Combination Of Dynamic Contrast-enhanced MRI Research Articles

Dynamic contrast-enhanced magnetic resonance imaging features and apparent diffusion coefficient value of HER2-positive/HR-negative breast carcinoma.

According to hormone receptor (HR) status, human epidermal growth factor 2 positive (HER2+) breast carcinoma can be divided into HR- and HR+, with different treatment and prognosis. We analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings, apparent diffusion coefficient (ADC) value and the combination of DCE-MRI and ADC value of HER2+/HR- breast carcinoma. Totally 259 cases (96 HR-, 163 HR+) of pathologically verified HER2+ breast carcinoma were collected. Patients underwent DCE-MRI and diffusion weighted imaging (DWI). The morphological characteristics, internal enhancement characteristics, early enhancement rate (EER), and time-signal intensity curves (TIC) were recorded, and ADC values were measured. The relationship between each feature and HER2+/HR- breast cancer was analyzed. Area under the cures (AUC) was used to compare diagnostic performance of DCE-MRI, ADC value and the combination of DCE-MRI and ADC value. HER2+/HR- breast cancer presented as non-mass enhancement (NME), mass with NME, whereas HER2+/HR+ breast cancer presented as mass (P<0.001). HR- cases showed a round or oval shape with circumscribed margins, whereas HR+ cases showed an irregular mass with irregular or spiculated margins (P=0.001, P=0.028). The size of the mass, the internal enhancement characteristics, EER, and TIC did not differ significantly between the two HER2+ breast carcinomas. The ADC values for HR- and HR+ breast cancers were [1.2 (1.14, 1.33)] ×10-3 mm2/s and [1.0 (0.89, 1.11)] ×10-3 mm2/s, respectively, which were statistically significant (Z=-9.119, P<0.001). The ADC value can be used for diagnosing HER2+/HR- breast carcinoma, with the threshold value of 1.095×10-3 mm2/s [negative predictive value (NPV) of 89.8%, sensitivity of 86.5% and specificity of 70.6%]. The AUCs of ADC value, DCE-MRI, and DCE-MRI combined with ADC value were 0.839, 0.689 and 0.860, respectively. AUC of the DCE-MRI combined with ADC value was significantly higher than DCE-MRI alone (P<0.0001). The diagnostic performance of the DCE-MRI combined with ADC value was good in diagnosing HER2+/HR- breast cancers. MRI is an effective tool in diagnosing HER2+/HR- breast carcinoma, which will help select the clinical treatment plan and determine the prognosis.

Distinguishing mesorectal tumor deposits from metastatic lymph nodes by using diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer.

This study aimed to identify whether apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are helpful in distinguishing mesorectal tumor deposits (TD) from metastatic lymph nodes (MLN) in rectal cancer (RC). Thirty patients (59 lesions, including 30 TD and 29 MLN) with RC who underwent pretreatment-MRI between February 2016 and August 2018 were enrolled. The morphological features, ADC values, and semi-quantitative parameters of DCE-MRI, including relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash-in rates (WIR), wash-out rates (WOR), brevity of enhancement (BRE), and area under the curve (AUC) were measured on lesions (TD or MLN) and RC. The parameters were compared between TD and MLN, tumor with and without TD group by using Fisher's exact test, independent-samples t-test, and Mann-Whitney U test. The ratio (lesion-to-tumor) of the parameters was compared between TD and MLN. Receiver operating characteristic curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing TD from MLN. The morphological features, including size, shape, and border, were significantly different between TD and MLN. TD exhibited significantly lower RE, MRE, RE-ratio, MRE-ratio, ADCmin-ratio, and ADCmean-ratio than MLN. RE-ratio showed the highest AUC (0.749) and accuracy (77.97%) among single parameters. The combination of DCE-MRI and DWI parameters together showed higher diagnostic efficiency (AUC = 0.825). Morphological features, ADC values, and DCE-MRI parameters can preoperatively help distinguish TD from MLN in RC. • DWI and DCE-MRI can facilitate early detection and distinguishing mesorectal TD (tumor deposits) from MLN (metastatic lymph nodes) in rectal cancer preoperatively. • TD has some specific morphological features, including relatively larger size, lower short- to long-axis ratio, irregular shape, and ill-defined border on T2-weighted MR images in rectal cancer. • The combination of ADC values and semi-quantitative parameters of DCE-MRI (RE, MRE) can help to improve the diagnostic efficiency of TD in rectal cancer.

