Identification of drug responsible glycogene signature in liver carcinoma from meta-analysis using RNA-seq data.

Glycans have attracted much attention in cancer therapeutic strategies, and cell surface proteins and lipids with glycans are known to be altered during the carcinogenic process. However, our understanding of how the glycogenes profile responds to drug stimulation remains incomplete. In this study, we search public databases for Sequence Read Archive data on drug-treated liver cancer cells, with the aim to comprehensively analyze the drug responses of glycogenes via bioinformatic meta-analysis. The study comprised 86 datasets, encompassing eight distinct liver cancer cell lines and 13 different drugs. Differentially expressed genes were quantified, and 399 glycogenes were identified. The glycogenes signature was then analyzed using bioinformatics methodologies. In the Protein-protein interaction network analysis, we identified drug-responsive glycogenes such as Beta-1,4-Galactosyltransferase 1, GDP-Mannose 4,6-Dehydratase, UDP-Glucose Ceramide Glucosyltransferase, and Solute Carrier Family 2 Member 4 as key glycan biomarkers. In the enrichment analysis using the pathway list of glycogenes, the results also demonstrated that drug stimulation resulted in alterations to glycopathway-related genes involved in several processes, namely O-Mannosylation, POMGNT2 Type, Capping, Heparan Sulfate Sulfation, and Glucuronidation pathways. These genes and pathways commonly exhibit variable expression across multiple liver cancer cells in response to the same drug, making them potential targets for new cancer therapies. In addition to their primary roles, drugs may also participate in the regulation of glycans. The insights from this study could pave the way for the development of liver cancer therapies that target the regulation of gene profiles involved in the biosynthesis of glycans.

Long-term outcomes of a phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumors of the stomach.

BACKGROUND: Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. METHODS: Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6-9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. RESULTS: A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. CONCLUSIONS: Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study.

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Im in this issue.

Phase II Study of the Reuse of Trastuzumab with Docetaxel beyond Progression after First-Line Treatment in Second-Line Treatment for Unresectable, Metastatic Gastric Cancer (T-CORE1203).

Whether trastuzumab use beyond disease progression is beneficial in second-line treatment for patients with unresectable human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains to be elucidated. We conducted this phase II study to assess whether trastuzumab plus docetaxel was effective for patients with previously treated advanced HER2-positive gastric cancer. This trial was a single-arm, open-label, multicenter, phase II study, conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE). Patients aged 20 years or older who had advanced HER2-positive gastric cancer and were refractory to trastuzumab, fluoropyrimidine, and cisplatin were enrolled. Patients were treated with 6 mg/kg trastuzumab and 60 mg/m2 docetaxel every 3 weeks. The primary endpoint was the overall response rate. The threshold overall response rate was estimated to be at 15%. Secondary endpoints were progression-free survival, 6-month survival rate, overall survival, and toxicities. A total of 27 patients were enrolled from 7 hospitals. The median age was 67 years. Partial response was seen in 3 patients among the 26 evaluated patients. The overall response rate was at 11.5% (90% confidence interval 1.2%-21.8%). The median progression-free survival was 3.2 months, the 6-month survival rate was 85%, and the median overall survival was 11.6 months. Febrile neutropenia was observed in 14.8%. The most frequently observed grade 3 non-hematologic toxicity was anorexia (14.8%). The primary endpoint was not achieved. The results support a current consensus that the continuation of trastuzumab in second-line therapy for gastric cancer is not a recommended option.

Hyperintense Liver Masses at Hepatobiliary Phase Gadoxetic Acid-enhanced MRI: Imaging Appearances and Clinical Importance.

