Measurement of Arteriolar Blood Volume in Brain Tumors Using MRI without Exogenous Contrast Agent Administration at 7T
Yuankui Wu1,2,3, Shruti Agarwal4, Craig K Jones2,3, Andrew G Webb5, Peter C.M. van Zijl2,3, Jun Hua2,3, and Jay J Pillai4

1Department of Medical Imaging, Nanfang Hospital, Southern Medical University, Guangzhou, China, People's Republic of, 2Neurosection, Div. of MRI Research, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5Department of Radiology, C.J.Gorter Center for High Field MRI, University Medical Center, Leiden, Netherlands

Synopsis

The purpose of this study is to evaluate the potential diagnostic value of inflow-based vascular-space-occupancy (iVASO) MRI in brain tumor patients by comparing it with the widely used dynamic-susceptibility-contrast (DSC) MRI. The iVASO approach can measure arteriolar cerebral blood volume (CBVa) without using an exogenous contrast agent. The measured CBVa by iVASO showed a stronger association with tumor grade than DSC CBV. As the total scan times for iVASO and DSC are comparable, iVASO MRI may be a useful alternative for the assessment of tumor perfusion, especially when exogenous contrast agent administration is difficult or contraindicated in certain patient populations.

PURPOSE

The degree of angiogenesis and ability to recruit vessels are important factors in the evaluation of brain tumor malignancy. Cerebral blood volume (CBV) and flow (CBF) are important indicators of the homeostasis of the microvasculature. CBV alterations may be more sensitive and may occur earlier than CBF changes in tumors(1). Dynamic susceptibility contrast (DSC) MRI is currently the standard perfusion MRI approach in brain tumors(2,3). Nevertheless, the gadolinium-based contrast agents used in DSC are associated with nephrogenic systemic fibrosis in subjects with renal insufficiency(4,5), which often occurs in tumor patients undergoing chemotherapy. This makes follow-up evaluation of tissue perfusion during chemotherapy difficult with DSC(6,7). The recently developed inflow-based vascular-space-occupancy (iVASO) MRI can quantify arteriolar CBV (CBVa) without need for an exogenous contrast agent(8-10). Because the generation of arterioles may occur before capillary growth and CBF changes in angiogenesis(11), the investigation of CBVa may furnish information that is not obtainable from total CBV/CBF measures. Here, we applied iVASO MRI to measure CBVa and arterial transit time (ATT) in primary cerebral glioma patients, and compared the results with DSC MRI to evaluate its potential additional value for tumor perfusion imaging.

METHODS

Twelve brain tumor patients were scanned (Table 1). Each subject underwent a clinical and a research MRI session with DSC and iVASO MRI, respectively. The clinical session was conducted on a 3T Siemens scanner with a 12-channel head coil: MPRAGE, FLAIR; DSC MRI (Gd-DTPA) with gradient-echo echo-planar-imaging (GRE-EPI), TR/TE=1640/35ms, voxel=2x2x4mm3, 6min. The research session was performed on a 7T Philips scanner with a 32-channel head coil. Dielectric pads(12) were used to mitigate B1 inhomogeneity(13). Single-slice iVASO MRI was performed with GRE-EPI: TR/TI=10000/1626, 5000/1382, 3100/1081, 2000/797, 1700/691, 1300/563ms; voxel=2.5x2.5x3mm3; crusher gradients Venc=10cm/s, z-direction; 7min. The iVASO slice was prescribed on MPRAGE images and centered on the tumoral region. Analysis: All data were pre-processed using SPM. DSC and iVASO images were analyzed using DSCoMAN/ImageJ and in-house Matlab routines(8), respectively. ROIs of tumoral and similar-sized contralateral gray matter (GM) regions were selected on anatomical images. The same ROIs were used for DSC and iVASO. Efforts were made to avoid necrotic/cystic regions and major macrovessels. GM was chosen as the internal reference mainly because iVASO is less sensitive in regions with very long ATT such as white matter(14). This choice is justified by the fact that most of the lesions in our study involved GM, and should not affect the correlation analysis (main finding, see below). To reduce influence from individual baseline differences, the ratio of tumor/contralateral was calculated. Group difference was examined by t-tests. Correlations were assessed using multiple regression with age included as an independent variable. Multiple comparisons were corrected with false discovery rate.

