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Myocardial native T1 and extracellular volume with healthy ageing and gender

Myocardial native T1 and extracellular volume with healthy ageing and gender Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 European Heart Journal - Cardiovascular Imaging (2018) 19, 615–621 doi:10.1093/ehjci/jey034 Myocardial native T1 and extracellular volume with healthy ageing and gender 1 1,2 1 1 Stefania Rosmini , Heerajnarain Bulluck , Gabriella Captur , Thomas A. Treibel , 1 1 1 3 Amna Abdel-Gadir , Anish N. Bhuva , Veronica Culotta , Ahmed Merghani , 4 5 1 6 Marianna Fontana , Viviana Maestrini , Anna S. Herrey , Kelvin Chow , 6 7 8 1 Richard B. Thompson , Stefan K. Piechnik , Peter Kellman , Charlotte Manisty , and 1,2 James C. Moon * 1 2 3 Barts Heart Centre, St. Bartholomew’s Hospital, London, UK; Institute of Cardiovascular Science, University College, West Smithfield, London EC1A 7BE, UK; Department of 4 5 Cardiovascular Sciences, St Georges, University of London, London, UK; National Amyloidosis Centre, Royal Free Hospital, London, UK; Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology, and Geriatric Sciences, “Sapienza” University of Rome, Rome, Italy; Department of Biomedical Engineering, Faculty of Medicine and 7 8 Dentistry, University of Alberta, Edmonton, Canada; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, USA Received 27 April 2017; editorial decision 25 January 2018; accepted 24 February 2018; online publish-ahead-of-print 30 March 2018 Aims To determine how native myocardial T1 and extracellular volume (ECV) change with age, both to understand aging and to inform on normal reference ranges. ................................................................................................................................................................................................... Methods Ninety-four healthy volunteers with no a history or symptoms of cardiovascular disease or diabetes underwent and results cardiovascular magnetic resonance at 1.5 T. Mid-ventricular short axis native and post-contrast T1 maps by Shortened MOdified Look-Locker Inversion-recovery (ShMOLLI), MOdified Look-Locker Inversion Recovery (MOLLI) [pre-contrast: 5s(3s)3s, post-contrast: 4s(1s)3s(1s)2s] and saturation recovery single-shot acquisition (SASHA) were acquired and ECV by these three techniques were derived for the mid anteroseptum. Mean age was 50 ± 14 years (range 20–76), male 52%, with no age difference between genders (males 51 ± 14 years; females 49 ± 15 years, P = 0.55). Quoting respectively ShMOLLI, MOLLI, SASHA throughout, mean myocardial T1 was 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms (P < 0.0001) and ECV 28.4 ± 3.0% [95% confidence interval (CI) 27.8– 29.0], 27.3 ± 2.7 (95% CI 26.8–27.9), 24.1 ± 2.9% (95% CI 23.5–24.7) (P < 0.0001), with all values higher in females for all techniques (T1 þ18 ms, þ35 ms, þ51 ms; ECV þ2.7%, þ2.6%, þ3.4%). Native myocardial T1 reduced 2 2 slightly with age (R = 0.042, P = 0.048; R = 0.131, P < 0.0001—on average by 8–11 ms/decade—but not for SASHA 2 2 2 2 (R = 0.033 and P = 0.083). ECV did not change with age (R = 0.003, P = 0.582; R = 0.002, P = 0.689; R = 0.003, P = 0.615). Heart rate decreased slightly with age (R = 0.075, coefficient = -0.273, P = 0.008), but there was no rela- tionship between age and other blood T1 influences (haematocrit, iron, high density lipoprotein-cholesterol). ................................................................................................................................................................................................... Conclusion Gender influences native T1 and ECV with women having a higher native T1 and ECV. Native T1 measured by MOLLI and ShMOLLI was slightly lower with increasing age but not with SASHA and ECV was independent of age for all techniques. Keywords T1 mapping myocardial T1 extracellular volume age gender healthy volunteers � � � � � myocardial fibrosis. The evidence is conflicting as to whether myocar- Introduction . dial fibrosis increases with age with some studies suggesting it decreses and others pointing to different age related processes, e.g. Measurement of native T1 and extracellular volume (ECV) by cardio- 2–4 myocardial lipofuschin or haemosiderin accumulation. Whether vascular magnetic resonance (CMR) allow quantification of diffuse This research was conducted at The Heart Hospital, 16-18 Westmoreland Street, London, W1G 9PH, UK (has now merged with Barts Heart Centre). * Corresponding author. E-mail: [email protected] V The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 616 S. Rosmini et al. the ECV increases with age is unclear. The Multi-Ethnic Study of Further details of the various T1 acquisition parameters are available from the online appendix. A four chamber and a mid ventricular short Atherosclerosis found a tiny correlation of ECV with age (R =0.021, axis slice were acquired for all the three T1 mapping sequences but only P =0.012) but used region of interest (ROI) based on measurement . the latter was used for all analysis. rather than mapping, and studied a population with high rates of . 6,7 . diabetes and hypertension. Others found no changes or found in- . 8 . MOLLI ECV maps creases but with small populations or with significant comorbid- . The previously described and validated automated method for producing 9,10 . ities. Using best available mapping techniques and a cohort . a pixel-wise ECV map was used for MOLLI T1 mapping. This method designed specifically to address healthy ageing curated by excluding . corrects for respiratory motion due to variation in breath-holding as well established confounding comorbidities or cardiac disease, we sought as patient movement between breath-holds and relies on co-registration to determine whether T1 and ECV increase with age—both in order of the native and post-contrast T1 pixel maps. An offline software (ECV to understand the aging biology and as a step towards developing . Mapping Tool Version 1.1) subsequently generated pixel-wise ECV maps normal reference ranges. after adjusting for Hct using a variety of post processing steps as previ- ously described. Methods T1 mapping analysis and ECV quantification All T1 maps were analysed using cvi software (Circle Cardiovascular The study comply with the Declaration of Helsinki and obtained approval Imaging Inc., Version 5.1.2[303], Calgary, Canada). For myocardial T1 ana- from the local research ethics committee. Healthy volunteers were re- . . lysis, manual epicardial and endocardial contours were drawn on the cruited through advertising in the hospital. Pre-consent, we excluded pa- . . MOLLI mid ventricular short axis slice and segmented according to the tients with a history or symptoms of cardiovascular disease or diabetes. . . American Heart Association (AHA) segmentation. The mid antero- All participants provided written informed consent. A stratified approach septum (segment 8) was used for the analysis. In order to avoid con- was adopted for recruitment to ensure adequate representation of par- founders, with blood partial voluming being a particular concern, the ticipants in each age decile. A blood sample was drawn from each subject effect of different degrees of endocardial and epicardial border erosion the same day just before (approximately 30 min) the CMR examination . . were initially assessed. The initial contours were drawn on what was visu- to acquire the main biochemical parameters and in particular haematocrit . ally considered to be the endocardial and epicardial boundaries on the (Hct) for ECV quantification. . maps and subsequently an off-set erosion of 10%, 20%, and 30% was The scans were performed at 1.5-T (Magnetom Avanto; Siemens applied on both the endocardial and epicardial borders using a function Medical Solutions, Erlangen, Germany) with 32-channel cardiac phased provided by the software as illustrated in Figure 1. With initial erosion array receiver. The imaging protocol included cines, native T1 mapping, . (0–10%), measured myocardial T1 pre-contrast was lower and post- T2 mapping, late gadolinium enhancement, and post-contrast T1 . contrast increased suggesting partial voluming was being reduced. Above mapping. . 