Managing blood glucose can affect important clinical outcomes during the intraoperative phase of surgery. However, currently available instruments for glucose monitoring during surgery are few and not optimized for the specific application. Here we report an attempt to exploit an enzymatic sensor in a vein replica that could continuously monitor glucose level in an authentic human bloodstream. First, detailed investigations of the superficial venous systems of volunteers were carried out using ocular and palpating examinations, as well as advanced ultrasound measurements. Second, a tubular glucose-sensitive biosensor mimicking a venous system was designed and tested. Almost ideal linear dependence of current output on glucose concentration in phosphate buffer saline was obtained in the range 2.2-22.0 mM, whereas the dependence in human plasma was less linear. Finally, the developed biosensor was investigated in whole blood under homeostatic conditions. A specific correlation was found between the current output and glucose concentration at the initial stage of the biodevice operation. However, with time, blood coagulation during measurements negatively affected the performance of the biodevice. When the experimental results were remodeled to predict the response without the influence of blood coagulation, the sensor output closely followed the blood glucose level.

BackgroundGlobally, hypertension represents an enormous health issue as it is a major, yet modifiable risk factor for developing cardiovascular disease. Recently, chitinase-3-like protein 1 (CHI3L1) was shown to be positively associated with the incidence of hypertension among prehypertensive subjects, and variants of CHI3L1 gene were associated with both CHI3L1-levels and hypertension.PurposeTo explore associations between prevalent hypertension and blood pressure, and 92 proteins with involvement in inflammation and cardiovascular disease.MethodsPlasma samples from 1713 individuals from a Swedish population-based cohort (mean age 67.3±6.0 years; 28.9% women) were analysed with a proximity extension assay panel, consisting of 92 proteins. Prior to all analyses, subjects with prevalent cardiovascular disease, defined as having a history of prevalent coronary or stroke event, were excluded (n=189). Univariate logistic regression models were carried out exploring associations between each of the 92 proteins and prevalent hypertension, defined as systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, or use of antihypertensive treatment (n=1168, 76.4%). Bonferroni-corrected significant associations between proteins and hypertension were further analysed using stepwise selection of covariates, namely age, body mass index, diabetes status, and cystatin C, in logistic regression models. Proteins with significant adjusted associations with prevalent hypertension were further analysed for associations with systolic and diastolic blood pressure individually in stepwise linear regression models. Complete data on all variables were available in 1527 subjects.ResultsSixteen proteins were significantly associated with prevalent hypertension in univariate analyses. After adjustment, three proteins remained significantly associated with prevalent hypertension (i.e., CHI3L1, low-density lipoprotein receptor (LDL receptor) and tissue plasminogen activator (tPA); Table 1). In analyses of associations with systolic blood pressure, CHI3L1 and LDL receptor showed significant associations. In analyses of associations with diastolic blood pressure, CHI3L1, LDL receptor and tPA showed significant associations (Table 1).ConclusionsHigher CHI3L1, tPA and LDL receptor levels were positively associated with prevalent hypertension after multivariable adjustment, among 1527 elderly subjects without established cardiovascular disease. Furthermore, higher CHI3L and LDL receptor levels were positively associated with mean systolic, as well as mean diastolic blood pressure in multivariable analyses.Funding AcknowledgementType of funding sources: Foundation. Main funding source(s): The Swedish Medical Research Council and The Swedish Heart and Lung Foundation

This review maps patterns in research on Challenge Based Learning (CBL) in higher education (HE) between 2009 and 2020. How is CBL defined in HE settings? How is CBL in HE grounded scientifically in the research? The results show a shift of CBL from being a concept coined by a multinational technology company targeting learning in schools, to being embraced by HE, first and foremost as a method for transformation of adult learning. A critical scientifically grounded approach towards learning is however absent or marginally present in the papers reviewed.

