Impact of three modeling approaches on the

reproducibility of perfusion parameters in CEUS studies

Maxime Doury1, Alexandre Dizeux2, Alain de Cesare1, Lori Bridal1, Frdrique Frouin3
1. Laboratoire dImagerie Biomdicale (LIB), UPMC, CNRS, Inserm, Paris, France
2. Institut Langevin, PSL Research University, CNRS, Paris, France
3. Imagerie Molculaire In Vivo (IMIV), Inserm, CEA, Universit Paris Sud, CNRS, Orsay, France

Introduction Results
Contrast-enhanced ultrasound (CEUS) is a functional im- Global analysis
aging technique that uses micro-bubbles as contrast The mean kinetics inside the perfused tumor area were
agent (CA). Main advantages of CEUS are its real-time, modeled using the LN, AIF and RT models.
non-ionizing, and cost-effective characteristics. Thus
CEUS is well indicated for monitoring tumors under ther- Regional analysis
apy. As a rst step, the reproducibility of perfusion pa- Tumors are automatically divided in 32 regions. The
rameters was studied in test-retest measurements. mean kinetics inside every region was modeled individ-
ually, yielding parametric maps (see below maps of rBF
and rBV).
Materials
50 8
CEUS sequences were acquired using a 15L8W trans-
40
ducer and a Sequoia 512 US system (Acuson) in an ecto- 6
pic murine model for Lewis Lung Carcinoma [1]. Four 30
4
mice were considered for this study. 20
A bolus of 50 L of SonoVue (Bracco) diluted to 20% was 10 2
injected using a controlled injection system to improve rBF (%)
0
rBV
0
acquisition reproducibility [2].
Imaging was repeated for each mouse every ten minutes Reproducibility study
with xed mechanical index (0.1), dynamic range (80 The parameters WIR, BF, and rBF are related to ow pa-
dB), and time gain compensation settings. rameters (FP), while the parameters AUC, fBV, and rBV
are related to volume parameters (VP).
Methods: quantication models Inter-exam coefcients of variation (CV) of all these pa-
rameters estimated at a global scale (inside the whole
Three different modeling approaches were implemented tumor area) are shown for the four mice (M1-4).
to describe the kinetics of CA inside the tumor region. CV
(%)
Global FP LN
AIF
CV
(%)
Global VP LN
AIF
RT RT

Log-normal model (LN) [3]

A usual explicitly dened model, based on the log-nor- 30 20
mal distribution, was tted to the kinetics. Conventional 20
parameters were derived, including the area under the 10
curve (AUC), the time to 10

peak (TTP), and the AUC

0 0
wash-in rate (WIR). WIR M1 M2 M3 M4 M1 M2 M3 M4

TTP Mean inter-exam CV values along with standard devia-

Arterial input function model (AIF) [4] tion (dotted lines) of the parameters estimated at a re-
A single-compartment model was dened to estimate ki- gional scale are displayed for the same four mice.
netics inside the tumor from the arterial input function CV LN CV LN
measured inside an artery present in the eld of view. (%)
Regional FP AIF
RT (%)
Regional VP AIF
RT
The model parameters are the blood ow (BF), the frac- 60
40
tional blood volume (fBV)
and the time delay (Td) re- BF BF / fBV
40

ecting the CA transit time AIF T 20

from the artery to the tumor. 20

0 0
Reference tissue model (RT) [5] M1 M2 M3 M4 M1 M2 M3 M4
This approach was based on the previous single-com-
partment model. Instead of estimating the AIF, the kinet-
ics inside a reference tissue region was used. Assuming Conclusion
that the model parameters do not vary from one study to
another inside this region, the relative blood ow (rBF), The three models reveal intra-tumoral heterogeneity with
the relative fractional blood volume (rBV) and the CA similar efciency. Furthermore parameters deduced from
transit time difference (T) between the tumor and the the RT model are the most reliable in test-retest studies.
reference tissue were estimated. Their usage for longitudinal exam comparison and tumor
monitoring is thus promising.
BFT / fBVT rBF = BFT / BFR
BFT
T rBV = fBVT / kR
References
AIF BFR / fBVR where kR is a constant
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R characterizing the refer-

1144-7, 2014. 1999.

BFR
[2] A. Dizeux et al., Implementation of a controlled injection system for [5] T. E. Yankeelov et al., Quantitative pharmacokinetic analysis of
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