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In fibroglandular breast tissue, conventional dynamic contrast-enhanced MR-mammography is known to be affected by water content changes during the menstrual cycle. Likewise, amide proton transfer (APT) chemical exchange saturation transfer (CEST)-MRI might be inherently prone to the menstrual cycle, as CEST signals are indirectly detected via the water signal. The purpose of this study was to investigate the influence of the menstrual cycle on APT CEST-MRI in fibroglandular breast tissue.Ten healthy premenopausal women (19-34 years) were included in this IRB approved prospective study and examined twice during their menstrual cycle. Examination one and two were performed during the first half (day 2-8) and the second half (day 15-21) of the menstrual cycle, respectively. As a reference for the APT signal in malignant breast tumor tissue, previously reported data of nine breast cancer patients were included in this study. CEST-MRI (BThe APT signal showed no significant difference in the fibroglandular breast tissue of healthy premenopausal volunteers throughout the menstrual cycle (p = 1.00) (examination 1 vs. examination 2: mean and standard deviation = 3.24 ± 0.68%Hz vs. 3.30 ± 0.73%Hz, median and IQR = 3.36%Hz and 0.87%Hz vs. 3.38%Hz and 0.71%Hz).The present study provides an important basis for the clinical application of APT CEST-MRI as an additional contrast mechanism in MR-mammography, as menstrual cycle-related APT signal fluctuations seem to be negligible compared to the APT signal increase in breast cancer tissue.

Purpose: Radiotherapy is used for the treatment of lung cancer, but at the same time induces acute pneumonitis and subsequent pulmonary fibrosis, where TGF-β signaling is considered to play an important role.Experimental Design: We irradiated thoraces of C57BL/6 mice (single dose, 20 Gy) and administered them a novel small-molecule TGF-β receptor I serine/threonine kinase inhibitor (LY2109761) orally for 4 weeks before, during, or after radiation. Noninvasive lung imaging including volume computed tomography (VCT) and MRI was conducted 6, 16, and 20 weeks after irradiation and was correlated to histologic findings. Expression profiling analysis and protein analysis was conducted in human primary fibroblasts.Results: Radiation alone induced acute pulmonary inflammation and lung fibrosis after 16 weeks associated with reduced life span. VCT, MRI, and histology showed that LY2109761 markedly reduced inflammation and pulmonary fibrosis resulting in prolonged survival. Mechanistically, we found that LY2109761 reduced p-SMAD2 and p-SMAD1 expression, and transcriptomics revealed that LY2109761 suppressed expression of genes involved in canonical and noncanonical TGF-β signaling and downstream signaling of bone morphogenetic proteins (BMP). LY2109761 also suppressed radiation-induced inflammatory [e.g., interleukin (IL)-6, IL-7R, IL-8] and proangiogenic genes (e.g., ID1) indicating that LY2109761 achieves its antifibrotic effect by suppressing radiation-induced proinflammatory, proangiogenic, and profibrotic signals.Conclusion: Small-molecule inhibitors of the TGF-β receptor I kinase may offer a promising approach to treat or attenuate radiation-induced lung toxicity or other diseases associated with fibrosis. Clin Cancer Res; 18(13); 3616–27. ©2012 AACR.

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Kira Knauer,1,2 Oliver Chaudry,2,3 Michael Uder,1 Matthias Kohl,4 Wolfgang Kemmler,1,2 Sebastian Bickelhaupt,1 Klaus Engelke2,3 1Institute of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, 91054, Germany; 2Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, 91052, Germany; 3Department of Medicine III, Friedrich-Alexander University of Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, 91054, Germany; 4Faculty Medical and Life Sciences, University of Furtwangen, Villingen-Schwenningen, 78054, GermanyCorrespondence: Kira Knauer, Institute of Radiology, Friedrich-Alexander University of Erlangen-Nürnberg, University Hospital Erlangen, Maximiliansplatz 3, Erlangen, 91054, Germany, Tel +49 9131/85-36065, Email Kira.knauer@fau.dePurpose: To evaluate the effect of a high-intensity resistance training (HIT-RT) on visceral adipose tissue (VAT) and abdominal aortic calcifications (AAC).Patients and Methods: We conducted a post hoc analysis of the Franconian Osteopenia and Sarcopenia Trial (FrOST). 43 community-dwelling men with osteosarcopenia aged 72 years and older were randomly allocated to a supervised high-intensity resistance training (HIT-RT) twice weekly for 18 months (EG; n=21) and a non-training control group (CG; n=22). Non-contrast enhanced 2-point Dixon MRI scans covering mid L2 to mid L3 were acquired to measure VAT volume inside the abdominal cavity. Volume of AAC and hard plaques in renal arteries, truncus celiacus and superior mesenteric artery was measured by computed tomography (CT) scans covering mid T12 to mid L3. Intention-to-treat analysis with imputation for missing data was used to determine longitudinal changes in VAT and AAC volume. Correlations were used to determine associations between VAT and AAC.Results: Significant reduction of VAT volume in the EG (− 7.7%; p< 0.001) combined with no change in the CG (− 1.3%; p=0.46) resulted in a significant 6.4% between group effect (p=0.022). We observed a significant increase of AAC volume in EG (+10.3%; p< 0.001) and CG (12.0%; p< 0.001). AAC differences between groups were not significant (p=0.57). In vascular outlets increases in volume of the hard plaques were observed in both groups, however, not all of them were significant. There was no significant correlation between changes in VAT and AAC volumes.Conclusion: The study confirmed a positive impact of HIT-RT on the metabolic and cardiovascular risk profile with respect to reduction of VAT volume. No positive exercise effect on AAC was observed. However, there was a further progression of AAC volume independent of group affiliation. Whether different exercise regimen may show a positive effect on AAC remains subject to further studies.Keywords: HIT-RT, VAT, AAC, osteopenia, sarcopenia

The objective of the current study was to assess sodium (

With the COVID-19 pandemic, repetitive lung examinations have become necessary to follow-up symptoms and associated alterations. Low-field MRI, benefiting from reduced susceptibility effects, is a promising alternative for lung imaging to limit radiations absorbed by patients during CT examinations, which also have limited capability to assess functional alterations. The aim of this investigative study was to explore the functional abnormalities that free-breathing 0.55 T MRI in combination with the phase-resolved functional lung (PREFUL) analysis could identify in patients with persistent symptoms after COVID-19 infection.Seventy-four COVID-19 patients and 8 healthy volunteers were prospectively scanned in free-breathing with a balanced steady-state free-precession sequence optimized at 0.55 T, 5 months postinfection on average. Normalized perfusion (Q), fractional ventilation (FV), and flow-volume loop correlation (FVLc) maps were extracted with the PREFUL technique. Q, FV, and FVLc defects as well as defect overlaps between these metrics were quantified. Morphological turbo-spin-echo images were also acquired, and the extent of abnormalities was scored by a board-certified radiologist. To investigate the functional correlates of persistent symptoms, a recursive feature elimination algorithm was applied to find the most informative variables to detect the presence of persistent symptoms with a logistic regression model and a cross-validation strategy. All MRI metrics, sex, age, body mass index, and the presence of preexisting lung conditions were included.The most informative variables to detect persistent symptoms were the percentage of concurrent Q and FVLc defects and of areas free of those defects. A detection accuracy of 71.4% was obtained with these 2 variables when fitting the model on the entire dataset. Although none of the single variables differed between patients with and without persistent symptoms ( Pgt; 0.05), the combined score of these 2 variables did ( Plt; 0.02). This score also showed a consistent increase from healthy volunteers (7.7) to patients without persistent symptoms (8.2) and with persistent symptoms (8.6). The morphological abnormality score showed poor correlation with the functional parameters.Functional pulmonary examinations using free-breathing 0.55 T MRI with PREFUL analysis revealed potential quantitative markers of impaired lung function in patients with persistent symptoms after COVID-19 infection, potentially complementing morphologic imaging. Future work is needed to explore the translational relevance and clinical implication of these findings.

