Reconstruction of 3D knee MRI using deep learning and compressed sensing: a validation study on healthy volunteers.

BACKGROUND: To investigate the potential of combining compressed sensing (CS) and artificial intelligence (AI), in particular deep learning (DL), for accelerating three-dimensional (3D) magnetic resonance imaging (MRI) sequences of the knee. METHODS: Twenty healthy volunteers were examined using a 3-T scanner with a fat-saturated 3D proton density sequence with four different acceleration levels (10, 13, 15, and 17). All sequences were accelerated with CS and reconstructed using the conventional and a new DL-based algorithm (CS-AI). Subjective image quality was evaluated by two blinded readers using seven criteria on a 5-point-Likert-scale (overall impression, artifacts, delineation of the anterior cruciate ligament, posterior cruciate ligament, menisci, cartilage, and bone). Using mixed models, all CS-AI sequences were compared to the clinical standard (sense sequence with an acceleration factor of 2) and CS sequences with the same acceleration factor. RESULTS: 3D sequences reconstructed with CS-AI achieved significantly better values for subjective image quality compared to sequences reconstructed with CS with the same acceleration factor (p ≤ 0.001). The images reconstructed with CS-AI showed that tenfold acceleration may be feasible without significant loss of quality when compared to the reference sequence (p ≥ 0.999). CONCLUSIONS: For 3-T 3D-MRI of the knee, a DL-based algorithm allowed for additional acceleration of acquisition times compared to the conventional approach. This study, however, is limited by its small sample size and inclusion of only healthy volunteers, indicating the need for further research with a more diverse and larger sample. TRIAL REGISTRATION: DRKS00024156. RELEVANCE STATEMENT: Using a DL-based algorithm, 54% faster image acquisition (178 s versus 384 s) for 3D-sequences may be possible for 3-T MRI of the knee. KEY POINTS: • Combination of compressed sensing and DL improved image quality and allows for significant acceleration of 3D knee MRI. • DL-based algorithm achieved better subjective image quality than conventional compressed sensing. • For 3D knee MRI at 3 T, 54% faster image acquisition may be possible.

Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial.

Ketogenic dietary interventions (KDIs) are beneficial in animal models of autosomal-dominant polycystic kidney disease (ADPKD). KETO-ADPKD, an exploratory, randomized, controlled trial, is intended to provide clinical translation of these findings (NCT04680780). Sixty-six patients were randomized to a KDI arm (ketogenic diet [KD] or water fasting [WF]) or the control group. Both interventions induce significant ketogenesis on the basis of blood and breath acetone measurements. Ninety-five percent (KD) and 85% (WF) report the diet as feasible. KD leads to significant reductions in body fat and liver volume. Additionally, KD is associated with reduced kidney volume (not reaching statistical significance). Interestingly, the KD group exhibits improved kidney function at the end of treatment, while the control and WF groups show a progressive decline, as is typical in ADPKD. Safety-relevant events are largely mild, expected (initial flu-like symptoms associated with KD), and transient. Safety assessment is complemented by nuclear magnetic resonance (NMR) lipid profile analyses.

Reconstruction of shoulder MRI using deep learning and compressed sensing: a validation study on healthy volunteers.

BACKGROUND: To investigate the potential of combining compressed sensing (CS) and deep learning (DL) for accelerated two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) of the shoulder. METHODS: Twenty healthy volunteers were examined using at 3-T scanner with a fat-saturated, coronal, 2D proton density-weighted sequence with four acceleration levels (2.3, 4, 6, and 8) and a 3D sequence with three acceleration levels (8, 10, and 13), all accelerated with CS and reconstructed using the conventional algorithm and a new DL-based algorithm (CS-AI). Subjective image quality was evaluated by two blinded readers using 6 criteria on a 5-point Likert scale (overall impression, artifacts, and delineation of the subscapularis tendon, bone, acromioclavicular joint, and glenoid labrum). Objective image quality was measured by calculating signal-to-noise-ratio, contrast-to-noise-ratio, and a structural similarity index measure. All reconstructions were compared to the clinical standard (CS 2D acceleration factor 2.3; CS 3D acceleration factor 8). Additionally, subjective and objective image quality were compared between CS and CS-AI with the same acceleration levels. RESULTS: Both 2D and 3D sequences reconstructed with CS-AI achieved on average significantly better subjective and objective image quality compared to sequences reconstructed with CS with the same acceleration factor (p ≤ 0.011). Comparing CS-AI to the reference sequences showed that 4-fold acceleration for 2D sequences and 13-fold acceleration for 3D sequences without significant loss of quality (p ≥ 0.058). CONCLUSIONS: For MRI of the shoulder at 3 T, a DL-based algorithm allowed additional acceleration of acquisition times compared to the conventional approach. RELEVANCE STATEMENT: The combination of deep-learning and compressed sensing hold the potential for further scan time reduction in 2D and 3D imaging of the shoulder while providing overall better objective and subjective image quality compared to the conventional approach. TRIAL REGISTRATION: DRKS00024156. KEY POINTS: • Combination of compressed sensing and deep learning improved image quality and allows for significant acceleration of shoulder MRI. • Deep learning-based algorithm achieved better subjective and objective image quality than conventional compressed sensing. • For shoulder MRI at 3 T, 40% faster image acquisition for 2D sequences and 38% faster image acquisition for 3D sequences may be possible.

