A Multiomics Signature Highlights Alterations Underlying Homologous Recombination Deficiency in Triple-Negative Breast Cancer.

BACKGROUND: Homologous recombination (HR) is a key pathway in DNA double-strand damage repair. HR deficiency (HRD) occurs more commonly in triple-negative breast cancers (TNBCs) than in other breast cancer subtypes. Several clinical trials have demonstrated the value of HRD in stratifying breast cancer patients into distinct groups based on their responses to poly(ADP ribose) polymerase inhibitors and chemotherapy. METHODS: We retrospectively collected TNBC samples to establish a multiomics cohort (n = 343) and explored the biological and phenotypic mechanisms underlying the better prognosis of patients with high HRD scores. Gene set enrichment analysis was conducted to elucidate the underlying pathways in patients with low HRD scores, and a radiomics model was established to predict the HRD score via a noninvasive method. RESULTS: Multivariable Cox analysis revealed the independent prognostic value of a low HRD score (hazard ratio 2.20, 95% confidence interval 1.05-4.59; p = 0.04). Furthermore, amino acid and lipid metabolism pathways were highly enriched in tumors from patients with low HRD scores, which was also demonstrated by differential abundant metabolite analysis. A noninvasive radiomics method was developed to predict the HRD status and it performed well in the independent validation cohort (support vector machine model: area under the curve [AUC] 0.739, sensitivity 0.571, and specificity 0.824; logistic regression model: AUC 0.695, sensitivity 0.571, and specificity 0.882). CONCLUSIONS: We revealed the prognostic value of the HRD score, predicted the HRD status with noninvasive radiomics features, and preliminarily explored druggable targets for TNBC patients with low HRD scores.

Development of MRI-Based Radiomics Model to Predict the Risk of Recurrence in Patients With Advanced High-Grade Serous Ovarian Carcinoma.

OBJECTIVE. The purpose of our study was to develop a radiomics model based on preoperative MRI and clinical information for predicting recurrence-free survival (RFS) in patients with advanced high-grade serous ovarian carcinoma (HGSOC). MATERIALS AND METHODS. This retrospective study enrolled 117 patients with HGSOC, including 90 patients with recurrence and 27 without recurrence; 1046 radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images using a manual segmentation method. L1 regularization-based least absolute shrinkage and selection operator (LASSO) regression was performed to select features, and the synthetic minority oversampling technique (SMOTE) was used to balance our dataset. A support vector machine (SVM) classifier was used to build the classification model. To validate the performance of the proposed models, we applied a leave-one-out cross-validation method to train and test the classifier. Cox proportional hazards regression, Harrell concordance index (C-index), and Kaplan-Meier plots analysis were used to evaluate the associations between radiomics signatures and RFS. RESULTS. The fusion radiomics-based model yielded a significantly higher AUC value of 0.85 in evaluating RFS than the model using contrast-enhanced T1-weighted imaging features alone or T2-weighted imaging features alone (AUC = 0.79 and 0.74 and p = .02 and .01, respectively). Kaplan-Meier survival curves showed significant differences between high and low recurrence risk in patients with HGSOC by different models. The fusion model combining radiomics features and clinical information showed higher performance than the clinical model (C-index = 0.62 and 0.60, respectively). CONCLUSION. The proposed MRI-based radiomics signatures may provide a potential way to develop a prediction model and can help identify patients with advanced HGSOC who have a high risk of recurrence.

Gastric Hepatoid Adenocarcinoma: Differentiation From Gastric Adenocarcinoma With Dynamic Contrast-Enhanced Computed Tomographic Findings.

