Deep learning analysis of the myocardium in coronary CT angiography for identification of patients with functionally significant coronary artery stenosis

In patients with coronary artery stenoses of intermediate severity, the functional significance needs to be determined. Fractional flow reserve (FFR) measurement, performed during invasive coronary angiography (ICA), is most often used in clinical practice. To reduce the number of ICA procedures, we present a method for automatic identification of patients with functionally significant coronary artery stenoses, employing deep learning analysis of the left ventricle (LV) myocardium in rest coronary CT angiography (CCTA). The study includes consecutively acquired CCTA scans of 166 patients with FFR measurements. To identify patients with a functionally significant coronary artery stenosis, analysis is performed in several stages. First, the LV myocardium is segmented using a multiscale convolutional neural network (CNN). To characterize the segmented LV myocardium, it is subsequently encoded using unsupervised convolutional autoencoder (CAE). Thereafter, patients are classified according to the presence of functionally significant stenosis using an SVM classifier based on the extracted and clustered encodings. Quantitative evaluation of LV myocardium segmentation in 20 images resulted in an average Dice coefficient of 0.91 and an average mean absolute distance between the segmented and reference LV boundaries of 0.7 mm. Classification of patients was evaluated in the remaining 126 CCTA scans in 50 10-fold cross-validation experiments and resulted in an area under the receiver operating characteristic curve of 0.74 +- 0.02. At sensitivity levels 0.60, 0.70 and 0.80, the corresponding specificity was 0.77, 0.71 and 0.59, respectively. The results demonstrate that automatic analysis of the LV myocardium in a single CCTA scan acquired at rest, without assessment of the anatomy of the coronary arteries, can be used to identify patients with functionally significant coronary artery stenosis.Comment: This paper was submitted in April 2017 and accepted in November 2017 for publication in Medical Image Analysis. Please cite as: Zreik et al., Medical Image Analysis, 2018, vol. 44, pp. 72-8

Disappearance of myocardial perfusion defects on prone SPECT imaging: Comparison with cardiac magnetic resonance imaging in patients without established coronary artery disease

<p>Abstract</p> <p>Background</p> <p>It is of great clinical importance to exclude myocardial infarction in patients with suspected coronary artery disease who do not have stress-induced ischemia. The diagnostic use of myocardial perfusion single-photon emission computed tomography (SPECT) in this situation is sometimes complicated by attenuation artifacts that mimic myocardial infarction. Imaging in the prone position has been suggested as a method to overcome this problem.</p> <p>Methods</p> <p>In this study, 52 patients without known prior infarction and no stress-induced ischemia on SPECT imaging were examined in both supine and prone position. The results were compared with cardiac magnetic resonance imaging (CMR) with delayed-enhancement technique to confirm or exclude myocardial infarction.</p> <p>Results</p> <p>There were 63 defects in supine-position images, 37 of which disappeared in the prone position. None of the 37 defects were associated with myocardial infarction by CMR, indicating that all of them represented attenuation artifacts. Of the remaining 26 defects that did not disappear on prone imaging, myocardial infarction was confirmed by CMR in 2; the remaining 24 had no sign of ischemic infarction but 2 had other kinds of myocardial injuries. In 3 patients, SPECT failed to detect small scars identified by CMR.</p> <p>Conclusion</p> <p>Perfusion defects in the supine position that disappeared in the prone position were caused by attenuation, not myocardial infarction. Hence, imaging in the prone position can help to rule out ischemic heart disease for some patients admitted for SPECT with suspected but not documented ischemic heart disease. This would indicate a better prognosis and prevent unnecessary further investigations and treatment.</p

New nuclear medicine techniques for the assessment of myocardial viability

Een dotterbehandeling of een bypassoperatie heeft alleen zin als er nog voldoende hartspierweefsel over is dat zich kan herstellen. Momenteel wordt de vitaliteit van de hartspier voor de ingreep nog onderzocht met een PET-scan, maar deze techniek is duur en maar in een paar ziekenhuizen in Nederland aanwezig. Riemer Slart constateert in zijn proefschrift dat een goedkopere scan het succes van een bypass of dotteren ook kan voorspellen.

