| 1. |
- Ressner, Marcus
(author)
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On Nonlinear Acoustics in Contrast Echocardiography
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Ultrasound is one of the most commonly used noninvasive medical imaging techniques. Ultrasound contrast agents (UCA), consisting of encapsulated gas-filled microbubbles, have shown to increase the diagnostic precision in selected low echogenic patients. UCA also holds promise for bedside evaluation of myocardial perfusion quantification, but is not yet reproducible and specific enough for clinical use. In addition risks have been addressed when used, as first recommended, together with high mechanical index (MI) for reperfusion assessment by contrast destruction. We clinically observed increased myocardial velocities after UCA-administration when applied simultaneously with color tissue Doppler imaging (CTDI) arising the question if this increase was due to physiological factors or physical changes in the backscattered signals when UCA were present. The aims of the thesis was to explain this velocity shift and simultaneously to contribute to a future safe and contrast specific application by further characterizing the non-linear acoustic properties of UCA when located in an acoustic field. Of specific interest was to evaluate in which way nonlinear wave propagation affects the response from UCA and if a change in pulse shape, length or polarity can be utilized to increase the nonlinear signal contribution. Twelve patients with ischemic heart disease were examined with CTDI before and after UCA-administration in order to verify the change in peak systolic velocity. An experimental in vitro model including flow and tissue phantoms for UCA was established for CTDI. Raw data from single-element transducers and clinical ultrasound systems were collected for three different UCA and analyzed to determine if the observed velocity shift could be reproduced in vitro and to find a possible cause. Our results show in vivo and in vitro that UCA will affect the autocorrelation phase shift estimator used for CTDI in terms of contribution from rupturing UCA microbubbles, which explains the velocity shift. CTDI during contrast infusion should therefore be avoided unless it can be performed at low MI where the majority of the UCA are intact. The computational model for spatial superposition of attenuated waves was modified to include an operator for pulse distortion from nonlinear wave propagation. The Matlab™ toolbox Bubblesim based on a modified Rayleigh-Plesset-equation and with insonation parameters such as frequency, pressure amplitude, pulse length and polarity was used to study the response from single microbubbles either for simulated pulses or for pulses generated by clinical ultrasound systems and single element transducers. The combination of the two models also provided a computational platform to asses pulse distortion from nonlinear wave propagation, the response of the UCA bubble and the linear backscatter of the low amplitude bubble echo. When evaluating the harmonic response in simulations and in vitro, the interaction of the excitation pulses with the contrast bubbles was identified as the main cause of nonlinear scattering, and a 2-3 dB increase of the second harmonic amplitude depends on nonlinear distortions of the incident pulse. By applying small changes of short (<3.5 cycles) and fragmented transmitted wideband pulses of 2-2.5 MHz, it is shown that inverted pulse polarity considerably modulates power without affecting a low and safe MI (<0.4), and the results lodged promise to further to enhance a contrast response.
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| 2. |
- Abtahi, Farhad, 1981-
(author)
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Towards Heart Rate Variability Tools in P-Health : Pervasive, Preventive, Predictive and Personalized
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.
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| 3. |
- Chen, Hongjian
(author)
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Exploring Polymer-Shelled Microbubbles: Detection Modeling and Application
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Ultrasound imaging (US) is widely used in clinical practice. Given the low cost and easy access to the ultrasound machine, US has a great potential to improve the health care condition for the majority of the population in the world. The US could be significantly improved by injecting ultrasound contrast agents to opacify the bloodstream. The polymer-shelled microbubbles (MB) are promising candidates for the next generation ultrasound contrast agent. In the current doctoral work, one of the polymer-shelled MBs, the polyvinyl alcohol (PVA) MB was investigated.In Study I and Study II, I developed a novel contrast pulse sequence, CPS4, to efficiently detect the PVA MBs. The CPS4 is a combination of the sub-harmonic (SH), ultra-harmonic, and pulse inversion techniques. The comparison of the performance of each individual technique and CPS4 was carried out in a tissue-mimicking phantom. The CPS4 demonstrated the highest contrast-to-tissue ratio among all four imaging techniques. However, the SH response of the CPS4 was not fully excited. The high SH pressure threshold, above which the SH response is generated, was suspected to be the reason for the weak SH signal. Therefore, I wanted to optimize the performance of the CPS4 for the PVA MBs detection by boosting the SH signal. The optimization strategy was to lower the frequency-dependent SH threshold by setting the SH excitation frequency, which is the frequency of the ultrasound wave that excites the SH response, at the damped resonance frequency of the PVA MBs. To estimate the damped resonance frequency, a mathematical model based on the Church’s model with frequency-dependent material properties was proposed. The mechanical parameters of the new model were estimated by fitting the measured attenuation coefficient of the PVA MBs suspension with the simulated one. The calibrated model was employed to predict the damped resonance frequency of the PVA MBs, i.e., the optimized SH excitation frequency for the CPS4. The performance of the CPS4 was evaluated in-vitro, driving the system at four SH excitation frequencies in the proximity of the damped resonance frequency of the PVA MBs suspension. The best performance was observed at the SH excitation frequency of 11.25 MHz, which is in line with the simulated damped resonance frequency of 10.85 MHz. The in vitro experiment also revealed that the small particles constituting the artificial blood solution might interact with the PVA MBs and decreased the response echoes in a nonlinear and frequency-dependent fashion. Thus, more efforts are needed to move our model-guided optimization methods for the CPS4 towards clinical application.In