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.

Pulmonary Dysfunction after Pediatric COVID-19.

Background Long COVID occurs at a lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field-strength MRI may help identify persistent pulmonary manifestations after SARS-CoV-2 infection. Purpose To characterize both morphologic and functional changes of lung parenchyma at low-field-strength MRI in children and adolescents with post-COVID-19 condition compared with healthy controls. Materials and Methods Between August and December 2021, a cross-sectional clinical trial using low-field-strength MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes at MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive reverse transcriptase-polymerase chain reaction test result, and serologic 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 those with long COVID. Results A total of 54 participants after COVID-19 infection (mean age, 11 years ± 3 [SD]; 30 boys [56%]) and nine healthy controls (mean age, 10 years ± 3; seven boys [78%]) 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 (ventilation-perfusion [V/Q] match) was higher in healthy controls (81% ± 6.1) compared with the recovered group (62% ± 19; P = .006) and the group with long COVID (60% ± 20; P = .003). V/Q match was lower in patients with time from COVID-19 infection to study participation of less than 180 days (63% ± 20; P = .03), 180-360 days (63% ± 18; P = .03), and 360 days (41% ± 12; P < .001) as compared with the never-infected healthy controls (81% ± 6.1). Conclusion Low-field-strength MRI showed persistent pulmonary dysfunction in children and adolescents who recovered from COVID-19 and those with long COVID. Clinical trial registration no. NCT04990531 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Paltiel in this issue.

Sodium and quantitative hydrogen parameter changes in muscle tissue after eccentric exercise and in delayed-onset muscle soreness assessed with magnetic resonance imaging.

The objective of the current study was to assess sodium (23 Na) and quantitative proton (1 H) parameter changes in muscle tissue with magnetic resonance imaging (MRI) after eccentric exercise and in delayed-onset muscle soreness (DOMS). Fourteen participants (mean age: 25 ± 4 years) underwent 23 Na/1 H MRI of the calf muscle on a 3-T MRI system before exercise (t0), directly after eccentric exercise (t1), and 48 h postintervention (t2). In addition to tissue sodium concentration (TSC), intracellular-weighted sodium (ICwS) signal was acquired using a three-dimensional density-adapted radial projection readout with an additional inversion recovery preparation module. Phantoms containing saline solution served as references to quantify sodium concentrations. The 1 H MRI protocol consisted of a T1 -weighted turbo spin echo sequence, a T2 -weighted turbo inversion recovery, as well as water T2 mapping and water T1 mapping. Additionally, blood serum creatine kinase (CK) levels were assessed at baseline and 48 h after exercise. The TSC and ICwS of exercised muscles increased significantly from t0 to t1 and decreased significantly from t1 to t2. In the soleus muscle (SM), ICwS decreased below baseline values at t2. In the tibialis anterior muscle (TA), TSC and ICwS remained at baseline levels at each measurement point. However, high-CK participants (i.e., participants with a more than 10-fold CK increase, n = 3) displayed different behavior, with 2- to 4-fold increases in TSC values in the medial gastrocnemius muscle (MGM) at t2. 1 H water T1 relaxation times increased significantly after 48 h in the MGM and SM. 1 H water T2 relaxation times and muscle volume increased in the MGM at t2. Sodium MRI parameters and water relaxation times peaked at different points. Whereas water relaxation times were highest at t2, sodium MRI parameters had already returned to baseline values (or even below baseline values, for low-CK participants) by this point. The observed changes in ion concentrations and water relaxation time parameters could enable a better understanding of the physiological processes during DOMS and muscle regeneration. In the future, this might help to optimize training and to reduce associated sports injuries.

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.

Advanced neural networks for classification of MRI in psoriatic arthritis, seronegative, and seropositive rheumatoid arthritis.

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.

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.

[Imaging of the lung using low-field magnetic resonance imaging]. / Lungenbildgebung in der Niederfeld-Magnetresonanztomographie.

BACKGROUND: 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. OBJECTIVES: 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. MATERIALS AND METHODS: 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. CONCLUSION: 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.

Ultra-High-b-Value Kurtosis Imaging for Noninvasive Tissue Characterization of Ovarian Lesions.

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.

A novel normalization for amide proton transfer CEST MRI to correct for fat signal-induced artifacts: application to human breast cancer imaging.

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.

Diffusion-weighted MRI for Unenhanced Breast Cancer Screening.

