Material-enhanced Magnetic Resonance Imaging Research Articles

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 patients. By using data from The Cancer Genome Atlas (TCGA), a radiogenomic map for the tumor-adjacent parenchymal tissue was created and molecular pathways associated with prognostic parenchymal imaging features were identified. Furthermore, a multigene signature of the parenchymal imaging feature was built in a training cohort (n = 126), and its prognostic relevance was evaluated in two independent cohorts (n = 879 and 159). Results One image feature measuring heterogeneity (ie, information measure of correlation) was significantly associated with prognosis (false-discovery rate < 0.1), and at a cutoff of 0.57 stratified patients into two groups with different recurrence-free survival rates (log-rank P = .024). The tumor necrosis factor signaling pathway was identified as the top enriched pathway (hypergeometric P < .0001) among genes associated with the image feature. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R2 = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. The prognostic value was confirmed in another independent cohort (Gene Expression Omnibus GSE 1456), with log-rank P = .00058 for recurrence-free survival and log-rank P = .0026 for overall survival. Conclusion Heterogeneous enhancement patterns of tumor-adjacent parenchyma at MR imaging are associated with the tumor necrosis signaling pathway and poor survival in breast cancer. © RSNA, 2017 Online supplemental material is available for this article.

Predictors of Clinical Outcome after Prostate Artery Embolization with Spherical and Nonspherical Polyvinyl Alcohol Particles in Patients with Benign Prostatic Hyperplasia.

Purpose To assess predictors of outcome after prostate artery embolization (PAE) for benign prostatic hyperplasia with spherical particle polyvinyl alcohol (sPVA) and compare outcomes with the use of nonspherical particle polyvinyl alcohol (nsPVA). Materials and Methods This was a single-center retrospective institutional review board-approved study conducted from 2009 to 2015 in patients undergoing PAE with sPVA (n = 186; mean age ± standard deviation, 65.5 years ± 7.7) and nsPVA (n = 300; mean age, 65.3 years ± 7.6). The two cohorts were compared and analyzed for predictors of outcome with a Cox proportional hazards model and linear regression. Post-PAE prostate ischemia was measured with contrast material-enhanced magnetic resonance (MR) imaging in 23 patients with nsPVA and 25 patients with sPVA. The 24-hour post-PAE prostate-specific antigen (PSA) level was registered in 133 patients with sPVA. Prognostic values of MR imaging and PSA levels 24 hours after PAE were assessed with Cox and random-effects regressions. Results Predictors of clinical failure were older age (age over 65 years, P = .002), unilateral procedure (P = .002), and higher baseline International Prostate Symptom Score (IPSS, P = .033). Adjusted hazard ratio for clinical failure of sPVA was 1.273 (P = .16). Acute urinary retention was a predictor of lower IPSS after PAE (P = .002). The mean proportion of prostate ischemia was 11% with sPVA and 10% with nsPVA (P = .65). Lower IPSS after PAE was associated with a higher proportion of prostate ischemia (P = .009). Patients with a PSA level of at least 75 ng/mL (75 μg/L) 24 hours after PAE had a greater decrease in IPSS (P = .01). Prostate ischemic volume and PSA level 24 hours after PAE were correlated (Pearson r = 0.64, P = .014). Conclusion Clinical outcome was similar after PAE with sPVA and nsPVA. Younger age (up to 65 years), bilateral PAE, lower baseline IPSS, and acute urinary retention were predictors of better clinical outcome. The PSA level 24 hours after PAE correlated with prostate ischemia, and both correlated with clinical outcome. (©) RSNA, 2016.

Effect of Radiofrequency Transmit Field Correction on Quantitative Dynamic Contrast-enhanced MR Imaging of the Breast at 3.0 T.