Background Long COVID occurs in lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field MRI may identify persistent pulmonary manifestations after SARS-CoV-2 infection. Purpose To characterize both morphologic and functional changes of lung parenchyma on low-field MRI in children and adolescents with post COVID-19 compared with healthy controls. Materials and Methods Between August and December 2021, a cross-sectional, prospective clinical trial using low-field MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes on MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive RT-PCR test and serological parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants and with long COVID. Results A total of 54 participants post COVID-19 infection (mean age, 11 years ±3 [SD], 56 males) and 9 healthy controls (mean age, 10 years ±3 [SD], 70 males) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (V/Q match) was reduced from 81±6.1% in healthy controls to 62±19% (

Magnetic resonance imaging (MRI) plays a pivotal role in diagnostic imaging. In today's clinical environment, scanners with field strengths of 1.5 to 3 T are most commonly used. However, recent technological advancements might help to augment the clinical usage and availability of MRI via the introduction of high-performance low-field MRI systems (ranging from ~0.1-0.55 T in current systems). The combination of low field strength and high-performance hardware is characterized by increased flexibility, excellent quality of results, and reduced cost. This review discusses the multifaceted potential advantages of a new generation of high-performance low-field MRI systems and presents the potential impact of such systems in terms of socioeconomic benefits as well as positive effects on patient care.

The autosomal dominant inherited Li-Fraumeni syndrome (LFS) increases the lifetime risk of developing a malignancy to almost 100%. Although breast cancer, central nervous system (CNS) tumors and sarcomas are particularly common, tumors can ultimately occur almost anywhere in the body. As causal therapy is not available, the primary focus for improving the prognosis is early cancer detection. To this end, current cancer surveillance recommendations include a series of examinations including regular imaging beginning at birth.Due to the wide range of tumor entities that can occur in individuals affected by LFS, a sensitive detection requires imaging of various tissue contrasts; however, because life-long screening is potentially initiated at a young age, this requirement for comprehensiveness must be balanced against the presumed high psychological burden associated with frequent or invasive examinations. As radiation exposure may lead to an increased (secondary) tumor risk, computed tomography (CT) and X‑ray examinations should be avoided as far as possible.Because annual whole-body magnetic resonance imaging (MRI) has no radiation exposure and yet a high sensitivity for many tumors, it forms the basis of the recommended imaging; however, due to the rarity of the syndrome, expertise is sometimes lacking and whole-body MRI examinations are performed heterogeneously and sometimes with limited diagnostic quality. Optimization and standardization of MRI protocols should therefore be pursued. In addition, the need for an intravenously administered contrast agent has not been conclusively clarified despite its high relevance.HINTERGRUND: Das autosomal-dominant vererbte Li-Fraumeni-Syndrom (LFS) erhöht bei Betroffenen das Lebenszeitrisiko für die Entwicklung eines Malignoms auf nahezu 100 %. Obwohl Mammakarzinome, Tumoren des Zentralnervensystems (ZNS) und Sarkome besonders häufig sind, können Tumoren letztlich nahezu im gesamten Körper auftreten. Da keine kausale Therapie existiert, stellt die Krebsfrüherkennung den wichtigsten Beitrag zur Verbesserung der Prognose dar. Die aktuellen Empfehlungen beinhalten hierzu eine Reihe an Untersuchungen, inklusive regelmäßiger Bildgebung ab der Geburt.Aufgrund der Vielfalt an Tumorentitäten, die bei LFS auftreten können, ist für eine sensitive Detektion die Abbildung verschiedener Gewebekontraste erforderlich. Da das Screening potenziell schon ab einem jungen Alter und für einen langen Zeitraum durchgeführt wird, muss dieser Anspruch auf Ausführlichkeit jedoch im Verhältnis zu der mutmaßlich hohen psychischen Belastung Betroffener durch häufige oder invasive Untersuchungen stehen. Da eine Strahlenexposition zu einem erhöhten (Zweit‑)Tumorrisiko führen kann, sollten CT- und Röntgenuntersuchungen, soweit möglich, vermieden werden.Da eine jährliche Ganzkörper-MRT keine Strahlenbelastung und dennoch eine hohe Sensitivität für die Detektion verschiedener Tumoren hat, bildet sie die Basis der empfohlenen Bildgebung. Aufgrund der Seltenheit des Syndroms fehlt jedoch teilweise die Expertise hierfür, und Ganzkörper-MRT-Untersuchungen werden heterogen und mit zum Teil eingeschränkter diagnostischer Qualität durchgeführt. Daher sollte eine Optimierung und Vereinheitlichung von MRT-Protokollen angestrebt werden. Zudem ist die Notwendigkeit einer intravenösen Kontrastmittelapplikation trotz ihrer hohen Relevanz nicht abschließend geklärt.

Lung magnetic resonance imaging (MRI) examinations are challenging and have not become established in the routine clinical setting. Recent developments in low-field MRI, combined with computer-assisted algorithms for acquisition and evaluation, promise new perspectives for imaging of pulmonary diseases.This review aims to inform about the physical advantages of low-field MRI for imaging the lungs, provide a review of the sparse literature, and present first results from a new low-field MRI scanner.This article provides information on the physical principles, an review of the literature, and our first experiences in lung imaging on a modern 0.55 T MRI.Low-field MRI ( 1 T) may have technical and economic advantages over higher field strength MRI in lung imaging. The physical preconditions of low-field MRI are advantageous for imaging the lungs due to reduced susceptibility effects, increased transversal relaxation times, and lower specific absorption rates. The lower investment and operating costs may enable increased availability and sustainability. Combining modern sequences and computer-based image processing may expand beyond morphological imaging by providing spatially and temporally resolved functional examinations of the lung parenchyma without ionizing radiation. In critical scenarios, like screening and short-term follow-up examinations, and patients at risk, low-field MRI may bridge the gap. These indications may include acute and chronic pulmonary diseases in pediatric patients and suspected pulmonary embolisms in pregnant women.HINTERGRUND: Die Untersuchung der Lunge mit der Magnetresonanztomographie (MRT) geht mit hohen Herausforderungen einher und konnte sich im klinischen Alltag bisher nicht durchsetzen. Aktuelle Entwicklungen der Niederfeld-MRT, in Kombination mit neuen computergestützten Aufnahme- und Auswertungsalgorithmen, versprechen neue Perspektiven für die bildgebende Diagnostik pulmonaler Erkrankungen.Diese Übersichtsarbeit soll ein Verständnis der physikalischen Vorteile der Niederfeld-MRT für die Lungenbildgebung vermitteln, einen Überblick über die spärlich vorhandenen Vorkenntnisse aus der Literatur bieten und erste Ergebnisse eines neu entwickelten Niederfeld-MRT präsentieren.Inhalte dieses Artikels basieren auf physikalischen Grundlagen, Recherchen in Literaturdatenbanken und eigenen Erfahrungen in der Lungenbildgebung mit einem modernen 0,55-T-MRT.Die Niederfeld-MRT ( 1 T) kann technische und ökonomische Vorteile gegenüber höheren Feldstärken für die Lungenbildgebung haben. Die physikalischen Voraussetzungen sind aufgrund geringerer Suszeptibilitätseffekte, längerer transversaler Relaxationszeiten und niedrigerer spezifischer Absorptionsraten besonders für die Anatomie der Lunge vorteilhaft. Die geringeren Anschaffungs- und Betriebskosten haben zudem ein großes Potenzial, die Verfügbarkeit zu erhöhen und gleichzeitig die Nachhaltigkeit zu verbessern. Durch die Kombination moderner Sequenzen und computergestützter Auswertungen kann die morphologische Bildgebung um orts- und zeitaufgelöste funktionelle Untersuchungen der Lunge ohne Strahlenbelastung ergänzt werden. Sowohl für kritische Szenarien, wie Screening und engmaschiges Therapiemonitoring, als auch für besonders gefährdete Patientengruppen könnten Lücken geschlossen werden. Dazu gehören beispielsweise akute und chronische Lungenerkrankungen bei Kindern oder die Abklärung einer Lungenembolie bei Schwangeren.

