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"Zemrak, Filip"
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Automated cardiovascular magnetic resonance image analysis with fully convolutional networks
2018
Background
Cardiovascular resonance (CMR) imaging is a standard imaging modality for assessing cardiovascular diseases (CVDs), the leading cause of death globally. CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors. It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images.
Methods
Deep neural networks have shown a great potential in image pattern recognition and segmentation for a variety of tasks. Here we demonstrate an automated analysis method for CMR images, which is based on a fully convolutional network (FCN). The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4,875 subjects with 93,500 pixelwise annotated images. The performance of the method has been evaluated using a number of technical metrics, including the Dice metric, mean contour distance and Hausdorff distance, as well as clinically relevant measures, including left ventricle (LV) end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV).
Results
By combining FCN with a large-scale annotated dataset, the proposed automated method achieves a high performance in segmenting the LV and RV on short-axis CMR images and the left atrium (LA) and right atrium (RA) on long-axis CMR images. On a short-axis image test set of 600 subjects, it achieves an average Dice metric of 0.94 for the LV cavity, 0.88 for the LV myocardium and 0.90 for the RV cavity. The mean absolute difference between automated measurement and manual measurement is 6.1 mL for LVEDV, 5.3 mL for LVESV, 6.9 gram for LVM, 8.5 mL for RVEDV and 7.2 mL for RVESV. On long-axis image test sets, the average Dice metric is 0.93 for the LA cavity (2-chamber view), 0.95 for the LA cavity (4-chamber view) and 0.96 for the RA cavity (4-chamber view). The performance is comparable to human inter-observer variability.
Conclusions
We show that an automated method achieves a performance on par with human experts in analysing CMR images and deriving clinically relevant measures.
Journal Article
Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort
2017
Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74.
Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45–54, 55–64, 65–74).
After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females.
We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population.
Journal Article
Automated quality control in image segmentation: application to the UK Biobank cardiovascular magnetic resonance imaging study
2019
Background
The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale. However, it is important to be able to automatically detect when a segmentation method fails in order to avoid inclusion of wrong measurements into subsequent analyses which could otherwise lead to incorrect conclusions.
Methods
To overcome this challenge, we explore an approach for predicting segmentation quality based on Reverse Classification Accuracy, which enables us to discriminate between successful and failed segmentations on a per-cases basis. We validate this approach on a new, large-scale manually-annotated set of 4800 cardiovascular magnetic resonance (CMR) scans. We then apply our method to a large cohort of 7250 CMR on which we have performed manual QC.
Results
We report results used for predicting segmentation quality metrics including Dice Similarity Coefficient (DSC) and surface-distance measures. As initial validation, we present data for 400 scans demonstrating 99% accuracy for classifying low and high quality segmentations using the predicted DSC scores. As further validation we show high correlation between real and predicted scores and 95% classification accuracy on 4800 scans for which manual segmentations were available. We mimic real-world application of the method on 7250 CMR where we show good agreement between predicted quality metrics and manual visual QC scores.
Conclusions
We show that Reverse classification accuracy has the potential for accurate and fully automatic segmentation QC on a per-case basis in the context of large-scale population imaging as in the UK Biobank Imaging Study.
Journal Article
Cardiovascular magnetic resonance reference values of mitral and tricuspid annular dimensions: the UK Biobank cohort
2020
Background
Mitral valve (MV) and tricuspid valve (TV) apparatus geometry are essential to define mechanisms and etiologies of regurgitation and to inform surgical or transcatheter interventions. Given the increasing use of cardiovascular magnetic resonance (CMR) for the evaluation of valvular heart disease, we aimed to establish CMR-derived age- and sex-specific reference values for mitral annular (MA) and tricuspid annular (TA) dimensions and tethering indices derived from truly healthy Caucasian adults.
Methods
5065 consecutive UK Biobank participants underwent CMR using cine balanced steady-state free precession imaging at 1.5 T. Participants with non-Caucasian ethnicity, prevalent cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Absolute and indexed reference ranges for MA and TA diameters and tethering indices were stratified by gender and age (45–54, 55–64, 65–74 years).
