Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography.

BACKGROUND: Computed 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. METHODS: From 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). RESULTS: The 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. CONCLUSION: We 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.

Effects of thoracic epidural analgesia on exercise-induced myocardial ischaemia in refractory angina pectoris.

BACKGROUND: Thoracic epidural analgesia (TEDA) was offered to patients with refractory angina pectoris. Our primary objectives were to evaluate TEDAs´ influence on quality of life (QoL, base for power analysis), and hypothesising that TEDA with bupivacaine during 1 month counteracts exercise-induced myocardial hypoperfusion and increase physical performance. METHODS: Patients with refractory angina and exercise inducible hypoperfusion, as demonstrated by myocardial perfusion imaging (MPI), were randomised to 1-month treatment with TEDA with bupivacaine (B-group, n = 9) or saline (P-group, n = 10) in a double-blind fashion. MPI and bicycle ergometry were performed before TEDA and after 1 month while subjective QoL on a visual analogue scale (VAS) reported by the patients was checked weekly. RESULTS: During this month VAS (mean [95%CI]) increased similarly in both groups (B-group from 33 [18-50] to 54 [30-78] P < 0.05; P-group from 40 [19-61] to 48 [25-70] P < 0.05). The B-group reduced their exertional-induced myocardial hypoperfusion (from 32% [12-52] to 21% [3-39]; n = 9; P < 0.05), while the P-group showed no significant change (before 21% [6-35]; at 1 month 23% [6-40]; n = 10). MPI at rest did not change and no improvement in physical performance was detected in neither of the groups. CONCLUSIONS: In refractory angina, TEDA with bupivacaine inhibits myocardial ischaemia in contrast to TEDA with saline. Regardless of whether bupivacaine or saline is applied intermittently every day, TEDA during 1 month improves the quality of life and reduces angina, even when physical performance remains low. A significant placebo effect has to be considered.

MET-values of standardised activities in relation to body fat: studies in pregnant and non-pregnant women.

BACKGROUND: Physical activity is associated with health in women. Published MET-values (MET: metabolic equivalent of task) may assess physical activity and energy expenditure but tend to be too low for subjects with a high total body fat (TBF) content and therefore inappropriate for many contemporary women. The MET-value for an activity is the energy expenditure of a subject performing this activity divided by his/her resting energy expenditure, often assumed to be 4.2 kJ/kg/h. Relationships between TBF and MET have been little studied although overweight and obesity is common in women. Available data indicate that MET-values decrease during pregnancy but more studies in pregnant contemporary women are needed. SUBJECTS AND METHODS: Using indirect calorimetry we measured energy expenditure and assessed MET-values in women, 22 non-pregnant (BMI: 18-34) and 22 in gestational week 32 (non-pregnant BMI: 18-32) when resting, sitting, cycling (30 and 60 watts), walking (3.2 and 5.6 km/h) and running (8 km/h). Relationships between TBF and MET-values were investigated and used to predict modified MET-values. The potential of such values to improve calculations of total energy expenditure of women was investigated. RESULTS: The resting energy expenditure was below 4.2 kJ/kg/h in both groups of women. Women in gestational week 32 had a higher resting energy metabolism (p < 0.001) and 7-15% lower MET-values (p < 0.05) than non-pregnant women. MET-values of all activities were correlated with TBF (p < 0.05) in non-pregnant women and modified MET-values improved estimates of total energy expenditure in such women. In pregnant women, correlations (p ≤ 0.03) between TBF and MET were found for running (8 km/h) and for walking at 5.6 km/h. CONCLUSIONS: Our results are relevant when attempts are made to modify the MET-system in contemporary pregnant and non-pregnant women. MET-values were decreased in gestational week 32, mainly due to an increased resting energy metabolism and studies describing how body composition affects the one MET-value (i.e. the resting energy metabolism in kJ/kg/h) during pregnancy are warranted. Studies of how pregnancy and TBF affect MET-values of high intensity activities are also needed. Corrections based on TBF may have a potential to improve the MET-system in non-pregnant women.

Investigation of polymer-shelled microbubble motions in acoustophoresis.

The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a red blood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acoustic standing-wave field and to compare the corresponding movements of solid polymer microbeads. The experimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with a resonance frequency of about 2.8MHz. The microfluidic channel consists of a rectangular chamber with a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one full wave ultrasound of a standing-wave pattern with two pressure nodes at w/4 and 3w/4 and three antinodes at 0, w/2, and w. The peak-to-peak amplitude of the electrical potential over the PZT was varied between 1 and 10V. The study is limited to no-flow condition. From Gor'kov's potential equation, the acoustic contrast factor, Φ, for the polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstrate that the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes. This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similar to what has been described for other acoustic contrast particles with a negative Φ. First, primary radiation forces dragged the polymer-shelled microbubbles into proximity with each other at the pressure antinode planes. Then, primary and secondary radiation forces caused them to quickly aggregate at different spots along the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter than that for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelled microbubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1V. In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negative acoustic contrast factor particles and thus can be trapped at the antinode plane and thereby separated from particles having a positive acoustic contrast factor, such as for example solid particles and cells. This phenomenon could be utilized in exploring future applications, such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.

