Feasibility and safety of synchrotron-based X-ray phase contrast imaging as a technique complementary to histopathology analysis.

X-ray phase contrast imaging (X-PCI) is a powerful technique for high-resolution, three-dimensional imaging of soft tissue samples in a non-destructive manner. In this technical report, we assess the quality of standard histopathological techniques performed on formalin-fixed, paraffin-embedded (FFPE) human tissue samples that have been irradiated with different doses of X-rays in the context of an X-PCI experiment. The data from this study demonstrate that routine histochemical and immunohistochemical staining quality as well as DNA and RNA analyses are not affected by previous X-PCI on human FFPE samples. From these data we conclude it is feasible and acceptable to perform X-PCI on FFPE human biopsies.

A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 µm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Comprehensive data integration-Toward a more personalized assessment of diastolic function.

BACKGROUND AND AIM: The main challenge of assessing diastolic function is the balance between clinical utility, in the sense of usability and time-efficiency, and overall applicability, in the sense of precision for the patient under investigation. In this review, we aim to explore the challenges of integrating data in the assessment of diastolic function and discuss the perspectives of a more comprehensive data integration approach. METHODS: Review of traditional and novel approaches regarding data integration in the assessment of diastolic function. RESULTS: Comprehensive data integration can lead to improved understanding of disease phenotypes and better relation of these phenotypes to underlying pathophysiological processes-which may help affirm diagnostic reasoning, guide treatment options, and reduce limitations related to previously unaddressed confounders. The optimal assessment of diastolic function should ideally integrate all relevant clinical information with all available structural and functional whole cardiac cycle echocardiographic data-envisioning a personalized approach to patient care, a high-reaching future goal in medicine. CONCLUSION: Complete data integration seems to be a long-lasting goal, the way forward in diastology, and machine learning seems to be one of the tools suited for the challenge. With perpetual evidence that traditional approaches to complex problems may not the optimal solution, there is room for a steady and cautious, and inherently very exciting paradigm shift toward novel diagnostic tools and workflows to reach a more personalized, comprehensive, and integrated assessment of cardiac function.

Machine Learning in Fetal Cardiology: What to Expect.

In fetal cardiology, imaging (especially echocardiography) has demonstrated to help in the diagnosis and monitoring of fetuses with a compromised cardiovascular system potentially associated with several fetal conditions. Different ultrasound approaches are currently used to evaluate fetal cardiac structure and function, including conventional 2-D imaging and M-mode and tissue Doppler imaging among others. However, assessment of the fetal heart is still challenging mainly due to involuntary movements of the fetus, the small size of the heart, and the lack of expertise in fetal echocardiography of some sonographers. Therefore, the use of new technologies to improve the primary acquired images, to help extract measurements, or to aid in the diagnosis of cardiac abnormalities is of great importance for optimal assessment of the fetal heart. Machine leaning (ML) is a computer science discipline focused on teaching a computer to perform tasks with specific goals without explicitly programming the rules on how to perform this task. In this review we provide a brief overview on the potential of ML techniques to improve the evaluation of fetal cardiac function by optimizing image acquisition and quantification/segmentation, as well as aid in improving the prenatal diagnoses of fetal cardiac remodeling and abnormalities.

Main Patterns of Fetal Cardiac Remodeling.

The heart is a central organ in the fetal adaptation to an adverse environment. Fetal cardiac changes may persist postnatally and increase the risk of cardiovascular disease in adulthood. Knowledge about fetal cardiac structural as well as functional remodeling has radically improved over the last few years. As it occurs in postnatal life, the fetal heart remodels - changing its structure and shape - to adapt to an insult. Several conditions have been reported to be associated with fetal cardiac remodeling including intrauterine growth restriction, diabetes, exposure to antiretroviral drugs, conception by assisted reproductive technologies, pulmonary stenosis, and other congenital heart diseases. Here we summarized the main observable patterns of cardiac remodeling, i.e., globular shape, hypertrophy without dilation, and hypertrophy with cardiomegaly. We discuss the potential pathophysiology behind different types of remodeling. Defining precisely the distinct patterns of fetal cardiac remodeling is critical for advancing in the understanding of fetal cardiovascular programming and its consequences on adult health, and potentially for the design of preventive strategies that might have an impact on long-term cardiovascular health.