Gadoxetic acid, a hepatobiliary-specific contrast medium used for MRI, is becoming increasingly important in the detection and characterization of hepatic mass lesions. This medium is taken up by functioning hepatocytes, and the liver parenchyma is strongly enhanced in the hepatobiliary phase (HBP), during which hepatic mass lesions without functioning hepatocytes commonly show hypointensity. However, some hepatic mass lesions show hyperintensity in the HBP. Focal nodular hyperplasia (FNH) and FNH-like lesions show hyperintensity in the HBP owing to the uptake of gadoxetic acid by hyperplastic normal hepatocytes. The tumor cells of some types of hepatocellular adenoma (eg, ß-catenin-activated type, inflammatory type) and hepatocellular carcinoma (eg, green hepatoma) can show uptake of gadoxetic acid. Retention of gadoxetic acid in the extracellular space can cause hyperintensity of fibrotic tumors or hemangiomas during the HBP owing to the extracellular contrast agent characteristics of gadoxetic acid. During the HBP, peritumoral retention is observed in some tumors, such as hepatocellular carcinomas, gastrointestinal stromal tumors, and neuroendocrine tumors. Gadoxetic acid is excreted into the bile; therefore, biliary tract enhancement can be observed in the cystic components of intraductal papillary neoplasms of the bile duct. Intratumoral bile ducts can be observed in malignant lymphomas. Knowledge of these specific mechanisms, which can cause hyperintensity during the HBP depending on the pathologic or molecular background, is important not only for precise imaging-based diagnoses but also for understanding the pathogenesis of hepatic mass lesions. ©RSNA, 2019 See discussion on this article by Lalwani.

Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features.

AIM: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. METHODS: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. RESULTS: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1-22.2%) was more than threefold that of elastin (median 0.9%, range 0.1-9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. CONCLUSION: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity.

Improved visualization of a fine intrahepatic biliary duct on drip infusion cholangiography-computed tomography: Impact of knowledge-based iterative model reconstruction.

AIM: The purpose of this study was to investigate the visualization of fine biliary ducts with knowledge-based iterative model reconstruction (IMR) in low-dose drip infusion computed tomography (CT) cholangiography (DIC-CT) as compared with filtered back projection (FBP) and hybrid iterative reconstruction (iDose4 ). METHODS: A total of 38 patients underwent DIC-CT for living donor liver transplantation. CT was performed approximately 20 min after the end of the infusion of meglumine iotroxate (100 mL). Images were reconstructed using FBP, iDose4 , and IMR, and 1-mm slice images at fixed window level and width were prepared for assessment. Two reviewers independently evaluated the quality of visualization of the fine biliary ducts of the caudate lobe (B1) using a 5-point scale. The visualization scores of three reconstructed images were compared using the Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: For reviewer 1, the visualization score of IMR was significantly higher than that of FBP (P = 0.012), and tended to be higher than that of iDose4 (P = 0.078). For reviewer 2, the visualization score of IMR was significantly higher than those of both FBP and iDose4 (P < 0.01). CONCLUSIONS: IMR showed better visualization of B1 on DIC-CT than FBP or iDose4 . DIC-CT reconstructed with IMR may be useful to the anatomical grasp of biliary tracts in cases of hepatectomy.

Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality.

Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality. Objectives: To determine the role of imaging patterns on the risk of death and ILA progression. Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality. Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3-6.8;P < 0.0001), respectively. Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.

Reducing contrast dose using virtual monoenergetic imaging for aortic CTA.

Three-dimensional computed tomographic angiography (3D-CTA) is widely used to evaluate the inner diameters of vessels and the anatomical vascular structure prior to endoscopic aortic surgery or transcatheter valve implantation. Virtual monoenergetic imaging (VMI) is a new application in dual-energy CT (DECT). We evaluated the potential for contrast dose reduction in preoperative aortic CTA using VMI. To evaluate performance in terms of image quality and vessel shape, we quantified the contrast-to-noise ratio (CNR) and the vessel diameter using a cylinder phantom we developed, and used volume rendering to assess visual quality. All VMI had improved CNR values compared with conventional 120 kVp images at an iodine content of 15 mgI/mL. In each image, a virtual mono-energy of 40 keV yielded the highest CNR value, and an iodine content of 9 mgI/mL was comparable to that of conventional images with an iodine content of 15 mgI/mL. The circularity indices (CI) of the vascular model at 15, 12, and 9 mgI/mL were similar to those of the reference condition using conventional voltages; however, CI was degraded at iodine contents of 6 and 3 mgI/mL with VMI. In the case of iodine content of 15 mgI/mL, VMI was superior, with conventional image by visual evaluation. In the cases of iodine contents of 12 and 9 mgI/mL, image quality was judged to be almost the same level when comparing 12 and 9 mgI/mL to conventional images. In the case of 6 and 3 mgI/mL, reference image using conventional technique was superior to that of VMI. We demonstrated in that decreasing contrast iodine content is possible using VMI with an energy of 40 keV for preoperative aortic 3D-CTA.