Background After completing university education, biomedical laboratory scientists work in clinical laboratories, in biomedical research laboratories, in biotech, and in pharmaceutical companies. Laboratory diagnostics have undergone rapid development over the recent years, with the pace showing no signs of abatement. This rapid development challenges the competence of the staff and will most certainly influence the education of future staff. This study aimed to examine what was considered the necessary competencies needed to pursue a career as a biomedical laboratory scientist. Methods A modified Delphi technique was used, with the panel of experts expressing their views in a series of three questionnaire. Consensus was defined as the point which 75 % or more of the panel participants agreed that a particular competency was necessary. Results The study highlights the perceived importance of mostly generic competencies that relate to quality, quality assurance, and accuracy, as well as different aspects of safety, respect, trustworthiness (towards patients/clients and colleagues), and communication skills. The results also stress the significance of self-awareness and professionality. Conclusions We identified important competencies for biomedical laboratory scientists. Together with complementary information from other sources, i.e., guidelines, laws, and scientific publications, the competencies identified can be used as learning outcomes in a competency-based education to provide students with all the competencies needed to work as professional biomedical laboratory scientists.

AbstractIn Sweden as well as internationally the teaching and research nexus has been described as the defining charac-teristics of higher education promoting generic skills such as information analysis and critical reflection. Vertically Integrated Projects has been proposed as one educational strategy where research and teaching are linked by in-viting students to take active part in actual research projects. The strategy is well aligned to Scholarship of teaching and learning enabling the transition from a teacher-centred accepted knowledge to a student-centred perspective where students are invited as producers of knowledge. The aim of the current study was to explore students’ experiences of participation in a research-based learning activity with academia and industrial partners, designed as a qualitative explorative study using focus group interviews. Findings describe not only factors students find motivating for learning, but also their experience of being part of professional life with its benefits and challenges.

Interprofessional Education (IPE) is essential to prepare future health-care professionals for collaborative practice, but IPE requires evaluation. One psychometrically sound instrument is the Interprofessional Education Collaborative Competence Self-Efficacy Tool consisting of nine items (IPECC-SET 9). This tool does not, to date, exist in a Swedish version. Therefore, the aim of this study was to translate and validate the Swedish version of the IPECC-SET 9. The English version was translated into Swedish and tested among 159 students in the 3-year Bachelor Programs in Nursing and in Biomedical Laboratory Science. The psychometric analysis was guided by a Rasch model, which showed that the items functioned well together, confirming unidimensionality, and that the person misfit was also lower than the set criterion. The separation index was 2.98, and the Rasch-equivalent Cronbach-alpha measure was estimated to .92, supporting internal consistency. No systematic differences on item level in IPECC-SET 9 further supported fairness in testing. The Swedish IPECC-SET 9 demonstrates sound psychometric properties and has the potential to be used as a measure of self-efficacy for competence in interprofessional collaborative practice among health profession students. However, the IPECC-SET 9 is recommended to be further tested in larger samples representing the entirety of health-care teams.

ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ± 9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models.Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant.Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.

Background: Echocardiography is a frequently used imaging modality requiring extensive training to master. In order to develop curriculums and teaching material fully favouring students learning within echocardiography, this study aims to investigate students’ experiences of learning echocardiography, focusing on that which is perceived as the main challenges as well as what might aid learning within the area. The findings could serve as a foundation in the development of new teaching material or curriculums. Methods: A qualitative study was performed with data gathered through two audio-recorded focus group interviews with four third year students from the biomedical laboratory programme at Malmö University in each group. Data was analysed by manifest content analysis. Results: Findings were clustered into two categories reflecting the main findings in the text – practical skills and bridging the theory-practice-gap. Students expressed that main challenges when initially learning echocardiography were the projections and handling the probe as well as connecting ultrasound physics and measurements to practical application. Things that aided their learning were immediate feedback, “playing” with the ultrasound machine, video lectures, the possibility to swiftly alternate between practice and theory as well as the learning by their mistakes in a risk-free environment. Conclusions: This study shows the main challenges when initially learning echocardiography and what might be helpful during the learning process. These findings may be useful when developing curriculums or new teaching material within echocardiography. One suggestion might be to develop digital resources such as virtual laboratories (vLABs).

