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Microvascular invasion (MVI) is an important risk factor in hepatocellular carcinoma (HCC), but its diagnosis mandates postoperative histopathologic analysis. We aimed to develop and externally validate a predictive scoring system for MVI.From July 2015 to November 2020, consecutive patients underwent surgery for HCC with preoperative gadoxetate disodium (EOB)-enhanced MRI was retrospectively enrolled. All MR images were reviewed independently by two radiologists who were blinded to the outcomes. In the training centre, a radio-clinical MVI score was developed via logistic regression analysis against pathology. In the testing centre, areas under the receiver operating curve (AUCs) of the MVI score and other previous MVI schemes were compared. Overall survival (OS) and recurrence-free survival (RFS) were analysed by the Kaplan-Meier method with the log-rank test.A total of 417 patients were included, 195 (47%) with pathologically-confirmed MVI. The MVI score included: non-smooth tumour margin (odds ratio [OR] = 4.4), marked diffusion restriction (OR = 3.0), internal artery (OR = 3.0), hepatobiliary phase peritumoral hypointensity (OR = 2.5), tumour multifocality (OR = 1.6), and serum alpha-fetoprotein400 ng/mL (OR = 2.5). AUCs for the MVI score were 0.879 (training) and 0.800 (testing), significantly higher than those for other MVI schemes (testing AUCs: 0.648-0.684). Patients with model-predicted MVI had significantly shorter OS (median 61.0 months vs not reached, P .001) and RFS (median 13.0 months vs. 42.0 months, P .001) than those without.A preoperative MVI score integrating five EOB-MRI features and serum alpha-fetoprotein level could accurately predict MVI and postoperative survival in HCC. Therefore, this score may aid in individualized treatment decision making.

The Liver Imaging Reporting and Data System (LI-RADS) is widely used for diagnosing hepatocellular carcinoma (HCC), however, with unsatisfactory sensitivity, complex ancillary features, and inadequate integration with gadoxetate disodium (EOB)-enhanced MRI.To modify LI-RADS (mLI-RADS) on EOB-MRI.Secondary analysis of a prospective observational study.Between July 2015 and September 2018, 224 consecutive high-risk patients (median age, 51 years; range, 26-83; 180 men; training/testing sets: 169/55 patients) with 742 (median size, 13 mm; interquartile range, 7-27; 498 HCCs) LR-3/4/5 observations.3.0 T TThree radiologists (with 5, 5, and 10 years of experience in liver MR imaging, respectively) blinded to the reference standard (histopathology or imaging follow-up) reviewed all MR images independently. In the training set, the optimal LI-RADS version 2018 (v2018) features selected by Random Forest analysis were used to develop mLI-RADS via decision tree analysis.In an independent testing set, diagnostic performances of mLI-RADS, LI-RADS v2018, and the Korean Liver Cancer Association (KLCA) guidelines were computed using a generalized estimating equation model and compared with McNemar's test. A two-tailed P 0.05 was statistically significant.Five features (nonperipheral "washout," restricted diffusion, nonrim arterial phase hyperenhancement [APHE], mild-moderate T2 hyperintensity, and transitional phase hypointensity) constituted mLI-RADS, and mLR-5 was nonperipheral washout coupled with either nonrim APHE or restricted diffusion. In the testing set, mLI-RADS was significantly more sensitive (72%) and accurate (80%) than LI-RADS v2018 (sensitivity, 61%; accuracy 74%; both P 0.001) and the KLCA guidelines (sensitivity, 64%; accuracy 74%; both P 0.001), without sacrificing positive predictive value (mLI-RADS, 94%; LI-RADS v2018, 94%; KLCA guidelines, 92%).In high-risk patients, the EOB-MRI-based mLI-RADS was simpler and more sensitive for HCC than LI-RADS v2018 while maintaining high positive predictive value.2 TECHNICAL EFFICACY: Stage 2.

BACKGROUND The Liver Imaging Reporting and Data System (LI-RADS) is widely accepted as a reliable diagnostic scheme for hepatocellular carcinoma (HCC) in at-risk patients. However, its application is hampered by substantial complexity and suboptimal diagnostic sensitivity. PURPOSE To propose data-driven modifications to the LI-RADS version 2018 (v2018) major feature system (rLI-RADS) on gadoxetate disodium (EOB)-enhanced magnetic resonance imaging (MRI) to improve sensitivity and simplicity while maintaining high positive predictive value (PPV) for detecting HCC. STUDY TYPE Retrospective. POPULATION Two hundred and twenty-four consecutive at-risk patients (training dataset: 169, independent testing dataset: 55) with 742 LR-3 to LR-5 liver observations (HCC: N = 498 [67%]) were analyzed from a prospective observational registry collected between July 2015 and September 2018. FIELD STRENGTH/SEQUENCE 3.0 T/T2-weighted fast spin-echo, diffusion-weighted spin-echo based echo-planar and three-dimensional (3D) T1-weighted gradient echo sequences. ASSESSMENT All images were evaluated by three independent abdominal radiologists who were blinded to all clinical, pathological, and follow-up information. Composite reference standards of either histopathology or imaging follow-up were used. STATISTICAL TESTS In the training dataset, LI-RADS v2018 major features were used to develop rLI-RADS based on their associated PPV for HCC. In an independent testing set, diagnostic performances of LI-RADS v2018 and rLI-RADS were computed using a generalized estimating equation model and compared with McNemar's test. A P value

Purpose Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. Theory and methods A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. Results Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. Conclusion Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Purpose To characterize the magnetic susceptibility changes of liver fibrosis using susceptibility tensor imaging. Methods Liver biopsy tissue samples of patients with liver fibrosis were obtained. Three-dimensional gradient-echo and diffusion-weighted images were acquired at 9.4 T. Susceptibility tensors of the samples were calculated using the gradient-echo phase signal acquired at 12 different orientations relative to the B0 field. Susceptibility anisotropy of the liver collagen fibers was quantified and compared with diffusion anisotropy, measured by DTI. For validation, a comparison was made to histology including hematoxylin and eosin staining, iron staining, and Masson's trichrome staining. Results Areas with strong diamagnetic susceptibility were observed in the tissue samples forming fibrous patterns. This diamagnetic susceptibility was highly anisotropic. Both the mean magnetic susceptibility and susceptibility anisotropy of collagen fibers exhibited a strong contrast against the surrounding nonfibrotic tissues. The same regions also showed an elevated diffusion anisotropy but with much lower tissue contrast. Masson's trichrome staining identified concentrated collagens in the fibrous regions with high susceptibility anisotropy, and a linear correlation was found between the susceptibility anisotropy and the histology-based staging. Conclusion Diamagnetic susceptibility indicates the presence of collagen in the fibrotic liver tissues. Mapping magnetic susceptibility anisotropy may serve as a potential marker to quantify collagen fiber changes in patients with liver fibrosis.

The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging, created specifically for patients at risk for hepatocellular carcinoma. Over the past years, LI-RADS has been progressively implemented into clinical practice, but pitfalls remain related to user error and inherent limitations of the system. User pitfalls include the inappropriate application of LI-RADS to a low-risk patient population, incorrect measurement techniques, inaccurate assumptions about LI-RADS requirements, and improper usage of LI-RADS terminology and categories. System pitfalls include areas of discordance with the Organ Procurement and Transplantation Network (OPTN) as well as pitfalls related to rare ancillary features. This article reviews common user pitfalls in applying LI-RADS v2018 and how to avoid preventable errors and also highlights deficiencies of the current version of LI-RADS and how it might be improved in the future. Level of Evidence:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2019;50:1673-1686.

Deep learning is a branch of artificial intelligence where networks of simple interconnected units are used to extract patterns from data in order to solve complex problems. Deep-learning algorithms have shown groundbreaking performance in a variety of sophisticated tasks, especially those related to images. They have often matched or exceeded human performance. Since the medical field of radiology mainly relies on extracting useful information from images, it is a very natural application area for deep learning, and research in this area has rapidly grown in recent years. In this article, we discuss the general context of radiology and opportunities for application of deep-learning algorithms. We also introduce basic concepts of deep learning, including convolutional neural networks. Then, we present a survey of the research in deep learning applied to radiology. We organize the studies by the types of specific tasks that they attempt to solve and review a broad range of deep-learning algorithms being utilized. Finally, we briefly discuss opportunities and challenges for incorporating deep learning in the radiology practice of the future. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:939-954.