Visualization of cerebrospinal fluid dynamics using multi-spin echo acquisition cine imaging (MUSACI).

PURPOSE: To evaluate the visualization of CSF dynamics using the novel method multi-spin echo acquisition cine imaging (MUSACI). METHODS: MUSACI is based on multi-echo volume isotropic turbo spin-echo acquisition (VISTA) with pulse gating. MUSACI images were acquired in 11 healthy volunteers (7 men, 4 women; age range, 24-46 y, mean age, 31.9 ± 5.51 y). We compared the CSF signal intensities (SIs) at multiple values of the effective echo time (TEeff ) at the lateral ventricle, the foramen of Monro, the third ventricle, and the fourth ventricle. We compared the CSF SI changes in MUSACI at multiple TEeff and the mean velocities in phase contrast (PC) at each trigger delay at the foramen of Monro, the third ventricle, and the fourth ventricle. RESULTS: The anterograde CSF motion from the aqueduct to the fourth ventricle, the retrograde motion from the aqueduct to the third ventricle, and the retrograde motion from the foramen of Monro to the lateral ventricle were observed with MUSACI. The CSF SIs at each TEeff in the foramen of Monro, the third ventricle, and the fourth ventricle were significantly lower than that at each TEeff in the lateral ventricle (P < 0.05). The CSF SI in MUSACI changed with the TEeff , and the CSF movements were observed at each trigger delay in PC. CONCLUSION: MUSACI can provide both high-resolution anatomical detail of the CSF passageways and physiologic information regarding CSF dynamics in a single scan.

In silico prediction of chromosome damage: comparison of three (Q)SAR models.

Two major endpoints for genotoxicity tests are gene mutation and chromosome damage (CD), which includes clastogenicity and aneugenicity detected by chromosomal aberration (CA) test or micronucleus (MN) test. Many in silico prediction systems for bacterial mutagenicity (i.e. Ames test results) have been developed and marketed. They show good performance for prediction of Ames mutagenicity. On the other hand, it seems that in silico prediction of CD does not progress as much as Ames prediction. Reasons for this include different mechanisms and detection methods, many false positives and conflicting test results. However, some (quantitative) structure-activity relationship ((Q)SAR) models (e.g. Derek Nexus [Derek], ADMEWorks [AWorks] and CASE Ultra [MCase]) can predict CA test results. Therefore, performances of the three (Q)SAR models were compared using the expanded Carcinogenicity Genotoxicity eXperience (CGX) dataset for understanding current situations and future development. The constructed dataset contained 440 chemicals (325 carcinogens and 115 non-carcinogens). Sensitivity, specificity, accuracy or applicability of each model were 56.0, 86.9, 68.6 or 89.1% in Derek, 67.7, 61.5, 65.2 or 99.3% in AWorks, and 91.0, 64.9, 80.5 or 97.7% in MCase, respectively. The performances (sensitivity and accuracy) of MCase were higher than those of Derek or AWorks. Analysis of predictivity of (Q)SAR models of certain chemical classes revealed no remarkable differences among the models. The tendency of positive prediction by (Q)SAR models was observed in alkylating agents, aromatic amines or amides, aromatic nitro compounds, epoxides, halides and N-nitro or N-nitroso compounds. In an additional investigation, high sensitivity but low specificity was noted in in vivo MN prediction by MCase. Refinement of test data to be used for in silico system (e.g. consideration of cytotoxicity or re-evaluation of conflicting test results) will be needed to improve performance of CD prediction.

A decision tree-based integrated testing strategy for tailor-made carcinogenicity evaluation of test substances using genotoxicity test results and chemical spaces.

