Phantoms for Quantitative Body MRI: a review and discussion of the phantom value.

In this paper, we review the value of phantoms for body MRI in the context of their uses for quantitative MRI methods research, clinical trials, and clinical imaging. Certain uses of phantoms are common throughout the body MRI community, including measuring bias, assessing reproducibility, and training. In addition to these uses, phantoms in body MRI methods research are used for novel methods development and the design of motion compensation and mitigation techniques. For clinical trials, phantoms are an essential part of quality management strategies, facilitating the conduct of ethically sound, reliable, and regulatorily compliant clinical research of both novel MRI methods and therapeutic agents. In the clinic, phantoms are used for development of protocols, mitigation of cost, quality control, and radiotherapy. We briefly review phantoms developed for quantitative body MRI, and finally, we review open questions regarding the most effective use of a phantom for body MRI.

Motion-robust, blood-suppressed, reduced-distortion diffusion MRI of the liver.

PURPOSE: To evaluate feasibility and reproducibility of liver diffusion-weighted (DW) MRI using cardiac-motion-robust, blood-suppressed, reduced-distortion techniques. METHODS: DW-MRI data were acquired at 3T in an anatomically accurate liver phantom including controlled pulsatile motion, in eight healthy volunteers and four patients with known or suspected liver metastases. Standard monopolar and motion-robust (M1-nulled, and M1-optimized) DW gradient waveforms were each acquired with single-shot echo-planar imaging (ssEPI) and multishot EPI (msEPI). In the motion phantom, apparent diffusion coefficient (ADC) was measured in the motion-affected volume. In healthy volunteers, ADC was measured in the left and right liver lobes separately to evaluate ADC reproducibility between the two lobes. Image distortions were quantified using the normalized cross-correlation coefficient, with an undistorted T2-weighted reference. RESULTS: In the motion phantom, ADC mean and SD in motion-affected volumes substantially increased with increasing motion for monopolar waveforms. ADC remained stable in the presence of increasing motion when using motion-robust waveforms. M1-optimized waveforms suppressed slow flow signal present with M1-nulled waveforms. In healthy volunteers, monopolar waveforms generated significantly different ADC measurements between left and right liver lobes ( p = 0 . 0078 $$ p=0.0078 $$ , reproducibility coefficients (RPC) =  470 × 1 0 - 6 $$ 470\times 1{0}^{-6} $$ mm 2 $$ {}^2 $$ /s for monopolar-msEPI), while M1-optimized waveforms showed more reproducible ADC values ( p = 0 . 29 $$ p=0.29 $$ , RPC = 220 × 1 0 - 6 $$ \mathrm{RPC}=220\times 1{0}^{-6} $$ mm 2 $$ {}^2 $$ /s for M1-optimized-msEPI). In phantom and healthy volunteer studies, motion-robust acquisitions with msEPI showed significantly reduced image distortion ( p < 0 . 001 $$ p<0.001 $$ ) compared to ssEPI. Patient scans showed reduction of wormhole artifacts when combining M1-optimized waveforms with msEPI. CONCLUSION: Synergistic effects of combined M1-optimized diffusion waveforms and msEPI acquisitions enable reproducible liver DWI with motion robustness, blood signal suppression, and reduced distortion.

Pulmonary MRA During Pregnancy: Early Experience With Ferumoxytol.

BACKGROUND: Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy. PURPOSE: To describe our clinical experience with Fe-MRA in pregnant women with suspected PE. STUDY TYPE: Retrospective, observational, cohort. POPULATION: A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women. FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T, 3D T1-weighted MRA. ASSESSMENT: After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings. STATISTICAL TESTS: Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers. RESULTS: The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia. CONCLUSION: Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Automated MR Image Prescription of the Liver Using Deep Learning: Development, Evaluation, and Prospective Implementation.