PURPOSE: This study aimed to describe the computed tomographic (CT) findings of gastric hepatoid adenocarcinoma (GHA) and determine features distinguishing it from gastric adenocarcinoma (GA). METHODS: Computed tomographic images of pathologically verified GHA (n = 11) and GA (n = 38) were retrospectively reviewed. α-Fetoprotein (AFP), carcinoembryonic antigen (CEA), and CT findings were assessed in our study. Computed tomographic findings included the location, distribution, growth pattern, ulceration, thickness of gastric wall, enhancement pattern, and the ratio of lesion attenuation to aorta CT attenuation. Short diameter of the metastatic lymph nodes, mean short diameter of metastatic lymph nodes, and the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically were measured and calculated. Data were compared using the χ and Student t tests; significant CT criteria were identified using receiver operating characteristic curve. RESULTS: α-Fetoprotein, CEA, and CT findings, including the longest short diameter, the mean short diameter, the ratio of the number of enlarged lymph node on CT to the number of metastatic lymph nodes pathologically, the lesion in arterial phase minus portal venous phase, and the lesion/aorta ratio, were statistically significant predictors for the differentiation of GHA from GA (P < 0.05). When only the aforementioned CT findings were used as criteria, the sensitivity and specificity for diagnosing GHA were 82.86% and 90.91%, respectively. When AFP, CEA, and CT findings were used as criteria, sensitivity of 97.14% and specificity of 90.91% were achieved. CONCLUSIONS: Elevated serum AFP level and CT findings could distinguish GHA and GA with a high degree of accuracy.

Feasibility of free-breathing dynamic contrast-enhanced MRI of gastric cancer using a golden-angle radial stack-of-stars VIBE sequence: comparison with the conventional contrast-enhanced breath-hold 3D VIBE sequence.

OBJECTIVES: To investigate the feasibility and diagnostic value of free-breathing, radial, stack-of-stars three-dimensional (3D) gradient echo (GRE) sequence ("golden angle") on dynamic contrast-enhanced (DCE) MRI of gastric cancer. METHODS: Forty-three gastric cancer patients were divided into cooperative and uncooperative groups. Respiratory fluctuation was observed using an abdominal respiratory gating sensor. Those who breath-held for more than 15 s were placed in the cooperative group and the remainder in the uncooperative group. The 3-T MRI scanning protocol included 3D GRE and conventional breath-hold VIBE (volume-interpolated breath-hold examination) sequences, comparing images quantitatively and qualitatively. DCE-MRI parameters from VIBE images of normal gastric wall and malignant lesions were compared. RESULTS: For uncooperative patients, 3D GRE scored higher qualitatively, and had higher SNRs (signal-to-noise ratios) and CNRs (contrast-to-noise ratios) than conventional VIBE quantitatively. Though 3D GRE images scored lower in qualitative parameters compared with conventional VIBE for cooperative patients, it provided images with fewer artefacts. DCE parameters differed significantly between normal gastric wall and lesions, with higher Ve (extracellular volume) and lower Kep (reflux constant) in gastric cancer. CONCLUSIONS: The free-breathing, golden-angle, radial stack-of-stars 3D GRE technique is feasible for DCE-MRI of gastric cancer. Dynamic enhanced images can be used for quantitative analysis of this malignancy. KEY POINTS: • Golden-angle radial stack-of-stars VIBE aids gastric cancer MRI diagnosis. • The 3D GRE technique is suitable for patients unable to suspend respiration. • Method scored higher in the qualitative evaluation for uncooperative patients. • The technique produced images with fewer artefacts than conventional VIBE sequence. • Dynamic enhanced images can be used for quantitative analysis of gastric cancer.

Assessment of fibrotic tissue and microvascular architecture by in-line phase-contrast imaging in a mouse model of liver fibrosis.

PURPOSE: To explore the value of in-line phase-contrast imaging with computed tomography (ILPCI-CT) by synchrotron radiation (SR) for liver fibrosis. MATERIALS AND METHODS: Liver fibrosis models were set up in 13 BALB/c mice by peritoneal injections of thioacetamide and evaluated by ILPCI-CT. Histological staging was used to categorize liver fibrosis into normal, mild fibrosis and advanced fibrosis groups. Microvessel density (MVD), the ratio of total vessel length to volume (L/V), the ratio of total number of branching points to liver volume (P/V) and the distribution of vessel diameter were assessed. RESULTS: The CT images showed slightly high-density shadows around the portal tracts in the fibrosis group. Three-dimensional reconstruction can detect vascular and nodular changes on the surface of fibrotic livers. The MVDs between the three groups were significantly different (P = 0.024). L/V was significantly different between the three groups (P = 0.014). There was a positive correlation between MVD and P/V. CONCLUSION: Fibrous material can be detected by ILPCI-CT even in the early stage of fibrosis. MVD, L/V, P/V and the distribution of vessel diameter were consistent with fibrosis-related angiogenesis progress. Three-dimensional reconstruction is a promising method to visualize morphological changes of the fibrotic liver. KEY POINTS: • ILPCI-CT can detect fibrous material even in the early stage of liver fibrosis. • MVD, L/V, P/V, and the distribution of vascular diameter reflect pathological angiogenesis. • 3D reconstruction could be a promising approach for detecting liver fibrosis.