To investigate the effects of radiofrequency transmit field (B1(+)) correction on (a) the measured T1 relaxation times of normal breast tissue and malignant lesions and (b) the pharmacokinetically derived parameters of malignant breast lesions at 3 T. Ethics approval and informed consent were obtained. Between May 2013 and January 2014, 30 women (median age, 58 years; range, 32-83 years) with invasive ductal carcinoma of at least 10 mm were recruited to undergo dynamic contrast material-enhanced magnetic resonance (MR) imaging before surgery. B1(+) and T1 mapping sequences were performed to determine the effect of B1(+) correction on the native tissue relaxation time (T10) of fat, parenchyma, and malignant lesions in both breasts. Pharmacokinetic parameters were calculated before and after correction for B1(+) variations. Results were correlated with histologic grade by using the Kruskal-Wallis test. Measurements showed a mean 37% flip angle difference between the right and left breast, which resulted in a 61% T10 difference in fat and a 41.5% difference in parenchyma between the two breasts. The T1 of lesions in the right breast increased by 58%, whereas that of lesions in the left breast decreased by 30% after B1(+) correction. The whole-tumor transendothelial permeability across the vascular compartment(K(trans)) of lesions in the right breast decreased by 41%, and that of lesions in the left breast increased by 46% after correction. A systematic increase in K(trans) was observed, with significant differences found across the histologic grades (P < .001). The effect size of B1(+) correction on K(trans) calculation was large for lesions in the right breast and moderate for lesions in the left breast (Cohen effect size, d = 0.86 and d = 0.59, respectively). B1(+) correction demonstrates a substantial effect on the results of quantitative dynamic contrast-enhanced analysis of breast tissue at 3 T, which propagates into the pharmacokinetic analysis of tumors that is dependent on whether the tumor is located in the right or left breast.

Improving the Accuracy of Computer-aided Diagnosis for Breast MR Imaging by Differentiating between Mass and Nonmass Lesions.

To determine suitable features and optimal classifier design for a computer-aided diagnosis (CAD) system to differentiate among mass and nonmass enhancements during dynamic contrast material-enhanced magnetic resonance (MR) imaging of the breast. Two hundred eighty histologically proved mass lesions and 129 histologically proved nonmass lesions from MR imaging studies were retrospectively collected. The institutional research ethics board approved this study and waived informed consent. Breast Imaging Reporting and Data System classification of mass and nonmass enhancement was obtained from radiologic reports. Image data from dynamic contrast-enhanced MR imaging were extracted and analyzed by using feature selection techniques and binary, multiclass, and cascade classifiers. Performance was assessed by measuring the area under the receiver operating characteristics curve (AUC), sensitivity, and specificity. Bootstrap cross validation was used to predict the best classifier for the classification task of mass and nonmass benign and malignant breast lesions. A total of 176 features were extracted. Feature relevance ranking indicated unequal importance of kinetic, texture, and morphologic features for mass and nonmass lesions. The best classifier performance was a two-stage cascade classifier (mass vs nonmass followed by malignant vs benign classification) (AUC, 0.91; 95% confidence interval (CI): 0.88, 0.94) compared with one-shot classifier (ie, all benign vs malignant classification) (AUC, 0.89; 95% CI: 0.85, 0.92). The AUC was 2% higher for cascade (median percent difference obtained by using paired bootstrapped samples) and was significant (P = .0027). Our proposed two-stage cascade classifier decreases the overall misclassification rate by 12%, with 72 of 409 missed diagnoses with cascade versus 82 of 409 missed diagnoses with one-shot classifier. Separately optimizing feature selection and training classifiers for mass and nonmass lesions improves the accuracy of CAD for breast MR imaging. By cascading classifiers, we achieved a significant improvement in performance with respect to the use of a one-shot classifier. Our cascaded classifier may provide an advantage for screening women at high risk for breast cancer, in whom the ability to diagnose cancers at an early stage is of primary importance.

The Diagnostic Performance of Dynamic Contrast-enhanced MR Imaging for Detection of Small Hepatocellular Carcinoma Measuring Up to 2 cm: A Meta-Analysis.