BACKGROUND: There is an unmet need for fully automated image prescription of the liver to enable efficient, reproducible MRI. PURPOSE: To develop and evaluate artificial intelligence (AI)-based liver image prescription. STUDY TYPE: Prospective. POPULATION: A total of 570 female/469 male patients (age: 56 ± 17 years) with 72%/8%/20% assigned randomly for training/validation/testing; two female/four male healthy volunteers (age: 31 ± 6 years). FIELD STRENGTH/SEQUENCE: 1.5 T, 3.0 T; spin echo, gradient echo, bSSFP. ASSESSMENT: A total of 1039 three-plane localizer acquisitions (26,929 slices) from consecutive clinical liver MRI examinations were retrieved retrospectively and annotated by six radiologists. The localizer images and manual annotations were used to train an object-detection convolutional neural network (YOLOv3) to detect multiple object classes (liver, torso, and arms) across localizer image orientations and to output corresponding 2D bounding boxes. Whole-liver image prescription in standard orientations was obtained based on these bounding boxes. 2D detection performance was evaluated on test datasets by calculating intersection over union (IoU) between manual and automated labeling. 3D prescription accuracy was calculated by measuring the boundary mismatch in each dimension and percentage of manual volume covered by AI prescription. The automated prescription was implemented on a 3 T MR system and evaluated prospectively on healthy volunteers. STATISTICAL TESTS: Paired t-tests (threshold = 0.05) were conducted to evaluate significance of performance difference between trained networks. RESULTS: In 208 testing datasets, the proposed method with full network had excellent agreement with manual annotations, with median IoU > 0.91 (interquartile range < 0.09) across all seven classes. The automated 3D prescription was accurate, with shifts <2.3 cm in superior/inferior dimension for 3D axial prescription for 99.5% of test datasets, comparable to radiologists' interreader reproducibility. The full network had significantly superior performance than the tiny network for 3D axial prescription in patients. Automated prescription performed well across single-shot fast spin-echo, gradient-echo, and balanced steady-state free-precession sequences in the prospective study. DATA CONCLUSION: AI-based automated liver image prescription demonstrated promising performance across the patients, pathologies, and field strengths studied. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Update on Gadolinium Based Contrast Agent Safety, From the AJR Special Series on Contrast Media.

Since its introduction 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. While extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include: acute allergic-like reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, while rare, serious reactions can occur. NSF is a rare, but serious, scleroderma-like condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) Group 1 GBCAs. Group 2 and 3 GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data demonstrate any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classification, and describes approaches for strengthening the evidence needed for regulatory decisions.

MRA as the Preferred Test for Pulmonary Embolism During the Iodinated Contrast Media Shortage of 2022: A Single-Center Experience.

BACKGROUND. Closure of a GE Healthcare facility in Shanghai, China, in 2022 disrupted the iodinated contrast media supply. Technologic advances have addressed limitations associated with the use of pulmonary MRA for diagnosis of pulmonary embolism (PE). OBJECTIVE. The purpose of this study was to describe a single institution's experience in the use of pulmonary MRA as an alternative to CTA for the diagnosis of PE in the general population during the iodinated contrast media shortage in 2022. METHODS. This retrospective single-center study included all CTA and MRA examinations performed to exclude PE from April 1 through July 31 (18 weekly periods) in 2019 (before the COVID-19 pandemic and contrast media shortage), 2021 (during the pandemic but before the shortage), and 2022 (during both the pandemic and the shortage). From early May through mid-July of 2022, MRA served as the preferred test for PE diagnosis, to preserve iodinated contrast media. CTA and MRA reports were reviewed. The total savings in iodinated contrast media volume resulting from preferred use of MRA was estimated. RESULTS. The study included 4491 examinations of 4006 patients (mean age, 57 ± 18 [SD] years; 1715 men, 2291 women): 1245 examinations (1111 CTA, 134 MRA) in 2019, 1547 examinations (1403 CTA, 144 MRA) in 2021, and 1699 examinations (1282 CTA, 417 MRA) in 2022. In 2022, the number of MRA examinations was four (nine when normalized to a 7-day period) in week 1, and this number increased to a maximum of 63 in week 10 and then decreased to 10 in week 18. During weeks 8-11, more MRA examinations (range, 45-63 examinations) than CTA examinations (range, 27-46 examinations) were performed. In 2022, seven patients with negative MRA underwent subsequent CTA within 2 weeks; CTA was negative in all cases. In 2022, 13.9% of CTA examinations (vs 10.3% of MRA examinations) were reported as having limited image quality. The estimated 4-month savings resulting from preferred use of MRA in 2022, under the assumption of uniform simple linear growth in CTA utilization annually and a CTA dose of 1 mL/kg, was 27 L of iohexol (350 mg I/mL). CONCLUSION. Preferred use of pulmonary MRA for PE diagnosis in the general population helped to conserve iodinated contrast media during the 2022 shortage. CLINICAL IMPACT. This single-center experience shows pulmonary MRA to be a practical substitute for pulmonary CTA in emergency settings.