PURPOSE To develop a bipolar multi-echo MRI method for the accurate estimation of the adipose tissue fatty acid composition (FAC) using clinically relevant protocols at clinical field strength. METHODS The proposed technique jointly estimates confounding factors (field map, R2* , eddy-current phase) and triglyceride saturation state parameters by fitting multi-echo gradient echo acquisitions to a complex signal model. The noise propagation behavior was improved by applying a low-rank enforcing denoising technique and by addressing eddy-current-induced phase discrepancies analytically. The impact of the total echo train duration on the FAC parameter map accuracy was analyzed in an oil phantom at 3T. Accuracy and reproducibility assessment was based on in vitro oil phantom measurements at two field strengths (3T and 1.5T) and with two different protocols. Repeatability was assessed in vivo in patients (n = 8) with suspected fatty liver disease using test-retest acquisitions in the abdominal subcutaneous, perirenal and mesenteric fat depots. RESULTS Echo train readout durations of at least five times the conventional in-phase time were required for accurate FAC estimation in areas of high fat content. In vitro, linear regression and Bland-Altman analyses demonstrated strong (r > 0.94) and significant (P ≪ 0.01) correlations between measured and reference FACs for all acquisitions, with smaller overall intercepts and biases at 3T compared to 1.5T. In vivo, reported mean absolute differences between test and retest were 1.54%, 3.31%, and 2.63% for the saturated, mono-unsaturated, and poly-unsaturated fat component, respectively. CONCLUSIONS Accurate and reproducible MRI-based FAC quantification within a breath-hold is possible at clinical field strengths.

Author(s): Bashir, Mustafa R; Wolfson, Tanya; Gamst, Anthony C; Fowler, Kathryn J; Ohliger, Michael; Shah, Shetal N; Alazraki, Adina; Trout, Andrew T; Behling, Cynthia; Allende, Daniela S; Loomba, Rohit; Sanyal, Arun; Schwimmer, Jeffrey; Lavine, Joel E; Shen, Wei; Tonascia, James; Van Natta, Mark L; Mamidipalli, Adrija; Hooker, Jonathan; Kowdley, Kris V; Middleton, Michael S; Sirlin, Claude B; NASH Clinical Research Network (NASH CRN) | Abstract: BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P l 0.0001) and at 3T (r = 0.586, P l 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength.Data conclusionHepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only.Level of evidence4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456-1466.

Author(s): Kielar, Ania Z; Chernyak, Victoria; Bashir, Mustafa R; Do, Richard K; Fowler, Kathryn J; Mitchell, Donald G; Cerny, Milena; Elsayes, Khaled M; Santillan, Cynthia; Kamaya, Aya; Kono, Yuko; Sirlin, Claude B; Tang, An | Abstract: The computed tomography / magnetic resonance imaging (CT/MRI) Liver Imaging Reporting a Data System (LI-RADS) is a standardized system for diagnostic imaging terminology, technique, interpretation, and reporting in patients with or at risk for developing hepatocellular carcinoma (HCC). Using diagnostic algorithms and tables, the system assigns to liver observations category codes reflecting the relative probability of HCC or other malignancies. This review article provides an overview of the 2017 version of CT/MRI LI-RADS with a focus on MRI. The main LI-RADS categories and their application will be described. Changes and updates introduced in this version of LI-RADS will be highlighted, including modifications to the diagnostic algorithm and to the optional application of ancillary features. Comparisons to other major diagnostic systems for HCC will be made, emphasizing key similarities, differences, strengths, and limitations. In addition, this review presents the new Treatment Response algorithm, while introducing the concepts of MRI nonviability and viability. Finally, planned future directions for LI-RADS will be outlined.Level of evidence5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:1459-1474.

Purpose To determine which of three gadoxetic acid injection techniques best reduced the contrast-related arterial-phase motion artifacts. Materials and Methods This Institutional Review Board (IRB)-approved, retrospective study included a cohort of 78 consecutive patients who each had serial gadoxetic acid-enhanced 3.0T magnetic resonance imaging (MRI) of the liver (0.025 mmol/kg body weight) performed with at least two of three injection techniques: M1 test bolus, undiluted, power-injected 1 mL/s; M2 test bolus, diluted 50% with saline, power-injected 1 mL/s; M3 fixed delay, undiluted, manually injected. Blinded to the injection method, three readers independently rated the randomized images for arterial-phase motion artifacts, arterial-phase timing, and arterial-phase lesion visibility using a four-point Likert scale. Results Regarding respiratory artifacts, gadoxetic acid arterial-phase images were judged better with M3 (2.7 ± 0.7) and were significantly less than those with M1 (2.1 ± 1.1) (P = 0.0001). Arterial-phase M2 (2.50 ± 0.89) images were rated significantly better than arterial-phase M1 images (P = 0.012), but the difference between arterial-phase images with M3 and M2 scores was not statistically significant (P = 0.49). Arterial-phase timing was significantly better for M1 compared to M3, and for M2 compared to M3 (P < 0.0001 for both). The area under the curve was 0.59–0.68. However, there was no significant difference between M1 and M2 (P = 0.35). With regard to arterial-phase lesion visibility, there was no significant difference in the ratings between any of the three injection techniques (P = 0.29–0.72). Interreader agreement was moderate to substantial (κ = 0.41–0.62). Conclusion A diluted, power-injected protocol (M2) seems to provide good timing and minimize artifacts compared with two other injection methods. No significant difference was found in lesion visibility between these three methods. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1107–1114.

Purpose Diffusion-weighted Magnetic Resonance Imaging (DWI) has been shown to be a powerful tool for cancer detection with high tumor-to-tissue contrast. This study aims to investigate the feasibility of developing a four-dimensional DWI technique (4D-DWI) for imaging respiratory motion for radiation therapy applications. Materials/methods Image acquisition was performed by repeatedly imaging a volume of interest (VOI) using an interleaved multislice single-shot echo-planar imaging (EPI) 2D-DWI sequence in the axial plane. Each 2D-DWI image was acquired with an intermediately low b-value (b = 500 s/mm2 ) and with diffusion-encoding gradients in x, y, and z diffusion directions. Respiratory motion was simultaneously recorded using a respiratory bellow, and the synchronized respiratory signal was used to retrospectively sort the 2D images to generate 4D-DWI. Cine MRI using steady-state free precession was also acquired as a motion reference. As a preliminary feasibility study, this technique was implemented on a 4D digital human phantom (XCAT) with a simulated pancreas tumor. The respiratory motion of the phantom was controlled by regular sinusoidal motion profile. 4D-DWI tumor motion trajectories were extracted and compared with the input breathing curve. The mean absolute amplitude differences (D) were calculated in superior-inferior (SI) direction and anterior-posterior (AP) direction. The technique was then evaluated on two healthy volunteers. Finally, the effects of 4D-DWI on apparent diffusion coefficient (ADC) measurements were investigated for hypothetical heterogeneous tumors via simulations. Results Tumor trajectories extracted from XCAT 4D-DWI were consistent with the input signal: the average D value was 1.9 mm (SI) and 0.4 mm (AP). The average D value was 2.6 mm (SI) and 1.7 mm (AP) for the two healthy volunteers. Conclusion A 4D-DWI technique has been developed and evaluated on digital phantom and human subjects. 4D-DWI can lead to more accurate respiratory motion measurement. This has a great potential to improve the visualization and delineation of cancer tumors for radiotherapy.

Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging (MRI) since the 1980s and are now administered in up to 35% of all MRI examinations. While GBCAs were initially felt to carry minimal risk, the subsequent identification of GBCAs as the key etiologic factor in the development of nephrogenic systemic fibrosis (NSF) has raised concerns about the broader health impacts of gadolinium exposure. Clinicians, radiologists, and patients should be aware of the most up-to-date data pertaining to the risks of GBCA administration. Specific issues covered in this review article include immediate adverse reactions; pregnancy and lactation; and gadolinium deposition and toxicity, with a special focus on NSF. Practice recommendations based on the presented data, as well as current professional society guidelines, are provided for each section. Level of Evidence: 1 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2017;46:338–353

Purpose To identify demographic and imaging features in magnetic resonance imaging (MRI) that are associated with upgrade of Liver Imaging Reporting and Data System (LI-RADS) category 4 (LR-4) observations to category 5 (LR-5), and to assess their effects on risk of upgrade and time to upgrade. Materials and Methods Institutional Review Board approval was obtained for this retrospective, dual-institution Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Radiologists reviewed 1.5T and 3T MRI examinations for 181 LR-4 observations in 139 patients, as well as follow-up computed tomography (CT) and MRI examinations and treatment. A stepwise multivariate Cox proportional hazards model analysis was performed to identify predictive risk factors for upgrade to LR-5, including patient demographics and LI-RADS imaging features. Overall cumulative risk of upgrade was calculated by using the Kaplan–Meier method. The cumulative risks were compared in the presence/absence of significant predictive risk factors using the log-rank test. Results The independent significant predictive risk factors in the 56 LR-4 observations that upgraded to LR-5 were mild–moderate T2 hyperintensity (P

MRI has emerged as the most comprehensive noninvasive diagnostic tool for focal liver lesions and diffuse hepatobiliary disorders. The introduction of hepatobiliary contrast agents, most notably gadoxetic acid (GA), has expanded the role of MRI, particularly in the functional imaging of chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD). GA-enhanced MRI (GA-MRI) may help to distinguish between the two subgroups of NAFLD, simple steatosis and nonalcoholic steatohepatitis. Furthermore, GA-MRI can be used to stage fibrosis and cirrhosis, predict liver transplant graft survival, and preoperatively estimate the risk of liver failure should major resection be undertaken. The amount of GA uptake can be estimated, using static images, by the relative liver enhancement, hepatic uptake index, and relaxometry of T1-mapping during the hepatobiliary phase. On the contrary, the hepatic extraction fraction and liver perfusion can be measured on dynamic imaging. Importantly, there is currently no clear consensus as to which of these MR-derived parameters is the most suitable for assessing liver dysfunction. This review article aims to describe the current role of GA-enhanced MRI in quantifying liver function, primarily in diffuse hepatobiliary disorders. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:646–659.

Purpose To determine the accuracy of ferumoxytol-enhanced magnetic resonance angiography (MRA) in assessing the severity of transplant renal artery stenosis (TRAS), using digital subtraction angiography (DSA) as the reference standard. Materials and methods Our Institutional Review Board approved this retrospective, Health Insurance Portability and Accountability Act-compliant study. Thirty-three patients with documented clinical suspicion for TRAS (elevated serum creatinine, refractory hypertension, edema, and/or audible bruit) and/or concerning sonographic findings (elevated renal artery velocity and/or intraparenchymal parvus tardus waveforms) underwent a 1.5T MRA with ferumoxytol prior to DSA. All DSAs were independently reviewed by an interventional radiologist and served as the reference standard. The MRAs were reviewed by three readers who were blinded to the ultrasound and DSA findings for the presence and severity of TRAS. Sensitivity, specificity, and accuracy for identifying substantial stenoses (>50%) were determined. Intraclass correlation coefficients (ICCs) were calculated among readers. Mean differences between the percent stenosis from each MRA reader and DSA were calculated. Results On DSA, a total of 42 stenoses were identified in the 33 patients. The sensitivity, specificity, and accuracy of MRA in detecting substantial stenoses were 100%, 75-87.5%, and 95.2-97.6%, respectively, among the readers. There was excellent agreement among readers as to the percent stenosis (ICC = 0.82). MRA overestimated the degree of stenosis by 3.9-9.6% compared to DSA. Conclusion Ferumoxytol-enhanced MRA provides high sensitivity, specificity, and accuracy for determining the severity of TRAS. Our results suggest that it can potentially be used as a noninvasive examination following ultrasound to reduce the number of unnecessary conventional angiograms. Level of evidence 3 J. Magn. Reson. Imaging 2017;45:779-785.

Author(s): Hernando, Diego; Sharma, Samir D; Aliyari Ghasabeh, Mounes; Alvis, Bret D; Arora, Sandeep S; Hamilton, Gavin; Pan, Li; Shaffer, Jean M; Sofue, Keitaro; Szeverenyi, Nikolaus M; Welch, E Brian; Yuan, Qing; Bashir, Mustafa R; Kamel, Ihab R; Rice, Mark J; Sirlin, Claude B; Yokoo, Takeshi; Reeder, Scott B | Abstract: PurposeTo evaluate the accuracy and reproducibility of quantitative chemical shift-encoded (CSE) MRI to quantify proton-density fat-fraction (PDFF) in a fat-water phantom across sites, vendors, field strengths, and protocols.MethodsSix sites (Philips, Siemens, and GE Healthcare) participated in this study. A phantom containing multiple vials with various oil/water suspensions (PDFF:0%-100%) was built, shipped to each site, and scanned at 1.5T and 3T using two CSE protocols per field strength. Confounder-corrected PDFF maps were reconstructed using a common algorithm. To assess accuracy, PDFF bias and linear regression with the known PDFF were calculated. To assess reproducibility, measurements were compared across sites, vendors, field strengths, and protocols using analysis of covariance (ANCOVA), Bland-Altman analysis, and the intraclass correlation coefficient (ICC).ResultsPDFF measurements revealed an overall absolute bias (across sites, field strengths, and protocols) of 0.22% (95% confidence interval, 0.07%-0.38%) and R2 g 0.995 relative to the known PDFF at each site, field strength, and protocol, with a slope between 0.96 and 1.02 and an intercept between -0.56% and 1.13%. ANCOVA did not reveal effects of field strength (P = 0.36) or protocol (P = 0.19). There was a significant effect of vendor (F = 25.13, P = 1.07 × 10-10 ) with a bias of -0.37% (Philips) and -1.22% (Siemens) relative to GE Healthcare. The overall ICC was 0.999.ConclusionCSE-based fat quantification is accurate and reproducible across sites, vendors, field strengths, and protocols. Magn Reson Med 77:1516-1524, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Ferumoxytol is an ultrasmall superparamagnetic iron oxide agent marketed for the treatment of anemia. There has been increasing interest in its properties as an MRI contrast agent as well as greater awareness of its adverse event profile. This mini-review summarizes the current state of knowledge of the risks of ferumoxytol and methods of administration.

Author(s): Kielar, Ania Z; Chernyak, Victoria; Bashir, Mustafa R; Do, Richard K; Fowler, Kathryn J; Santillan, Cynthia; Sirlin, Claude B; Mitchell, Donald G; Cerny, Milena; Tang, An; Elsayes, Khaled M; Kamaya, Aya; Kono, Yuko; Arora, Sandeep S

Author(s): Sofue, Keitaro; Sirlin, Claude B; Allen, Brian C; Nelson, Rendon C; Berg, Carl L; Bashir, Mustafa R | Abstract: PurposeTo determine whether reader perception of a capsule affects reader interpretation of washout in hypervascular liver nodules at dynamic magnetic resonance imaging (MRI) in patients at risk for hepatocellular carcinoma (HCC).Materials and methodsThis retrospective study was Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant, with waiver of informed consent. MRI reports for 111 hypervascular liver nodules (median 2.0 cm, range 1.0-17.8 cm) in 62 patients were reviewed, and the presence/absence of capsule and washout were recorded for one reading. A second independent study reading was also performed. The signal intensity ratio (SIR) for each nodule and liver parenchyma was measured. An objective SIR threshold was identified for nodules without capsules that correctly classified the presence/absence of washout, then applied to nodules with capsules to classify them as having / not having objective washout. Nodules were categorized as definite / not definite HCC using subjective and objective washout, based on LI-RADS, OPTN, AASLD, and EASL criteria, and proportions compared using McNemar's test.ResultsAgreement on nodule features was high for Readings 1 and 2 (κ = 0.70-0.82). For Reading 1, 71 nodules lacked capsules (43 with and 28 without subjective washout); an SIR threshold of 0.88 classified the presence/absence of washout correctly in 94% (67/71, P l 0.001). Forty nodules had capsules; although all had subjective washout (100%, 40/40), 75% (30/40) had objective washout (P l 0.05). Using objective washout caused 4.5% (3/66; LI-RADS, OPTN) and 12% (10/83; AASLD, EASL) of nodules to be recategorized from definite HCC to not definite HCC.ConclusionReader perception of capsule affects interpretation of washout. This effect can influence nodule categorization using imaging-based diagnostic systems. J. Magn. Reson. Imaging 2016;43:1337-1345.