High variability in strain estimation errors when using a commercial ultrasound speckle tracking algorithm on tendon tissue.

BACKGROUND: Ultrasound speckle tracking offers a non-invasive way of studying strain in the free Achilles tendon where no anatomical landmarks are available for tracking. This provides new possibilities for studying injury mechanisms during sport activity and the effects of shoes, orthotic devices, and rehabilitation protocols on tendon biomechanics. PURPOSE: To investigate the feasibility of using a commercial ultrasound speckle tracking algorithm for assessing strain in tendon tissue. MATERIAL AND METHODS: A polyvinyl alcohol (PVA) phantom, three porcine tendons, and a human Achilles tendon were mounted in a materials testing machine and loaded to 4% peak strain. Ultrasound long-axis cine-loops of the samples were recorded. Speckle tracking analysis of axial strain was performed using a commercial speckle tracking software. Estimated strain was then compared to reference strain known from the materials testing machine. Two frame rates and two region of interest (ROI) sizes were evaluated. RESULTS: Best agreement between estimated strain and reference strain was found in the PVA phantom (absolute error in peak strain: 0.21 ± 0.08%). The absolute error in peak strain varied between 0.72 ± 0.65% and 10.64 ± 3.40% in the different tendon samples. Strain determined with a frame rate of 39.4 Hz had lower errors than 78.6 Hz as was the case with a 22 mm compared to an 11 mm ROI. CONCLUSION: Errors in peak strain estimation showed high variability between tendon samples and were large in relation to strain levels previously described in the Achilles tendon.

In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.

OBJECTIVES: Quantification of myocardial perfusion by contrast echocardiography remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled. To contribute toward an improvement, we developed a contrast echocardiographic perfusion imaging platform based on an isolated rat heart coupled to an ultrasound scanner. METHODS: Perfusion was assessed by using 3 different types of contrast agents: dextran-based Promiten (Meda AB, Solna, Sweden), phospholipid-shelled SonoVue (Bracco Diagnostics, Inc, Princeton, NJ), and polymer-shelled MB-pH5-RT, developed in-house. The myocardial video intensity was monitored over time from contrast agent administration to peak, and 2 characteristic constants were calculated by using an exponential fit: A, representing capillary volume; and ß, representing inflow velocity. RESULTS: Acquired experimental evidence demonstrates that the application of all 3 contrast agents allows sonographic estimation of myocardial perfusion in the isolated rat heart. Video intensity maps show that an increase in contrast concentration increases the late-plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to A × ß, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by a flowmeter attached to the aortic cannula. CONCLUSIONS: The contrast echocardiographic perfusion imaging platform described holds promise for standardized evaluation and optimization of contrast perfusion ultrasound imaging in which real-time inflow curves at low acoustic power semiquantitatively reflect coronary flow.

A novel method for discrimination between innocent and pathological heart murmurs.

This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice.

The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 µm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs' suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6-8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs.

Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: an acoustic characterization and optical visualization.

This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.

Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent.

BACKGROUND: A novel polymer-shelled contrast agent (CA) with multimodal and target-specific potential was developed recently. To determine its ultrasonic diagnostic features, we evaluated the endocardial border delineation as visualized in a porcine model and the concomitant effect on physiological variables. METHODS: Three doses of the novel polymer-shelled CA (1.5 ml, 3 ml, and 5 ml [5 × 10(8) microbubbles (MBs)/ml]) and the commercially available CA SonoVue (1.5 ml [2-5 × 10(8) MBs/ml]) were used. Visual evaluations of ultrasound images of the left ventricle were independently performed by three observers who graded each segment in a 6-segment model as either 0 = not visible, 1 = weakly visible, or 2 = visible. Moreover, the duration of clinically useful contrast enhancement and the left ventricular opacification were determined. During anesthesia, oxygen saturation, heart rate, and arterial pressure were sampled every minute and the effect of injection of CA on these physiological variables was evaluated. RESULTS: The highest dose of the polymer-shelled CA gave results comparable to SonoVue. Thus, no significant difference in the overall segment score distribution (2-47-95 vs. 1-39-104), time for clinically sufficient contrast enhancement (20-40 s for both) and left ventricular overall opacification was found. In contrast, when comparing the endocardial border delineation capacity for different regions SonoVue showed significantly higher segment scores for base and mid, except for the mid region when injecting 1.5 ml of the polymer-shelled CA. Neither high nor low doses of the polymer-shelled CA significantly affected the investigated physiological variables. CONCLUSIONS: This study demonstrated that the novel polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological variables.

