Chung-Yao Yu

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BackgroundT1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.MethodsHealthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.ResultsIn healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.ConclusionWe show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure

OBJECTIVES The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome. BACKGROUND NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping. METHODS This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint. RESULTS During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively. CONCLUSIONS Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study

Background— The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results— Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension ( P 15 mm ( P 2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions— Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.Background—The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results—Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P− subjects (P<0.0001) and 65% of G+P− subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions—Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.

Accuracy and Clinical Outcomes of Computed Tomography Coronary Angiography in the Presence of a High Coronary Calcium Score

BACKGROUND A high coronary calcium burden may adversely affect image quality of CT coronary angiography (CTCA). The ability to rule out clinically significant disease in this setting is uncertain. METHODS We examined CTCA findings in patients with a calcium score of >600. Utilising a search of death notices, structured patient interview and medical records, downstream investigations, cardiovascular events, revascularisation and mortality were recorded. RESULTS Sixty patients with a calcium score >600 had CTCA performed on the same day. Coronary disease findings were: mild 28%, moderate 33%, severe 32% and non-diagnostic 7%. During a median 1.75-year follow-up, 31 (53%) of patients underwent further assessment for coronary disease, eight patients (13%) underwent revascularisation and there were two non-cardiovascular and one cardiovascular deaths. No patient with mild or moderate disease at CTCA had subsequently demonstrated ischaemia, was deemed to require PCI or suffered cardiac mortality. The negative predictive value of CTCA for subsequent PCI and all-cause mortality was 97% (100% for cardiac mortality only). The positive predictive value of CTCA for revascularisation or CV death was 42%. CONCLUSION In patients with an elevated coronary calcium score, a negative CTCA implies an excellent short-term outcome and appears to exclude clinically significant coronary disease.

Defining the mid-diastolic imaging period for cardiac CT – lessons from tissue Doppler echocardiography

BackgroundAggressive dose reduction strategies for cardiac CT require the prospective selection of limited cardiac phases. At lower heart rates, the period of mid-diastole is typically selected for image acquisition. We aimed to identify the effect of heart rate on the optimal CT acquisition phase within the period of mid-diastole.MethodsWe utilized high temporal resolution tissue Doppler to precisely measure coronary motion within diastole. Tissue-Doppler waveforms of the myocardium corresponding to the location of the circumflex artery (100 patients) and mid-right coronary arteries (50 patients) and the duration and timing of coronary motion were measured. Using regression analysis an equation was derived for the timing of the period of minimal coronary motion within the RR interval. In a validation set of 50 clinical cardiac CT examinations, we assessed coronary motion artifact and the effect of using a mid-diastolic imaging target that was adjusted according to heart rate vs a fixed 75% phase target.ResultsTissue Doppler analysis shows the period of minimal cardiac motion suitable for CT imaging decreases almost linearly as the RR interval decreases, becoming extinguished at an average heart rate of 91 bpm for the circumflex (LCX) and 78 bpm for the right coronary artery (RCA). The optimal imaging phase has a strong linear relationship with RR duration (R2 = 0.92 LCX, 0.89 RCA). The optimal phase predicted by regression analysis of the tissue-Doppler waveforms increases from 74% at a heart rate of 55 bpm to 77% at 75 bpm. In the clinical CT validation set, the optimal CT acquisition phase similarly occurred later with increasing heart rate. When the selected cardiac phase was adjusted according to heart rate the result was closer to the optimal phase than using a fixed 75% phase. While this effect was statistically significant (p < 0.01 RCA/LCx), the mean effect of heart-rate adjustment was minor relative to typical beat-to-beat variability and available precision of clinical phase selection.ConclusionHigh temporal resolution imaging of coronary motion can be used to predict the optimal acquisition phase in cardiac CT. The optimal phase for cardiac CT imaging within mid-diastole increases with increasing heart rate although the magnitude of change is small.

