Geraint Morton

Inter-study reproducibility of cardiovascular magnetic resonance myocardial feature tracking

BackgroundCardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a recently described method of post processing routine cine acquisitions which aims to provide quantitative measurements of circumferentially and radially directed ventricular wall strain. Inter-study reproducibility is important for serial assessments however has not been defined for CMR-FT.Methods16 healthy volunteers were imaged 3 times within a single day. The first examination was performed at 0900 after fasting and was immediately followed by the second. The third, non-fasting scan, was performed at 1400.CMR-FT measures of segmental and global strain parameters were calculated. Left ventricular (LV) circumferential and radial strain were determined in the short axis orientation (EccSAX and ErrSAX respectively). LV and right ventricular longitudinal strain and LV radial strain were determined from the 4-chamber orientation (EllLV, EllRV, and ErrLAX respectively). LV volumes and function were also analysed.Inter-study reproducibility and study sample sizes required to demonstrate 5% changes in absolute strain were determined by comparison of the first and second exams. The third exam was used to determine whether diurnal variation affected reproducibility.ResultsCMR-FT strain analysis inter-study reproducibility was variable. Global strain assessment was more reproducible than segmental analysis. Overall EccSAX was the most reproducible measure of strain: coefficient of variation (CV) 38% and 20.3% and intraclass correlation coefficient (ICC) 0.68 (0.55-0.78) and 0.7 (0.32-0.89) for segmental and global analysis respectively. The least reproducible segmental measure was EllRV: CV 60% and ICC 0.56 (0.41-0.69) whilst the least reproducible global measure was ErrLAX: CV 33.3% and ICC 0.44 (0–0.77). Variable reproducibility was also reflected in the calculated sample sizes, which ranged from 11 (global EccSAX) to 156 subjects (segmental EllRV). The reproducibility of LV volumes and function was excellent. There was no diurnal variation in global strain or LV volumetric measurements.ConclusionsInter-study reproducibility of CMR-FT varied between different parameters, as summarized above and was better for global rather than segmental analysis. It was not measurably affected by diurnal variation. CMR-FT may have potential for quantitative wall motion analysis with applications in patient management and clinical trials. However, inter-study reproducibility was relatively poor for segmental and long axis analyses of strain, which have yet to be validated, and may benefit from further development.

Registration of 3D trans-esophageal echocardiography to x-ray fluoroscopy using image-based probe tracking

Two-dimensional (2D) X-ray imaging is the dominant imaging modality for cardiac interventions. However, the use of X-ray fluoroscopy alone is inadequate for the guidance of procedures that require soft-tissue information, for example, the treatment of structural heart disease. The recent availability of three-dimensional (3D) trans-esophageal echocardiography (TEE) provides cardiologists with real-time 3D imaging of cardiac anatomy. Increasingly X-ray imaging is now supported by using intra-procedure 3D TEE imaging. We hypothesize that the real-time co-registration and visualization of 3D TEE and X-ray fluoroscopy data will provide a powerful guidance tool for cardiologists. In this paper, we propose a novel, robust and efficient method for performing this registration. The major advantage of our method is that it does not rely on any additional tracking hardware and therefore can be deployed straightforwardly into any interventional laboratory. Our method consists of an image-based TEE probe localization algorithm and a calibration procedure. While the calibration needs to be done only once, the GPU-accelerated registration takes approximately from 2 to 15s to complete depending on the number of X-ray images used in the registration and the image resolution. The accuracy of our method was assessed using a realistic heart phantom. The target registration error (TRE) for the heart phantom was less than 2mm. In addition, we assess the accuracy and the clinical feasibility of our method using five patient datasets, two of which were acquired from cardiac electrophysiology procedures and three from trans-catheter aortic valve implantation procedures. The registration results showed our technique had mean registration errors of 1.5-4.2mm and 95% capture range of 8.7-11.4mm in terms of TRE.

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease

BackgroundIn patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation.Trial designThe MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807.ConclusionMR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

A direct comparison of the sensitivity of CT and MR cardiac perfusion using a myocardial perfusion phantom