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.

Classification of Cancer at Prostate MRI: Deep Learning versus Clinical PI-RADS Assessment.

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.

Abbreviated MRI Protocols in Breast Cancer Diagnostics.

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.

Chemical exchange saturation transfer (CEST) signal intensity at 7T MRI of WHO IV° gliomas is dependent on the anatomic location.

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.

Relaxation-compensated amide proton transfer (APT) MRI signal intensity is associated with survival and progression in high-grade glioma patients.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. KEY POINTS: • 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.

Threshold Isocontouring on High b-Value Diffusion-Weighted Images in Magnetic Resonance Mammography.

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.

Radiomics Based on Adapted Diffusion Kurtosis Imaging Helps to Clarify Most Mammographic Findings Suspicious for Cancer.

Purpose To evaluate a radiomics model of Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 breast lesions extracted from breast-tissue-optimized kurtosis magnetic resonance (MR) imaging for lesion characterization by using a sensitivity threshold similar to that of biopsy. Materials and Methods This institutional study included 222 women at two independent study sites (site 1: training set of 95 patients; mean age ± standard deviation, 58.6 years ± 6.6; 61 malignant and 34 benign lesions; site 2: independent test set of 127 patients; mean age, 58.2 years ± 6.8; 61 malignant and 66 benign lesions). All women presented with a finding suspicious for cancer at x-ray mammography (BI-RADS 4 or 5) and an indication for biopsy. Before biopsy, diffusion-weighted MR imaging (b values, 0-1500 sec/mm2) was performed by using 1.5-T imagers from different MR imaging vendors. Lesions were segmented and voxel-based kurtosis fitting adapted to account for fat signal contamination was performed. A radiomics feature model was developed by using a random forest regressor. The fixed model was tested on an independent test set. Conventional interpretations of MR imaging were also assessed for comparison. Results The radiomics feature model reduced false-positive results from 66 to 20 (specificity 70.0% [46 of 66]) at the predefined sensitivity of greater than 98.0% [60 of 61] in the independent test set, with BI-RADS 4a and 4b lesions benefiting from the analysis (specificity 74.0%, [37 of 50]; 60.0% [nine of 15]) and BI-RADS 5 lesions showing no added benefit. The model significantly improved specificity compared with the median apparent diffusion coefficient (P < .001) and apparent kurtosis coefficient (P = .02) alone. Conventional reading of dynamic contrast material-enhanced MR imaging provided sensitivity of 91.8% (56 of 61) and a specificity of 74.2% (49 of 66). Accounting for fat signal intensity during fitting significantly improved the area under the curve of the model (P = .001). Conclusion A radiomics model based on kurtosis diffusion-weighted imaging performed by using MR imaging machines from different vendors allowed for reliable differentiation between malignant and benign breast lesions in both a training and an independent test data set. © RSNA, 2018 Online supplemental material is available for this article.

Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab.

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.

Pediatric Brain: No Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-weighted MR Images after Consecutive Exposure to a Macrocyclic Gadolinium-based Contrast Agent.

Purpose To determine the effect of at least five serial injections of the macrocyclic gadolinium-based contrast agent (GBCA) gadoterate meglumine on the signal intensity (SI) of the dentate nucleus (DN) of the pediatric brain on nonenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 41 pediatric patients (age range, 3-17 years) who were imaged in at least five consecutive 1.5-T MR examinations with the exclusive use of gadoterate meglumine (plus a final additional nonenhanced MR imaging examination) were evaluated. SI ratio differences between the first and last MR examination were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios in a region-of-interest-based analysis, and one-sample t tests were used to examine if the SI ratio differences differed from 0. Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 8.6 ± 3.9 GBCA administrations (mean accumulated dose, 32.07 mmol ± 17.62, with an average of 16.7 weeks ± 7.9 between every administration). Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0012 ± 0.0101, P = .436; DN-to-MCP ratio: 0.0007 ± 0.0088, P = .604), and one-sided Bayes factors provided substantial evidence against an SI ratio increase (0.10 for DN-to-pons ratio; 0.27 for DN-to-MCP ratio). Conclusion No increase of the SI in the DN was found after a mean of 8.6 serial injections of the macrocyclic GBCA gadoterate meglumine in pediatric patients, confirming previous studies that did not find this effect after serial injections of macrocyclic GBCAs in adults. © RSNA, 2017.

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.