Enhanced Masses on Contrast-Enhanced Breast: Differentiation Using a Combination of Dynamic Contrast-Enhanced MRI and Quantitative Evaluation with Synthetic MRI.

The addition of synthetic MRI might improve the diagnostic performance of dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer. To evaluate the diagnostic value of a combination of DCE-MRI and quantitative evaluation using synthetic MRI for differentiation between benign and malignant breast masses. Retrospective, observational. In all, 121 patients with 131 breast masses who underwent DCE-MRI with additional synthetic MRI were enrolled. 3.0 Tesla, T1 -weighted DCE-MRI and synthetic MRI acquired by a multiple-dynamic, multiple-echo sequence. All lesions were differentiated as benign or malignant using the following three diagnostic methods: DCE-MRI type based on the Breast Imaging-Reporting and Data System; synthetic MRI type using quantitative evaluation values calculated by synthetic MRI; and a combination of the DCE-MRI + Synthetic MRI types. The diagnostic performance of the three methods were compared. Univariate (Mann-Whitney U-test) and multivariate (binomial logistic regression) analyses were performed, followed by receiver-operating characteristic curve (AUC) analysis. Univariate and multivariate analyses showed that the mean T1 relaxation time in a breast mass obtained by synthetic MRI prior to injection of contrast agent (pre-T1 ) was the only significant quantitative value acquired by synthetic MRI that could independently differentiate between malignant and benign breast masses. The AUC for all enrolled breast masses assessed by DCE-MRI + Synthetic MRI type (0.83) was significantly greater than that for the DCE-MRI type (0.70, P < 0.05) or synthetic MRI type (0.73, P < 0.05). The AUC for category 4 masses assessed by the DCE-MRI + Synthetic MRI type was significantly greater than that for those assessed by the DCE-MRI type (0.74 vs. 0.50, P < 0.05). A combination of synthetic MRI and DCE-MRI improves the accuracy of diagnosis of benign and malignant breast masses, especially category 4 masses. Level of Evidence 4 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:381-391.

Diagnosis of Cervical Cancer With Parametrial Invasion on Whole-Tumor Dynamic Contrast-Enhanced Magnetic Resonance Imaging Combined With Whole-Lesion Texture Analysis Based on T2- Weighted Images.

Purpose: To evaluate the diagnostic value of the combination of whole-tumor dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and whole-lesion texture features based on T2–weighted images for cervical cancer with parametrial invasion.Materials and Methods: Sixty-two patients with cervical cancer (27 with parametrial invasion and 35 without invasion) preoperatively underwent routine MRI and DCE-MRI examinations. DCE-MRI parameters (Ktrans, Kep, and Ve) and texture features (mean, skewness, kurtosis, uniformity, energy, and entropy) based on T2-weighted images were acquired by two observers. All parameters of parametrial invasion and non-invasion were analyzed by one-way analysis of variance. The diagnostic efficiency of significant variables was assessed using receiver operating characteristic analysis.Results: The invasion group of cervical cancer demonstrated significantly higher Ktrans (0.335 ± 0.050 vs. 0.269 ± 0.079; p < 0.001), lower energy values (0.503 ± 0.093 vs. 0.602 ± 0.087; p < 0.001), and higher entropy values (1.391 ± 0.193 vs. 1.24 ± 0.129; p < 0.001) than those in the non-invasion group. Optimal diagnostic performance [area under curve [AUC], 0.925; sensitivity, 0.935; specificity, 0.829] could be obtained by the combination of Ktrans, energy, and entropy values. The AUC values of Ktrans (0.788), energy (0.761), entropy (0.749), the combination of Ktrans and energy (0.814), the combination of Ktrans and entropy (0.727), and the combination of energy and entropy (0.619) were lower than those of the combination of Ktrans, energy, and entropy values.Conclusion: The combination of DCE-MRI and texture analysis is a promising method for diagnosis cervical cancer with parametrial infiltration. Moreover, the combination of Ktrans, energy, and entropy is more valuable than any one alone, especially in improving diagnostic sensitivity.