Purpose To determine whether triple-arterial phase acquisition with fluoroscopic triggering can provide both well-timed early and late hepatic arterial phase (HAP) images more frequently than when using a fixed-time delay during gadoxetic acid-enhanced magnetic resonance imaging (MRI). Materials and Methods Written informed consent was obtained for this Institutional Review Board (IRB)-approved prospective, Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Ninety patients underwent gadoxetic acid-enhanced MRI at 3T with a single-breath-hold triple-arterial phase acquisition using either a fixed-time delay (n = 45) or fluoroscopic triggering injection protocol (n = 45). Three radiologists, blinded to method of timing and other data, independently determined whether well-timed early or late HAP were obtained for each arterial phase image set and assessed for transient severe motion (TSM). Rates of successful HAP acquisitions and of TSM were compared between the two protocols using χ2 or Fisher's exact test. Results The rate of successful acquisition of late HAP images was similar in the two groups (93% [42/45] for fixed-time delay vs. 98% [44/45] for fluoroscopic triggering, P = 0.62). There was a trend toward higher rates of successful acquisition of both early and late HAP images in the fluoroscopic triggering group (69% [31/45] vs. 49% [22/45], P = 0.05). TSM occurred in five patients (6% [5/90]) and at similar frequencies in the two groups (2% [1/45] vs. 9% [4/45], P = 0.36). Conclusion Triple-arterial phase acquisition with fluoroscopic triggering tended to provide both well-timed early and late HAP images more frequently than when using a fixed-time delay during gadoxetic acid-enhanced MRI. J. Magn. Reson. Imaging 2015.

Purpose: T2-weighted MRI provides excellent tumor-to-tissue contrast for target volume delineation in radiation therapy treatment planning. This study aims at developing a novel T2-weighted retrospective four dimensional magnetic resonance imaging (4D-MRI) phase sorting technique for imaging organ/tumor respiratory motion. Methods: A 2D fast T2-weighted half-Fourier acquisition single-shot turbo spin-echo MR sequence was used for image acquisition of 4D-MRI, with a frame rate of 2–3 frames/s. Respiratory motion was measured using an external breathing monitoring device. A phase sorting method was developed to sort the images by their corresponding respiratory phases. Besides, a result-driven strategy was applied to effectively utilize redundant images in the case when multiple images were allocated to a bin. This strategy, selecting the image with minimal amplitude error, will generate the most representative 4D-MRI. Since we are using a different image acquisition mode for 4D imaging (the sequential image acquisition scheme) with the conventionally used cine or helical image acquisition scheme, the 4D dataset sufficient condition was not obviously and directly predictable. An important challenge of the proposed technique was to determine the number of repeated scans (NR ) required to obtain sufficient phase information at each slice position. To tackle this challenge, the authors first conducted computer simulations using real-time position management respiratory signals of the 29 cancer patients under an IRB-approved retrospective study to derive the relationships between NR and the following factors: number of slices (NS ), number of 4D-MRI respiratory bins (NB ), and starting phase at image acquisition (P 0). To validate the authors’ technique, 4D-MRI acquisition and reconstruction were simulated on a 4D digital extended cardiac-torso (XCAT) human phantom using simulation derived parameters. Twelve healthy volunteers were involved in an IRB-approved study to investigate the feasibility of this technique. Results: 4D data acquisition completeness (Cp ) increases as NR increases in an inverse-exponential fashion (Cp = 100 − 99 × exp(−0.18 × NR ), when NB = 6, fitted using 29 patients’ data). The NR required for 4D-MRI reconstruction (defined as achieving 95% completeness, Cp = 95%, NR = N R,95) is proportional to NB (N R,95 ∼ 2.86 × NB , r = 1.0), but independent of NS and P 0. Simulated XCAT 4D-MRI showed a clear pattern of respiratory motion. Tumor motion trajectories measured on 4D-MRI were comparable to the average input signal, with a mean relative amplitude error of 2.7% ± 2.9%. Reconstructed 4D-MRI for healthy volunteers illustrated clear respiratory motion on three orthogonal planes, with minimal image artifacts. The artifacts were presumably caused by breathing irregularity and incompleteness of data acquisition (95% acquired only). The mean relative amplitude error between critical structure trajectory and average breathing curve for 12 healthy volunteers is 2.5 ± 0.3 mm in superior–inferior direction. Conclusions: A novel T2-weighted retrospective phase sorting 4D-MRI technique has been developed and successfully applied on digital phantom and healthy volunteers.

Purpose To assess the interexamination repeatability and spatial heterogeneity of liver iron and fat measurements using a magnetic resonance imaging (MRI)-based multistep adaptive fitting algorithm. Materials and Methods This prospective observational study was Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant. Written informed consent was waived. In all, 150 subjects were imaged on 3T MRI systems. A whole-liver volume acquisition was performed twice using a six-echo 3D spoiled gradient echo sequence during two immediately adjacent examinations. Colocalized regions of interest (ROIs) in three different hepatic segments were placed for R2* and proton density fat fraction (PDFF) measurements by two readers independently. Mean R2* and PDFF values between readers and acquisitions were compared using the Wilcoxon signed-rank test, intraclass correlation coefficients (ICCs), linear regression, Bland–Altman analysis, and analysis of variance (ANOVA). Results The mean R2* and PDFF values across all ROIs and measurements were 51.2 ± 25.2 s−1 and 6.9 ± 6.4%, respectively. Mean R2* and PDFF values showed no significant differences between the two acquisitions (P = 0.05–0.87). Between the two acquisitions, R2* and PDFF values demonstrated almost perfect agreement (ICCs = 0.979–0.994) and excellent correlation (R2 = 0.958–0.989). Bland–Altman analysis also demonstrated excellent agreement. In the ANOVA, the individual patient and ROI location were significant effects for both R2* and PDFF values (P

Introduction Previous examination of whole-body muscle involvement in Pompe disease has been limited to physical examination and/or qualitative magnetic resonance imaging (MRI). In this study we assess the feasibility of quantitative proton-density fat-fraction (PDFF) whole-body MRI in late-onset Pompe disease (LOPD) and compare the results with manual muscle testing. Methods Seven LOPD patients and 11 disease-free controls underwent whole-body PDFF MRI. Quantitative MR muscle group assessments were compared with physical testing of muscle groups. Results The 95% upper limits of confidence intervals for muscle groups were 4.9–12.6% in controls and 6.8–76.4% in LOPD patients. LOPD patients showed severe and consistent tongue and axial muscle group involvement, with less marked involvement of peripheral musculature. MRI was more sensitive than physical examination for detection of abnormality in multiple muscle groups. Conclusion This integrated, quantitative approach to muscle assessment provides more detailed data than physical examination and may have clinical utility for monitoring disease progression and treatment response. Muscle Nerve 51:722–730, 2015

Purpose: A projection onto convex sets reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE) is developed to reduce motion-related artifacts, including respiration artifacts in abdominal imaging and aliasing artifacts in interleaved diffusion-weighted imaging. Theory: Images with reduced artifacts are reconstructed with an iterative projection onto convex sets (POCS) procedure that uses the coil sensitivity profile as a constraint. This method can be applied to data obtained with different pulse sequences and k-space trajectories. In addition, various constraints can be incorporated to stabilize the reconstruction of illconditioned matrices. Methods: The POCSMUSE technique was applied to abdominal fast spin-echo imaging data, and its effectiveness in respiratory-triggered scans was evaluated. The POCSMUSE method was also applied to reduce aliasing artifacts due to shot-to-shot phase variations in interleaved diffusion-weighted imaging data corresponding to different k-space trajectories and matrix condition numbers. Results: Experimental results show that the POCSMUSE technique can effectively reduce motion-related artifacts in data obtained with different pulse sequences, k-space trajectories and contrasts. Conclusion: POCSMUSE is a general post-processing algorithm for reduction of motion-related artifacts. It is compatible with different pulse sequences, and can also be used to further reduce residual artifacts in data produced by existing motion artifact reduction methods. Magn Reson Med 000:000–000, 2014. V C 2014 Wiley Periodicals, Inc.