Genotoxicity evaluation has been widely used to estimate the carcinogenicity of test substances during safety evaluation. However, the latest strategies using genotoxicity tests give more weight to sensitivity; therefore, their accuracy has been very low. For precise carcinogenicity evaluation, we attempted to establish an integrated testing strategy for the tailor-made carcinogenicity evaluation of test materials, considering the relationships among genotoxicity test results (Ames, in vitro mammalian genotoxicity and in vivo micronucleus), carcinogenicity test results and chemical properties (molecular weight, logKow and 179 organic functional groups). By analyzing the toxicological information and chemical properties of 230 chemicals, including 184 carcinogens in the Carcinogenicity Genotoxicity eXperience database, a decision tree for carcinogenicity evaluation was optimised statistically. A decision forest model was generated using a machine-learning method-random forest-which comprises thousands of decision trees. As a result, balanced accuracies in cross-validation of the optimised decision tree and decision forest model, considering chemical space (71.5% and 75.5%, respectively), were higher than balanced accuracy of an example regulatory decision tree (54.1%). Moreover, the statistical optimisation of tree-based models revealed significant organic functional groups that would cause false prediction in standard genotoxicity tests and non-genotoxic carcinogenicity (e.g., organic amide and thioamide, saturated heterocyclic fragment and aryl halide). In vitro genotoxicity tests were the most important parameters in all models, even when in silico parameters were integrated. Although external validation is required, the findings of the integrated testing strategies established herein will contribute to precise carcinogenicity evaluation and to determine new mechanistic hypotheses of carcinogenicity.

Clinical usefulness of right ventricular 3D area strain in the assessment of treatment effects of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: comparison with 2D feature-tracking MRI.

OBJECTIVES: To evaluate the usefulness of right ventricular (RV) area strain analysis via cardiac MRI (CMRI) as a tool for assessing the treatment effects of balloon pulmonary angioplasty (BPA) in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), RV area strain was compared to two-dimensional (2D) strain with feature-tracking MRI (FTMRI) before and after BPA. METHODS: We retrospectively analyzed 21 CTEPH patients who underwent BPA. End-systolic global area strain (GAS), longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were measured before and after BPA. Changes in GAS and RV ejection fraction (RVEF) values after BPA were defined as ΔGAS and ΔRVEF. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff of the strain at after BPA for detection of improved patients with decreased mean pulmonary artery pressure (mPAP) less than 30 mmHg and increased RVEF more than 50%. RESULTS: ROC analysis revealed the optimal cutoffs of strains (GAS, LS, CS, and RS) for identifying improved patients with mPAP < 30 mmHg (cutoff (%) = - 41.2, - 13.8, - 16.7, and 14.4: area under the curve, 0.75, 0.56, 0.65, and 0.75) and patients with RVEF > 50% (cutoff (%) = - 37.2, - 29.5, - 2.9, and 14.4: area under the curve, 0.81, 0.60, 0.56, and 0.56). CONCLUSIONS: Area strain analysis via CMRI may be a more useful tool for assessing the treatment effects of BPA in patients with CTEPH than 2D strains with FTMRI. KEY POINTS: • Area strain values can detect improvement of right ventricular (RV) pressure and function after balloon pulmonary angioplasty (BPA) equally or more accurately than two-dimensional strains. • Area strain analysis is a useful analytical method that reflects improvements in complex RV myocardial deformation by BPA. • Area strain analysis is a robust method with reproducibility equivalent to that of 2D strain analysis.

Amide proton transfer imaging to predict tumor response to neoadjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND AND AIM: The amount of proteins and peptides can be estimated with amide proton transfer (APT) imaging. Previous studies demonstrated the usefulness of APT imaging to predict tumor malignancy. We determined whether APT imaging can predict the tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC). METHODS: Seventeen patients with LARC who underwent a pretherapeutic magnetic resonance examination including APT imaging and NAC (at least two courses) were enrolled. The APT-weighted imaging (WI) signal intensity (SI) (%) was defined as magnetization transfer ratio asymmetry (MTRasym ) at the offset of 3.5 ppm. Each tumor was histologically evaluated for the degree of degeneration and necrosis and then classified as one of five histological Grades (0, none; 1a, less than 1/3; 1b, 1/3 to 2/3; 2, more than 2/3; 3, all). We compared the mean APTWI SIs of the tumors between the Grade 0/1a/1b (low-response group) and Grade 2/3 (high-response group) by Student's t-test. We used receiver operating characteristics curves to determine the diagnostic performance of the APTWI SI for predicting the tumor response. RESULTS: The mean APTWI SI of the low-response group (n = 12; 3.05 ± 1.61%) was significantly higher than that of the high-response group (n = 5; 1.14 ± 1.13%) (P = 0.029). The area under the curve for predicting the tumor response using the APTWI SI was 0.87. When ≥2.75% was used as an indicator of low-response status, 75% sensitivity and 100% specificity of the APTWI SI were obtained. CONCLUSION: Pretherapeutic APT imaging can predict the tumor response to NAC in patients with LARC.