Background Direct comparison of CT and magnetic resonance (MR) perfusion techniques has been limited and in vivo assessment is affected by physiological variability, timing of image acquisition, and parameter selection. Objective We precisely compared high-resolution k-t SENSE MR cardiac perfusion at 3 T with single-phase CT perfusion (CTP) under identical imaging conditions. Methods We used a customized MR imaging and CT compatible dynamic myocardial perfusion phantom to represent the human circulation. CT perfusion studies were performed with a Philips iCT (256 slice) CT, with isotropic resolution of 0.6 mm3. MR perfusion was performed with k-t SENSE acceleration at 3 T and spatial resolution of 1.2 × 1.2 × 10 mm. The image contrast between normal and underperfused myocardial compartments was quantified at various perfusion and photon energy settings. Noise estimates were based on published clinical data. Results Contrast by CTP highly depends on photon energy and also timing of imaging within the myocardial perfusion upslope. For an identical myocardial perfusion deficit, the native image contrast-to-noise ratio (CNR) generated by CT and MR are similar. If slice averaging is used, the CNR of a perfusion deficit is expected to be greater for CTP than MR perfusion (MRP). Perfect timing during single time point CTP imaging is difficult to achieve, and CNR by CT decreases by 24%–31% two seconds from the optimal imaging time point. Although single-phase CT perfusion offers higher spatial resolution, MRP allows multiple time point sampling and quantitative analysis. Conclusion The ability of CTP and current optimal MRP techniques to detect simulated myocardial perfusion deficits is similar.

Value of cardiovascular magnetic resonance imaging in myocardial hypertrophy.

Sirs: A 72-year-old Afro-American male with known hypertension and increasing shortness of breath underwent routine echocardiography. Echo showed concentric left ventricular (LV)-hypertrophy (maximal wall thickness 1.9 cm of the interventriclar septum) with preserved systolic function. There were signs of raised diastolic filling pressures (E/E’ 13) and impaired longitudinal function. The patient was subsequently referred for an outpatient cardiovascular magnetic resonance (CMR) scan to further characterize the distribution of hypertrophy and assess for potential fibrosis. Images showed normal systolic function of the hypertrophied ventricles with diffuse subendocardial late gadolinium enhancement (LGE) in the myocardium and in the hypertrophied interatrial septum (See Fig. 1). The patient underwent CMRguided endomyocardial biopsy of the LV lateral wall showing extensive subendocardial amorphous amyloid deposits, replacing cardiac muscle with typical apple green birefringence under cross-polarized light (See Fig. 1). Immunohistochemical staining revealed Amyloid of transthyretin (ATTR) type related to senile amyloidosis. The patient was put on heart failure medication including diuretic treatment with bumetanide. Cardiac involvement is a common finding and CMR is particularly valuable for initial diagnosis and detection of hypertrophy and LGE changes during the follow-up. CMR should be considered early in unclear cardiomyopathies [1], since it may provide an unsuspected new diagnosis leading to adapted treatment in every fifth patient [2].

Prognostic utility of BCIS myocardial jeopardy score for classification of coronary disease burden and completeness of revascularization.

Several coronary disease scoring systems have been developed to predict procedural risk during revascularization. Many vary in complexity, do not specifically account for myocardium at risk, and are not applicable across all patient subsets. The British Cardiovascular Intervention Society myocardial jeopardy score (BCIS-JS) addresses these limitations and is applicable to all patients, including those with coronary artery bypass grafts or left main stem disease. We assessed the prognostic relevance of the BCIS-JS in patients undergoing percutaneous coronary intervention (PCI). A total of 663xa0patients who underwent PCI with previous left ventricular function assessment were retrospectively assessed for inclusion, incorporating 221 with previous coronary artery bypass grafting. Blinded observers calculated the BCIS-JS, before (BCIS-JS(PRE)) and after (BCIS-JS(POST)) PCI, using the revascularization index (RI) (RIxa0= [BCIS-JS(PRE)xa0- BCIS-JS(POST)]/BCIS-JS(PRE)), quantifying the extent of revascularization, 1 indicating full revascularization and 0 indicating no revascularization. The primary end point all-cause mortality, tracked via the Office of National Statistics. A total of 660 patients were included (66xa0± 10.7 years), with 43 deaths (6.5%) occurring during 2.6 ± 1.1 years after PCI. All-cause mortality was directly related to BCIS-JS(PRE) (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.71 to 5.15, pxa0= 0.001) and BCIS-JS(POST) (HR 4.02, 95% CI 2.41 to 6.68, pxa0= 0.001). A RI of <0.67 was associated with increased mortality compared to a RI of ≥0.67 (HR 4.13, 95% CI 1.91 to 8.91, pxa0= 0.0001). On multivariate analysis, a RI <0.67 (HR 1.99, 95% CI 1.03 to 3.87, pxa0= 0.04), left ventricular dysfunction (HR 2.03, 95% CI 1.25 to 3.30, pxa0= 0.004) and renal impairment (HR 3.75, 95% CI 1.48 to 8.64, pxa0= 0.005) were independent predictors of mortality. In conclusion, the BCIS-JS predicts mortality after PCI and can assess the degree of revascularization, with more complete revascularization conferring a survival advantage in the medium term.