Purpose To determine the rate of agreement between the Organ Procurement and Transplant Network (OPTN) and Liver Imaging Reporting and Data System (LI-RADS) classifications for hypervascular liver nodules at least 1 cm in diameter, and for patient eligibility for hepatocellular/MELD (Model for Endstage Liver Disease) exception points. Materials and Methods This retrospective study was approved by our Institutional Review Board and was compliant with the Health Insurance Portability and Accountability Act. The requirement for informed consent was waived. This study included 200 hypervascular hepatocellular nodules at least 1 cm in diameter on computed tomography (CT) or magnetic resonance imaging (MRI) examinations in 105 patients with chronic liver disease. Three radiologists blinded to clinical data independently evaluated nodule characteristics, including washout, capsule, size, and size on prior examination. Based on those characteristics, nodules were automatically classified as definite hepatocellular carcinoma (HCC) or not definite HCC using both the OPTN and LI-RADS classifications. Using these classifications and the Milan criteria, each examination was determined to be "below transplant criteria," "within transplant criteria," or "beyond transplant criteria." Agreement was assessed between readers and classification systems, using Fleiss' kappa, intraclass correlation coefficients (ICCs), and simple proportions. Results Interreader agreement was moderate for nodule features (κ = 0.59–0.69) and nodule classification (0.66–0.69). The two systems were in nearly complete agreement on nodule category assignment (98.7% [592/600]) and patient eligibility for transplant exemption priority (99.4% [313/315]). A few discrepancies occurred for the nodule feature of growth (1.3% [8/600]) and for nodule category assignment (1.3% [8/600]). Conclusion Agreement between the OPTN and LI-RADS classifications is very strong for categorization of hypervascular liver nodules at least 1 cm in diameter, and for patient eligibility for hepatocellular/MELD exception points. Interreader variability is much higher than intersystem variability. J. Magn. Reson. Imaging 2015;42:305–314.

Purpose To evaluate the feasibility of a respiratory-gated noncontrast magnetic resonance angiography (MRA) sequence for imaging the central veins of the chest. Materials and Methods Eleven healthy subjects underwent MRA of the central veins of the chest with a respiratory-gated noncontrast (SPACE) sequence. Qualitative visualization and signal homogeneity of each central venous segment were scored by two radiologists on a scale of 1–4. Signal-to-noise and contrast-to-noise ratios (SNR and CNR) were also calculated. Retrospective review of our imaging database revealed 13 patients with suspected pathology of the central veins who underwent a clinical MRA examination using the SPACE sequence as well as reference standard central venous imaging with contrast-enhanced MRA or conventional venography. Results In healthy subjects, all central venous segments demonstrated good to excellent venous visualization and homogeneity scores with the noncontrast SPACE sequence. The mean SNR and CNR of the central venous system were 192.7 and 175.0, respectively. In the 13 clinical examinations, the sensitivity and specificity for detection of stenosis or occlusions was 100% and 100% for reader 1 and 95% and 91% for reader 2, respectively. Conclusion The respiratory-gated noncontrast SPACE sequence provided excellent imaging characteristics of the central veins in healthy subjects with promising diagnostic accuracy in patients with central venous pathology. J. Magn. Reson. Imaging 2015;41:67–73. © 2013 Wiley Periodicals, Inc.

Purpose The purpose of this study was to develop a multi-step adaptive fitting approach for liver proton density fat fraction (PDFF) and quantification, and to perform an initial validation on a broadly available hardware platform. Theory and Methods The proposed method uses a multi-echo three-dimensional gradient echo acquisition, with initial guesses for the fat and water signal fractions based on a Dixon decomposition of two selected echoes. Based on magnitude signal equations with a multi-peak fat spectral model, a multi-step nonlinear fitting procedure is then performed to adaptively update the fat and water signal fractions and values. The proposed method was validated using numeric phantoms as ground truth, followed by preliminary clinical validation of PDFF calculations against spectroscopy in 30 patients. Results The results of the proposed method agreed well with the ground truth of numerical phantoms, and were relatively insensitive to changes in field strength, field homogeneity, monopolar/bipolar readout, signal to noise ratio, and echo time selections. The in vivo patient study showed excellent consistency between the PDFF values measured with the proposed approach compared with spectroscopy. Conclusion This multi-step adaptive fitting approach performed well in both simulated and initial clinical evaluation, and shows potential in the quantification of hepatic steatosis. Magn Reson Med 72:1353–1365, 2014. © 2013 Wiley Periodicals, Inc.

Aim Patients with rectal cancer often undergo multiple CT scans prior to surgical resection. We propose that in patients with locally advanced rectal cancer without evidence of metastatic disease at presentation, CT imaging of the chest and abdomen after preoperative neoadjuvant therapy does not change clinical information or surgical management. Method An institutional review board-approved medical record review identified patients with contrast enhanced CT of the chest, abdomen and pelvis alone or in conjunction with 18F-fluoro-2-deoxy-d-glucose/positron emission tomography imaging for staging of rectal cancer prior to and after neoadjuvant therapy. Eighty-eight patients were included in the study. Scans were reviewed for the presence of metastatic disease on initial and follow-up imaging prior to surgical resection. Results Seventy-six (86%) of 88 patients had no evidence of metastasis at presentation. None of these patients developed metastatic disease after neoadjuvant therapy. Twelve (14%) had metastases at presentation. No study patient developed metastatic disease in a new organ. Conclusion Imaging after preoperative neoadjuvant therapy in rectal cancer does not change the designation of metastatic disease. Patients with locally advanced rectal adenocarcinoma without evidence of metastases may not benefit from repeat imaging of the chest and abdomen after neoadjuvant therapy.

PURPOSE To investigate variation in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameter measurements between different methods of precontrast tissue relaxation (T10) estimation: pixel-based mapping versus a fixed reference value. MATERIALS AND METHODS In 15 DCE-MRI studies the female pelvis, uterine fibroids, the left psoas muscle, and the fifth lumbar vertebral body were chosen to represent tissues with varying perfusion characteristics. All DCEMRI studies were processed using a variable flip angle T10 map and a fixed T10 reference value of 1000 msec. A subset of five DCE-MRI studies were each processed multiple times using the fixed T10 method with the reference T10 ranging from 0–2000 msec in 100-msec increments. Pharmacokinetic measurements of Ktrans, kep, ve, and initial area under the gadolinium curve (iAUGC) were performed maintaining the identical position for region of interest placement on each structure. RESULTS The mean difference in pharmacokinetic output between the pixel-based T10 map and the fixed T10 reference value ranged from 6.6% for kep in the muscle to 54.9% for iAUGC in the vertebral body. At lower T10 (

Purpose To compare abdominopelvic and lower extremity venous enhancement in contrast-enhanced magnetic resonance venography (ceMRV), using iron-based ferumoxytol and gadolinium-based gadofosveset. Materials and Methods This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study. Thirty-four patients were identified who had undergone ceMRV using either ferumoxtyol (Group A, all with chronic renal insufficiency) or gadofosveset (Group B). Two radiologists rated confidence for evaluation of the major abdominopelvic and lower extremity veins from 4 (excellent confidence) to 1 (nondiagnostic). A third radiologist measured signal intensity ratios (SIRs) of venous segments compared with adjacent muscles. Scores were compared using repeated-measures analysis of variance (ANOVA). The medical record was searched for contemporaneous imaging to confirm the ceMRV findings. Results In Group A, 14/225 venous segments were thrombosed, compared with 18/282 in Group B. There was no statistically significant difference between confidence scores (3.79 ± 0.44 vs. 3.85 ± 0.44, P = 0.34) or SIRs (2.40 ± 0.73 vs. 2.38 ± 0.51, P = 0.51) for patent segments in the two groups, nor were confidences scores (3.89 ± 0.29 vs. 3.72 ± 0.46, P = 0.31) or SIRs (0.90 ± 0.12 vs. 0.84 ± 0.19, P = 0.31) significantly different for thrombosed segments. Contemporaneous imaging confirmed ceMRV findings in 227 segments. Conclusion ceMRV can be performed with ferumoxytol, yielding similar image quality to a blood pool gadolinium-based contrast agent. J. Magn. Reson. Imaging 2014;40:113–118. © 2013 Wiley Periodicals, Inc.