Acceleration-selective arterial spin labeling MR angiography for visualization of brain arteriovenous malformations.

PURPOSE: To evaluate the performance of acceleration-selective arterial spin labeling (AccASL) MR angiography in the visualization of brain arteriovenous malformations (AVMs) in comparison with digital subtraction angiography (DSA) and time-of-flight (TOF) MR angiography. METHODS: Twenty-one patients with brain AVM (mean age 31.1 ± 18.6 years; 11 males, 10 females) underwent TOF and AccASL MR angiography and DSA. Two neuroradiologists conducted an observer study for detection, nidus size, eloquence, venous drainage pattern, and Spetzler-Martin (SM) grade. The evaluations included the visualization of each AVM component with reference to DSA and assessments of contrast-to-noise ratio (CNR). The kappa statistic, repeated measures analysis of variance, Wilcoxon matched pairs test, and paired t test were used. RESULTS: Both observers detected more AVMs with AccASL (95.2%, 90.5% for Observers 1 and 2) than with TOF (76.2% and 71.4%, respectively). The inter-modality agreement between AccASL and DSA was almost perfect for the eloquence, venous drainage pattern, and SM grade for Observer 1 and moderate for the venous drainage pattern and substantial for the eloquence and SM grade for Observer 2. The visualization scores were higher with AccASL than with TOF for the feeding artery (AccASL, 4.5 ± 1.0 vs. TOF, 3.9 ± 1.5, p = 0.0214), nidus (4.6 ± 1.1 vs. 3.2 ± 1.5, p = 0.0006), and draining vein (4.6 ± 1.0 vs. 2.2 ± 1.1, p < 0.0001), respectively. The CNRs in the nidus were higher in AccASL than in TOF (29.9 ± 16.7 vs. 20.8 ± 16.5, p = 0.0002), as in the draining vein (23.2 ± 13.0 vs. 12.6 ± 12.0, p = 0.0010), respectively. CONCLUSIONS: AccASL better visualized brain AVMs compared with TOF and was useful for grading without the use of contrast agents.

Degenerative changes in cartilage likely occur in the medial compartment after anterior cruciate ligament reconstruction.

PURPOSE: Magnetic resonance imaging with T1ρ mapping is used to quantify the amount of glycosaminoglycan in articular cartilage, which reflects early degenerative changes. The purposes of this study were to evaluate early degenerative changes in knees after anterior cruciate ligament (ACL) reconstruction by comparing T1ρ values before and 2 years after surgery and investigate whether surgical factors and clinical outcomes are related to differences in T1ρ values. METHODS: Fifty patients who underwent unilateral primary ACL reconstruction were evaluated using T1ρ mapping before and 2 years after surgery. Three regions of interest (ROIs) were defined in the cartilage associated with the medial (M) and lateral (L) weight-bearing areas of the femoral condyle (FC) (anterior: MFC1 and LFC1, middle: MFC2 and LFC2, and posterior: MFC3 and LFC3). Two ROIs associated with the tibial plateau (T) were defined (anterior: MT1 and LT1, and posterior: MT2 and LT2). T1ρ values within the ROIs were measured before and 2 years after surgery and compared using the paired t test. Correlations between the difference in T1ρ values at these two time points and patient characteristics, presence of a cartilaginous lesion, graft type, and postoperative anteroposterior laxity were also evaluated using Pearson's and Spearman's correlation coefficients. RESULTS: There was a significant increase in T1ρ before versus 2 years after surgery in the MT1, MT2, LFC1, and LT1 areas, and a significant decrease in the LFC3 and LT2 areas. There was a significant correlation between postoperative anterior-posterior laxity and a postoperative increase in T1ρ values in the MFC3 (r = 0.37, P = 0.013) and MT2 (r = 0.35, P = 0.021) areas. Increases in T1ρ values in the MFC2 area were negatively correlated with KOOS symptoms (ρ = - 0.349, P = 0.027) and quality of life (ρ = - 0.374, P = 0.017) subscale scores. CONCLUSION: Early degenerative changes in medial articular cartilage were observed with T1ρ mapping at 2 years after ACL reconstruction. Postoperative anterior-posterior laxity is correlated with an increase in T1ρ values in the posteromedial femur and tibia. An increase in T1ρ values in the central medial femoral condyle was associated with knee symptoms. LEVEL OF EVIDENCE: III.