Cardiac performance after an endurance open water swimming race.

PURPOSE: Endurance exercise competitions have shown a transient negative effect on global right ventricular (RV) performance. Most published studies are based on terrestrial sports. The aim of our study was to evaluate the cardiac effects after an open water swimming race. METHODS: We evaluated 33 healthy swimmers (mean age 40.9 ± 7.2) participating in a 9.5 km open water swimming race. All subjects underwent a standard transthoracic echocardiography including an evaluation of dimensions and myocardial ventricular deformation. Echocardiography was performed 24 h before and within the first hour of arrival at the finish line. Cardiac troponin I (cTn I), NT-ProBNP and leukocytes were also evaluated. RESULTS: No changes in left ventricle (LV) ejection fraction or LV global longitudinal strain were observed. A significant increase in RV end-diastolic area (RVEDA) was noted after the race (RVEDA at baseline 15.12 ± 1.86; RVEDA after race 16.06 ± 2.27, p < 0.05), but no changes were seen in RV fractional area change or RV global longitudinal strain. Cardiac biomarkers and leukocytes significantly increased. No association was detected between the increase in cTn I or NT-proBNP and the RV acute dilatation or LV performance. A significant association was observed between cTn I and leukocytes (r = 0.375, p < 0.05). CONCLUSIONS: An acute RV dilatation but without an impairment in RV deformation was observed after participating in an endurance swimming race. The correlation between the increase in cTn I and leukocytes, but not with ventricular performance, may support the hypothesis of an exercise-induced increase in myocardial sarcolemmal permeability due to an inflammatory response rather than myocardial injury.

Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension.

The objective of the present study was to investigate mechanisms of heart rate (HR) reduction on biventricular function and interactions in experimental pulmonary arterial hypertension (PAH). We compared cardiac cycle mechanics and interventricular interactions in 15 sham, 8 monocrotaline-PAH, 9 PAH + carvedilol, and 8 PAH + ivabradine rats. We used echocardiography to assess biventricular function, timing of cardiac cycle events, and septal position in PAH rats and related HR reduction effects on biventricular function measured by echocardiography and conductance catheter. HR was 302 beats/min in PAH + carvedilol rats and 303 beats/min in PAH + ivabradine rats versus 359 beats/min in PAH rats ( P < 0.01). Sham rats showed temporal alignment between right ventricular (RV) and left ventricular (LV) events, whereas PAH rats showed increased biventricular isovolumic contraction times (ICTs), delayed RV peak radial motion, and impaired early relaxation. Temporal malalignment was associated with decreased tricuspid and mitral diastolic annular peak velocities (3.7 vs. 6.4 and 3.4 vs. 5.3 cm/s, respectively, P < 0.001), delayed and shortened biventricular filling, and reduced early diastolic LV filling velocity (0.56 vs. 0.81 cm/s, P < 0.01). LV eccentricity index was increased at systole (2.0 vs. 1.2, P < 0.001), early diastole (2.1 vs. 1.1, P < 0.001), and end diastole (1.6 vs. 1.1, P < 0.001) in PAH versus sham rats. HR reduction with carvedilol and ivabradine shortened biventricular ICTs and the time to biventricular peak radial motion, improved RV relaxation, and increased early diastolic LV filling through reduced interventricular interaction and improved timing. These improvements corresponded with enhanced hemodynamics (increased cardiac output, RV contractility, and diastolic relaxation). In conclusion, HR reduction by carvedilol and ivabradine improves biventricular filling and hemodynamics in experimental PAH through realignment of RV-LV cardiac cycle events and improved interventricular interactions. NEW & NOTEWORTHY Carvedilol improves biventricular function in experimental pulmonary arterial hypertension, but the mechanisms of heart rate reduction versus ß-blocker effect are inadequately defined. Here, we demonstrate that reducing heart rate using either carvedilol or ivabradine (hyperpolarization-activated current inhibitor without ß-blocker effect) improves right ventricular filling and biventricular hemodynamics through the realignment of right ventricular-left ventricular cardiac cycle events and improved interventricular interactions.

Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise.

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): -2.9 ± 0.5 vs. -3.3 ± 0.6 s-1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: -3.3 ± 0.6 vs. -3.0 ± 0.4 s-1 and basal SR: -3.3 ± 0.7 vs. -2.7 ± 0.6 s-1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive.NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function.

Experimentally induced intrauterine growth restriction in rabbits leads to differential remodelling of left versus right ventricular myocardial microstructure.

Intrauterine growth restriction (IUGR) is associated with foetal cardiac remodelling and dysfunction together with increased risk of cardiovascular disease in adulthood. Experimental data concerning effects of IUGR on cardiomyocyte and microvascularization anatomy are inconsistent and it is unknown whether both ventricles are similarly susceptible to in utero undersupply. Foetal IUGR was induced in pregnant rabbits at 25 days of gestation by selective ligation of uteroplacental vessels. Foetal echocardiography showed systolic and diastolic dysfunction of both ventricles and body and heart weight were significantly reduced in response to IUGR. Design-based stereology revealed a decrease in cardiomyocyte number in both ventricles which was only in the left ventricle accompanied by a significantly higher cardiomyocyte mean volume. The proportion of mono- and bi-nucleated cardiomyocytes was unaltered between the groups indicating a similar maturation status. The number and length of cardiac capillaries in IUGR offspring was diminished in left but not in right ventricles. Foetal left and right ventricles are differently affected by placental insufficiency. While cardiomyocyte numbers are diminished in both ventricles, hypertrophic remodelling of cardiomyocytes and alterations in microvascularization is rather a left ventricular adaptation to IUGR. These unequal structural changes may be related to loading and developmental differences of the left and right ventricles.

Left ventricular dysfunction is related to the presence and extent of a septal flash in patients with right ventricular pacing.

Aims: Septal flash (SF), a marker of left ventricular (LV) dyssynchrony in the presence of a left bundle branch block (LBBB), has been shown to predict improved ventricular function and outcome when corrected with cardiac resynchronization therapy. We hypothesized that a SF is present in patients receiving right ventricular (RV) pacing and its presence and extent could predict the development of LV dysfunction and remodelling. Methods and Results: Seventy-four consecutive patients receiving conventional RV pacing (>6 months, >85% paced) were studied with two-dimensional (2D) echocardiography. Indications for pacing were sinus-node dysfunction and atrioventricular conduction disorders. The presence of a SF was determined on stepwise advanced 2D echocardiographic views and confirmed using greyscale M-mode. Septal flash excursion was quantified by the amplitude of the early inward motion, measured from QRS onset to maximal inward motion. Fifty-seven (of 74; 77%) patients receiving RV pacing had a detectable SF. Patients with a SF had lower LV ejection fraction (EF) (52 ± 10 vs. 60 ± 4%, P < 0.001) and greater indexed end-systolic volume (33 ± 16 vs. 23 ± 5 mL/m2, P < 0.001). Receiver operating characteristic analysis demonstrated that a SF of 3.5 mm was the optimal cut-off value (area under the curve = 0.95) to identify reduced LV function (EF < 50%) with a sensitivity of 91% and a specificity of 90%. Conclusion: A SF was present in a majority of patients receiving conventional RV pacing and its magnitude was related to LV dysfunction and adverse remodelling. Given the similarities observed in LBBB and pacemaker-induced dyssynchrony, SF magnitude might be a predictor for the development of LV dysfunction and adverse remodelling in patients receiving conventional RV pacing.

Influence of gender on right ventricle adaptation to endurance exercise: an ultrasound two-dimensional speckle-tracking stress study.

