Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Children's exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography. METHODS: Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150 min·wk-1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0 mL·kg-1·min-1) on cardiac parameters. RESULTS: Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness. CONCLUSION: This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors' cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.

Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

Relationship between cardiac mechanical properties and cardiac magnetic resonance imaging at rest in childhood acute lymphoblastic leukemia survivors.

The characterization of cardiac mechanical properties may contribute to better understanding of doxorubicin-induced cardiotoxicity. Our study aims to investigate the relationship between cardiac mechanical properties, T1 and T2 relaxation times and partition coefficient. Fifty childhood acute lymphoblastic leukemia survivors underwent a cardiac magnetic resonance (CMR) at rest on a 3T MRI system and included a standard ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Partition coefficient, ejection fraction, end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated. CircAdapt model was used to study cardiac mechanical performance (left ventricle stiffness (LVS), contractility (LVC) and pressure (Pmin and Pmax), cardiac work efficiency (CWE) and ventricular arterial coupling). In the whole cohort, our results showed that LVC (R2 = 69.2%, r = 0.83), Pmin (R2 = 62.9%, r = 0.79) and Pmax can be predicted by significant CMR parameters, while T1 (R2 = 23.2%, r = 0.48) and partition coefficient (R2 = 13.8%, r = 0.37) can be predicted by significant cardiac mechanical properties. In SR group LVS (R2 = 94.8%, r = 0.97), LVC (R2 = 93.7%, r = 0.96) and Pmin (R2 = 90.6%, r = 0.95) can be predicted by significant cardiac mechanical properties, while in HR + DEX group CWE (R2 = 49.8%, r = 0.70) can be predicted by significant cardiac mechanical properties. Partition coefficient (R2 = 72.6%, r = 0.85) can be predicted by significant CMR parameters in SR group. Early characterization of cardiac mechanical properties from CMR parameters has the potential to early detect doxorubicin-induced cardiotoxicity.

Cardiac Mechanical Performance Assessment at Different Levels of Exercise in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments. METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated. RESULTS: We observed significant differences between the different levels of exercise for both VAC ( P <0.0001) and CWE parameters ( P =0.001). No significant differences were reported between prognostic risk groups at rest and during the CPET. Nevertheless, we observed that survivors in the SR group had a VAC value slightly lower than heart rate (HR)+DEX and HR groups throughout the CPET. Moreover, survivors in the SR group had a CWE parameter slightly higher than HR+DEX and HR groups throughout the CPET. CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.

Exercise stress cardiac magnetic resonance imaging in the assessment of induced cardiovascular responses in cardiac patients: a scoping review protocol.

OBJECTIVE: This scoping review will describe cardiac magnetic resonance imaging testing protocols used in combination with exercise (Ex-CMR) to assess cardiovascular responses. The review will document the advantages and limitations of these protocols in cardiac patients. INTRODUCTION: Ex-CMR characterizes the heart, differentiating between normal and pathological cardiac remodeling with considerable accuracy. However, there is no review detailing existing Ex-CMR protocols. This is particularly important since not all Ex-CMR protocols seem to induce enough stress to effectively characterize cardiac remodeling, hence the need for a review to report on the current evidence. INCLUSION CRITERIA: This review will consider studies that use Ex-CMR testing protocols to assess cardiovascular responses, revealing cardiac remodeling in patients whose age at the time of the study was ≥ 18 years. METHODS: The review will be conducted in accordance with the JBI methodology for scoping reviews and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The following databases will be searched: PubMed, Embase, ISI Web of Science, OpenGrey, Grey Matters, and OAlster. Articles in English and French will be included and there will be no limitation set for the date of publication. Data will be extracted from papers included in the scoping review by 2 independent reviewers and will be classified in summary tables. REVIEW REGISTRATION: Open Science Framework https://osf.io/hvn75/?view_only=f6cf8fc2112e498d89c39639dbce70d1 .

Modelling cardiac mechanics in doxorubicin-induced cardiotoxicity following childhood acute lymphoblastic leukemia using a combination of cardiac magnetic resonance imaging, cardiopulmonary exercise testing and the CircAdapt model.