Imaging Manifestation of Adenoid Cystic Carcinoma of the Breast.

OBJECTIVE: This study aimed to describe the imaging features of adenoid cystic carcinoma (ACC) of the breast using multimode imaging. MATERIALS AND METHODS: The findings from mammography, sonography, magnetic resonance imaging, or digital breast tomosynthesis in 11 patients with histopathologically confirmed ACC of the breast were reviewed. The imaging criteria included location, shape, size, number, margin, calcification, attenuation, echo and/or signal intensity, internal mass enhancement pattern, and dynamic-enhancement characteristics. RESULTS: On mammography (n = 9), ACC demonstrated as an irregular or lobulated mass with indistinct or spiculated margins. Sonographically (n = 11), ACCs appeared as a hypoechoic solid or heterogeneous mass with minimum vascularity on color Doppler examination. With regard to magnetic resonance imaging (n = 9), 2 of the largest masses had an extensive high T2-weighted imaging (T2WI) signal and hypointense internal septations, which demonstrated delayed enhancement. Dynamic enhancement illustrated washout kinetics. The 7 smaller masses appeared isointense on T2WI, and their internal septations were unenhanced. Among them, 5 demonstrated plateau kinetics and 2 demonstrated persistent kinetics. CONCLUSIONS: Although ACC is a rare event in the breast, we believe that the following signs may suggest the diagnosis of this entity: a well-defined border, extensive high T2WI signals, and internal septations that demonstrate delayed enhancement in larger lesions.

Comparison of gadobenate dimeglumine-enhanced breast MRI and gadopentetate dimeglumine-enhanced breast MRI with mammography and ultrasound for the detection of breast cancer.

PURPOSE: To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue. MATERIALS AND METHODS: In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3­5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared. RESULTS: In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8­17.5%; P < 0.0001), ultrasound (Δ18.3­20.0%; P < 0.0001), and mammography and/or ultrasound (Δ8.6­10.7%; P ≤ 0.0105) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0­5.5% vs. 11.1% at mammography; 6.3­8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2­97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2­84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2­96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7­88.5% on gadopentetate dimeglumine-enhanced MRI vs. 77.0­84.4% with conventional techniques). Overall diagnostic performance for the detection of cancer was superior on gadobenate dimeglumine-enhanced MRI than on conventional imaging or gadopentetate dimeglumine-enhanced MRI. CONCLUSION: Gadobenate dimeglumine-enhanced MRI significantly improves cancer detection compared to gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound in a selected group of patients undergoing breast MRI for preoperative staging or because of inconclusive findings at conventional imaging.

Comparison of ADC values of intracranial hemangiopericytomas and angiomatous and anaplastic meningiomas.

PURPOSE: This study aimed to determine whether the use of apparent diffusion coefficient (ADC) values can improve the diagnostic efficacy of magnetic resonance imaging (MRI) to differentiate hemangiopericytoma (HPC) from angiomatous and anaplastic meningioma. MATERIALS AND METHODS: Preoperative diffusion-weighted imaging (DWI) studies of 38 patients with pathologically proven intracranial HPC (n = 12) and angiomatous (n = 13) or anaplastic meningioma (n = 13) were retrospectively reviewed. ADC values were measured in the tumor parenchyma and peritumoral edema, and used to obtain normalized ADC (NADC) ratios (ADC of tumor/ADC of normal white matter). RESULTS: Mean ADC values were significantly different between HPC and anaplastic meningioma (1.17 ± 0.30 × 10(-3) mm(2)/s and 0.75 ± 0.11 × 10(-3) mm(2)/s, respectively). Mean NADC ratios were also significantly lower in the malignant cases (0.95 ± 0.13) compared with the benign HPCs (1.53 ± 0.39; P < 0.05). Mean ADC values and NADC ratios did not differ significantly between angiomatous meningioma and HPC (P > 0.05), whereas mean ADC values and NADC ratios were lower for anaplastic meningioma than for either angiomatous meningioma or HPC (P < 0.05). Mean ADC value in peritumoral edema in HPC (1.48 ± 0.11 × 10(-3) mm(2)/s) was lower than in either angiomatous (1.73 ± 0.28 × 10(-3) mm(2)/s) or anaplastic (1.72 ± 0.25 × 10(-3) mm(2)/s) meningioma (P < 0.05), and there was no significant difference between ADC values in anaplastic versus angiomatous meningioma (P > 0.05). CONCLUSION: ADC values in tumor parenchyma and peritumoral edema can provide helpful information that is otherwise not available from conventional MRI to differentiate HPC from angiomatous and anaplastic meningioma.