Combined DCE-MRI- and FDG-PET enable histopathological grading prediction in a rat model of hepatocellular carcinoma

PurposeTo test combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-FDG positron emission tomography (FDG-PET)-derived parameters for prediction of histopathological grading in a rat Diethyl Nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) model. Methods15 male Wistar rats, aged 10 weeks were treated with oral DEN 0.01 % in drinking water and monitored until HCCs were detectable. DCE-MRI and PET were performed consecutively on small animal scanners. 38 tumors were identified and manually segmented based on HCC-specific contrast enhancement patterns. Grading (G2/3: 24 tumors, G1:14 tumors) alongside other histopathological parameters, tumor volume, contrast agent and 18F-FDG uptake metrics were noted. Class imbalance was addressed using SMOTE and collinearity was removed using hierarchical clustering and principal component analysis. A logistic regression model was fit separately to the individual parameter groups (DCE-MRI-derived, PET-derived, tumor volume) and the combined parameters. ResultsThe combined model using all imaging-derived parameters achieved a mean ± STD sensitivity of 0.88 ± 0.16, specificity of 0.70 ± 0.20 and AUC of 0.90 ± 0.03. No correlation was found between tumor grading and tumor volume, morphology, necrosis, extracellular matrix, immune cell infiltration or underlying liver fibrosis. ConclusionA combination of DCE-MRI- and 18F-FDG-PET-derived parameters provides high accuracy for histopathological grading of hepatocellular carcinoma in a relevant translational model system.

Preoperative Prediction of Lymph Node Metastasis from Clinical DCE MRI of the Primary Breast Tumor Using a 4D CNN.

In breast cancer, undetected lymph node metastases can spread to distal parts of the body for which the 5-year survival rate is only 27%, making accurate nodal metastases diagnosis fundamental to reducing the burden of breast cancer, when it is still early enough to intervene with surgery and adjuvant therapies. Currently, breast cancer management entails a time consuming and costly sequence of steps to clinically diagnose axillary nodal metastases status. The purpose of this study is to determine whether preoperative, clinical DCE MRI of the primary tumor alone may be used to predict clinical node status with a deep learning model. If possible then many costly steps could be eliminated or reserved for only those with uncertain or probable nodal metastases. This research develops a data-driven approach that predicts lymph node metastasis through the judicious integration of clinical and imaging features from preoperative 4D dynamic contrast enhanced (DCE) MRI of 357 patients from 2 hospitals. Innovative deep learning classifiers are trained from scratch, including 2D, 3D, 4D and 4D deep convolutional neural networks (CNNs) that integrate multiple data types and predict the nodal metastasis differentiating nodal stage N0 (non metastatic) against stages N1, N2 and N3. Appropriate methodologies for data preprocessing and network interpretation are presented, the later of which bolster radiologist confidence that the model has learned relevant features from the primary tumor. Rigorous nested 10-fold cross-validation provides an unbiased estimate of model performance. The best model achieves a high sensitivity of 72% and an AUROC of 71% on held out test data. Results are strongly supportive of the potential of the combination of DCE MRI and machine learning to inform diagnostics that could substantially reduce breast cancer burden.

Diagnosis of solitary pulmonary lesions with intravoxel incoherent motion diffusion-weighted MRI and semi-quantitative dynamic contrast-enhanced MRI

