Tong San Koh

Objective. The variable flip angle (VFA) method for longitudinal relaxation time (T ₁) measurement is inherently sensitive to inaccuracies in the radiofRequency transmit field (B ₁) and incomplete spoiling of transverse magnetization. The objective of this study is to devise a computational method that addresses the problems of incomplete spoiling and B ₁ inhomogeneity in the estimation of T ₁ using VFA method. Approach. Using an analytical expression of the gradient echo signal with account of incomplete spoiling, we first showed that ill-posedness in the simultaneous estimation of B ₁ and T ₁ can be lifted with the use of flip angles larger than the Ernst angle. We then devised a nonlinear optimization method based on this signal model of incomplete spoiling for simultaneous estimation of B ₁ and T ₁. Main results. We evaluated the proposed method on a graded-concentration phantom to show that the derived T ₁ estimates offers an improvement over the regular VFA method and compares well with reference values measured by inversion recovery. Reduction of the number of flip angles from 17 to 5 yielded consistent results indicating that the proposed method is numerically stable. T ₁ estimates derived from in-vivo brain imaging were consistent with literature values for gray and white matter tissues. Significance. Contrary to the common notion that B ₁ correction in the VFA method for T ₁ mapping should be performed separately, we show that combined estimation of B ₁ and T ₁ is feasible by the proposed method simply with the acquisition of 5 flip angles, as demonstrated on both phantom and in-vivo imaging data.

The double-angle method (DAM) is commonly used as a reference standard in radiofrequency field ( B ₁ ) mapping studies. This study explored two aspects of DAM: (i) use of small flip angle pairs to reduce the repetition time (TR) needed for adequate longitudinal relaxation ( T ₁ ); and (ii) the effect of using different flip angle ratios for B ₁ mapping. Results of phantom studies show that B ₁ correction using small flip angle pairs ≤ 60° with TR = 5000 ms can allow for accurate estimation of T ₁ up to about 1500 ms; and that increasing the ratio of the two flip angles used for B ₁ correction resulted in more accurate estimation of T ₁ . These modifications allow 3-dimensional (3D) B ₁ mapping to be consistently performed with the same 3D spoiled gradient echo sequence used for T ₁ mapping in dynamic contrast-enhanced MRI.

The transfer constant K ^trans is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of K ^trans as a potential biomarker of tumor vasculature remains unclear. In this study, computer simulations based on a comprehensive tracer kinetic model with multiple pathways was used to provide clarification on the interpretation and application of K ^trans . Tissue concentration-time curves pertaining to a wide range of transport conditions were simulated using the multiple-pathway (MP) model and fitted using the generalized kinetic (GK) and extended GK models. Relationships between K ^trans and plasma flow F _p , vessel permeability PS and extraction rate EF _p under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of K ^trans based on the vascular transit time. K ^trans is primarily associated with F _p and EF _p respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and F _p only serve as secondary constraints for which K ^trans can be further associated with EF _p and PS in the slow and rapid transit states, respectively.

Contrary to the common notion that tumor necrotic regions are non‐enhancing after contrast administration, recent evidence has shown that necrotic regions exhibit delayed and slow uptake of gadolinium tracer on dynamic contrast‐enhanced MRI (DCE MRI). The purpose of this study is to explore whether the mapping of tumor voxels with delayed and slow enhancement on DCE MRI can be used to derive estimates of tumor necrotic fraction. Patient‐derived tumor xenograft lines of seven human cancers were implanted in 26 mice which were subjected to DCE MRI performed using a spoiled gradient recalled sequence. Gadolinium tracer concentration was estimated using the variable flip angle technique. To identify tumor voxels exhibiting delayed and slow uptake of contrast medium, clustering analysis was performed using a k‐means clustering algorithm that classified tumor voxels according to their contrast enhancement patterns. Comparison of the percentage of tumor voxels exhibiting delayed and slow enhancement with the tumor necrotic fraction estimated on histology showed a strong correlation (r = 0.962, p < 0.001). The mapping of tumor regions with delayed and slow contrast uptake on DCE MRI correlated strongly with tumor necrotic fraction, and can potentially serve as a non‐invasive imaging surrogate for the in vivo assessment of necrotic fraction. Copyright © 2014 John Wiley & Sons, Ltd.

To compare four different tracer kinetic models for the analysis of dynamic contrast material-enhanced computed tomographic (CT) data with respect to the prediction of 5-year overall survival in primary colorectal cancer. This study was approved by the ethical review board. Archival dynamic contrast-enhanced CT data from 46 patients with colorectal cancer, obtained as part of a research study, were analyzed retrospectively by using the distributed parameter, conventional compartmental, adiabatic tissue homogeneity, and generalized kinetic models. Blood flow, blood volume, mean transit time (MTT), permeability-surface area product, extraction fraction, extravascular extracellular volume (v(e)), and volume transfer constant (K(trans)) were compared by using the Friedman test, with statistical significance at 5%. Following receiver operating characteristic analysis, parameters of the different kinetic models and tumor stage were compared with respect to overall survival discrimination, with use of Kaplan Meier analysis and a univariate Cox proportional hazard model, with additional cross-validation and permutation testing. Blood flow was lower with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001), and blood flow values determined with the conventional compartmental and adiabatic tissue homogeneity models were similar. Conversely, MTT was longer with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001). Blood volume, permeability-surface area product, and v(e) were higher with the conventional compartmental model than with the adiabatic tissue homogeneity, distributed parameter, or generalized kinetic models (P < .0001). The extraction fraction was higher with the distributed parameter model than with the adiabatic tissue homogeneity model. With respect to 5-year overall survival, only the distributed parameter model-derived v(e) was predictive of 5-year overall survival with a threshold value of 15.48 mL/100 mL after cross-validation and permutation testing. Parameter values differ significantly between models. Of the models investigated, the distributed parameter model was the best predictor of 5-year overall survival. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120186/-/DC1.

Computer simulations based on a physiologically realistic tracer kinetic model with multiple pathways was used to provide insights on the applicability and interpretation of tissue enhancement metrics such as the maximum slope, peak enhancement and area under curve, commonly used in dynamic contrast-enhanced (DCE) MRI. Results show that physiological conditions of the tissue that could affect the accuracy of the maximal slope method include a high blood flow, increased variability of flow within the vasculature or a low vascular volume. Interestingly, changes in permeability and interstitial volume might not affect the accuracy of the maximal slope method. Time-to-peak and peak value of the tissue enhancement curve are not strictly properties of the tissue alone, and they cannot be linearly related to intrinsic tissue parameters such as blood flow, blood volume, capillary permeability, interstitial volume and mean transit time. Similar to the normalized initial area under tissue concentration curve, an alternative estimate of the total tracer distribution volume can be simply given by the ratio of tracer concentration in the tissue and artery sampled at the final DCE scan.