A deep learning-based reconstruction approach for accelerated magnetic resonance image of the knee with compressed sense: evaluation in healthy volunteers.

OBJECTIVES: To evaluate the feasibility of combining compressed sense (CS) with a newly developed deep learning-based algorithm (CS-AI) using convolutional neural networks to accelerate 2D MRI of the knee. METHODS: In this prospective study, 20 healthy volunteers were scanned with a 3T MRI scanner. All subjects received a fat-saturated sagittal 2D proton density reference sequence without acceleration and four additional acquisitions with different acceleration levels: 2, 3, 4 and 6. All sequences were reconstructed with the conventional CS and a new CS-AI algorithm. Two independent, blinded readers rated all images by seven criteria (overall image impression, visible artifacts, delineation of anterior ligament, posterior ligament, menisci, cartilage, and bone) using a 5-point Likert scale. Signal- and contrast-to-noise ratios were calculated. Subjective ratings and quantitative metrics were compared between CS and CS-AI with similar acceleration levels and between all CS/CS-AI images and the non-accelerated reference sequence. Friedman and Dunn´s multiple comparison tests were used for subjective, ANOVA and the Tukey Kramer test for quantitative metrics. RESULTS: Conventional CS images at the lowest acceleration level (CS2) were already rated significantly lower than reference for 6/7 criteria. CS-AI images maintained similar image quality to the reference up to CS-AI three for all criteria, which would allow for a reduction in scan time of 64% with unchanged image quality compared to the unaccelerated sequence. SNR and CNR were significantly higher for all CS-AI reconstructions compared to CS (all p < 0.05). CONCLUSIONS: AI-based image reconstruction showed higher image quality than CS for 2D knee imaging. Its implementation in the clinical routine yields the potential for faster MRI acquisition but needs further validation in non-healthy study subjects. ADVANCES IN KNOWLEDGE: Combining compressed SENSE with a newly developed deep learning-based algorithm using convolutional neural networks allows a 64% reduction in scan time for 2D imaging of the knee. Implementation of the new deep learning-based algorithm in clinical routine in near future should enable better image quality/resolution with constant scan time, or reduced acquisition times while maintaining diagnostic quality.

RESET-PKD: a pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease.

BACKGROUND: Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease (PKD), but data from clinical trials are lacking. METHODS: Ten autosomal dominant PKD (ADPKD) patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3-6 weeks until V4. At each visit, magnetic resonance imaging kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility. RESULTS: All participants [KD n = 5, WF n = 5; age 39.8 ± 11.6 years; estimated glomerular filtration rate 82 ± 23.5 mL/min/1.73 m2; total kidney volume (TKV) 2224 ± 1156 mL] were classified as Mayo Class 1C-1E. Acetone levels in breath and beta-hydroxybutyrate (BHB) blood levels increased in both study arms (V1 to V2 average acetone: 2.7 ± 1.2 p.p.m., V2 to V3: 22.8 ± 11.9 p.p.m., P = .0006; V1 to V2 average BHB: 0.22 ± 0.08 mmol/L, V2 to V3: 1.88 ± 0.93 mmol/L, P = .0008). Nine of 10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, P = .01), mediated by changes in its non-cystic fraction. CONCLUSIONS: RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.

