ABSTRACT: Current guidelines for measuring cardiac function by tissue Doppler recommend using multiple beats, but this has a time cost for human operators. We present an open-source, vendor-independent, drag-and-drop software capable of automating the measurement process. A database of ~8000 tissue Doppler beats (48 patients) from the septal and lateral annuli were analyzed by three expert echocardiographers. We developed an intensity- and gradient-based automated algorithm to measure tissue Doppler velocities. We tested its performance against manual measurements from the expert human operators. Our algorithm showed strong agreement with expert human operators. Performance was indistinguishable from a human operator: for algorithm, mean difference and SDD from the mean of human operators' estimates 0.48?±?1.12 cm/s (R2?=?0.82); for the humans individually this was 0.43?±?1.11 cm/s (R2?=?0.84), -0.88?±?1.12 cm/s (R2?=?0.84) and 0.41?±?1.30 cm/s (R2?=?0.78). Agreement between operators and the automated algorithm was preserved when measuring at either the edge or middle of the trace. The algorithm was 10-fold quicker than manual measurements (p?
Project description:Stem cell therapy has the potential to regenerate cardiac function after myocardial infarction. In this study, we sought to examine if fibrin microthread technology could be leveraged to develop a contractile fiber from human pluripotent stem cell derived cardiomyocytes (hPS-CM). hPS-CM seeded onto fibrin microthreads were able to adhere to the microthread and began to contract seven days after initial seeding. A digital speckle tracking algorithm was applied to high speed video data (>60 fps) to determine contraction behaviour including beat frequency, average and maximum contractile strain, and the principal angle of contraction of hPS-CM contracting on the microthreads over 21 days. At day 7, cells seeded on tissue culture plastic beat at 0.83 ± 0.25 beats/sec with an average contractile strain of 4.23±0.23%, which was significantly different from a beat frequency of 1.11 ± 0.45 beats/sec and an average contractile strain of 3.08±0.19% at day 21 (n = 18, p < 0.05). hPS-CM seeded on microthreads beat at 0.84 ± 0.15 beats/sec with an average contractile strain of 3.56±0.22%, which significantly increased to 1.03 ± 0.19 beats/sec and 4.47±0.29%, respectively, at 21 days (n = 18, p < 0.05). At day 7, 27% of the cells had a principle angle of contraction within 20 degrees of the microthread, whereas at day 21, 65% of hPS-CM were contracting within 20 degrees of the microthread (n = 17). Utilizing high speed calcium transient data (>300 fps) of Fluo-4AM loaded hPS-CM seeded microthreads, conduction velocities significantly increased from 3.69 ± 1.76 cm/s at day 7 to 24.26 ± 8.42 cm/s at day 21 (n = 5-6, p < 0.05). hPS-CM seeded microthreads exhibited positive expression for connexin 43, a gap junction protein, between cells. These data suggest that the fibrin microthread is a suitable scaffold for hPS-CM attachment and contraction. In addition, extended culture allows cells to contract in the direction of the thread, suggesting alignment of the cells in the microthread direction.
Project description:BACKGROUND:Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. METHODS:The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). RESULTS:Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). CONCLUSIONS:The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CLINICAL TRIAL REGISTRATION:CHILL-MI: NCT01379261 . MITOCARE:NCT01374321 .
Project description:The coronary microcirculation (CM) plays a critical role in the regulation of blood flow and nutrient exchange to support the viability of the heart. In many disease states, the CM becomes structurally and functionally impaired, and transthoracic Doppler echocardiography can be used as a non-invasive surrogate to assess CM disease. Analysis of Doppler echocardiography is prone to user bias and can be laborious, especially if additional parameters are collected. We hypothesized that we could develop a MATLAB algorithm to automatically analyze clinically-relevant and non-traditional parameters from murine PW Doppler coronary flow patterns that would reduce intra- and inter-operator bias, and analysis time. Our results show a significant reduction in intra- and inter-observer variability as well as a 30 fold decrease in analysis time with the automated program vs. manual analysis. Finally, we demonstrated good agreement between automated and manual analysis for clinically-relevant parameters under baseline and hyperemic conditions. Resulting coronary flow velocity reserve calculations were also found to be in good agreement. We present a MATLAB algorithm that is user friendly and robust in defining and measuring Doppler coronary flow pattern parameters for more efficient and potentially more insightful analysis assessed via Doppler echocardiography.