Fully automated intracardiac 4D flow MRI post-processing using deep learning for biventricular segmentation.

OBJECTIVES: 4D flow MRI allows for a comprehensive assessment of intracardiac blood flow, useful for assessing cardiovascular diseases, but post-processing requires time-consuming ventricular segmentation throughout the cardiac cycle and is prone to subjective errors. Here, we evaluate the use of automatic left and right ventricular (LV and RV) segmentation based on deep learning (DL) network that operates on short-axis cine bSSFP images. METHODS: A previously published DL network was fine-tuned via retraining on a local database of 106 subjects scanned at our institution. In 26 test subjects, the ventricles were segmented automatically by the network and manually by 3 human observers on bSSFP MRI. The bSSFP images were then registered to the corresponding 4D flow images to apply the segmentation to 4D flow velocity data. Dice coefficients and the relative deviation between measurements (automatic vs. manual and interobserver manual) of various hemodynamic parameters were assessed. RESULTS: The automated segmentation resulted in similar Dice scores (LV: 0.92, RV: 0.86) and lower relative deviations from manual segmentation in left ventricular (LV) average kinetic energy (KE) (8%) and RV KE (15%) than the Dice scores (LV: 0.91, RV: 0.87) and relative deviations between manual segmentation observers (LV KE: 11%, p = 0.01; RV KE: 19%, p = 0.03). CONCLUSIONS: The automated post-processing method using deep learning resulted in hemodynamic measurements that differ from a manual observer's measurements equally or less than the variation between manual observers. This approach can be used to decrease post-processing time on intraventricular 4D flow data and mitigate interobserver variability. KEY POINTS: • Our proposed method allows for fully automated post-processing of intraventricular 4D flow MRI data. • Our method resulted in hemodynamic measurements that matched those derived from manual segmentation equally as well as interobserver variability. • Our method can be used to greatly accelerate intraventricular 4D flow post-processing and improve interobserver repeatability.

Improved free-breathing liver fat and iron quantification using a 2D chemical shift-encoded MRI with flip angle modulation and motion-corrected averaging.