Background MRI with contrast material enhancement is the imaging modality of choice to evaluate sonographically indeterminate adnexal masses. The role of diffusion-weighted MRI, however, remains controversial. Purpose To evaluate the diagnostic performance of ultra-high-b-value diffusion kurtosis MRI in discriminating benign and malignant ovarian lesions. Materials and Methods This prospective cohort study evaluated consecutive women with sonographically indeterminate adnexal masses between November 2016 and December 2018. MRI at 3.0 T was performed, including diffusion-weighted MRI (b values of 0-2000 sec/mm2). Lesions were segmented on b of 1500 sec/mm2 by two readers in consensus and an additional independent reader by using full-lesion segmentations on a single transversal slice. Apparent diffusion coefficient (ADC) calculation and kurtosis fitting were performed. Differences in ADC, kurtosis-derived ADC (Dapp), and apparent kurtosis coefficient (Kapp) between malignant and benign lesions were assessed by using a logistic mixed model. Area under the receiver operating characteristic curve (AUC) for ADC, Dapp, and Kapp to discriminate malignant from benign lesions was calculated, as was specificity at a sensitivity level of 100%. Results from two independent reads were compared. Histopathologic analysis served as the reference standard. Results A total of 79 ovarian lesions in 58 women (mean age ± standard deviation, 48 years ± 14) were evaluated. Sixty-two (78%) lesions showed benign and 17 (22%) lesions showed malignant histologic findings. ADC and Dapp were lower and Kapp was higher in malignant lesions: median ADC, Dapp, and Kapp were 0.74 µm2/msec (range, 0.52-1.44 µm2/msec), 0.98 µm2/msec (range, 0.63-2.12 µm2/msec), and 1.01 (range, 0.69-1.30) for malignant lesions, and 1.13 µm2/msec (range, 0.35-2.63 µm2/msec), 1.45 µm2/msec (range, 0.44-3.34 µm2/msec), and 0.65 (range, 0.44-1.43) for benign lesions (P values of .01, .02, < .001, respectively). AUC for Kapp of 0.85 (95% confidence interval: 0.77, 0.94) was higher than was AUC from ADC of 0.78 (95% confidence interval: 0.67, 0.89; P = .047). Conclusion Diffusion-weighted MRI by using quantitative kurtosis variables is superior to apparent diffusion coefficient values in discriminating benign and malignant ovarian lesions and might be of future help in clinical practice, especially in patients with contraindication to contrast media application. © RSNA, 2020 Online supplemental material is available for this article.

OBJECTIVES Quantitative T1 relaxometry is the benchmark in imaging potential gadolinium deposition and known to be superior to semiquantitative signal intensity ratio analyses. However, T1 relaxometry studies are rare, commonly limited to a few target structures, and reported results are inconsistent.We systematically investigated quantitative T1 relaxation times (qT1) of a variety of brain nuclei after serial application of gadobutrol. MATERIALS AND METHODS Retrospectively, qT1 measurements were performed in a patient cohort with a mean number of 11 gadobutrol applications (n = 46) and compared with a control group with no prior gadolinium-based contrast agent administration (n = 48). The following target structures were evaluated: dentate nucleus, globus pallidus, thalamus, hippocampus, putamen, caudate, amygdala, and different white matter areas. Subsequently, multivariate regression analysis with adjustment for age, presence of brain metastases and previous cerebral radiotherapy was performed. RESULTS No assessed site revealed a significant correlation between qT1 and number of gadobutrol administrations in multivariate regression analysis. However, a significant negative correlation between qT1 and age was found for the globus pallidus as well as anterior and lateral thalamus (P < 0.05 each). CONCLUSIONS No T1 relaxation time shortening due to gadobutrol injection was found in any of the assessed brain structures after serial administration of 11 doses of gadobutrol.

INTRODUCTION Magnetic resonance imaging (MRI) of the abdomen increasingly incorporates diffusion-weighted imaging (DWI) sequences. Whereas DWI can substantially aid in detecting and characterizing suspicious findings, it remains unclear to what extent the use of ultra-high b-value DWI might further be of aid for the radiologist especially when using DWI sequences with advanced processing. The target of this study was therefore to compare high and ultra-high b-value DWI in abdominal MRI examinations. METHODS This institutional review board-approved, prospective study included abdominal MRI examinations of 70 oncologic patients (mean age, 58 years; range, 21-90 years) examined with a clinical 1.5 T MRI scanner (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) with an advanced echo planar DWI sequence (b = 0, 50, 900, and 1500 s/mm) after ex vivo phantom and in vivo volunteer investigations. High b900 and ultra-high b1500 DWIs were compared by a qualitative reading for image quality and lesion conspicuity using a 5-point Likert scale with 2 radiologists as readers. The ratios of apparent signal intensities of suspicious lesions/normal tissue of the same organ (LNTRs) were calculated. Appropriate methods were used for statistical analysis, including Wilcoxon signed-rank test and κ statistic for interreader agreement analysis (P < 0.05/0.0125/0.005 after Bonferroni correction). RESULTS Image quality was significantly increased with b900 as compared with b1500 DWI (P < 0.001) despite using an advanced DWI sequence. A total of 153 suspicious lesions were analyzed. Overall reader confidence for characterization/detection of malignant lesions and, correspondingly, the LNTR (mean, 2.7 ± 1.8 vs 2.4 ± 1.6) were significantly higher with b900 than with b1500 DWI (P < 0.001 and P < 0.001). The increased confidence of lesion recognition and LNTR in the b900 DWI remained significant qualitatively in lymphatic and hepatic lesions and quantitatively in lymphatic, pulmonal, and osseous lesions. CONCLUSIONS Using high b-value DWI (900 s/mm) provided an improved image quality and also lesion conspicuity as compared with ultra-high b-value DWI (1500 s/mm) in oncologic abdominal examinations despite using advanced processing. Consequently, the value for additional ultra-high b-value DWI in oncologic examinations should be critically evaluated in future studies.