Background: Long-term intensive training leads to morphological and mechanical changes in the heart generally known as “athlete’s heart”. Previous studies have suggested that the diastolic and systolic function of the ventricles is unaltered in athletes compared to sedentary. The purpose of this study was to investigate myocardial performance index (MPI) by pulsed wave Doppler (PWD) and by tissue Doppler imaging (TDI) in female elite athletes compared to sedentary controls. Methods: The study consisted of 32 athletes (mean age 20 ± 2 years) and 34 sedentary controls (mean age 23 ± 2 years). MPI by PWD and TDI were measured in the left (LV) and right ventricle (RV) in both groups. Moreover, comparisons of MPI by the two methods and between the LV and RV within the two groups were made. Results: There were no significant differences in MPI between athletes and controls (p > 0.05), whereas the LV had significantly higher MPI compared to RV (p < 0.001, in athletes and controls). The agreement and the correlation between the two methods measuring MPI showed low agreement and no correlation (athletes RV r = −0.027, LV r = 0.12; controls RV r = 0.20, LV r = 0.30). Conclusion: The global function of the LV and RV measured by MPI with PWD and TDI is similar in female athletes compared to sedentary controls. Conversely, both MPI by PWD and by TDI shows a significant difference between the LV and RV. However, the agreement and correlation between conventional methods of measuring MPI by PWD compared to MPI by TDI is very poor in both these populations.

Here we report an enzymic fuel cell in a vein replica that generates sustained electricity, enough to power an e-​ink display, in an authentic human blood stream. We also detail a simple and safe approach for fuel cell evaluation under homeostatic conditions. Our results demonstrate proof-​of-​principle operation of a biocompatible and safe biodevice that could be implanted in superficial human veins, which we anticipate to be a starting point for more sophisticated investigations of personal sources of electricity.

AIM: Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. METHODS: A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). RESULTS: Left atrium and left ventricle volumes were significantly (P<0.001) larger in elite female handball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (P<0.001) larger in elite female handball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. CONCLUSION: The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

In this paper we present a model for describing the position distribution of the endocardium in the two-chamber apical long-axis view of the heart in clinical B-mode ultrasound cycles. We propose a novel Bayesian formulation, including priors for spatial and temporal smoothness, and preferred shapes and position. The shape model takes into account both endocardium, atrial region and apex. The likelihood is built using a statistical signal model, which attempts to closely model a censored signal. In addition, the use of a censored Gamma mixture model with unknown censoring point, to handle artefacts resulting from left-censoring of the in US clinical B-mode, is to our knowledge novel. The posterior density is sampled by the Gibbs method to estimate the expected latent variable representation of the endocardium, which we call the Bayesian Probability Map; the map describes the probability of pixels being classified as being within the endocardium. The regularization parameters of the model are estimated by cross-validation, and the results are compared against the two-chamber apical model of Chen et al.

BACKGROUND: Epidemiological studies have shown considerable heritability of blood pressure, thus suggesting a role for genetic factors. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the NPPA locus gene with higher levels of circulating atrial natriuretic peptide as well as with lower intra individual blood pressure, but up to date, no association between rs5068 and cardiac organ damage, i.e. left ventricular hypertrophy, has been accounted for in humans. Our sought explore if rs5068 is associated with left ventricular hypertrophy as measured by echocardiographic examination in a non-diabetic population. METHODS: 968 non-diabetic individuals from the Malmo Preventive Project (mean age 67 years; 31% women) were genotyped and examined with echocardiography. Logistic regression was used to adjust for covariates. RESULTS: The minor allele of rs5068 was associated with decreased prevalence of left ventricular hypertrophy (p = 0.021) after adjustment for sex and age. In the multivariate logistic analysis including; age, sex, systolic blood pressure, antihypertensive and/or cardioprotective treatment, body mass index and fasting plasma glucose, the association of rs5068 with left ventricular hypertrophy was, as expected, attenuated (p = 0.061). CONCLUSION: In a non-diabetic population, the minor allele of rs5068 was associated with lower left ventricular mass. These findings suggest that rs5068, or genetic variants in linkage disequilibrium, might affect susceptibility to left ventricular hypertrophy and support the possible protective role of natriuretic peptides.