OBJECTIVES: 3D chemical shift-encoded (CSE) MRI enables accurate and precise quantification of proton density fat fraction (PDFF) and R2*, biomarkers of hepatic fat and iron deposition. Unfortunately, 3D CSE-MRI requires reliable breath-holding. Free-breathing 2D CSE-MRI with sequential radiofrequency excitation is a motion-robust alternative but suffers from low signal-to-noise-ratio (SNR). To overcome this limitation, this work explores the combination of flip angle-modulated (FAM) 2D CSE imaging with a non-local means (NLM) motion-corrected averaging technique. METHODS: In this prospective study, 35 healthy subjects (27 children/8 adults) were imaged on a 3T MRI-system. Multi-echo 3D CSE ("3D") and 2D CSE FAM ("FAM") images were acquired during breath-hold and free-breathing, respectively, to obtain PDFF and R2* maps of the liver. Multi-repetition FAM was postprocessed with direct averaging (DA)- and NLM-based averaging and compared to 3D CSE using Bland-Altmann and regression analysis. Image qualities of PDFF and R2* maps were reviewed by two radiologists using a Likert-like scale (score 1-5, 5 = best). RESULTS: Compared to 3D CSE, multi-repetition FAM-NLM showed excellent agreement (regression slope = 1.0, R2 = 0.996) for PDFF and good agreement (regression slope 1.08-1.15, R2 ≥ 0.899) for R2*. Further, multi-repetition FAM-NLM PDFF and R2* maps had fewer artifacts (score 3.8 vs. 3.2, p < 0.0001 for PDFF; score 3.2 vs. 2.6, p < 0.001 for R2*) and better overall image quality (score 4.0 vs. 3.5, p < 0.0001 for PDFF; score 3.4 vs. 2.7, p < 0.0001 for R2*). CONCLUSIONS: Free-breathing FAM-NLM provides superior image quality of the liver compared to the conventional breath-hold 3D CSE-MRI, while minimizing bias for PDFF and R2* quantification. KEY POINTS: • 2D CSE FAM-NLM is a free-breathing method for liver fat and iron quantification and viable alternative for patients unable to hold their breath. • 2D CSE FAM-NLM is a feasible alternative to breath-hold 3D CSE methods, with low bias in proton density fat fraction (PDFF) and no clinically significant bias in R2*. • Quantitatively, multiple repetitions in 2D CSE FAM-NLM lead to improved SNR.

Quantification of Liver Fat Content with CT and MRI: State of the Art.

Hepatic steatosis is defined as pathologically elevated liver fat content and has many underlying causes. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an increasing prevalence among adults and children. Abnormal liver fat accumulation has serious consequences, including cirrhosis, liver failure, and hepatocellular carcinoma. In addition, hepatic steatosis is increasingly recognized as an independent risk factor for the metabolic syndrome, type 2 diabetes, and, most important, cardiovascular mortality. During the past 2 decades, noninvasive imaging-based methods for the evaluation of hepatic steatosis have been developed and disseminated. Chemical shift-encoded MRI is now established as the most accurate and precise method for liver fat quantification. CT is important for the detection and quantification of incidental steatosis and may play an increasingly prominent role in risk stratification, particularly with the emergence of CT-based screening and artificial intelligence. Quantitative imaging methods are increasingly used for diagnostic work-up and management of steatosis, including treatment monitoring. The purpose of this state-of-the-art review is to provide an overview of recent progress and current state of the art for liver fat quantification using CT and MRI, as well as important practical considerations related to clinical implementation.

Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

Characterization and correction of cardiovascular motion artifacts in diffusion-weighted imaging of the pancreas.

PURPOSE: To assess the effects of cardiovascular-induced motion on conventional DWI of the pancreas and to evaluate motion-robust DWI methods in a motion phantom and healthy volunteers. METHODS: 3T DWI was acquired using standard monopolar and motion-compensated gradient waveforms, including in an anatomically accurate pancreas phantom with controllable compressive motion and healthy volunteers (n = 8, 10). In volunteers, highly controlled single-slice DWI using breath-holding and cardiac gating and whole-pancreas respiratory-triggered DWI were acquired. For each acquisition, the ADC variability across volunteers, as well as ADC differences across parts of the pancreas were evaluated. RESULTS: In motion phantom scans, conventional DWI led to biased ADC, whereas motion-compensated waveforms produced consistent ADC. In the breath-held, cardiac-triggered study, conventional DWI led to heterogeneous DW signals and highly variable ADC across the pancreas, whereas motion-compensated DWI avoided these artifacts. In the respiratory-triggered study, conventional DWI produced heterogeneous ADC across the pancreas (head: 1756 ± 173 × 10-6 mm2 /s; body: 1530 ± 338 × 10-6 mm2 /s; tail: 1388 ± 267 × 10-6 mm2 /s), with ADCs in the head significantly higher than in the tail (P < .05). Motion-compensated ADC had lower variability across volunteers (head: 1277 ± 102 × 10-6 mm2 /s; body: 1204 ± 169 × 10-6 mm2 /s; tail: 1235 ± 178 × 10-6 mm2 /s), with no significant difference (P ≥ .19) across the pancreas. CONCLUSION: Cardiovascular motion introduces artifacts and ADC bias in pancreas DWI, which are addressed by motion-robust DWI.

