Measuring Dynamic CT Perfusion Based on Time-Resolved Quantitative DECT Iodine Maps: Comparison to Conventional Perfusion at 80 kVp for Pancreatic Carcinoma Objectives Using dual-energy computed tomography (DECT) for quantifying iodine content after injection of contrast agent could provide a quantitative basis for dynamic computed tomography (CT) perfusion measurements by means of established mathematical models of contrast agent kinetics, thus improving results by combining the strength of both techniques, which was investigated in this study. Materials and Methods A dynamic DECT acquisition over 51 seconds performed at 80/Sn140 kVp in 17 patients with pancreatic carcinoma was used to calculate iodine-enhancement images for each time point by means of 3-material decomposition. After motion correction, perfusion maps of blood flow were calculated using the maximum-slope model from both 80 kVp image data and iodine-enhancement images. Blood flow was measured in regions of interest placed in healthy pancreatic tissue and carcinoma for both of the derived perfusion maps. To assess image quality of input data, an adjusted contrast-to-noise ratio was calculated for 80 kVp images and iodine-enhancement images. Susceptibility of perfusion results to residual patient breathing motion during acquisition was investigated by measuring blood flow in fatty tissue surrounding the pancreas, where blood flow should be negligible compared with the pancreas. Results For both 80 kVp and iodine-enhancement images, blood flow was significantly higher in healthy tissue (114.2 ± 37.4 mL/100 mL/min or 115.1 ± 36.2 mL/100 mL/min, respectively) than in carcinoma (46.5 ± 26.6 mL/100 mL/min or 49.7 ± 24.7 mL/100 mL/min, respectively). Differences in blood flow between 80 kVp image data and iodine-enhancement images were statistically significant in healthy tissue, but not in carcinoma. For 80 kVp images, adjusted contrast-to-noise ratio was significantly higher (1.3 ± 1.1) than for iodine-enhancement images (1.1 ± 0.9). When evaluating fatty tissue surrounding the pancreas for estimating influence of patient motion, measured blood flow was significantly lower for iodine-enhancement images (30.7 ± 12.0 mL/100 mL/min) than for 80 kVp images (39.0 ± 19.1 mL/100 mL/min). Average patient radiation exposure was 8.01 mSv for dynamic DECT acquisition, compared with 4.60 mSv for dynamic 80 kVp acquisition. Discussion Iodine enhancement images can be used to calculate CT perfusion maps of blood flow, and compared with 80 kVp images, results showed only a small difference of 1 mL/100 mL/min in blood flow in healthy tissue, whereas patient radiation exposure was increased for dynamic DECT. Perfusion maps calculated based on iodine-enhancement images showed lower blood flow in fatty tissues surrounding the pancreas, indicating reduced susceptibility to residual patient breathing motion during the acquisition. Received for publication March 27, 2019; and accepted for publication, after revision, May 17, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Wolfram Stiller, PhD, Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. E-mail: wolfram.stiller@med.uni-heidelberg.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Improved Liver Diffusion-Weighted Imaging at 3 T Using Respiratory Triggering in Combination With Simultaneous Multislice Acceleration Objectives The aim of this study was to retrospectively compare optimized respiratory-triggered diffusion-weighted imaging with simultaneous multislice acceleration (SMS-RT-DWI) of the liver with a standard free-breathing echo-planar DWI (s-DWI) protocol at 3 T with respect to the imaging artifacts inherent to DWI. Materials and Methods Fifty-two patients who underwent a magnetic resonance imaging study of the liver were included in this retrospective study. Examinations were performed on a 3 T whole-body magnetic resonance system (MAGNETOM Skyra; Siemens Healthcare, Erlangen, Germany). In all patients, both s-DWI and SMS-RT-DWI of the liver were obtained. Images were qualitatively evaluated by 2 independent radiologists with regard to overall image quality, liver edge sharpness, sequence-related artifacts, and overall scan preference. For quantitative evaluation, signal-to-noise ratio was measured from signal-to-noise ratio maps. The mean apparent diffusion coefficient (ADC) was measured in each liver quadrant. The Wilcoxon rank-sum test was used for analysis of the qualitative parameters and the paired Student t test for quantitative parameters. Results Overall image quality, liver edge sharpness, and sequence-related artifacts of SMS-RT-DWI received significantly better ratings compared with s-DWI (P < 0.05 for all). For 90.4% of the examinations, both readers overall preferred SMS-RT-DWI to s-DWI. Acquisition time for SMS-RT-DWI was 34% faster than s-DWI. Signal-to-noise ratio values were significantly higher for s-DWI at b50 but did not statistically differ at b800, and they were more homogenous for SMS-RT-DWI, with a significantly lower standard deviation at b50. Mean ADC values decreased from the left to right hepatic lobe as well as from cranial to caudal for s-DWI. With SMS-RT-DWI, mean ADC values were homogeneous throughout the liver. Conclusions Optimized, multislice, respiratory-triggered DWI of the liver at 3 T substantially improves image quality with a reduced scan acquisition time compared with s-DWI. Received for publication April 15, 2019; and accepted for publication, after revision, May 22, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Andrej Tavakoli, MD, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. E-mail: s.tavakoli@gmx.