Multicenter radio-multiomic analysis for predicting breast cancer outcome and unravelling imaging-biological connection.

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Visualising liver fibrosis by phase-contrast X-ray imaging in common bile duct ligated mice.

OBJECTIVES: To determine whether phase-contrast X-ray imaging can be used to visualise directly the accumulated extracellular matrix proteins associated with liver fibrosis in common bile duct ligated mice. METHODS: Twenty-six-week-old C57BL female mice were randomised into three groups. In groups 1 (n = 5) and 2 (n = 10), common bile duct ligation was conducted to produce secondary biliary cirrhosis. Mouse livers were then excised 15 (group 1) and 40 days (group 2) after the ligation of the common bile duct for imaging. In the control group, the livers of 5 mice were excised 40 days after the sham operation. Images were then acquired using the analyser crystal set at different positions of the rocking curve. RESULTS: The results show that the fibrotic septa and hepatic lobules enclosed by fibrotic septa can be visualised clearly at the whole organ level via phase-contrast X-ray imaging without any contrast agent. CONCLUSION: These results suggest that phase-contrast X-ray imaging can easily reveal the accumulated extracellular matrix proteins associated with liver fibrosis without using any contrast agent and has great potential in the study of liver fibrosis.

Intra-arterial infusion chemotherapy for advanced non-small-cell lung cancer: preliminary experience on the safety, efficacy, and clinical outcomes.

PURPOSE: To investigate the effectiveness and toxicity of intra-arterial infusion chemotherapy as a therapeutic modality for advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: In a retrospective study, 40 patients with stage III NSCLC received intra-arterial infusion chemotherapy with gemcitabine and cisplatin. Tumor staining was graded based on angiography, and the number of NSCLC feeding arteries detected was recorded. Toxicity was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events. The response to treatment was evaluated per Response Evaluation Criteria In Solid Tumors (RECIST). Efficacy was assessed based on time to tumor progression (TTP), and survival was estimated by Kaplan-Meier analysis. Prognostic factors influencing TTP and overall survival rate were evaluated by Cox regression analysis. RESULTS: The most frequent drug-related adverse events were cough (n = 17; 42.5%), anorexia (n = 14; 35%), and pain (n = 9; 22.5%). Evaluated per RECIST, a total of 47.5% of patients (n = 19) exhibited response to therapy after completion of the first three cycles of intra-arterial infusion chemotherapy. The median TTP was 5 months. Patients had a median life expectancy of 9 months. By Cox regression analysis, tumor staining was shown to be an independent prognostic factor for TTP (relative risk, 0.405; 95% confidence interval, 0.216-0.760) and overall survival (relative risk, 0.348; 95% confidence interval, 0.185-0.656). CONCLUSIONS: Intra-arterial infusion chemotherapy for advanced lung cancer has the potential to reduce the size of tumors and has no severe adverse effects.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients: a multicenter, open-label, phase III study.

BACKGROUND: Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. METHODS: This was a single-arm, open-label, multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were evaluated by clinical study investigators and three independent, blinded radiologists. The primary efficacy endpoint was sensitivity in lesion detection. RESULTS: Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46% compared with pre-contrast imaging for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA vs pre-contrast, respectively). Improvements in detection were more pronounced in lesions less than 1 cm. Gd-EOB-DTPA improved diagnostic accuracy in lesion classification. CONCLUSIONS: This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly in those smaller than 1 cm. Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification, and furthermore, Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

Safety and efficacy of splenic artery coil embolization for hypersplenism in liver cirrhosis.

