Magne Kleppestø^{1}, Christopher Larsson^{1}, and Atle Bjørnerud^{1}

^{1}Oslo University Hospital, Oslo, Norway

### Synopsis

This work
compares three kinetic models for evaluation of DCE-MRI in high-grade
gliomas: the
Tofts-Kermode (TK) model, the extended Tofts model (ETM) and the two-compartment
exchange (TCE) model. 25 patients underwent a combined 238 examinations, and
kinetic analysis was performed using the three models. In tumor regions where the
data was better fitted using TK or TCE, median *K*^{trans} estimates obtained from this model was compared
to that from using ETM. It was found that in tumor regions in which TCE
provides the best fit, median *K*^{trans}
was significantly underestimated when applying ETM.

### Introduction

Dynamic
Contrast-Enhanced (DCE)-MRI uses tracer kinetic modeling for estimation of
functional parameters. Several models are in use, ranging from one- to four-parameter models. A more advanced model will often provide a better fit, but it
is generally recommended to use the simplest model that explains the data^{1}.
The model most commonly used at present in gliomas is the Extended Tofts Model^{2}
(ETM), which is a three parameter model that produces estimates of blood volume
(*v*_{p}), extravascular,
extracellular space (*v*_{e})
and leakage of contrast agent through the blood-brain barrier (*K*^{trans}). The aim of this
study was to investigate the consequence for estimates of *K*^{trans} when the ETM is applied in tumor regions where a
different model provides a better fit to the tissue concentration curve.**Methods**

A total of 238
examinations from 25 patients with high-grade
gliomas were included in the
study. The patients were repeatedly imaged at regular intervals as part of a
prospective treatment assessment study. DCE data was obtained by a 3D
saturation recovery gradient echo sequence (resolution: 1.88x1.88x4 mm^{3},
temporal resolution: 2.1 s). The
DCE series were analyzed using incremental modeling, where each voxel was
analyzed using increasingly more advanced kinetic models with increasing number
of parameters. An F-test was applied to test if the more advanced model gave a
significant better fit than the former. Each tumor ROI was divided into sub-ROIs
based on the chosen kinetic model.The DCE series were analyzed using three different
kinetic models: the two parameter Tofts-Kermode (TK) model^{3}, the three
parameter ETM and the four parameter two-compartment exchange (TCE) model^{4}.
This enabled a comparison of suitability of each model on a voxel-for-voxel
basis. Tumors in which a sub-ROI could be defined of at least 50 voxels that
was determined to be better fitted by a model other than ETM was included in
the analysis. The median *K*^{trans}
estimates as produced by ETM and the better fitted model were compared using
Wilcoxon signed rank test.**Results**

Figure
1 shows the distribution of the chosen model for more than 140,000 voxels from
all tumor ROIs. 70 % of voxels are best fitted using ETM, 16 % using TCE and 13
% using TK. Figure 2 displays a boxplot of the median *K*^{trans} estimated using ETM relative to TCE and TK in
sub-ROIs in which TCE (n = 75) and TK (n = 80), respectively, was found to
provide better model fits. As can be seen, when using ETM, *K*^{trans} is underestimated in the TCE sub-ROIs (p < 10-9),
while little deviation is seen in the TK sub-ROIs (p > 0.8). An example slice showing an incremental model map is shown in figure 3. The different colors indicate which model is chosen in each voxel.

**Discussion**

The global distribution
of voxels from
the incremental model analysis in figure 1 indicates
that ETM is a reasonable choice in
our materal of high-grade gliomas. However, 16
% of the tumor voxels in the herein assessed dataset are found to be better described
by using the more advanced TCE. The non-significant variation in median K^{trans} estimates when using
ETM or TK in the TK sub-ROIs is an expected outcome in tumor regions where *v*_{p} is indeed negligible, thus
enabling the simpler TK model to provide a sufficient description of the tissue
kinetics. While the TCE model offers an attractive method of supplying more
detailed information about tumor tissue, it requires input data of proportionally
higher quality. A question that is raised from the results of this study is whether
it is reasonable and useful to combine different models within the same tumor.
This may be especially relevant for high-grade
gliomas, which are known to exhibit great
variation in vascular properties within a single specimen.### Conclusion

The present
work has shown that a single kinetic model may not be sufficiently able to describe all
tissue in the same tumor. ### Acknowledgements

No acknowledgement found.### References

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