BACKGROUND: Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. The aim of this study was to investigate mitral annular plane systolic excursion (MAPSE) in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome. METHODS: In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) measuring LV function was performed within 12 hours after admission and daily for a 7-day observation period. TTE and laboratory measurements were related to 28-day mortality. RESULTS: MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (é, E/é) and high-sensitive troponin T (hsTNT) (p< 0.001, p= 0.039, p= 0.009, p= 0.003 respectively) whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury. Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5-11] versus 11 [IQR 8.9-13] mm; p= 0.028). Other univariate predictors were age (p=0.033), hsTNT (p=0.014) and Sequential Organ Failure Assessment (SOFA) scores (p=0.007). By multivariate analysis MAPSE (OR 0.6 (95% CI 0.5- 0.9), p= 0.015) and SOFA score (OR 1.6 (95% CI 1.1- 2.3), p= 0.018) were identified as independent predictors of mortality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p<0.05 at day 1-2, 4-6). CONCLUSIONS: MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality.

INTRODUCTION. Assessing left ventricular (LV) dysfunction by echocardiography in ICU patients is common. In patients with cardiovascular disease mitral annular plane sys- tolic excursion (MAPSE) is known to be more sensitive in detecting abnormalities in LV function at an early stage, easily obtainable and related to prognosis. OBJECTIVES. The aim of this study was to investigate MAPSE in critically ill patients with shock and its relation to LV systolic and diastolic function, myocardial injury and to outcome. METHODS. In a prospective, observational, cohort study we enrolled 50 patients with SIRS and shock despite fluid resuscitation. Transthoracic echocardiography (TTE) mea- suring LV systolic and diastolic function was performed within 12 h after admission and daily for a 7-day observation period. TTE and laboratory measurements (high-sensitive troponin T (hsTNT), B-natriuretic peptide [BNP]) were related to 28-day mortality. Spearman rank correlation was used. RESULTS. MAPSE on day 1 correlated significantly with LV ejection fraction (LVEF), tissue Doppler indices of LV diastolic function (e ́ , E/e ́ ) and hsTNT whereas LVEF did not correlate significantly with any marker of LV diastolic function or myocardial injury; tissue Doppler of LV systolic function (TDIs) correlated significantly with LVEF and e ́ (Table 1). Compared to survivors, non-survivors had a significantly lower MAPSE (8 [IQR 7.5–11] versus 11 [IQR 8.9–13] mm; p = 0.028). Other univariate predictors were age (p = 0.033), hsTNT (p = 0.014) and Sequential Organ Failure Assessment (SOFA) scores (p = 0.007). By multivariate analysis MAPSE (OR 0.6 (95 % CI 0.5–0.9) p = 0.015) and SOFA score (OR 1.6 (95 % CI 1.1–2.3) p = 0.018) were identified as independent predictors of mor- tality. Daily measurements showed that MAPSE, as sole echocardiographic marker, was significantly lower in most days in non-survivors (p \ 0.05 at day 1–2, 4–6). CONCLUSIONS. MAPSE seemed to reflect LV systolic and diastolic function as well as myocardial injury in critically ill patients with shock. The combination of MAPSE and SOFA added to the predictive value for 28-day mortality

BACKGROUND: Left ventricular (LV) dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. METHODS: A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP), highsensitive troponin T (hsTNT) and transthoracic echocardiography (TTE) were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm), peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler indices (e, a, E/e) and left atrial volume (La volume). APACHE II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores were calculated. RESULTS: hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/e (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and nonsurvivors did not differ regarding BNP (p = 0.26) or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable logistic regression analysis identified hsTNT (p = 0.010) as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5). CONCLUSIONS: hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.