Purpose To determine the reproducibility of TWIST-derived (Time-Resolved Angiography with Interleaved Stochastic Trajectories) quantitative dynamic contrast enhanced (DCE) MRI in a uterine fibroid model. Materials and Methods The institutional review board approved this retrospective study. Dynamic contrast-enhanced TWIST datasets from 15 randomly selected 1.5 Tesla pelvic MR studies were postprocessed. Five readers recorded kinetic parameters (Ktrans [volume transfer constant], ve [extracellular extravascular space volume], kep [flux rate constant], iAUC [initial area under the gadolinium-time curve]) of the largest uterine fibroid using three region-of-interest (ROI) selection methods. Measurements were randomized and repeated three times, and measures of reproducibility were calculated. Results The intra-rater coefficients of variation (CVs, brackets indicate 95% confidence intervals) varied from 4.6% to 7.6% (Ktrans 7.6% [6.1%, 9.1%], kep 7.2% [5.9%, 8.5%], ve 4.6% [3.8%, 5.4%], and iAUC 7.2% [6.1%, 8.3%]). ve was the most reproducible (P < 0.05). Inter-rater reproducibility was significantly (P < 0.05) greater for the large ROI method (range of intraclass correlation coefficients [ICCs] = 0.80–0.98 versus 0.48–0.63 [user-defined ROI] versus 0.41–0.69 [targeted ROI]). The uterine fibroid accounted for the greatest fraction of variance for the large ROI method (range across kinetic parameters: 83–98% versus 56–69% [user-defined ROI] versus 47–74% [targeted ROI]). The reader accounted for the greatest fraction of variance for the user-defined ROI method (0.4–14.1% versus 0.1–3.0% [large ROI] versus

PURPOSE: To evaluate the value of hepatobiliary phase imaging for detection and characterization of hepatocellular carcinoma (HCC) in liver MRI with Gd-EOB-DTPA, in a North American population. MATERIALS AND METHODS: One hundred MRI examinations performed with the intravenous injection of Gd-EOB-DTPA in patients with cirrhosis were reviewed retrospectively. Nodules were classified as HCC (n = 70), indeterminate (n = 33), or benign (n = 22). Five readers independently reviewed each examination with and without hepatobiliary phase images (HBP). Lesion conspicuity scores were compared between the two readings. Lesion detection, confidence scores, and receiver operating characteristic (ROC) analysis were compared. RESULTS: Lesion detection was slightly improved for all lesion types with the inclusion of the HBP, and was substantially higher for small HCCs (96.0% versus 85.3%). Mean confidence scores for the diagnosis of HCC increased for HCCs overall and each size category (P < 0.001). Diagnostic performance improved with the addition of the HBP (aggregate AROC 87.7% versus 80.0%, P < 0.01), and sensitivity for characterization improved (90.9% versus 78.3%, P < 0.01) while specificity was unchanged. CONCLUSION: Hepatobiliary phase imaging may improve small lesion detection (

Magnetic resonance spectroscopy of the liver requires input from a physicist or physician at the time of acquisition to insure proper voxel selection, while in multiecho chemical shift imaging, numerous regions of interest must be manually selected in order to ensure analysis of a representative portion of the liver parenchyma. A fully automated technique could improve workflow by selecting representative portions of the liver prior to human analysis. Complete volumes from three-dimensional gradient dual-echo acquisitions with two-point Dixon reconstruction acquired at 1.5 and 3 T were analyzed in 100 subjects, using an automated liver sampling algorithm, based on ratio pairs calculated from signal intensity image data as fat-only/water-only and log(in-phase/opposed-phase) on a voxel-by-voxel basis. Using different gridding variations of the algorithm, the average correct liver volume samples ranged from 527 to 733 mL. The average percentage of sample located within the liver ranged from 95.4 to 97.1%, whereas the average incorrect volume selected was 16.5–35.4 mL (2.9–4.6%). Average run time was 19.7–79.0 s. The algorithm consistently selected large samples of the hepatic parenchyma with small amounts of erroneous extrahepatic sampling, and run times were feasible for execution on an MRI system console during exam acquisition. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.

Introduction: Fatty infiltration of muscles may be seen in many neuromuscular disorders, including glycogen storage disease (GSD), muscular dystrophy, and amyotrophic lateral sclerosis. Recording pathologic involvement of musculature in these patients is cumbersome, given marked disease heterogeneity within each individual. We describe a novel method for simplifying this process and present its application in a patient with GSD type IIIa. Methods: A color-coded visual mapping tool was developed based on a commonly used spreadsheet platform. Results: This tool depicts individual muscle groups as shapes linked to data cells corresponding to quantitative MRI-based measures of fatty infiltration and weakness assessed by physical examination. It allows for rapid evaluation and chronological comparison of all mapped muscle groups on a single graphical sheet, as well as assessment of response to therapy. Conclusion:This approach can be applied in any neuromuscular disorder where muscle function is assessed by clinical or imaging scores. Muscle Nerve, 48: 293–295, 2013

Purpose: The unreliable stability of internal respiratory surrogates and inconvenience of external respiratory surrogates for current retrospective 4D-MRI techniques largely affects the image quality of 4D-MRI. This study aims at developing image-based surrogate, a sagittal-coronal-diaphragm point of intersection (SCD-PoI) motion tracking method for retrospective 4D-MRI reconstruction.Methods/materials: As a pre-estimate of respiratory motion pattern, single-slice sagittal cines (FIESTA) were acquired at a location near the dome of the diaphragm. Subsequently, multi-slice coronal cines (FIESTA) were acquired and used for 4D-MRI reconstruction with phase sorting. Diaphragm motion trajectories were measured from the point of intersection between sagittal MRI cine plane, coronal MRI cine plain and the diaphragm dome surface. This point is defined as sagittal-coronal-diaphragm point of intersection (SCD-PoI). We pre-estimate respiraotyr motion by tracking SCD-PoI on sagitall cine. Then coronal images were then re-binned to different phased bins according to SCD-PoI motion tracking on coronal cine. This 4D-MRI technique was evaluated on a 4D Digital Extended Cardiac-Torso (XCAT) human phantom with a hypothesized moving tumor, six healthy voluneteers and two cancer patients under an IRB-approved study. Region of interest (ROI: tumor for XCAT and patients, dome of left kidney for healthy volunteers) trajectories on 4D-MRI were measured and compared with the reference (input respiratory curve for XCAT and ROI trajectories extracted from reference single-slice MRI cine (FIESTA) for human subjects). Superior-inferior (SI) mean absolute amplitude difference (D) and cross-correlation coefficient (CC) were calculated. Results: 4D-MRI on XCAT demonstrated highly accurate motion information with a low D (1.13mm) and a high CC (0.98) in the SI direction. Minimal artifacts were observed in human participants’ 4D-MRI, and images were adequate to reveal the respiratory motion of organs and tumor (D=1.08±1.03mm; CC=0.96). Conclusion: A novel 4D-MRI technique with image-based respiratory surrogate has been developed and tested on a digital phantom and human subjects.

Purpose: Diffusion-weighted imaging(DWI) has been shown to have superior tumor-to-tissue contrast for cancer detection.This study aims at developing and evaluating a four dimensional DWI(4D-DWI) technique using retrospective sorting method for imaging respiratory motion for radiotherapy planning,and evaluate its effect on Apparent Diffusion Coefficient(ADC) measurement. Materials/Methods: Image acquisition was performed by repeatedly imaging a volume of interest using a multi-slice single-shot 2D-DWI sequence in the axial planes and cine MRI(served as reference) using FIESTA sequence.Each 2D-DWI image were acquired in xyz-diffusion-directions with a high b-value(b=500s/mm2).The respiratory motion was simultaneously recorded using bellows.Retrospective sorting was applied in each direction to reconstruct 4D-DWI.The technique was evaluated using a computer simulated 4D-digital human phantom(XCAT),a motion phantom and a healthy volunteer under an IRB-approved study.Motion trajectories of regions-of-interests(ROI) were extracted from 4D-DWI and compared with reference.The mean motion trajectory amplitude differences(D) between the two was calculated.To quantitatively analyze the motion artifacts,XCAT were controlled to simulate regular motion and the motions of 10 liver cancer patients.4D-DWI,free-breathing DWI(FB- DWI) were reconstructed.Tumor volume difference(VD) of each phase of 4D-DWI and FB-DWI from the input static tumor were calculated.Furthermore, ADC was measured for each phase of 4D-DWI and FB-DWI data,and mean tumor ADC values(M-ADC) were calculated.Mean M-ADC over all 4D-DWI phases was compared with M-ADC calculated from FB-DWI. Results: 4D-DWI of XCAT,the motion phantom and the healthy volunteer demonstrated the respiratory motion clearly.ROI D values were 1.9mm,1.7mm and 2.0mm,respectively.For motion artifacts analysis,XCAT 4D-DWI images show much less motion artifacts compare to FB-DWI.Mean VD for 4D-WDI and FB-DWI were 8.5±1.4% and 108±15%,respectively.Mean M-ADC for ADC measured from 4D-DWI and M-ADC measured from FB-DWI were (2.29±0.04)*0.001*mm2/s and (3.80±0.01)*0.001*mm2/s,respectively.ADC value ground-truth is 2.24*0.001*mm2/s from the input of the simulation. Conclusion: A respiratory correlated 4D-DWI technique has been initially evaluated in phantoms and a human subject.Comparing to free breathing DWI,4D-DWI can lead to more accurate measurement of ADC.