Study III, I modified the PVA MBs to support the dual-modal imaging of CT and US. The main idea of the modification is to incorporate the gold nanoparticles with the PVA MBs. The success of the modification is dependent on the amount of the gold nanoparticles carried by the modified PVA MBs. Two routes were proposed to fabricate candidates that support dual-modal imaging. In the first route, the gold nanoparticles were added during the fabrication of PVA MBs. Thus, the gold nanoparticles were embedded in the PVA shell during its formation (candidate named AuNP-S-MB). In the second route, the gold nanoparticles were loaded into the core of the PVA MBs, substituting air by increasing the permeability (candidate named AuNP-Capsule). The CT revealed an insignificant amount of gold nanoparticles was embedded in the shell of AuNP-S-MB, while detectable gold nanoparticles were loaded into AuNP-Capsule. Moreover, the CT-number of the surrounding liquid of AuNP-Capsule is low, i.e., the gold nanoparticles were locked in the AuNP-Capsule, making the second route a promising step towards the further development of the dual-modal contrast agent for CT and US.In Study IV, I studied the effect of PVA MBs on the cavitation flows in microscale. The cavitation in clinical practices generates great pressure, which might be harmful and damage cells or beneficial and facilitate the treatment. A better understanding of cavitation generation mechanisms could avoid harmful cavitation, increase the safety of the clinical protocol, and increase the therapeutic cavitation, empower the treatments. Therefore, the effect of PVA MBs on cavitation is of great interest. More specifically, the effect of PVA MBs on the hydrodynamic cavitation was studied. Three microfluidic devices with different wall roughness and structure were fabricated. Two working fluids, PVA MBs suspension and water, were driven with controlled pressure through different microfluidic devices. The high-speed visualization revealed that the PVA MBs trigger the inception of hydrodynamic cavitation at a lower upstream pressure and enhance the cavitation flow in all three microfluidic devices. Furthermore, it takes a longer time for the cavitation bubbles to disappear in the PVA MB suspension.To conclude the doctoral work, I developed a novel detection sequence, CPS4, optimized it for PVA MBs with a model-guided method, modified the PVA MB to extend its application, and studied the effect of PVA MB on hydrodynamic cavitation. The work promotes the PVA MBs for pre-clinical study, as well as provides an insight into the studies of other clinically approved ultrasound contrast agents. The methodology developed and presented within the thesis can be transferred to other clinically approved ultrasound contrast agents. For instance, the CPS4 and model-guided optimization method could be employed to improve CPS4 to other ultrasound contrast agents.
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| 4. |
- Ghareh Baghi, Ghareh Baghi
(author)
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Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.
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| 5. |
- Hübbert, Laila
(author)
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Between the Probe and the Pump : An experimental study on cardiac performance analysis based on Echocardiography, tissue and laser Doppler
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Echocardiography is an ultrasound-based bedside, non-invasive and easily available cardiac diagnostic technique visualising the heart’s morphology and function. Quantification of cardiac wall motion can be measured with the tissue Doppler Imaging (TDI) modality which provides in humans a high diagnostic capacity to differentiate healthy from diseased myocardium with reduced function. Heart failure, as a consequence of, for example, myocardial or ischaemic heart disease, demands both bedside and intraoperative diagnostic procedures for myocardial functional and perfusion assessment. In the late stages of heart failure cardiac left ventricular assist devices (LVAD) may be the treatment of choice. Such new technologies are commonly evaluated in large animals before application in humans is accepted.With the aim of evaluating TDI´s applicability and feasibility in a large animal model 21 calves (aged 3 months and weight around 70 kg), were studied with colour TDI (Paper I). Analysis was performed either during coronary artery occlusion when the laser Doppler perfusion imaging technique (LDMP) was refined (Paper II), or after implantation of the LVAD, Heart Mate II® (Papers III, IV). All animals were haemodynamically monitored (pressures, flows, heart rate) and ECG was continuously recorded. Transthoracic and epicardial echocardiography (TTE) were performed before and after sternotomy and intraoperatively during experimental progressive heart failure. Heart chamber dimensions, native stroke volume, systolic and diastolic regional basal myocardial peak velocities (cm/s; systolic S´, early diastolic E´, and atrial A´, strain (%), strain rate (s-1) and displacement (mm) were determined. Second harmonic imaging (SHI) was applied in order to better visualise air bubbles (Paper IV).In Paper I compiled baseline values were established before and after sternotomy for central haemodynamic and echocardiographic parameters, including the TDI myocardial motion variables velocity, strain rate, strain and displacement. Blood pressure and heart rate changed significantly after sternotomy, but the TDI derived data did not change significantly.In Paper II we report that movement artifacts of the laser Doppler myocardial perfusion measurements can be reduced, both when myocardium is normally perfused and during coronary occlusion, by using the TDI velocity registrations showing wall motion to be minimal. The optimum interval depends on the application but late systole as well as late diastole is preferred.After LVAD implantation in Paper III the flow characteristics and myocardial motion during variations in afterload TDI show that myocardial velocities decrease concomitantly with myocardial depression and are significantly correlated to native stroke volume, heart rate, systemic arterial resistance and cardiac output, but not with left ventricular size, fractional shortening or pump speed. Echocardiography together with TDI thereby offers additional means for monitoring and quantifying residual myocardial function during LVAD treatment.SHI is superior in the early detection of single air-bubbles in the ascending aorta prior to significant air embolism during manipulation of the LVAD pump speed, as shown in Paper IV. A prompt decrease in size of the left atrium during speed adjustment may be a warning that massive air embolism is imminent whereas the commonly used left atrial pressure not provide the same warning.
