Systolic ejection murmurs and the left ventricular outflow tract in boxer dogs

Turbulence of various genesis in the left ventricular outflow tract (LVOT) causes systolic ejection murmurs. The prevalence of murmurs in adult boxer dogs is 50-80%, the majority of which are of low intensity. Some of the murmurs are caused by aortic stenosis (AS), while the origin of the others is unclear. The aim of this thesis was to study the physiology and clinical evaluation of systolic ejection murmurs and their relation to the development of the LVOT in boxers with and without AS. Growing and adult boxer dogs were examined by the standard methods cardiac auscultation, ECG, phonocardiography and echocardiography. Additionally, the complementary methods time-frequency and complexity analyses of heart murmurs and contrast echocardiography were evaluated. Studies on inter-observer variation in cardiac auscultation proved the importance of experience in detection and grading of low intensity ejection murmurs. Excitement of the dogs by exercise or noise stimulation (barking dog and squeaky toy) caused higher murmur grades, longer murmur duration and increased aortic flow velocities. No differences were found between diameters measured at different levels of the LVOT in growing boxers. Contrast echocardiography enhanced Doppler signals, but did not allow evaluation of myocardial blood flow. Using time-frequency analysis, duration of murmur frequency >200 Hz proved useful for differentiation between dogs with mild AS and dogs without. Combining assessment of murmur duration >200 Hz and complexity analysis using the correlation dimension (T2), a sensitivity of 94% and a specificity of 82% for differentiation between dogs with and without AS was achieved. The variability in presence and intensity of low intensity murmurs during growth was high. None of the young dogs developed AS, whereas 3 out of 16 individuals developed mild-moderate aortic insufficiency. Aortic or pulmonic flow velocities did not differ significantly between growing dogs with or without low intensity murmurs. In conclusion, the variability in presence and intensity of low intensity ejection murmurs in boxers is high during growth with no obvious progression. Both in young and adult boxers the murmur grade increased during excitement, which may be due to rapid flow in a comparatively small LVOT that has been suggested for the boxer breed. Experience is important in cardiac auscultation of low intensity murmurs. Therefore, assessment of murmur duration > 200 Hz combined with T2 analysis may be a useful complementary method for diagnosis of cardiovascular function in dogs

Hemodynamics in the Stenosed Carotid Bifurcation with Plaque Ulceration

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in an ensemble of matched model vessel geometries determined that ulceration as small as 2 mm can generate significant disturbances in the downstream flow field in a moderately stenosed carotid artery, which are detectable using the DUS velocity-derived parameter turbulence intensity (TI) measured with a clinical system. Further experimental results showed that distal TI was significantly elevated (P \u3c 0.001) due to proximal plaque ulceration in the mild and moderately stenosed carotid bifurcation (30%, 50%, 60% diameter reduction), and also increased with stenosis severity. Pulsatile computational fluid dynamics (CFD) models, with simulated particle tracking, demonstrated enhanced flow disruption of the stenotic jet and slight elevations in path-dependent shear exposure parameters in a stenosed carotid bifurcation model with ulceration. In addition, CFD models were used to evaluate the DUS index TI using finite volume sampling

TURBULENCE ACCUMULATION AND AVERAGE IN THE SYMMETRICALLY AND ASYMMETRICALLY STENOSED CAROTID BIFURCATION

Ischemic stroke due to atherosclerotic disease has been studied widely in the recent past. Most studies focus on either the correlation between stroke risk and stenosis severity (narrowing of the plaque in the vessel) or mechanisms affecting platelet activation and aggregation. Shear stress has been identified as a strong indicator for platelet activation/aggregation, resulting in both thrombus formation and plaque growth. This has subsequently been correlated with regions of elevated turbulence. Doppler ultrasound offers a method of characterizing these flow disturbances using a well-established parameter—turbulence intensity (Tl), which is the root mean squared deviation in the spectral mean velocity. Using an in-house in vitro flow system, Doppler spectra are obtained at each of over 1000, 1-mm3 isotropically spaced sites in the central plane of seven Teflon phantoms simulating varying degrees of arterial disease. An average of Tl over a 25 mm2 region of interest, as well as the volume of Tl and the cumulative Tl over the internal carotid artery showed that downstream turbulence increased significantly with both stenosis severity (30% - 650% increase) and plaque asymmetry (10% - 30% increase)

Measurement and monitoring of atheromatous lesions of the femoral artery by duplex ultrasound.