Purpose: The authors have recently developed a novel 4D-MRI technique for imaging organ respiratory motion employing cine acquisition in the axial plane and using body area (BA) as a respiratory surrogate. A potential disadvantage associated with axial image acquisition is the space-dependent phase shift in the superior–inferior (SI) direction, i.e., different axial slice positions reach the respiratory peak at different respiratory phases. Since respiratory motion occurs mostly in the SI and anterior–posterior (AP) directions, sagittal image acquisition, which embeds motion information in these two directions, is expected to be more robust and less affected by phase-shift than axial image acquisition. This study aims to develop and evaluate a 4D-MRI technique using sagittal image acquisition. Methods: The authors evaluated axial BA and sagittal BA using both 4D-CT images (11 cancer patients) and cine MR images (6 healthy volunteers and 1 cancer patient) by comparing their corresponding space-dependent phase-shift in the SI direction ( δ SPS SI ) and in the lateral direction ( δ SPS LAT ) , respectively. To evaluate sagittal BA 4D-MRI method, a motion phantom study and a digital phantom study were performed. Additionally, six patients who had cancer(s) in the liver were prospectively enrolled in this study. For each patient, multislice sagittal MR images were acquired for 4D-MRI reconstruction. 4D retrospective sorting was performed based on respiratory phases. Single-slice cine MRI was also acquired in the axial, coronal, and sagittal planes across the tumor center from which tumor motion trajectories in the SI, AP, and medial–lateral (ML) directions were extracted and used as references from comparison. All MR images were acquired in a 1.5 T scanner using a steady-state precession sequence (frame rate ∼ 3 frames/s). Results: 4D-CT scans showed that δ SPS SI was significantly greater than δ SPS LAT (p-value: 0.012); the median phase-shift was 16.9% and 7.7%, respectively. Body surface motion measurement from axial and sagittal MR cines also showed δ SPS SI was significantly greater than δ SPS LAT . The median δ SPS SI and δ SPS LAT was 11.0% and 9.2% (p-value = 0.008), respectively. Tumor motion trajectories from 4D-MRI matched with those from single-slice cine MRI: the mean (±SD) absolute differences in tumor motion amplitude between the two were 1.5 ± 1.6 mm, 2.1 ± 1.9 mm, and 1.1 ± 1.0 mm in the SI, ML, and AP directions from this patient study. Conclusions: Space-dependent phase shift is less problematic for sagittal acquisition than for axial acquisition. 4D-MRI using sagittal acquisition was successfully carried out in patients with hepatic tumors.

Purpose: It is of clinical interest to study liver deformation during breathing by applying deformable image registration (DIR) on respiratory correlated 4D images. This study aims to evaluate and compare the accuracy of DIR-derived liver deformation based on 4D CT and 4D MRI. Methods: 4D CT, 4D MR and cine MR images of liver region were acquired from 5 patients with liver cancer under an IRB-approved protocol. Tumor trajectories were tracked from cine MR images. DVFs from 4D CT and 4D MR were generated via DIR implemented in Velocity AI. To enable comparison between DVFs and tumor trajectories from cine images, deformation vectors from each frame were linked together, forming DVF-based trajectories. All DVF-based trajectories within each tumor region were averaged. Absolute difference, relative difference and correlation coefficient between each pair of averaged DVF-based trajectory and trajectory from cine MR images were calculated. Results: All metrics did not give consistent indications of which modality can provide more accurate DVFs. In superior-inferior (SI) direction, averaging over all the five patients, 4D CT trajectories exhibited smaller absolute (2.05±0.52mm) and relative difference (0.43±0.14) and larger correlation coefficient (0.92±0.06) than 4D MR trajectories (2.54±1.45mm, 0.47±0.18, 0.88±0.10) whereas 4D MR (1.02±1.20mm, 0.90±0.69, 0.59±0.30) surpassed 4D CT (1.35±1.42mm, 1.35±1.25, 0.12±0.64) in every metric in right-left direction. In anterior-posterior direction, 4D MR trajectories has smaller absolute (1.17±0.74mm) and relative difference (0.50±0.18) with slightly smaller correlation coefficient (0.72±0.23) than 4D CT trajectories (1.51±0.64mm, 0.69±0.09, 0.75±0.26). Conclusion: We have implemented a novel approach for evaluating accuracy of DVFs based on 4D imaging for studying liver deformation. Initial results indicate that DVFs from 4D CT and 4D MRI are comparable. Further study on more patients is warranted and is undergoing to determine whether there is significant difference between 4D CT and 4D MRI.

Purpose: Quantitative imaging of hepatic stiffness has significant potential in radiation therapy, ranging from treatment planning to response assessment. This study aims to develop a novel, noninvasive method to quantify liver stiffness with 3D strains liver maps using 4D-MRI and deformable image registration (DIR). Methods: Five patients with liver cancer were imaged with an institutionally developed 4D-MRI technique under an IRB-approved protocol. Displacement vector fields (DVFs) across the liver were generated via DIR of different phases of 4D-MRI. Strain tensor at each voxel of interest (VOI) was computed from the relative displacements between the VOI and each of the six adjacent voxels. Three principal strains (E1, E2 and E3) of the VOI were derived as the eigenvalue of the strain tensor, which represent the magnitudes of the maximum and minimum stretches. Strain tensors for two regions of interest (ROIs) were calculated and compared for each patient, one within the tumor (ROI1) and the other in normal liver distant from the heart (ROI2). Results: 3D strain maps were successfully generated fort each respiratory phase of 4D-MRI for all patients. Liver deformations induced by both respiration and cardiac motion were observed. Differences in strain values adjacent to the distant from the heart indicate significant deformation caused by cardiac expansion during diastole. The large E1/E2 (∼2) and E1/E2 (∼10) ratios reflect the predominance of liver deformation in the superior-inferior direction. The mean E1 in ROI1 (0.12±0.10) was smaller than in ROI2 (0.15±0.12), reflecting a higher degree of stiffness of the cirrhotic tumor. Conclusion: We have successfully developed a novel method for quantitatively evaluating regional hepatic stiffness based on DIR of 4D-MRI. Our initial findings indicate that liver strain is heterogeneous, and liver tumors may have lower principal strain values than normal liver. Thorough validation of our method is warranted in future studies. NIH (1R21CA165384-01A1)

Purpose: To investigate whether diaphragm motion is a good surrogate for liver tumor motion by comparing their motion trajectories obtained from cine-MRI. Methods: Fourteen patients with hepatocellular carcinoma (10/14) or liver metastases (4/14) undergoing radiation therapy were included in this study. All patients underwent single-slice 2D cine-MRI simulations across the center of the tumor in three orthogonal planes. Tumor and diaphragm motion trajectories in the superior-inferior (SI), anteriorposterior (AP), and medial-lateral (ML) directions were obtained using the normalized cross-correlation based tracking technique. Agreement between tumor and diaphragm motions was assessed by calculating the phase difference percentage (PDP), intra-class correlation coefficient (ICC), Bland-Altman analysis (Diffs) and paired t-test. The distance (D) between tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between tumor and diaphragm motions. Results: Of all patients, the means (±standard deviations) of PDP were 7.1 (±1.1)%, 4.5 (±0.5)% and 17.5 (±4.5)% in the SI, AP and ML directions, respectively. The means of ICC were 0.98 (±0.02), 0.97 (±0.02), and 0.08 (±0.06) in the SI, AP and ML directions, respectively. The Diffs were 2.8 (±1.4) mm, 2.4 (±1.1) mm, and 2.2 (±0.5) mm in the SI, AP and ML directions, respectively. The p-values derivedmore » from the paired t-test were 0.58 in ML direction primarily due to the small motion in ML direction. Tumor and diaphragmatic motion had high concordance when the distance between the tumor and tracked diaphragm areas was small. Conclusion: Preliminary results showed that liver tumor motion had good correlations with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be a reliable surrogate for liver tumor motion. NIH (1R21CA165384-01A1), Golfers Against Cancer (GAC) Foundation, The China Scholarship Council (CSC)« less