Results
Overall, 721 (14.2%) truly healthy participants aged 45–74 years (54% women) formed the reference cohort. Absolute MA and TA diameters, MV tenting length and MV tenting area, were significantly larger in men. Mean ± standard deviation (SD) end-diastolic and end-systolic MA diameters in the 3-chamber view (anteroposterior diameter) were 2.9 ± 0.4 cm (1.5 ± 0.2 cm/m
2
) and 3.3 ± 0.4 cm (1.7 ± 0.2 cm/m
2
) in men, and 2.6 ± 0.4 cm (1.6 ± 0.2 cm/m
2
) and 3.0 ± 0.4 cm (1.8 ± 0.2 cm/m
2
) in women, respectively. Mean ± SD end-diastolic and end-systolic TA diameters in the 4-chamber view were 3.2 ± 0.5 cm (1.6 ± 0.3 cm/m
2
) and 3.2 ± 0.5 cm (1.7 ± 0.3 cm/m
2
) in men, and 2.9 ± 0.4 cm (1.7 ± 0.2 cm/m
2
) and 2.8 ± 0.4 cm (1.7 ± 0.3 cm/m
2
) in women, respectively. With advancing age, end-diastolic TA diameter became larger and posterior MV leaflet angle smaller in both sexes. Reproducibility of measurements was good to excellent with an inter-rater intraclass correlation coefficient (ICC) between 0.92 and 0.98 and an intra-rater ICC between 0.90 and 0.97.
Conclusions
We described age- and sex-specific reference ranges of MA and TA dimensions and tethering indices in the largest validated healthy Caucasian population. Reference ranges presented in this study may help to improve the distinction between normal and pathological states, prompting the identification of subjects that may benefit from advanced cardiac imaging for annular sizing and planning of valvular interventions.
Journal Article
Physical activity and left ventricular trabeculation in the UK Biobank community-based cohort study
2019
ObjectiveVigorous physical activity (PA) in highly trained athletes has been associated with heightened left ventricular (LV) trabeculation extent. It has therefore been hypothesised that LV trabeculation extent may participate in exercise-induced physiological cardiac remodelling. Our cross-sectional observational study aimed to ascertain whether there is a ‘dose–response’ relationship between PA and LV trabeculation extent and whether this could be identified at opposite PA extremes.MethodsIn a cohort of 1030 individuals from the community-based UK Biobank study (male/female ratio: 0.84, mean age: 61 years), PA was measured via total metabolic equivalent of task (MET) min/week and 7-day average acceleration, and trabeculation extent via maximal non-compaction/compaction ratio (NC/C) in long-axis images of cardiovascular magnetic resonance studies. The relationship between PA and NC/C was assessed by multivariate regression (adjusting for potential confounders) as well as between demographic, anthropometric and LV phenotypic parameters and NC/C.ResultsThere was no significant linear relationship between PA and NC/C (full adjustment, total MET-min/week: ß=−0.0008, 95% CI −0.039 to –0.037, p=0.97; 7-day average acceleration: ß=−0.047, 95% CI −0.110 to –0.115, p=0.13, per IQR increment in PA), or between extreme PA quintiles (full adjustment, total MET-min/week: ß=−0.026, 95% CI −0.146 to –0.094, p=0.67; 7-day average acceleration: ß=−0.129, 95% CI −0.299 to –0.040, p=0.49), across all adjustment levels. A negative relationship was identified between left ventricular ejection fraction and NC/C, significantly modified by PA (ß difference=−0.006, p=0.03).ConclusionsIn a community-based general population cohort, there was no relationship at, or between, extremes, between PA and NC/C, suggesting that at typical general population PA levels, trabeculation extent is not influenced by PA changes.
Journal Article
The impact of cardiovascular risk factors on cardiac structure and function: Insights from the UK Biobank imaging enhancement study
2017
The UK Biobank is a large-scale population-based study utilising cardiovascular magnetic resonance (CMR) to generate measurements of atrial and ventricular structure and function. This study aimed to quantify the association between modifiable cardiovascular risk factors and cardiac morphology and function in individuals without known cardiovascular disease.