Ketogenic dietary interventions in autosomal dominant polycystic kidney disease-a retrospective case series study: first insights into feasibility, safety and effects.

Background: Our laboratory published the first evidence that nutritional ketosis, induced by a ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in polycystic kidney disease (PKD) animal models. We reasoned that, due to their frequent use for numerous health benefits, some autosomal dominant PKD (ADPKD) patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect the first real-life observations of ADPKD patients about safety, feasibility and possible benefits of KDIs in ADPKD as part of a translational project pipeline. Methods: Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects and the feasibility and safety of KDIs in questionnaire-based interviews. Results: A total of 131 ADPKD patients took part in this study. About 74 executed a KD and 52 a TRD for 6 months on average. A total of 86% of participants reported that KDIs had improved their overall health, 67% described improvements in ADPKD-associated health issues, 90% observed significant weight loss, 64% of participants with hypertension reported improvements in blood pressure, 66% noticed adverse effects that are frequently observed with KDIs, 22 participants reported safety concerns like hyperlipidemia, 45 participants reported slight improvements in estimated glomerular filtration rate and 92% experienced KDIs as feasible while 53% reported breaks during their diet. Conclusions: Our preliminary data indicate that KDIs may be safe, feasible and potentially beneficial for ADPKD patients, highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.

Automated Kidney and Liver Segmentation in MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease: A Multicenter Study.

Background: Imaging-based total kidney volume (TKV) and total liver volume (TLV) are major prognostic factors in autosomal dominant polycystic kidney disease (ADPKD) and end points for clinical trials. However, volumetry is time consuming and reader dependent in clinical practice. Our aim was to develop a fully automated method for joint kidney and liver segmentation in magnetic resonance imaging (MRI) and to evaluate its performance in a multisequence, multicenter setting. Methods: The convolutional neural network was trained on a large multicenter dataset consisting of 992 MRI scans of 327 patients. Manual segmentation delivered ground-truth labels. The model's performance was evaluated in a separate test dataset of 93 patients (350 MRI scans) as well as a heterogeneous external dataset of 831 MRI scans from 323 patients. Results: The segmentation model yielded excellent performance, achieving a median per study Dice coefficient of 0.92-0.97 for the kidneys and 0.96 for the liver. Automatically computed TKV correlated highly with manual measurements (intraclass correlation coefficient [ICC]: 0.996-0.999) with low bias and high precision (-0.2%±4% for axial images and 0.5%±4% for coronal images). TLV estimation showed an ICC of 0.999 and bias/precision of -0.5%±3%. For the external dataset, the automated TKV demonstrated bias and precision of -1%±7%. Conclusions: Our deep learning model enabled accurate segmentation of kidneys and liver and objective assessment of TKV and TLV. Importantly, this approach was validated with axial and coronal MRI scans from 40 different scanners, making implementation in clinical routine care feasible.Clinical Trial registry name and registration number: The German ADPKD Tolvaptan Treatment Registry (AD[H]PKD), NCT02497521.

Validation of Deep Learning-based Augmentation for Reduced 18F-FDG Dose for PET/MRI in Children and Young Adults with Lymphoma.

