scholarly journals Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Prediction of Monoclonal Antibody Tumor Disposition

2022 ◽  
Vol 23 (2) ◽  
pp. 679
Author(s):  
Brandon M. Bordeau ◽  
Joseph Ryan Polli ◽  
Ferdinand Schweser ◽  
Hans Peter Grimm ◽  
Wolfgang F. Richter ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Monoclonal Antibody ◽  
Pbpk Model ◽  
A Priori ◽  
Mri Imaging ◽  
Resonance Imaging ◽  
Dce Mri ◽  
High Affinity ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

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.

scholarly journals Radiomic and Artificial Intelligence Analysis with Textural Metrics, Morphological and Dynamic Perfusion Features Extracted by Dynamic Contrast-Enhanced Magnetic Resonance Imaging in the Classification of Breast Lesions

2021 ◽  
Vol 11 (4) ◽  
pp. 1880
Author(s):  
Roberta Fusco ◽  
Adele Piccirillo ◽  
Mario Sansone ◽  
Vincenza Granata ◽  
Paolo Vallone ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Artificial Intelligence ◽  
Feature Selection ◽  
Resonance Imaging ◽  
Dynamic Features ◽  
Surgical Specimen ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
Malignant Lesions

Purpose: The aim of the study was to estimate the diagnostic accuracy of textural, morphological and dynamic features, extracted by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images, by carrying out univariate and multivariate statistical analyses including artificial intelligence approaches. Methods: In total, 85 patients with known breast lesion were enrolled in this retrospective study according to regulations issued by the local Institutional Review Board. All patients underwent DCE-MRI examination. The reference standard was pathology from a surgical specimen for malignant lesions and pathology from a surgical specimen or fine needle aspiration cytology, core or Tru-Cut needle biopsy for benign lesions. In total, 91 samples of 85 patients were analyzed. Furthermore, 48 textural metrics, 15 morphological and 81 dynamic parameters were extracted by manually segmenting regions of interest. Statistical analyses including univariate and multivariate approaches were performed: non-parametric Wilcoxon–Mann–Whitney test; receiver operating characteristic (ROC), linear classifier (LDA), decision tree (DT), k-nearest neighbors (KNN), and support vector machine (SVM) were utilized. A balancing approach and feature selection methods were used. Results: The univariate analysis showed low accuracy and area under the curve (AUC) for all considered features. Instead, in the multivariate textural analysis, the best performance (accuracy (ACC) = 0.78; AUC = 0.78) was reached with all 48 metrics and an LDA trained with balanced data. The best performance (ACC = 0.75; AUC = 0.80) using morphological features was reached with an SVM trained with 10-fold cross-variation (CV) and balanced data (with adaptive synthetic (ADASYN) function) and a subset of five robust morphological features (circularity, rectangularity, sphericity, gleaning and surface). The best performance (ACC = 0.82; AUC = 0.83) using dynamic features was reached with a trained SVM and balanced data (with ADASYN function). Conclusion: Multivariate analyses using pattern recognition approaches, including all morphological, textural and dynamic features, optimized by adaptive synthetic sampling and feature selection operations obtained the best results and showed the best performance in the discrimination of benign and malignant lesions.

scholarly journals Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration—a randomized in vivo study in rabbits

2021 ◽  
Author(s):  
L. A. R. Righesso ◽  
M. Terekhov ◽  
H. Götz ◽  
M. Ackermann ◽  
T. Emrich ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Bone Regeneration ◽  
Blood Perfusion ◽  
Autogenous Bone ◽  
Resonance Imaging ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Abstract Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

scholarly journals The Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Evaluation of Blood-Brain Barrier Disruption in Traumatic Brain Injury: What Is the Evidence?

