Applications of Rapid Cardiac Micro-CT

Mouse models are an important tool in cardiovascular disease research and a non-invasive imaging method is an advantageous way of monitoring disease progression. Cardiac micro-CT is rapid imaging technique capable of quantifying changes in cardiac structure and function in mice. The goal of this thesis was to demonstrate the utility of this technique in monitoring disease progression in a longitudinal study, as well as its capability for evaluating other methods of measuring cardiac function in mice. In a longitudinal study, a mouse model of myocardial infarction was scanned weekly for four weeks; left ventricular volume and ejection fraction were measured from the images. Cardiac micro-CT was capable of tracking small changes in cardiac structure and function, with the MI mice demonstrating a significant increase in volume and a significant decrease in ejection fraction. Both inter- and intra-variability was low, indicating the results were highly reproducible. Contrast agents are essential to evaluating the heart in micro-CT images. A new blood-pool agent was evaluated to determine its suitability for use in cardiac micro-CT studies. The agent produced excellent enhancement for the first 30 minutes post-injection, and had a unique characteristic of enhancing the myocardium, which may prove useful in studies evaluating wall motion. The effect of x-ray dose delivered during a longitudinal micro-CT study was also evaluated. C57BL/6 mice were scanned weekly for six weeks; the total entrance dose delivered over the study was 5.04 Gy. No significant changes to the heart or lungs were detectable on the micro-CT images at six weeks, and the histology performed on myocardial and pulmonary tissue showed no indication of early inflammation at a cellular level. Micro-CT can therefore be used in longitudinal studies without concern of adverse effects. Cardiac micro-CT was used to evaluate conductance catheters, and found that the catheter volumes were drastically underestimated compared to the micro-CT volumes. It was also determined that catheterization has the potential for causing cardiac enlargement; 40% of the mice demonstrated enlarged hearts following the catheterization procedure. Overall, cardiac-gated micro-CT is a rapid and reproducible imaging technique, and is proving to be valuable tool in cardiovascular disease research

Особенности эластических свойств дилатированной и аневризматически расширенной грудной аорты по данным ЭКГ-синхронизированной КТ-ангиографии

Purpose: to compare the indicators of elasticity of the thoracic aorta, determined by ECG-Gated-CT angiography, in patients with ascending aortic aneurysm and dilatation.Materials and methods. The study included 20 patients with dilatation of the ascending aorta (40 mm ≤ maximum aortic diameter (Dmax) < 50 mm) (group 1a), 30 patients with non-syndromic aneurysms of the ascending aorta (n = 30, Dmax ≥ 50 mm) (group 1b), as well as 19 patients with normal aortic sizes (Dmax < 40 mm) as controls (group 2). All patients underwent multispiral computed tomography angiography of the aorta in ECG-Gated mode (ECG-Gated -CT). Maximum systolic and diastolic aortic diameters (Dmax) were measured at different levels of the thoracic aorta, followed by calculation of the difference between them and calculation of the circular deformation (CS), compliance, stiffness (Stiff), wall distensibility, longitudinal deformation (LS).Results. Moderate negative correlation between the age of the patients and CS at all levels of the thoracic aorta (rmaximum = –0.33, rminimum = –0.41) was revealed. Groups 1a and 1b did not differ significantly in all parameters. Group 1a differed from the control group (p < 0.05) in Stiff at the level of the aortic annulus (AA) (0.07 [–0.14; 0.15] vs –0.04 [–0.1; 0.06]), as well as CS at the level of AA and sinuses of Valsalva (SV ) (0.49 [–2.94; 3.36] vs –1.18 [–4.51; 3.87]), and group 1b – in CS at the level of SV (3.73 [0.24; 6.56] vs 0.13 [–1.42; 3.04]) and proximal part of the descending aorta (distal to the left subclavian artery) (5.48 [1.27; 8.40] vs 1.97 [–0.32; 6.08]), also in LS (5.96 [–8.98; 9.25] vs –2.58 [–7.75; 1.89]) at the level of the aortic arch.Conclusion. According to ECG-Gated-CT angiography, the indicators of elasticity of the thoracic aorta in patients with ascending aortic aneurysm and dilatation did not differ. Compared with the control group, patients with aneurysm of the ascending aorta showed an increased pulse deformity of the non-dilated aortic arch.Цель исследования: сопоставить показатели эластичности грудной аорты, определенные по данным ЭКГ-синхронизированной КТ-ангиографии, у пациентов с аневризмой и дилатацией восходящего отдела.Материал и методы. В исследование было включено 20 пациентов c дилатацией восходящей аорты (40 мм ≤ максимальный диаметр аорты (Dmax) < 50 мм) (подгруппа 1а), 30 больных с несиндромными аневризмами восходящей аорты (n = 30, Dmax ≥ 50 мм) (подгруппа 1б), а также 19 больных с нормальными размерами сосуда (Dmax < 40 мм) в качестве контроля (группа 2). Всем пациентам была выполнена мультиспиральная компьютерно-томографическая ангиография аорты в ЭКГ-синхронизированном режиме (ЭКГсинхр.-КТ). На различных уровнях грудной аорты измеряли максимальный систолический и диастолический диаметр сосуда (Dmax) с последующим расчетом разницы между ними и индексов циркулярной деформации (CS), комплаенса, жесткости (Stiff), растяжимости стенки (для всех уровней), продольной деформации (LS).Результаты. По результатам анализа была выявлена умеренная отрицательная корреляционная взаимосвязь между возрастом пациентов и CS на всех уровнях грудной аорты (rmax = –0,33, rmin = –0,41). Подгруппы 1а и 1б по всем показателям значимо не различались. От группы контроля подгруппа 1а отличалась (p < 0,05) по Stiff на уровне фиброзного кольца (ФК) аортального клапана (0,07 [–0,14; 0,15] vs –0,04 [–0,1; 0,06]), а также CS на уровне ФК и синусов Вальсальвы (СВ) (0,49 [–2,94; 3,36] vs –1,18 [–4,51; 3,87]), а подгруппа 1б – по CS на уровне СВ (3,73 [0,24; 6,56] vs 0,13 [–1,42; 3,04]) и проксималного отдела нисходящей аорты (дистальнее устья левой подключичной артерии) (5,48 [1,27; 8,40] vs 1,97 [–0,32; 6,08]), также по LS (5,96 [–8,98; 9,25] vs –2,58 [–7,75; 1,89]) на уровне дуги аорты.Заключение. По данным ЭКГсинхр. КТ-ангиографии показатели эластичности грудной аорты у пациентов с аневризмой и дилатацией восходящего отдела не различаются. По сравнению с группой контроля у больных с аневризмой восходящего отдела аорты отмечается увеличение пульсовой деформации в недилатированной зоне (дуге аорты)