Impact of a standardized training program on midwives' ability to assess fetal heart anatomy by ultrasound.

BACKGROUND: Studies of prenatal detection of congenital heart disease (CHD) in the UK, Italy, and Norway indicate that it should be possible to improve the prenatal detection rate of CHD in Sweden. These studies have shown that training programs, visualization of the outflow tracts and color-Doppler all can help to speed up and improve the detection rate and accuracy. We aimed to introduce a more accurate standardized fetal cardiac ultrasound screening protocol in Sweden. METHODS: A novel pedagogical model for training midwives in standardized cardiac imaging was developed, a model using a think-aloud analysis during a pre- and post-course test and a subsequent group reflection. The self-estimated difficulties and knowledge gaps of two experienced and two beginner midwives were identified. A two-day course with mixed lectures, demonstrations and hands-on sessions was followed by a feedback session three months later consisting of an interview and check-up. The long-term effects were tested two years later. RESULTS: At the post-course test the self-assessed uncertainty was lower than at the pre-course test. The qualitative evaluation showed that the color Doppler images were difficult to interpret, but the training seems to have improved their ability to use the new technique. The ability to perform the method remained at the new level at follow-up both three months and two years later. CONCLUSIONS: Our results indicate that by implementing new imaging modalities and providing hands-on training, uncertainty can be reduced and examination time decreased, but they also show that continuous on-site training with clinical and technical back-up is important.

Closed-loop real-time simulation model of hemodynamics and oxygen transport in the cardiovascular system.

BACKGROUND: Computer technology enables realistic simulation of cardiovascular physiology. The increasing number of clinical surgical and medical treatment options imposes a need for better understanding of patient-specific pathology and outcome prediction. METHODS: A distributed lumped parameter real-time closed-loop model with 26 vascular segments, cardiac modelling with time-varying elastance functions and gradually opening and closing valves, the pericardium, intrathoracic pressure, the atrial and ventricular septum, various pathological states and including oxygen transport has been developed. RESULTS: Model output is pressure, volume, flow and oxygen saturation from every cardiac and vascular compartment. The model produces relevant clinical output and validation of quantitative data in normal physiology and qualitative directions in simulation of pathological states show good agreement with published data. CONCLUSION: The results show that it is possible to build a clinically relevant real-time computer simulation model of the normal adult cardiovascular system. It is suggested that understanding qualitative interaction between physiological parameters in health and disease may be improved by using the model, although further model development and validation is needed for quantitative patient-specific outcome prediction.

Effect of long-term thoracic epidural analgesia on refractory angina pectoris: a 10-year experience.

OBJECTIVES: In patients with refractory angina, the adjuvant effects of long-term home self-treatment with thoracic epidural analgesia on angina, quality of life, and safety were evaluated. DESIGN: A prospective, consecutive study. SETTING: A university hospital. PARTICIPANTS AND INTERVENTION: Between January 1998 and August 2007, 152 consecutive patients with refractory angina began treatment with thoracic epidural analgesia by intermittent injections of bupivacaine (139 home treatment and 13 palliative). Data were collected until August 2008; therefore, the follow-up for each patient was between 1 and 9 years. MEASUREMENTS AND MAIN RESULTS: All but 7 of the patients improved symptomatically, and the improvement was maintained throughout the period of treatment (median = 19 months; range, 1 month-8.9 years). After 1 to 2 weeks, the median (interquartile range [IQR]) Canadian Cardiovascular Society angina class decreased from 4.0 (3.0-4.0) to 2.0 (1.0-2.0), the mean ± standard deviation frequency of anginal attacks decreased from 36 ± 19 to 4.4 ± 6.8 a week, the nitroglycerin intake decreased from 27.7 ± 15.7 to 2.7 ± 4.9 a week, and the median (IQR) overall self-rated quality of life assessed by the visual analog scale increased from 25 (20-30) to 70 (50-75) (all p < 0.001). About one-third of the patients had a dislodgement of the epidural catheter. Apart from 1 epidural hematoma that appeared in 1 patient with a previously undiagnosed bleeding defect, no other serious catheter-related complications occurred. CONCLUSIONS: Long-term self-administered home treatment with thoracic epidural analgesia is a safe, widely available adjuvant treatment for patients with severe refractory angina. It produces symptomatic relief of angina and improves quality of life. The technical development of the method to protect the catheter against dislodgement is needed.

Parental support for newborn screening for cystic fibrosis.

