Delphine Perie^{1}, Egidie Uwase^{1}, Tanguy Artz^{1}, Marianna Gamba^{1}, and Daniel Curnier^{2}

^{1}Mechanical Engineering, Polytechnique Montreal, Montreal, QC, Canada, ^{2}Kinesiology, University of Montreal, Montreal, QC, Canada

### Synopsis

Swine myocardium mechanical properties were found related to a combination of CMR
relaxations times, magnetization transfer and diffusion parameters. Thus we
assessed the relationships between mechanical properties and CMR parameters in
childhood acute lymphoblastic leukemia survivors. The results showed that the pressure
at diastasis, contractility and stiffness properties of the left ventricle can
be partially predicted from the relaxation times T1 and T2 and the partition coefficient,
reflecting cardiac health in childhood acute lymphoblastic leukemia. This
indirect estimation of the mechanical behavior of the myocardium from multiparametric
MRI could solve the challenging early cardiac sequelae detection.

### Introduction

Doxorubicin-based chemotherapy entails
dose-dependent cardiotoxicity [1] but both echocardiography and MRI
investigations result in late detection, even when using strain quantification.
Contrast enhanced T1 imaging is one of the most expected to
early detect doxorubicin-induced cardiotoxicity [2,3]. Mechanical
properties of the myocardium are considered as early biomarker of subtle
changes in cardiomyopathy. Moreover, swine myocardium mechanical properties can
be quantified from a linear combination of relaxations times, magnetization
transfer and diffusion parameters [4]. The objective of this study was to investigate the
relationships between mechanical properties computed from the CircAdapt model [5]
and CMR parameters in childhood lymphoblastic leukemia survivors.### Methods

Forty-seven acute lymphoblastic leukemia survivors
(23±7 years old), treated with doxorubicin, were prospectively included in this
study approved by our IRB. The CMR acquisitions were performed on a Siemens
Skyra 3T MR system using a 18-channel phased array body matrix coil and
included a MOLLI sequence for T1 mapping, a T2-prepared TrueFISP sequence for
T2 mapping at apical, mid-ventricular and basal levels (pixel resolution
1.4mmx1.4mmx8.0mm), and an ECG-gated cine TruFISP sequence (14 slices in short
axis and 5 slices in long axis, slice thickness 8mm, repetition time 34.6ms,
effective echo time 1.2ms, flip angle 38°, iPAT factor 3, matrix 208x210 and
in-plane pixel size 1.25x1.25 mm). The volunteers also underwent an exercise
test using cardiac hemodynamic monitoring (PhysioFlow, Manatec Biomedical) to
measure the arterial pressure, cardiac ouput and heart rate that were used as
input data to the CircAdapt model [5]. The left ventricle stiffness (LVS) and
contractility (LVC) were computed from the minimization of the differences between the left ventricle MRI volumes
segmented using CIM (Figure 1, [6]) and the CircAdapt simulated volumes (Figure
2). Multiple
linear regressions were investigated between the left ventricular pressure at
diastasis (Pd), the left ventricular contractility or stiffness and the native relaxation times T1 and T2, the partition coefficient (PC), and the end-diastolic (EDV) and end-systolic (ESV) left
ventricular volumes using SigmaStat (Systat
Software, Inc.).### Results

Low statistical power was obtained because
CircAdapt optimizations succeeded only in 24 subjects over the 47 subjects (only
mean differences between volumes less than 12mL were accepted). However, 46% of
the left ventricular pressure at diastasis can be determined (r=0.68) from a
linear combination of the CMR parameters (Equation 1) with a significant
contribution of the partition coefficient (p=0.002). 23% of the left ventricular stiffness can be determined (r=0.47) from a
linear combination of the CMR parameters (Equation 2) with a contribution of
the partition coefficient (p=0.05). 36% of
the left ventricular contractility can be determined (r=0.60) from a linear
combination of the CMR parameters (Equation 3) with a significant contribution
of the partition coefficient (p=0,02).

Pd
= -0,24 + (0.0001*T1) + (0.0007*T2) + (1.2*PC) Eq.
1

LVS = 0,01 +
(0.0002*T1) - (0.007*T2) + (2.4*PC) Eq.
2

LVC = 4.3 - (0.001 T1) - (0.01*T2) -
(2.9*PC) Eq. 3### Discussion

The partition coefficient of gadolinium is
related to fibrosis [1], which should be associated to a stiffer behavior of
the tissue due to more collagen fibers and less interstitial fluids. This is in
agreement with the significant contribution of the partition coefficient in the
determination of the left ventricular pressure at diastasis, the myocardium
stiffness and the contractility. The variance inflation factors of T1, T2 and PC
were always around 1 while preliminary analysis showed that the variance
inflation factors of EDV and ESV were 10 times higher, suggesting that these
parameters were likely candidates for elimination in the equation. However,
based on our in-vitro study [4], T2 was expected to have a more significant
contribution than the one we found. Magnetization transfer ratio and MRI
diffusion parameters such as fraction of anisotropy and mean diffusivity should
also be included to improve the relationship with the hyperelastic property of
the myocardium.### Conclusion

The pressure,
contractility and stiffness properties in the left ventricle can be partially
predicted from CMR parameters reflecting cardiac health in childhood acute
lymphoblastic leukemia. This relationship can be improved with diffusion
parameters, which in vivo acquisition remains challenging. This indirect
estimation of the mechanical behavior of the myocardium from multiparametric
MRI could solve the challenging early cardiac sequelae detection.### Acknowledgements

NSERC and Polytechnique Montreal for the financial support, researchers
from the PETALE study for the opportunity to do this complementary analysis on
the cancer survivors.### References

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