The intra-observer reproducibility of cardiovascular magnetic resonance myocardial feature tracking strain assessment is independent of field strength

Methods We studied 2 groups, each consisting of 10 healthy subjects, at 1.5 or 3 Tesla. Analysis was performed at baseline and after 4 weeks using dedicated CMR-FT prototype software (Tomtec, Germany) to analyse standard SSFP cine images. Right ventricular (RV) and left ventricular (LV) longitudinal strain (EllRV and EllLV) and LV long-axis radial strain (ErrLAX) were derived from the 4-chamber cine, and LV short-axis circumferential and radial strains (EccSAX, ErrSAX) from the short-axis orientation. Strain parameters were assessed together with LV ejection fraction (EF) and volumes. Intra-observer reproducibility was determined by comparison of the first and the second analysis in both groups.

Validation of dynamic three-dimensional whole heart magnetic resonance myocardial perfusion imaging at 3.0 Tesla against fractional flow reserve for the detection of flow-limiting coronary heart disease

Summary We demonstrate the feasibility of 3D myocardial perfusion CMR at 3 Tesla against fractional flow reserve (FFR) in 53 patients for the detection of flow-limiting coronary artery disease and show good agreement between the techniques. This technique shows excellent diagnostic sensitivity and specificity and may offer an alternative method of detecting ischaemia for the purpose of guiding revascularisation and risk stratification. Background Three-dimensional (3D) myocardial perfusion cardiovascular magnetic resonance (CMR) has recently been proposed to overcome the limited spatial coverage of conventional perfusion CMR methods1. The method has shown good diagnostic accuracy for the detection of coronary artery disease determined by quantitative coronary angiography (QCA)2. However the relationship between the severity of a coronary stenosis on QCA and its functional significance is variable. Pressure wirederived fractional flow reserve (FFR) <0.75 correlates closely with objective evidence of reversible ischemia and it has been demonstrated that ischaemia-guided PCI confers a prognostic benefit. Aim To determine the diagnostic accuracy of whole heart 3D myocardial perfusion CMR against invasively determined FFR.

Advanced techniques improve the performance of myocardial perfusion imaging

Methods A standard ultrafast gradient echo perfusion sequence (st-GrE) was compared with an advanced kt-accelerated steady state free precession sequence (kt-SSFP) at 1.5T in a hardware perfusion phantom, healthy volunteers (n=16) and patients (n=31) with known or suspected coronary artery disease. Volunteers had both sequences at rest in alternating order. Patients underwent stress imaging with either st-GrE (15) or kt-SSFP (16) prior to X-ray coronary angiography. The phantom was used to generate signal intensity curves and noise maps for SNR and CNR analysis. Human images were analysed by a blinded observer using a nominal scale for quality (0 non-diagnostic, 1 poor, 2 moderate, 3 good, 4 excellent) and respiratory artefacts (0 non-diagnostic, 1 severe, 2 moderate, 3 minor, 4 nil) and also for the presence of CAD in patients. Other analyses included the extent (% affected segments), transmurality (1: 1-25%, 2: 26-50%, 3: 5175%, 4 76-100%) and duration (frames) of dark rim artefacts (DRA). Segmental SNR and CNR were also quantified using the mid ventricular slice in volunteers.

Quantitative assessment of magnetic resonance derived perfusion measurements using advanced techniques: comparison with microspheres in an explanted pig heart system

Background Quantitative cardiovascular magnetic resonance (CMR) myocardial perfusion imaging has the potential to evolve into a routine clinical method allowing for the assessment of myocardial blood flow (MBF). Multiple quantification pathways are available based on different algorithms. These algorithms involve complex modeling and quantitative results may not necessarily be the same. At present it remains unclear which algorithm is the most accurate. An isolated perfused, magnetic resonance (MR) compatible pig heart model allows very accurate titration of MBF and in combination with high-resolution assessment of fluorescently-labeled microspheres represents a near optimal platform for validation. We sought to investigate which algorithm is most suited to quantify myocardial perfusion by CMR imaging at 1.5 and 3 Tesla using state of the art CMR perfusion techniques and quantification algorithms. Methods First-pass CMR perfusion was performed in a MR compatible blood perfused pig heart model. We acquired perfusion images at resting flow (100%), 50% flow and during adenosine induced hyperemia in control and coronary occlusion conditions. MR myocardial perfusion imaging was performed at 1.5 Tesla (n=4) and at 3 Tesla (n=4). Fluorescently-labeled microspheres and externally controlled coronary blood flow served as reference standards for comparison of different quantification strategies, namely Fermi function constrained deconvolution, autoregressive moving average modeling, deconvolution using an exponential basis and deconvolution using a B-spline basis. Results All CMR derived MBF estimates agreed well with microsphere results. The best correlation was achieved with Fermi function constrained deconvolution both at 1.5 Tesla (r=0.93, p 0.05).The weakest correlation at 1.5 Tesla was found using B-spline deconvolution (r=0.74, p<0.001) and at 3 Tesla using exponential deconvolution (r=0.49, p<0.001). Conclusions