Free-breathing liver fat and R2∗ quantification using motion-corrected averaging based on a nonlocal means algorithm.

PURPOSE: To propose a motion-robust chemical shift-encoded (CSE) method with high signal-to-noise (SNR) for accurate quantification of liver proton density fat fraction (PDFF) and R2∗ . METHODS: A free-breathing multi-repetition 2D CSE acquisition with motion-corrected averaging using nonlocal means (NLM) was proposed. PDFF and R2∗ quantified with 2D CSE-NLM were compared to two alternative 2D techniques: direct averaging and single acquisition (2D 1ave) in a digital phantom. Further, 2D NLM was compared in patients to 3D techniques (standard breath-hold, free-breathing and navigated), and the alternative 2D techniques. A reader study and quantitative analysis (Bland-Altman, correlation analysis, paired Student's t-test) were performed to evaluate the image quality and assess PDFF and R2∗ measurements in regions of interest. RESULTS: In simulations, 2D NLM resulted in lower standard deviations (STDs) of PDFF (2.7%) and R2∗ (8.2  s-1 ) compared to direct averaging (PDFF: 3.1%, R2∗ : 13.6  s-1 ) and 2D 1ave (PDFF: 8.7%, R2∗ : 33.2  s-1 ). In patients, 2D NLM resulted in fewer motion artifacts than 3D free-breathing and 3D navigated, less signal loss than 2D direct averaging, and higher SNR than 2D 1ave. Quantitatively, the STDs of PDFF and R2∗ of 2D NLM were comparable to those of 2D direct averaging (p>0.05). 2D NLM reduced bias, particularly in R2∗ (-5.73 to -0.36  s-1 ) that arises in direct averaging (-3.96 to 11.22  s-1 ) in the presence of motion. CONCLUSIONS: 2D CSE-NLM enables accurate mapping of PDFF and R2∗ in the liver during free-breathing.

No Cases of Nephrogenic Systemic Fibrosis after Administration of Gadoxetic Acid.

Background Gadoxetic acid (GA) has distinctive pharmacokinetic properties with important applications in hepatobiliary imaging. However, there are limited data evaluating the safety of GA administration in patients with impaired kidney function and the incidence of nephrogenic systemic fibrosis (NSF). Purpose To evaluate safety of GA regarding risk of NSF in patients with impaired kidney function. Materials and Methods This retrospective study identified all GA-enhanced MRI (hereafter, GA MRI) examinations performed between July 2008 and December 2019 through a search of the electronic medical record. Serum creatinine values within 180 days or less of each GA MRI examination were retrieved and estimated glomerular filtration rate (eGFR) was calculated. The eGFR value nearest to each MRI examination was used. A separate search in the electronic medical record was also performed to identify patients with NSF. Dermatologists, nephrologists, and nephrologists at our institution were surveyed for any cases of NSF. In patients with NSF, all MRI examinations performed and contrast agents administered to these patients were recorded. Results Overall, 7820 GA MRI examinations were identified, performed in 5351 patients (3022 women and 2329 men). These included 299 examinations (242 patients) with eGFR of 30-44 mL/min/1.73 m2 and 183 examinations (157 patients) with eGFR less than 30 mL/min/1.73 m2. There were 109 examinations (in 94 patients) with eGFR of 15-29 mL/min/1.73 m2, 40 examinations (in 39 patients) with eGFR less than 15 mL/min/1.73 m2, and 34 examinations in 27 patients undergoing hemodialysis. Seventeen patients with eGFR less than 30 mL/min/1.73 m2 or undergoing dialysis underwent GA MRI two or more times. Eighteen patients with biopsy-confirmed NSF were identified, none of whom were exposed to GA. The mean follow-up period for GA MRI examinations performed in patients with severe kidney impairment was 4.2 years (range, 0.2-11.3 years). Conclusion Gadoxetic acid may be safe with respect to nephrogenic systemic fibrosis in this patient population, although further studies are needed to confirm this. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Davenport and Shankar in this issue.

