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.

RATIONALE AND OBJECTIVES: To 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 METHODS: A 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. RESULTS: GTKM 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. CONCLUSION: Ktrans 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.

Evaluating feasibility of high resolution T1-perfusion MRI with whole brain coverage using compressed SENSE: Application to glioma grading.

PURPOSE: To evaluate the efficacy of optimized T1-Perfusion MRI protocol (protocol-2) with whole brain coverage and improved spatial resolution using Compressed-SENSE (CSENSE) to differentiate high-grade-glioma (HGG) and low-grade-glioma (LGG) and to compare it with the conventional protocol (protocol-1) with partial brain coverage used in our center. METHODS: This study included MRI data from 5 healthy volunteers, a phantom and 126 brain tumor patients. Current study had two parts: To analyze the effect of CSENSE on 3D-T1-weighted (W) fast-field-echo (FFE) images, T1-W, dual-PDT2-W turbo-spin-echo images and T1 maps, and to evaluate the performance of high resolution T1-Perfusion MRI protocol with whole brain coverage optimized using CSENSE. Coefficient-of-Variation (COV), Relative-Percentage-Error (RPE), Normalized-Mean-Squared-Error (NMSE) and qualitative scoring were used for the former study. Tracer-kinetic (Ktrans,ve,vp) and hemodynamic (rCBV,rCBF) parameters computed from both protocols were used to differentiate LGG and HGG. RESULTS: The image quality of all structural images was found to be of diagnostic quality till R = 4. NMSE in healthy T1-W-FFE images and COV in phantom images increased with-respect-to R and images provided optimum quality till R = 4. Structural images and maps exhibited artefacts from R = 6. All parameters in tumor tissue and hemodynamic parameters in healthy gray matter tissue computed from both protocols were not significantly different. Parameters computed from protocol-2 performed better in terms of glioma grading. For both protocols, rCBF performed least (AUC = 0.759 and 0.851) and combination of all parameters performed best (AUC = 0.890 and 0.964). CONCLUSION: CSENSE (R = 4) can be used to improve the resolution and brain coverage for T1-Perfusion analysis used to differentiate gliomas.