To determine the performance of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the diagnosis of small (≤2-cm) hepatocellular carcinoma (HCC) and to identify factors that influence this performance. Medline and Embase databases were searched for studies performed from January 2000 to March 2014 in which the performance of MR imaging was reported for the detection of HCC up to 2 cm on either a lesion- or patient-based level, with sufficient data to construct 2 × 2 contingency tables. Diagnostic performance was quantitatively pooled for all studies by using a bivariate random-effects model with exploration involving subgroup analysis, meta-regression, and determination of study heterogeneity. Twenty-two studies with 1387 small HCC lesions in 1908 patients met inclusion criteria. Heterogeneity was higher for sensitivity (range, 30%-99%) than specificity (range, 61%-100%). Overall sensitivity was 78% (95% confidence interval [CI]: 68%, 85%; I(2) = 89%), and overall specificity was 92% (95% CI: 88%, 95%; I(2) = 69%). The primary potential source of bias was use of explant as the reference standard in only 13% of studies, although lower sensitivity in such studies was not significant (59% vs 80%, P = .165). Sensitivities were significantly higher for studies that originated from Asia compared with those that originated elsewhere (89% vs 71%, P = .028), those performed with hepatobiliary phase imaging compared with those without (87% vs 65%, respectively; P = .004), and those in which gadoxetate disodium was used versus an extracellular agent (92% vs 67%, P ≤ .001). Specificity was not significantly different between subgroups (P ≥ .122). At pairwise meta-regression analysis with either study origin from Asia or performance of hepatobiliary phase imaging, only gadoxetate disodium contrast agent showed significant independent association with higher sensitivity (P = .002-.007). Results of this meta-analysis suggest that dynamic contrast-enhanced MR imaging has moderate sensitivity and excellent specificity in the detection of HCC up to 2 cm. Gadoxetate disodium contrast agent showed the strongest association with increased sensitivity.

Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer.

To retrospectively investigate whether parenchymal enhancement in dynamic contrast material-enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. After obtaining approval of the institutional review board and patients' written informed consent, 531 women with unilateral invasive breast cancer underwent dynamic contrast-enhanced MR imaging between 2000 and 2008. The contralateral parenchyma was segmented automatically, in which the mean of the top 10% late enhancement was calculated. Cox regression was used to test associations between parenchymal enhancement, patient and tumor characteristics, and overall survival and invasive disease-free survival. Subset analyses were performed and stratified according to immunohistochemical subtypes and type of adjuvant treatment received. Median follow-up was 86 months. Age (P < .001) and immunohistochemical subtype (P = .042) retained significance in multivariate analysis for overall survival. In patients with estrogen receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer (n = 398), age (P < .001), largest diameter on MR images (P = .049), and parenchymal enhancement (P = .011) were significant. In patients who underwent endocrine therapy (n = 174), parenchymal enhancement was the only significant covariate for overall survival and invasive disease-free survival (P < .001). Results suggest that parenchymal enhancement in the contralateral breast of patients with invasive unilateral breast cancer is significantly associated with long-term outcome, particularly in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Lower value of the mean top 10% enhancement of the parenchyma shows potential as a predictive biomarker for relatively poor outcome in patients who undergo endocrine therapy. These results should, however, be validated in a larger study.

Dynamic Contrast-enhanced MR Lymphangiography: Feasibility Study in Swine

To demonstrate the feasibility of dynamic four-dimensional ( 4D four-dimensional ) intranodal contrast material-enhanced magnetic resonance (MR) lymphangiography with inguinal lymph node injection of gadopentetate dimeglumine. All procedures were performed in accordance with the guidelines on the use of animals in research and were approved by the animal care and use committee. Five swine underwent nonenhanced MR lymphangiography with a heavily T2-weighted MR sequence, bilateral inguinal lymph node injection of 2 mL of undiluted gadopentetate at a rate of 1 mL/min, and 60 minutes of MR imaging with T1-weighted high-spatial- and high-temporal-resolution MR angiography. Images were reviewed by a radiologist with expertise in lymphatic imaging and a pediatric cardiac MR imaging specialist for visualization of the thoracic duct ( TD thoracic duct ). Categorical variables were compared by using the exact conditional McNemar test. A difference with a P value less than .05 was considered significant. The TD thoracic duct was visualized in three of the five animals (60%) on T2-weighted images. In contrast, the TD thoracic duct was visualized in all five of the animals (100%) after contrast agent injection (P = .25). The median time for flow of the contrast agent through the lymphatic system to the TD thoracic duct outlet was 244 seconds (range, 201-387 seconds). Enhancement was seen in the TD thoracic duct up to 1 hour after injection. All animals survived without any complications. Dynamic 4D four-dimensional contrast-enhanced MR lymphangiography with intranodal injection of gadopentetate dimeglumine is feasible, produces good images of the central lymphatic system, and demonstrates the time course of flow of contrast agent up the central lymphatic ducts. On the basis of the results of this initial animal experiment, it appears that dynamic 4D four-dimensional contrast-enhanced MR lymphangiography is potentially feasible and safe with commercially available contrast agents.