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Three Tesla 3D High-Resolution Vessel Wall MRI of the Orbit may Differentiate Arteritic From Nonarteritic Anterior Ischemic Optic Neuropathy Background Anterior ischemic optic neuropathy (AION) is the most common cause of acute optic neuropathy in older patients. Distinguishing between arteritic AION (A-AION) and nonarteritic (NA-AION) is paramount for improved patient management. Purpose The aim of this study was to evaluate 3-dimensional high-resolution vessel wall (HR-VW) magnetic resonance imaging (MRI) at 3 T to discriminate A-AION from NA-AION. Materials and Methods This prospective single-center study was approved by a national research ethics board and included 27 patients (17 A-AION and 10 NA-AION) with 36 AIONs from December 2014 to August 2017 who underwent 3 T HR-VW MRI. Two radiologists blinded to clinical data individually analyzed the imaging separately and in random order. Discrepancies were resolved by consensus with a third neuroradiologist. The primary diagnostic criterion was the presence of inflammatory changes of the ophthalmic artery. Secondary diagnostic criteria included the presence of an enhancement of the optic nerve or its sheath, the optic disc, or inflammatory changes of posterior ciliary or extracranial arteries. A Fisher exact test was used to compare A-AION from NA-AION patients. Results Inflammatory changes of the ophthalmic artery were present in all patients with A-AION but in none of NA-AION (P < 0.0001). Its sensitivity, specificity, positive predictive value, and negative predictive value were 100%. Inflammatory changes of posterior ciliary arteries were significantly more likely in A-AOIN (82% vs 0%, P < 0.0001). Interreader and intrareader agreements were almost perfect (κ = 0.82–1). Conclusions High-resolution vessel wall MRI seems highly accurate when distinguishing A-AION from NA-AION and might be useful to improve patient management. Received for publication April 8, 2019; and accepted for publication, after revision, June 1, 2019. Conflicts of interest and sources of funding: none declared. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com). Correspondence to: Augustin Lecler, MD, PhD, Department of Neuroradiology, Foundation Adolphe de Rothschild Hospital, 29 Rue Manin, 75019 Paris, France. E-mail: alecler@for.paris. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ultrasound Time-Harmonic Elastography of the Aorta: Effect of Age and Hypertension on Aortic Stiffness Objectives The aim of this study was to investigate ultrasound time-harmonic elastography for quantifying aortic stiffness in vivo in the context of aging and arterial hypertension. Materials and Methods Seventy-four participants (50 healthy participants and 24 participants with long-standing hypertension) were prospectively included between January 2018 and October 2018, and underwent ultrasound time-harmonic elastography of the upper abdominal aorta. Compound maps of shear-wave speed (SWS) as a surrogate of tissue stiffness were generated from multifrequency wave fields covering the full field-of-view of B-mode ultrasound. Blood pressure and pulse wave velocity were measured beforehand. Interobserver and intraobserver agreement was determined in 30 subjects. Reproducibility of time-harmonic elastography was assessed in subgroups with repeated measurements after 20 minutes and after 6 months. Linear regression analysis, with subsequent age adjustment of SWS obtained, receiver operating characteristic analysis, and intraclass correlation coefficients (ICCs) were used for statistical evaluation. Results Linear regression analysis revealed a significant effect of age on SWS with an increase by 0.024 m/s per year (P < 0.001). Age-adjusted SWS was significantly greater in hypertensives (0.24 m/s; interquartile range [IQR], 0.17–0.40 m/s) than in healthy participants (0.07 m/s; IQR, −0.01 to 0.06 m/s; P < 0.001). A cutoff value of 0.15 m/s was found to differentiate best between groups (area under the receiver operating characteristic curve, 0.966; 95% confidence interval, 0.93–1.0; P < 0.001; 83% sensitivity and 98% specificity). Interobserver and intraobserver variability