Jin Zhang1, Karl Kiser1, Ayesha Bharadwaj Das1, Chongda Zhang1, and Sungheon Gene Kim1
1New York University School of Medicine, New York, NY, United States
Synopsis
Cellular-interstitial water exchange rate is an important property of tumor, potentially
associated with tumor aggressiveness and treatment response. It is not trivial to
measure the water exchange rate, not to mention the challenges in measuring it
at a high spatial resolution. In this study, we use the 3D-UTE-GRASP method1
to generate water exchange rate maps and compare them with those measured using
diffusion time-dependent diffusion kurtosis imaging2.
Introduction
Water exchange rate (τex) may indicate tumor microstructural changes as well as the cellular metabolism that is related to tumor treatment response. Previously, we proposed a T1-weighted dynamic contrast enhancing (DCE)-MRI method3 to measure tumor intracellular water life time (τi) using more than one flip angle during the dynamic scan. In this study, we utilized the proposed method to map the water exchange rate parameter of the whole tumor at an isotropic high resolution. The DCE-MRI measured water exchange rate was compared with that from diffusion time-dependent diffusion kurtosis imaging (tDKI) measurement2.Methods
Six to eight-week-old C57BL6 mice (n = 3) with GL261 mouse glioma models were used for this study. MRI
experiments were performed on a Bruker 7T micro-MRI system, with 1H
four-channel phased array receive-only MRI coil. DCE-MRI acquisition with
double flip angle (DFA) acquisition was used in order to reduce the uncertainty
in estimation of the intracellular water lifetime (τi)3. Pre contrast T1 mapping was obtained with
3D-UTE-GRASP1 sequence (TR
= 4 ms and TE = 0.028 ms) combined with three flip angles (8o, 2o,
and 12o)4. Both the DCE-MRI and T1 measurement has image matrix size = 128x128x128,
field of view (FOV) = 20x20x20 mm and the spatial resolution was 0.156x0.156x0.156
mm. DCE-MR images were reconstructed to have a temporal resolution of T = 5s/frame. The arterial input
function (AIF) was estimated from multiple vessel voxels using the Principal
Component Analysis (PCA) method reported previously3. The two
compartment exchange model5 (2CXM) and three site two exchange water
exchange model6 (3S2X) were used for DCE-MRI pharmacokinetic model
analysis. Five parameters, interstitial space volume fraction (ve), vascular space volume
fraction (vp), blood flow
(Fp), permeability surface
area product (PS) and intracellular
water life time (τi) were estimated from
the model fit. The water exchange rate τex = τi ve was computed
from the estimated pharmacokinetic parameters. To cross-validate the estimated τex of tumor, tDKI method2
was implemented with diffusion times 200/400/600/800 ms and b-value of 200/500/1000/1500/2000/3000.
The data analysis of tDKI for τex estimation was performed for the slice at the tumor center with slice
thickness 1.2 mm and image matrix 80x80 and FOV=20 x 20 mm. Voxel size was 0.25
x 0.25 x 1.2 mm. The τex
data from 8 slices (1.25 mm =0.156 mm x 8) of DCE-MRI measurement was compared
with that from tDKI measurement from one
slice. The mice were treated in strict accordance with the National Institutes
of Health Guide for the Care and Use of Laboratory Animals, and this study was
approved by the Institutional Animal Care and Use Committee.Results
Figure 1 shows the 3D rendering of the τex map of a tumor along with cross-sectional images in sagittal/coronal/axial
slices. Figure 2 shows examples of τex
maps generated from tDKI method (1
slice with voxel size 0.25x0.25x1.2mm) and DCE-MRI method (8 slices with voxel
size 0.156x0.156x0.156 mm). Figure 3 shows comparison of τex between the two methods for the three animals. It can be observed that τex from tDKI method has smaller
inter quartile range (IQR) possibly due to the large voxel size and a small
number of voxels. However, our preliminary result shows that the τex estimated from the two methods are within a comparable range of each
other.Discussion and Conclusion
In this study, we demonstrated
the feasibility that the water exchange rate can be measured for whole tumor
with the 3D-UTE-GRASP method with a 3D isotropic high resolution as well as tDKI measurement. Further study is
warranted to investigate how each method can be used to characterize the tumor
characteristics related to the water exchange rate in a complementary way.Acknowledgements
NIH R01CA160620, NIH R01CA219964, P41EB017183, NIH/NCI
5P30CA016087References
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