Purpose: To reduce deformable image registration error by fitting the displacement vector field (DVF) to smooth the motion trajectory of each pixel in synthetic 4D-MRI. Methods: Five patients with cancers in the liver were enrolled in this study. For a 4D MR image data set, the DVF matrices relative to a specific reference phase were calculated using an in-house deformable image registration based on b-spline. The displacement trajectory of each voxel throughout the respiratory cycle was constituted by concatenating the corresponding displacement values from all DVF matrices. A linear polynomial fitting model was then used to fit the DVFs in three spatial and the temporal dimension, respectively. By warpping the source MR images using the remodeled DVFs, we synthesized MR images at selected phases. Tumor motion trajectories were derived from source 4DMRI, original synthetic images and improved synthetic images. These were analyzed in the superior-inferior (SI), anterior-posterior (AP), and mediallateral (ML) directions, respectively. Correlation coefficients (CC) and differences in motion amplitude (D) were calculated for comparison. Results: For all patients, tumor motion trajectories were strongly correlated between source 4D-MRI images and improved synthetic 4D-MRI (mean CC 0.98±0.01). Differences in motion amplitude were small (mean D 0.46±0.14 mm) in all directions. Correlation between source 4D-MRI and original synthetic 4D-MRI was slightly less strong (mean CC 0.97±0.01) and motion amplitude differences were slightly larger (0.55±0.19 mm). Conclusion: The feasibility of synthesizing T2w 4D-MRI using remodeled DVFs has been investigated in this study. Preliminary results in oncologic patients demonstrated the potential of reducing inaccuracies in original synthetic 4DMRI caused by registration errors using the linear polynomial fitting model without much loss of respiratory motion information. NIH (1R21CA165384-01A1), Golfers Against Cancer (GAC) Foundation, The China Scholarship Council (CSC)

Purpose: To investigate the accuracy of 4D-MRI in determining the Internal Target Volume (ITV) used in radiation oncology treatment planning of liver cancers. Cine MRI is used as the standard baseline in establishing the feasibility and accuracy of 4D-MRI tumor motion within the liver. Methods: IRB approval was obtained for this retrospective study. Analysis was performed on MR images from four patients receiving external beam radiation therapy for liver cancer at our institution. Eligible patients received both Cine and 4D-MRI scans before treatment. Cine images were acquired sagittally in real time at a slice bisecting the tumor, while 4D images were acquired volumetrically. Cine MR DICOM headers were manipulated such that each respiratory frame was assigned a unique slice location. This approach permitted the treatment planning system (Eclipse, Varian Medical Systems) to recognize a complete respiratory cycle as a “volume”, where the gross tumor was contoured temporally. Software was developed to calculate the union of all frame contours in the structure set, resulting in the corresponding plane of the ITV projecting through the middle of the tumor, defined as the Internal Target Area (ITA). This was repeated for 4D-MRI, at the corresponding slice location, allowing a direct comparison of ITAs obtained from each modality. Results: Four patients have been analyzed. ITAs contoured from 4D-MRI correlate with contours from Cine MRI. The mean error of 4D values relative to Cine values is 7.67 +/− 2.55 %. No single ITA contoured from 4D-MRI demonstrated more than 10.5 % error compared to its Cine MRI counterpart. Conclusion: Motion management is a significant aspect of treatment planning within dynamic environments such as the liver, where diaphragmatic and cardiac activity influence plan accuracy. This small pilot study suggests that 4D-MRI based ITA measurements agree with Cine MRI based measurements, an important step towards clinical implementation. NIH 1R21CA165384-01A1

Purpose: T2‐weighted MR provides excellent delineation of malignant liver lesions due to its superior tumor‐to‐tissue contrast. This study aims to develop a novel T2‐weighted retrospective 4D‐MRI technique for imaging organ/tumor respiratory motion with improved soft‐tissue contrast. Method and Materials: Determine the number of repeated scans (NR) required obtaining sufficient phase information for each slice is the critical component in developing this technique and needs substantial testing with many samples. To do that, computer simulations using RPM respiratory signals of 29 cancer patients were performed to derive the relationships between NR and the following factors: number of slice to scanned (Ns), number of respiratory phases of the 4D‐MRI (Np), and starting phase at image acquisition (P0). Assuming T2‐w HASTE/SSFSE MR sequence to be used to acquire raw images for 4D‐MRI, frame rate of 2 frames/s was used in the simulation. To validate our technique, 4D‐MRI acquisition and reconstruction were simulated on a 4D digital human phantom using parameters derived from the above studies. Retrospective sorting of 4D‐MRI was achieved using a novel phase and amplitude hybrid sorting algorithm by effectively utilizing redundant images. Result: Percentage of complete acquisition of all required phases (Cp) increased as NR increased in an inverse‐exponential (Cp=100*[1‐exp(−0.11*NR)],when Ns=50,Np=10) fashion. NR to achieve 95% completion (Cp=95%) of all required phases, defined as the NR needed for 4D‐MRI, is linearly proportional to Np (Nr∼2.86*Np, r=1.0) but independent of NS and P0. Simulated 4D‐MRI on the digital phantom showed clear pattern of respiratory motion. Tumor motion trajectories measured on 4D‐MRI were comparable to the average input signal, with a mean relative difference in motion amplitude of 16%, presumably due to breathing irregularity. Conclusions: A novel T2‐weighted 4D‐MRI technique based on HASTE/SSFSE sequence have been developed and validated. Future evaluation on patients is desired. This work is partly supported by funding from NIH (1R21CA165384‐01A1) and a research grant from the Golfers Against Cancer (GAC) Foundation.

Purpose: We have previously developed a novel 4D‐MRI technique using body area (BA) as internal respiratory surrogate. This study is to demonstrate our initial patient results via validating the accuracy of tumor motion measurements and the improvement of tumor‐to‐tissue contrast‐to‐signal ratio (CNR) in the 4D‐MRI. Methods: Five patients with cancer (s) in the liver were enrolled in an IRB‐approved study. All patients underwent 3D/4D CT and MR simulation for treatment planning. 4D‐MRI image were generated by firstly acquiring multiple‐slice multiple‐phase cine‐MR images in the axial plane and then retrospectively binning the images based on respiratory phases. Respiratory signals were determined by tracking changes of the BA of axial MR images. Single‐slice 2D cine MR images were also acquired across the center of the tumor in orthogonal planes (axial, sagittal, and coronal). For data analysis, tumor motion trajectories in the superior‐inferior (SI), anterior‐posterior (AP), and medial‐lateral (ML) directions, were determined from 4D‐MRI and compared to those determined from cine‐MR images, which were used as references. The correlation coefficients (CC) and the differences in tumor motion amplitude were determined between the two. Tumor‐to‐liver CNR was compared between 4D‐MRI and 4D‐CT. Results: 4D‐MRI clearly revealed respiratory motion in all patients. Tumor motion trajectories were comparable between 4D‐MRI and cine‐MR: the mean (± standard deviation (SD)) CC was 0.97(±0.03), 0.97(±0.02), and 0.99(±0.04) in the SI, AP and ML directions, respectively. The mean (±SD) difference in tumor motion amplitude was 0.61(±0.17)mm, 0.32(±0.17)mm, 0.14(±0.06)mm in the SI, AP and ML directions, respectively. The mean tumor‐to‐tissue CNR were improved from 1.52(±2.04) in 4D‐CT images to 7.57(±5.64) in 4D‐MRIs. Conclusion: 4D‐MRI using BA as respiratory surrogate and axial image acquisition has been successfully demonstrated in patients. It is a promising technique for more accurately imaging tumor respiratory motion with improved soft‐tissue contrast. This work is partly supported by funding from NIH (1R21CA165384‐01A1) and a research grant from the Golfers Against Cancer (GAC) Foundation.