The onset of rheumatic diseases such as rheumatoid arthritis is typically subclinical, which results in challenging early detection of the disease. However, characteristic changes in the anatomy can be detected using imaging techniques such as MRI or CT. Modern imaging techniques such as chemical exchange saturation transfer (CEST) MRI drive the hope to improve early detection even further through the imaging of metabolites in the body. To image small structures in the joints of patients, typically one of the first regions where changes due to the disease occur, a high resolution for the CEST MR imaging is necessary. Currently, however, CEST MR suffers from an inherently low resolution due to the underlying physical constraints of the acquisition. In this work we compared established up-sampling techniques to neural network-based super-resolution approaches. We could show, that neural networks are able to learn the mapping from low-resolution to high-resolution unsaturated CEST images considerably better than present methods. On the test set a PSNR of 32.29 dB (+10%), a NRMSE of 0.14 (+28%), and a SSIM of 0.85 (+15%) could be achieved using a ResNet neural network, improving the baseline considerably. This work paves the way for the prospective investigation of neural networks for super-resolution CEST MRI and, followingly, might lead to a earlier detection of the onset of rheumatic diseases.

Objectives To evaluate whether neural networks can distinguish between seropositive RA, seronegative RA, and PsA based on inflammatory patterns from hand MRIs and to test how psoriasis patients with subclinical inflammation fit into such patterns. Methods ResNet neural networks were utilized to compare seropositive RA vs PsA, seronegative RA vs PsA, and seropositive vs seronegative RA with respect to hand MRI data. Results from T1 coronal, T2 coronal, T1 coronal and axial fat-suppressed contrast-enhanced (CE), and T2 fat-suppressed axial sequences were used. The performance of such trained networks was analysed by the area under the receiver operating characteristics curve (AUROC) with and without presentation of demographic and clinical parameters. Additionally, the trained networks were applied to psoriasis patients without clinical arthritis. Results MRI scans from 649 patients (135 seronegative RA, 190 seropositive RA, 177 PsA, 147 psoriasis) were fed into ResNet neural networks. The AUROC was 75% for seropositive RA vs PsA, 74% for seronegative RA vs PsA, and 67% for seropositive vs seronegative RA. All MRI sequences were relevant for classification, however, when deleting contrast agent–based sequences the loss of performance was only marginal. The addition of demographic and clinical data to the networks did not provide significant improvements for classification. Psoriasis patients were mostly assigned to PsA by the neural networks, suggesting that a PsA-like MRI pattern may be present early in the course of psoriatic disease. Conclusion Neural networks can be successfully trained to distinguish MRI inflammation related to seropositive RA, seronegative RA, and PsA.

Background Men suspected of having clinically significant prostate cancer (sPC) increasingly undergo prostate MRI. The potential of deep learning to provide diagnostic support for human interpretation requires further evaluation. Purpose To compare the performance of clinical assessment to a deep learning system optimized for segmentation trained with T2-weighted and diffusion MRI in the task of detection and segmentation of lesions suspicious for sPC. Materials and Methods In this retrospective study, T2-weighted and diffusion prostate MRI sequences from consecutive men examined with a single 3.0-T MRI system between 2015 and 2016 were manually segmented. Ground truth was provided by combined targeted and extended systematic MRI-transrectal US fusion biopsy, with sPC defined as International Society of Urological Pathology Gleason grade group greater than or equal to 2. By using split-sample validation, U-Net was internally validated on the training set (80% of the data) through cross validation and subsequently externally validated on the test set (20% of the data). U-Net-derived sPC probability maps were calibrated by matching sextant-based cross-validation performance to clinical performance of Prostate Imaging Reporting and Data System (PI-RADS). Performance of PI-RADS and U-Net were compared by using sensitivities, specificities, predictive values, and Dice coefficient. Results A total of 312 men (median age, 64 years; interquartile range [IQR], 58-71 years) were evaluated. The training set consisted of 250 men (median age, 64 years; IQR, 58-71 years) and the test set of 62 men (median age, 64 years; IQR, 60-69 years). In the test set, PI-RADS cutoffs greater than or equal to 3 versus cutoffs greater than or equal to 4 on a per-patient basis had sensitivity of 96% (25 of 26) versus 88% (23 of 26) at specificity of 22% (eight of 36) versus 50% (18 of 36). U-Net at probability thresholds of greater than or equal to 0.22 versus greater than or equal to 0.33 had sensitivity of 96% (25 of 26) versus 92% (24 of 26) (both P > .99) with specificity of 31% (11 of 36) versus 47% (17 of 36) (both P > .99), not statistically different from PI-RADS. Dice coefficients were 0.89 for prostate and 0.35 for MRI lesion segmentation. In the test set, coincidence of PI-RADS greater than or equal to 4 with U-Net lesions improved the positive predictive value from 48% (28 of 58) to 67% (24 of 36) for U-Net probability thresholds greater than or equal to 0.33 (P = .01), while the negative predictive value remained unchanged (83% [25 of 30] vs 83% [43 of 52]; P > .99). Conclusion U-Net trained with T2-weighted and diffusion MRI achieves similar performance to clinical Prostate Imaging Reporting and Data System assessment. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Padhani and Turkbey in this issue.

Diffusion-weighted (DW) MRI is a rapid technique that measures the mobility of water molecules within tissue, reflecting the cellular microenvironment. At DW MRI, breast cancers typically exhibit reduced diffusivity and appear hyperintense to surrounding tissues. On the basis of this characteristic, DW MRI may offer an unenhanced method to detect breast cancer without the costs and safety concerns associated with dynamic contrast material–enhanced MRI, the current reference standard in the setting of high-risk screening. This application of DW MRI has not been widely explored but is particularly timely given the growing health concerns related to the long-term use of gadolinium-based contrast material. Moreover, increasing breast density notification legislation across the United States is raising awareness of the limitations of mammography in women with dense breasts, emphasizing the need for additional cost-effective supplemental screening examinations. Preliminary studies suggest unenhanced MRI with DW MRI may provide higher sensitivity than screening mammography for the detection of breast malignancies. Larger prospective multicenter trials are needed to validate single-center findings and assess the performance of DW MRI for generalized breast cancer screening. Standardization of DW MRI acquisition and interpretation is essential to ensure reliable sensitivity and specificity, and an optimal approach for screening using readily available techniques is proposed here. © RSNA, 2019 Online supplemental material is available for this article.

Objectives Contrast-enhanced (CE) magnetic resonance imaging (MRI) is the most effective imaging modality for breast cancer detection. A contrast agent-free examination technique would be desirable for breast MRI screening. The purpose of this study was to evaluate the capability to detect and characterize suspicious breast lesions with an abbreviated, non-contrast-enhanced MRI protocol featuring ultra-high b-value diffusion-weighted imaging (DWI) compared with CE images. Materials and methods The institutional review board-approved prospective study included 127 female subjects with different clinical indications for breast MRI. Magnetic resonance imaging examinations included DWI sequences with b-values of 1500 s/mm2 (b1500) and 2500 s/mm2 (b2500), native T1- and T2-weighted images, and CE sequences at 1.5 T and 3 T scanners. Two reading rounds were performed, including either the b1500 or the b2500 DWI in consecutive assessment steps: (A) maximum intensity projections (MIPs) of DWI, (B) DWI and apparent diffusion coefficient maps, (C) as (B) but with additional native T1- and T2-weighted images, and (D) as (C) but with additional CE images (full-length protocol). Two readers independently determined the presence of a suspicious lesion. Histological confirmation was obtained for conspicuous lesions, whereas the full MRI data set was obtained for inconspicuous and clearly benign lesions. Statistical analysis included calculation of diagnostic accuracy and interrater agreement via the intraclass correlation coefficient. Results The cohort comprised 116 cases with BI-RADS 1 findings and 138 cases with BI-RADS ≥2 findings, including 38 histologically confirmed malignancies. For (A), breasts without pathological findings could be recognized with high diagnostic accuracy (negative predictive value, ≥97.0%; sensitivity, ≥92.1% for both readers), but with a limited specificity (≥58.3%; positive predictive value, ≥28.6%). Within the native readings, approach (C) with b2500 performed best (negative predictive value, 99.5%; sensitivity, 97.4%; specificity, 88.4%). The intraclass correlation coefficient was between 0.683 (MIP b1500) and 0.996 (full protocol). Conclusions A native abbreviated breast MRI protocol with advanced high b-value DWI might allow nearly equivalent diagnostic accuracy as CE breast MRI and seems to be well suited for lesion detection purposes.

