POSTER SECTIONS Coverpage Aims and objectives Methods and materials Results Conclusion Personal information References

ECR 2014 / C-1846

"The link between microcirculation and energetic metabolism in tumours : in vivo DCE-MRI imaging approach in xenografted mice."

This poster is published under an open license. Please read the disclaimer for further details.

Congress:

ECR 2014

Poster Number:

C-1846

Type:

Scientific Exhibit

Keywords:

Neoplasia, Haemodynamics / Flow dynamics, Physiological studies, Contrast agent-intravenous, MR-Diffusion/Perfusion, Vascular, Oncology

Authors:

J.-F. Grellier, L. Pidial, D. Balvay, G. Autret, C. A. Cuenod, O. Clement, B. Tavitian; Paris/FR

DOI:

10.1594/ecr2014/C-1846

DOI-Link:

https://dx.doi.org/10.1594/ecr2014/C-1846

Fig. 9: comparison of AUC inside each group between HEZ and PEZ was statistically...

Fig. 7: The growth curves and statistical analysis at two time points after inoculation...

Fig. 8: comparison of AUC inside each group between HEZ and PEZ was statistically...

Results

TUMOUR GROWTH CURVES and

TUMOUR VOLUME MEASUREMENTS Fig. 7

A total of 24 NUDE mice were studied. Tumours in injection sites were initially detected at 23, 19 and 13 days in the Wt, MCT4 and Res- group, respectively.

Growth in the Wt group was slower than in MCT4 and Res – groups. At the first end timepoint after inoculation (day 25), the tumour volumes in the Res– group were statistically greater than in the MCT4+ and the Wt groups (Kruskal-Wallis : H=31,37, df2, P<0.0001). At the second end timepoint (day=35), there was a statistical difference between the MCT4 and Res- groups (non-paired Wilcoxon’s p<0, 0001). At this time, Res- mice had already been sacrificed for ethical reasons.

Fig. 7: The growth curves and statistical analysis at two time points after inoculation of tumours. 4-A: Growth in the Wt group was slower than in the MCT4 and Res – groups. 4-B : At day=25,the tumour volumes in the Res – group were statistically greater than in the MCT4+ group and in the Wt group Wt (Kruskal-Wallis : H=31.37, df2, P<0.0001). 4-C: At day=35, there was a statistical difference between the MCT4 and Res- groups (non-paired Wilcoxon’s p<0.0001).

MACROSCOPIC EXAMINATION

In the three groups, some tumours induced overlying skin ulcerations. MRI acquisitions were made when the tumour length was greater than 10 mm.

Mice of the Wt, MCT4 and Res- groups were sacrificed after 40, 33 and 24 days respectively.

The Wt type tumour showed frequent haemorrhagic rearrangements. Between days 35 and 40, the average volume of Wt tumours dramatically increased with the frequent formation of haematoma bleeding inside the tumour.

In the Res- group, tumour were polylobulated, and there was frequent invasion of surrounding tissue by tumour cells.

DCE MRI

DCE MRI curves were obtained for each tumour. We excluded some acquisitions because of high residual values after compartment modelization, due to respiratory movement artefacts or low signal to noise ratios (i.e. the error margin showed high dispersion in the residual curve (blue curve fig. 3B and3C). Excluded datapoints were as follows :

One study in the Wt group leading to a total of 11 tumours studied in this group.

Three studies in the MCT4+ group leading to a total of 11 tumours studied in this group.

Four studies in the Res- group leading to a total of 9 tumours studied in this group.

REPARTITION OF ENHANCED ZONE INSIDE EACH TUMOUR Fig. 8

In each group, the global enhancement in tumours was distributed in a peripheric HEZ with high enhancement and a central PEZ with poor or no enhancement. In each group, AUC was significantly different between HEZ and PEZ (Wilcoxon’s paired test for Wt, MCT4+ and Res- (p=0.001, p=0.0005 and p=0.0005) respectively.