10%, this reduction stopped (e.g. MOLLI: 10%, 20%, 30% erosion: native T1 1028 ms, 1019 ms, 1014 ms) so (given a predilection for fibrosis to be T1 mapping . endocardial), a 10% erosion offset was used. These endocardial and epi- T1 maps were acquired using three different sequences: Shortened . cardial borders were then copied on to the pre-contrast ShMOLLI and 11 . Modified Look-Locker Inversion recovery (ShMOLLI), a MOdified . SASHA T1 maps and MOLLI ECV map and ShMOLLI and SASHA post- Look-Locker Inversion Recovery (MOLLI), and a saturation recovery contrast T1 maps with manual adjustment if needed. An example of the single-shot acquisition (SASHA) pre and at approximately 15 min after myocardial and blood ROI is provided in Figure 1. the injection of 0.1 mmol/kg of Gadoterate meglumine (Gd-DOTA mar- For blood analysis, a ROI was drawn in the left ventricular (LV) blood keted as Dotarem, Guerbet S.A., Paris, France). pool of the mid ventricular short axis slice of the pre-contrast MOLLI T1 For the ShMOLLI technique, pre- and post-contrast T1 maps were map and care was taken to avoid papillary muscles. This ROI was then generated inline by merging images from three consecutive inversion re- . copied on to the native ShMOLLI and SASHA T1 maps. Very limited ad- 11 . covery experiments as previously described. The typical acquisition justments were needed due to changes in cardiac position, movement/ parameters were: echo time = 1.05 ms; imaging duration = 210 ms; ma- different breath-holds and slightly smaller cavity in some ShMOLLI trix = 192 140; phase partial Fourier 6/8; minimum TI= 110 ms; TI in- images. crement = 80 ms; flip angle 35 ; slice thickness = 8 mm. Extracellular volume was calculated using the mean segmental pixel value from the MOLLI ECV maps and using the formula ECV = (D[1/ For the MOLLI technique (work-in-progress 448b), sampling was in se- conds and optimised for expected measured T1s [pre-contrast 5s(3s)3s, T1myo]/D[1/T1blood]) * [1-Hct]) for ShMOLLI and SASHA. 14 . post-contrast 4s(1s)3s(1s)2s] with shortened inversion pulse for im- . proved efficiency and reduced T2 dependence. The acquisition param- . Statistical analysis eters were: pixel bandwidth 977 Hz/pixel; echo time = 1.14 ms; flip Statistical analysis was performed using R (version 3.0.1, 2013) and SPSS angle = 35 ; matrix = 256 144; slice thickness = 6 mm. Inline motion . (Version 22, IBM Corporation, IL, USA). Apriori, we set out to define nor- correction and a non-linear least-square curve fitting were performed mal values for native T1 and ECV in health by MOLLI, ShMOLLI, and with the set of images acquired at different inversion times to generate a SASHA as the range of values containing the central 95% (2 SD) of native pixel-wise coloured T1 map. . T1 and ECV readings in the ‘healthy’ population, with reference limits of 11 . For the SASHA technique, the acquisition parameters for pre and 2.5% and 97.5%. This definition results in 5% of the ‘healthy’ population post contrast maps were: echo time = 1.36 ms; matrix = 256 149; flip . being classified as ‘abnormal’ or as high native T1/ECV candidates. The angle = 70 ; slice thickness = 8 mm, and with a variable flip angle readout. study was therefore designed to enrol a representative group of healthy Saturation recovery images were acquired and reconstructed as previ- volunteers which would allow at least two subjects (1 male, 1 female) for ously described using a two parameter model with motion correction each 2.5% interval of native T1/ECV for testing that is n =80. Apriori,we to generate pixel-wise coloured T1 map from the scanner. inflated recruitment to 105 to account for potential participant exclusion Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 617 Figure 1 Example of myocardial and blood ROIs in ShMOLLI native (left) and post-contrast (right) T1 maps. Manual epicardial (green) and endo- cardial (red) contours with 10% erosion offset (white borders) drawn in the native ShMOLLI T1 map (left) and exported on to the post-contrast map (right) are shown. The myocardial ROI is segmented according to the AHA model. A blood ROI was also drawn in the native T1 map and copied on to the post-contrast map. (in fact, we excluded 11). Our final reference group of n =94 thus . post-contrast images not available. The result was a final study popu- allowed us close to three subjects for testing across the majority of 2.5% lation of 94 volunteers (Figure 2). As expected, these had some native T1/ECV intervals for understanding normal variation in health. cardiovascular risk factors: smoking [1 (1%) active, 17 (18% ex- Shapiro–Wilk test was used to assess for normality. Normally distrib- smokers); hypertension [none diagnosed; 7 (7%) had blood pressure uted continuous variables were presented as mean ± standard deviation. >140/90 mmHg on attendance); family history: 1 (1%) of coronary ar- Categorical data were reported as frequencies and percentages. A two- tery disease in a first degree relative (mother suffering a myocardial sample independent t-test was used to compared normally distributed infarction aged 64), 1 (1%) of premature sudden cardiac death continuous variables. . . <40 year old in first degree relative. Five (5%) had hypercholesterol- To adjust for clustering among and by groups, a varying intercept . . emia and were on statins for primary prevention and 15 (16%) had a model was fitted using R package ‘lme4’ to provide a mixed-effect model- . . total cholesterol (here unfasted) above 6.2 mmol/L (240 mg/dL). The ling framework for studying the impact of age and gender on group-level . average body mass index (BMI) was 24.4 ± 3.7 with nine volunteers variation in native T1 and ECV in study subjects. For each of T1 and ECV we compared the full model (with the fixed effects of age and gender) having BMI > 30 with one having the highest value of 36. No one had against a reduced model without the fixed effects to determine whether . peripheral vascular disease. Ethnicity was 68 (72%), Caucasian, 14 the fixed effects were significant based on the difference between the . (15%) Asian, 7 (7%) Black/Afro-caribbean, 5 (5%) other. Six (6%) had likelihood of these two models by conducting the likelihood ratio test medications for primary prevention (five on statins, one on aspirin). using the ANOVA function to determine v values. All volunteers had a normal 12-lead ECG and all the CMR scans All statistical tests were two-tailed, and P-values of less than 0.05 were were reported as normal by experienced Level 3 CMR physicians. considered statistically significant. Mean age was 50 ± 14 years, range 20–76 years, 52% male. The age . decile distribution was: 20–29 (n = 10), 30–39 (n = 14), 40–49 . (n = 24), 50–59 (n = 21), 60–69 (n =16), and 70–79 (n = 9). Clinical Results . characteristics of the overall population and according to gender are One hundred and five healthy volunteers were recruited and under- described in Table 1. There were no gender differences in age (males went blood tests, 12-lead electrocardiogram (ECG) and CMR. Any 51 ± 14 years and females 49 ± 15 years, P =0.55). Heart rate subject found with abnormalities on ECG or CMR (with the excep- decreased slightly with age (R =0.075, P =0.008) (Figure 2, top right). tion of inconsequential extra-cardiac findings such as liver cysts which There was no relationship between age and other blood variables that have influences on blood T1, in particular Hct (R = 0.008, were allowed) was excluded. There were 11 such exclusions: 3 not completing the CMR (1 contrast reaction resulting in premature ter- P = 0.402), iron bound to transferrin (R = 0.003, P =0.617) and high mination of the scan, 2 for claustrophobia); 4 for incidental findings (1 density lipoprotein-cholesterol (R = 0.020, P =0.182) (Supplemen- CMR finding of pulmonary valve stenosis, 1 CMR finding of biventric- tary data online, Figure S1, top left and bottom right and left). ular impairment, 1 blood test high glucose—subsequently confirmed . Acquisition of the mapping sequences was particularly careful in diabetes, 1 high blood pressure and ECG criteria for LV hypertro- . the context of the research project and the need for repeat acquisi- phy); 2 for post-enrolment disclosures (1 on beta-blockers therapy . tion was limited to <5% of healthy volunteers. This was typically one . additional breath-hold per slice, although there were two outlier sub- for atrial ectopics, 1 due to previous breast cancer treatment includ- ing left sided radiotherapy), and 2 due to scanner crashes with jects where multiple breath-holds were needed. There was one Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 618 S. Rosmini et al. Table 2 T1 mapping data in the overall population of 94 healthy volunteers. Overall Males Females P-value (n594) (n549, (n545, 52%) 48%) ................................................................................................. Myocardial native T1 ShMOLLI (ms) 957 ± 30 948 ± 26 966 ± 31 0.003 MOLLI (ms) 1024 ± 39 1008 ± 33 1043 ± 37 <0.0001 SASHA (ms) 1144 ± 45 1120 ± 35 1171 ± 41 <0.0001 ECV ShMOLLI (%) 28.4 ± 3.0 27.1 ± 2.7 29.8 ± 2.7 <0.0001 MOLLI (%) 27.3 ± 2.7 26.1 ± 2.3 28.7 ± 2.6 <0.0001 SASHA (%) 24.1 ± 2.9 22.6 ± 2.3 26.0 ± 2.4 <0.0001 ECV, extra-cellular volume; MOLLI, MOdified Look-Locker Inversion recovery; ShMOLLI, Shortened MOdified Look-Locker Inversion recovery; SASHA, satur- ation recovery single-shot acquisition. Figure 2 Population selection process. In the flow chart is illus- trated the final population selection process. CV, cardiovascular. ECV: 28.4 ± 3.0% [95% confidence interval (CI) 27.8–29.0], 27.3 ± 2.7 (95% CI 26.8–27.9), 24.1 ± 2.9% (95% CI 23.5–24.7), Table 2. Gender: For both native T1 and ECV, females had higher values Table 1 Clinical characteristics of the 94 healthy . by all techniques (T1 þ18 ms, þ35 ms, þ51 ms; ECV þ2.7%, þ2.6%, volunteers . . þ3.4%, P-value being statistically significant for all parameters), . Table 2. Overall Males Females population (n549, 52%) (n545, 48%) . Age: native myocardial T1 was slightly lower with increasing age . 