scholarly journals Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI

2002 ◽  
Vol 1 (3) ◽  
pp. 153535002002021
Author(s):  
Nick G. Costouros ◽  
Dominique Lorang ◽  
Yantian Zhang ◽  
Marshall S. Miller ◽  
Felix E. Diehn ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Tumor Heterogeneity ◽  
Protein Translation ◽  
Pharmacokinetic Parameters ◽  
Transcriptional Level ◽  
Target Tissue ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

scholarly journals Quantitative Evaluation of Temporal Regularizers in Compressed Sensing Dynamic Contrast Enhanced MRI of the Breast

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Wang ◽  
Lori R. Arlinghaus ◽  
Thomas E. Yankeelov ◽  
Xiaoping Yang ◽  
David S. Smith
Keyword(s):  
Compressed Sensing ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Pharmacokinetic Parameters ◽  
Transfer Constant ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
Space Data

Purpose. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used in cancer imaging to probe tumor vascular properties. Compressed sensing (CS) theory makes it possible to recover MR images from randomly undersampled k-space data using nonlinear recovery schemes. The purpose of this paper is to quantitatively evaluate common temporal sparsity-promoting regularizers for CS DCE-MRI of the breast. Methods. We considered five ubiquitous temporal regularizers on 4.5x retrospectively undersampled Cartesian in vivo breast DCE-MRI data: Fourier transform (FT), Haar wavelet transform (WT), total variation (TV), second-order total generalized variation (TGVα2), and nuclear norm (NN). We measured the signal-to-error ratio (SER) of the reconstructed images, the error in tumor mean, and concordance correlation coefficients (CCCs) of the derived pharmacokinetic parameters Ktrans (volume transfer constant) and ve (extravascular-extracellular volume fraction) across a population of random sampling schemes. Results. NN produced the lowest image error (SER: 29.1), while TV/TGVα2 produced the most accurate Ktrans (CCC: 0.974/0.974) and ve (CCC: 0.916/0.917). WT produced the highest image error (SER: 21.8), while FT produced the least accurate Ktrans (CCC: 0.842) and ve (CCC: 0.799). Conclusion. TV/TGVα2 should be used as temporal constraints for CS DCE-MRI of the breast.

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 Quantitative dynamic contrast-enhanced MR imaging can be used to predict the pathologic stages of oral tongue squamous cell carcinoma

2020 ◽  
Author(s):  
Na Guo ◽  
Weike Zeng ◽  
Hong Deng ◽  
Huijun Hu ◽  
Ziliang Cheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Predictive Value ◽  
Roc Analysis ◽  
Pharmacokinetic Parameters ◽  
Oral Tongue ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Abstract Background: To investigate whether quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters can be used to predict the pathologic stages of oral tongue squamous cell carcinoma (OTSCC). Methods: For this prospective study, DCE-MRI was performed in participants with OTSCC from May 2016 to June 2017. The pharmacokinetic parameters, including K trans , K ep , V e , and V p , were derived from DCE-MRI by utilizing a two-compartment extended Tofts model and a three-dimensional volume of interest. The postoperative pathologic stage was determined in each patient based on the 8th AJCC cancer staging manual. The quantitative DCE-MRI parameters were compared between stage I-II and stage III-IV lesions. Logistic regression analysis was used to determine independent predictors of tumor stages, followed by receiver operating characteristic (ROC) analysis to evaluate the predictive performance. Results: The mean K trans , K ep and V p values were significantly lower in stage III-IV lesions compared with stage I-II lesions ( p = 0.013, 0.005 and 0.011, respectively). K ep was an independent predictor for the advanced stages as determined by univariate and multivariate logistic analysis. ROC analysis showed that K ep had the highest predictive capability, with a sensitivity of 64.3%, a specificity of 82.6%, a positive predictive value of 81.8%, a negative predictive value of 65.5%, and an accuracy of 72.5%. Conclusion: The quantitative DCE-MRI parameter K ep can be used as a biomarker for predicting pathologic stages of OTSCC.

scholarly journals Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Inge C. M. Verheggen ◽  
Joost J. A. de Jong ◽  
Martin P. J. van Boxtel ◽  
Alida A. Postma ◽  
Frans R. J. Verhey ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Gray Matter ◽  
Circumventricular Organs ◽  
Brain Barrier ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Blood Brain ◽  
Contrast Enhanced ◽  
The Brain

Abstract Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

scholarly journals Pharmacokinetic parameters and radiomics model based on dynamic contrast enhanced MRI for the preoperative prediction of sentinel lymph node metastasis in breast cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Meijie Liu ◽  
Ning Mao ◽  
Heng Ma ◽  
Jianjun Dong ◽  
Kun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Lymph Node ◽  
Regression Method ◽  
Pharmacokinetic Parameters ◽  
Combined Model ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Preoperative Prediction ◽  
Contrast Enhanced