BACKGROUND: Characteristic right ventricle (RV) remodelling is related to endurance exercise in male athletes (MAs), but data in female athletes (FAs) are scarce. Our aim was to evaluate sex-related influence on exercise-induced RV remodelling and on RV performance during exercise. METHODS: Forty endurance athletes (>10 training hours/week, 50% female) and 40 age-matched controls (<3 h moderate exercise/week, 50% female) were included. Echocardiography was performed at rest and at maximum cycle-ergometer effort. Both ventricles were analysed by standard and speckle-tracking echocardiography. RESULTS: Endurance training induced similar structural and functional cardiac remodelling in MAs and FAs, characterized by bi-ventricular dilatation [~34%, left ventricle (LV); 29%, RV] and normal bi-ventricular function. However, males had larger RV size (p < 0.01), compared to females: RV end-diastolic area (cm2/m2): 15.6 ± 2.2 vs 11.6 ± 1.7 in athletes; 12.2 ± 2.7 vs 8.6 ± 1.6 in controls, respectively, and lower bi-ventricular deformation (RV global longitudinal strain (GLS) (%): -24.0 ± 3.6 vs -29.2 ± 3.1 in athletes; -24.9 ± 2.5 vs -30.0 ± 1.9 in controls, and LVGLS: -17.5 ± 1.4 vs -21.9 ± 1.9 in athletes; -18.7 ± 1.2 vs -22.5 ± 1.5 in controls, respectively, p < 0.01). During exercise, the increase in LV function was positively correlated (p < 0.01) with increased cardiac output (∆%LV ejection fraction, r = +0.46 and ∆%LVGLS, r = +0.36). Improvement in RV performance was blunted at high workloads, especially in MAs. CONCLUSION: Long-term endurance training induced similar bi-ventricular remodelling in MAs and FAs. Independently of training load, males had larger RV size and lower bi-ventricular deformation. Improvement in RV performance during exercise was blunted at high workloads, especially in MAs. The potential mechanisms underlying these findings warrant further investigation.

Assessment of myocardial ischemia by strain dobutamine stress echocardiography and cardiac magnetic resonance perfusion imaging before and after coronary artery bypass grafting.

BACKGROUND: Following coronary artery bypass grafting (CABG), testing for myocardial ischemia by noninvasive imaging is often hampered by false-positive results. The aim of this study was to find test parameters with the best potential to identify myocardial ischemia in post-CABG patients. METHODS: Fifty-two consecutive patients scheduled for CABG, underwent both dobutamine stress echocardiography (DSE) and cardiac magnetic resonance first-pass perfusion imaging (CMR-FPPI) with adenosine vasodilation, before and 8-10 months after the surgical revascularization. A pathologic biphasic stress response (PBR) expresses the presence of contractile reserve during low-dose dobutamine that decreases to hypo- or akinesia provoked by high-dose dobutamine. During DSE, potential PBR, segmental wall-motion score (WMS) as well as peak-systolic longitudinal strain (PLS) at peak-dose dobutamine were assessed. RESULTS: Post-CABG, there was still a relatively high prevalence of ischemia-positive segments evaluated by deformation imaging, but the number of such segments was significantly lower by PBR (20% and 22%) compared with peak-dose strain and WMS (62% and 77%, respectively; P<.05). The use of PBR instead of peak-dose WMS and strain could reduce the number of false-positive test results post-CABG. CONCLUSION: Among all imaging modalities tested, PBR by WMS and strain may be useful parameters for identifying patients with the need for new revascularization. We furthermore found that DSE may be interpreted as positive when revealing at least three ischemia-positive segments. The sensitivity of these test modalities for detecting coronary restenosis needs to be determined in further studies on a cohort of symptomatic post-CABG patients.

Understanding the Aortic Isthmus Doppler Profile and Its Changes with Gestational Age Using a Lumped Model of the Fetal Circulation.

OBJECTIVE: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the changes of AoI flow through gestation. METHODS: A validation of the model was performed by fitting patient-specific data from two normal fetuses. Then, different parametric analyses were performed to evaluate the major determinants of the appearance of the end-systolic notch. The changes in the AoI flow profile through gestation were assessed. RESULTS: Our model allows to simulate the AoI waveform. The delay in the onset of ejection together with the longer ejection duration of the right ventricle are the most relevant factors in the origin of the notch. It appears around 25 weeks of gestation and becomes more pronounced with advancing gestation. DISCUSSION: We demonstrated that the end-systolic notch on the AoI flow occurs mainly as a result of a delayed and longer ejection of the right ventricle. Our findings improve the understanding of hemodynamic changes in the fetal circulation and the interpretation of clinical imaging.

Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction.

BACKGROUND: Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). METHODS: A cohort study including 81 children with birthweight <10th centile (FGR) and 121 with adequate fetal growth for gestational age (AGA) was conducted. Cardiovascular endpoints were left ventricular sphericity index (LVSI), carotid intima-media thickness (cIMT), and blood pressure (BP) at 4-5 y of age. The combined effect of FGR and postnatal variables-including breastfeeding, fat dietary intake, and BMI-on cardiovascular endpoints was assessed by linear and robust regressions. RESULTS: FGR was the strongest predictor of cardiovascular remodeling in childhood, leading to lower LVSI and increased cIMT and BP as compared with AGA. Breastfeeding >6 mo (coefficient: 0.0982) and healthy-fat dietary intake (coefficient: -0.0128) showed an independent beneficial effect on LVSI and cIMT, respectively. Overweight/obesity induced an additional increment of 1 SD on cIMT in FGR children (interaction coefficient: 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient: 0.7830) while weight catch-up increased diastolic BP (coefficient: 4.8929). CONCLUSIONS: Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life.

Heart morphology differences induced by intrauterine growth restriction and preterm birth measured on the ECG at preadolescent age.

Intrauterine Growth Restriction (IUGR) and premature birth are associated with higher risk of cardiovascular diseases throughout adulthood. The aim of this study was to evaluate the influence of these factors in ventricular electrical remodeling in preadolescents. Electrocardiography was performed in a cohort of 33-IUGR, 32-preterm with appropriate weight and 60 controls. Depolarization and repolarization processes were studied by means of the surface ECG, including loops and angles corresponding to QRS and T-waves. The angles between the dominant vector of QRS and the frontal plane XY were different among the study groups: controls [20.03°(10.11°-28.64°)], preterm [25.48°(19.79°-33.56°)], and IUGR [27.77°(16.59°-33.23°)]. When compared to controls, IUGR subjects also presented wider angles between the difference of QRS and T-wave dominant vectors and the XY-plane [5.28°±12.15° vs 0.49°±14.15°, p<0.05] while preterm ones showed smaller frontal QRS-T angle [4.68°(2.20°-12.89°) vs 6.57°(2.72°-11.31°), p<0.05]. Thus, electrical remodeling is present in IUGR and preterm preadolescents, and might predispose them to cardiovascular diseases in adulthood. Follow-up studies are warranted.

Comparison of Two Different Ultrasound Systems for the Evaluation of Tissue Doppler Velocities in Fetuses.

INTRODUCTION: Recent studies have reported variations of up to 30% between different ultrasound machines for tissue Doppler imaging (TDI), a problem that can significantly impact clinical diagnosis, patient management and research studies. The objective of this study was to assess repeatability and agreement between fetal myocardial peak velocities evaluated by TDI with two different ultrasound systems. MATERIALS AND METHODS: Systolic (S'), early (E') and late (A') diastolic myocardial peak velocities at mitral and tricuspid annuli as well as at the basal septum were evaluated by spectral TDI in 150 fetuses using two different ultrasound systems: Siemens Antares (Siemens Medical Systems, Malvern, Pa., USA) and Vivid Q (General Electric Healthcare, Horten, Norway). A method comparison study was performed, calculating intraclass correlation coefficients (ICC), and agreement was assessed by Bland-Altman plots. RESULTS: Annular peak velocities showed lower values when measured by Vivid Q compared to values measured by Siemens Antares. ICC ranged from 0.07 (septal S') to 0.33 (right A'), showing very poor repeatability for clinical application. Agreement between the two systems was also poor, with high coefficients of variation for all measurements. CONCLUSIONS: Fetal annular peak velocities obtained with different ultrasound systems are not directly comparable. This is consistent with previous data in adults and warrants the need of system-specific reference values, suggesting that the same ultrasound machine should be used for longitudinal follow-up.

A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.