Pattern Analysis of Dynamic Susceptibility Contrast-enhanced MR Imaging Demonstrates Peritumoral Tissue Heterogeneity

To augment the analysis of dynamic susceptibility contrast material-enhanced magnetic resonance (MR) images to uncover unique tissue characteristics that could potentially facilitate treatment planning through a better understanding of the peritumoral region in patients with glioblastoma. Institutional review board approval was obtained for this study, with waiver of informed consent for retrospective review of medical records. Dynamic susceptibility contrast-enhanced MR imaging data were obtained for 79 patients, and principal component analysis was applied to the perfusion signal intensity. The first six principal components were sufficient to characterize more than 99% of variance in the temporal dynamics of blood perfusion in all regions of interest. The principal components were subsequently used in conjunction with a support vector machine classifier to create a map of heterogeneity within the peritumoral region, and the variance of this map served as the heterogeneity score. The calculated principal components allowed near-perfect separability of tissue that was likely highly infiltrated with tumor and tissue that was unlikely infiltrated with tumor. The heterogeneity map created by using the principal components showed a clear relationship between voxels judged by the support vector machine to be highly infiltrated and subsequent recurrence. The results demonstrated a significant correlation (r = 0.46, P < .0001) between the heterogeneity score and patient survival. The hazard ratio was 2.23 (95% confidence interval: 1.4, 3.6; P < .01) between patients with high and low heterogeneity scores on the basis of the median heterogeneity score. Analysis of dynamic susceptibility contrast-enhanced MR imaging data by using principal component analysis can help identify imaging variables that can be subsequently used to evaluate the peritumoral region in glioblastoma. These variables are potentially indicative of tumor infiltration and may become useful tools in guiding therapy, as well as individualized prognostication.

Adult Bile Duct Strictures: Role of MR Imaging and MR Cholangiopancreatography in Characterization

Bile duct strictures in adults are secondary to a wide spectrum of benign and malignant pathologic conditions. Benign causes of bile duct strictures include iatrogenic causes, acute or chronic pancreatitis, choledocholithiasis, primary sclerosing cholangitis, IgG4-related sclerosing cholangitis, liver transplantation, recurrent pyogenic cholangitis, Mirizzi syndrome, acquired immunodeficiency syndrome cholangiopathy, and sphincter of Oddi dysfunction. Malignant causes include cholangiocarcinoma, pancreatic adenocarcinoma, and periampullary carcinomas. Rare causes include biliary inflammatory pseudotumor, gallbladder carcinoma, hepatocellular carcinoma, metastases to bile ducts, and extrinsic bile duct compression secondary to periportal or peripancreatic lymphadenopathy. Contrast material-enhanced magnetic resonance (MR) imaging with MR cholangiopancreatography is extremely helpful in the noninvasive evaluation of patients with obstructive jaundice, an obstructive pattern of liver function, or incidentally detected biliary duct dilatation. Some of these conditions may show characteristic findings at MR imaging-MR cholangiopancreatography that help in making a definitive diagnosis. Although endoscopic retrograde cholangiopancreatography with tissue biopsy or surgery is needed for the definitive diagnosis of many of these strictures, certain MR imaging characteristics of the narrowed segment (eg, thickened wall, long-segment involvement, asymmetry, indistinct outer margin, luminal irregularity, hyperenhancement relative to the liver parenchyma) may favor a malignant cause. Awareness of the various causes of bile duct strictures in adults and familiarity with their appearances at MR imaging-MR cholangiopancreatography are important for accurate diagnosis and optimal patient management.

Outcome prediction in patients with glioblastoma by using imaging, clinical, and genomic biomarkers: focus on the nonenhancing component of the tumor.

To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.

Background Parenchymal Signal Enhancement Ratio at Preoperative MR Imaging: Association with Subsequent Local Recurrence in Patients with Ductal Carcinoma in Situ after Breast Conservation Surgery