Nitric Oxide-Based Treatment of Poor-Grade Patients After Severe Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) require close treatment in neuro intensive care units (NICUs). The treatments available to counteract secondary deterioration and delayed ischemic events remain restricted; moreover, available neuro-monitoring of comatose patients is undependable. In comatose patients, clinical signs are hidden, and timing interventions to prevent the evolution of a perfusion disorder in response to fixed ischemic brain damage remain a challenge for NICU teams. Consequently, comatose patients often suffer secondary brain infarctions. The outcomes for long-term intubated patients w/wo pupil dilatation are the worst, with only 10% surviving. We previously added two nitroxide (NO) donors to the standard treatment: continuous intravenous administration of Molsidomine in patients with mild-to-moderate aSAH and, if required as a supplement, intraventricular boluses of sodium nitroprusside (SNP) in high-risk patients to overcome the so-called NO-sink effect, which leads to vasospasm and perfusion disorders. NO boluses were guided by clinical status and promptly reversed recurrent episodes of delayed ischemic neurological deficit. In this study, we tried to translate this concept, the initiation of intraventricular NO application on top of continuous Molsidomine infusion, from awake to comatose patients who lack neurological-clinical monitoring but are primarily monitored using frequently applied transcranial Doppler (TCD). METHODS: In this observational, retrospective, nonrandomized feasibility study, 18 consecutive aSAH comatose/intubated patients (Hunt and Hess IV/V with/without pupil dilatation) whose poor clinical status precluded clinical monitoring received standard neuro-intensive care, frequent TCD monitoring, continuous intravenous Molsidomine plus intraventricular SNP boluses after TCD-confirmed macrospasm during the daytime and on a fixed nighttime schedule. RESULTS: Very likely associated with the application of SNP, which is a matter of further investigation, vasospasm-related TCD findings promptly and reliably reversed or substantially weakened (p < 0.0001) afterward. Delayed cerebral ischemia (DCI) occurred only during loose, low-dose or interrupted treatment (17% vs. an estimated 65% with secondary infarctions) in 17 responders. However, despite their worse initial condition, 29.4% of the responders survived (expected 10%) and four achieved Glasgow Outcome Scale Extended (GOSE) 8-6, modified Rankin Scale (mRS) 0-1 or National Institutes of Health Stroke Scale (NIHSS) 0-2. CONCLUSIONS: Even in comatose/intubated patients, TCD-guided dual-compartment administration of NO donors probably could reverse macrospasm and seems to be feasible. The number of DCI was much lower than expected in this specific subgroup, indicating that this treatment possibly provides a positive impact on outcomes. A randomized trial should verify or falsify our results.

Feasibility of Submillisievert CT of the Skeletal Pelvis Using Iterative Reconstruction: A Human Cadaver Study.