was excellent (ICC, 0.987 and 0.937, respectively). Reproducibility was excellent in the short term (ICC, 0.968; confidence interval, 0.878–0.992) and good in the long term (ICC, 0.844; confidence interval, 0.491–0.959). Conclusions Ultrasound time-harmonic elastography of the upper abdominal aorta allows quantification of aortic wall stiffness in vivo and shows significantly higher values in patients with arterial hypertension. Received for publication February 6, 2019; and accepted for publication, after revision, May 10, 2019. Conflicts of interest and sources of funding: This study was in part funded by a research grant from the German Research Foundation (Bonn, Germany) to Thomas Elgeti (grant number: EL606/2-1). The authors gratefully acknowledge support from the German Research Foundation (GRK2260 BIOQIC, SFB1340 Matrix-in-Vision). Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com). Correspondence to: Thomas Elgeti, MD, Department of Radiology, Charité–Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany. E-mail: thomas.elgeti@charite.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Free-Breathing Fast Low-Angle Shot Quiescent-Interval Slice-Selective Magnetic Resonance Angiography for Improved Detection of Vascular Stenoses in the Pelvis and Abdomen: Technical Development Objectives Balanced steady-state free precession-based quiescent-interval slice-selective (bSSFP QISS) magnetic resonance angiography (MRA) is accurate for the noncontrast evaluation of peripheral arterial disease (PAD); however, drawbacks include the need for breath-holding when imaging the abdomen and pelvis, and sensitivity to off-resonance artifacts. The purpose of this study was to evaluate the image quality and diagnostic accuracy in the pelvis and abdomen of free-breathing fast low-angle shot-based QISS (FLASH QISS) techniques in comparison to bSSFP QISS in patients with PAD, using computed tomographic angiography as the reference. Materials and Methods Twenty-seven patients (69 ± 10 years, 17 men) with PAD were enrolled in this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant prospective study between April and December 2018. Patients underwent noncontrast MRA using standard bSSFP QISS and prototype free-breathing radial-FLASH and Cartesian-FLASH QISS at 3 T. A subset of patients (n = 22) also underwent computed tomographic angiography as the reference standard. Nine arterial segments per patient were evaluated spanning the abdomen, pelvis, and upper thigh regions. Objective (signal intensity ratio and relative standard deviation) and subjective image quality (4-point scale) and stenosis (>50%) were evaluated by 2 readers and compared using one-way analysis of variance, Wilcoxon, and McNemar tests, respectively. Results A total of 179 vascular segments were available for analysis by all QISS techniques. No significant difference was observed among bSSFP, radial-FLASH, and Cartesian-FLASH QISS techniques in signal intensity ratio (P = 0.428) and relative standard deviation (P = 0.220). Radial-FLASH QISS demonstrated the best image quality (P < 0.0001) and the highest interreader agreement (κ = 0.721). The sensitivity values of bSSFP, radial-FLASH, and Cartesian-FLASH QISS for the detection of greater than 50% stenosis were 76.0%, 84.0%, and 80.0%, respectively, whereas specificity values were 97.6%, 94.0%, and 92.8%, respectively. Moreover, FLASH QISS consistently reduced off-resonance artifacts compared with bSSFP QISS. Conclusions Free-breathing FLASH QISS MRA techniques provide improved image quality and sensitivity, high specificity, and reduced off-resonance artifacts for vascular stenosis detection in the abdomen and pelvis. Received for publication April 19, 2019; and accepted for publication, after revision, May 19, 2019. Conflicts of interest and sources of funding: U. Joseph Schoepf is a consultant for and/or receives research support from Astellas, Bayer, Elucid Bioimaging, Guerbet, HeartFlow Inc, and Siemens Healthcare. Akos Varga-Szemes receives institutional research and travel support from Siemens Healthcare and is a consultant for Elucid Bioimaging. Robert R. Edelman receives grant support and royalties from Siemens Healthcare. Ioannis Koktzoglou receives research support from Siemens Healthcare. This study was supported by NIH NHLBI R01 HL130093 (R.R.E.). Correspondence to: Robert R. Edelman, MD, Department of Radiology, NorthShore University HealthSystem, Walgreen Bldg, G534, 2650 Ridge Ave, Evanston, IL 60201. E-mail: redelman999@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Back to the Future: Lipiodol in Lymphography—From Diagnostics to Theranostics Lipiodol is an iodinated poppy seed oil first synthesized in 1901. Originally developed for therapeutic purposes, it has mainly become a diagnostic contrast medium since the 1920s. At the end of the 20th century, Lipiodol underwent a transition back to a therapeutic