Dataset Information

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

ABSTRACT: The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent bilateral DCE-MRI of the breast at 7T. PK parameters (K^Trans, k_ep, V_e) were evaluated with two region of interest (ROI) approaches (2D whole-tumor ROI or 2D 10 mm standardized ROI) manually drawn by two readers (senior reader, R1, and R2) independently. Histopathology served as the reference standard. PK parameters differentiated benign and malignant lesions (n = 16, 27, respectively) with good accuracy (AUCs = 0.655-0.762). The addition of quantitative PK analysis to subjective BI-RADS classification improved breast cancer detection from 88.4% to 97.7% for R1 and 86.04% to 97.67% for R2. Different ROI approaches did not influence diagnostic accuracy for both readers. Except for K^Trans for whole-tumor ROI for R2, none of the PK parameters were valuable to predict molecular subtypes, histologic grade, or proliferation rate in breast cancer. In conclusion, PK-enhanced BI-RADS is promising for the noninvasive differentiation of benign and malignant breast tumors.

SUBMITTER: Ochoa-Albiztegui RE

PROVIDER: S-EPMC7765071 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

Ochoa-Albiztegui R Elena RE Sevilimedu Varadan V Horvat Joao V JV Thakur Sunitha B SB Helbich Thomas H TH Trattnig Siegfried S Morris Elizabeth A EA Reiner Jeffrey S JS Pinker Katja K

Cancers 20201214 12

The purpose of this study was to investigate whether ultra-high-field dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast at 7T using quantitative pharmacokinetic (PK) analysis can differentiate between benign and malignant breast tumors for improved breast cancer diagnosis and to predict molecular subtypes, histologic grade, and proliferation rate in breast cancer. In this prospective study, 37 patients with 43 lesions suspicious on mammography or ultrasound underwent b ...[more]

PMID: 33327532

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Project description:BackgroundThe purpose of this study was to develop a deep learning-based system with a cascade feature pyramid network for the detection and classification of breast lesions in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).MethodsThis retrospective study enrolled 191 consecutive patients with pathological confirmed breast lesions who underwent preoperative magnetic resonance imaging (MRI) at the Second Affiliated Hospital of Xi'an Jiaotong University. Patients were randomly divided into a training set comprising 153 patients with 126 malignant and 27 benign lesions and a validation set containing 38 patients with 31 malignant and 7 benign lesions under 5-fold cross-validation. Two radiologists annotated the location and classification of all lesions. After augmentation with pseudo-color image fusion, MRI images were fed into the developed cascade feature pyramid network system, feature pyramid network, and faster region-based convolutional neural network (CNN) for breast lesion detection and classification, respectively. The performance on large (>2 cm) and small (≤2 cm) breast lesions was further evaluated. Average precision (AP), mean AP, F1-score, sensitivity, and false positives were used to evaluate different systems. Cohen's kappa scores were calculated to assess agreement between different systems, and Student's t-test and the Holm-Bonferroni method were used to compare multiple groups.ResultsThe cascade feature pyramid network system outperformed the other systems with a mean AP and highest sensitivity of 0.826±0.051 and 0.970±0.014 (at 0.375 false positives), respectively. The F1-score of the cascade feature pyramid network in real detection was also superior to that of the other systems at both the slice and patient levels. The mean AP values of the cascade feature pyramid network reached 0.779±0.152 and 0.790±0.080 in detecting large and small lesions, respectively. Especially for small lesions, the cascade feature pyramid network achieved the best performance in detecting benign and malignant breast lesions at both the slice and patient levels.ConclusionsThe deep learning-based system with the developed cascade feature pyramid network has the potential to detect and classify breast lesions on DCE-MRI, especially small lesions.

Project description:The prediction of monoclonal antibody (mAb) disposition within solid tumors for individual patients is difficult due to inter-patient variability in tumor physiology. Improved a priori prediction of mAb pharmacokinetics in tumors may facilitate the development of patient-specific dosing protocols and facilitate improved selection of patients for treatment with anti-cancer mAb. Here, we report the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with tumor penetration of the contrast agent gadobutrol used as a surrogate, to improve physiologically based pharmacokinetic model (PBPK) predictions of cetuximab pharmacokinetics in epidermal growth factor receptor (EGFR) positive xenografts. In the initial investigations, mice bearing Panc-1, NCI-N87, and LS174T xenografts underwent DCE-MRI imaging with the contrast agent gadobutrol, followed by intravenous dosing of an 125Iodine-labeled, non-binding mAb (8C2). Tumor concentrations of 8C2 were determined following the euthanasia of mice (3 h-6 days after 8C2 dosing). Potential predictor relationships between DCE-MRI kinetic parameters and 8C2 PBPK parameters were evaluated through covariate modeling. The addition of the DCE-MRI parameter Ktrans alone or Ktrans in combination with the DCE-MRI parameter Vp on the PBPK parameters for tumor blood flow (QTU) and tumor vasculature permeability (σTUV) led to the most significant improvement in the characterization of 8C2 pharmacokinetics in individual tumors. To test the utility of the DCE-MRI covariates on a priori prediction of the disposition of mAb with high-affinity tumor binding, a second group of tumor-bearing mice underwent DCE-MRI imaging with gadobutrol, followed by the administration of 125Iodine-labeled cetuximab (a high-affinity anti-EGFR mAb). The MRI-PBPK covariate relationships, which were established with the untargeted antibody 8C2, were implemented into the PBPK model with considerations for EGFR expression and cetuximab-EGFR interaction to predict the disposition of cetuximab in individual tumors (a priori). The incorporation of the Ktrans MRI parameter as a covariate on the PBPK parameters QTU and σTUV decreased the PBPK model prediction error for cetuximab tumor pharmacokinetics from 223.71 to 65.02%. DCE-MRI may be a useful clinical tool in improving the prediction of antibody pharmacokinetics in solid tumors. Further studies are warranted to evaluate the utility of the DCE-MRI approach to additional mAbs and additional drug modalities.

Dataset Information

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

Publications

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging at 7T for Breast Cancer Diagnosis and Characterization.

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