2 2 (n594) . (R = 0.042, P =0.048; R =0.131, P < 0.0001), on average by 8 and ................................................................................................. . 11 ms/decade by ShMOLLI and MOLLI but not by SASHA Age (years) 50 ± 14 51 ± 14 49 ± 15 . 2 2 . (R = 0.033, P =0.083) (Figure 3). This was in both males (R = 0.130, SBP (mmHg) 122 ± 13 125 ± 12 120 ± 13 . P = 0.011) and females (R =0.150, P = 0.009). ECV did not change DBP (mmHg) 76 ± 9 77 ± 7 75 ± 10 . significantly with age by any technique: (R =0.003, P = 0.582; EDV (mL) 132 ± 32 149 ± 34 115 ± 19 . 2 2 R =0.001, P = 0.733 and R = 0.003, P = 0.615, Figure 4). ESV (mL) 44 ± 13 51 ± 14 37 ± 9 . Adjusting for clustered data, analysis for T1 by the three se- LV mass (g) 123 ± 34 144 ± 30 100 ± 20 . quences using linear models with age and gender as fixed effects, LVSV (mL) 88 ± 21 97 ± 24 77 ± 12 . confirmed how female gender affected T1 (v2 (1)= 62.87, LVEF (%) 67 ± 4 66 ± 4 68 ± 4 . P =<0.0001), increasing it by about 33 ms and how increasing age 2 2 LAAi (cm /m ) 11± 2 11± 2 11± 2 . 2 . also affected T1 (v (1)= 25.62, P = 0.0001), decreasing it by 28, Hct (L/L) 0.42 ± 0.04 0.44 ± 0.03 0.39 ± 0.03 . 25, 26, 33, and 41 ms across 2nd, 3rd, 4th, 5th, and 6th decades, Data reported as mean ± SD. . respectively. DBP, diastolic blood pressure; EDV, end-diastolic volume; ESV, end-systolic vol- . Similar analysis for ECV by the three sequences confirmed how fe- ume; Hct, haematocrit; LAAi, left atrial area indexed; LVEF, left ventricular ejec- male gender affected ECV (v (1)= 82.07, P = <0.0001), increasing it tion fraction; SBP, systolic blood pressure; SD: standard deviation; LVSV, left . ventricular stroke volume. by about 2.9 ECV points and how increasing age did not significantly affect ECV (v (1)= 10.98, P = 0.05), describing small changes of the order -0.83, -0.13, 0.28, 0.62 and -0.79 ECV points across 2nd, 3rd, 4th, 5th, and 6th decades, respectively. power-cut (requiring restart) and one period where the SASHA se- . quence did not work for post-contrast acquisitions. Artefacts were typically breathing artefacts for ShMOLLI (a non-MOCO sequence, Discussion albeit shorter breath-hold) with misgating more common in MOLLI and SASHA. In three subjects, the source images were good, but the Native myocardial T1 and ECV allow quantification of myocardial ECV map failed—these required post-acquisition individualised post- fibrosis and are increasingly used in the clinical practice for the diag- processing (author P.K.) for reconstruction. . nosis of several cardiac disorders, such as cardiomyopathies, myocar- . 18,19 Considering all study subjects of all ages and across both genders, . ditis, iron overload and ischaemic heart disease, so the need for overall mean values of native T1 and ECV (reported in the order . accurately establishing normal reference ranges and understanding of ShMOLLI, MOLLI, and SASHA, respectively throughout the manu- . variations with physiological parameters is clear. We, therefore, pro- script) were T1: 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms and spectively aimed to understand changes in these parameters with Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 619 Figure 3 Relationship between age and native myocardial T1 according to MOLLI, ShMOLLI and SASHA. Native myocardial T1 decreased slightly 2 2 2 with age by (A)MOLLI (R =0.131, P <0.0001) and (B) ShMOLLI (R =0.042, P = 0.048), while this was not the case for (C) SASHA (R =0.033, P =0.083). 2 2 Figure 4 Relationship between ECV and age according to MOLLI, ShMOLLI and SASHA. R =0.001, P =0.733 by MOLLI (A), R =0.003, P =0.582 by ShMOLLI (B)and R =0.003, P =0.615 by SASHA (C). healthy aging and gender, using best available technology including aging—our subjects had no comorbidities (no diabetes, no hyperten- three T1 mapping sequences and two ECV analysis techniques. We sion), both of which increased in prevalence with age. found that native T1 and ECV were higher in females, as previously A recent group similarly showed in a smaller cohort of 44 individ- 20,21 found but, that native T1 was slight lower with age (ShMOLLI uals free from cardiovascular disease, diabetes, hypertension, and not and MOLLI), and ECV does not change. The known measurement . on any cardiovascular medication, that native myocardial T1 meas- differences by ShMOLLI, MOLLI, and SASHA were present for T1 ured by SASHA was higher in women compared to men and did not and although reduced for ECV were still present. The meticulous se- vary significantly with age (P = 0.59) while ECV did not vary signifi- lection of the cohort to be healthy, its size, the prospective nature of cantly with age (P = 0.20) or gender (P =0.14). the study, the way blood dependent variables were checked as con- . Other authors point to other age related changes e.g. myocardial . 2–4 founders, the use of three sequences and their quality control by the . lipofuschin or haemosiderin accumulation. These could well ac- physicists that wrote them and the use of two analysis techniques count for the native T1 being lower with age with constant ECV. The (both drawn regions of interest and ECV mapping), are strengths of . native T1 technique measures signal from both myocytes and intersti- the study and suggest the results are robust. . tum, and the ECV measurement includes plasma volume. There are There is a belief that myocardial fibrosis increases with age. There plausible reasons that, for example capilliary density or resting re- is little supporting evidence and some studies say the opposite with cruitment could be different with age, but this is not convincing as an increase in myocyte size and volume fraction with a decrease in vasodilatation would increase both native T1 and ECV. Little data is 1 23,24 therelativeamount of interstitium. This study explored healthy available in this area on healthy ageing. The gender differences . Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 620 S. Rosmini et al. found are similar to all other literature. Partial voluming of blood Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at The Oxford University Hospitals Trust at the University of Oxford. pool has always been a plausible reason for this with the thinner (on The views expressed are those of the author(s) and not necessarily those average) female heart more predisposed to this. This, and the longer . 25 . of the NHS, the NIHR or the Department of Health. blood T1 in capilliaries within myocardium remain plausible but . look increasingly unlikely to be the whole explanation. . References As with other studies (e.g. reference ranges for volume analysis), 1. Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging the data here is described as being related to ageing. This is not human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 1991;68: strictly true—they are all single timepoint study of different birth- 1560–8. 2. Kurz T, Terman A, Gustafsson B, Brunk UT. Lysosomes and oxidative stress in cohorts. There is the potential that 60 and 70 year olds, whose fetal . aging and apoptosis. Biochim Biophys Acta 2008;1780:1291–303. development and early growth occurred in the immediate post war 3. Terman A, Brunk UT. The aging myocardium: roles of mitochondrial damage and period could be different to that of 20–30 year olds. Long term . lysosomal degradation. Heart Lung Circ 2005;14:107–14. . 4. Terman A, Brunk UT. Autophagy in cardiac myocyte homeostasis, aging, and follow-up studies with paired data decades apart are extraordinarily pathology. Cardiovasc Res 2005;68:355–65. difficult to do as the technology changes so fast. These will however . 5. Liu CY, Liu YC, Wu C, Armstrong A, Volpe GJ, van der Geest RJ et al. be needed in the future. . Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of We used three sequences: one Saturation recovery based . Atherosclerosis). J Am Coll Cardiol 2013;62:1280–7. (SASHA) and two inversion recovery based sequences (ShMOLLI . 