Age, sex, ethnicity (non-modifiable) and systolic blood pressure, diastolic blood pressure, smoking status, exercise, body mass index (BMI), high cholesterol, diabetes, alcohol intake (modifiable) were considered important cardiovascular risk factors. Multivariable regression models were built to ascertain the association of risk factors on left ventricular (LV), right ventricular (RV), left atrial (LA) and right atrial (RA) CMR parameters.
4,651 participants were included in the analysis. All modifiable risk factors had significant effects on differing atrial and ventricular parameters. BMI was the modifiable risk factor most consistently associated with subclinical changes to CMR parameters, particularly in relation to higher LV mass (+8.3% per SD [4.3 kg/m2], 95% CI: 7.6 to 8.9%), LV (EDV: +4.8% per SD, 95% CI: 4.2 to 5.4%); ESV: +4.4% per SD, 95% CI: 3.5 to 5.3%), RV (EDV: +5.3% per SD, 95% CI: 4.7 to 5.9%; ESV: +5.4% per SD, 95% CI: 4.5 to 6.4%) and LA maximal (+8.6% per SD, 95% CI: 7.4 to 9.7%) volumes. Increases in SBP were associated with higher LV mass (+6.8% per SD, 95% CI: 5.9 to 7.7%), LV (EDV: +4.5% per SD, 95% CI: 3.6 to 5.4%; ESV: +2.0% per SD, 95% CI: 0.8 to 3.3%) volumes. The presence of diabetes or high cholesterol resulted in smaller volumes and lower ejection fractions.
Modifiable risk factors are associated with subclinical alterations in structure and function in all four cardiac chambers. BMI and systolic blood pressure are the most important modifiable risk factors affecting CMR parameters known to be linked to adverse outcomes.
Journal Article
Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study
by
Vogel-Claussen, Jens
,
Smith, Benjamin M.
,
Lima, Joao A. C.
in
Adults
,
Aged
,
Aged, 80 and over
2017
Evaluation of impaired left ventricular (LV) filling has focused on intrinsic causes of LV dysfunction; however, pulmonary vascular changes may contribute to reduced LV filling and dyspnea. We hypothesized that lower total pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated with dyspnea and decrements in LV end-diastolic volume, particularly among ever-smokers.
The Multi-Ethnic Study of Atherosclerosis recruited adults without clinical cardiovascular disease in 2000-02. In 2010-12, TPVV was ascertained as the volume of arteries and veins in the lungs detectable on non-contrast chest CT (vessels ≥1 mm diameter). Cardiac measures were assessed by magnetic resonance imaging (MRI). Dyspnea was self-reported.
Of 2303 participants, 53% had ever smoked cigarettes. Among ever-smokers, a lower TPVV was associated with a lower LV end-diastolic volume (6.9 mL per SD TPVV), stroke volume, and cardiac output and with dyspnea (all P-values <0.001). Findings were similar among those without lung disease and those with 0-10 pack-years but were mostly non-significant among never-smokers. TPVV was associated smaller left atrial volume but not with LV ejection fraction or MRI measures of impaired LV relaxation. In a second sample of ever-smokers, a lower pulmonary microvascular blood volume on contrast-enhanced MRI was also associated with a lower LV end-diastolic volume (P-value = 0.008).
Reductions in pulmonary vascular volume were associated with lower LV filling and dyspnea among ever-smokers, including those without lung disease, suggesting that smoking-related pulmonary vascular changes may contribute to symptoms and impair cardiac filling and function without evidence of impaired LV relaxation.
Journal Article
Extracellular volume quantification in isolated hypertension - changes at the detectable limits?
2015
Background
Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.
Methods
In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.
Results
Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m
2
; female > 78 g/m
2
). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms,
p = 0.16
). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03,
p = 0.06
). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02,
p < 0.001
).
Conclusion
In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.