OBJECTIVE. The purpose of this study is to investigate the feasibility of submillisievert CT of the skeletal pelvis of human cadavers using a standard-dose protocol and four different reduced-dose protocols reconstructed with filtered back projection (FBP) and iterative reconstruction (IR). MATERIALS AND METHODS. The pelvis of 25 human cadavers was repeatedly examined using different reduced-dose CT (RDCT) protocols with decreasing reference tube current-exposure time products (RDCT protocol 1, 80 mAs; RDCT protocol 2, 60 mAs; RDCT protocol 3, 40 mAs; and RDCT protocol 4, 10 mAs) and a tube voltage of 120 kV. A standard-dose CT (SDCT) protocol (reference tube current-exposure time product, 100 mAs; tube voltage, 120 kV) used for the same cadavers served as the reference. Raw data were reconstructed using FBP and two increasing levels of IR (IR levels 4 and 6). The image quality and diagnostic acceptability of images of the anterior pelvic ring, acetabulum, and posterior pelvic ring including the sacroiliac joints were evaluated on a 5-point scale. A mixed-effects model for repeated measures was performed. RESULTS. The image quality of all anatomic structures was rated as diagnostically acceptable for all protocols reconstructed with IR, except for 11 cadavers that were imaged using RDCT protocol 4. For reconstructions with FBP, image quality was generally rated lower and was diagnostically acceptable only for images obtained using SDCT and RDCT protocol 1 and 2. RDCT protocol 3 with IR was the RDCT protocol with the largest reduced dose still allowing diagnostically acceptable image quality for all anatomic structures in all cadavers. Compared with SDCT, the RDCT protocols resulted in significantly reduced mean (± SD) effective radiation doses (SDCT, 2.0 ± 0.7 mSv; RDCT protocol 1, 1.6 ± 0.6 mSv; RDCT protocol 2, 1.2 ± 0.4 mSv; RDCT protocol 3, 0.8 ± 0.3 mSv; and RDCT protocol 4, 0.3 ± 0.1 mSv; p = 0.001). CONCLUSION. Diagnostically acceptable submillisievert CT of the skeletal pelvis is feasible using IR. To adhere to the ALARA (as low as reasonably achievable) principle, submillisievert pelvic CT protocols combined with IR should be implemented as part of routine clinical practice.

Impact of Myocardial Fibrosis on Left Ventricular Function Evaluated by Feature-Tracking Myocardial Strain Cardiac Magnetic Resonance in Competitive Male Triathletes With Normal Ejection Fraction.

BACKGROUND: To analyze the effect of myocardial fibrosis on left ventricular (LV) function evaluated by feature-tracking strain analysis by cine cardiac magnetic resonance (CMR) in competitive male triathletes with normal ejection fraction (EF).Methods and Results:78 asymptomatic male triathletes with >10 weekly training hours (43±11 years) and 28 male age-matched controls were studied by late gadolinium enhancement (LGE) and cine CMR. Global and segmental radial, longitudinal and circumferential strains were analyzed using feature-tracking cine CMR. Focal non-ischemic LGE was observed in 15 of 78 triathletes (19%, LGE+) with predominance in the basal inferolateral segments. LVEF was normal in LGE+ (62±6%) and LGE- triathletes (62±5%, P=0.958). In contrast, global radial strain was lower in LGE+ triathletes at 40±7% compared with LGE- triathletes (45±7%, P<0.05). Reduced segmental radial strain occurred either in LGE+ segments or in directly adjacent segments. Strain analysis revealed regional differences in controls, with the highest radial and longitudinal strain in the inferolateral segments, which were typically affected by fibrosis in LGE+ triathletes. CONCLUSIONS: Reduced global and regional radial strain suggests a negative effect of myocardial fibrosis on LV function in LGE+ triathletes with normal EF. The observed regional differences in controls with the highest radial and longitudinal strain in the inferolateral segments may explain the typical occurrence of fibrosis in this myocardial region in triathletes.

Precision of liver and pancreas apparent diffusion coefficients using motion-compensated gradient waveforms in DWI.

