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=2x2x4mm
3,
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=2.5x2.5x3mm
3; crusher gradients V
enc=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
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