The outbreak of coronavirus disease 2019 (COVID-19) with the origin of the spread assumed to be located in Wuhan, China, began in December 2019, and is continuing until now. With the COVID-19 pandemic showing a progressive spread throughout the countries of the world, there is emerging interest for the potential long-term consequences of suffering from a COVID-19 pneumonia. Imaging plays a central role in the diagnosis and management of COVID-19 pneumonia, with chest X-ray examinations and computed tomography (CT) being undoubtedly the modalities most widely used, allowing for a fast and sensitive detection of infiltration patterns associated with COVID-19 pneumonia. For a better understanding of underlying pathomechanisms of pulmonary damage, longitudinal imaging series are warranted, for which CT is of limited usability due to repeated exposure of X-rays. Recent advances in MRI suggested that high-performance low-field MRI might represent a valuable method for pulmonary imaging without the need of radiation exposure. However, so far, low-field MRI has not been applied to study pulmonary damage after COVID-19 pneumonia. We present a case report of a patient who suffered from COVID-19 pneumonia using 0.55 T MRI for follow-up examinations three months after initial infection. Low-field MRI enables a precise visualization of persistent pulmonary changes including ground-glass opacities, which are consistent with CT performed on the same day. Low-field MRI seems to be feasible in the detection of pulmonary involvement in patients with COVID-19 pneumonia and may have the potential for repetitive lung examinations in monitoring the reconvalescence after pulmonary infections.

Background Diffusion weighted magnetic resonance imaging (DWI) is known to differentiate between malignant and benign lesions via the apparent diffusion coefficient (ADC). Here, the value of diffusion kurtosis imaging (DKI) for differentiation and further characterization of benign and malignant breast lesions and their subtypes in a clinically feasible protocol is investigated. Material and methods This study included 85 patients (with 68 malignant and 73 benign lesions) who underwent 3 T breast DWI using three b values (50, 750, 1500 s/mm2), with a total measurement time Results ADC, DK and K showed significant differences between malignant and benign lesions (p Conclusion DKI parameters and conventional ADC can differentiate between malignant and benign lesions. Differentiation performance was best for ADC. Different tumor grades were significantly different in ADC and DK, which may have an impact on therapy planning and monitoring. In our study, K did not add value to the diagnostic performance of DWI in a clinical setting.

Purpose: The application of amide proton transfer (APT) CEST MRI for diagnosis of breast cancer is of emerging interest. However, APT imaging in the human breast is affected by the ubiquitous fat signal preventing a straightforward application of existing acquisition protocols. Although the spectral region of the APT signal does not coincide with fat resonances, the fat signal leads to an incorrect normalization of the Z‐spectrum, and therefore to distorted APT effects. In this study, we propose a novel normalization for APT‐CEST MRI that corrects for fat signal–induced artifacts in the postprocessing without the need for application of fat saturation schemes or water–fat separation approaches. Methods The novel normalization uses the residual signal at the spectral position of the direct water saturation to estimate the fat contribution. A comprehensive theoretical description of the normalization for an arbitrary phase relation of the water and fat signal is provided. Functionality and applicability of the proposed normalization was demonstrated by in vitro and in vivo experiments. Results In vitro, an underestimation of the conventional APT contrast of approximately −1.2% per 1% fat fraction was observed. The novel normalization yielded an APT contrast independent of the fat contribution, which was also independent of the water‐fat phase relation. This allowed APT imaging in patients with mamma carcinoma corrected for fat signal contribution, field inhomogeneities, spillover dilution, and water relaxation effects. Conclusion The proposed normalization increases the specificity of APT imaging in tissues with varying fat content and represents a time‐efficient and specific absorption rate–efficient alternative to fat saturation and water–fat separation approaches.

Medical research in the field of oncologic imaging diagnostics using magnetic resonance imaging increasingly includes diffusion-weighted imaging (DWI) sequences. The DWI sequences allow insights into different microstructural diffusion properties of water molecules in tissues depending on the sequence modification used and enable visual and quantitative analysis of the acquired imaging data. In DWI, the application of intravenous gadolinium-containing contrast agents is unnecessary and only the mobility of naturally occurring water molecules in tissues is quantified. These characteristics predispose DWI as a potential candidate for emerging as an independent diagnostic tool in selected cases and specific points in question. Current clinical diagnostic studies and the ongoing technical developments, including the increasing influence of artificial intelligence in radiology, support the growing importance of DWI. Especially with respect to selective approaches for early detection of malignancies, DWI could make an essential contribution as an eligible diagnostic tool; however, prior to discussing a broader clinical implementation, challenges regarding reliable data quality, standardization and quality assurance must be overcome.

Objectives Motivated by the similar appearance of malignant breast lesions in high b-value diffusion-weighted imaging (DWI) and positron emission tomography, the purpose of this work was to evaluate the applicability of a threshold isocontouring approach commonly used in positron emission tomography to analyze DWI data acquired from female human breasts with minimal interobserver variability. Methods Twenty-three female participants (59.4 ± 10.0 years) with 23 lesions initially classified as suggestive of cancers in x-ray mammography screening were subsequently imaged on a 1.5-T magnetic resonance imaging scanner. Diffusion-weighted imaging was performed prior to biopsy with b values of 0, 100, 750, and 1500 s/mm. Isocontouring with different threshold levels was performed on the highest b-value image to determine the voxels used for subsequent evaluation of diffusion metrics. The coefficient of variation was computed by specifying 4 different regions of interest drawn around the lesion. Additionally, a receiver operating statistical analysis was performed. Results Using a relative threshold level greater than or equal to 0.85 almost completely suppresses the intra-individual and inter-individual variability. Among 4 studied diffusion metrics, the diffusion coefficients from the intravoxel incoherent motion model returned the highest area under curve value of 0.9. The optimal cut-off diffusivity was found to be 0.85 μm/ms with a sensitivity of 87.5% and specificity of 90.9%. Conclusion Threshold isocontouring on high b-value maps is a viable approach to reliably evaluate DWI data of suspicious focal lesions in magnetic resonance mammography.

