A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in KRAS-mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct Kras- or Braf-driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in KRAS- or BRAF-mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of KRAS- or BRAF-driven cancers.

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.

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.

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.

Latest Generation of Balloon-Expandable Valve, the Edwards Sapien 3 Valve: Less Paravalvular Regurgitation but Higher Transvalvular Pressure Gradients.

BACKGROUND: The latest generation of balloon-expandable valve, the Edwards Sapien 3 valve (S3V), was designed to reduce paravalvular regurgitation (PVR). We retrospectively compared S3V with Edwards Sapien XT valve (SXTV) with regard to postprocedural transvalvular pressure gradients (PGs). METHODS: Analysis of 152 patients receiving SXTV and 125 patients receiving S3V between February 2009 and April 2015 was performed. Transvalvular PGs and the incidence and extent of aortic regurgitation (AR) were compared postprocedurally by echocardiography for each valve size. RESULTS: Postprocedurally, mean PGs for the 23 mm valves were 10.9 ± 5.3 versus 13.9 ± 5.1 (p = 0.017), whereas maximum PGs were 19.9 ± 8.3 versus 26.1 ± 10.4 mm Hg (p = 0.005) in SXTV and S3V patients, respectively. For the 26 mm valves, gradients were also significantly higher in S3V patients (mean PG: 11.6 ± 4.9 vs. 9.2 ± 4.2 [p = 0.004]; maximum PG: 23.0 ± 10.1 vs. 17.2 ± 7.4 mm Hg [p < 0.001]). Analysis revealed no significant differences in postprocedural transvalvular PGs for 29 mm valves (mean PG of 9.3 ± 3.9 and 11.2 ± 4.3 mm Hg [p = ns] and maximum PG of 17.5 ± 7.2 vs. 20.9 ± 6.8 mm Hg [p = ns]) between SXTV and S3V groups, respectively. With respect to PVR, the incidence of AR was significantly lower in S3V group (p = 0.001). CONCLUSION: S3V shows lower incidence of PVR; however, it is associated with significantly higher postprocedural transvalvular PGs for 23 and 26 mm valve sizes. These data might contribute to the scientific discussion, especially with respect to prosthesis selection in individual patients with small annular dimension.

Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper extremity using BOLD imaging at 3T.

OBJECTIVE: Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known-e.g. drug toxicity, contrast agent exposure or ischemia during surgery-targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers. MATERIALS AND METHODS: In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups. RESULTS: Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group. CONCLUSION: RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care.

Thoracic-abdominal imaging with a novel dual-layer spectral detector CT: intra-individual comparison of image quality and radiation dose with 128-row single-energy acquisition.

BACKGROUND: A novel, multi-energy, dual-layer spectral detector computed tomography (SDCT) is commercially available now with the vendor's claim that it yields the same or better quality of polychromatic, conventional CT images like modern single-energy CT scanners without any radiation dose penalty. PURPOSE: To intra-individually compare the quality of conventional polychromatic CT images acquired with a dual-layer spectral detector (SDCT) and the latest generation 128-row single-energy-detector (CT128) from the same manufacturer. MATERIAL AND METHODS: Fifty patients underwent portal-venous phase, thoracic-abdominal CT scans with the SDCT and prior CT128 imaging. The SDCT scanning protocol was adapted to yield a similar estimated dose length product (DLP) as the CT128. Patient dose optimization by automatic tube current modulation and CT image reconstruction with a state-of-the-art iterative algorithm were identical on both scanners. CT image contrast-to-noise ratio (CNR) was compared between the SDCT and CT128 in different anatomic structures. Image quality and noise were assessed independently by two readers with 5-point-Likert-scales. Volume CT dose index (CTDIvol), and DLP were recorded and normalized to 68 cm acquisition length (DLP68). RESULTS: The SDCT yielded higher mean CNR values of 30.0% ± 2.0% (26.4-32.5%) in all anatomic structures ( P < 0.001) and excellent scores for qualitative parameters surpassing the CT128 (all P < 0.0001) with substantial inter-rater agreement (κ ≥ 0.801). Despite adapted scan protocols the SDCT yielded lower values for CTDIvol (-10.1 ± 12.8%), DLP (-13.1 ± 13.9%), and DLP68 (-15.3 ± 16.9%) than the CT128 (all P < 0.0001). CONCLUSION: The SDCT scanner yielded better CT image quality compared to the CT128 and lower radiation dose parameters.

Accuracy of 3D fluoroscopy-navigated anterior transpedicular screw insertion in the cervical spine: an experimental study.

PURPOSE: The technique of pedicle screw stabilization is finding increasing popularity for use in the cervical spine. Implementing anterior transpedicular screws (ATPS) in cervical spine offers theoretical advantages compared to posterior stabilization. The goal of the current study was the development of a new setting for navigated insertion of ATPS, combining the advantage of reduced invasiveness of an anterior approach with the technical advantages of navigation. METHODS: 20 screws were implanted in levels C3 to C6 of four cervical spine models (SAWBONES(®) Cervical Vertebrae with Anterior Ligament) with the use of 3D fluoroscopy navigation system [Arcadis Orbic 3D, Siemens and VectorVision fluoro 3D trauma software (BrainLAB)]. The accuracy of inserted screws was analyzed according to postoperative CT scans and following the modified Gertzbein and Robbins classification. RESULTS: 20 anterior pedicle screws were placed in four human cervical spine models. Of these, eight screws were placed in C3, two screws in C4, six screws in C5, and four screws in C6. 16 of 20 screws (80 %) reached a grade 1 level of accuracy according to the modified Gertzbein and Robbins Classification. Three screws (15 %) were grade 2, and one screw (5 %) was grade 3. Grade 4 and 5 positions were not evident. Summing grades 1 and 2 together as "good" positions, 95 % of the screws achieved this level. Only a single screw did not fulfill these criteria. CONCLUSION: The setting introduced in this study for navigated insertion of ATPS into cervical spine bone models is well implemented and shows excellent results, with an accuracy of 95 % (Gertzbein and Robbins grade 2 or better). Thus, this preliminary study represents a prelude to larger studies with larger case numbers on human specimens.

[Efficient patient preparation in computed tomography coronary angiography]. / Effiziente Patientenvorbereitung in der Computertomographie-Koronarangiographie.

BACKGROUND: In the coming years, a significant increase in the number of computed tomography coronary angiographies (CCTA) is expected, leading to an additional burden on existing structures. OBJECTIVES: Discussion of effective processes and patient preparation in the context of high-volume CCTA. MATERIALS AND METHODS: The relevance of patient education and optimized workflows in clinical practice, including pharmacological heart rate control and vasodilation. RESULTS: To conduct resource-efficient and effective patient examinations, comprehensive and clear patient education is crucial. This can be provided to the patient during scheduling or delivered digitally, so that the patient arrives with a thorough understanding of the examination process. In addition, targeted optimization of workflows tailored to CCTA is important. For high image quality, the administration of ß­blockers is necessary in most cases. This can be done intravenously to save time. The administration of nitrates immediately before the examination is recommended by current guidelines for all patients without contraindications and is ideally applied sublingually shortly before the examination. CONCLUSION: The anticipated increase in CCTA will significantly strain existing structures not only in terms of reporting. Especially standardized and structured workflows pre- and periprocedurally are essential for handling a high number of examinations, while maintaining sufficient image quality in clinical practice.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.