In Western Societies atheromatous stenosis and occlusion of the superficial femoral artery cause intermittent claudication in up to 5% of the population over 55 years of age, and the associated morbidity and disability are considerable. A foreknowledge of impending lesion progression might allow prevention of clinical deterioration by early intervention. However, the natural history of these lesions needs to be more fully evaluated. Critical to the monitoring of early lesions is the need for accurate, repeatable and non-invasive investigations. The role of duplex ultrasound in this area is largely unexplored. In this thesis clinical and laboratory data demonstrate the accuracy and repeatability of duplex ultrasound in the measurement of femoral stenoses. A prospective study was carried out to determine the incidence of progression from stenosis to occlusion. There has been an enormous increase in the use of percutaneous transluminal angioplasty (PTA) in the treatment of patients with claudication. However, the relative benefits of PTA over conventional treatment have not been established. A study to determine the role of duplex in screening patients with claudication prior to PTA was carried out. The results demonstrate its accuracy and the consequent clinical benefits. A randomised controlled trial of PTA for patients with intermittent claudication has been established and the early patient data at trial entry are presented

Methods for Improved Estimation of Low Blood Velocities Using Vector Doppler Ultrasound

Accurate estimation of low 3D blood velocities, such as near the wall in recirculation or disturbed flow regions, is important for accurate mapping of velocities to improve estimations of wall shear stress and turbulence, which are associated risk factors for vascular disease and stroke. Doppler ultrasound non-invasively measures blood-velocities but suffers from two major limitations addressed in this thesis. These are angle dependence of the measurements, which requires the knowledge of beam-to-flow angle, and the wall-filter. The high-pass wall filter that is applied to attenuate the high-intensity low-frequency signal from tissue and slowly moving vessel wall also attenuates any low velocity signals from blood thus causing inaccurate estimation of these velocities. This thesis presents two methods to alleviate the angle-dependence limitation and to minimize the effect of the wall filter on low blood-velocity estimates: a multi-receiver technique – vector Doppler ultrasound (VDUS), and a novel method called aperture-translation technique. For the first method – VDUS, theoretical and experimental studies were performed to assess the comparative benefit of three to eight receivers (3R–8R) in Doppler ultrasound configurations in terms of the number of receiver beams, inter-beam angle, and beam- selection method (criterion for discriminating between tissue and blood Doppler signals) for a range of velocity orientations. Accuracy and precision for ≥5 receivers were consistently better over all flow velocity orientations and for all beam-selection methods. Asymmetry in the 5R configuration led to improved accuracy and precision compared to symmetrical 6R and 8R configurations. Second, a novel 2D-VDUS aperture-translation technique using mechanical or electronic translation of the transmit-receive apertures was introduced and assessed experimentally. Both versions of the technique outperformed the conventional 2D-VDUS method for detection of low flow velocities in terms of accuracy and precision. The electronic version, which is more relevant and feasible clinically, showed comparable reliability and better accuracy compared with the idealized mechanical version, therefore suggesting its potential for future development. This work demonstrated that a minimum of five receivers, preferably with an inherent asymmetry with respect to the flow direction, should be considered when designing a 2D-array configuration for improved estimation of low velocities. For estimation of low velocities not measurable with conventional VDUS methods, the aperture-translation technique could be a potential candidate

Pressure drop and recovery in cases of cardiovascular disease: a computational study