BACKGROUND: Diffusion weighted imaging (DWI) with optimized motion-compensated gradient waveforms reduces signal dropouts in the liver and pancreas caused by cardiovascular-associated motion, however its precision is unknown. We hypothesized that DWI with motion-compensated DW gradient waveforms would improve apparent diffusion coefficient (ADC)-repeatability and inter-reader reproducibility compared to conventional DWI in these organs. METHODS: In this IRB-approved, prospective, single center study, subjects recruited between October 2019 and March 2020 were scanned twice on a 3 T scanner, with repositioning between test and retest. Each scan included two respiratory-triggered DWI series with comparable acquisition time: 1) conventional (monopolar) 2) motion- compensated diffusion gradients. Three readers measured ADC values. One-way ANOVA, Bland-Altman analysis were used for statistical analysis. RESULTS: Eight healthy participants (4 male/4 female), with a mean age of 29 ± 4 years, underwent the liver and pancreas MRI protocol. Four patients with liver metastases (2 male/2 female) with a mean age of 58 ± 5 years underwent the liver MRI protocol. In healthy participants, motion-compensated DWI outperformed conventional DWI with mean repeatability coefficient of 0.14 × 10-3 (CI:0.12-0.17) vs. 0.31 × 10-3 (CI:0.27-0.37) mm2/s for liver, and 0.11 × 10-3 (CI:0.08-0.15) vs. 0.34 × 10-3 (CI:0.27-0.49) mm2/s for pancreas; and with mean reproducibility coefficient of 0.20 × 10-3 (CI:0.18-0.23) vs. 0.51 × 10-3 (CI:0.46-0.58) mm2/s for liver, and 0.16 × 10-3 (CI:0.13-0.20) vs. 0.42 × 10-3 (CI:0.34-0.52) mm2/s for pancreas. In patients, improved repeatability was observed for motion-compensated DWI in comparison to conventional with repeatability coefficient of 0.51 × 10- 3 mm2/s (CI:0.35-0.89) vs. 0.70 × 10-3 mm2/s (CI:0.49-1.20). CONCLUSION: Motion-compensated DWI enhances the precision of ADC measurements in the liver and pancreas compared to conventional DWI.

Prognostic Relevance of Ischemic Late Gadolinium Enhancement in Apparently Healthy Endurance Athletes: A Follow-up Study Over 5 years.

BACKGROUND: In many cardiac diseases, myocardial scar tissue detected by late gadolinium enhancement (LGE) is a risk factor for cardiac arrhythmia and sudden cardiac death. Previous studies in athletes reported an increased risk for cardiac events in this group of ostensibly healthy subjects. However, the currently available longitudinal studies on this topic included fairly old marathon runners with a mean age of 57 ± 6 years or represent a case-control study in athletes with preexisting ventricular arrhythmia. The purpose of this prospective study was to analyze the prognostic relevance of LGE cardiac magnetic resonance (CMR) in middle-aged endurance athletes without known preexisting cardiac disorders. METHODS: Three-hundred and twelve apparently healthy athletes were prospectively enrolled. Inclusion criteria were a training for a minimum of 10 h per week and regularly participation in competitions. LGE CMR was obtained at baseline in all athletes and presence of LGE was classified visually according to established criteria as ischemic LGE, major or minor non-ischemic LGE or absent LGE. Follow-up consisted of a standardized questionnaire and an additional phone call in case of incomplete data. An event was defined as fatal myocardial infarction, ventricular tachycardia, ventricular fibrillation or sudden cardiac death (SCD). RESULTS: Complete follow-up was available for 293/312 athletes (94%) including 145 triathletes, 74 marathon runners and 74 cyclists after a median of 5.6 [quartiles 4,3, 6,4] years. Median age was 44 [35, 50] years at study enrollment. Spiroergometry did not reveal heart rhythm disturbances or significant ECG changes in the study population. LGE CMR revealed myocardial scar/focal fibrosis in 80 of 293 athletes (27%) including 7 athletes (2%) with ischemic subendocardial LGE of the left ventricle (LV), 16 athletes (6%) with major non-ischemic LGE of the LV and 57 athletes (19%) with minor non-ischemic LGE. During follow-up, two athletes experienced SCD. One marathon runner died during a training run and one cyclist died suddenly at rest. Both athletes had ischemic LGE of the LV. The event rate for SCD was 0.7% in the entire study population and 28% in the 7 athletes with ischemic LGE (p < 0.001 compared to athletes without LGE). CONCLUSIONS: Our findings indicate that athletes with ischemic LGE due to unrecognized myocardial infarction are at increased risk for SCD. Our findings highlight the value of LGE CMR to detect occult ischemic scar in asymptomatic apparently healthy athletes, which is of importance, since current guidelines do not recommend to incorporate routine cardiac imaging in pre-participation screening. Athletes with ischemic myocardial scar should at least consider to refrain from high-level exercise as an individual decision.