To compare image quality of an optimized diffusion weighted imaging (DWI) sequence with advanced post-processing and motion correction (advanced-EPI) to a standard DWI protocol (standard-EPI) in pancreatic imaging.62 consecutive patients underwent abdominal MRI at 1.5 T were included in this retrospective analysis of data collected as part of an IRB approved study. All patients received a standard-EPI and an advanced-EPI DWI with advanced post-processing and motion correction. Two blinded radiologists evaluated the parameters image quality, detail of parenchyma, sharpness of boundaries and discernibility from adjacent structures on b = 900 s/mmThe advanced-EPI yielded significantly higher scores for pancreatic parameters of image quality, detail level of parenchyma, sharpness of boundaries and discernibility from adjacent structures in comparison to standard-EPI (p 0.001 for all, kappa = [0.46,0.71]) and was preferred in 96% of the cases when directly compared. ADC of the pancreas was 7% lower in advanced-EPI (1.236 ± 0.152 vs. 1.146 ± 0.126 μmAn advanced DWI sequence might increase image quality for focused imaging of the pancreas and providing improved parenchymal detail levels compared to a standard DWI.

OBJECTIVES The aim of this study was to compare intraindividual diffusion-weighted imaging (DWI) of the liver acquired with free breathing (FB) versus navigator triggering (NT) for assessing small focal liver lesions (FLLs) in noncirrhotic patients. MATERIALS AND METHODS Patients with known or suspected multiple FLLs were prospectively included, and spin-echo echo-planar DWI with NT and FB acquisition was performed (b-values, 50 and 800 s/mm2 [b50 and b800]). NT and FB DWI sequences with similar acquisitions times were used. Liver and lesion signal-to-noise ratios were measured at b800. The DWI scans were analyzed independently by 2 readers. Liver edge delineation, presence of stair-step artifacts, vessel sharpness, severity of cardiac motion artifacts, overall image quality, and lesion conspicuity were rated with 5-point Likert scales. Small and large FLLs (ie

Magnetic resonance (MR) diffusion-weighted imaging (DWI) is often used to detect focal liver lesions (FLLs), though DWI image quality can be limited in the left liver lobe owing to the pulsatile motion of the nearby heart. Flow-compensated (FloCo) diffusion encoding has been shown to reduce this pulsation artifact. The purpose of this prospective study was to intra-individually compare DWI of the liver acquired with conventional monopolar and FloCo diffusion encoding for assessing metastatic FLLs in non-cirrhotic patients. Forty patients with known or suspected multiple metastatic FLLs were included and measured at 1.5 T field strength with a conventional (monopolar) and a FloCo diffusion encoding EPI sequence (single refocused; b-values, 50 and 800 s/mm2). Two board-certified radiologists analyzed the DWI images independently. They issued Likert-scale ratings (1 = worst, 5 = best) for pulsation artifact severity and counted the difference of lesions visible at b = 800 s/mm² separately for small and large FLLs (i.e., < 1 cm or > 1 cm) and separately for left and right liver lobe. Differences between the two diffusion encodings were assessed with the Wilcoxon signed-rank test. Both readers found a reduction in pulsation artifact in the liver with FloCo encoding (p < 0.001 for both liver lobes). More small lesions were detected with FloCo diffusion encoding in both liver lobes (left lobe: six and seven additional lesions by readers 1 and 2, respectively; right lobe: five and seven additional lesions for readers 1 and 2, respectively). Both readers found one additional large lesion in the left liver lobe. Thus, flow-compensated diffusion encoding appears more effective than monopolar diffusion encoding for the detection of liver metastases.

Purpose We aimed to investigate whether quantitative diffusivity variables of healthy ovaries vary during the menstrual cycle and to evaluate alterations in women using oral contraceptives (OC). Methods This prospective study (S-339/2016) included 30 healthy female volunteers, with (n = 15) and without (n = 15) intake of OC between 07/2017 and 09/2019. Participants underwent 3T diffusion-weighted MRI (b-values 0–2000 s/mm2) three times during a menstrual cycle (T1 = day 1–5; T2 = day 7–12; T3 = day 19–24). Both ovaries were manually three-dimensionally segmented on b = 1500 s/mm2; apparent diffusion coefficient (ADC) calculation and kurtosis fitting (Dapp, Kapp) were performed. Differences in ADC, Dapp and Kapp between time points and groups were compared using repeated measures ANOVA and t-test after Shapiro-Wilk and Brown-Forsythe test for normality and equal variance. Results In women with a natural menstrual cycle, ADC and kurtosis variables showed significant changes in ovaries with the dominant follicle between T1 vs T2 and T1 vs T3, whilst no differences were observed between T2 vs T3: ADC ± SD for T1 1.524 ± 0.160, T2 1.737 ± 0.160, and T3 1.747 ± 0.241 μm2/ms (p = 0.01 T2 vs T1; p = 1.0 T2 vs T3, p = 0.003 T3 vs T1); Dapp ± SD for T1 2.018 ± 0.140, T2 2.272 ± 0.189, and T3 2.230 ± 0.256 μm2/ms (p = 0.003 T2 vs T1, p = 1.0 T2 vs T3, p = 0.02 T3 vs T1); Kapp ± SD for T1 0.614 ± 0.0339, T2 0.546 ± 0.0637, and T3 0.529 ± 0.0567 (p Conclusion Physiological cycle-dependent changes in quantitative diffusivity variables of ovaries should be considered especially when interpreting radiomics analyses in reproductive women.

Recent studies showed the potential of diffusion kurtosis imaging (DKI) as a tool for improved classification of suspicious breast lesions. However, in diffusion-weighted imaging of the female breast, sufficient fat suppression is one of the main factors determining the success. In this study, the data of 198 patients examined in two study centres was analysed using standard diffusion and kurtosis evaluation methods and three DKI fitting approaches accounting phenomenologically for fat-related signal contamination of the lesions. Receiver operating characteristic curve analysis showed the highest area under the curve (AUC) for the method including fat correction terms (AUC = 0.85, p p = 0.036) using a fat correction term for the first centre, while no significant difference with no adverse effects was observed for the second centre (AUC 0.89 vs. 0.90, p = 0.95). Contamination of the signal in breast lesions with unsuppressed fat causing a reduction of diagnostic performance of diffusion kurtosis imaging may potentially be counteracted by proposed adapted evaluation methods.

Background MRI with contrast material enhancement is the imaging modality of choice to evaluate sonographically indeterminate adnexal masses. The role of diffusion-weighted MRI, however, remains controversial. Purpose To evaluate the diagnostic performance of ultra-high

PurposeThe purpose of this study was to investigate whether the cardiac motion artifact that regularly appears in diffusion-weighted imaging of the left liver lobe might be reduced by acquiring images in inspiration, when the coupling between heart and liver might be minimal.Materials and methods43 patients with known or suspected focal liver lesions were examined at 1.5 T with breath hold acquisition, once in inspiration and once in expiration. Data were acquired with a diffusion-weighted echo planar imaging sequence and two b-values (b50 = 50 s/mm² and b800 = 800 s/mm²). The severity of the cardiac motion artifact in the left liver lobe was rated by two experienced radiologists for both b-values with a 5 point Likert scale. Additionally, the normalized signal S(b800)/S(b50) in the left liver lobe was computed. The Wilcoxon signed-rank test was used comparing the scores of the two readers obtained in inspiration and expiration, and to compare the normalized signal in inspiration and expiration.ResultsThe normalized signal in inspiration was slightly higher than in expiration (0.349±0.077 vs 0.336±0.058), which would indicate a slight reduction of the cardiac motion artifact, but this difference was not significant (p = 0.24). In the qualitative evaluation, the readers did not observe a significant difference for b50 (reader 1: p = 0.61; reader 2: p = 0.18). For b800, reader 1 observed a significant difference of small effect size favouring expiration (p = 0.03 with a difference of mean Likert scores of 0.27), while reader 2 observed no significant difference (p = 0.62).ConclusionAcquiring the data in inspiration does not lead to a markedly reduced cardiac motion artifact in diffusion-weighted imaging of the left liver lobe and is in this regard not to be preferred over acquiring the data in expiration.