To retrospectively investigate whether the background parenchymal features around a tumor at preoperative dynamic contrast material-enhanced magnetic resonance (MR) imaging are associated with ipsilateral breast tumor recurrence (IBTR)-free survival in patients with ductal carcinoma in situ (DCIS) after breast conservation surgery. The institutional review board approved this study, and the requirement for informed consent was waived. Between 2004 and 2009, 215 consecutive women with pure DCIS who had undergone preoperative dynamic contrast-enhanced MR imaging and curative breast conservation surgery were identified. Clinical-pathologic features (age, menopausal status, presentation of clinical findings, biopsy method, tumor size, nuclear grade, hormonal receptor status, margin status, and adjuvant therapy) and MR imaging features (lesion size, background parenchymal enhancement grade, fibroglandular density, parenchymal signal enhancement ratio [SER] around the tumor, lesion type, and lesion kinetics) were analyzed. A Cox proportional hazards model was used to determine the association between MR imaging variables and IBTR-free survival after controlling for clinical-pathologic variables. Reproducibility of SER measurements was evaluated by using the intraclass correlation coefficient. There were 15 of 215 (7.0%) IBTR cases (nine DCIS cases and six invasive cases) at a median of 36 months (range, 11-61 months). Multivariate analysis showed that higher parenchymal SER (hazard ratio [HR] = 2.028, P < .001 for reader 1; HR = 1.652, P < .001 for reader 2) and larger histologic tumor size (HR = 1.360, P = .009 for reader 1; HR = 1.402, P = .006 for reader 2) were independent factors associated with worse IBTR-free survival. The intraclass correlation coefficient of SER measurements between two readers was 0.852 (95% confidence interval: 0.811, 0.885). Higher parenchymal SER around the tumor at preoperative dynamic contrast-enhanced MR imaging and larger histologic tumor size were independent factors associated with worse IBTR-free survival in patients with DCIS after breast conservation surgery.

Patterns of Nonmasslike Enhancement at Screening Breast MR Imaging of High-Risk Premenopausal Women

Current U.S. recommendations for breast cancer screening of women with at least a 20%-25% lifetime risk of developing breast cancer include contrast material-enhanced magnetic resonance (MR) imaging of the breasts. The cancer detection rate in high-risk women undergoing screening MR imaging is approximately 10 times higher than that in normal-risk women undergoing screening mammography. Many of these high-risk women commence MR imaging screening while they are premenopausal, when the breasts are most influenced by cyclical hormonal changes. Healthy premenopausal breast tissue enhances in a cyclical and variable manner. This enhancement is described as background enhancement. Typically, enhancement of normal breast tissue occurs in a symmetric and diffuse pattern, and there is little diagnostic difficulty in classifying it as normal background parenchymal enhancement. However, sometimes the pattern is more focal, asymmetric, or regional. It may then be described as nonmasslike enhancement, an observation associated with both benign and malignant breast pathologic conditions. A review of the morphologic features and internal enhancement patterns in normal but nondiffuse background enhancement and abnormal nonmasslike enhancement in high-risk premenopausal women can help improve interpretive specificity and decrease false-positive interpretations. MR imaging pitfalls and interpretation strategies for localized background enhancement and pathologic nonmasslike enhancement in this high-risk population are highlighted. In evaluating nonmasslike enhancement, the use of the Breast Imaging Reporting and Data System (BI-RADS) lexicon to perform careful analysis of morphologic features, along with an understanding of the role and limitations of kinetic information, will help balance early breast cancer detection against false-positive interpretation.

Imaging of Juvenile Idiopathic Arthritis: A Multimodality Approach

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by synovial inflammation and is the most common rheumatic complaint in children. To facilitate research and treatment, JIA has been further classified on the basis of the number of joints involved, additional symptoms, family history, and serologic findings. Imaging in patients with JIA has historically relied on radiography, which allows the accurate assessment of chronic changes of JIA, including growth disturbances, periostitis, and joint malalignment. However, radiographic findings of active inflammation are nonspecific, and, in the past, clinical evaluation has taken precedence over imaging of acute disease. Recent advances in disease-modifying therapeutic agents that can help prevent long-term disability in patients with JIA have led to greater emphasis on the detection of early joint-centered inflammation that cannot be accurately assessed radiographically and may not be evident clinically. Both contrast material-enhanced magnetic resonance (MR) imaging and Doppler ultrasonography (US) are well suited for this application and are playing an increasingly important role in diagnosis, risk stratification, treatment monitoring, and problem solving. Contrast-enhanced MR imaging is the most sensitive technique for the detection of synovitis and is the only modality that can help detect bone marrow edema, both of which indicate active inflammation. US is more sensitive than radiography for the detection of synovial proliferation and effusions and is particularly useful in the evaluation of small peripheral joints. The complexity of the temporomandibular and sacroiliac joints limits the usefulness of radiographic or US evaluation, and contrast-enhanced MR imaging is the preferred modality for evaluation of these structures.