Children with acute lymphoblastic leukemia (ALL) are treated with doxorubicin-based chemotherapy that can lead to cardiotoxicity which is a well-known cause of mortality. This study aims to characterize myocardial subtle changes induced by doxorubicin-related cardiotoxicity. We used the combination of cardiac magnetic resonance (CMR) imaging, cardiopulmonary exercise testing and the CircAdapt model to explore hemodynamics and intraventricular mechanisms at rest and during exercise in 53 childhood ALL survivors. A sensitivity analysis of the CircAdapt model identified the most influencing parameters on the left ventricle volume. ANOVA were performed to explore significant differences between left ventricle stiffness, contractility, and arteriovenous pressure drop, as well as survivors' prognostic risk groups. No significant differences were observed between prognostic risk groups. The left ventricle stiffness and left ventricle contractility were non-significantly higher in survivors receiving cardioprotective agents (94.3 %), compared to those at standard and high prognostic risk (77 % and 86 %, respectively). In both left ventricle stiffness and left ventricle contractility, we observed that survivors receiving cardioprotective agents were close to the nominal value of CircAdapt (healthy reference group value is 100 %). This study allowed to improve our knowledge of potential subtle myocardial changes induced by doxorubicin-related cardiotoxicity in childhood ALL survivors. This study confirms that survivors exposed to a high cumulative dose of doxorubicin during treatments are at potential risk of myocardial changes many years after the end of their cancer, while cardio-protective agents may prevent changes in cardiac mechanical properties.

Cardiorespiratory Fitness and Cardiac Magnetic Resonance Imaging in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Childhood acute lymphoblastic leukemia survivors' anthracycline-induced cardiotoxicity could be prevented with good cardiorespiratory fitness levels and regular physical activity. This cross-sectional study aimed to assess the association between cardiorespiratory fitness and physical activity with cardiac magnetic resonance parameters. METHODS: A total of 96 childhood acute lymphoblastic leukemia survivors underwent a maximal cardiopulmonary exercise test and answered physical activity questionnaires. We calculated the odds ratio of the preventive fraction of regular physical activity (≥150 min/wk) and adequate cardiorespiratory fitness levels (above the median ≥31.4 mL·kg-1·min-1) on cardiac magnetic resonance parameters (left ventricular [LV] and right ventricular [RV] morphological and functional parameters). RESULTS: An adequate cardiorespiratory fitness was associated with a significant preventive fraction for LV (up to 84% for LV end-diastolic volume) and RV volumes (up to 88% for RV end-systolic volume). The adjusted analyses highlighted a preventive fraction of 36% to 91% between an adequate cardiorespiratory fitness and LV and RV parameters, late gadolinium enhancement fibrosis, and cardiac magnetic resonance relaxation times. No associations were reported with regular physical activity. CONCLUSIONS: This study provides additional evidence regarding the benefits of an adequate cardiorespiratory fitness level for childhood cancer survivors' cardiac health.

Estimation of anisotropic properties of CMR patient-specific left ventricle using the virtual field method.

Left ventricle (LV) myocardial dysfunction has been recently investigated using the estimation of isotropic myocardial stiffness from magnetic resonance imaging (MRI). However, Myocardium is known to have a 3D complex geometry with anisotropic stiffness. The assessment of the anisotropy properties characterizes structural changes in myocardium as a consequence of heart failure (HF). From image data, the virtual field method (VFM) can determine material stiffness in a non-invasive manner. In the present work, the objective is to compare two inverse identification methods, given the isotropic and anisotropic models in the characterization of properties of myocardium in acute lymphoblastic leukemia (ALL) survivors using VFM and MRI. Two types of VFM approach are presented. Using the first, the virtual displacements (VFs) allow whole-field LV to be imposed into VFM formulation and caused to directly estimate two independent parameters from isotropic constitutive relation. With the second, anisotropic parameters are estimated using piece-wise (Finite element-based) VFM. The resulting values showed significant differences between the subjects in comparative study of leukemia survivors, and variance in estimated parameters by two different VFM approach. This approach would be an efficient tool to characterize early cardiac dysfunction. This work elucidates the benefits and shortcomings of using VFM to determine anisotropic parameters of LV myocardium in linear elastic and of using the FEM application to generate meshes of patient-specific LVs from MRI images.

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments.