PURPOSE: To investigate if a deep learning convolutional neural network (CNN) could enable low-dose fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI for correct treatment response assessment of children and young adults with lymphoma. MATERIALS AND METHODS: In this secondary analysis of prospectively collected data (ClinicalTrials.gov identifier: NCT01542879), 20 patients with lymphoma (mean age, 16.4 years ± 6.4 [standard deviation]) underwent 18F-FDG PET/MRI between July 2015 and August 2019 at baseline and after induction chemotherapy. Full-dose 18F-FDG PET data (3 MBq/kg) were simulated to lower 18F-FDG doses based on the percentage of coincidence events (representing simulated 75%, 50%, 25%, 12.5%, and 6.25% 18F-FDG dose [hereafter referred to as 75%Sim, 50%Sim, 25%Sim, 12.5%Sim, and 6.25%Sim, respectively]). A U.S. Food and Drug Administration-approved CNN was used to augment input simulated low-dose scans to full-dose scans. For each follow-up scan after induction chemotherapy, the standardized uptake value (SUV) response score was calculated as the maximum SUV (SUVmax) of the tumor normalized to the mean liver SUV; tumor response was classified as adequate or inadequate. Sensitivity and specificity in the detection of correct response status were computed using full-dose PET as the reference standard. RESULTS: With decreasing simulated radiotracer doses, tumor SUVmax increased. A dose below 75%Sim of the full dose led to erroneous upstaging of adequate responders to inadequate responders (43% [six of 14 patients] for 75%Sim; 93% [13 of 14 patients] for 50%Sim; and 100% [14 of 14 patients] below 50%Sim; P < .05 for all). CNN-enhanced low-dose PET/MRI scans at 75%Sim and 50%Sim enabled correct response assessments for all patients. Use of the CNN augmentation for assessing adequate and inadequate responses resulted in identical sensitivities (100%) and specificities (100%) between the assessment of 100% full-dose PET, augmented 75%Sim, and augmented 50%Sim images. CONCLUSION: CNN enhancement of PET/MRI scans may enable 50% 18F-FDG dose reduction with correct treatment response assessment of children and young adults with lymphoma.Keywords: Pediatrics, PET/MRI, Computer Applications Detection/Diagnosis, Lymphoma, Tumor Response, Whole-Body Imaging, Technology AssessmentClinical trial registration no: NCT01542879 Supplemental material is available for this article. © RSNA, 2021.

Speeding up the clinical routine: Compressed sensing for 2D imaging of lumbar spine disc herniation.

PURPOSE: Increasing economic pressure and patient demands for comfort require an ever-increasing acceleration of scan times without compromising diagnostic certainty. This study tested the new acceleration technique Compressed SENSE (CS-SENSE) as well as different reconstruction methods for the lumbar spine. METHODS: In this prospective study, 10 volunteers and 14 patients with lumbar disc herniation were scanned using a sagittal 2D T2 turbo spin echo (TSE) sequence applying different acceleration factors of SENSE and CS-SENSE. Gradient echo (GRE), autocalibration (CS-Auto) and TSE prescans were tested for reconstruction. Images were analysed by two readers regarding anatomical delineation, diagnostic certainty (for patients only) and image quality as well as objectively calculating the root mean square error (RMSE), structural similarity index (SSIM), SNR and CNR. The Friedman test and Chi-squared were used for ordinal, ANOVA for repeated measurements and Tukey Kramer test for continuous data. Cohen's kappawas calculated for interreader reliability. RESULTS: CS-SENSE outperformed SENSE and CS-Auto regarding RMSE (e.g. CS-SENSE 1.5: 43.03 ±â€¯11.64 versus SENSE 1.5: 80.41 ±â€¯17.66; p = 0.0038) and SSIM as well as in the subjective rating for CS-SENSE 3 TSE. In the patient setting image quality was unchanged in all subjective criteria up to CS-SENSE 3 TSE (all p > 0.05) compared to standard T2 with 43 % less scan time while the GRE prescan only allowed a reduction of 32 %. CONCLUSION: Combining a TSE prescan with CS-SENSE enables significant scan time reductions with unchanged ratings for lumbar spine disc herniation making this superior to the currently used SENSE acceleration or GRE reconstructions.

Insights into extrinsic foot muscle activation during a 75 min run using T2 mapping.

The extrinsic foot muscles are essentially for controlling the movement path but our knowledge of their behavior during prolonged running is still very limited. Therefore, this study analyzed the time-course of muscle activation using T2 mapping during 75 min of running. In this prospective study, 19 recreational active runners completed 75 min of treadmill running at a constant speed. Interleaved T2 mapping sequences were acquired and segmented at timepoints 0, 2.5, 5, 10, 15, 45, and 75 min. ANOVA for repeated measurements followed by a Tukey post hoc test and Pearson correlation between running speed and initial signal increase at 2.5 min were calculated. All muscles showed a significant signal increase between baseline and 2.5 min (e.g. medial gastrocnemius: + 15.48%; p < 0.01). This was followed by a plateau phase till 15 min for all but the extensor digitorum longus muscle and a significant decrease at 45 or 75 min for all muscles (all p < 0.05). Correlation between running speed and signal increase was negative for all muscles and significant for both gastrocnemii (e.g. medial: r = - 0.57, p = 0.0104) and soleus (r = - 0.47, p = 0.0412). The decrease of relaxation times times in the later running phases was less pronounced for faster runners (≥ 10 km/h). T2 relaxation times do not only decrease after cessation of exercise but already during prolonged running. The lesser initial increase and later decrease in faster runners may indicate training induced changes.

Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). / Strukturierte Befundung von soliden und zystischen Pankreasläsionen im CT und MRT: Konsensus-basierte Befundvorlagen der Deutschen Röntgengesellschaft (DRG).

BACKGROUND: Radiological reports of pancreatic lesions are currently widely formulated as free texts. However, for optimal characterization, staging and operation planning, a wide range of information is required but is sometimes not captured comprehensively. Structured reporting offers the potential for improvement in terms of completeness, reproducibility and clarity of interdisciplinary communication. METHOD: Interdisciplinary consensus finding of structured report templates for solid and cystic pancreatic tumors in computed tomography (CT) and magnetic resonance imaging (MRI) with representatives of the German Society of Radiology (DRG), German Society for General and Visceral Surgery (DGAV), working group Oncological Imaging (ABO) of the German Cancer Society (DKG) and other radiologists, oncologists and surgeons. RESULTS: Among experts in the field of pancreatic imaging, oncology and pancreatic surgery, as well as in a public online survey, structured report templates were developed by consensus. These templates are available on the DRG homepage under www.befundung.drg.de and will be regularly revised to the current state of scientific knowledge by the participating specialist societies and responsible working groups. CONCLUSION: This article presents structured report templates for solid and cystic pancreatic tumors to improve clinical staging (cTNM, ycTNM) in everyday radiology. KEY POINTS: · Structured report templates offer the potential of optimized radiological reporting with regard to completeness, reproducibility and differential diagnosis.. · This article presents consensus-based, structured reports for solid and cystic pancreatic lesions in CT and MRI.. · These structured reports are available open source on the homepage of the German Society of Radiology (DRG) under www.befundung.drg.de.. CITATION FORMAT: · Persigehl T, Baumhauer M, Baeßler B et al. Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). Fortschr Röntgenstr 2020; 192: 641 - 655.

Quantification of metal artifacts in computed tomography: methodological considerations.

Numerous methods for artifact quantification in computed tomography (CT) imaging have been suggested. This study evaluated their utility with regards to correspondence with visual artifact perception and reproducibility. Two titanium rods (5 and 10 mm) were examined with 25 different scanning- and image-reconstruction parameters resulting in different types and extents of artifacts. Four radiologists evaluated every image against each other using an in-house developed software. Rating was repeated two times (2,400 comparisons = 2 times × 4 readers × 300 comparisons). Rankings were combined to obtain a reference ranking. Proposed approaches for artifact quantification include manual measurement of attenuation, standard deviation and noise and sophisticated algorithm-based approaches within the image- and frequency-domain. Two radiologists conducted manual measurements twice while the aforementioned algorithms were implemented within the Matlab-Environment allowing for automated image analysis. The reference ranking was compared to all aforementioned methods for artifact quantification to identify suited approaches. Besides visual analysis, Kappa-statistics and intraclass correlation coefficients (ICC) were used. Intra- and Inter-reader agreements of visual artifact perception were excellent (ICC 0.85-0.92). No quantitative method was able to represent the exact ranking of visually perceived artifacts; however, ICC for manual measurements were low (ICC 0.25-0.97). The method that showed best correspondence and reproducibility used a Fourier-transformed linear ROI and lower-end frequency bins. Automated measurements of artifact extent should be preferred over manual measurements as the latter show a limited reproducibility. One method that allows for automated quantification of such artefacts is made available as an electronic supplement.

Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI.

Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

Differentiation of benign and malignant lymph nodes in pediatric patients on ferumoxytol-enhanced PET/MRI.