Recurrent Glioblastoma: Optimum Area under the Curve Method Derived from Dynamic Contrast-enhanced T1-weighted Perfusion MR Imaging

To determine whether the ratio of the initial area under the time-signal intensity curve (AUC) (IAUC) to the final AUC--or AUCR--derived from dynamic contrast material-enhanced magnetic resonance (MR) imaging can be an imaging biomarker for distinguishing recurrent glioblastoma multiforme (GBM) from radiation necrosis and to compare the diagnostic accuracy of the AUCR with commonly used model-free dynamic contrast-enhanced MR imaging parameters. The institutional review board approved this retrospective study and waived the informed consent requirement. Fifty-seven consecutive patients with pathologically confirmed recurrent GBM (n = 32) or radiation necrosis (n = 25) underwent dynamic contrast-enhanced MR imaging. Histogram parameters of the IAUC at 30, 60, and 120 seconds and the AUCR, which included the mean value at the higher curve of the bimodal histogram (mAUCR(H)), as well as 90th percentile cumulative histogram cutoffs, were calculated and were correlated with final pathologic findings. The best predictor for differentiating recurrent GBM from radiation necrosis was determined by means of receiver operating characteristic (ROC) curve analysis. The demographic data were not significantly different between the two patient groups. There were statistically significant differences in all of the IAUC and AUCR parameters between the recurrent GBM and the radiation necrosis patient groups (P < .05 for each). ROC curve analyses showed mAUCR(H) to be the best single predictor of recurrent GBM (mAUCR(H) for recurrent GBM = 0.35 ± 0.11 [standard deviation], vs 0.19 ± 0.17 for radiation necrosis; P < .0001; optimum cutoff, 0.23), with a sensitivity of 93.8% and a specificity of 88.0%. A bimodal histogram analysis of AUCR derived from dynamic contrast-enhanced MR imaging can be a potential noninvasive imaging biomarker for differentiating recurrent GBM from radiation necrosis. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130016/-/DC1.

Measurement of Tissue Interstitial Volume in Healthy Patients and Those with Amyloidosis with Equilibrium Contrast-enhanced MR Imaging

To investigate equilibrium contrast material-enhanced magnetic resonance (MR) imaging measurement of extracellular volume (ECV) fraction within healthy abdominal tissues and to test the hypotheses that tissue ECV in systemic amyloid light-chain (AL) amyloidosis is greater than in healthy patients and show that this increase correlates with organ amyloid burden. A local ethics committee approved the study and all patients gave written informed consent. Forty healthy volunteers (18 men, 22 women; median age, 43 years; age range, 24-88 years) and 67 patients with AL amyloidosis (43 men, 24 women; median age, 65 years; age range, 38-81 years) underwent equilibrium MR imaging of the upper abdomen. ECV was measured in the liver, spleen, and paravertebral muscle. Patients with amyloidosis also underwent serum amyloid P (SAP) component scintigraphy so that specific organ involvement by amyloid could be scored. Variation in ECV between tissues was assessed by using a Friedman Test. Tissue ECV in healthy and amyloidosis groups were compared by using a Mann-Whitney U test. Spearman correlation was used to test for an association between the organ SAP score and ECV. ECV measured at equilibrium MR imaging varied significantly between organs in healthy volunteers (χ(2) = 31.0; P < .001). ECV was highest in the spleen (0.34), followed by liver (0.29) and muscle (0.09). ECVs measured within the spleen (0.39; P< .001), liver (0.31; P = .005), and muscle (0.16; P< .001) were significantly higher in patients with amyloidosis than in healthy control subjects. ECV measured in the liver and spleen showed increasing organ amyloid burden assessed at SAP scintigraphy (liver, rs = 0.54; spleen, rs = 0.57). Equilibrium MR imaging can be used to define ECV within healthy tissues. ECV is increased in amyloidosis compared with healthy tissues, and this increase correlates with rising tissue amyloid burden.

Neuroendocrine Liver Metastasis Treated by Using Intraarterial Therapy: Volumetric Functional Imaging Biomarkers of Early Tumor Response and Survival

To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.