To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted (DWI) magnetic resonance imaging (MRI) and semi-quantitative dynamic contrast-enhanced MRI (DCE-MRI) to help diagnose indeterminate solitary pulmonary lesions (SPLs) and the subgroups of lung cancer (LC), and to explore the relationship between IVIM and DCE-MRI. Sixty-four consecutive patients (44 male, 20 female; age, 52.77±10.46 years) from February 2014 to September 2016 with SPLs, were involved in this prospective study. Total apparent diffusion coefficient (ADCtotal), tissue diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (F), maximum enhancement ratio (MER), Tmax, slope, and washout were compared between the lung cancer (LC) and benign group and among the subtypes of LC. Time-intensity curves (TICs) were drawn. Receiver operating characteristic (ROC) curves were constructed to estimate the diagnostic performance. The correlation of both tools was assessed. ADCtotal, D, and Tmax were significantly higher for benignity than for LC (p=0.005, p=0.002 and p<0.001 respectively). D* and slope were significantly higher in LC than benignity (p=0.005 and p=0.011, respectively). D and Tmax had the highest sensitivity and accuracy, respectively. A combination of D and Tmax improved the sensitivity to 90.5%, the specificity to 86.4%, and the accuracy to 89.1%. Poor correlations were found between parameters derived from IVIM and DCE-MRI. ADCtotal values of SCC and SCLC were found to be significantly lower compared with that in adenocarcinoma. Both IVIM-DWI and DCE-MRI were useful for discriminating benignity from LC. ADCtotal was helpful for distinguishing adenocarcinoma and non-adenocarcinoma. A combination of DCE-MRI and IVIM could provide a robust method to determine the microstructural characteristics of SPLs.

Lithium chloride treatment increases serotonergic gene expression in the midbrain raphe nuclei of male mice in the chronic social defeat stress model

To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) diffusion-weighted (DWI) magnetic resonance imaging (MRI) and semi-quantitative dynamic contrast-enhanced MRI (DCE-MRI) to help diagnose indeterminate solitary pulmonary lesions (SPLs) and the subgroups of lung cancer (LC), and to explore the relationship between IVIM and DCE-MRI.Sixty-four consecutive patients (44 male, 20 female; age, 52.77±10.46 years) from February 2014 to September 2016 with SPLs, were involved in this prospective study. Total apparent diffusion coefficient (ADCtotal), tissue diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (F), maximum enhancement ratio (MER), Tmax, slope, and washout were compared between the lung cancer (LC) and benign group and among the subtypes of LC. Time–intensity curves (TICs) were drawn. Receiver operating characteristic (ROC) curves were constructed to estimate the diagnostic performance. The correlation of both tools was assessed.ADCtotal, D, and Tmax were significantly higher for benignity than for LC (p=0.005, p=0.002 and p<0.001 respectively). D* and slope were significantly higher in LC than benignity (p=0.005 and p=0.011, respectively). D and Tmax had the highest sensitivity and accuracy, respectively. A combination of D and Tmax improved the sensitivity to 90.5%, the specificity to 86.4%, and the accuracy to 89.1%. Poor correlations were found between parameters derived from IVIM and DCE-MRI. ADCtotal values of SCC and SCLC were found to be significantly lower compared with that in adenocarcinoma.Both IVIM-DWI and DCE-MRI were useful for discriminating benignity from LC. ADCtotal was helpful for distinguishing adenocarcinoma and non-adenocarcinoma. A combination of DCE-MRI and IVIM could provide a robust method to determine the microstructural characteristics of SPLs.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Combined with Positron Emission Tomography-Computed Tomography (PET-CT) and Video-Electroencephalography (VEEG) Have Excellent Diagnostic Value in Preoperative Localization of Epileptic Foci in Children with Epilepsy.

BackgroundTo investigate the effect that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has on surgical decision making relative to video-electroencephalography (VEEG) and positron emission tomography-computed tomography (PET-CT), and if the differences in these variables translates to differences in surgical outcomes.Material/MethodsA total of 166 children with epilepsy undergoing preoperative DCE-MRI, VEEG, and PET-CT examinations, surgical resection of epileptic foci, and intraoperative electrocorticography (ECoG) monitoring were enrolled. All children were followed up for 12 months and grouped by Engles prognostic classification for epilepsy. Based on intraoperative ECoG as gold standard, the diagnostic values of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and combined application of DCE-MRI, VEEG, and PET-CT in preoperative localization for epileptic foci were evaluated.ResultsThe sensitivity of DCE-MRI, VEEG, and PET-CT was 59.64%, 76.51%, and 93.98%, respectively; the accuracy of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, and DCE-MRI combined with PET-CT was 57.58%, 67.72%, 91.03%, 91.23%, and 96.49%, respectively. Localization accuracy rate of the combination of DCE-MRI, VEEG, and PET-CT was 98.25% (56/57), which was higher than that of DCE-MRI combined with VEEG and of DCE-MRI combined with PET-CT. No statistical difference was found in the accuracy rate of localization between these three combined techniques. During the 12-month follow-up, children were grouped into Engles grade I (n=106), II (n=31), III (n=21), and IV (n=8) according to postoperative conditions.ConclusionsAll DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and DCE-MRI combined with VEEG and PET-CT examinations have excellent accuracy in preoperative localization of epileptic foci and present excellent postoperative efficiency, suggesting that these combined imaging methods are suitable for serving as the reference basis in preoperative localization of epileptic foci in children with epilepsy.