INTRODUCTION: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). METHODS: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). RESULTS: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). CONCLUSIONS: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.

Background Left ventricular (LV) diastolic dysfunction has been associated with impaired glucometabolic status. However, studies of older subjects are lacking. We examined associations between echocardiographic indices of LV diastolic function and LV mass index (LVMI) and glucometabolic status among middle-aged and elderly subjects free from heart disease, hypothesizing that the associations would be comparative to younger cohorts. Methods We examined the Age Gene/Environment Susceptibility Reykjavik Study (Iceland; n = 607, 76 ± 6 years) and the Malmö Preventive Project Re-Examination Study (MPP-RES) cohorts (Sweden; n = 1,519, 67 ± 6 years), evaluating associations with multivariable regression analysis. Results In the Age Gene/Environment Susceptibility Reykjavik Study, LVMI was positively correlated with glycosylated hemoglobin (HbA1c) (P = .001). Otherwise, echocardiographic variables were not associated with glucometabolic status. In the MPP-RES, LVMI increased with increasing glucometabolic disturbance among both older (70-80 years) and middle-aged (57-69 years) subjects. Among older subjects, HbA1c was positively correlated with 2 variables reflecting LV diastolic function: late transmitral peak flow velocity (A) (P = .001) and early transmitral peak flow velocity (E)/early diastolic peak tissue velocity (Em) (P = .046). In middle-aged MPP-RES subjects, increasing glucometabolic disturbance was correlated with increasing late diastolic peak tissue velocity (Am) (P = .002) and, after age adjustment, with increasing A (P = .001) and decreasing Em/Am (P = .009). With age adjustment, Am and A were positively correlated with fasting glucose and HbA1c. Conclusions Contrary to our hypothesis, in 2 independent cohorts of older individuals, associations between glucometabolic status and LV diastolic function were generally weak. These contrast with previous reports, as well as with observations among middle-aged subjects in the present study. Changes in LV diastolic function may be more age-related than associated with glucose metabolism in older subjects.

SUMMARY BACKGROUND: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast((R))-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. METHODS: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast-generated A, beta and Axbeta images, at different time points during rest and stress, were blindly compared to SPECT. RESULTS: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, beta and Axbeta image interpretation significantly identified ischaemia in all territories (area under the curve 0.66-0.80, P = 0.001-0.05). Combined A, beta and Axbeta image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0.63; P<0.001. CONCLUSION: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast-generated images, especially by combined A, beta and Axbeta image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.

BACKGROUND: Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF. METHODS: A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter- and intraobserver variability was analyzed. RESULTS: SB modality showed significantly lower inter- and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p<0.001) and EF (p<0.05) with SB in comparison to 4B in group B. CONCLUSION: Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes.

In this paper we propose a Bayesian approach for describing the position distribution of the endocardium in cardiac ultrasound image sequences. The problem is formulated using a latent variable model, which represents the inside and outside of the endocardium, for which the posterior density is estimated. As the Rayleigh distribution has been previously shown to be a suitable model for blood and tissue in cardiac ultrasound image, we start our construction by assuming a Rayleigh mixture model and estimate its parameters by expectation maximization. The model is refined by incorporating priors for spatial and temporal smoothness, in the form of total variation, preferred shapes and position, by using the principal components and location distribution of manually segmented training shapes. The posterior density is sampled by a Gibbs method to estimate the expected latent variable image which we call the Bayesian Probability Map, since it describes the probability of pixels being classified as either heart tissue or within the endocardium. Our experiments showed promising results indicating the usefulness of the Bayesian Probability Maps for the clinician since, instead of producing a single segmenting curve, it highlights the uncertain areas and suggests possible segmentations.

