Characterization of D-maltose as a T2 -exchange contrast agent for dynamic contrast-enhanced MRI.
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ABSTRACT:
SUBMITTER: Goldenberg JM
PROVIDER: S-EPMC6010162 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Characterization of D-maltose as a T<sub>2</sub> -exchange contrast agent for dynamic contrast-enhanced MRI.
Goldenberg Joshua M JM Pagel Mark D MD Cárdenas-Rodríguez Julio J
Magnetic resonance in medicine 20180125 3
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Project description:The volume transfer constant Ktrans , which describes the leakage of contrast agent (CA) from vasculature into tissue, is the most commonly reported quantitative parameter for dynamic contrast-enhanced (DCE-) MRI. However, the variation in reported Ktrans values between studies from different institutes is large. One of the primary sources of uncertainty is quantification of the arterial input function (AIF). The aim of this study is to determine the influence of the CA injection duration on the AIF and tracer kinetic analysis (TKA) parameters (i.e. Ktrans , kep and ve ). Thirty-one patients with prostate cancer received two DCE-MRI examinations with an injection duration of 5 s in the first examination and a prolonged injection duration in the second examination, varying between 7.5 s and 30 s. The DCE examination was carried out on a 3.0 T MRI scanner using a transversal T1 -weighted 3D spoiled gradient echo sequence (300 s duration, dynamic scan time of 2.5 s). Data of 29 of the 31 were further analysed. AIFs were determined from the phase signal in the left and right femoral arteries. Ktrans , kep and ve were estimated with the standard Tofts model for regions of healthy peripheral zone and tumour tissue. We observed a significantly smaller peak height and increased width in the AIF for injection durations of 15 s and longer. However, we did not find significant differences in Ktrans , kep or ve for the studied injection durations. The study demonstrates that the TKA parameters Ktrans , kep and ve , measured in the prostate, do not show a significant change as a function of injection duration.
| S-EPMC6175355 | biostudies-literature
Project description:We explored the prognostic impact of the dynamic contrast enhanced MR imaging (DCE-MRI) parameter ABrix in cervical cancer combined with global gene expression data to reveal the underlying molecular phenotype of the parameter and construct a gene signature that reflected ABrix. Based on 78 cervical cancer patients subjected to curative chemoradiotherapy, we identified a prognostic ABrix parameter by pharmacokinetic analysis of DCE-MR images based on the Brix model, where tumors with low ABrix appeared to be most aggressive. Gene set enrichment analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to proliferation, radioresistance, and wound healing were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including targets of the hypoxia inducible factor (HIF1M-NM-1) and the unfolded protein response (UPR), were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1M-NM-1 protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. Based on the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Gene expression correlating with the DCE-MRI parameter ABrix were identified in 46 patients (DCE-MRI cohort) and used to find a hypoxia gene signature. The prognsotic impact of the gene signature was validated in an independent cohort of 109 patients (validation chort). Cell culture experiments were performed to generate cervical cancer specific gene lists associated with hypoxia (GSM897799 - GSM897804).
2012-08-16 | E-GEOD-36562 | biostudies-arrayexpress
Project description:PurposeTo propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast-enhanced (DCE) examinations undertaken with standard clinical fat-suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas.MethodsA standard fat-suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)-weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre-, peak-, and post-contrast agent administration) for 20 patients, pre-treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank-sum test).ResultsThe calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat-suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre-, peak-, and post-contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post-contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post-contrast T1 values, potentially related to their infiltrative growth pattern.ConclusionsThis work has demonstrated the feasibility of fat-suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.
| S-EPMC5814859 | biostudies-literature
Project description:PurposeTo investigate the feasibility of using multiple flip angles in dynamic contrast enhanced (DCE) MRI to reduce the uncertainty in estimation of intracellular water lifetime (τi ).MethodsNumerical simulation studies were conducted to assess the uncertainty in estimation of τi using dynamic contrast enhanced MRI with one or two flip angles. In vivo experiments with a murine brain tumor model were conducted at 7T using two flip angles. The in vivo data were used to compare τi estimation using the single-flip-angle (SFA) protocol with that using the double-flip-angle (DFA) protocol. Data analysis was conducted using the two-compartment exchange model combined with the three-site-two-exchange model for water exchange.ResultsIn the numerical simulation studies with a range of contrast kinetic parameters and signal-to-noise ratio = 20, the median bias of τi estimation decreased from 72 ms with SFA to 65 ms with DFA, and the corresponding median inter-quartile range reduced from 523 ms to 156 ms. In the in vivo studies, τi estimation with SFA was not successful in most voxels in the tumors, as the estimated τi values reached the upper limit of the parameter range (2 s). In contrast, the estimated τi values with DFA were mostly between 0.2 and 1.5 s and homogeneously distributed spatially across the tumor. The τi estimation with DFA was less sensitive to arterial input function scaling but more sensitive to pre-contrast T1 than the other contrast kinetic parameters.ConclusionThis study results demonstrate the feasibility of using multiple flip angles to encode the post-contrast time-intensity curve with different weighting of water exchange effect to reduce the uncertainty in τi estimation.
| S-EPMC6817382 | biostudies-literature
Project description:We explored the prognostic impact of the dynamic contrast enhanced MR imaging (DCE-MRI) parameter ABrix in cervical cancer combined with global gene expression data to reveal the underlying molecular phenotype of the parameter and construct a gene signature that reflected ABrix. Based on 78 cervical cancer patients subjected to curative chemoradiotherapy, we identified a prognostic ABrix parameter by pharmacokinetic analysis of DCE-MR images based on the Brix model, where tumors with low ABrix appeared to be most aggressive. Gene set enrichment analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to proliferation, radioresistance, and wound healing were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response (UPR), were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. Based on the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients.