The composition of lymph nodes in pediatric patients is different from that in adults. Most notably, normal lymph nodes in children contain less macrophages. Therefore, previously described biodistributions of iron oxide nanoparticles in benign and malignant lymph nodes of adult patients may not apply to children. The purpose of our study was to evaluate if the iron supplement ferumoxytol improves the differentiation of benign and malignant lymph nodes in pediatric cancer patients on 18F-FDG PET/MRI. Methods: We conducted a prospective clinical trial from May 2015 to December 2018 to investigate the value of ferumoxytol nanoparticles for staging of children with cancer with 18F-FDG PET/MRI. Ferumoxytol is an FDA-approved iron supplement for the treatment of anemia and has been used "off-label" as an MRI contrast agent in this study. Forty-two children (7-18 years, 29 male, 13 female) received a 18F-FDG PET/MRI at 2 (n=20) or 24 hours (h) (n=22) after intravenous injection of ferumoxytol (dose 5 mg Fe/kg). The morphology of benign and malignant lymph nodes on ferumoxytol-enhanced T2-FSE sequences at 2 and 24 h were compared using a linear regression analysis. In addition, ADCmean-values, SUV-ratio (SUVmax lesion/SUVmean liver) and R2*-relaxation rate of benign and malignant lymph nodes were compared with a Mann-Whitney-U test. The accuracy of different criteria was assessed with a receiver operating characteristics (ROC) curve. Follow-up imaging for at least 6 months served as the standard of reference. Results: We examined a total of 613 lymph nodes, of which 464 (75.7%) were benign and 149 (24.3%) were malignant. On ferumoxytol-enhanced T2-FSE images, benign lymph nodes showed a hypointense hilum and hyperintense parenchyma, while malignant lymph nodes showed no discernible hilum. This pattern was not significantly different at 2 h and 24 h postcontrast (p=0.82). Benign and malignant lymph nodes showed significantly different ferumoxytol enhancement patterns, ADCmean values of 1578 and 852 x10-6 mm2/s, mean SUV-ratios of 0.5 and 2.8, and mean R2*-relaxation rate of 127.8 and 84.4 Hertz (Hz), respectively (all p<0.001). The accuracy of ADCmean, SUV-ratio and pattern (area under the curve (AUC): 0.99; 0.98; 0.97, respectively) was not significantly different (p=0.07). Compared to these three parameters, the accuracy of R2* was significantly lower (AUC: 0.93; p=0.001). Conclusion: Lymph nodes in children show different ferumoxytol-enhancement patterns on MRI than previously reported for adult patients. We found high accuracy (>90%) of ADCmean, SUV-ratio, pattern, and R2* measurements for the characterization of benign and malignant lymph nodes in children. Ferumoxytol nanoparticle accumulation at the hilum can be used to diagnose a benign lymph node. In the future, the delivery of clinically applicable nanoparticles to the hilum of benign lymph nodes could be harnessed to deliver theranostic drugs for immune cell priming.

Respiratory motion artefacts in Gd-EOB-DTPA (Primovist/Eovist) and Gd-DOTA (Dotarem)-enhanced dynamic phase liver MRI after intensified and standard pre-scan patient preparation: A bi-institutional analysis.

OBJECTIVE: The objective of this study is to evaluate if intensified pre-scan patient preparation (IPPP) that comprises custom-made educational material on dynamic phase imaging and supervised pre-imaging breath-hold training in addition to standard informative conversation with verbal explanation of breath-hold commands (standard pre-scan patient preparation-SPPP) might reduce the incidence of gadoxetate disodium (Gd-EOB-DTPA)-related transient severe respiratory motion (TSM) and severity of respiratory motion (RM) during dynamic phase liver MRI. MATERIAL AND METHODS: In this bi-institutional study 100 and 110 patients who received Gd-EOB-DTPA for dynamic phase liver MRI were allocated to either IPPP or SPPP at site A and B. The control group comprised 202 patients who received gadoterate meglumine (Gd-DOTA) of which each 101 patients were allocated to IPPP or SPPP at site B. RM artefacts were scored retrospectively in dynamic phase images (1: none- 5: extensive) by five and two blinded readers at site A and B, respectively, and in the hepatobiliary phase of the Gd-EOB-DTPA-enhanced scans by two blinded readers at either site. RESULTS: The incidence of TSM was 15% at site A and 22.7% at site B (p = 0.157). IPPP did not reduce the incidence of TSM in comparison to SPPP: 16.7% vs. 21.6% (p = 0.366). This finding was consistent at site A: 12% vs. 18% (p = 0.401) and site B: 20.6% vs. 25% (p = 0.590). The TSM incidence in patients with IPPP and SPPP did not differ significantly between both sites (p = 0.227; p = 0.390). IPPP did not significantly mitigate RM in comparison to SPPP in any of the Gd-EOB-DTPA-enhanced dynamic phases and the hepatobiliary phase in patients without TSM (all p≥0.072). In the Gd-DOTA control group on the other hand, IPPP significantly mitigated RM in all dynamic phases in comparison to SPPP (all p≤0.031). CONCLUSIONS: We conclude that Gd-EOB-DTPA-related TSM cannot be mitigated by education and training and that Gd-EOB-DTPA-related breath-hold difficulty does not only affect the subgroup of patients with TSM or exclusively the arterial phase as previously proposed.

