Purpose

Although dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and intravoxel incoherent motion (IVIM) has been applied in gliomas to estimate the perfusion characteristics and to differentiate low- from high-grade tumors.^{1, 2} However, it is necessary to develop a less time-consuming and no contrast agent needed approach. The purpose of this study was to evaluate the feasibility of simplified perfusion fraction (SPF) based on diffusion-weighted imaging (DWI) acquired with three b-values to measure tissue perfusion linked to microcirculation, to validate it against from perfusion-related parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging, and to investigate its utility to differentiate low- from high-grade gliomas.

Methods

The prospective study was approved by the local institutional review board and written informed consent was obtained from all patients. Between May 2016 and May 2017, a total of 50 patients with pathologically confirmed gliomas were included in this study, 19 of 50 patients (38%) were confirmed with low-grade (WHO grade II) gliomas and 31 patients (62%) with high-grade (WHO grades III and IV) gliomas. All MR images were obtained with a 3.0-T MR imager (Signa HDxt; GE Medical Systems, Milwaukee, Wis). All patients received multi-b-value DWI and DCE MR imaging. For DWI, we performed a single shot echo-planar sequence in the axial plane with the following parameters: repetition time msec/echo time msec, 3000/106; section thickness, 5 mm; intersection gap, 1 mm; field of view , 260 × 260 mm; matrix, 192 × 192; number of sections, 15; b-values, 0, 20, 50, 80, 150, 200, 300, 500, 800, 1000 sec/mm². Dynamic contrast-enhanced MR images were obtained with a three-dimensional gradient-echo T1-weighted sequence. Besides conventional apparent diffusion coefficient (ADC_0,1000) map, perfusion-related parametric maps for IVIM-derived perfusion fraction (f) and pseudodiffusion coefficient (D*), DCE MR imaging-derived pharmacokinetic metrics, including K^trans, v_e, and v_p, as well as SPF, were generated. We introduced an additional parameter called SPF (SPF=(ADC_0,200-ADC_200,1000)/ADC_0,200), which represents the relative fraction of perfusion. Similar simplified method was confirmed by Thoeny et al and Teruel et al,^{3, 4} respectively. Two neuroradiologists carefully placed round-shaped regions of interest (ROI) in the solid portion of tumor on parametric maps with reference to conventional MR images by using the hot-spot method.^{5, 6} Correlation between perfusion-related parameters was computed by using the nonparametric Spearman rank correlation. The Mann-Whitney U test was used for the comparison of each parameter between low- and high-grade gliomas. Receiver operating characteristic (ROC) curves were employed to calculate the area under the curve (AUC) and to determine the optimal thresholds for grading gliomas by maximizing the Youden index.

Result

There was a statistically significant strong positive correlation between SPF and f (ρ = 0.732; P < 0.001), and between SPF and D* (ρ = 0.716; P < 0.001). Notably, SPF exhibited a stronger correlation with Ktrans compared with f (ρ = 0.607 and 0.558, respectively; both P < 0.001). Additionally, we also observed a weak correlation between SPF and v_p (ρ = 0.397; P = 0.004), which was more significant than the correlation between f and vp (ρ = 0.362; P = 0.010). Perfusion-related parameters including DWI derived SPF, f, and D*, and DCE-MR imaging derived K^trans, v_e and v_p all exhibited significantly elevated values in high-grade gliomas than those in low-grade gliomas (all P < 0.05). Among all imaging parameters, SPF achieved the highest AUC value of 0.942, followed by f (0.896), D* (0.891) and K^trans (0.854), whereas the AUC values of diffusion indexes were relatively low (0.752 for ADC_0,1000 and 0.732 for D, respectively). Further, the AUC of SPF was significantly higher than that of ADC_0,1000 (P = 0.004). No significant difference in AUC values was detected between SPF and f (P = 0.317), as well as between SPF and K^trans (P = 0.065).

Discussion and Conclusion

The preliminary results showed that the perfusion-related parameter obtained from this 3-b-value approach, named SPF, correlated well with IVIM derived f and D*, and DCE MR imaging derived K^trans and v_p. Furthermore, SPF proved to be useful in differentiating low- from high-grade gliomas, and showed higher diagnostic accuracy compared with ADC, IVIM and DCE MR imaging parameters. Thus, SPF may serve as a valuable alternative to measure tumor perfusion in gliomas in a noninvasive, convenient and efficient way.

Acknowledgements

Funded by National Natural Science Foundation of China (grants 81501458, 81701642 and 81571650), Shanghai Science and Technology Committee Medical Guide Project (western medicine) (grant 17411964300), and Medical Engineering Cross Research Foundation of Shanghai Jiao Tong University (grant YG2015QN37).