2012-08-16 | GSE36562 | GEO
Project description:PurposeThis study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T2 exchange (T2ex ) properties after interacting with a molecular biomarker.MethodsThe contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O2 . The R1 and R2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r2ex relaxivities.ResultsThe reaction of Tm-DO3A-oAA with NO and O2 caused a 6.4-fold increase in the r2 relaxivity of the agent, whereas r1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T2ex agent. The effects of pH and temperature on the r2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand.ConclusionsT2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665-1670, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
| S-EPMC5071101 | biostudies-literature
Project description:The passage of a vascular-injected paramagnetic contrast reagent (CR) bolus through a region-of-interest affects tissue (1)H(2)O relaxation and thus MR image intensity. For longitudinal relaxation [R(1) identical with (T(1))(-1)], the CR must have transient molecular interactions with water. Because the CR and water molecules are never uniformly distributed in the histological-scale tissue compartments, the kinetics of equilibrium water compartmental interchange are competitive. In particular, the condition of the equilibrium trans cytolemmal water exchange NMR system sorties through different domains as the interstitial CR concentration, [CR(o)], waxes and wanes. Before CR, the system is in the fast-exchange-limit (FXL). Very soon after CR(o) arrival, it enters the fast-exchange-regime (FXR). Near maximal [CR(o)], the system could enter even the slow-exchange-regime (SXR). These conditions are defined herein, and a comprehensive description of how they affect quantitative pharmacokinetic analyses is presented. Data are analyzed from a population of 22 patients initially screened suspicious for breast cancer. After participating in our study, the subjects underwent biopsy/pathology procedures and only 7 (32%) were found to have malignancies. The transient departure from FXL to FXR (and apparently not SXR) is significant in only the malignant tumors, presumably because of angiogenic capillary leakiness. Thus, if accepted, this analysis would have prevented the 68% of the biopsies that proved benign.
| S-EPMC2582941 | biostudies-literature
Project description:PurposeThe aim of this study was to assess the uncertainty in estimation of MR tracer kinetic parameters and water exchange rates in T1-weighted dynamic contrast enhanced (DCE) MRI.MethodsSimulated DCE-MRI data were used to assess four kinetic models; general kinetic model with a vascular compartment (GKM2), GKM2 combined with water exchange (SSM2), adiabatic approximation of the tissue homogeneity model (ATH), and ATH combined with water exchange (ATHX).ResultsIn GKM2 and SSM2, increase in transfer constant (K(trans)) led to underestimation of vascular volume fraction (vb), and increase in vb led to overestimation of K(trans). Such coupling between K(trans) and vb was not observed in ATH and ATHX. The precision of estimated intracellular water lifetime (τi) was substantially improved in both SSM2 and ATHX when K(trans) > 0.3 min(-1). K(trans) and vb from ATHX model had significantly smaller errors than those from ATH model (P < 0.05).ConclusionThe results of this study demonstrated the feasibility of measuring τi from DCE-MRI data albeit low precision. While the inclusion of water exchange improved the accuracy of K(trans), vb, and the interstitial volume fraction estimation (ve), it lowered the precision of other kinetic model parameters within the conditions investigated in this study.
| S-EPMC3942367 | biostudies-literature
Project description:Diabetes is associated with hepatic metabolic dysfunction predisposing patients to drug-induced liver injury. Mouse models of type 2 diabetes (T2D) have dramatically reduced expression of organic anion transporting polypeptide (OATP)1A1, a transporter expressed in hepatocytes and in the kidneys. The effects of diabetes on OATP1B2 expression are less studied and less consistent. OATP1A1 and OATP1B2 both transport endogenous substrates such as bile acids and hormone conjugates as well as numerous drugs including gadoxetate disodium (Gd-EOB-DTPA). As master pharmacokinetic regulators, the altered expression of OATPs in diabetes could have a profound and clinically significant influence on drug therapies. Here, we report a method to noninvasively measure OATP activity in T2D mice by quantifying the transport of hepatobiliary-specific gadolinium-based contrast agents (GBCAs) within the liver and kidneys using dynamic contrast-enhanced MRI (DCE-MRI). By comparing GBCA uptake in control and OATP knockout mice, we confirmed liver clearance of the hepatobiliary-specific GBCAs, Gd-EOB-DTPA, and gadobenate dimeglumine, primarily though OATP transporters. Then, we measured a reduction in the hepatic uptake of these hepatobiliary GBCAs in T2D ob/ob mice, which mirrored significant reductions in the mRNA and protein expression of OATP1A1 and OATP1B2. As these GBCAs are U.S. Food and Drug Administration-approved agents and DCE-MRI is a standard clinical protocol, studies to determine OATP1B1/1B3 deficiencies in human individuals with diabetes can be easily envisioned.
| S-EPMC6341305 | biostudies-literature
Project description:To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI.The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol.The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30° and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves.The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions.
| S-EPMC3195376 | biostudies-other