Comparison of ferumoxytol- and gadolinium chelate-enhanced MRI for assessment of sarcomas in children and adolescents.

OBJECTIVES: We compared the value of ferumoxytol (FMX)- and gadolinium (Gd)-enhanced MRI for assessment of sarcomas in paediatric/adolescent patients and hypothesised that tumour size and morphological features can be equally well assessed with both protocols. METHODS: We conducted a retrospective study of paediatric/adolescent patients with newly diagnosed bone or soft tissue sarcomas and both pre-treatment FMX- and Gd-MRI scans, which were maximal 4 weeks apart. Both protocols included T1- and T2-weighted sequences. One reader assessed tumour volumes, signal-to-noise ratios (SNR) of the primary tumour and adjacent tissues and contrast-to-noise ratios (CNR) of FMX- and Gd-MRI scans. Additionally, four readers scored FMX- and Gd-MRI scans according to 15 diagnostic parameters, using a Likert scale. The results were pooled across readers and compared between FMX- and Gd-MRI scans. Statistical methods included multivariate analyses with different models. RESULTS: Twenty-two patients met inclusion criteria (16 males, 6 females; mean age 15.3 ± 5.0). Tumour volume was not significantly different on T1-LAVA (p = 0.721), T1-SE (p = 0.290) and T2-FSE (p = 0.609) sequences. Compared to Gd-MRI, FMX-MRI demonstrated significantly lower tumour SNR on T1-LAVA (p < 0.001), equal tumour SNR on T1-SE (p = 0.104) and T2-FSE (p = 0.305), significantly higher tumour-to-marrow CNR (p < 0.001) on T2-FSE as well as significantly higher tumour-to-liver (p = 0.021) and tumour-to-vessel (p = 0.003) CNR on T1-LAVA images. Peritumoural and marrow oedema enhanced significantly more on Gd-MRI compared to FMX-MRI (p < 0.001/p = 0.002, respectively). Tumour thrombi and neurovascular bundle involvement were assessed with a significantly higher confidence on FMX-MRI (both p < 0.001). CONCLUSIONS: FMX-MRI provides equal assessment of the extent of bone and soft tissue sarcomas compared to Gd-MRI with improved tumour delineation and improved evaluation of neurovascular involvement and tumour thrombi. Therefore, FMX-MRI is a possible alternative to Gd-MRI for tumour staging in paediatric/adolescent sarcoma patients. KEY POINTS: • Ferumoxytol can be used as an alterative to gadolinium chelates for MRI staging ofpaediatric sarcomas. • Ferumoxytol-enhanced MRI provides equal assessment of tumour size and other diagnostic parameters compared to gadolinium chelate-enhanced MRI. • Ferumoxytol-enhanced MRI provides improved delineation of sarcomas from bone marrow, liver and vessels compared to gadolinium chelate-enhanced MRI.