Abstract Background To establish pharmacokinetic parameters and a radiomics model based on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for predicting sentinel lymph node (SLN) metastasis in patients with breast cancer. Methods A total of 164 breast cancer patients confirmed by pathology were prospectively enrolled from December 2017 to May 2018, and underwent DCE-MRI before surgery. Pharmacokinetic parameters and radiomics features were derived from DCE-MRI data. Least absolute shrinkage and selection operator (LASSO) regression method was used to select features, which were then utilized to construct three classification models, namely, the pharmacokinetic parameters model, the radiomics model, and the combined model. These models were built through the logistic regression method by using 10-fold cross validation strategy and were evaluated on the basis of the receiver operating characteristics (ROC) curve. An independent validation dataset was used to confirm the discriminatory power of the models. Results Seven radiomics features were selected by LASSO logistic regression. The radiomics model, the pharmacokinetic parameters model, and the combined model yielded area under the curve (AUC) values of 0.81 (95% confidence interval [CI]: 0.72 to 0.89), 0.77 (95% CI: 0.68 to 0.86), and 0.80 (95% CI: 0.72 to 0.89), respectively, for the training cohort and 0.74 (95% CI: 0.59 to 0.89), 0.74 (95% CI: 0.59 to 0.90), and 0.76 (95% CI: 0.61 to 0.91), respectively, for the validation cohort. The combined model showed the best performance for the preoperative evaluation of SLN metastasis in breast cancer. Conclusions The model incorporating radiomics features and pharmacokinetic parameters can be conveniently used for the individualized preoperative prediction of SLN metastasis in patients with breast cancer.

scholarly journals Dynamic contrast-enhanced magnetic resonance imaging of the lung reveals important pathobiology in idiopathic pulmonary fibrosis

2021 ◽  
pp. 00907-2020
Author(s):  
Sydney B. Montesi ◽  
Iris Zhou ◽  
Lloyd L. Liang ◽  
Subba R. Digumarthy ◽  
Sarah Mercaldo ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Extracellular Space ◽  
Progressive Disease ◽  
Functional Information ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Peak Enhancement ◽  
Contrast Enhanced

IntroductionEvidence suggest that abnormalities occur in the lung microvasculature in idiopathic pulmonary fibrosis (IPF). We hypothesized that dynamic contrast-enhanced (DCE)-MRI could detect alterations in permeability, perfusion, and extracellular extravascular volume in idiopathic pulmonary fibrosis thus providing in vivo regional functional information not otherwise available.MethodsHealthy controls and IPF subjects underwent DCE-MRI of the thorax using a dynamic volumetric radial sampling sequence and administration of gadoterate meglumine at a dose of 0.1 mmol·kg−1 at 2 mL·s−1. Model-free analysis of signal intensity versus time curves in regions of interest from a lower, middle, and upper axial plane and a posterior coronal plane yielded parameters reflective of perfusion and permeability (peak enhancement and rate of contrast arrival, kwashin) and the extracellular extravascular space (rate of contrast clearance, kwashout). These imaging parameters were compared between IPF and healthy control subjects, and between fast/slow IPF progressors.ResultsIPF subjects (n=16, M=56%, age=67.5 (range 60–79)) had significantly reduced peak enhancement and slower kwashin in all measured lung regions compared to the healthy volunteers (n=17, M=65%, age=58 (range 51–63)) on unadjusted analyses consistent with microvascular alterations. kwashout, as a measure of the extravascular extracellular space, was significantly slower in the lower lung and posterior coronal regions in the IPF subjects consistent with an increased extravascular extracellular space. All estimates were attenuated after adjusting for age. Similar trends were observed, but only the associations with kwashin remained statistically significant. Among IPF subjects, kwashout rates nearly perfectly discriminated between those with rapidly progressive disease versus those with stable/slowly progressive disease.ConclusionsDCE-MRI detects changes in the microvasculature and extravascular extracellular space in IPF thus providing in vivo regional functional information.

scholarly journals Permeability of the windows of the brain: Feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

2020 ◽  
Author(s):  
Inge C.M. Verheggen ◽  
Joost J.A. de Jong ◽  
Martin P.J. van Boxtel ◽  
Alida A. Postma ◽  
Frans R.J. Verhey ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Gray Matter ◽  
Circumventricular Organs ◽  
Brain Barrier ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Blood Brain ◽  
Contrast Enhanced ◽  
The Brain