agent, as exemplified by its increasing use in lymphangiography and lymphatic interventions. Nowadays, indications for lymphangiography include chylothorax, chylous ascites, chyluria, and peripheral lymphatic fistula or lymphoceles. In these indications, Lipiodol alone has a therapeutic effect with clinical success in 51% to 100% of cases. The 2 main access sites to the lymphatic system for lymphangiography are cannulation of lymphatic vessels in the foot (transpedal) and direct puncture of (mainly inguinal) lymph nodes (transnodal). In case of failure of lymphangiography alone to occlude the leaking lymphatic vessel as well as in indications such as protein-losing enteropathy, postoperative hepatic lymphorrhea, or plastic bronchitis, lymphatic vessels can also be embolized directly by injecting a mixture of Lipiodol and surgical glues (most commonly in thoracic duct embolization). The aim of this article is to review the historical role of Lipiodol and the evolution of its clinical application in lymphangiography over time until the current state-of-the-art lymphatic imaging techniques and interventions. Received for publication February 18, 2019; and accepted for publication, after revision, April 2, 2019. Conflicts of interest and sources of funding: C.C.P. is part of the speakers bureau of and/or received educational grants from Philips Healthcare, Bayer Vital, Boston Scientific, Guerbet, and Medserena; G.M. and C.M.S. are both part of the speakers bureau at Guerbet; M.I. is part of the speakers bureau at and received research grants from Guerbet. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com). Correspondence to: Claus Christian Pieper, MD, Department of Radiology, University Hospital Bonn, Sigmund-Freud Strasse 25, 53127 Bonn, Germany. E-mail: claus.christian.pieper@ukbonn.de; pieper.lymphatic@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Gadolinium Deposition in the Brain in a Large Animal Model: Comparison of Linear and Macrocyclic Gadolinium-Based Contrast Agents Objective Recent studies reported a signal intensity increase in the deep cerebellar nuclei (DCN) on magnetic resonance images caused by gadolinium deposition after the injection of gadolinium-based contrast agents (GBCAs). There is an ongoing debate if the propensity of a GBCA to deposit gadolinium is primarily determined by its class as either linear or macrocyclic. In the current study, we aimed to compare the amount and the distribution of retained gadolinium of linear and macrocyclic GBCAs in the DCN after a single injection at a dose comparable to a human patient's in a large animal model. Materials and Methods Eighteen sheep were randomly assigned in 6 groups of 3 animals, which received a single injection of 0.1 mmol/kg body weight of either the macrocyclic GBCAs gadobutrol, gadoteridol, or gadoterate meglumine; the linear GBCAs gadobenate dimeglumine or gadodiamide; or saline. Animals were euthanized 10 weeks after injection. Local distribution and concentration of gadolinium and colocalization to other metals (iron, zinc, copper) in the DCN was assessed by laser ablation-inductively coupled plasma-mass spectrometry. Results Average gadolinium concentration for the macrocyclic GBCAs and the saline group was below the limit of quantification (5.7 ng/g tissue). In contrast, 14 (for gadobenate) and 27 (for gadodiamide) times more gadolinium than the limit of quantification was found for the linear GBCAs gadobenate (mean, 83 ng/g) or gadodiamide (mean, 155 ng/g brain tissue). Gadolinium distribution colocalized with other metals for linear GBCAs and a specific accumulation in the DCN was found. Discussion The current study supports the hypothesis that the amount of gadolinium deposited in the brain is primarily determined by its class as either macrocyclic or linear. The accumulation of gadolinium in the DCN for linear GBCAs explains the hyperintensities in the DCN found in previous patient studies with linear GBCAs. Received for publication January 26, 2019; and accepted for publication, after revision, March 27, 2019. Alexander Radbruch and Henning Richter contributed equally to this study. The study was not supported by any funding. Alexander Radbruch lectures for Guerbet and Bayer, and he is also part of the Advisory Boards for GE, Bracco, and Guerbet. This study was supported by Bayer and Guerbet. For the remaining authors, no conflicts of interest are declared. Correspondence to: Alexander Radbruch, MD, JD, Department of Diagnostic and Interventional Radiology and Neuroradiology, University Clinic Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: a.radbruch@dkfz.