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| 6. |
- Bak, Zoltan, 1950-
(author)
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Cardiovascular response to hyperoxemia, hemodilution and burns : a clinical and experimental study
- 2007
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Doctoral thesis (other academic/artistic)abstract
- The last decades less invasive monitoring and analytical tools have been developed for the evaluation of myocardial mechanics in clinical praxis. In critical care, these are longed-for complements to pulmonary artery catheter monitoring, additionally offering previously inaccessible information. This work is aimed, during fluid-replacement and oxygen therapy, to determine the physiological interface of ventricular and vascular mechanical properties, which result in the transfer of blood from the heart to appropriate circulatory beds. In prospective clinical studies we investigated previously cardiovascular healthy adults during hyperoxemia, and during preoperative acute normovolemic hemodilution or early fluid resuscitation of severe burn victims. Echocardiography was used in all studies, transthoracic for healthy volunteers and transesophageal for patients. For vascular parameters and for control purposes pulmonary artery Swan-Ganz catheter, calibrated external pulse recordings, whole body impedance cardiography, and transpulmonel thermodilution method were applied.We detected no significant change in blood pressure or heart rate, the two most often used parameters for patient monitoring. During preoperative acute normovolemic hemodilution a reduction of hemoglobin to 80 g/l did not compromise systolic or diastolic myocardial function. Cardiac volumes and flow increased with a concomitant fall in systemic vascular resistance while oxygen delivery seemed maintained. Supplemental oxygen therapy resulted in a linear dose-response between arterial oxygen and cardiovascular parameters, suggesting a direct vascular effect. Cardiac flow decreased and vascular resistance increased from hyperoxemia, and a decrease of venous return implied extracardial blood-pooling. Severe burns result in hypovolemic shock if not properly treated. The commonly used Parkland fluid replacement strategy, with urinary output and mean arterial pressure as endpoints, has recently been questioned. Applying this strategy, only transient early central hypovolemia was recorded, while dimensional preload, global left ventricular systolic function and oxygen delivery or consumption remained within normal ranges during the first 36 hours after accident. Signs of restrictive left ventricular diastolic function were detected in all patients and regional unstable systolic dysfunction was recognized in every other patient, and was consistent with myocardial marker leakage. Severe burns thereby cause myocardial stiffness and systolic regional dysfunction, which may not be prevented only by central normovolemia and adequate oxygenation.
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| 7. |
- Bäcklin, Emelie, et al.
(author)
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Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography
- 2024
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 44:4, s. 340-348
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Journal article (peer-reviewed)abstract
- BackgroundComputed tomography (CT) offers pulmonary volumetric quantification but is not commonly used in healthy individuals due to radiation concerns. Chronic airflow limitation (CAL) is one of the diagnostic criteria for chronic obstructive pulmonary disease (COPD), where early diagnosis is important. Our aim was to present reference values for chest CT volumetric and radiodensity measurements and explore their potential in detecting early signs of CAL.MethodsFrom the population-based Swedish CArdioPulmonarybioImage Study (SCAPIS), 294 participants aged 50–64, were categorized into non-CAL (n = 258) and CAL (n = 36) groups based on spirometry. From inspiratory and expiratory CT images we compared lung volumes, mean lung density (MLD), percentage of low attenuation volume (LAV%) and LAV cluster volume between groups, and against reference values from static pulmonary function test (PFT).ResultsThe CAL group exhibited larger lung volumes, higher LAV%, increased LAV cluster volume and lower MLD compared to the non-CAL group. Lung volumes significantly deviated from PFT values. Expiratory measurements yielded more reliable results for identifying CAL compared to inspiratory. Using a cut-off value of 0.6 for expiratory LAV%, we achieved sensitivity, specificity and positive/negative predictive values of 72%, 85% and 40%/96%, respectively.ConclusionWe present volumetric reference values from inspiratory and expiratory chest CT images for a middle-aged healthy cohort. These results are not directly comparable to those from PFTs. Measures of MLD and LAV can be valuable in the evaluation of suspected CAL. Further validation and refinement are necessary to demonstrate its potential as a decision support tool for early detection of COPD.
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