Purpose The purpose of this study was to investigate whether the cardiac motion artifact that regularly appears in diffusion-weighted imaging of the left liver lobe might be reduced by acquiring images in inspiration, when the coupling between heart and liver might be minimal. Materials and methods 43 patients with known or suspected focal liver lesions were examined at 1.5 T with breath hold acquisition, once in inspiration and once in expiration. Data were acquired with a diffusion-weighted echo planar imaging sequence and two b-values (b50 = 50 s/mm² and b800 = 800 s/mm²). The severity of the cardiac motion artifact in the left liver lobe was rated by two experienced radiologists for both b-values with a 5 point Likert scale. Additionally, the normalized signal S(b800)/S(b50) in the left liver lobe was computed. The Wilcoxon signed-rank test was used comparing the scores of the two readers obtained in inspiration and expiration, and to compare the normalized signal in inspiration and expiration. Results The normalized signal in inspiration was slightly higher than in expiration (0.349±0.077 vs 0.336±0.058), which would indicate a slight reduction of the cardiac motion artifact, but this difference was not significant (p = 0.24). In the qualitative evaluation, the readers did not observe a significant difference for b50 (reader 1: p = 0.61; reader 2: p = 0.18). For b800, reader 1 observed a significant difference of small effect size favouring expiration (p = 0.03 with a difference of mean Likert scores of 0.27), while reader 2 observed no significant difference (p = 0.62). Conclusion Acquiring the data in inspiration does not lead to a markedly reduced cardiac motion artifact in diffusion-weighted imaging of the left liver lobe and is in this regard not to be preferred over acquiring the data in expiration.

Oncologic imaging focused on the detection of breast cancer is of increasing importance, with over 1.7 million new cases detected each year worldwide. MRI of the breast has been described to be one of the most sensitive imaging modalities in breast cancer detection; however, clinical use is limited due to high costs. In the past, the objective and clinical routine of oncologic imaging was to provide one extended imaging protocol covering all potential needs and clinical implications regardless of the specific clinical indication or question. Future protocols might be more focused according to a "keep it short and simple" approach, with a reduction of patient magnet time and a limited number of images to review. Rather than replacing conventional full-diagnostic breast MRI protocols, these approaches aim at introducing a new thinking in oncologic imaging using a diversification of available imaging approaches targeted to the dedicated clinical needs of the individual patient. Here we review current approaches on using abbreviated protocols that aim to increase the clinical availability and use of breast MRI for improved early detection of breast cancer. Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:647-658.

Background Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients. Purpose To investigate the anatomic location dependence of CEST MRI obtained at 7T and histopathological/molecular parameters in WHO IV° glioma patients. Study type Analytic prospective study. Population Twenty-one patients with newly diagnosed WHO IV° gliomas were studied prior to surgery; 11 healthy volunteers were investigated. Field strength/sequence Conventional MRI (contrast-enhanced, T2 w and diffusion-weighted imaging) at 3T and T2 w and CEST MRI at 7T was performed for patients and both patients and volunteers. Assessment Mean CEST signal intensities (nuclear-Overhauser-enhancement [NOE], amide-proton-transfer [APT], downfield NOE-suppressed APT [dns-APT]), ADC values, and histopathological/molecular parameters were evaluated with regard to hemisphere location and contact with the subventricular zone. CEST signal intensities of cerebral tissue of healthy volunteers were evaluated with regard to hemisphere discrimination. Statistical tests Spearman correlation, Mann-Whitney U-test, Wilcoxon signed-rank-test, Fisher's exact test, and area under the receiver operating curve. Results Maximum APT and dns-APT signal intensities were significantly different in right vs. left hemisphere gliomas (P = 0.037 and P = 0.007), but not in right vs. left hemisphere cerebral tissue of healthy subjects (P = 0.062-0.859). Mean ADC values were significantly decreased in right vs. left hemisphere gliomas (P = 0.044). Mean NOE signal intensity did not differ significantly between gliomas of either hemisphere (P = 0.820), but in case of subventricular zone contact (P = 0.047). A significant correlation was observed between APT and dns-APT and ADC signal intensities (rs = -0.627, P = 0.004 and rs = -0.534, P = 0.019), but not between NOE and ADC (rs = -0.341, P = 0.154). Histopathological/molecular parameters were not significantly different concerning the tumor location (P = 0.104-1.000, P = 0.286-0.696). Data conclusion APT, dns-APT, and ADC were inversely correlated and depended on the gliomas' hemisphere location. NOE showed significant dependence on subventricular zone contact. Location dependency of APT- and NOE-mediated CEST effects should be considered in clinical investigations of CEST MRI. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:777-785.

Background Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. Methods To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch’s t-tests) and principal components analyses were performed in Genespring. Results At the mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT-induced radiologic, histologic and functional lung deficits was correlated with the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT and attenuated by pamrevlumab, and likely contribute to the cross-talk between enriched cell-types in injured lung. Conclusions CTGF inhibition had a normalizing effect on select cell-types, including immune cells not typically regarded as being regulated by CTGF. These results suggest that interactions between RT-recruited cell-types are critical to maintaining the injured state; that CTGF plays a key role in this process; and that pamrevlumab can ameliorate RT-induced lung injury in mice and may provide therapeutic benefit in other immune and fibrotic disorders. Electronic supplementary material The online version of this article (10.1186/s12931-018-0720-4) contains supplementary material, which is available to authorized users.

Diffusion-weighted imaging (DWI) in the female breast is a magnetic resonance imaging (MRI) technique that complements clinical routine protocols, and that might provide an independent diagnostic value for specific clinical tasks in breast imaging. To further improve specificity of DWI in the breast, stronger and faster diffusion weighting is advantageous. Here, a dedicated gradient coil is designed, targeted at diffusion weighting in the female breast, with the peak gradient magnitude exceeding that of the current clinical MR scanners by an order of a magnitude. Design of application-tailored gradient coils in MRI has recently attracted increased attention. With the target application in mind, the gradient coil is designed on an irregularly shaped semi-open current-carrying surface. Due to the coil former closely fitting the non-spherical target region, non-linear encoding fields become particularly advantageous for achieving locally exceptionally high gradient strengths. As breast tissue has a predominantly isotropic cellular microstructure, the direction of the diffusion-weighting gradient may be allowed to vary within the target volume. However, due to the quadratic dependency of the b-factor on the gradient strength, variation of the gradient magnitude should be carefully controlled. To achieve the above design goals the corresponding multi-objective optimization problem is reformulated as a constrained optimization, allowing for flexible and precise control of the coil properties. A novel constraint is proposed, limiting gradient magnitude variation within every slice while allowing for variations in both the direction of the gradient within the slice and the magnitude across the slices. These innovations enable the design of a unilateral coil for diffusion weighting in the female breast with local gradient strengths exceeding 1 T/m with highly homogeneous diffusion weighting for imaging in the coronal slice orientation.