Project description:High-altitude (HA) exposure has been widely considered as a cardiac stress, and associated with altered cardiac function. However, the characteristics of cardiac responses to HA exposure are unclear. In total, 240 healthy men were enrolled and ascended to 4100 m by bus within 7 days. Standard echocardiography and color tissue Doppler imaging were performed at sea level and at 4100 m. In all subjects, HA exposure increased HR [65 (59, 71) vs. 72 (63, 80) beats/min, p?<?0.001] but decreased the stroke volume index (SVi) [35.5 (30.5, 42.3) vs. 32.9 (27.4, 39.5) ml/m2, p?<?0.001], leading to an unchanged cardiac index (CI). Moreover, baseline HR was negatively correlated with HA exposure-induced changes in HR (r?=?-?0.410, p?<?0.001) and CI (r?=?-?0.314, p?<?0.001). Following HA exposure, subjects with lowest tertile of baseline HR showed an increased HR [56 (53, 58) vs. 65 (58, 73) beats/min, p?<?0.001], left ventricular ejection fraction (LVEF) [61.7 (56.5, 68.0) vs. 66.1 (60.7, 71.5) %, p?=?0.004] and mitral S' velocity [5.8?±?1.4 vs. 6.5?±?1.9 cm/s, p?=?0.040]. However, subjects with highest tertile of baseline HR showed an unchanged HR, LVEF and mitral S' velocity, but a decreased E' velocity [9.2?±?2.0 vs. 8.4?±?1.8 cm/s, p?=?0.003]. Our findings indicate that baseline HR at sea level could determine cardiac responses to HA exposure; these responses were characterized by enhanced LV function in subjects with a low baseline HR and by reduced LV myocardial velocity in early diastole in subjects with a high baseline HR.
Project description:BACKGROUND:Frequent premature ventricular contractions (PVCs) have been associated with PVC-induced cardiomyopathy (CM) in some patients. OBJECTIVE:The purpose of this study was to understand the cardiac consequences of different PVC burdens and the minimum burden required to induce left ventricular (LV) dysfunction. METHODS:Right ventricular apical PVCs at a coupling interval of 240 ms were introduced at different PVC burdens in 9 mongrel canines. A stepwise increase in PVC burden was implemented every 8 weeks from 0% (baseline), 7%, 14%, 25%, 33% to 50% using our premature pacing algorithm. Echocardiogram and 24-hour Holter were obtained at 4- and 8-week period for each PVC burden with a single blinded reader assessing all echocardiographic parameters including those assessed by speckle tracking imaging (EchoPAC workstation, General Electric). CM was defined as left ventricular ejection fraction (LVEF) <50% or LVEF drop >10% points. Interleukin-6 and pro-brain natriuretic peptide levels were obtained at the end of each PVC burden. RESULTS:The mean LVEF (mean heart rate) at 8 weeks for each PVC burden (0%, 7%, 14%, 33%, and 50%) were 57% ± 2.9% (85 ± 13 beats/min), 54.4% ± 3% (81 ± 10 beats/min), 53.3% ± 5% (77 ± 12 beats/min), 51.1% ± 4.2% (79 ± 14 beats/min), 47.7% ± 3.8% (80 ± 14 beats/min), and 44.7% ± 1.9% (157 ± 43 beats/min). PVC-induced CM was present in 11.1%, 44.4%, and 100% of animals with 25%, 33%, and 50% PVC burden, respectively. E/A ratio and radial strain decreased while left atrial size increased beyond 33% PVC burden. No changes in pro-brain natriuretic peptide and interleukin-6 levels were noted at any PVC burden. CONCLUSION:LV systolic function (LVEF and radial strain) declined linearly as PVC burden increased. PVC-induced CM developed in some canines with 25% and 33% PVC burden, but developed in all animals with 50% PVC burden.