Abstract. In this paper we present improvements to our Bayesian approach for describing the position distribution of the endocardium in cardiac ultrasound image sequences. The problem is represented as a latent variable model, which represents the inside and outside of the endocardium, for which the posterior density is estimated. We start our construction by assuming a three-component Rayleigh mixture model: for blood, echocardiographic artifacts, and tissue. The Rayleigh distribution has been previously shown to be a suitable model for blood and tissue in cardiac ultrasound images. From the mixture model parameters we build a latent variable model, with two realizations: tissue and endocardium. The model is refined by incorporating priors for spatial and temporal smoothness, in the form of total variation, connectivity, preferred shapes and position, by using the principal components and location distribution of manually segmented training shapes. The posterior density is sampled by a Gibbs method to estimate the expected latent variable image which we call the Bayesian ProbabilityMap, since it describes the probability of pixels being classified as either heart tissue or within the endocardium. By sampling the translation distribution of the latent variables, we improve the convergence rate of the algorithm. Our experiments show promising results indicating the usefulness of the Bayesian Probability Maps for the clinician since, instead of producing a single segmenting curve, it highlights the uncertain areas and suggests possible segmentations.

Background: Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia. Methods: Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue® infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest. Results: In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed evidence of ischemia in 13 out of 50 patients. There was no significant difference between AM and HR in detecting ischemia (p = 0.08). The agreement for AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and 0.75, respectively (p < 0.001). Conclusion: There was no significant difference between AM and HR in correctly detecting myocardial ischemia as judged by SPECT. This suggests that different types of RTP modalities give comparable data during RTP-ASE in patients with known or suspected CAD.

Aims: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast® software, generating values of peak signal intensity (A), myocardial blood flow velocity (β) and myocardial blood flow (Axβ). By comparing rest and stress values, their respective reserve values (A-r, β-r, Axβ-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast® quantification, compared to visual perfusion evaluation with 99mTc-tetrofosmin singlephoton emission computed tomography (SPECT). Methods and Results: Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue® infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast® quantification, were blindly compared to one another and to SPECT, at different time points off-line. We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for β-r and Axβ-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both β-r and Axβ- r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories. Conclusion: In this agreement study with SPECT, RTP-ASE Qontrast® quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.

Background: Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method. Methods: Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE. Results: There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 ± 3.7% and -0.2 ± 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP. Conclusion: Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant.

BACKGROUND: Relatively limited and conflicting data are available on the effects of cardiac resynchronization therapy (CRT) on coronary blood flow (CBF). AIMS: To investigate changes in the left anterior descending coronary artery (LAD) flow under different CRT pacing modes by means of transthoracic Doppler echocardiography (TTE). METHODS: Twenty-two responders to CRT (67+/-11 years) with idiopathic dilated cardiomyopathy underwent TTE assessment of LAD flow and Tissue Velocity Imaging during 4 programming modes: intrinsic conduction (IC), right ventricular pacing (RV), simultaneous biventricular pacing (BVP), BVP with left ventricular (LV) pre-activation. RESULTS: Mean coronary flow velocity (CFV) was increased by simultaneous BVP (p=0.0063 vs. IC) and BVP with LV pre-activation (p<0.0001 vs. IC; p=0.027 vs. simultaneous BVP). Peak CFV and LAD flow velocity/time integral were highest during BVP with LV pre-activation. A reduction in septal-to-lateral delay and an increase in peak systolic velocity in the basal septum were observed during simultaneous BVP and BVP with LV pre-activation. CONCLUSIONS: In CRT responders with idiopathic dilated cardiomyopathy, an increase in LAD flow, assessed by TTE, was observed during simultaneous BVP and BVP with LV pre-activation. This was associated with an improvement in regional myocardial contraction and a decrease in intraventricular dyssynchrony.