Purpose To explore the value and reproducibility of a novel magnetic resonance based attenuation correction (MRAC) using a CAIPIRINHA-accelerated T1-weighted Dixon 3D-VIBE sequence for whole-body PET/MRI compared to the clinical standard. Methods The PET raw data of 19 patients from clinical routine were reconstructed with standard MRAC (MRAC std ) and the novel MRAC (MRAC caipi ), a prototype CAIPIRINHA accelerated Dixon 3D-VIBE sequence, both acquired in 19 s/bed position. Volume of interests (VOIs) for liver, lung and all voxels of the total image stack were created to calculate standardized uptake values (SUV mean ) followed by inter-method agreement (Passing-Bablok regression, Bland-Altman analysis). A voxel-wise SUV comparison per patient was performed for intra-individual correlation between MRAC std and MRAC caipi . Difference images (MRAC std -MRAC caipi ) of attenuation maps and SUV images were calculated. The image quality of in/opposed-phase water and fat images obtained from MRAC caipi was assessed by two readers on a 5-point Likert-scale including intra-class coefficients for inter-reader agreement. Results SUV mean correlations of VOIs demonstrated high linearity (0.95 8 pixels). Outliers could be explained by different physiological conditions between the scans such as different segmentation of air-containing tissue, lungs, kidneys, metal implants, diaphragm edge or small air bubbles in the gastrointestinal tracts that moved between MRAC acquisitions. Nasal sinuses and the trachea were better segmented in MRAC caipi . High-resolution T1w Dixon 3D VIBE images were acquired in all cases and could be used for PET/MRI fusion. MRAC caipi images were of high diagnostic quality (4.2 ± 0.8) with 0.92-0.96 intra-class correlation. Conclusions The novel prototype MRAC caipi extends the value for attenuation correction by providing a high spatial resolution DIXON-based dataset suited for diagnostic assessment towards time-efficient whole-body PET/MRI.

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, (T2w), 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

INTRODUCTION Diffusion-weighted imaging (DWI) is an important part of oncological magnetic resonance imaging (MRI) examinations, especially for tertiary cancer prevention in terms of early detection of recurrent disease. However, abdominal studies can be challenged by motion artifacts, poor signal-to-noise ratios, and visibility of retroperitoneal structures, which necessitates sequence optimization depending on the investigated region. This study aims at prospectively evaluating an adapted DWI sequence ex vivo and in vivo in oncologic patients undergoing abdominal MRI. METHODS This institutional review board-approved, prospective study included phantom measurements, volunteer examinations, and oncologic patient examinations of the abdomen. Fifty-seven MRI examinations in 54 patients (mean age, 58 years; range, 21-90 years) were included into the analysis. The MRI examination were performed at a 1.5 T MRI scanner (MAGNETOM Aera; Siemens Healthcare, Erlangen, Germany) and included both a standard EPI-DWI (s-DWI; b = 50, 900 s/mm) and an adapted DWI (opt-DWI; EPI-DWI with b = 0, 50, 900, 1500 s/mm, acquisition with higher spatial resolution and optimized processing for the abdomen including motion correction, adaptive image combination, and background suppression). For b = 900 s/mm, the ratio of signal intensity in the normal tissue and the standard deviation of the noise in the surrounding air was quantitatively calculated; image quality and tissue differentiation parameters were rated by 2 independent, blinded readers using a 5-point Likert scale. Statistics included Wilcoxon signed-rank test and kappa statistic (P < 0.05/0.0125 after Bonferroni correction). RESULTS The DWI phantom demonstrated an optimized contour sharpness and inlay differentiation for opt-DWI. The apparent ratio of normal tissue signal/standard deviation of background noise at b = 900 s/mm of the right/left hemiabdomen was significantly increased in opt-DWI (mean, 71.9 ± 23.5/86.0 ± 43.3) versus s-DWI (mean, 51.4 ± 15.4/63.4 ± 36.5; P < 0.001). Image quality parameters (contour sharpness and tissue differentiation of upper abdominal and retroperitoneal structures) were significantly increased in opt-DWI versus s-DWI (P < 0.001). Interreader reliability test showed good agreement (kappa = 0.768; P < 0.001). DISCUSSION This study prospectively evaluated the potential of adapted DWI for screening in tertiary prevention of oncologic patients. An optimized DWI protocol with advanced processing achieved improved image quality in quantitative and qualitative analyses. Oncological optimization of DWI should be performed before its application in cancer patients to improve both screening and follow-up examinations, to better unleash the diagnostic potential of DWI.

The purpose of this study was to investigate the association of relaxation-compensated chemical exchange saturation transfer (CEST) MRI with overall survival (OS) and progression-free survival (PFS) in newly diagnosed high-grade glioma (HGG) patients. Twenty-six patients with newly diagnosed high-grade glioma (WHO grades III–IV) were included in this prospective IRB-approved study. CEST MRI was performed on a 7.0-T whole-body scanner. Association of patient OS/PFS with relaxation-compensated CEST MRI (amide proton transfer (APT), relayed nuclear Overhauser effect (rNOE)/NOE, downfield-rNOE-suppressed APT (dns-APT)) and diffusion-weighted imaging (apparent diffusion coefficient) were assessed using the univariate Cox proportional hazards regression model. Hazard ratios (HRs) and corresponding 95% confidence intervals were calculated. Furthermore, OS/PFS association with clinical parameters (age, gender, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status, and therapy: biopsy + radio-chemotherapy vs. debulking surgery + radio-chemotherapy) were tested accordingly. Relaxation-compensated APT MRI was significantly correlated with patient OS (HR = 3.15, p = 0.02) and PFS (HR = 1.83, p = 0.009). The strongest association with PFS was found for the dns-APT metric (HR = 2.61, p = 0.002). These results still stand for the relaxation-compensated APT contrasts in a homogenous subcohort of n = 22 glioblastoma patients with isocitrate dehydrogenase (IDH) wild-type status. Among the tested clinical parameters, patient age (HR = 1.1, p = 0.001) and therapy (HR = 3.68, p = 0.026) were significant for OS; age additionally for PFS (HR = 1.04, p = 0.048). Relaxation-compensated APT MRI signal intensity is associated with overall survival and progression-free survival in newly diagnosed, previously untreated glioma patients and may, therefore, help to customize treatment and response monitoring in the future. • Amide proton transfer (APT) MRI signal intensity is associated with overall survival and progression in glioma patients. • Relaxation compensation enhances the information value of APT MRI in tumors. • Chemical exchange saturation transfer (CEST) MRI may serve as a non-invasive biomarker to predict prognosis and customize treatment.

Introduction To evaluate the feasibility and accuracy of a semiautomatic, three-dimensional volume of interest (3D sphere) for measuring the apparent diffusion coefficient (ADC) in suspicious breast lesions compared to conventional single-slice two-dimensional regions of interest (2D ROIs). Method This institutional-review-board-approved study included 56 participants with Breast Imaging Reporting and Data System 4/5 lesion. All received diffusion-weighted imaging magnetic resonance imaging prior to biopsy ( b =0–1500 s/mm 2 ). ADC values were measured in the lesions with both methods. Reproducibility and accuracies were compared. Results Area under the curve was 0.93 [95% confidence interval (CI) 0.86–0.99] for the 3D sphere and 0.91 (95% CI 0.84–0.98) for the 2D ROIs without significantly differing reproducibility ( P =.45). Conclusion A semiautomatic 3D sphere could reliably estimate ADC values in suspicious breast lesions without significant difference compared to conventional 2D ROIs.