Abstract Background: Circumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence.Methods: Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.Results: In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.Conclusions: Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

scholarly journals Quantitative Three-Dimensional Assessment of the Pharmacokinetic Parameters of Intra- and Peri-tumoural Tissues on Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging

2021 ◽  
Author(s):  
A. Niukkanen ◽  
H. Okuma ◽  
M. Sudah ◽  
P. Auvinen ◽  
A. Mannermaa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Resonance Imaging ◽  
Three Dimensional ◽  
Pharmacokinetic Parameters ◽  
High Grade ◽  
Breast Cancers ◽  
Resonance Imaging ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

AbstractWe aimed to assess the feasibility of three-dimensional (3D) segmentation and to investigate whether semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are associated with traditional prognostic factors for breast cancer. In addition, we evaluated whether both intra-tumoural and peri-tumoural DCE parameters can differentiate the breast cancers that are more aggressive from those that are less aggressive. Consecutive patients with newly diagnosed invasive breast cancer and structural breast MRI (3.0 T) were included after informed consent. Fifty-six patients (mean age, 57 years) with mass lesions of > 7 mm in diameter were included. A semi-automatic image post-processing algorithm was developed to measure 3D pharmacokinetic information from the DCE-MRI images. The kinetic parameters were extracted from time-signal curves, and the absolute tissue contrast agent concentrations were calculated with a reference tissue model. Markedly, higher intra-tumoural and peri-tumoural tissue concentrations of contrast agent were found in high-grade tumours (n = 44) compared to low-grade tumours (n = 12) at every time point (P = 0.006–0.040), providing positive predictive values of 90.6–92.6% in the classification of high-grade tumours. The intra-tumoural and peri-tumoural signal enhancement ratios correlated with tumour grade, size, and Ki67 activity. The intra-observer reproducibility was excellent. We developed a model to measure the 3D intensity data of breast cancers. Low- and high-grade tumours differed in their intra-tumoural and peri-tumoural enhancement characteristics. We anticipate that pharmacokinetic parameters will be increasingly used as imaging biomarkers to model and predict tumour behavior, prognoses, and responses to treatment.

Reproducibility and Reliability of Pancreatic Pharmacokinetic Parameters Derived from Dynamic Contrast-Enhanced Magnetic Resonance Imaging

2021 ◽  
Author(s):  
Weiwei Zhao ◽  
Jing Yu ◽  
Yuyu Bi ◽  
Yi Huan ◽  
Yuanqiang Zhu ◽  
...  
Keyword(s):  
Age Groups ◽  
Pancreatic Head ◽  
Pharmacokinetic Parameters ◽  
Intra Class Correlation ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced ◽  
In Virtue Of ◽  
Intra Class Correlation Coefficient ◽  
Selection Of

Abstract Objectives Dynamic contrast-enhanced MRI (DCE-MRI) with Extended Tofts Linear (ETL) model has been used in tissue and tumor evaluation. However, its reliability and reproducibility in pancreatic evaluation has been unclear. It is also unclear whether pancreatic DCE-MRI pharmacokinetic parameters were consistent and stable among different pancreatic regions, ages and genders. Methods Pancreatic pharmacokinetic parameters of 54 volunteers were calculated using DCE-MRI with ETL model. Firstly, Intra- and inter-observer reproducibility was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CoV). Secondly, subgroup evaluation of pancreatic DCE-MRI pharmacokinetic parameters was performed. 54 subjects were divided into three groups in virtue of pancreatic region, three groups according to age, two groups according to gender, which pharmacokinetic parameters among and between different groups were calculated and compared. Results There was excellent agreement and low variability of intra- and inter-observer to pancreatic DCE-MRI pharmacokinetic parameters. The intra- and inter-observer ICCs of Ktrans, kep, ve, vp were 0.971, 0.952, 0.959, 0.944 and 0.947, 0.911, 0.978, 0.917, respectively. The intra- and inter-observer CoVs of Ktrans, kep, ve, vp were 9.98%, 5.99%, 6.47%, 4.76% and 10.15%, 5.22%, 6.28%, 5.40%, respectively. There were no significant differences of Ktrans, kep among different pancreatic regions, among different age groups, between male and female groups (P all > 0.10). Only, pancreatic ve of old group was higher than that of young and middle-aged groups (P = 0.042, 0.001), and vp of pancreatic head was higher than that of pancreatic body and tail (P = 0.014, 0.043). Conclusions DCE-MRI with ETL model is reliable and reproducible for quantitative assessment of pancreatic pharmacokinetic parameters. ve varies with age and vp varies with pancreatic region, which can provide guidance for the selection of normal reference in the pharmacokinetics study of pancreatic diseases.

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