 45, 1.5, and 60 in units of s/mm2 . Low b-values were much more frequent than high b-values. The optimized b-value distribution resulted in a higher fit stability compared to distributions used in literature in both, simulation and in vivo measurements. Using more than 6 b-values, ideally 16 or more, increased the fit stability considerably. CONCLUSION: Using optimized b-values, the fit uncertainty in triexponential IVIM can be largely reduced. Ideally, 16 or more b-values should be acquired.

Combined diffusion-relaxometry microstructure imaging: Current status and future prospects.

Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article reviews an emerging paradigm that has the potential to provide a more detailed assessment of tissue microstructure-combined diffusion-relaxometry imaging. Combined diffusion-relaxometry acquisitions vary multiple MR contrast encodings-such as b-value, gradient direction, inversion time, and echo time-in a multidimensional acquisition space. When paired with suitable analysis techniques, this enables quantification of correlations and coupling between multiple MR parameters-such as diffusivity, T1 , T2 , and T2∗ . This opens the possibility of disentangling multiple tissue compartments (within voxels) that are indistinguishable with single-contrast scans, enabling a new generation of microstructural maps with improved biological sensitivity and specificity.