Ultrasonic Pulse Wave Imaging for in vivo Assessment of Vascular Wall Dynamics and Characterization of Arterial Pathologies

Arterial diseases such as hypertension, carotid stenosis, and abdominal aortic aneurysm (AAA) may progress silently without symptoms and contribute to acute cardiovascular events such as heart attack, stroke, and aneurysm rupture, which are consistently among the leading causes of death worldwide. The arterial pulse wave, regarded as one of the fundamental vital signs of clinical medicine, originates from the heart and propagates throughout the arterial tree as a pressure, flow velocity, and wall displacement wave, giving rise to the natural pulsation of the arteries. The dynamic properties of the pulse wave are intimately related to the physical state of the cardiovascular system. Thus, the assessment of the arterial wall dynamics driven by the pulse wave may provide valuable insights into vascular mechanical properties for the early detection and characterization of arterial pathologies. The focus of this dissertation was to develop and clinically implement Pulse Wave Imaging (PWI), an ultrasound elasticity imaging-based method for the visualization and spatio-temporal mapping of the pulse wave propagation at any accessible arterial location. Motion estimation algorithms based on cross-correlation of the ultrasound radio-frequency (RF) signals were used to track the arterial walls and capture the pulse wave-induced displacements over the cardiac cycle. PWI facilitates the image-guided measurement of clinically relevant pulse wave features such as propagation speed (pulse wave velocity, or PWV), uniformity, and morphology as well as derivation of the pulse pressure waveform. A parametric study investigating the performance of PWI in two canine aortas ex vivo and 10 normal, healthy human arteries in vivo established the optimal image acquisition and signal processing parameters for reliable measurement of the PWV and wave propagation uniformity. Using this framework, three separate clinical feasibility studies were conducted in patients diagnosed with hypertension, AAA, and carotid stenosis. In a pilot study comparing hypertensive and aneurysmal abdominal aortas with normal controls, the AAA group exhibited significantly higher PWV and lower wave propagation uniformity. A “teetering” motion upon pulse wave arrival was detected in the smaller aneurysms ( 5.5 cm in diameter). While no significant difference in PWV or propagation uniformity was observed between normal and hypertensive aortas, qualitative differences in the pulse wave morphology along the imaged aortic segment may be an indicator of increased wave reflection caused by elevated blood pressure and/or arterial stiffness. Pulse Wave Ultrasound Manometry (PWUM) was introduced as an extension of the PWI method for the derivation of the pulse pressure (PP) waveform in large central arteries. A feasibility study in 5 normotensive, 9 pre-hypertensive, and 5 hypertensive subjects indicated that a significantly higher PP in the hypertensive group was detected in the abdominal aorta by PWUM but not in the peripheral arteries by alternative devices (i.e. a radial applanation tonometer and the brachial sphygmomanometer cuff). A relatively strong positive correlation between aortic PP and both radial and brachial PP was observed in the hypertensive group but not in the normal and pre-hypertensive groups, confirming the notion that PP variation throughout the arterial tree may not be uniform in relatively compliant arteries. The application of PWI in 10 stenotic carotid arteries identified phenomenon such as wave convergence, elevated PWV, and decreased cumulative displacement around and/or within regions of atherosclerotic plaque. Intra-plaque mapping of the PWV and cumulative strain demonstrated the potential to quantitatively differentiate stable (i.e. calcified) and vulnerable (i.e. lipid) plaque components. The lack of correlation between quantitative measurements (PWV, modulus, displacement, and strain) and expected plaque stiffness illuminates to need to consider several physiological and imaging-related factors such as turbulent flow, wave reflection, imaging location, and the applicability of established theoretical models in vivo. PWI presents a highly translational method for visualization of the arterial pulse wave and the image-guided measurement of several clinically relevant pulse wave features. The aforementioned findings collectively demonstrated the potential of PWI to detect, diagnose, and characterize vascular disease based on qualitative and quantitative information about arterial wall dynamics under pathological conditions