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Computed Tomography Cholangiography Using the Magnetic Resonance Contrast Agent Gadoxetate Disodium: A Phantom Study Objective The purpose of this work is to determine whether low doses of gadoxetate disodium (Eovist; Bayer Healthcare LLC, Whippany, NJ), a gadolinium-based contrast agent used for magnetic resonance liver imaging, can be visualized for computed tomography (CT) cholangiography using a phantom setup. Materials and Methods Vials containing 4 concentrations of gadoxetate disodium (1.9, 3.4, 4.8, and 9.6 mg Gd/mL) were placed in a 35 × 26-cm2 water phantom and imaged on 2 CT scanners: Siemens Somatom Flash and Force (Siemens Healthcare, Erlangen, Germany). These concentrations correspond to the estimated concentration in the bile duct for a 40-, 70-, or 100-kg patient, and twice the concentration of a 100-kg patient, respectively. Single-energy (SE) scans were acquired at 70, 80, 90, 100, 120, and 140 kVp, and dual-energy scans were acquired at 90/150Sn (Force) and 100/150 (Flash) for 2 dose levels (CTDIvol 13 and 23 mGy). Virtual monoenergetic images at 50 keV were created (Mono+; Siemens Healthcare, Erlangen, Germany). The mean intensity and standard deviation for each concentration of gadoxetate disodium and the water background were extracted from each image set and used to compute the contrast and contrast-to-noise ratio (CNR). To determine whether the signal provided by gadoxetate disodium was clinically sufficient, the measures were compared with those acquired from 12 clinical CT cholangiography examinations performed with iodine-containing iodipamide meglumine. Results From the retrospective clinical cohort, mean contrast (± standard deviation) of 239 ± 107 HU and CNR of 12.8 ± 4.2 were found in the bile duct relative to the liver. Comparing these metrics to the gadoxetate disodium samples, the highest concentration (9.6 mg Gd/mL) surpassed these thresholds at all energy levels. The 4.8 mg Gd/mL had sufficient CNR in the Force, but not in the Flash. The 3.4 mg Gd/mL had clinically relevant CNR at low kV of SE (<100 kVp) and 50 keV of dual energy in the Force but was insufficient in the Flash. Images acquired by the Force had a lower noise level and greater CNR compared with the Flash. Similar trends were seen at both dose levels. Conclusions Gadoxetate disodium shows promise as a viable contrast agent for CT cholangiography, with CNR similar to those seen clinically with an iodine-based contrast agent. Dual-energy CT or low kV SE-CT is helpful to enhance the signal. Received for publication February 14, 2019; and accepted for publication, after revision, April 9, 2019. Selected sections presented during oral presentation at the RSNA Annual Meeting in November 2018. Conflicts of interest and sources of funding: Drs McCollough and Fletcher receive grant support given to our institution from Siemens Healthineers, the manufacturer for the computed tomography scanners used in this study. For the remaining authors, none were declared. No funding was provided for this work. Correspondence to: Lifeng Yu, PhD, Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: yu.lifeng@mayo.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Can Virtual Contrast Enhancement in Brain MRI Replace Gadolinium?: A Feasibility Study Objectives Gadolinium-based contrast agents (GBCAs) have become an integral part in daily clinical decision making in the last 3 decades. However, there is a broad consensus that GBCAs should be exclusively used if no contrast-free magnetic resonance imaging (MRI) technique is available to reduce the amount of applied GBCAs in patients. In the current study, we investigate the possibility of predicting contrast enhancement from noncontrast multiparametric brain MRI scans using a deep-learning (DL) architecture. Materials and Methods A Bayesian DL architecture for the prediction of virtual contrast enhancement was developed using 10-channel multiparametric MRI data acquired before GBCA application. The model was quantitatively and qualitatively evaluated on 116 data sets from glioma patients and healthy subjects by comparing the virtual contrast enhancement maps to the ground truth contrast-enhanced T1-weighted imaging. Subjects were split in 3 different groups: enhancing tumors (n = 47), nonenhancing tumors (n = 39), and patients without pathologic changes (n = 30). The tumor regions were segmented for a detailed analysis of subregions. The influence of the different MRI sequences was determined. Results Quantitative results of the virtual contrast enhancement yielded a sensitivity of 91.8% and a specificity of 91.2%. T2-weighted imaging, followed by diffusion-weighted imaging, was the most influential sequence for the prediction of virtual contrast enhancement. Analysis of the whole brain showed a mean area under the curve of 0.969 ± 0.019, a peak signal-to-noise ratio of 22.967 ± 1.162 dB, and a structural similarity index of 0.872 ± 0.031. Enhancing and nonenhancing tumor subregions performed worse (except for the peak signal-to-noise ratio of the nonenhancing tumors). The qualitative evaluation by 2 raters using a 4-point Likert scale showed good to excellent (3–4) results