Differentiation of pancreatic carcinoma and mass-forming focal pancreatitis: qualitative and quantitative assessment by dynamic contrast-enhanced MRI combined with diffusion-weighted imaging.

Differentiation between pancreatic carcinoma (PC) and mass-forming focal pancreatitis (FP) is invariably difficult. For the differential diagnosis, we qualitatively and quantitatively assessed the value of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in PC and FP in the present study. This study included 32 PC and 18 FP patients with histological confirmation who underwent DCE-MRI and DWI. The time-signal intensity curve (TIC) of PC and FP were classified into 5 types according to the time of reaching the peak, namely, type I, II, III, IV, and V, respectively, and two subtypes, namely, subtype-a (washout type) and subtype-b (plateau type) according to the part of the TIC profile after the peak. Moreover, the mean and relative apparent diffusion coefficient (ADC) value between PC and FP on DWI were compared. The type V TIC was only recognized in PC group (P < 0.01). Type IV b were more frequently observed in PC (P = 0.036), while type- IIa (P < 0.01), type- Ia (P = 0.037) in FP. We also found a significant difference in the mean and relative ADC value between PC and FP. The combined image set of DCE-MRI and DWI yielded an excellent sensitivity, specificity, and diagnostic accuracy (96.9%, 94.4%, and 96.0%). The TIC of DCE-MRI and ADC value of DWI for pancreatic mass were found to provide reliable information in differentiating PC from FP, and the combination of DCE-MRI and DWI can achieve a higher sensitivity, specificity, and diagnostic accuracy.

Abstract B51: Metabolic imaging with hyperpolarized [1-13C]-pyruvate and DCE-MRI

Abstract Purpose: To improve the quality and specificity of metabolic imaging with hyperpolarized pyruvate using prior information from dynamic contrast-enhanced MRI (DCE-MRI). Background: Dynamic nuclear polarization (DNP) and MR spectroscopic imaging of [1-13C]-pyruvate shows tremendous promise for imaging aerobic glycolysis with sensitivity, specificity, and resolution that was previously impossible. Exogeneous, enriched hyperpolarized (HP) pyruvate is injected as a bolus and traverses multiple biological barriers before it is exposed to intracellular enzymes that mediate its fate. Preservation of the spin label through chemical reaction allows visualization of pyruvate and its chemical endpoints (lactate, alanine, and carbon dioxide/bicarbonate). We have previously observed a strong correlation between tumor perfusion and the normalized area under the curve for HP lactate, the chemical endpoint associated with aerobic glycolysis. A pharmacokinetic model of HP substrate evolution that balances physiological accuracy and computational burden includes two physical pools (intravascular/extravascular) and two chemical pools (pyruvate/lactate). In the analytical solution for this model, terms for substrate extravasation and the fractional intravascular volume can be recognized as analogues for KTRANS and Vb that are derived from analysis of DCE-MRI data using the extended Tofts model. Use of these DCE-MRI parameters as prior information could eliminate unknowns in the measurement of HP agents and improve the specificity of quantitative estimates for kPL, the apparent conversion rate for HP pyruvate into lactate. Experimental Procedures: Athymic nude mice bearing orthotopic anaplastic thyroid cancer tumors were anesthetized and scanned using a 7T Biospec small animal MR system (Bruker Biospin Corp.). A dual-tuned 1H/13C volume resonator was used for anatomic imaging and for 13C excitation, and a surface coil was used for 13C detection. HP pyruvate was prepared using a HyperSense DNP system (Oxford Instruments). Dynamic 13C spectroscopic imaging data was acquired using a radial multi-band frequency encoding sequence beginning prior to intravascular administration of HP pyruvate via tail-vein catheter. DCE-MRI data was acquired after HP measurements, using a fast spoiled gradient echo sequence. DCE-MRI data was fit to the extended Tofts model on a pixel-by-pixel basis using software developed in Matlab (The Mathworks). Parametric maps for perfusion and vascular blood volume fraction were resampled to the resolution of HP 13C scans and used as priors in a constrained reconstruction algorithm that enforces consistency between undersampled 13C projection data, the kinetic model, and prior information from 1H MRI. Results: With prior information about extravasation and fractional intravascular blood volume, the constrained reconstruction algorithm needs only solve for a global parameterized vascular input function and values for chemical conversion (kPL) and signal relaxation/loss for each voxel in the imaging volume. Elimination of nuisance parameters with strongly correlated effects reduces the computational burden of constrained reconstruction and clarifies interpretation of changes in biomarkers due to disease progression or response to therapy. Conclusions: The combination of DCE-MRI with constrained reconstruction reduces the number of unknowns in quantitative metabolic imaging using HP pyruvate, eases the computational burden, and decouples correlated effects of perfusion and chemical exchange. Citation Format: James A. Bankson, Christopher M. Walker, Yunyun Chen, Stephen Y. Lai, John D. Hazle. Metabolic imaging with hyperpolarized [1-13C]-pyruvate and DCE-MRI. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B51.

