In vitro pharmacokinetic phantom for two-compartment modeling in DCE-MRI.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established minimally-invasive method for assessment of extravascular leakage, hemodynamics, and tissue viability. However, differences in acquisition protocols, variety of pharmacokinetic models, and uncertainty on physical sources of MR signal hamper the reliability and widespread use of DCE-MRI in clinical practice. Measurements performed in a controlled in vitro setup could be used as a basis for standardization of the acquisition procedure, as well as objective evaluation and comparison of pharmacokinetic models. In this paper, we present a novel flow phantom that mimics a two-compartmental (blood plasma and extravascular extracellular space/EES) vascular bed, enabling systemic validation of acquisition protocols. The phantom consisted of a hemodialysis filter with two compartments, separated by hollow fiber membranes. The aim of this phantom was to vary the extravasation rate by adjusting the flow in the two compartments. Contrast agent transport kinetics within the phantom was interpreted using two-compartmental pharmacokinetic models. Boluses of gadolinium-based contrast-agent were injected in a tube network connected to the hollow fiber phantom; time-intensity curves (TICs) were obtained from image series, acquired using a T1-weighted DCE-MRI sequence. Under the assumption of a linear dilution system, the TICs obtained from the input and output of the system were then analyzed by a system identification approach to estimate the trans-membrane extravasation rates in different flow conditions. To this end, model-based deconvolution was employed to determine (identify) the impulse response of the investigated dilution system. The flow rates in the EES compartment significantly and consistently influenced the estimated extravasation rates, in line with the expected trends based on simulation results. The proposed phantom can therefore be used to model a two-compartmental vascular bed and can be employed to test and optimize DCE-MRI acquisition sequences in order to determine a standardized acquisition procedure leading to consistent quantification results.

Model-Based Characterization of the Transpulmonary Circulation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Heart Failure and Healthy Volunteers.

OBJECTIVES: Novel quantitative measures of transpulmonary circulation status may allow the improvement of heart failure (HF) patient management. In this work, we propose a method for the assessment of the transpulmonary circulation using measurements from indicator time intensity curves, derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) series. The derived indicator dilution parameters in healthy volunteers (HVs) and HF patients were compared, and repeatability was assessed. Furthermore, we compared the parameters derived using the proposed method with standard measures of cardiovascular function, such as left ventricular (LV) volumes and ejection fraction. MATERIALS AND METHODS: In total, 19 HVs and 33 HF patients underwent a DCE-MRI scan on a 1.5 T MRI scanner using a T1-weighted spoiled gradient echo sequence. Image loops with 1 heartbeat temporal resolution were acquired in 4-chamber view during ventricular late diastole, after the injection of a 0.1-mmol gadoteriol bolus. In a subset of subjects (8 HFs, 2 HVs), a second injection of a 0.3-mmol gadoteriol bolus was performed with the same imaging settings. The study was approved by the local institutional review board.Indicator dilution curves were derived, averaging the MR signal within regions of interest in the right and left ventricle; parametric deconvolution was performed between the right and LV indicator dilution curves to identify the impulse response of the transpulmonary dilution system. The local density random walk model was used to parametrize the impulse response; pulmonary transit time (PTT) was defined as the mean transit time of the indicator. λ, related to the Péclet number (ratio between convection and diffusion) for the dilution process, was also estimated. RESULTS: Pulmonary transit time was significantly prolonged in HF patients (8.70 ± 1.87 seconds vs 6.68 ± 1.89 seconds in HV, P < 0.005) and even stronger when normalized to subject heart rate (normalized PTT, 9.90 ± 2.16 vs 7.11 ± 2.17 in HV, dimensionless, P < 0.001). λ was significantly smaller in HF patients (8.59 ± 4.24 in HF vs 12.50 ± 17.09 in HV, dimensionless, P < 0.005), indicating a longer tail for the impulse response. Pulmonary transit time correlated well with established cardiovascular parameters (LV end-diastolic volume index, r = 0.61, P < 0.0001; LV ejection fraction, r = -0.64, P < 0.0001). The measurement of indicator dilution parameters was repeatable (correlation between estimates based on the 2 repetitions for PTT: r = 0.94, P < 0.001, difference between 2 repetitions 0.01 ± 0.60 second, for λ: r = 0.74, P < 0.01, difference 0.69 ± 4.39). CONCLUSIONS: Characterization of the transpulmonary circulation by DCE-MRI is feasible in HF patients and HVs. Significant differences are observed between indicator dilution parameters measured in HVs and HF patients; preliminary results suggest good repeatability for the proposed parameters.

Comparison of the threshold for peripheral nerve stimulation during gradient switching in whole body MR systems.

PURPOSE: To compare thresholds for peripheral nerve stimulation from gradient switching in whole body magnetic resonance (MR) equipment of different design. MATERIALS AND METHODS: Threshold data obtained in three experiments were reformatted into a single joint data set describing thresholds for anterio-posterior (AP) gradient orientation and Echo Planar Imaging (EPI) waveforms with bipolar ramp times between 0.07 and 1.2 ms. Reformatting included the use of: a) the rate of change of the maximum field in the patient space as a measure of gradient output, b) lowest observable thresholds, c) lognormal distribution of thresholds, and d) equal standard deviation (SD) of all samples. RESULTS: The joint data fit a hyperbolic threshold function. The residues were not significantly different between experiments. CONCLUSION: Then expressed in appropriate format, the thresholds for peripheral nerve stimulation in volunteers for whole body MR equipment can be described with a hyperbolic threshold curve with rheobase 18.8 +/- 0.6 Tesla/second and chronaxie 0.36 +/- 0.02 milliseconds.

Automated quantitative evaluation of diseased and nondiseased renal transplants with MR renography.

PURPOSE: To present a method of automated parametric quantification of dynamic MR enhancement curves of renal transplants and evaluate the disease-discriminating properties of the resulting MR renography (MRR) data. MATERIALS AND METHODS: This study included 27 patients with nondiseased renal transplants and eight patients with diseased renal transplants. The examination was repeated in 10 patients and the reproducibility of the enhancement parameters was estimated by analysis of variance (ANOVA). The disease-discriminating properties of the transplant volumes and enhancement parameters were tested with t-tests and logistic regression analysis. RESULTS: The enhancement parameters were reproducible. The mean medullary nephronal washout rate (lambda1) and cortical arterial blood volume (mu0) were lower in diseased renal transplants. The combination of these parameters was a strong predictor of renal transplant disease (area under ROC curve 0.98; 95% confidence interval 0.96-1.0). CONCLUSION: Automated parametric quantification of cortical and medullary enhancement is feasible and allows the accurate detection of nonsurgical disease in renal transplants by MRR.