A comprehensive evaluation and impact of normalization of generalized tracer kinetic model parameters to characterize blood-brain-barrier permeability in normal-appearing and tumor tissue regions of patients with glioma

Abstract

Rationale and objectivesTo comprehensively evaluate robustness and variations of DCE-MRI derived generalized-tracer-kinetic-model (GTKM) parameters in healthy and tumor tissues and impact of normalization in mitigating these variations on application to glioma. Materials (patients) and methodsA retrospective study included pre-operative 31 high-grade-glioma(HGG), 22 low-grade-glioma(LGG) and 33 follow-up data from 10 patients a prospective study with 4 HGG subjects. Voxel-wise GTKM was fitted to DCE-MRI data to estimate Ktrans, ve, vb. Simulations were used to evaluate noise sensitivity. Variation of parameters with-respect-to arterial-input-function (AIF) variation and data length were studied. Normalization of parameters with-respect-to mean values in gray-matter (GM) and white-matter (WM) regions (GM-Type-2, WM-Type-2) and mean curves (GM-Type-1, WM-Type-1) were also evaluated. Co-efficient-of-variation(CoV), relative-percentage-error (RPE), Box-Whisker plots, bar graphs and t-test were used for comparison. ResultsGTKM was fitted well in all tissue regions. Ktrans and ve in contrast-enhancing (CE) has shown improved noise sensitivity in longer data. vb was reliable in all tissues. Mean AIF and C(t) peaks showed ~38% and ~35% variations. During simulation, normalizations have mitigated variations due to changes in AIF amplitude in Ktrans and vb.. ve was less sensitive to normalizations. CoV of Ktrans and vb has reduced ~70% after GM-Type-1 normalization and ~80% after GM-Type-2 normalization, respectively. GM-Type-1 (p = 0.003) and GM-Type-2 (p = 0.006) normalizations have significantly improved differentiation of HGG and LGG using Ktrans. ConclusionKtrans and vb can be reliably estimated in normal-appearing brain tissues and can be used for normalization of corresponding parameters in tumor tissues for mitigating inter-subject variability due to errors in AIF. Normalized Ktrans and vb provided improved differentiation of HGG and LGG.