Magnetic Resonance Kidney Parenchyma-T2 as a Novel Imaging Biomarker for Autosomal Dominant Polycystic Kidney Disease.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is a chronic progressive disorder with a significant disease burden leading to end-stage renal disease in more than 75% of the affected individuals. Although prediction of disease progression is highly important, all currently available biomarkers-including height-adjusted total kidney volume (htTKV)-have important drawbacks in the everyday clinical setting. Thus, the purpose of this study was to evaluate T2 mapping as a source of easily obtainable and accurate biomarkers, which are needed for improved patient counseling and selection of targeted treatment options. MATERIALS AND METHODS: A total of 139 ADPKD patients from The German ADPKD Tolvaptan Treatment Registry and 10 healthy controls underwent magnetic resonance imaging on a clinical 1.5-T system including acquisition of a Gradient-Echo-Spin-Echo T2 mapping sequence. The ADPKD patients were divided into 3 groups according to kidney cyst fraction (0%-35%, 36%-70%, >70%) as a surrogate marker for disease severity. The htTKV was calculated based on standard T2-weighted imaging. Mean T2 relaxation times of both kidneys (kidney-T2) as well as T2 relaxation times of the residual kidney parenchyma (parenchyma-T2) were measured on the T2 maps. RESULTS: Calculation of parenchyma-T2 was 6- to 10-fold faster than determination of htTKV and kidney-T2 (0.78 ± 0.14 vs 4.78 ± 1.17 minutes, P < 0.001; 0.78 ± 0.14 vs 7.59 ± 1.57 minutes, P < 0.001). Parenchyma-T2 showed a similarly strong correlation to cyst fraction (r = 0.77, P < 0.001) as kidney-T2 (r = 0.76, P < 0.001), the strongest correlation to the serum-derived biomarker copeptin (r = 0.37, P < 0.001), and allowed for the most distinct separation of patient groups divided according to cyst fraction. In contrast, htTKV showed an only moderate correlation to cyst fraction (r = 0.48, P < 0.001). These observations were even more evident when considering only patients with preserved kidney function. CONCLUSIONS: The rapidly assessable parenchyma-T2 shows a strong association with disease severity early in disease and is superior to htTKV when it comes to correlation with renal cyst fraction.

Computed tomography pulmonary angiograms using a novel dual-layer spectral detector: Adjusted window settings are essential for diagnostic image quality.

OBJECTIVE: The aim of this study was to determine optimal window settings for conventional polyenergetic and virtual monoenergetic images derived from computed tomography pulmonary angiogram (CTPA) examinations of a novel dual-layer spectral detector computed tomography system (DLCT). METHODS: Monoenergetic (40 keV) and polyenergetic images of 50 CTPA examinations were calculated and the best individual window width and level (W/L) values were manually assessed. Optimized values were obtained afterwards based on regression analysis. Diameters of standardized pulmonary artery segments and subjective image quality parameters were evaluated and compared. RESULTS: Attenuation and contrast-to-noise values were higher in monoenergetic than in polyenergetic images (P≤.001). Averaged best individual W/L for polyenergetic and monoenergetic were 1020/170 and 2070/480 HU, respectively.All adjusted W/L-settings varied significantly compared to standard settings (700/100 HU) and obtained higher subjective image quality scores. A systematic overestimation of artery diameters for standard window settings in monoenergetic images was observed. CONCLUSIONS: Appropriate W/L-settings are required to assess polyenergetic and monoenergetic CTPA images of a novel DLCT. W/L-settings of 1020/170 HU and 2070/480 HU were found to be the best averaged values for polyenergetic and monoenergetic CTPA images, respectively.

Dual Inhibition of GLUT1 and the ATR/CHK1 Kinase Axis Displays Synergistic Cytotoxicity in KRAS-Mutant Cancer Cells.

The advent of molecularly targeted therapeutic agents has opened a new era in cancer therapy. However, many tumors rely on nondruggable cancer-driving lesions. In addition, long-lasting clinical benefits from single-agent therapies rarely occur, as most of the tumors acquire resistance over time. The identification of targeted combination regimens interfering with signaling through oncogenically rewired pathways provides a promising approach to enhance efficacy of single-agent-targeted treatments. Moreover, combination drug therapies might overcome the emergence of drug resistance. Here, we performed a focused flow cytometry-based drug synergy screen and identified a novel synergistic interaction between GLUT1-mediated glucose transport and the cell-cycle checkpoint kinases ATR and CHK1. Combined inhibition of CHK1/GLUT1 or ATR/GLUT1 robustly induced apoptosis, particularly in RAS-mutant cancer cells. Mechanistically, combined inhibition of ATR/CHK1 and GLUT1 arrested sensitive cells in S-phase and led to the accumulation of genotoxic damage, particularly in S-phase. In vivo, simultaneous inhibition of ATR and GLUT1 significantly reduced tumor volume gain in an autochthonous mouse model of KrasG12D -driven soft tissue sarcoma. Taken together, these findings pave the way for combined inhibition of GLUT1 and ATR/CHK1 as a therapeutic approach for KRAS-driven cancers. SIGNIFICANCE: Dual targeting of the DNA damage response and glucose transport synergistically induces apoptosis in KRAS-mutant cancer, suggesting this combination treatment for clinical validation in KRAS-stratified tumor patients.