The presence of disease in the cardiovascular system results in changes in flow and pressure patterns. Increased resistance to the flow observed in cases of aortic valve and coronary artery disease can have as a consequence abnormally high pressure gradients, which may lead to overexertion of the heart muscle, limited tissue perfusion and tissue damage. In the past, computational fluid dynamics (CFD) methods have been used coupled with medical imaging data to study haemodynamics, and it has been shown that CFD has great potential as a way to study patient-specific cases of cardiovascular disease in vivo, non-invasively, in great detail and at low cost. CFD can be particularly useful in evaluating the effectiveness of new diagnostic and treatment techniques, especially at early ‘concept’ stages. The main aim of this thesis is to use CFD to investigate the relationship between pressure and flow in cases of disease in the coronary arteries and the aortic valve, with the purpose of helping improve diagnosis and treatment, respectively. A transitional flow CFD model is used to investigate the phenomenon of pressure recovery in idealised models of aortic valve stenosis. Energy lost as turbulence in the wake of a diseased valve hinders pressure recovery, which occurs naturally when no energy losses are observed. A “concept” study testing the potential of a device that could maximise pressure recovery to reduce the pressure load on the heart muscle was conducted. The results indicate that, under certain conditions, such a device could prove useful. Fully patient-specific CFD studies of the coronary arteries are fewer than studies in larger vessels, mostly due to past limitations in the imaging and velocity data quality. A new method to reconstruct coronary anatomy from optical coherence tomography (OCT) data is presented in the thesis. The resulting models were combined with invasively acquired pressure and flow velocity data in transient CFD simulations, in order to test the ability of CFD to match the invasively measured pressure drop. A positive correlation and no bias were found between the calculated and measured results. The use of lower resolution reconstruction methods resulted in no correlation between the calculated and measured results, highlighting the importance of anatomical accuracy in the effectiveness of the CFD model. However, it was considered imperative that the limitations of CFD in predicting pressure gradients be further explored. It was found that the CFD-derived pressure drop is sensitive to changes in the volumetric flow rate, while bench-top experiments showed that the estimation of volumetric flow rate from invasively measured velocity data is subject to errors and uncertainties that may have a random effect on the CFD pressure result. This study demonstrated that the relationship between geometry, pressure and flow can be used to evaluate new diagnostic and treatment methods. In the case of aortic stenosis, further experimental work is required to turn the concept of a pressure recovery device into a potential clinical tool. In the coronary study it was shown that, though CFD has great power as a study tool, its limitations, especially those pertaining to the volumetric flow rate boundary condition, must be further studied and become fully understood before CFD can be reliably used to aid diagnosis in clinical practice.Open Acces

Investigation of the assessment of low degree (\u3c50%) renal artery stenosis based on velocity flow profile analysis using Doppler ultrasound: An in-vitro study

Purpose: Renal arterial stenosis can lead to disrupted renal function due to reduced blood flow to the kidneys and is largely thought to be caused by atherosclerosis. Current diagnostic strategies for renal arterial stenosis rely on detecting large degree stenoses (\u3e50%). This study aimed to test the viability of using Doppler ultrasound to assess velocity profiles to detect the presence of low degree (\u3c50%) stenoses. Methods: A series of anatomically realistic renal artery flow phantoms were constructed exhibiting a range of low degree stenoses (symmetric and asymmetric). The behaviour of fluid flow in the phantoms was examined using Doppler ultrasound and analysed to calculate the clinical biomarker, wall shear stress. Results: A number of fluid behaviours were observed in relation to stenosis degree: asymmetric stenoses tended to result in a skewing of peak velocities away from the centre of the vessel towards the outer wall, the magnitude of increase in velocity was observed to correlate with stenosis degree, and the wall shear stress curves observed large peaks in the presence of even the lowest degree stenosis (20%). Conclusions: Doppler ultrasound could potentially be utilised to diagnose low degree stenoses in a clinical setting. Doppler ultrasound in conjunction with wall shear stress analysis in particular has significant potential in the diagnosis of renal artery stenosis