Evaluation of humeral head cartilage using magnetic resonance imaging T1 rho mapping for patients with small-to-medium rotator cuff tears: A pilot study.

BACKGROUND: It is unclear whether smaller rotator cuff tears cause cartilage degeneration. This study was designed to detect early humeral head cartilage degeneration in patients with small-to-medium cuff tears using magnetic-resonance-imaging T1 rho mapping. METHODS: Five male and 5 female volunteers without shoulder symptoms (control group) and 5 male and 5 female patients with small-to-medium (<3 cm) rotator cuff tears underwent 3.0-T magnetic resonance imaging of a single shoulder. T1 rho values of the humeral head cartilage were measured and analyzed. RESULTS: The total mean T1 rho value was 40.4 ± 3.4 ms for the control group and 45.0 ± 5.3 ms for the patient group. In the control group, the T1 rho values in the inferior articular cartilage were significantly higher than those in the superior and middle articular cartilage. In the patient group, there was no significant difference between all regions. A comparison between the patient and control groups showed that the mean T1 rho values in the superior-to-middle articular cartilage were significantly higher for the patient group than for the control group. However, in the inferior articular cartilage, there was no significant difference between both groups. CONCLUSIONS: This study showed the possibility of early cartilage degenerative changes in the superior-to-middle humeral head articular cartilage of patients with small-to-medium rotator cuff tears.

Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.

Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.

Acceleration-selective Arterial Spin-labeling MR Angiography Used to Visualize Distal Cerebral Arteries and Collateral Vessels in Moyamoya Disease.

Purpose To evaluate and compare the performance of acceleration-selective arterial spin labeling (AccASL) magnetic resonance (MR) angiography in the visualization of cerebral arteries and collateral vessels in patients with Moyamoya disease with that of time-of-flight (TOF) MR angiography, with digital subtraction angiography (DSA) as the reference standard. Materials and Methods Thirty-six cerebral hemispheres from 22 patients with Moyamoya disease underwent TOF and AccASL MR angiography and DSA. Qualitative evaluations included imaging of the terminal internal carotid artery (ICA), distal middle cerebral arteries (MCAs), Moyamoya vessels, and leptomeningeal anastomosis (LMA) collaterals with reference to DSA. Quantitative evaluations included assessment of contrast-to-noise ratio (CNR) and number of vessels in MCA branches. The linear mixed-effect model was used to compare the two methods. Results Mean scores for qualitative evaluation were significantly higher with AccASL angiography than with TOF angiography for imaging distal MCAs (3.9 ± 0.3 [standard deviation] vs 2.9 ± 1.1; P < .001), Moyamoya vessels (3.6 ± 0.6 vs 2.7 ± 0.9, P < .001), and LMA collaterals (3.8 ± 0.6 vs 1.8 ± 0.7, P < .001). Scores for steno-occlusive degree around the terminal ICAs were better with TOF angiography than with AccASL angiography (2.6 ± 0.5 vs 2.4 ± 0.6, P = .023). CNRs in the M4 segment were significantly higher with AccASL angiography (11.9 ± 12.9, P < .001) than with TOF angiography (4.1 ± 7.9). The number of vessels was significantly higher with AccASL angiography (18.3 ± 5.0, P < .001) than with TOF angiography (8.9 ± 4.9). The increase in the number of vessels from TOF angiography to AccASL angiography was greater in patients with severe ICA steno-occlusion (late ICA stage group, 11.4 ± 4.5; early ICA stage group, 6.8 ± 4.0; P = .007) and well-developed leptomeningeal anastomosis (mildly developed LMA group, 7.1 ± 4.3; well-developed LMA group, 11.3 ± 4.5; P = .011). Conclusion AccASL MR angiography enables better visualization of distal cerebral arteries and collateral vessels in patients with Moyamoya disease than does TOF MR angiography, while TOF MR angiography enables better visualization of stenosis of proximal arteries. Both methods work in a mutually beneficial manner in the assessment of cerebral arteries. © RSNA, 2017 Online supplemental material is available for this article.

Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10-3 mm2/sec ± 0.2, and 0.6 × 10-3 mm2/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. © RSNA, 2017 Online supplemental material is available for this article.