Journal Article
Effect of sodium-glucose cotransporter 2 inhibitors on ventricular function in systemic right ventricular failure
by
Walker, Niki L
,
Mertens, Bart JA
,
Jongbloed, Monique RM
in
Adult
,
Cardiovascular disease
,
Congenital diseases
2025
BackgroundSystemic right ventricle (sRV) patients are at an increased risk of developing heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be a valuable treatment option. This study investigated the changes in ventricular function in sRV failure patients in the first year after starting SGLT2i.MethodsAdult sRV patients from the international, real-world ACHIEVE-SGLT2i registry were included if they had a clinical diagnosis of sRV failure, a transthoracic echocardiogram before starting SGLT2i, and at least one in the first year after starting available for analysis. The primary outcomes were changes in sRV global longitudinal strain (GLS) and fractional area change (FAC). Longitudinal changes were evaluated using linear mixed models.ResultsThirty-nine sRV failure patients (46±9.3 years old, 41% female) were included. Twenty-five (64%) had transposition of the great arteries after an atrial switch procedure and 14 (36%) had congenitally corrected transposition. sRV GLS improved significantly in the first 50 days (−1.4%-point per month, p<0.001) and stabilised afterwards (<0.1%-point per month, p=0.520). Though age had a significant overall negative effect on sRV GLS (0.1%-point per year of age, p=0.049), it did not influence the longitudinal changes after starting SGLT2i. sRV FAC also improved in the first 50 days (3.2%-point per month, p=0.002), after which sRV FAC deteriorated in patients with subpulmonary left ventricular pacing (−0.9%-point per month, p=0.012) while it stabilised in patients without pacing (0.1%-point per month, p=0.573). In the first 50 days, tricuspid annular plane systolic excursion also improved significantly in all patients (1.2 mm per month, p=0.006), and stabilised afterwards (p=0.721).ConclusionsSGLT2i therapy is associated with improvements in systolic ventricular function in sRV failure patients. Despite early improvement in sRV FAC, there was a negative longer term correlation with subpulmonary left ventricular pacing, potentially reflecting adverse effects of subpulmonary ventricular pacing on sRV function.
Journal Article
The impact of menopausal hormone therapy (MHT) on cardiac structure and function: Insights from the UK Biobank imaging enhancement study
by
Sanghvi, Mihir M.
,
Thomson, Ross J.
,
Neubauer, Stefan
in
Aging
,
Biology and Life Sciences
,
Biomedical research
2018
The effect of menopausal hormone therapy (MHT)-previously known as hormone replacement therapy-on cardiovascular health remains unclear and controversial. This cross-sectional study examined the impact of MHT on left ventricular (LV) and left atrial (LA) structure and function, alterations in which are markers of subclinical cardiovascular disease, in a population-based cohort.
Post-menopausal women who had never used MHT and those who had used MHT ≥3 years participating in the UK Biobank who had undergone cardiovascular magnetic resonance (CMR) imaging and free of known cardiovascular disease were included. Multivariable linear regression was performed to examine the relationship between cardiac parameters and MHT use ≥3 years. To explore whether MHT use on each of the cardiac outcomes differed by age, multivariable regression models were constructed with a cross-product of age and MHT fitted as an interaction term.
Of 1604 post-menopausal women, 513 (32%) had used MHT ≥3 years. In the MHT cohort, median age at menopause was 50 (IQR: 45-52) and median duration of MHT was 8 years. In the non-MHT cohort, median age at menopause was 51 (IQR: 48-53). MHT use was associated with significantly lower LV end-diastolic volume (122.8 ml vs 119.8 ml, effect size = -2.4%, 95% CI: -4.2% to -0.5%; p = 0.013) and LA maximal volume (60.2 ml vs 57.5 ml, effect size = -4.5%, 95% CI: -7.8% to -1.0%; p = 0.012). There was no significant difference in LV mass. MHT use significantly modified the effect between age and CMR parameters; MHT users had greater decrements in LV end-diastolic volume, LV end-systolic volume and LA maximal volume with advancing age.
MHT use was not associated with adverse, subclinical changes in cardiac structure and function. Indeed, significantly smaller LV and LA chamber volumes were observed which have been linked to favourable cardiovascular outcomes. These findings represent a novel approach to examining MHT's effect on the cardiovascular system.
Journal Article