6. Sado DM, Flett AS, Banypersad SM, White SK, Maestrini V, Quarta G et al. and MOLLI). We did this for generalizability of results but also be- Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart 2012;98:1436–41. cause the accuracy and precision of the sequences are not known, . 7. Dabir D, Child N, Kalra A, Rogers T, Gebker R, Jabbour A et al. Reference values particularly when applied in vivo. There are also differences in what is for healthy human myocardium using a T1 mapping methodology: results from being measured—in particular SASHA is less magnetization transfer the International T1 Multicenter cardiovascular magnetic resonance study. . J Cardiovasc Magn Reson 2014;16:69. sensitive than infrared based sequences. We were looking for the 8. Schelbert EB, Testa SM, Meier CG, Ceyrolles WJ, Levenson JE, Blair AJ et al. biology of healthy ageing. Trends (or lack of trends) appearing in all . Myocardial extravascular extracellular volume fraction measurement by gadolin- three sequences would therefore be robust. . ium cardiovascular magnetic resonance in humans: slow infusion versus bolus. J Cardiovasc Magn Reson 2011;13:16. 9. Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH et al. Extracellular Limitations . volume imaging by magnetic resonance imaging provides insights into overt and The slice thickness for MOLLI was 6 mm (Avanto 6 mm by Siemens) . sub-clinical myocardial pathology. Eur Heart J 2012;33:1268–78. 10. Roy C, Slimani A, de Meester C, Amzulescu M, Pasquet A, Vancraeynest D et al. compared to 8 mm for ShMOLLI and SASHA. Corresponding auto- . . Age and sex corrected normal reference values of T1, T2 T2* and ECV in mated ECV map for ShMOLLI and SASHA were not available at the healthy subjects at 3T CMR. J Cardiovasc Magn Reson 2017;19:72. time of this study. We adopted a stratified approach to recruiting pa- 11. Piechnik SK, Ferreira VM, Dall’Armellina E, Cochlin LE, Greiser A, Neubauer S . et al. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical tients but this was done to ensure satisfactory distribution of partici- myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold. pants in each age decile. J Cardiovasc Magn Reson 2010;12:69. . 12. Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004;52:141–6. Conclusion . 13. Chow K, Flewitt JA, Green JD, Pagano JJ, Friedrich MG, Thompson RB. Saturation recovery single-shot acquisition (SASHA) for myocardial T(1) map- In health, gender influences native myocardial T1 and ECV with ping. Magn Reson Med 2014;71:2082–95. women having a higher native T1 and ECV compared with males. . 14. Kellman P, Hansen MS. T1-mapping in the heart: accuracy and precision. J Cardiovasc Magn Reson 2014;16:2. Native myocardial T1 is slightly lower with increasing age while ECV 15. Kellman P, Herzka DA, Hansen MS. Adiabatic inversion pulses for myocardial T1 is not influenced by aging. . . mapping. Magn Reson Med 2014;71:1428–34. 16. Kellman P, Wilson JR, Xue H, Ugander M, Arai AE. Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. . J Cardiovasc Magn Reson 2012;14:63. Supplementary data 17. Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Supplementary data are available at European Heart Journal - Cardiovascular Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the Imaging online. European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92. Conflict of interest: None declared. . . 18. Bulluck H, Maestrini V, Rosmini S, Abdel-Gadir A, Treibel TA, Castelletti S et al. Myocardial T1 mapping. Circ J 2015;79:487–94. Funding . 19. Messroghli DR, Ferreira V, Grosse-Wortmann L, He T, Kellman P, Mascherbauer G et al. Clinical recommendations for cardiac mapping of T1, extracellular vol- S.R. is supported by Borse di studio SIC e MSD Italia-Merck Sharp & . ume, T2, and T2*: A consensus statement by the Society for Cardiovascular Dohme. M.F is supported by Clinical Research Training Fellowship from the Magnetic Resonance (SCMR) endorsed by the European Association for British Heart Foundation (FS/12/56/29723). T.A.T is supported by Doctoral . Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson 2017;19:75. Research Fellowship from the NIHR, UK (NIHR-DRF-2013-06-102). . 20. Rauhalammi SM, Mangion K, Barrientos PH, Carrick DJ, Clerfond G, McClure J et al. Native myocardial longitudinal (T) relaxation time: regional, age, and A.A.G. is supported by the Rosetrees Trust. J.C.M. has received grant funding . sex associations in the healthy adult heart. J Magn Reson Imaging 2016;44: from GlaxoSmithKline. This work was undertaken at University College 541–8. London Hospital, which received a proportion of funding from the UK 21. Piechnik SK, Ferreira VM, Lewandowski AJ, Ntusi NA, Banerjee R, Holloway C Department of Health National Institute for Health Research Biomedical . et al. Normal variation of magnetic resonance T1 relaxation times in the human Research Centers funding scheme. SKP is supported by the National population at 1.5 T using ShMOLLI. J Cardiovasc Magn Reson 2013;15:13. Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 621 22. Pagano JJ, Chow K, Paterson I, Thompson RB. Aging and gender effects in native 24. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E et al. The cel- T1 and extracellular volume fraction assessment using SASHA. J Cardiovasc Magn lular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol 1995;27: Reson 2016;18:Q3. 291–305. 23. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E et al. 25. Piechnik SK, Chiarelli PA, Jezzard P. Modelling vascular reactivity to investigate Structural basis of end-stage failure in ischemic cardiomyopathy in humans. . the basis of the relationship between cerebral blood volume and flow under Circulation 1994;89:151–63. CO2 manipulation. NeuroImage 2008;39:107–18. IMAGE FOCUS doi:10.1093/ehjci/jey056 Online publish-ahead-of-print 30 March 2018 .................................................................................................................................................... Tetralogy of Fallot with aortopulmonary window and interrupted aortic arch: multimodality imaging in a rare association 1 2 1 1 1 Miarisoa Ratsimandresy *, Fabio Cuttone , Yves Dulac , Philippe Acar , and Khaled Hadeed 1 2 Department of Paediatric Cardiology, Toulouse University Hospital, Toulouse, France; and Department of Congenital Cardiac Surgery, Toulouse University Hospital, Toulouse, France * Corresponding author. Tel 133 (0)5 34 55 74 59. E-mail: [email protected] A newborn was referred for assessment of suspected complex congenital heart disease. Chromosomes were normal including fluorescent in situ hybridization analysis for 22q11 deletion. There was a saturation difference between right upper arm and lower limbs. The 2D echocardiogram (Epic, Philips) established the diagnosis of tet- ralogy of Fallot (TOF) with infundibular stenosis and hypoplasia of the pulmo- nary annulus. This was associated with a large aortopulmonary window (APW) between the ascending aorta (AA) and main pulmonary artery (MPA) (asterisk). The aortic arch appeared interrupted beyond the left carotid artery (Panel A and Supplementary data online, Videos S1 and S2) with a large ductus arteriosus (DA) supplying the left subclavian artery (LSA) and descending aorta. Computed tomogra- phy (CT) scan confirmed the echocar- diographic diagnosis and further allowed visualization of the APW between the left edge of the aorta and the right edge of the MPA. It further confirmed the type B interrupted aortic arch (IAA) between the left carotid and LSA. There was a large patent DA (Panel B). On the basis of CT images, 3D reconstruction was performed, and 3D model created (Mimics Materialise, Belgium). These allowed better understanding of the spatial relationships between the cardiac and vascular structures (Panel C). A full repair was performed in neonatal period including TOF repair, reconstruction of the aortic arch, and closure of APW. The association between TOF, APW, and IAA is a very unusual form of TOF. Multimodality imaging with 3D reconstructions can be help- ful for establishing an accurate diagnosis. Supplementary data are available at European Heart Journal – Cardiovascular Imaging online. V C Published on behalf of the European Society of Cardiology. All rights reserved. The Author(s) 2018. For permissions, please email: [email protected]. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal - Cardiovascular Imaging Oxford University Press

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Copyright © 2022 European Society of Cardiology
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Abstract

Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 European Heart Journal - Cardiovascular Imaging (2018) 19, 615–621 doi:10.1093/ehjci/jey034 Myocardial native T1 and extracellular volume with healthy ageing and gender 1 1,2 1 1 Stefania Rosmini , Heerajnarain Bulluck , Gabriella Captur , Thomas A. Treibel , 1 1 1 3 Amna Abdel-Gadir , Anish N. Bhuva , Veronica Culotta , Ahmed Merghani , 4 5 1 6 Marianna Fontana , Viviana Maestrini , Anna S. Herrey , Kelvin Chow , 6 7 8 1 Richard B. Thompson , Stefan K. Piechnik , Peter Kellman , Charlotte Manisty , and 1,2 James C. Moon * 1 2 3 Barts Heart Centre, St. Bartholomew’s Hospital, London, UK; Institute of Cardiovascular Science, University College, West Smithfield, London EC1A 7BE, UK; Department of 4 5 Cardiovascular Sciences, St Georges, University of London, London, UK; National Amyloidosis Centre, Royal Free Hospital, London, UK; Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology, and Geriatric Sciences, “Sapienza” University of Rome, Rome, Italy; Department of Biomedical Engineering, Faculty of Medicine and 7 8 Dentistry, University of Alberta, Edmonton, Canada; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; and National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, USA Received 27 April 2017; editorial decision 25 January 2018; accepted 24 February 2018; online publish-ahead-of-print 30 March 2018 Aims To determine how native myocardial T1 and extracellular volume (ECV) change with age, both to understand aging and to inform on normal reference ranges. ................................................................................................................................................................................................... Methods Ninety-four healthy volunteers with no a history or symptoms of cardiovascular disease or diabetes underwent and results cardiovascular magnetic resonance at 1.5 T. Mid-ventricular short axis native and post-contrast T1 maps by Shortened MOdified Look-Locker Inversion-recovery (ShMOLLI), MOdified Look-Locker Inversion Recovery (MOLLI) [pre-contrast: 5s(3s)3s, post-contrast: 4s(1s)3s(1s)2s] and saturation recovery single-shot acquisition (SASHA) were acquired and ECV by these three techniques were derived for the mid anteroseptum. Mean age was 50 ± 14 years (range 20–76), male 52%, with no age difference between genders (males 51 ± 14 years; females 49 ± 15 years, P = 0.55). Quoting respectively ShMOLLI, MOLLI, SASHA throughout, mean myocardial T1 was 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms (P < 0.0001) and ECV 28.4 ± 3.0% [95% confidence interval (CI) 27.8– 29.0], 27.3 ± 2.7 (95% CI 26.8–27.9), 24.1 ± 2.9% (95% CI 23.5–24.7) (P < 0.0001), with all values higher in females for all techniques (T1 þ18 ms, þ35 ms, þ51 ms; ECV þ2.7%, þ2.6%, þ3.4%). Native myocardial T1 reduced 2 2 slightly with age (R = 0.042, P = 0.048; R = 0.131, P < 0.0001—on average by 8–11 ms/decade—but not for SASHA 2 2 2 2 (R = 0.033 and P = 0.083). ECV did not change with age (R = 0.003, P = 0.582; R = 0.002, P = 0.689; R = 0.003, P = 0.615). Heart rate decreased slightly with age (R = 0.075, coefficient = -0.273, P = 0.008), but there was no rela- tionship between age and other blood T1 influences (haematocrit, iron, high density lipoprotein-cholesterol). ................................................................................................................................................................................................... Conclusion Gender influences native T1 and ECV with women having a higher native T1 and ECV. Native T1 measured by MOLLI and ShMOLLI was slightly lower with increasing age but not with SASHA and ECV was independent of age for all techniques. Keywords T1 mapping myocardial T1 extracellular volume age gender healthy volunteers � � � � � myocardial fibrosis. The evidence is conflicting as to whether myocar- Introduction . dial fibrosis increases with age with some studies suggesting it decreses and others pointing to different age related processes, e.g. Measurement of native T1 and extracellular volume (ECV) by cardio- 2–4 myocardial lipofuschin or haemosiderin accumulation. Whether vascular magnetic resonance (CMR) allow quantification of diffuse This research was conducted at The Heart Hospital, 16-18 Westmoreland Street, London, W1G 9PH, UK (has now merged with Barts Heart Centre). * Corresponding author. E-mail: [email protected] V The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 616 S. Rosmini et al. the ECV increases with age is unclear. The Multi-Ethnic Study of Further details of the various T1 acquisition parameters are available from the online appendix. A four chamber and a mid ventricular short Atherosclerosis found a tiny correlation of ECV with age (R =0.021, axis slice were acquired for all the three T1 mapping sequences but only P =0.012) but used region of interest (ROI) based on measurement . the latter was used for all analysis. rather than mapping, and studied a population with high rates of . 6,7 . diabetes and hypertension. Others found no changes or found in- . 8 . MOLLI ECV maps creases but with small populations or with significant comorbid- . The previously described and validated automated method for producing 9,10 . ities. Using best available mapping techniques and a cohort . a pixel-wise ECV map was used for MOLLI T1 mapping. This method designed specifically to address healthy ageing curated by excluding . corrects for respiratory motion due to variation in breath-holding as well established confounding comorbidities or cardiac disease, we sought as patient movement between breath-holds and relies on co-registration to determine whether T1 and ECV increase with age—both in order of the native and post-contrast T1 pixel maps. An offline software (ECV to understand the aging biology and as a step towards developing . Mapping Tool Version 1.1) subsequently generated pixel-wise ECV maps normal reference ranges. after adjusting for Hct using a variety of post processing steps as previ- ously described. Methods T1 mapping analysis and ECV quantification All T1 maps were analysed using cvi software (Circle Cardiovascular The study comply with the Declaration of Helsinki and obtained approval Imaging Inc., Version 5.1.2[303], Calgary, Canada). For myocardial T1 ana- from the local research ethics committee. Healthy volunteers were re- . . lysis, manual epicardial and endocardial contours were drawn on the cruited through advertising in the hospital. Pre-consent, we excluded pa- . . MOLLI mid ventricular short axis slice and segmented according to the tients with a history or symptoms of cardiovascular disease or diabetes. . . American Heart Association (AHA) segmentation. The mid antero- All participants provided written informed consent. A stratified approach septum (segment 8) was used for the analysis. In order to avoid con- was adopted for recruitment to ensure adequate representation of par- founders, with blood partial voluming being a particular concern, the ticipants in each age decile. A blood sample was drawn from each subject effect of different degrees of endocardial and epicardial border erosion the same day just before (approximately 30 min) the CMR examination . . were initially assessed. The initial contours were drawn on what was visu- to acquire the main biochemical parameters and in particular haematocrit . ally considered to be the endocardial and epicardial boundaries on the (Hct) for ECV quantification. . maps and subsequently an off-set erosion of 10%, 20%, and 30% was The scans were performed at 1.5-T (Magnetom Avanto; Siemens applied on both the endocardial and epicardial borders using a function Medical Solutions, Erlangen, Germany) with 32-channel cardiac phased provided by the software as illustrated in Figure 1. With initial erosion array receiver. The imaging protocol included cines, native T1 mapping, . (0–10%), measured myocardial T1 pre-contrast was lower and post- T2 mapping, late gadolinium enhancement, and post-contrast T1 . contrast increased suggesting partial voluming was being reduced. Above mapping. . 