AIM: To describe the attitudes among parents towards including cystic fibrosis (CF) in the newborn screening programme and towards the potential knowledge of their own carrier status. METHODS: A questionnaire with three to five response categories and an information leaflet was posted to 143 CF parents, 3 matched diabetes and 3 matched population parents, the response rate being 85%, 74% and 70%, respectively. Comparisons between groups were made with statistical tests for independent groups. RESULTS: Eighty-six percent of CF, 70% of diabetes and 77% of population parents were in favour of newborn screening for CF, 47%, 45% and 50%, respectively, wished to know their CF carrier status. The parental attitude was independent of the age of the child, as well as delay of diagnosis and well-being of the CF child at the time of diagnosis. Sixty percent of the CF parents experienced the diagnosis as delayed. CONCLUSION: Parents in Sweden support CF newborn screening. Half of the parents wanted to know their CF carrier status.

Echo-guided presentation of the aortic valve minimises contrast exposure in transcatheter valve recipients.

OBJECTIVES: We have developed a method using transthoracic echocardiography in establishing optimal visualization of the aortic root, to reduce the amount of contrast medium used in each patient. BACKGROUND: During transcatheter aortic valve implantation, it is necessary to obtain an optimal fluoroscopic projection for deployment of the valve showing the aortic ostium with the three cusps aligned in the beam direction. This may require repeat aortic root angiograms at this stage of the procedure with a high amount of contrast medium with a risk of detrimental influence on renal function. METHODS: We studied the conventional way and an echo guided way to optimize visualisation of the aortic root. Echocardiography was used initially allowing easier alignment of the image intensifier with the transducer's direction. RESULTS: Contrast volumes, radiation/fluoroscopy exposure times, and postoperative creatinine levels were significantly less in patients having the echo-guided orientation of the optimal fluoroscopic angles compared with patients treated with the conventional approach. CONCLUSION: We present a user-friendly echo-guided method to facilitate fluoroscopy adjustment during transcatheter aortic valve implantation. In our series, the amounts of contrast medium and radiation have been significantly reduced, with a concomitant reduction in detrimental effects on renal function in the early postoperative phase.

Second harmonic echocardiography and spontaneous contrast during implantation of a left ventricular assist device.

Implantable mechanical left ventricular assist devices (LVADs) are used as a bridge or alternative to heart transplantation. Peroperative transesophageal echocardiography is commonly applied during implantation. Significant air embolism may occur as a result of air leakage at connections and anastomoses when LV filling becomes inadequate, and this must be prevented. Early suspicion and detection of air is mandatory to avoid negative circulatory effects. We hypothesized that monitoring of heart chamber size and occurrence of single air bubbles using second harmonic imaging (SHI) echocardiography may prevent risk for significant air embolism. After implantation of the LVAD in 10 calves, invasive hemodynamic monitoring and epicardial SHI were performed while increasing pump speed. Air bubbles in the ascending aorta were monitored and the left heart visualized for off-line dimensional analysis. Detection of air bubbles in the ascending aorta preceded their appearance in the left ventricle. They occurred exclusively but not always after a decrease in left atrial (LA) size. Decrease in LA pressure did not predict bubble detection or reduction in LA size. We conclude that SHI detects spontaneous ultrasound contrast during implantation of a LVAD and that a decrease in LA size is a warning that air embolism is imminent.

Hemodynamic changes during resuscitation after burns using the Parkland formula.

BACKGROUND: The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly. METHODS: Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body surface area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints. RESULTS: Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung water: intrathoracal blood volume ratio was increased 12 hours after the burn. CONCLUSIONS: Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.

Contrast biases the autocorrelation phase shift estimation in Doppler tissue imaging.

Quantitative assessment of regional myocardial function at rest and during stress with Doppler tissue imaging (DTI) plays an important role in daily routine echocardiography. However, reliable visual analysis is largely dependent on image quality and adequate border delineation, which still remains a challenge in a significant number of patients. In this respect, an ultrasound contrast agent (UCA) is often used to improve visualization in patients with suboptimal image quality. The knowledge of how DTI measurements will be affected by UCA present in the tissue is therefore of significant importance for an accurate interpretation of local myocardial motion. The aim of this paper was to investigate how signal contribution from UCA and nonlinear wave propagation influence the performance of the autocorrelation phase shift estimator used for DTI applications. Our results are based on model experiments with a clinical 2-D grayscale scanner and computational simulations of the DTI velocity estimator for synthetically-derived pulses, simulated bubble echoes and experimentally-sampled RF data of transmitted pulses and backscattered contrast echoes. The results show that destruction of UCA present in the tissue will give rise to an apparent bidirectional velocity bias of individual velocity estimates, but that spatial averaging of individual velocity measurements within a region-of-interest will result in a negative bias (away from the transducer) of the estimated mean or mean peak velocity. The UCA destruction will also have a significant impact on the measured integrated mean velocity over time, i.e., displacement. To achieve improved visualization with UCA during DTI-examinations, we either recommend that it is performed at low acoustic powers, mechanical index