INTRODUCTION: Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. METHODS: A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices. RESULTS: Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid ( P =0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S' wave amplitudes were lower in HR than in SR and HR+DEX groups ( P =0.028, P =0.048, and P =0.005, respectively). The LV lateral E' in diastolic function was lower in the HR than in SR and HR+DEX groups ( P =0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups ( P =0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements. CONCLUSIONS: This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.

The effect of different aero handlebar positions on aerodynamic and gas exchange variables.

Adopting the time trial position (TTP) represents a notable improvement for cycling aerodynamic performance. Aero handlebars are designed to enable the cyclist to adopt a more aerodynamic TTP. However, it is unclear to what realistic extent the aero handlebar configuration affects the aerodynamics and physiological functioning. Thus this study aimed to investigate the effect of aero handlebar alterations on gas exchange parameters and aerodynamics of TTP. Seven male competitive cyclists and triathletes performed submaximal tests on a cycle ergometer at six different TTPs. Oxygen uptake, respiratory exchange ratio, minute ventilation and tidal volume were collected. Using the computational fluid dynamics (CFD) method, the detailed airflow patterns around the cyclist were investigated. The results were analyzed in terms of drag area, velocity and pressure distributions around the cyclist, surface pressure coefficient and wall shear stress magnitude. It was revealed that varying the aero handlebar position significantly influences aerodynamic performance, while maximal values of all the gas exchange variables remained unchanged. Compared to the cyclist's preferred TTP, the frontal area, drag coefficient and drag area were reduced by 4.1%, 4.6% and 8.5%, respectively, when lowering the handlebar position by 5 cm, which overcomes the metabolic costs.

Detection of doxorubicin-induced cardiotoxicity using myocardial T1 and T2 relaxation times in childhood acute lymphoblastic leukemia survivors.

Doxorubicin leads to dose-dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. The first aim was to propose a contour-based estimation of T1 and T2 relaxation times based on the myocardial area, while our second aim was to evaluate native T1, post-gadolinium T1 and T2 relaxation time sensitivity to detect myocardial changes. A total of 84 childhood ALL survivors were stratified in regard to their prognostic risk groups: standard risk (SR), n = 20), high-risk with and without dexrazoxane (HR + DEX, n = 39 and HR, n = 25). Survivors' mean age was of 22.0 ± 6.9 years, with a mean age at cancer diagnosis of 8.0 ± 5.2 years. CMR acquisitions were performed on a 3 T MRI system and included an ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Myocardial contours were semi-automatically segmented using an interactive implementation of cubic Bezier curves. We found excellent repeatability between operators for native T1 (ICC = 0.91), and good repeatability between operators for post-gadolinium T1 (ICC = 0.84) and T2 (ICC = 0.79). Bland and Altman tests demonstrated a strong agreement between our contour-based method and images analyzed using the CVI42 software on the measure of native T1, post-gadolinium T1, and T2. No significant differences between survivors' prognostic risk groups in native T1 were reported, while we observed significant differences between survivors' prognostic risk groups in post-gadolinium T1 and T2. Significant differences were observed between male and female survivors. Differences between groups were also observed in partition coefficients, but no significant differences were observed between male and female survivors. The use of CMR parameters with native T1, post-gadolinium T1, and T2 allowed to show that survivors at a high-risk prognostic were more exposed to doxorubicin-related cardiotoxicity than those who were at a standard risk prognostic or who received dexrazoxane treatments.

Doxorubicin treatments induce significant changes on the cardiac autonomic nervous system in childhood acute lymphoblastic leukemia long-term survivors.

AIMS: Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system. METHODS AND RESULTS: A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed. CONCLUSION: Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.

To distinguish flexible and rigid lumbar curve from MRI texture analysis in adolescent idiopathic scoliosis: A feasibility study.