10%, this reduction stopped (e.g. MOLLI: 10%, 20%, 30% erosion: native T1 1028 ms, 1019 ms, 1014 ms) so (given a predilection for fibrosis to be T1 mapping . endocardial), a 10% erosion offset was used. These endocardial and epi- T1 maps were acquired using three different sequences: Shortened . cardial borders were then copied on to the pre-contrast ShMOLLI and 11 . Modified Look-Locker Inversion recovery (ShMOLLI), a MOdified . SASHA T1 maps and MOLLI ECV map and ShMOLLI and SASHA post- Look-Locker Inversion Recovery (MOLLI), and a saturation recovery contrast T1 maps with manual adjustment if needed. An example of the single-shot acquisition (SASHA) pre and at approximately 15 min after myocardial and blood ROI is provided in Figure 1. the injection of 0.1 mmol/kg of Gadoterate meglumine (Gd-DOTA mar- For blood analysis, a ROI was drawn in the left ventricular (LV) blood keted as Dotarem, Guerbet S.A., Paris, France). pool of the mid ventricular short axis slice of the pre-contrast MOLLI T1 For the ShMOLLI technique, pre- and post-contrast T1 maps were map and care was taken to avoid papillary muscles. This ROI was then generated inline by merging images from three consecutive inversion re- . copied on to the native ShMOLLI and SASHA T1 maps. Very limited ad- 11 . covery experiments as previously described. The typical acquisition justments were needed due to changes in cardiac position, movement/ parameters were: echo time = 1.05 ms; imaging duration = 210 ms; ma- different breath-holds and slightly smaller cavity in some ShMOLLI trix = 192 140; phase partial Fourier 6/8; minimum TI= 110 ms; TI in- images. crement = 80 ms; flip angle 35 ; slice thickness = 8 mm. Extracellular volume was calculated using the mean segmental pixel value from the MOLLI ECV maps and using the formula ECV = (D[1/ For the MOLLI technique (work-in-progress 448b), sampling was in se- conds and optimised for expected measured T1s [pre-contrast 5s(3s)3s, T1myo]/D[1/T1blood]) * [1-Hct]) for ShMOLLI and SASHA. 14 . post-contrast 4s(1s)3s(1s)2s] with shortened inversion pulse for im- . proved efficiency and reduced T2 dependence. The acquisition param- . Statistical analysis eters were: pixel bandwidth 977 Hz/pixel; echo time = 1.14 ms; flip Statistical analysis was performed using R (version 3.0.1, 2013) and SPSS angle = 35 ; matrix = 256 144; slice thickness = 6 mm. Inline motion . (Version 22, IBM Corporation, IL, USA). Apriori, we set out to define nor- correction and a non-linear least-square curve fitting were performed mal values for native T1 and ECV in health by MOLLI, ShMOLLI, and with the set of images acquired at different inversion times to generate a SASHA as the range of values containing the central 95% (2 SD) of native pixel-wise coloured T1 map. . T1 and ECV readings in the ‘healthy’ population, with reference limits of 11 . For the SASHA technique, the acquisition parameters for pre and 2.5% and 97.5%. This definition results in 5% of the ‘healthy’ population post contrast maps were: echo time = 1.36 ms; matrix = 256 149; flip . being classified as ‘abnormal’ or as high native T1/ECV candidates. The angle = 70 ; slice thickness = 8 mm, and with a variable flip angle readout. study was therefore designed to enrol a representative group of healthy Saturation recovery images were acquired and reconstructed as previ- volunteers which would allow at least two subjects (1 male, 1 female) for ously described using a two parameter model with motion correction each 2.5% interval of native T1/ECV for testing that is n =80. Apriori,we to generate pixel-wise coloured T1 map from the scanner. inflated recruitment to 105 to account for potential participant exclusion Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 617 Figure 1 Example of myocardial and blood ROIs in ShMOLLI native (left) and post-contrast (right) T1 maps. Manual epicardial (green) and endo- cardial (red) contours with 10% erosion offset (white borders) drawn in the native ShMOLLI T1 map (left) and exported on to the post-contrast map (right) are shown. The myocardial ROI is segmented according to the AHA model. A blood ROI was also drawn in the native T1 map and copied on to the post-contrast map. (in fact, we excluded 11). Our final reference group of n =94 thus . post-contrast images not available. The result was a final study popu- allowed us close to three subjects for testing across the majority of 2.5% lation of 94 volunteers (Figure 2). As expected, these had some native T1/ECV intervals for understanding normal variation in health. cardiovascular risk factors: smoking [1 (1%) active, 17 (18% ex- Shapiro–Wilk test was used to assess for normality. Normally distrib- smokers); hypertension [none diagnosed; 7 (7%) had blood pressure uted continuous variables were presented as mean ± standard deviation. >140/90 mmHg on attendance); family history: 1 (1%) of coronary ar- Categorical data were reported as frequencies and percentages. A two- tery disease in a first degree relative (mother suffering a myocardial sample independent t-test was used to compared normally distributed infarction aged 64), 1 (1%) of premature sudden cardiac death continuous variables. . . <40 year old in first degree relative. Five (5%) had hypercholesterol- To adjust for clustering among and by groups, a varying intercept . . emia and were on statins for primary prevention and 15 (16%) had a model was fitted using R package ‘lme4’ to provide a mixed-effect model- . . total cholesterol (here unfasted) above 6.2 mmol/L (240 mg/dL). The ling framework for studying the impact of age and gender on group-level . average body mass index (BMI) was 24.4 ± 3.7 with nine volunteers variation in native T1 and ECV in study subjects. For each of T1 and ECV we compared the full model (with the fixed effects of age and gender) having BMI > 30 with one having the highest value of 36. No one had against a reduced model without the fixed effects to determine whether . peripheral vascular disease. Ethnicity was 68 (72%), Caucasian, 14 the fixed effects were significant based on the difference between the . (15%) Asian, 7 (7%) Black/Afro-caribbean, 5 (5%) other. Six (6%) had likelihood of these two models by conducting the likelihood ratio test medications for primary prevention (five on statins, one on aspirin). using the ANOVA function to determine v values. All volunteers had a normal 12-lead ECG and all the CMR scans All statistical tests were two-tailed, and P-values of less than 0.05 were were reported as normal by experienced Level 3 CMR physicians. considered statistically significant. Mean age was 50 ± 14 years, range 20–76 years, 52% male. The age . decile distribution was: 20–29 (n = 10), 30–39 (n = 14), 40–49 . (n = 24), 50–59 (n = 21), 60–69 (n =16), and 70–79 (n = 9). Clinical Results . characteristics of the overall population and according to gender are One hundred and five healthy volunteers were recruited and under- described in Table 1. There were no gender differences in age (males went blood tests, 12-lead electrocardiogram (ECG) and CMR. Any 51 ± 14 years and females 49 ± 15 years, P =0.55). Heart rate subject found with abnormalities on ECG or CMR (with the excep- decreased slightly with age (R =0.075, P =0.008) (Figure 2, top right). tion of inconsequential extra-cardiac findings such as liver cysts which There was no relationship between age and other blood variables that have influences on blood T1, in particular Hct (R = 0.008, were allowed) was excluded. There were 11 such exclusions: 3 not completing the CMR (1 contrast reaction resulting in premature ter- P = 0.402), iron bound to transferrin (R = 0.003, P =0.617) and high mination of the scan, 2 for claustrophobia); 4 for incidental findings (1 density lipoprotein-cholesterol (R = 0.020, P =0.182) (Supplemen- CMR finding of pulmonary valve stenosis, 1 CMR finding of biventric- tary data online, Figure S1, top left and bottom right and left). ular impairment, 1 blood test high glucose—subsequently confirmed . Acquisition of the mapping sequences was particularly careful in diabetes, 1 high blood pressure and ECG criteria for LV hypertro- . the context of the research project and the need for repeat acquisi- phy); 2 for post-enrolment disclosures (1 on beta-blockers therapy . tion was limited to <5% of healthy volunteers. This was typically one . additional breath-hold per slice, although there were two outlier sub- for atrial ectopics, 1 due to previous breast cancer treatment includ- ing left sided radiotherapy), and 2 due to scanner crashes with jects where multiple breath-holds were needed. There was one Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 618 S. Rosmini et al. Table 2 T1 mapping data in the overall population of 94 healthy volunteers. Overall Males Females P-value (n594) (n549, (n545, 52%) 48%) ................................................................................................. Myocardial native T1 ShMOLLI (ms) 957 ± 30 948 ± 26 966 ± 31 0.003 MOLLI (ms) 1024 ± 39 1008 ± 33 1043 ± 37 <0.0001 SASHA (ms) 1144 ± 45 1120 ± 35 1171 ± 41 <0.0001 ECV ShMOLLI (%) 28.4 ± 3.0 27.1 ± 2.7 29.8 ± 2.7 <0.0001 MOLLI (%) 27.3 ± 2.7 26.1 ± 2.3 28.7 ± 2.6 <0.0001 SASHA (%) 24.1 ± 2.9 22.6 ± 2.3 26.0 ± 2.4 <0.0001 ECV, extra-cellular volume; MOLLI, MOdified Look-Locker Inversion recovery; ShMOLLI, Shortened MOdified Look-Locker Inversion recovery; SASHA, satur- ation recovery single-shot acquisition. Figure 2 Population selection process. In the flow chart is illus- trated the final population selection process. CV, cardiovascular. ECV: 28.4 ± 3.0% [95% confidence interval (CI) 27.8–29.0], 27.3 ± 2.7 (95% CI 26.8–27.9), 24.1 ± 2.9% (95% CI 23.5–24.7), Table 2. Gender: For both native T1 and ECV, females had higher values Table 1 Clinical characteristics of the 94 healthy . by all techniques (T1 þ18 ms, þ35 ms, þ51 ms; ECV þ2.7%, þ2.6%, volunteers . . þ3.4%, P-value being statistically significant for all parameters), . Table 2. Overall Males Females population (n549, 52%) (n545, 48%) . Age: native myocardial T1 was slightly lower with increasing age . 