Myocardial perfusion in heart disease

Heart disease: Coronary heart disease is a major cause of mortality and morbidity in the UK and globally. It is managed with medical therapy and coronary revascularisation to reduce symptoms and reduce risk of major adverse cardiovascular events. When patients present with chest pain, it is important to risk stratify those that would most benefit from invasive coronary assessment and those that can be managed with medical therapy alone. Myocardial perfusion techniques have been developed in order to do this. Cardiovascular magnetic resonance (CMR) with stress perfusion: CMR allows the non-invasive assessment of coronary artery disease (CAD). Under conditions of vasodilator stress, a gadolinium based contrast agent is injected and during the first pass through the left ventricle, perfusion defects can be observed. There is a strong evidence base for perfusion CMR but the technique is qualitative, relies on experienced operators and potentially misses globally low perfusion such as in cases of “balanced” ischaemia. Quantitative perfusion CMR: In contrast, quantitative perfusion techniques allow the calculation of myocardial blood flow (MBF). It is more objective, less reliant on the expert observer and can give additional insights into microvascular disease and cardiomyopathy. As well as being less subjective, quantitative perfusion has other advantages for example it allows full assessment of ischaemic burden and may contain prognostic information that could be used to risk stratify and improve patient care. However, quantitative perfusion has been outside the realm of routine clinical practice due to difficulties in acquiring suitable data for full quantification and the laborious nature of analysing it. Perfusion mapping: Peter Kellman, Hui Xue and colleagues at the National Institutes for Health, USA developed the “perfusion mapping” technique to address these limitations. Perfusion maps are generated automatically and inline during the CMR scan and each voxel encodes myocardial blood flow. This allows the instant quantification of MBF without complex acquisition techniques and post processing. In this thesis I have taken perfusion mapping and deployed in the real-world at a scale an order of magnitude higher than prior quantitative perfusion studies, developing the evidence base for routine clinical use across a broad range of diseases and scenarios: In coronary artery disease: I have shown that perfusion mapping is accurate to detect coronary artery stenosis as defined by 3D quantitative coronary angiography in a single centre, 50 patient study. Transmural and subendocardial perfusion are particularly sensitive to detect coronary stenoses with performances similar to expert readers. There is a high sensitivity and high negative predictive value making perfusion mapping a good “rule-out” test for coronary disease. Quantitative perfusion and prognosis: I investigated whether stress MBF and myocardial perfusion reserve (MPR) calculated by perfusion mapping would encode prognostic information in a 1049 patient multi-centre study over a mean follow up time of 605 days. Both stress MBF and MPR were independently associated with death and major adverse cardiovascular events (MACE). The hazard ratio for MACE was 2.14 for each 1ml/g/min decrease in stress MBF and 1.74 for each unit decrease in MPR. This work can now be taken forward with prospective studies in order to better risk stratify patients, including those without perfusion defects on clinical read. Reference ranges and non-obstructive coronary disease: I sought to determine the factors that contribute to perfusion in a multi-centre registry study. In patients with no obstructive coronary artery disease, stress MBF was reduced with age, diabetes, left ventricular hypertrophy (LVH) and the use of beta blockers. Rest MBF was influenced by sex (higher in females) and reduced with beta blockers. This study suggests patient factors beyond coronary artery disease (and therefore likely microvascular disease) should also be considered when interpreting quantitative perfusion studies. In cardiomyopathy: I also investigated myocardial perfusion in cardiomyopathy looking at Fabry disease as an example disease. In a prospective, observational, single centre study of 44 patients and 27 controls I found Fabry patients had reduced perfusion (and therefore likely microvascular dysfunction), particularly in the subendocardium and was associated with left ventricular hypertrophy (LVH), glycophospholipid storage and scar. Perfusion was reduced even in patients without LVH suggesting it is an early disease marker. In conclusion, in this thesis, I have developed an evidence base for quantitative perfusion CMR and demonstrated how it can be integrated into routine clinical care. Perfusion mapping is accurate for detecting coronary artery stenosis and encodes prognostic information. Further work in this area could enable patients to be risk stratified based on their myocardial perfusion in order to reduce the morbidity and mortality associated with epicardial and microvascular coronary artery disease. Following on from this work, two further British Heart Foundation Clinical Research Training Fellowships have been awarded to further investigate quantitative perfusion in patients following surgical revascularisation of coronary disease and in patients with hypertrophic cardiomyopathy

Dysfunctional but viable myocardium - ischemic heart disease assessed by magnetic resonance imaging and single photon emission computed tomography

The assessment of ischemic heart disease (IHD) often focuses on the detection of dysfunctional but viable myocardium which may improve in function following revascularization. Dysfunctional but viable myocardium is identified by distinct characteristics with regards to function, perfusion and viability. Therefore, in Paper I we developed a method for quantitative polar representation of left ventricular myocardial function, perfusion and viability using single photon emission computed tomography (SPECT) and cardiac magnetic resonance (CMR). Polar representation of these parameters was feasible, and the quantitative method agreed with visual assessment. Paper II showed that wall thickening decreases with increasing infarct transmurality. However, the variation in wall thickening was large, and importantly, influenced more so by the function of adjacent myocardium than by infarct transmurality. This underscores the difficulty of using resting function alone to accurately assess myocardial infarction in revascularized IHD. In Paper III we assessed the relationship between left ventricular ejection fraction (LVEF) and infarct size and found that LVEF cannot be used to estimate infarct size, and vice versa. However, the study showed that LVEF can be used to estimate a maximum predicted infarct size, and that infarct size can be used to estimate a maximum predicted LVEF. These results emphasize the importance of direct infarct imaging by CMR when attempting to estimate the size of infarction in patients with IHD. Paper IV was designed to assess the time course of recovery of myocardial perfusion and function after revascularization. The recovery of perfusion was found to occur in the first month, while the recovery of function was delayed in segments with non-transmural infarction. In summary, the presented studies emphasize the importance of direct infarct imaging by CMR for the accurate identification of infarction in the assessment of dysfunctional myocardium. Neither regional nor global myocardial function have a close correlation to infarction, but the presence of non-transmural infarction is a marker for delayed recovery of function following revascularization