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.

Parameter optimization for proton density fat fraction quantification in skeletal muscle tissue at 7 T.

OBJECTIVE: To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7 T. MATERIALS AND METHODS: Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12). Additionally, methods to reduce phase errors arising at 7 T were evaluated. Finally, PDFF values measured at 7 T in calf muscle tissue of healthy subjects (n = 9) and patients with fatty replacement of muscle tissue (n = 3) were compared to 3 T results. RESULTS: Simulations, phantom and in vivo measurements showed the importance of using optimized TEs for the fat-water separation at 7 T. Fat-water swaps could be mitigated using a phase demodulation with an additional B0 map, or by shifting the TEs to longer values. Muscular PDFF values measured at 7 T were comparable to measurements at 3 T in both healthy subjects and patients with increased fatty replacement. CONCLUSION: PDFF determination in calf muscle tissue is feasible at 7 T using a chemical shift-based approach with optimized acquisition and post-processing parameters.

Initial experience with a next-generation low-field MRI scanner: Potential for breast imaging?

PURPOSE: Broader clinical adoption of breast magnetic resonance imaging (MRI) faces challenges such as limited availability and high procedural costs. Low-field technology has shown promise in addressing these challenges. We report our initial experience using a next-generation scanner for low-field breast MRI at 0.55T. METHODS: This initial cases series was part of an institutional review board-approved prospective study using a 0.55T scanner (MAGNETOM Free.Max, Siemens Healthcare, Erlangen/Germany: height < 2 m, weight < 3.2 tons, no quench pipe) equipped with a seven-channel breast coil (Noras, Höchberg/Germany). A multiparametric breast MRI protocol consisting of dynamic T1-weighted, T2-weighted, and diffusion-weighted sequences was optimized for 0.55T. Two radiologists with 12 and 20 years of experience in breast MRI evaluated the examinations. RESULTS: Twelve participants (mean age: 55.3 years, range: 36-78 years) were examined. The image quality was diagnostic in all examinations and not impaired by relevant artifacts. Typical imaging phenotypes were visualized. The scan time for a complete, non-abbreviated breast MRI protocol ranged from 10:30 to 18:40 min. CONCLUSION: This initial case series suggests that low-field breast MRI is feasible at diagnostic image quality within an acceptable examination time.

Compensation of concomitant field effects in double diffusion encoding by means of added oscillating gradients.

Maxwell or concomitant fields imprint additional phases on the transverse magnetization. This concomitant phase may cause severe image artifacts like signal voids or distort the quantitative parameters due to the induced intravoxel dephasing. In particular, double diffusion encoding (DDE) schemes with two pairs of bipolar diffusion-weighting gradients separated by a refocusing radiofrequency (RF) pulse are prone to concomitant field-induced artifacts. In this work, a method for reducing concomitant field effects in these DDE sequences based on additional oscillating gradients is presented. These oscillating gradient pulses obtained by constrained optimization were added to the original gradient waveforms. The modified sequences reduced the accumulated concomitant phase without significant changes in the original sequence characteristics. The proposed method was applied to a DDE acquisition scheme consisting of 60 pairs of diffusion wave vectors. For phantom as well as for in vivo experiments, a considerable increase in the signal-to-noise ratio (SNR) was obtained. For phantom measurements with a diffusion weighting of b = 2000 s/mm2 for each of the gradient pairs, an SNR increase of up to 40% was observed for a transversal slice that had a distance of 5 cm from the isocenter. For equivalent slice parameters, in vivo measurements in the brain of a healthy volunteer exhibited an increase in SNR of up to 35% for b = 750 s/mm2 for each weighting. These findings are supported by corresponding simulations, which also predict a positive effect on the SNR. In summary, the presented method leads to an SNR gain without additional RF refocusing pulses.

Diffusion-Weighted Imaging for Skin Pathologies of the Breast-A Feasibility Study.

Several breast pathologies can affect the skin, and clinical pathways might differ significantly depending on the underlying diagnosis. This study investigates the feasibility of using diffusion-weighted imaging (DWI) to differentiate skin pathologies in breast MRIs. This retrospective study included 88 female patients who underwent diagnostic breast MRI (1.5 or 3T), including DWI. Skin areas were manually segmented, and the apparent diffusion coefficients (ADCs) were compared between different pathologies: inflammatory breast cancer (IBC; n = 5), benign skin inflammation (BSI; n = 11), Paget's disease (PD; n = 3), and skin-involved breast cancer (SIBC; n = 11). Fifty-eight women had healthy skin (H; n = 58). The SIBC group had a significantly lower mean ADC than the BSI and IBC groups. These differences persisted for the first-order features of the ADC (mean, median, maximum, and minimum) only between the SIBC and BSI groups. The mean ADC did not differ significantly between the BSI and IBC groups. Quantitative DWI assessments demonstrated differences between various skin-affecting pathologies, but did not distinguish clearly between all of them. More extensive studies are needed to assess the utility of quantitative DWI in supplementing the diagnostic assessment of skin pathologies in breast imaging.