Dynamic Contrast-enhanced MR Imaging of Carotid Atherosclerotic Plaque: Model Selection, Reproducibility, and Validation

To compare four known pharmacokinetic models for their ability to describe dynamic contrast material-enhanced magnetic resonance (MR) imaging of carotid atherosclerotic plaques, to determine reproducibility, and to validate the results with histologic findings. The study was approved by the institutional medical ethics committee. Written informed consent was obtained from all patients. Forty-five patients with 30%-99% carotid stenosis underwent dynamic contrast-enhanced MR imaging. Plaque enhancement was measured at 16 time points at approximately 25-second image intervals by using a gadolinium-based contrast material. Pharmacokinetic parameters (volume transfer constant, K(trans); extracellular extravascular volume fraction, v(e); and blood plasma fraction, v(p)) were determined by fitting a two-compartment model to plaque and blood gadolinium concentration curves. The relative fit errors and parameter uncertainties were determined to find the most suitable model. Sixteen patients underwent imaging twice to determine reproducibility. Carotid endarterectomy specimens from 16 patients who were scheduled for surgery were collected for histologic validation. Parameter uncertainties were compared with the Wilcoxon signed rank test. Reproducibility was assessed by using the coefficient of variation. Correlation with histologic findings was evaluated with the Pearson correlation coefficient. The mean relative fit uncertainty (±standard error) for K(trans) was 10% ± 1 with the Patlak model, which was significantly lower than that with the Tofts (20% ± 1), extended Tofts (33% ± 3), and extended graphical (29% ± 3) models (P < .001). The relative uncertainty for v(p) was 20% ± 2 with the Patlak model and was significantly higher with the extended Tofts (46% ± 9) and extended graphical (35% ± 5) models (P < .001). The reproducibility (coefficient of variation) for the Patlak model was 16% for K(trans) and 26% for v(p). Significant positive correlations were found between K(trans) and the endothelial microvessel content determined on histologic slices (Pearson ρ = 0.72, P = .005). The Patlak model is most suited for describing carotid plaque enhancement. Correlation with histologic findings validated K(trans) as an indicator of plaque microvasculature, and the reproducibility of K(trans) was good.

Incidence of Nephrogenic Systemic Fibrosis after Adoption of Restrictive Gadolinium-based Contrast Agent Guidelines

To retrospectively determine the incidence of nephrogenic systemic fibrosis (NSF) in a large academic medical center after the adoption of restrictive gadolinium-based contrast agent (GBCA) administration guidelines. For this retrospective HIPAA-compliant study, institutional review board approval was obtained and the requirement for informed consent was waived. Restrictive GBCA guidelines were adopted in May 2007. The guidelines (a) require a recent serum creatinine level measurement in any patient who is aged 60 years or older and/or at risk for renal disease, (b) limit the maximal weight-based GBCA dose administered to any patient with an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/m(2) to 20 mL, and (c) prohibit the administration of any GBCA in patients who have an eGFR lower than 30 mL/min/m(2) and/or are undergoing chronic dialysis treatment (except in emergency situations). The electronic medical records were searched for all contrast material-enhanced magnetic resonance (MR) imaging examinations performed during the post-guidelines adoption period between January 2008 and March 2010 and the pre-guidelines adoption and transitional period between January 2002 and December 2007. Separate pathology records were searched for biopsy-confirmed cases of NSF during the same study periods. The incidences of NSF during the pre-guidelines adoption and transitional period and post-guidelines adoption period were compared by using the paired Z test. A total of 52,954 contrast-enhanced MR examinations were performed during the post-guidelines adoption period. Of these 52,954 examinations, 46,464 (88%) were performed in adult patients with an eGFR of 60 mL/min/m(2) or higher or presumed normal renal function and 6454 (12%) were performed in patients with an eGFR of 30-59 mL/min/m(2). Thirty-six patients with an eGFR lower than 30 mL/min/m(2) underwent contrast-enhanced MR imaging for emergent indications. Review of the pathology records for January 2008 to September 2010 revealed no new cases of NSF resulting from GBCA exposure. After restrictive guidelines regarding GBCA administration were instituted, no new cases of NSF were identified among 52,954 contrast-enhanced MR examinations, including those performed in patients with an eGFR lower than 60 mL/min/m(2).