BACKGROUND: This study explores the feasibility of non-invasive evaluation of left ventricular (LV) flow-volume dynamics using 3-dimensional (3D) echocardiography, and the capacity of such an approach to identify altered LV hemodynamic states caused by valvular abnormalities. METHODS: Thirty-one patients with moderate-severe aortic (AS) and mitral (MS) stenoses (21 and 10 patients, respectively) and 10 healthy volunteers underwent 3D echocardiography with full volume acquisition using Philips Sonos 7500 equipment. The digital 3D data were post- processed using TomTec software. LV flow-volume loops were subsequently constructed for each subject by plotting instantaneous LV volume data sampled throughout the cardiac cycle vs. their first derivative representing LV flow. After correction for body surface area, an average flow-volume loop was calculated for each subject group. RESULTS: Flow-volume loops were obtainable in all subjects, except 3 patients with AS. The flow-volume diagrams displayed clear differences in the form and position of the loops between normal individuals and the respective patient groups. In patients with AS, an "obstructive" pattern was observed, with lower flow values during early systole and larger end-systolic volume. On the other hand, patients with MS displayed a "restrictive" flow-volume pattern, with reduced diastolic filling and smaller end-diastolic volume. CONCLUSION: Non-invasive evaluation of LV flow-volume dynamics using 3D-echocardiographic data is technically possible and the approach has a capacity to identify certain specific types of alteration of LV flow-volume pattern caused by valvular abnormalities, thus reflecting underlying hemodynamic states specific for these abnormalities.

Echocardiography is an ideal clinical method for obtaining information about morphology and function of the heart. Echocardiography is more accessible, mobile and inexpensive compared to other imaging techniques and has become the perhaps most used diagnostic method in cardiology during recent years. To assess myocardial ischemia, different types of stress echocardiography have been available, where mainly wall motion analysis at rest and stress has been used to evaluate the presence and extent of ischemia. During the last few years, second generation contrast agents have become clinically available. This has improved image quality in echocardiography, which, combined with new ultrasound technical developments, has made it possible to obtain echocardiographic images of myocardial perfusion. When this myocardial contrast echocardiography technique is carried out in real-time, as in the studies of this thesis, it is labelled real-time perfusion (RTP). RTP in combination of adenosine stress (RTP-ASE) has the potential to become a valuable clinical tool to evaluate myocardial ischemia. If proven as accurate as other clinically and scientifically accepted methods, such as 99mTc-sestamibi single-photon emission computed tomography (SPECT), RTP-ASE might become an alternative method. Compared to SPECT, it is more accessible, mobile, inexpensive, and without radiation, compared to dobutamine-atropine stress echocardiography (DSE) it is more tolerable and swifter, and it is more accurate than exercise ECG. In all studies of this thesis, we performed RTP-ASE in patients with known or suspected stable coronary artery disease (CAD), admitted to adenosine SPECT evaluation. Adenosine was infused to provoke relative regional hypo-perfusion in ischemic myocardial territories. Using a SONOS 5500 echocardiography machine, patients underwent RTP imaging during Sonovue infusion, before and throughout the adenosine stress, also used for SPECT. RTP images were stored for later, blinded, off-line analysis. In studies III and IV, the commercially available software Qontrast was used to generate parametric images of myocardial perfusion and quantitative values of perfusion replenishment from RTP-ASE image loops. Method of reference for the ischemia evaluation in the thesis was the presence or absence of reversible ischemia at SPECT. The left ventricular myocardium was divided into three territories corresponding to the distribution territories of the three main coronary arteries; left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA). In studies I and II, we investigated the feasibility of RTP-ASE for the detection of ischemia using visual interpretation of RTP-ASE loops acquired at rest and stress. Study III was carried out to examine the value of quantitatively generated parametric perfusion images from RTP-ASE loops, in detecting myocardial ischemia. In study IV, the usefulness of quantitative detection of myocardial ischemia from RTP-ASE loops was assessed. Data comparing quantitative measurements of perfusion replenishment from RTP-ASE images at rest and stress were used as markers of ischemia. The results from the studies in this thesis suggest that visual evaluation of ischemia from RTP-ASE images, using angio-mode as well as high resolution grey scale mode, is accurate and feasible. It is therefore a clinically useful method in patients with known or suspected stable CAD. Quantification of ischemia or parametric imaging for ischemia evaluation using Qontrast, are not yet suitable for clinical use, as judged by the findings of this thesis. However, since further technical development can be expected, quantitative assessment of myocardial perfusion may well be a clinically useful method in the near future.