Improved differentiation of benign and malignant breast tumors with multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging: a feasibility study.

To assess whether multiparametric (18)fluorodeoxyglucose positron emission tomography magnetic resonance imaging (MRI) (MP (18)FDG PET-MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), three-dimensional proton MR spectroscopic imaging (3D (1)H-MRSI), and (18)FDG-PET enables an improved differentiation of benign and malignant breast tumors. Seventy-six female patients (mean age, 55.7 years; range, 25-86 years) with an imaging abnormality (BI-RADS 0, 4-5) were included in this Institutional Review Board (IRB)-approved study. Patients underwent fused PET-MRI of the breast with (18)FDG-PET/CT and MP MRI at 3T. The likelihood of malignancy was assessed for all single parameters, for MP MRI with two/three parameters, and for MP (18)FDG PET-MRI. Histopathology was used as the standard of reference. Appropriate statistical tests were used to assess sensitivity, specificity, and diagnostic accuracy for each assessment combination. There were 53 malignant and 23 benign breast lesions. MP (18)FDG PET-MRI yielded a significantly higher area under the cure (AUC) of 0.935 than DCE-MRI (AUC, 0.86; P = 0.044) and the combination of DCE-MRI and another parameter (AUC, 0.761-0.826; P = 0.013-0.020). MP (18)FDG PET-MRI showed slight further improvement to MP MRI with three parameters (AUC, 0.925; P = 0.317). Using MP (18)FDG PET-MRI there would have been a reduction of the unnecessary breast biopsies recommended by MP imaging with one or two parameters (P = 0.002-0.011). This feasibility study shows that MP (18)FDG PET-MRI enables an improved differentiation of benign and malignant breast tumors when several MRI and PET parameters are combined. MP (18)FDG PET-MRI may lead to a reduction in unnecessary breast biopsies.

Application value of 3T 1H-magnetic resonance spectroscopy in diagnosing breast tumors