BACKGROUND: Imaging in side bending, supine, traction, fulcrum, and push prone are examples of methods used to evaluate the curve reduction of scoliotic spine. However, being able to determine spine curve flexibility from MRI would eliminate the need of additional X-ray radiation related to radiograph acquisition in side-bending. PURPOSE/HYPOTHESIS: To find specific texture features of lumbar postural muscles on MRI that can distinguish flexible from rigid lumbar scoliotic curves. We hypothesized that the changes occurring in postural muscles with scoliosis can be seen with MRI. STUDY TYPE: Retrospective study case control. POPULATION: With Institutional Review Board approval and informed consent, 15 adolescents with idiopathic scoliosis and scheduled for surgery were involved. FIELD STRENGTH/SEQUENCE: T1 -weighted MR images were performed on a 1.5T system using a spin echo sequence in the axial direction. ASSESSMENT: The spinal erector, quadratus lumborum and psoas major muscles were analyzed using textural features. STATISTICAL TESTS: Principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) were used to classify the lumbar postural muscles and calculate performance metrics. The lumbar flexibility index, measured from suspension tests, was used as ground truth measurement. RESULTS: The five discriminant features (out of 34 tested features) obtained from PCA were able to keep over 90% of the variability of the dataset. The right and left spinal erector and the left psoas major had the highest performance metrics to classify the spinal curve flexibility, with an accuracy over 0.80, a sensitivity over 0.82, a specificity over 0.68, and a Matthews correlation coefficient over 0.57. DATA CONCLUSION: This study analyzed MRI using texture information of muscle to distinguish flexible from rigid scoliotic curves. Some postural muscle such as the spinal erector and the psoas major are more likely to reflect the curve flexibility of a scoliotic participant. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

Sensitivity of MRI parameters within intervertebral discs to the severity of adolescent idiopathic scoliosis.

PURPOSE: To measure magnetic resonance imaging (MRI) parameters including relaxation times (T1 ρ, T2 ), magnetization transfer (MT) and diffusion parameters (mean diffusivity [MD], fractional anisotropy [FA]) of intervertebral discs in adolescents with idiopathic scoliosis, and to investigate the sensitivity of these MR parameters to the severity of the spine deformities. MATERIALS AND METHODS: Thirteen patients with adolescent idiopathic scoliosis and three control volunteers with no history of spine disease underwent an MRI acquisition at 3T including the mapping of T1 ρ, T2 , MT, MD, and FA. The apical zone included all discs within the scoliotic curve while the control zone was composed of other discs. The severity was analyzed through low (<32°) versus high (>40°) Cobb angles. One-way analysis of variance (ANOVA) and agglomerative hierarchical clustering (AHC) were performed. RESULTS: Significant differences were found between the apical zone and the control zone for T2 (P = 0.047), and between low and high Cobb angles for T2 (P = 0.014) and MT (P = 0.002). AHC showed two distinct clusters, one with mainly low Cobb angles and one with mainly high Cobb angles, for the MRI parameters measured within the apical zone, with an accuracy of 0.9 and a Matthews correlation coefficient (MCC) of 0.8. Within the control zone, the AHC showed no clear classification (accuracy of 0.6 and MCC of 0.2). CONCLUSION: We successfully performed an in vivo multiparametric MRI investigation of young patients with adolescent idiopathic scoliosis. The MRI parameters measured within the intervertebral discs were found to be sensitive to intervertebral disc degeneration occurring with scoliosis and to the severity of scoliosis. J. Magn. Reson. Imaging 2016;44:1123-1131.

Sensitivity of MRI signal distribution within the intervertebral disc to image segmentation and data normalisation.

There is a lack of early biomarkers of intervertebral disc (IVD) degeneration. Thus, the authors developed the analysis of magnetic resonance signal intensity distribution (AMRSID) method to analyse the 3D distribution of the T2-weighted MR signal intensity within the IVD using normalised histograms, weighted centres and volume ratios. The objective was to assess the sensitivity of the AMRSID method to the segmentation process and data normalisation. Repetition of the semi-automatic segmentation by the same operator did not influence the quality of the contour or our new MR distribution parameters whereas the skills of the operator influenced only the MR distribution parameters, and the instructions given prior to the segmentation influenced both the quality of the contour and the MR distribution parameters. Bone normalisation produces an index that jointly highlights IVD and bone health, whereas cerebrospinal fluid normalisation only suppresses the effect of the acquisition gain. This robust AMRSID method has the potential to improve the diagnostic with earlier biomarkers and the prognosis of evolution.

Imaging of early modification in cardiomyopathy: the doxorubicin-induced model.