2 2 (n594) . (R = 0.042, P =0.048; R =0.131, P < 0.0001), on average by 8 and ................................................................................................. . 11 ms/decade by ShMOLLI and MOLLI but not by SASHA Age (years) 50 ± 14 51 ± 14 49 ± 15 . 2 2 . (R = 0.033, P =0.083) (Figure 3). This was in both males (R = 0.130, SBP (mmHg) 122 ± 13 125 ± 12 120 ± 13 . P = 0.011) and females (R =0.150, P = 0.009). ECV did not change DBP (mmHg) 76 ± 9 77 ± 7 75 ± 10 . significantly with age by any technique: (R =0.003, P = 0.582; EDV (mL) 132 ± 32 149 ± 34 115 ± 19 . 2 2 R =0.001, P = 0.733 and R = 0.003, P = 0.615, Figure 4). ESV (mL) 44 ± 13 51 ± 14 37 ± 9 . Adjusting for clustered data, analysis for T1 by the three se- LV mass (g) 123 ± 34 144 ± 30 100 ± 20 . quences using linear models with age and gender as fixed effects, LVSV (mL) 88 ± 21 97 ± 24 77 ± 12 . confirmed how female gender affected T1 (v2 (1)= 62.87, LVEF (%) 67 ± 4 66 ± 4 68 ± 4 . P =<0.0001), increasing it by about 33 ms and how increasing age 2 2 LAAi (cm /m ) 11± 2 11± 2 11± 2 . 2 . also affected T1 (v (1)= 25.62, P = 0.0001), decreasing it by 28, Hct (L/L) 0.42 ± 0.04 0.44 ± 0.03 0.39 ± 0.03 . 25, 26, 33, and 41 ms across 2nd, 3rd, 4th, 5th, and 6th decades, Data reported as mean ± SD. . respectively. DBP, diastolic blood pressure; EDV, end-diastolic volume; ESV, end-systolic vol- . Similar analysis for ECV by the three sequences confirmed how fe- ume; Hct, haematocrit; LAAi, left atrial area indexed; LVEF, left ventricular ejec- male gender affected ECV (v (1)= 82.07, P = <0.0001), increasing it tion fraction; SBP, systolic blood pressure; SD: standard deviation; LVSV, left . ventricular stroke volume. by about 2.9 ECV points and how increasing age did not significantly affect ECV (v (1)= 10.98, P = 0.05), describing small changes of the order -0.83, -0.13, 0.28, 0.62 and -0.79 ECV points across 2nd, 3rd, 4th, 5th, and 6th decades, respectively. power-cut (requiring restart) and one period where the SASHA se- . quence did not work for post-contrast acquisitions. Artefacts were typically breathing artefacts for ShMOLLI (a non-MOCO sequence, Discussion albeit shorter breath-hold) with misgating more common in MOLLI and SASHA. In three subjects, the source images were good, but the Native myocardial T1 and ECV allow quantification of myocardial ECV map failed—these required post-acquisition individualised post- fibrosis and are increasingly used in the clinical practice for the diag- processing (author P.K.) for reconstruction. . nosis of several cardiac disorders, such as cardiomyopathies, myocar- . 18,19 Considering all study subjects of all ages and across both genders, . ditis, iron overload and ischaemic heart disease, so the need for overall mean values of native T1 and ECV (reported in the order . accurately establishing normal reference ranges and understanding of ShMOLLI, MOLLI, and SASHA, respectively throughout the manu- . variations with physiological parameters is clear. We, therefore, pro- script) were T1: 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms and spectively aimed to understand changes in these parameters with Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 619 Figure 3 Relationship between age and native myocardial T1 according to MOLLI, ShMOLLI and SASHA. Native myocardial T1 decreased slightly 2 2 2 with age by (A)MOLLI (R =0.131, P <0.0001) and (B) ShMOLLI (R =0.042, P = 0.048), while this was not the case for (C) SASHA (R =0.033, P =0.083). 2 2 Figure 4 Relationship between ECV and age according to MOLLI, ShMOLLI and SASHA. R =0.001, P =0.733 by MOLLI (A), R =0.003, P =0.582 by ShMOLLI (B)and R =0.003, P =0.615 by SASHA (C). healthy aging and gender, using best available technology including aging—our subjects had no comorbidities (no diabetes, no hyperten- three T1 mapping sequences and two ECV analysis techniques. We sion), both of which increased in prevalence with age. found that native T1 and ECV were higher in females, as previously A recent group similarly showed in a smaller cohort of 44 individ- 20,21 found but, that native T1 was slight lower with age (ShMOLLI uals free from cardiovascular disease, diabetes, hypertension, and not and MOLLI), and ECV does not change. The known measurement . on any cardiovascular medication, that native myocardial T1 meas- differences by ShMOLLI, MOLLI, and SASHA were present for T1 ured by SASHA was higher in women compared to men and did not and although reduced for ECV were still present. The meticulous se- vary significantly with age (P = 0.59) while ECV did not vary signifi- lection of the cohort to be healthy, its size, the prospective nature of cantly with age (P = 0.20) or gender (P =0.14). the study, the way blood dependent variables were checked as con- . Other authors point to other age related changes e.g. myocardial . 2–4 founders, the use of three sequences and their quality control by the . lipofuschin or haemosiderin accumulation. These could well ac- physicists that wrote them and the use of two analysis techniques count for the native T1 being lower with age with constant ECV. The (both drawn regions of interest and ECV mapping), are strengths of . native T1 technique measures signal from both myocytes and intersti- the study and suggest the results are robust. . tum, and the ECV measurement includes plasma volume. There are There is a belief that myocardial fibrosis increases with age. There plausible reasons that, for example capilliary density or resting re- is little supporting evidence and some studies say the opposite with cruitment could be different with age, but this is not convincing as an increase in myocyte size and volume fraction with a decrease in vasodilatation would increase both native T1 and ECV. Little data is 1 23,24 therelativeamount of interstitium. This study explored healthy available in this area on healthy ageing. The gender differences . Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 620 S. Rosmini et al. found are similar to all other literature. Partial voluming of blood Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at The Oxford University Hospitals Trust at the University of Oxford. pool has always been a plausible reason for this with the thinner (on The views expressed are those of the author(s) and not necessarily those average) female heart more predisposed to this. This, and the longer . 25 . of the NHS, the NIHR or the Department of Health. blood T1 in capilliaries within myocardium remain plausible but . look increasingly unlikely to be the whole explanation. . References As with other studies (e.g. reference ranges for volume analysis), 1. Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging the data here is described as being related to ageing. This is not human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 1991;68: strictly true—they are all single timepoint study of different birth- 1560–8. 2. Kurz T, Terman A, Gustafsson B, Brunk UT. Lysosomes and oxidative stress in cohorts. There is the potential that 60 and 70 year olds, whose fetal . aging and apoptosis. Biochim Biophys Acta 2008;1780:1291–303. development and early growth occurred in the immediate post war 3. Terman A, Brunk UT. The aging myocardium: roles of mitochondrial damage and period could be different to that of 20–30 year olds. Long term . lysosomal degradation. Heart Lung Circ 2005;14:107–14. . 4. Terman A, Brunk UT. Autophagy in cardiac myocyte homeostasis, aging, and follow-up studies with paired data decades apart are extraordinarily pathology. Cardiovasc Res 2005;68:355–65. difficult to do as the technology changes so fast. These will however . 5. Liu CY, Liu YC, Wu C, Armstrong A, Volpe GJ, van der Geest RJ et al. be needed in the future. . Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of We used three sequences: one Saturation recovery based . Atherosclerosis). J Am Coll Cardiol 2013;62:1280–7. (SASHA) and two inversion recovery based sequences (ShMOLLI . 