RESULTS

All DSC and iVASO measures are listed in Table 1 and statistical results are summarized in Table 2. DSC CBV in tumors were all higher than contralateral regions in grade IV patients, but were comparable in grade II/III patients. DSC mean transit time (MTT) was comparable between tumoral and contralateral regions in all patients. The iVASO CBVa was significantly lower in grade II tumors than in contralateral GM. CBVa in all grade IV patients was greater in tumor than contralateral (but not significant). The iVASO ATTs were all shorter in tumor than contralateral except for case 1. Correlations: The iVASO CBVa ratio showed the strongest correlation with tumor grade (Figure 1b). The DSC CBV ratio showed a trend for correlation with tumor grade (Figure 1a). Subject age showed negligible contribution in all correlations analyzed. A trend of correlation between DSC CBV ratio and iVASO CBVa ratio was observed (Figure 2).

DISCUSSION & CONCLUSION

The DSC results are consistent with the literature(15,16). Our main finding is that iVASO CBVa in tumors demonstrated a stronger correlation with tumor grade than DSC CBV in the same patients. Also, the average difference between grades II and III oligodendrogliomas was greater in iVASO CBVa. This implies that changes in CBVa might be a better classifier than changes in the total microvasculature for the stratification of brain tumors, especially between grades II and III. This may be of potential diagnostic value since differences between grade II and IV tumors are usually evident on contrast-enhanced MRI images, while differentiation between grade II and III tumors is often more difficult. Further investigation is warranted to validate our findings in a larger cohort. We will use the recently improved 3D iVASO MRI(17) with whole-brain coverage and same scan time in follow-up studies to evaluate CBVa changes in the entire tumor and potential heterogeneities among different sub-regions.

Acknowledgements

Funding: Johns Hopkins University Brain Science Institute grant, and NCRR NIBIB P41 EB015909.

References

(1)Oku, T, et al. Cancer Res 1998;58:4185. (2)Cha, S, et al. Radiology 2002;223:11. (3)Knutsson, L, et al. MAGMA 2010;23:1. (4)Grobner, T Nephrol Dial Transplant 2006;21:1104. (5)Marckmann, P, et al. J Am Soc Nephrol 2006;17:2359. (6)Fujima, N, et al. J Magn Reson Imaging 2015;41:983. (7)Truong, MT, et al. AJNR Am J Neuroradiol 2011;32:1195. (8)Hua, J, et al. NMR Biomed 2011;24:1313. (9)Hua, J, et al. Magn Reson Med 2011;66:40. (10)Donahue, MJ, et al. J Cereb Blood Flow Metab 2010;30:1329. (11)Hansen-Smith, F, et al. Microvasc Res 2001;62:1. (12)Haines, K, et al. J Magn Reson 2010;203:323. (13)Teeuwisse, WM, et al. Magn Reson Med 2012;67:1285. (14)van Osch, MJ, et al. Magn Reson Med 2009;62:165. (15)Law, M, et al. Am J Neuroradiol 2004;25:746. (16)Cha, S, et al. Am J Neuroradiol 2005;26:266. (17)Hua, J, et al. Proc. 23rd Annual Meeting ISMRM 2015

Figures

Figure 1. Correlation analysis between the DSC and iVASO measures (ratio of tumor/contralateral) with WHO tumor grade. The open circles represent data points, and the trend lines from linear regression are shown with dotted lines. (a) DSC CBV; (b) iVASO CBVa; (c) DSC MTT; (d) iVASO ATT.

Figure 2. Correlation analysis between corresponding iVASO and DSC measures (ratio of tumor/contralateral). The open circles represent data points, and the trend lines from linear regression are shown with dotted lines. (a) DSC CBV vs. iVASO CBVa. (b) DSC MTT vs. iVASO ATT.

Table 1

Table 2



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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