Use of Dynamic Contrast-enhanced MR Imaging to Predict Survival in Patients with Primary Breast Cancer Undergoing Neoadjuvant Chemotherapy

To investigate whether early changes in vascular parameters determined with dynamic contrast material-enhanced magnetic resonance (MR) imaging after two cycles of neoadjuvant chemotherapy (NAC) are predictive of disease-free and overall survival in primary breast cancer. Institutional ethics approval and informed consent were obtained. Patients with primary breast cancer (median age, 45 years; age range, 22-70 years) recruited from January 2001 to September 2008 underwent dynamic contrast-enhanced MR imaging before and after two cycles of NAC. Quantitative and semiquantitative kinetic parameters were calculated, including the volume transfer constant (K(trans)) and the initial area under the gadolinium concentration-time curve over 60 seconds (IAUGC(60)). Cut points optimized to the receiver operating characteristic curve were used to dichotomize MR imaging data for Kaplan-Meier survival analysis. MR imaging parameters and known prognostic indicators in primary breast cancer were correlated with disease-free and overall survival by using the Cox proportional hazards model for univariate and multivariate analyses. MR imaging was performed before (n = 62) and after (n = 58) two cycles of NAC. The median follow-up time was 43.9 months for disease-free survival and 60.3 months for overall survival. There were 28 recurrences; 26 patients had distant metastases (two had additional local recurrence) and two had local recurrence only. There were 20 deaths, all of which were related to breast cancer. At univariate analysis, progesterone receptor status, the type of surgery performed, higher posttreatment K(trans) (P = .048), and larger posttreatment IAUGC(60) (P = .035) were significant predictors of worse disease-free survival. At multivariate analysis, progesterone receptor status (P = .002) and mean transit time (P = .025) were significant predictors of disease-free survival. Univariate analysis showed that clinical tumor stage (P = .005), progesterone receptor status (P = .025), and type of surgery performed (P = .017) were significant predictors of overall survival. Higher posttreatment K(trans) (P = .043), larger IAUGC(60) (P = .029), and larger tumor size at posttreatment MR imaging were predictive of worse overall survival (P = .018). Of these variables, K(trans) remained an independent indicator of overall survival (P = .038). Higher posttreatment tumor vascularization as depicted with dynamic contrast-enhanced MR imaging may be associated with higher recurrence and lower survival rates. Dynamic contrast-enhanced MR imaging parameters, in conjunction with traditional prognostic factors, have the potential to be prognostic biomarkers for disease-free and overall survival in primary breast cancer.

Kidney Function: Glomerular Filtration Rate Measurement with MR Renography in Patients with Cirrhosis

To assess the accuracy of glomerular filtration rate (GFR) measurements obtained with low-contrast agent dose dynamic contrast material-enhanced magnetic resonance (MR) renography in patients with liver cirrhosis who underwent routine liver MR imaging, with urinary clearance of technetium 99m ((99m)Tc) pentetic acid (DTPA) as the reference standard. This HIPAA-compliant study was institutional review board approved. Written informed patient consent was obtained. Twenty patients with cirrhosis (14 men, six women; age range, 41-70 years; mean age, 54.6 years) who were scheduled for routine 1.5-T liver MR examinations to screen for hepatocellular carcinoma during a 6-month period were prospectively included. Five-minute MR renography with a 3-mL dose of gadoteridol was performed instead of a routine test-dose timing examination. The GFR was estimated at MR imaging with use of two kinetic models. In one model, only the signal intensities in the aorta and kidney parenchyma were considered, and in the other, renal cortical and medullary signal intensities were treated separately. The GFR was also calculated by using serum creatinine levels according to the Cockcroft-Gault and modification of diet in renal disease (MDRD) formulas. All patients underwent a (99m)Tc-DTPA urinary clearance examination on the same day to obtain a reference GFR measurement. The accuracies of all MR- and creatinine-based GFR estimations were compared by using Wilcoxon signed rank tests. The mean reference GFR, based on (99m)Tc-DTPA clearance, was 74.9 mL/min/1.73 m(2) ± 27.7 (standard deviation) (range, 10.3-120.7 mL/min/1.73 m(2)). With both kinetic models, 95% of MR-based GFRs were within 30% of the reference values, whereas only 40% and 60% of Cockcroft-Gault- and MDRD-based GFRs, respectively, were within this range. MR-based GFR estimates were significantly more accurate than creatinine level-based estimates (P < .001). GFR assessment with MR imaging, which outperformed the Cockcroft-Gault and MDRD formulas, adds less than 10 minutes of table time to a clinically indicated liver MR examination without ionizing radiation. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101338/-/DC1.