Doxorubicin chemotherapy is effective and widely used to treat acute lymphoblastic leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity including both morphological and functional changes, affecting primarily the myocardium. Non-invasive imaging techniques are used for the diagnosis and monitoring of these cardiotoxic effects. The purpose of this review is to summarize and compare the most common imaging techniques used in early detection and therapeutic monitoring of doxorubicin-induced cardiotoxicity and the suggested mechanisms of such side effects. Imaging techniques using echocardiography including conventional 2D and 3D echocardiography along with MRI sequences including Tagging, Cine, and quantitative MRI in detecting early myocardial damage are also reviewed. As there is a multitude of reported indices and imaging methods to assess particular functional alterations, we limit this review to the most relevant techniques based on their clinical application and their potential to early detection of doxorubicin-induced cardiotoxic effects.

Multi-parametric MRI as an indirect evaluation tool of the mechanical properties of in-vitro cardiac tissues.

BACKGROUND: Early detection of heart failure is essential to effectively reduce related mortality. The quantification of the mechanical properties of the myocardium, a primordial indicator of the viability of the cardiac tissue, is a key element in patient's care. Despite an incremental utilization of multi-parametric magnetic resonance imaging (MRI) for cardiac tissue characteristics and function, the link between multi-parametric MRI and the mechanical properties of the heart has not been established. We sought to determine the parametric relationship between the myocardial mechanical properties and the MR parameters. The specific aim was to develop a reproducible evaluative quantitative tool of the mechanical properties of cardiac tissue using multi-parametric MRI associated to principal component analysis. METHODS: Samples from porcine hearts were submitted to a multi-parametric MRI acquisition followed by a uniaxial tensile test. Multi linear regressions were performed between dependent (Young's modulus E) and independent (relaxation times T1, T2 and T2*, magnetization transfer ratio MTR, apparent diffusion coefficient ADC and fractional anisotropy FA) variables. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. RESULTS: Values of 46.1 ± 12.7 MPa for E, 729 ± 21 ms for T1, 61 ± 6 ms for T2, 26 ± 7 for T2*, 35 ± 5% for MTR x 100, 33.8 ± 4.7 for FA x 10⁻², and 5.85 ± 0.21 mm²/s for ADC x 10⁻4 were measured. Multi linear regressions showed that only 45% of E can be explained by the MRI parameters. The principal component analysis reduced our seven variables to two principal components with a cumulative variability of 63%, which increased to 80% when considering the third principal component. CONCLUSIONS: The proposed multi-parametric MRI protocol associated to principal component analysis is a promising tool for the evaluation of mechanical properties within the left ventricle in the in vitro porcine model. Our in vitro experiments will now allow us focused in vivo testing on healthy and infracted hearts in order to determine useful quantitative MR-based biomarkers.

Sensitivity of multi-parametric MRI to the compressive state of the isolated intervertebral discs.

OBJECTIVE: Magnetic resonance imaging (MRI) offers great potential as a sensitive and noninvasive technique for describing the alterations in mechanical properties, as shown in vitro on intervertebral disc (IVD) or cartilage tissues. However, in vivo, the IVD is submitted to complex loading stimuli. Thus, the present question focuses on the influence of the mechanical loading during an MRI acquisition on the relaxation times, magnetization transfer and diffusion parameters within the IVD. METHODS: An apparatus allowing the compression of isolated IVDs was designed and manufactured in acrylonitrile butadiene styrene. IVDs were dissected from fresh young bovine tail, measured for their thickness and submitted to compression just before the MRI acquisition. Six discs received 0% (platen positioned at the initial disc thickness), 5% (platen positioned at 95% of the initial disc thickness), 10%, 20% and 40% deformation. The MRI parameters were compared between the loading states using mean and standard deviation for T1 and T2, and matrix subtraction for Magnetization Transfer, fractional anisotropy and apparent diffusion coefficient. RESULTS: The compression of the IVD did not lead to any significant change of the MRI parameters, except for the diffusion that decreased in the direction of the compressive stress. DISCUSSION: This experimental in vitro study shows that multi-parametric MRI on isolated discs in vitro is not sensitive to compression or to the partial confined relaxation that followed the compression.

MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis.