BACKGROUND: Partial splenic artery embolization is an effective treatment for hypersplenism but often lacks long-term benefits. PURPOSE: To evaluate the long-term effects of coil embolization of the splenic artery in patients with liver cirrhosis and hypersplenism. MATERIAL AND METHODS: Forty-nine patients with liver cirrhosis and hypersplenism underwent coil embolization of the main splenic artery. The coils were deployed in the mid- or distal segment of the splenic artery to allow collateral blood flow to the spleen. The following data were collected from 2 weeks to 4 years after the embolization: technical success, length of hospital stay, white blood cell count, platelet count, splenic volume, and complication. RESULTS: The technical success rate of splenic artery coil embolization was 100%. The post embolization syndrome rate was 75% (36/49) with no incidence of major complications. The mean length of hospital stay was 9 days. After embolization, the patient's white blood and platelet counts increased significantly, peaked at 2 weeks, and gradually decreased during the 4-year follow-up period, but remained at significantly higher levels than pre-embolization levels. Follow-up CT scans demonstrated a gradual increase in the volume of the enhanced portions of the spleens with a decrease in the volume of unenhanced portion. No significant changes occurred in the red blood cell count and liver function after the embolization. CONCLUSION: Embolization of the mid-and distal main splenic artery with coils is a safe and effective treatment of hypersplenism in cirrhosis with long-term hematologic benefits.

[Neuroendocrine carcinoma of the breast: mammographic features correlated with sonography and histopathological findings].

OBJECTIVE: The purpose of this study was to describe the X-ray features of the neuroendocrine carcinoma (NEC) of breast to raise the awareness for the disease. METHODS: The mammography, sonography and clinicopathologic features in a total of 16 cases of pathologically proven breast neuroendocrine carcinoma in Fudan University Cancer Hospital were analyzed retrospectively. RESULTS: All the 16 patients were women with a mean age of 67.3 years old (ranged from 45 to 75 years old). Twelve patients had palpable masses and the other four patients had outflow from the nipple. Pathological diagnosis included endocrine ductal carcinoma in situ (E-DCIS) in 4 cases, E-DCIS with microinvasion in 5, and invasive solid neuroendocrine carcinoma in 7. On mammography, 9 of 16 cases exhibited round or slightly lobulated masses. Five of the 16 cases exhibited irregular or asymmetric opacities. Two of the 16 cases had negative findings. The borders of the 14 masses detected on mammography were vague in 7, partly unclear in 3 and clear-cut in 4 cases. Malignant microcalcification was not found in all cases. The accuracy rates of preoperative qualitative diagnosis for NEC with mammography and sonography were 68.8% (11/16) and 81.3% (13/16), respectively. Given the application of combined mammography and sonography, the accuracy rates could be improved to 87.5% (14/16). CONCLUSIONS: A round mass and irregular or asymmetric opacities without malignant calcification are the most frequent appearances of mammography in neuroendocrine carcinoma of the breast. Combination of mammography and sonography may be useful to improve the accuracy of diagnosis and early detection of neuroendocrine carcinoma of the breast.

The Value of Whole-Tumor Histogram and Texture Analysis Using Intravoxel Incoherent Motion in Differentiating Pathologic Subtypes of Locally Advanced Gastric Cancer.

PURPOSE: To determine if whole-tumor histogram and texture analyses using intravoxel incoherent motion (IVIM) parameters values could differentiate the pathologic characteristics of locally advanced gastric cancer. METHODS: Eighty patients with histologically confirmed locally advanced gastric cancer who received surgery in our institution were retrospectively enrolled into our study between April 2017 and December 2018. Patients were excluded if they had lesions with the smallest diameter < 5 mm and severe image artifacts. MR scanning included IVIM sequences (9 b values, 0, 20, 40, 60, 100, 150,200, 500, and 800 s/mm2) used in all patients before treatment. Whole tumors were segmented by manually drawing the lesion contours on each slice of the diffusion-weighted imaging (DWI) images (with b=800). Histogram and texture metrics for IVIM parameters values and apparent diffusion coefficient (ADC) values were measured based on whole-tumor volume analyses. Then, all 24 extracted metrics were compared between well, moderately, and poorly differentiated tumors, and between different Lauren classifications, signet-ring cell carcinomas, and other poorly cohesive carcinomas using univariate analyses. Multivariate logistic analyses and multicollinear tests were used to identify independent influencing factors from the significant variables of the univariate analyses to distinguish tumor differentiation and Lauren classifications. ROC curve analyses were performed to evaluate the diagnostic performance of these independent influencing factors for determining tumor differentiation and Lauren classifications and identifying signet-ring cell carcinomas. The interobserver agreement was also conducted between the two observers for image quality evaluations and parameter metric measurements. RESULTS: For diagnosing tumor differentiation, the ADCmedian, pure diffusion coefficient median (Dslowmedian), and pure diffusion coefficient entropy (Dslowentropy) showed the greatest AUCs: 0.937, 0.948, and 0.850, respectively, and no differences were found between the three metrics, P>0.05). The 95th percentile perfusion factor (FP P95th) was the best metric to distinguish diffuse-type GCs vs. intestinal/mixed (AUC=0.896). The ROC curve to distinguish signet-ring cell carcinomas from other poorly cohesive carcinomas showed that the Dslowmedian had AUC of 0.738. For interobserver reliability, image quality evaluations showed excellent agreement (interclass correlation coefficient [ICC]=0.85); metrics measurements of all parameters indicated good to excellent agreement (ICC=0.65-0.89), except for the Dfast metric, which showed moderate agreement (ICC=0.41-0.60). CONCLUSIONS: The whole-tumor histogram and texture analyses of the IVIM parameters based on the biexponential model provided a non-invasive method to discriminate pathologic tumor subtypes preoperatively in patients with locally advanced gastric cancer. The metric FP P95th derived from IVIM performed better in determining Lauren classifications than the mono-exponential model.

Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MR imaging (DETECT Trial).

PURPOSE: To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS: Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION: Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis. © RSNA, 2010 Clinical trial registration no. NCT00486473 (http://www.clinicaltrials.gov/). SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100968/-/DC1.

Anticoagulation with warfarin for Budd-Chiari syndrome with chronic inferior vena cava thrombosis: an initial clinical experience.

BACKGROUND: To evaluate the initial clinical safety and feasibility of anticoagulation using warfarin for Budd-Chiari syndrome (BCS) with chronic inferior vena cava (IVC) thrombosis. METHODS: Between October 2005 and June 2009, a total of 16 consecutive BCS patients with chronic IVC thrombosis were treated with warfarin. Warfarin was administered orally at 2.5 mg/d for approximately 3-12 months. Transluminal balloon dilatation of the IVC with a 30-mm balloon catheter was applied for the patients with complete resolution of the thrombus. Data relating to the technical success, angiographic results, complications, and final clinical outcome were collected retrospectively and follow-ups were performed at 1, 3, 6, and 12 months after the stent placement, and annually thereafter. RESULTS: Warfarin was successfully used for anticoagulation in all patients without any complications. Patients were followed up as outpatients for 6.43 ± 2.19 months, and in 14 cases, complete disappearance of the thrombosis was achieved with successful treatment by balloon dilation. In two patients with partial resolution of the thrombosis, Z-stent placement was initiated to compress the thrombus to prevent migration of the thrombosis, followed by dilation of the IVC. During the follow-up for 20.94 ± 10.31 months after the procedure, all the IVC remained patent without complications or pulmonary embolus, and all patients were alive with resolution of symptoms at the time of this study. CONCLUSIONS: The use of warfarin for anticoagulation proved to be simple, safe, and feasible for BCS with chronic IVC thrombosis.

Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer's disease.

OBJECTIVE: Bushen Tiansui formula (BSTSF), a traditional Chinese medicine prescription, has been widely used to treat Alzheimer's disease (AD). However, the mechanisms underlying its effects remain largely unknown. In this study, a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs (tsRNAs) in the hippocampus, to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs, a novel small non-coding RNA. METHODS: To generate a validated AD model, oligomeric amyloid-ß1-42 (Aß1-42) was injected intracerebroventricularly into rats. The Morris water maze (MWM) test was used to evaluate rat cognitive performance, and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus. Potential targets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs. RESULTS: The learning and memory deficits of Aß1-42-induced AD rats, assessed by MWM tests, were clearly ameliorated by BSTSF treatment. A total of 387 tsRNAs were detected in the rat hippocampus. Among them, 13 were significantly dysregulated in AD rats compared with sham control rats, while 57 were markedly altered by BSTSF treatment, relative to untreated AD rats (fold change ≥ 2 and P < 0.05). Moreover, six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR. Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles, via multiple signaling pathways and Gene Ontology biological functions, including cyclic adenosine monophosphate and retrograde endocannabinoid signaling. CONCLUSION: This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aß1-42-induced AD rats, demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.