2021 ◽  
Vol 11 (6) ◽  
pp. 775
Author(s):  
Sung-Suk Oh ◽  
Eun-Hee Lee ◽  
Jong-Hoon Kim ◽  
Young-Beom Seo ◽  
Yoo-Jin Choo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Magnetic Resonance ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Resonance Imaging ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

(1) Background: Blood brain barrier (BBB) disruption following traumatic brain injury (TBI) results in a secondary injury by facilitating the entry of neurotoxins to the brain parenchyma without filtration. In the current paper, we aimed to review previous dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to evaluate the occurrence of BBB disruption after TBI. (2) Methods: In electronic databases (PubMed, Scopus, Embase, and the Cochrane Library), we searched for the following keywords: dynamic contrast-enhanced OR DCE AND brain injury. We included studies in which BBB disruption was evaluated in patients with TBI using DCE-MRI. (3) Results: Four articles were included in this review. To assess BBB disruption, linear fit, Tofts, extended Tofts, or Patlak models were used. KTrans and ve were increased, and the values of vp were decreased in the cerebral cortex and predilection sites for diffusion axonal injury. These findings are indicative of BBB disruption following TBI. (4) Conclusions: Our analysis supports the possibility of utilizing DCE-MRI for the detection of BBB disruption following TBI.

scholarly journals Establishment of a Swine Model for Validation of Perfusion Measurement by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Anika Sauerbrey ◽  
Stefan Hindel ◽  
Marc Maaß ◽  
Christine Krüger ◽  
Andreas Wissmann ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Blood Flow ◽  
Femoral Artery ◽  
Resonance Imaging ◽  
Flow Probe ◽  
Dce Mri ◽  
Perfusion Measurement ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
Perfusion Measurements

The aim of the study was to develop a suitable animal model for validating dynamic contrast-enhanced magnetic resonance imaging perfusion measurements. A total of 8 pigs were investigated by DCE-MRI. Perfusion was determined on the hind leg musculature. An ultrasound flow probe placed around the femoral artery provided flow measurements independent of MRI and served as the standard of reference. Images were acquired on a 1.5 T MRI scanner using a 3D T1-weighted gradient-echo sequence. An arterial catheter for local injection was implanted in the femoral artery. Continuous injection of adenosine for vasodilation resulted in steady blood flow levels up to four times the baseline level. In this way, three different stable perfusion levels were induced and measured. A central venous catheter was used for injection of two different types of contrast media. A low-molecular weight contrast medium and a blood pool contrast medium were used. A total of 6 perfusion measurements were performed with a time interval of about 20–25 min without significant differences in the arterial input functions. In conclusion the accuracy of DCE-MRI-based perfusion measurement can be validated by comparison of the integrated perfusion signal of the hind leg musculature with the blood flow values measured with the ultrasound flow probe around the femoral artery.

Diagnostic performance of diffusion-weighted imaging combined with dynamic contrast-enhanced magnetic resonance imaging for prostate cancer: a systematic review and meta-analysis

2020 ◽  
pp. 028418512095626
Author(s):  
Lu Yang ◽  
Yuchuan Tan ◽  
Hanli Dan ◽  
Lin Hu ◽  
Jiuquan Zhang
Keyword(s):  
Magnetic Resonance Imaging ◽  
Prostate Cancer ◽  
Magnetic Resonance ◽  
Likelihood Ratio ◽  
Diffusion Weighted Imaging ◽  
Diagnostic Performance ◽  
Resonance Imaging ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Background The diagnostic performance of diffusion-weighted imaging (DWI) combined with dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for the detection of prostate cancer (PCa) has not been studied systematically to date. Purpose To investigate the value of DWI combined with DCE-MRI quantitative analysis in the diagnosis of PCa. Material and Methods A systematic search was conducted through PubMed, MEDLINE, the Cochrane Library, and EMBASE databases without any restriction to language up to 10 December 2019. Studies that used a combination of DWI and DCE-MRI for diagnosing PCa were included. Results Nine studies with 778 participants were included. The combination of DWI and DCE-MRI provide accurate performance in diagnosing PCa with pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratios of 0.79 (95% confidence interval [CI] = 0.76–0.81), 0.85 (95% CI = 0.83–0.86), 6.58 (95% CI = 3.93–11.00), 0.24 (95% CI = 0.17–0.34), and 36.43 (95% CI = 14.41–92.12), respectively. The pooled area under the summary receiver operating characteristic curve was 0.9268. Moreover, 1.5-T MR scanners demonstrated a slightly better performance than 3.0-T scanners. Conclusion Combined DCE-MRI and DWI could demonstrate a highly accurate area under the curve, sensitivity, and specificity for detecting PCa. More studies with large sample sizes are warranted to confirm these results.

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