Assessment of breast lesions with magnetic resonance imaging (MRI) provides a means for lesion detection and diagnosis. Proton (hydrogen-1) magnetic resonance spectroscopy ((1)H-MRS) has been proposed as a useful diagnostic technique in providing metabolic information of suspicious breast lesions. To determine the clinical significance of in-vivo single voxel (1)H-MRS at 3T in the assessment of benign and malignant breast lesions in combination with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Twenty-four women with known breast abnormalities from conventional imaging (mammography, ultrasonography) underwent DCE-MRI at a 3T MR scanner and 26 breast lesions were detected. Breast lesions were assessed according BI-RADS classification. Single voxel (1)H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. All lesions were confirmed histologically from the surgically excised specimens. Sensitivity, specificity, and accuracy of the (1)H-MRS, of the BI-RADS classification and of their combination (DCE-MRI + (1)H-MRS) were calculated. Fifteen out of 26 lesions proved to be malignant and 11 proved to be benign. In our study (1)H-MRS showed sensitivity 80%, specificity 81.8%, and accuracy 80.7%. DCE-MRI showed sensitivity 100%, specificity 63.6%, and accuracy 84.6%. The combination of DCE-MRI and (1)H-MRS provided higher accuracy (96.4%), as well as higher specificity 81.8% compared to BI-RADS classification. The combined use of (1)H-MRS and DCE-MRI found to have improved diagnostic performance in the assessment of equivocal breast lesions. (1)H-MRS can be used as a useful adjunct during lesion characterization in clinical routine in cases classified as BI-RADS 3 and 4.

Abstract P1-06-01: Upregulation of metabolism as a potential resistance mechanism to bevacizumab in primary breast cancer

Abstract Background: Recently the FDA has withdrawn the indication for bevacizumab in metastatic breast cancer after several clinical studies failed to demonstrate an overall survival benefit. These studies however did report an increase in response rates to chemotherapy and improvement in progression free survival, suggesting a pattern of response to the drug followed by the development of resistance. We have little knowledge of the molecular mechanisms driving the development of resistance to bevacizumab. To better understand these mechanisms, we have conducted a window of opportunity study using a single cycle of bevacizumab with detailed pharmacodynamic assessments using gene expression arrays and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: After ethical approval, 47 newly diagnosed locally advanced breast cancer patients were prospectively enrolled in this trial. Patients received single dose bevacizumab (15mg/ kg) 2 weeks prior to neoadjuvant chemotherapy and underwent core biopsies for gene expression and immunohistochemistry analysis and DCE-MRI scans before and 2 weeks after bevacizumab. 35 patients who had invasive ductal carcinoma together with good quality MRI scans and core biopsies before and after bevacizumab were included in this analysis. Pharmacokinetic (PK) modelling techniques were used to quantify PK parameters (Ktrans, kep, ve) from the DCE-MRI data. Gene expression profiling was performed using the Affymetrix Human Exon 1.0 ST arrays. Results: The majority of patients (28/35) showed a significant reduction in vessel permeability and blood flow of at least 30% following bevacizumab, with a mean decrease in the forward transfer constant (P &amp;lt; 0.0001) and the reverse rate constant kep (P &amp;lt; 0.0001). From gene expression and immunohistochemistry analyses, we identified several key metabolism-related genes that are significantly up-regulated after bevacizumab treatment, including pyruvate dehydrogenase kinase isozyme 1 (PDK1) (fig.1) and carbonic anhydrase 9 (CA9). In addition, we found a number of interesting genes that are down-regulated after bevacizumab treatment, including sulfatase-1 (SULF1), and cyclin E1 (CCNE1). Discussion: This study highlights that the combination of DCE-MRI and gene expression arrays can lead to an improved understanding of the molecular mechanisms governing response and resistance to anti-angiogenic therapy. Heterogeneity of response to bevacizumab was demonstrated, with some tumours showing increases or no change in Ktrans and others marked reductions, which may be of value in early stratification for therapy maintenance. Furthermore, the gene expression analysis showed activation of pathways, which could contribute to the development of resistance. For example, we observed significant up regulation of genes involved in regulating the switch from mitochondrial metabolism to glycolysis, such as PDK1. This suggests that using bevacizumab with the other targeted agents such as Dichloroacetate, a PDK1 inhibitor might be helpful in overcoming the development of resistance and ultimately lead to improved patient survival. Our preclinical studies strongly support this possibility. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-06-01.