for 91.5% of the enhancing and 92.3% of the nonenhancing gliomas. However, despite the good scores and ratings, there were visual deviations between the virtual contrast maps and the ground truth, including a more blurry, less nodular-like ring enhancement, few low-contrast false-positive enhancements of nonenhancing gliomas, and a tendency to omit smaller vessels. These “features” were also exploited by 2 trained radiologists when performing a Turing test, allowing them to discriminate between real and virtual contrast-enhanced images in 80% and 90% of the cases, respectively. Conclusions The introduced model for virtual gadolinium enhancement demonstrates a very good quantitative and qualitative performance. Future systematic studies in larger patient collectives with varying neurological disorders need to evaluate if the introduced virtual contrast enhancement might reduce GBCA exposure in clinical practice. Received for publication March 9, 2019; and accepted for publication, after revision, April 15, 2019. The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com). Correspondence to: Jens Kleesiek, PhD, MD, Division of Radiology, German Cancer Research Center, Im Neuenheimer Feld 223, 69120 Heidelberg, Germany. E-mail: j.kleesiek@dkfz.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Real-Time Magnetic Resonance Imaging: Radial Gradient-Echo Sequences With Nonlinear Inverse Reconstruction Objective The aim of this study is to evaluate a real-time magnetic resonance imaging (MRI) method that not only promises high spatiotemporal resolution but also practical robustness in a wide range of scientific and clinical applications. Materials and Methods The proposed method relies on highly undersampled gradient-echo sequences with radial encoding schemes. The serial image reconstruction process solves the true mathematical task that emerges as a nonlinear inverse problem with the complex image and all coil sensitivity maps as unknowns. Extensions to model-based reconstructions for quantitative parametric mapping further increase the number of unknowns, for example, by adding parameters for phase-contrast flow or T1 relaxation. In all cases, an iterative numerical solution that minimizes a respective cost function is achieved with use of the iteratively regularized Gauss-Newton method. Convergence is supported by regularization, for example, to the preceding frame, whereas temporal fidelity is ensured by downsizing the regularization strength in comparison to the data consistency term in each iterative step. Practical implementations of highly parallelized algorithms are realized on a computer with multiple graphical processing units. It is “invisibly” integrated into a commercial 3-T MRI system to allow for conventional usage and to provide online reconstruction, display, and storage of regular DICOM image series. Results Depending on the application, the proposed method offers serial imaging, that is, the recording of MRI movies, with variable spatial resolution and up to 100 frames per second (fps)—corresponding to 10 milliseconds image acquisition times. For example, movements of the temporomandibular joint during opening and closing of the mouth are visualized with use of simultaneous dual-slice movies of both joints at 2 × 10 fps (50 milliseconds per frame). Cardiac function may be studied at 30 to 50 fps (33.3 to 20 milliseconds), whereas articulation processes typically require 50 fps (20 milliseconds) or orthogonal dual-slice acquisitions at 2 × 25 fps (20 milliseconds). Methodological extensions to model-based reconstructions achieve improved quantitative mapping of flow velocities and T1 relaxation times in a variety of clinical scenarios. Conclusions Real-time gradient-echo MRI with extreme radial undersampling and nonlinear inverse reconstruction allows for direct monitoring of arbitrary physiological processes and body functions. In many cases, pertinent applications offer hitherto impossible clinical studies (eg, of high-resolution swallowing dynamics) or bear the potential to replace existing MRI procedures (eg, electrocardiogram-gated cardiac examinations). As a consequence, many novel opportunities will require a change of paradigm in MRI-based radiology. At this stage, extended clinical trials are needed. Received for publication March 25, 2019; and accepted for publication, after revision, April 25, 2019. Conflicts of interest and sources of funding: The authors hold a patent and software knowhow about the real-time magnetic resonance imaging technique used here. M.U. gratefully acknowledges financial support by the German Centre for Cardiovascular Research. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com). Correspondence to: Jens Frahm, PhD, Biomedizinische NMR, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, 37070 Göttingen, Germany. E-mail: jfrahm@gwdg.de. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.