Quantitative Detection of Circulating Embolic Materials With Doppler Ultrasound

1. Detection, quantification and differentiation of circulating embolic materials and other related heamodynamic phenomena was performed in middle cerebral artery (MCA) in vitro models using trancranial Doppler (TCD) ultrasonography. Signal intensity analysis was used as a major measurement method to quantify the Doppler signals in this study. The validity of this method was also examined in experimental and clinical settings 2. In an MCA in vitro model, the ability of TCD to detect microbubbles was initially evaluated. Two sizes of microbubbles (5 mum and 30 mum) were prepared in Ultravist 370 (a contrast medium) and 5% albumin respectively. TCD proved to be sensitive to detect microbubbles as small as 5 mum in diameter. The correlation between embolic signal intensity and the number of microbubbles was investigated in twoconcentrations of microbubbles with signal intensity analysis. It was found that embolic signal intensity was proportional to the increase in the number of microbubbles present in the Doppler sample volume. However, this relationship tended to weaken at higher concentrations of microbubbles. 3. In the same model, the relationship between embolic signal intensity and the size of emboli of different sources was examined and the signal intensities caused by different embolic materials were compared. Seven types of embolic material were prepared and studied in this test. A quantitative relationship existed between the embolic signal intensity and the size of all the types of emboli tested. Air bubble emboli caused higher signal intensity than that caused by any solid embolic materials. Among the solid emboli at an average size of 100 mum, platelet-rich thrombin produced the highest signal intensity. Further, the suitability of using total embolic signal intensity to differentiate the different sources of embolic was studied. It was found that an assigned embolic signal intensity could be produced by a small but highly reflective type of embolus or a larger but less reflective type of embolus. 4. In an modified MCA model, spontaneous contrast echo was reproduced in a expansion chamber under low flow conditions. With a two-dimensional cardiosonography system and TCD, the differentiation of spontaneous contrast from emboli was carried out by both visual observation of the echo images and Doppler signal intensity analysis. Spontaneous contrast was distinct from emboli (whole blood clots, platelet-rich thrombin, and microbubbles) in echographic appearances and Doppler signal intensity. 5. The relationship between average signal intensity and the degree of stenosis of the MCA and the differentiation of turbulence from embolic signals were examined in a stenotic in vitro MCA model. A series of short, asymmetric stenoses were prepared in this test. Transition of turbulence from the laminar flow began to occur at a moderate degree of stenosis (55%) but became dump at the high degrees of stenoses (75% and 85%). Turbulence caused a significant increase in Doppler signal intensity. However, The degree of stenosis was not associated with signal intensity at the region of the turbulence but was related to the mean flow velocity through the narrowed region. Air bubbles (30 mum) and platelet-rich clots (100 mum) had a significantly higher signal intensity than the signal intensity through areas of turbulence. All the tested embolic signals showed different Doppler characteristics from the signals associated with turbulent flow. 6. The effect of transmitting frequency and flow velocity on ultrasonic quantification of emboli was investigated in an modified MCA model. A measured platelet-rich clot (2 x 2 x 2 mm for flow velocity test and l x l x l mm for transmitting frequency test) was repeatedly introduced into the model at different settings (23 cm/sec and 40 cm/sec for mean velocity settings; 2 MHz, 4 MHz, and 8 MHz for transmitting frequency settings). An embolus floating at a high flow velocity had a lower increase in total signal intensity and shorter duration of passage than an embolus passing at low flow velocity. The intensity of embolic signals recorded from a probe with lower transmitting frequency was significantly higher than that by a probe with higher frequency. Similarly, the duration of embolic signal was inversely proportional to the transmitting frequency of the probe. 7. Quantitative detection of cerebral emboli from the MCA was studied in 16 patients undergoing cardiac catheterisation. A continuous TCD recording was made throughout the procedure and the occurrence and intensity of embolic signals were examined in relation to different steps of the catheerisation. Embolic signal intensity was also correlated to the in vitro findings. In descending order of frequency, ventriculogram, change of the catheter guidewire, and catheter manipulation contributed to the highest incidence of cerebral emboli and to the highest embolic signal intensities. Embolic signals occurring during catheter insertion and catheter manipulation often showed lower intensities compared to those generated by the injection of normal saline at the level of the ascending aorta or within the left ventricle. The intensities from the former were equal to the intensities caused by atheroma materials (100 mum) in vitro and the intensities from the latter were similar to the intensities produced by microbubbles (30 mum) in vitro