Four-dimensional image processing of myocardial CT perfusion for improved image quality and noise reduction

BACKGROUND Image noise and multiple sources of artifact may affect the accurate interpretation of myocardial CT perfusion (CTP) studies. Although artifact within the image is often time dependent, tissue characteristics remain unchanged irrespective of cardiac phase. OBJECTIVE We assessed a new technique of 4-dimensional, spatiotemporal analysis, using redundant time domain information within additional phase acquisitions to reduce CTP image noise. METHODS Four-dimensional analysis was assessed in a static phantom and in 10 CTP studies with invasive fractional flow reserve (FFR) correlation. For each voxel within the CTP study the distribution of local Hounsfield values was measured in both time and space with the use of a customized program within MATLAB software. These values were filtered to eliminate those likely to represent noise or rapidly changing beam hardening artifact. All CTP images were acquired within a single heartbeat with 320 detector-row CT. Image noise was quantified as the SD of voxel values within myocardial segments. Contrast was measured between normal and abnormal vascular territories as assessed by FFR. RESULTS The mean image noise within the unprocessed CTP images was 30 HU (range, 23-42 HU). After 4-dimensional filtering the mean image noise was 22 HU (range, 15-29 HU). The mean reduction in image noise was 28% (P < 0.001). The mean contrast between normally perfused and ischemic segments was not significantly changed. The mean increase in contrast-to-noise ratio between ischemic territories and the myocardial average was 52% (P < 0.001). CONCLUSION Four-dimensional analysis of CTP significantly reduces image noise and may assist in the assessment of myocardial perfusion studies.

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic CardiomyopathyCLINICAL PERSPECTIVE

Background— The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results— Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension ( P 15 mm ( P 2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions— Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.Background—The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results—Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P− subjects (P<0.0001) and 65% of G+P− subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions—Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.

Multiparametric mapping in the diagnosis and management of cardiac transplant rejection: a prospective, histologically-validated study

Multiparametric mapping in the diagnosis and management of cardiac transplant rejection: a prospective, histologically-validated study Muhammad Imran, Louis Wang, Jane McCrohon, Cameron Holloway, James Otton, Chung-Yao Yu, Justyn Huang, Christian Stehning, Valentina Puntmann, Kirsten Moffat, Joanne Ross, Vassilis Vassiliou, Sanjay Prasad, Eugene Kotlyar, Anne Keogh, Christopher Hayward, Peter Macdonald, Andrew Jabbour

Native T1 myocardial tissue characterisation in patients with pulmonary hypertension: findings from International T1 Multicentre Study

Background Pulmonary hypertension is a severe disorder characterized by elevated pulmonary artery pressure leading to right ventricular (RV) failure and premature death. We have recently shown that high signal in septal myocardium by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging indicates more severe disease. This study investigated whether markers of interstitial septal changes by T1 mapping relate to parameters of biventricular function and structure and makers of disease severity in pulmonary hypertension. Methods Patients with a suspected or established diagnosis of pulmonary hypertension, based on a previous echocardiography or catheterisation, respectively, and control subjects underwent routine clinical CMR protocol (1.5 and 3 Tesla) and T1 mapping prior to and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. T1 values were measured in mid-ventricular slices conservatively within septal myocardium. To transform native T1 values into a binary variable (normal/abnormal), the established cut-offs of >990ms at 1.5T or >1090ms at 3T, respectively, were used. For comparison of two and more than two normally distributed variables, Student’s t-test and one-way analysis of variance (ANOVA, with Bonferroni’s post-hoc test) as appropriate. Associations were explored by single and multivariate linear regressions. Results

ACCURACY AND CLINICAL OUTCOMES OF COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY IN THE PRESENCE OF A HIGH CORONARY CALCIUM SCORE

A high coronary calcium burden may adversely affect the image quality of contrast-enhanced CT coronary angiography (CTCA), however the impact on diagnostic accuracy and overall utility of CTCA in this setting is controversial. We sought to assess the clinical outcome, coronary intervention rate and