There was no difference between groups in the PEZ/HEZ ratio (Kruskal Wallis: H=3.84, df2, P=0.147) suggesting that the relative proportion of enhanced tissue within a tumour is not dependant on mutations in metabolic pathways. The Res- cells tumour, which theoretically do not need oxygen for their metabolism, showed a peripheral vascularised zone similar to that of the other groups.

Fig. 8: comparison of AUC inside each group between HEZ and PEZ was statistically different for Wt (Wilcoxon’s paired test : p=0,001) (fig. 6A) ; MCT4+ (Wilcoxon’s paired test : p<0,001) (fig. 6B) and Res- (Wilcoxon’s paired test : p<0,001) (fig. 6C). 6-D : the area of enhanced tissue within a tumour does not change aaccording to the mutation of metabolic pathway : there was no significant difference between each group for the PEZ/HEZ ratio (Kruskal-Wallis: H=3.84, df2, P=0.147)

COMPARISON OF PERFUSION PARAMETERS IN THE HEZ Fig. 9

The median AUC/AIF in the HEZ were 0.44 and 0.47 and 0.35 in the Wt, MCT4+ and Res- groups, respectively. There were no differences between the three groups in the AUC of contrast enhancement in the HEZ (Kruskal Wallis : H=3.24, df2, P=0.192), indicating that there was no quantitative difference between the groups with respect to global enhancement inside the peripheral zone.

The median F values of the HEZ were 78.0 ; 62.8 and 34.9 mL/min/100mL in the Wt, MCT4+ and Res- groups, respectively. The value of F HEZ in the Res- group was significantly lower than in the MCT4+ and the Wt groups (Kruskal-Wallis : H=6.39, df=2, P=0.0409). There was no significant difference between the Wt and the MCT4 groups. This indicates that the perfusion flow of the Res- tumours was lower than that of the Wt and MCT4+ tumours.

The median values of Vb f were 28.10 ; 27.30 and 20.45 % in the Wt, MCT4+ and Res- groups, respectively. The value of Vb HEZ in the Res- group was lower than in the Wt and MCT4+ group, but the difference was not significant (Kruskal-Wallis : H=5.75, df2, P=0.06).

The median Ve in the HEZ were 18.3 ; 24.8 and 27.5% in the Wt, MCT4+ and Res- groups, respectively. The value of Ve HEZ in the Wt group was significantly lower than in the MCT4+ and Res- groups (Kruskal-Wallis : H=9.31, df2, P=0.01).

The Vb / Ve ratio was significantly lower in the Res- group than in the Wt group (Kruskal-Wallis: H=8.3, df2, P=0.02).

The median PS in the HEZ were 6.1 ; 6.32 and 6.17 mL/min/100mL in the Wt, MCT4+ and Res- groups, respectively. Curiously, in spite of differences in blood flow and extra-cellular volumes between the three groups, there were no significant differences in the PS values (Kruskal-Wallis : H=0.14, df2, P=0.93).

Finally, the Wt group had a higher blood volume and blood flow, and a lower interstitial volume with respect to that of the Res- group, which showed low blood Volume and low blood flow and high extracellular volumes. The MCT4 group showed intermediate values for these three parameters.

Perfusion parameters were not calculated in PEZ, due to the large dispersion of values because of the poor signal/noise ratio. Visually, the enhancement curves in PEZ did not show differences between the three groups.

Fig. 9: comparison of AUC inside each group between HEZ and PEZ was statistically different for Wt (Wilcoxon’s paired test : p=0,001) (fig. 6A) ; MCT4+ (Wilcoxon’s paired test : p<0,001) (fig. 6B) and Res- (Wilcoxon’s paired test : p<0,001) (fig. 6C). 6-D : the area of enhanced tissue within a tumour does not change aaccording to the mutation of metabolic pathway : there was no significant difference between each group for the PEZ/HEZ ratio (Kruskal-Wallis: H=3.84, df2, P=0.147)