6. Sado DM, Flett AS, Banypersad SM, White SK, Maestrini V, Quarta G et al. and MOLLI). We did this for generalizability of results but also be- Cardiovascular magnetic resonance measurement of myocardial extracellular volume in health and disease. Heart 2012;98:1436–41. cause the accuracy and precision of the sequences are not known, . 7. Dabir D, Child N, Kalra A, Rogers T, Gebker R, Jabbour A et al. Reference values particularly when applied in vivo. There are also differences in what is for healthy human myocardium using a T1 mapping methodology: results from being measured—in particular SASHA is less magnetization transfer the International T1 Multicenter cardiovascular magnetic resonance study. . J Cardiovasc Magn Reson 2014;16:69. sensitive than infrared based sequences. We were looking for the 8. Schelbert EB, Testa SM, Meier CG, Ceyrolles WJ, Levenson JE, Blair AJ et al. biology of healthy ageing. Trends (or lack of trends) appearing in all . Myocardial extravascular extracellular volume fraction measurement by gadolin- three sequences would therefore be robust. . ium cardiovascular magnetic resonance in humans: slow infusion versus bolus. J Cardiovasc Magn Reson 2011;13:16. 9. Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH et al. Extracellular Limitations . volume imaging by magnetic resonance imaging provides insights into overt and The slice thickness for MOLLI was 6 mm (Avanto 6 mm by Siemens) . sub-clinical myocardial pathology. Eur Heart J 2012;33:1268–78. 10. Roy C, Slimani A, de Meester C, Amzulescu M, Pasquet A, Vancraeynest D et al. compared to 8 mm for ShMOLLI and SASHA. Corresponding auto- . . Age and sex corrected normal reference values of T1, T2 T2* and ECV in mated ECV map for ShMOLLI and SASHA were not available at the healthy subjects at 3T CMR. J Cardiovasc Magn Reson 2017;19:72. time of this study. We adopted a stratified approach to recruiting pa- 11. Piechnik SK, Ferreira VM, Dall’Armellina E, Cochlin LE, Greiser A, Neubauer S . et al. Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical tients but this was done to ensure satisfactory distribution of partici- myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold. pants in each age decile. J Cardiovasc Magn Reson 2010;12:69. . 12. Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004;52:141–6. Conclusion . 13. Chow K, Flewitt JA, Green JD, Pagano JJ, Friedrich MG, Thompson RB. Saturation recovery single-shot acquisition (SASHA) for myocardial T(1) map- In health, gender influences native myocardial T1 and ECV with ping. Magn Reson Med 2014;71:2082–95. women having a higher native T1 and ECV compared with males. . 14. Kellman P, Hansen MS. T1-mapping in the heart: accuracy and precision. J Cardiovasc Magn Reson 2014;16:2. Native myocardial T1 is slightly lower with increasing age while ECV 15. Kellman P, Herzka DA, Hansen MS. Adiabatic inversion pulses for myocardial T1 is not influenced by aging. . . mapping. Magn Reson Med 2014;71:1428–34. 16. Kellman P, Wilson JR, Xue H, Ugander M, Arai AE. Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. . J Cardiovasc Magn Reson 2012;14:63. Supplementary data 17. Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Supplementary data are available at European Heart Journal - Cardiovascular Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the Imaging online. European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92. Conflict of interest: None declared. . . 18. Bulluck H, Maestrini V, Rosmini S, Abdel-Gadir A, Treibel TA, Castelletti S et al. Myocardial T1 mapping. Circ J 2015;79:487–94. Funding . 19. Messroghli DR, Ferreira V, Grosse-Wortmann L, He T, Kellman P, Mascherbauer G et al. Clinical recommendations for cardiac mapping of T1, extracellular vol- S.R. is supported by Borse di studio SIC e MSD Italia-Merck Sharp & . ume, T2, and T2*: A consensus statement by the Society for Cardiovascular Dohme. M.F is supported by Clinical Research Training Fellowship from the Magnetic Resonance (SCMR) endorsed by the European Association for British Heart Foundation (FS/12/56/29723). T.A.T is supported by Doctoral . Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson 2017;19:75. Research Fellowship from the NIHR, UK (NIHR-DRF-2013-06-102). . 20. Rauhalammi SM, Mangion K, Barrientos PH, Carrick DJ, Clerfond G, McClure J et al. Native myocardial longitudinal (T) relaxation time: regional, age, and A.A.G. is supported by the Rosetrees Trust. J.C.M. has received grant funding . sex associations in the healthy adult heart. J Magn Reson Imaging 2016;44: from GlaxoSmithKline. This work was undertaken at University College 541–8. London Hospital, which received a proportion of funding from the UK 21. Piechnik SK, Ferreira VM, Lewandowski AJ, Ntusi NA, Banerjee R, Holloway C Department of Health National Institute for Health Research Biomedical . et al. Normal variation of magnetic resonance T1 relaxation times in the human Research Centers funding scheme. SKP is supported by the National population at 1.5 T using ShMOLLI. J Cardiovasc Magn Reson 2013;15:13. Downloaded from https://academic.oup.com/ehjcimaging/article/19/6/615/4956822 by DeepDyve user on 19 July 2022 Myocardial T1 and ECV with age and gender 621 22. Pagano JJ, Chow K, Paterson I, Thompson RB. Aging and gender effects in native 24. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E et al. The cel- T1 and extracellular volume fraction assessment using SASHA. J Cardiovasc Magn lular basis of dilated cardiomyopathy in humans. J Mol Cell Cardiol 1995;27: Reson 2016;18:Q3. 291–305. 23. Beltrami CA, Finato N, Rocco M, Feruglio GA, Puricelli C, Cigola E et al. 25. Piechnik SK, Chiarelli PA, Jezzard P. Modelling vascular reactivity to investigate Structural basis of end-stage failure in ischemic cardiomyopathy in humans. . the basis of the relationship between cerebral blood volume and flow under Circulation 1994;89:151–63. CO2 manipulation. NeuroImage 2008;39:107–18. IMAGE FOCUS doi:10.1093/ehjci/jey056 Online publish-ahead-of-print 30 March 2018 .................................................................................................................................................... Tetralogy of Fallot with aortopulmonary window and interrupted aortic arch: multimodality imaging in a rare association 1 2 1 1 1 Miarisoa Ratsimandresy *, Fabio Cuttone , Yves Dulac , Philippe Acar , and Khaled Hadeed 1 2 Department of Paediatric Cardiology, Toulouse University Hospital, Toulouse, France; and Department of Congenital Cardiac Surgery, Toulouse University Hospital, Toulouse, France * Corresponding author. Tel 133 (0)5 34 55 74 59. E-mail: [email protected] A newborn was referred for assessment of suspected complex congenital heart disease. Chromosomes were normal including fluorescent in situ hybridization analysis for 22q11 deletion. There was a saturation difference between right upper arm and lower limbs. The 2D echocardiogram (Epic, Philips) established the diagnosis of tet- ralogy of Fallot (TOF) with infundibular stenosis and hypoplasia of the pulmo- nary annulus. This was associated with a large aortopulmonary window (APW) between the ascending aorta (AA) and main pulmonary artery (MPA) (asterisk). The aortic arch appeared interrupted beyond the left carotid artery (Panel A and Supplementary data online, Videos S1 and S2) with a large ductus arteriosus (DA) supplying the left subclavian artery (LSA) and descending aorta. Computed tomogra- phy (CT) scan confirmed the echocar- diographic diagnosis and further allowed visualization of the APW between the left edge of the aorta and the right edge of the MPA. It further confirmed the type B interrupted aortic arch (IAA) between the left carotid and LSA. There was a large patent DA (Panel B). On the basis of CT images, 3D reconstruction was performed, and 3D model created (Mimics Materialise, Belgium). These allowed better understanding of the spatial relationships between the cardiac and vascular structures (Panel C). A full repair was performed in neonatal period including TOF repair, reconstruction of the aortic arch, and closure of APW. The association between TOF, APW, and IAA is a very unusual form of TOF. Multimodality imaging with 3D reconstructions can be help- ful for establishing an accurate diagnosis. Supplementary data are available at European Heart Journal – Cardiovascular Imaging online. V C Published on behalf of the European Society of Cardiology. All rights reserved. The Author(s) 2018. For permissions, please email: [email protected].

Journal

European Heart Journal - Cardiovascular ImagingOxford University Press

Published: Jun 1, 2018

Keywords: myocardium; gender; external cephalic version; maps; healthy aging; diabetes mellitus; diabetes mellitus, type 2; reference values

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