Operator dependency of arterial input function in dynamic contrast-enhanced MRI.

OBJECTIVE: To investigate the effect of inter-operator variability in arterial input function (AIF) definition on kinetic parameter estimates (KPEs) from dynamic contrast-enhanced (DCE) MRI in patients with high-grade gliomas. METHODS: The study included 118 DCE series from 23 patients. AIFs were measured by three domain experts (DEs), and a population AIF (pop-AIF) was constructed from the measured AIFs. The DE-AIFs, pop-AIF and AUC-normalized DE-AIFs were used for pharmacokinetic analysis with the extended Tofts model. AIF-dependence of KPEs was assessed by intraclass correlation coefficient (ICC) analysis, and the impact on relative longitudinal change in Ktrans was assessed by Fleiss' kappa (κ). RESULTS: There was a moderate to substantial agreement (ICC 0.51-0.76) between KPEs when using DE-AIFs, while AUC-normalized AIFs yielded ICC 0.77-0.95 for Ktrans, kep and ve and ICC 0.70 for vp. Inclusion of the pop-AIF did not reduce agreement. Agreement in relative longitudinal change in Ktrans was moderate (κ = 0.591) using DE-AIFs, while AUC-normalized AIFs gave substantial (κ = 0.809) agreement. DISCUSSION: AUC-normalized AIFs can reduce the variation in kinetic parameter results originating from operator input. The pop-AIF presented in this work may be applied in absence of a satisfactory measurement.

Prediction of survival and progression in glioblastoma patients using temporal perfusion changes during radiochemotherapy.

BACKGROUND: The aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma. METHODS: Twenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (Ktrans) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated. RESULTS: Median survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in Ktrans/CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in Ktrans and relative CBV from DSC significantly corresponding with survival time in months (r2 = 0.843; p < 0.001). CONCLUSIONS: Significant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information.

T1 in high-grade glioma and the influence of different measurement strategies on parameter estimations in DCE-MRI.

BACKGROUND: To investigate the evolution of T1 in tumor and the necessity of baseline T1 (T1 (0)) mapping for the accurate estimation of kinetic parameters during standard therapy using dynamic contrast enhanced (DCE) MRI in patients with high-grade glioma (HGG). METHODS: Longitudinal DCE-MRI was performed in 23 patients (196 scans) with confirmed HGG. Kinetic parameters were derived from the extended Tofts model and analyzed both using fixed and pixel-wise T1 (0) values estimated from a Look-Locker sequence. Median tumor T1 value from all scans was used for fixed T1 (0) analysis. Dependence of accurate T1 (0) mapping for the estimation of the kinetic parameters was further investigated through computer simulations and histogram analysis. RESULTS: T1 in tumor increased significantly during and after treatment (P < 0.001). There was a linear correlation between the error in 1/T1 (0) and the resulting error in estimated parameters in both simulations and clinical data (r(2) >0.98 for all parameters). A strong correlation between the estimated longitudinal change in all kinetic parameters obtained using pixel-wise and fixed T1 (0) was observed (r(2) > 0.84 for all parameters). Histogram analysis revealed a linear change (r(2) > 0.62) in K(trans) normalized histogram peak height ratio as function of percentage deviation from the nominal T1 (0) value. No effect of T1 (0) histogram distribution on K(trans) was observed (P = 0.52). CONCLUSION: Temporal changes in the median kinetic parameters in tumor were equally well described using pixel-wise and fixed T1 (0) despite an increase in T1 (0) over time, suggesting that T1 mapping is not generally required in DCE-MRI based monitoring of glioma patients.

T2*-correction in dynamic contrast-enhanced MRI from double-echo acquisitions.

PURPOSE: To evaluate the importance of T2*-effects on the arterial input function (AIF) and on the resulting dynamic parameter estimation in dynamic contrast-enhanced (DCE) MRI of high-grade gliomas. MATERIALS AND METHODS: Seven patients with high-grade gliomas were imaged in total 50 times using a double-echo DCE sequence. Kinetic analysis using the extended Tofts model was performed using AIFs with and without correction for T2*-effects, and the resulting estimates of the transfer constant (K(trans) ), blood plasma volume (vp ), and the rate constant (kep ) were compared. Numerical simulations were done for comparison with clinical results as well as to further investigate the dependency of parameter values on the magnitude of T2*-induced errors. RESULTS: All kinetic parameters were found to be overestimated if T2*-effects in the AIF were not accounted for; with vp being most severely affected. The relative error in each parameter was dependent on the absolute parameter magnitude, resulting in incorrect parametric tumor distributions in the presence of uncorrected AIF T2*-effects. CONCLUSION: In DCE, a sufficiently short echo time should be used or corrections for T2*-effects based on double-echo acquisition should be made for correct quantification of kinetic parameters.

Sampling requirements in DCE-MRI based analysis of high grade gliomas: simulations and clinical results.

PURPOSE: To investigate the effect of variations in temporal resolution and total measurement times on the estimations of kinetic parameters derived from dynamic contrast-enhanced (DCE) MRI in patients with high-grade gliomas (HGGs). MATERIALS AND METHODS: DCE-MRI with high temporal resolution (dynamic sampling time (T(s)) = 2.1 s and 3.4 s) and total sampling time (T(acq)) of 5.2 min was acquired in 101 examinations from 15 patients. Using the modified Tofts model K(trans), k(ep) v(e) and v(p) were estimated. The effects of increasing T(s) and reducing T(acq) on the estimated kinetic parameters were estimated through down-sampling and data truncation, and the results were compared with numerical simulations. RESULTS: There was an overall dependence of all four kinetic parameters on T(s) and T(acq). Increasing T(s) resulted in under-estimation of K(trans) and over-estimation of V(p), whereas k(ep) and V(e) varied in a less predictable manner. Reducing T(acq) resulted in over-estimation of K(trans) and k(ep) and under-estimation of v(p) and v(e). Increasing T(s) and reducing T(acq) resulted in increased relative error for all four parameters. CONCLUSION: Estimated K(trans), K(ep), and V(e) in HGGs were within 15% of the high sampling rate reference values for T(s) <20 s. Increasing T(s) and reducing T(acq) leads to reduced precision of the estimated values.