Diagnostic Value of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in the Evaluation of the Biliary Obstruction

Purpose. In this study, our purpose was to investigate the diagnostic efficacy of the dynamic contrast-enhanced magnetic resonance imaging (MRI) method in the patients with bile duct obstruction. Materials and Methods. 108 consecutive patients (53 men, 55 women, mean age; 55.77 ± 14.62, range 18–86 years) were included in this study. All the patients underwent conventional upper abdomen MRI using intravenous contrast material (Gd-DTPA) and MRCP in 1.5 Tesla MRI scanner. MRCP images were evaluated together with the T1 and T2w images, and both biliary ducts and surrounding tissues were examined for possible pathologies that may cause obstruction. Results. MRI/MRCP findings compared with final diagnoses, MRI/MRCP in the demonstration of bile duct obstruction sensitivity 96%, the specificity 100%, and accuracy 96.3%, in the detection of presence and level of obstruction, the sensitivity 96.7%, specificity 100%, and accuracy 97.2%, in the diagnosis of choledocholithiasis, the sensitivity 82.3%, specificity 96%, and accuracy 91.7%, and in the determination of the character of the stenosis, sensitivity 95.6%, specificity 91.3%, and accuracy 94.5% were found. Conclusion. The combination of dynamic contrast-enhanced MRI and MRCP techniques in patients with suspected biliary obstruction gives the detailed information about the presence of obstruction, location, and causes and is a highly specific and sensitive method.

Contribution of Diffusion-Weighted Imaging to Dynamic Contrast-Enhanced MRI in the Characterization of Breast Tumors

The purpose of our study was to evaluate the diagnostic value of an imaging protocol that combines dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with suspicious breast lesions and to determine if additional information provided by DWI improves the diagnostic value of breast MRI. Eighty-four patients with breast tumors (37 benign, 47 malignant) underwent DCE-MRI and DWI before biopsy. Morphologic and kinetic analyses were performed on DCE-MRI and findings were classified according to the BI-RADS lexicon. Apparent diffusion coefficient (ADC) values were calculated from the DWI. The ADCs of the benign and malignant lesions were compared. For the combined MRI protocol, morphologic kinetic features and ADCs were evaluated together. Diagnostic values of DCE-MRI, DWI, and combined MRI were calculated. Median ADCs of the benign and malignant lesions were 1.26 × 10(-3) mm(2)/s and 0.75 × 10(-3) mm(2)/s, respectively. Cutoff value of 0.92 × 10(-3) mm(2)/s for ADC provided 91.5% sensitivity and 86.5% specificity. DCE-MRI alone showed 97.9% sensitivity and 75.7% specificity. The combination of DCE-MRI with DWI provided 95.7% sensitivity and 89.2% specificity. The specificity of breast MRI improved by 13.5% (p = 0.063) without a significant decrease in the sensitivity (p = 1.000). The combination of DWI and DCE-MRI has the potential to increase the specificity of breast MRI.

Added Value of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Predicting Advanced Stage Disease in Patients With Endometrial Carcinoma

To assess the added value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting advanced stage disease in patients with endometrial carcinoma. Fifty patients with endometrial carcinoma underwent preoperative MRI assessment in a single gynecological cancer center during a 2-year period. Magnetic resonance imaging examinations included high-resolution sagittal, axial, and axial-oblique T2-weighted images (T2WI) of the pelvis, and axial T1-weighted images (T1WI) of the pelvis and upper abdomen followed by DCE-MRI using a multiphase 3-dimensional gradient refocused echo T1WI sequence. The T2W images were evaluated initially, and local and overall staging was assigned according to the FIGO classification. An identical scoring system was used to evaluate the combination of DCE-MRI and T2WI. The presence of potential pitfalls in the accurate assessment of depth of myometrial invasion (leiomyoma, adenomyosis, loss of junctional zone definition, polypoid tumor, poor tumor-to-myometrium contrast, and tumor extension to uterine cornu) was also recorded. Surgical histology constituted the standard of reference. The depth of myometrial invasion was correctly determined in 78% (39/50) of the cases on T2WI alone, increasing to 92% (46/50) with the addition of DCE-MRI (95% confidence interval for improvement, 4.4%-23.6%, P = 0.016). The addition of DCE-MRI led to the correct detection of deep myometrial invasion in all cases. Tumor extension to uterine cornu was the only variable significantly associated (P = 0.014) with incorrect estimation of depth of myometrial invasion. The addition of multiphase 3-dimensional DCE-MRI to T2WI can effectively assess the depth of myometrial invasion in endometrial carcinoma and may be a useful tool to guide the surgical approach.