BACKGROUND: Early stages of scoliosis and spondylolisthesis entail changes in the intervertebral disc (IVD) structure and biochemistry. The current clinical use of MR T2-weighted images is limited to visual inspection. Our hypothesis is that the distribution of the MRI signal intensity within the IVD in T2-weighted images depends on the spinal pathology and on its severity. Therefore, this study aims to develop the AMRSID (analysis of MR signal intensity distribution) method to analyze the 3D distribution of the MR signal intensity within the IVD and to evaluate their sensitivity to scoliosis and spondylolisthesis and their severities. METHODS: This study was realized on 79 adolescents who underwent a MRI acquisition (sagittal T2-weighted images) before their orthopedic or surgical treatment. Five groups were considered: low severity scoliosis (Cobb angle ≤50°), high severity scoliosis (Cobb angles >50°), low severity spondylolisthesis (Meyerding grades I and II), high severity spondylolisthesis (Meyerding grades III, IV and V) and control. The distribution of the MRI signal intensity within the IVD was analyzed using the descriptive statistics of histograms normalized by either cerebrospinal fluid or bone signal intensity, weighted centers and volume ratios. Differences between pathology and severity groups were assessed using one- and two-way ANOVAs. RESULTS: There were significant (p < 0.05) variations of indices between scoliosis, spondylolithesis and control groups and between low and high severity groups. The cerebrospinal fluid normalization was able to detect differences between healthy and pathologic IVDs whereas the bone normalization, which reflects both bone and IVD health, detected more differences between the severities of these pathologies. CONCLUSIONS: This study proves for the first time that changes in the intervertebral disc, non visible to the naked eye on sagittal T2-weighted MR images of the spine, can be detected from specific indices describing the distribution of the MR signal intensity. Moreover, these indices are able to discriminate between scoliosis and spondylolisthesis and their severities, and provide essential information on the composition and structure of the discs whatever the pathology considered. The AMRSID method may have the potential to complement the current diagnostic tools available in clinics to improve the diagnostic with earlier biomarkers, the prognosis of evolution and the treatment options of scoliosis and spondylolisthesis.

Assessment of mechanical properties of isolated bovine intervertebral discs from multi-parametric magnetic resonance imaging.

BACKGROUND: The treatment planning of spine pathologies requires information on the rigidity and permeability of the intervertebral discs (IVDs). Magnetic resonance imaging (MRI) offers great potential as a sensitive and non-invasive technique for describing the mechanical properties of IVDs. However, the literature reported small correlation coefficients between mechanical properties and MRI parameters. Our hypothesis is that the compressive modulus and the permeability of the IVD can be predicted by a linear combination of MRI parameters. METHODS: Sixty IVDs were harvested from bovine tails, and randomly separated in four groups (in-situ, digested-6h, digested-18h, digested-24h). Multi-parametric MRI acquisitions were used to quantify the relaxation times T1 and T2, the magnetization transfer ratio MTR, the apparent diffusion coefficient ADC and the fractional anisotropy FA. Unconfined compression, confined compression and direct permeability measurements were performed to quantify the compressive moduli and the hydraulic permeabilities. Differences between groups were evaluated from a one way ANOVA. Multi linear regressions were performed between dependent mechanical properties and independent MRI parameters to verify our hypothesis. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. Agglomerative Hierarchical Clustering was performed on the 3 principal components. RESULTS: Multilinear regressions showed that 45 to 80% of the Young's modulus E, the aggregate modulus in absence of deformation HA0, the radial permeability kr and the axial permeability in absence of deformation k0 can be explained by the MRI parameters within both the nucleus pulposus and the annulus pulposus. The principal component analysis reduced our variables to two principal components with a cumulative variability of 52-65%, which increased to 70-82% when considering the third principal component. The dendograms showed a natural division into four clusters for the nucleus pulposus and into three or four clusters for the annulus fibrosus. CONCLUSIONS: The compressive moduli and the permeabilities of isolated IVDs can be assessed mostly by MT and diffusion sequences. However, the relationships have to be improved with the inclusion of MRI parameters more sensitive to IVD degeneration. Before the use of this technique to quantify the mechanical properties of IVDs in vivo on patients suffering from various diseases, the relationships have to be defined for each degeneration state of the tissue that mimics the pathology. Our MRI protocol associated to principal component analysis and agglomerative hierarchical clustering are promising tools to classify the degenerated intervertebral discs and further find biomarkers and predictive factors of the evolution of the pathologies.