Project description:BACKGROUND:Automatic analyses of echocardiograms may support inexperienced users in quantifying left ventricular (LV) function. We have developed an algorithm for fully automatic measurements of mitral annular plane systolic excursion (MAPSE) and mitral annular systolic (S') and early diastolic (e') peak velocities. We aimed to study the influence of user experience of automatic measurements of these indices in echocardiographic recordings acquired by medical students and clinicians. METHODS:We included 75 consecutive patients referred for echocardiography at a university hospital. The patients underwent echocardiography by clinicians (cardiologists, cardiology residents and sonographers), who obtained manual reference measurements of MAPSE by M-mode and of S' and e' by colour tissue Doppler imaging (cTDI). Immediately after, each patient was examined by 1 of 39 medical students who were instructed in image acquisition on the day of participation. Each student acquired cTDI recordings from 1 to 4 patients. All cTDI recordings by students and clinicians were analysed for MAPSE, S' and e' using a fully automatic algorithm. The automatic measurements were compared to the manual reference measurements. RESULTS:Correct tracking of the mitral annulus was feasible in 50 (67%) and 63 (84%) of the students' and clinicians' recordings, respectively (p?=?0.007). Image quality was highest in the clinicians' recordings. Mean difference?±?standard deviation of the automatic measurements of the students' recordings compared to the manual reference was -?0.0?±?2.0?mm for MAPSE, 0.3?±?1.1?cm/s for S' and 0.6?±?1.4?cm/s for e'. The corresponding intraclass correlation coefficients for MAPSE, S' and e' were 0.85 (good), 0.89 (good) and 0.92 (excellent), respectively. Automatic measurements from the students' and clinicians' recordings were in similar agreement with the reference when mitral annular tracking was correct. CONCLUSIONS:In case of correct tracking of the mitral annulus, the agreement with reference for the automatic measurements was overall good. Low image quality reduced feasibility. Adequate image acquisition is essential for automatic analyses of LV function indices, and thus, appropriate education of the operators is mandatory. Automatic measurements may help inexperienced users of ultrasound, but do not remove the need for dedicated education and training.
Project description:In macular spectral domain optical coherence tomography (SD-OCT) volumes, detection of the foveal center is required for accurate and reproducible follow-up studies, structure function correlation, and measurement grid positioning. However, disease can cause severe obscuring or deformation of the fovea, thus presenting a major challenge in automated detection. We propose a fully automated fovea detection algorithm to extract the fovea position in SD-OCT volumes of eyes with exudative maculopathy. The fovea is classified into 3 main appearances to both specify the detection algorithm used and reduce computational complexity. Based on foveal type classification, the fovea position is computed based on retinal nerve fiber layer thickness. Mean absolute distance between system and clinical expert annotated fovea positions from a dataset comprised of 240 SD-OCT volumes was 162.3?µm in cystoid macular edema and 262?µm in nAMD. The presented method has cross-vendor functionality, while demonstrating accurate and reliable performance close to typical expert interobserver agreement. The automatically detected fovea positions may be used as landmarks for intra- and cross-patient registration and to create a joint reference frame for extraction of spatiotemporal features in "big data." Furthermore, reliable analyses of retinal thickness, as well as retinal structure function correlation, may be facilitated.
Project description:Guidelines for quantifying mitral regurgitation (MR) using "proximal isovelocity surface area" (PISA) instruct operators to measure the PISA radius from valve orifice to Doppler flow convergence "hemisphere". Using clinical data and a physically-constructed MR model we (A) analyse the actually-observed colour Doppler PISA shape and (B) test whether instructions to measure a "hemisphere" are helpful.In part A, the true shape of PISA shells was investigated using three separate approaches. First, a systematic review of published examples consistently showed non-hemispherical, "urchinoid" shapes. Second, our clinical data confirmed that the Doppler-visualized surface is non-hemispherical. Third, in-vitro experiments showed that round orifices never produce a colour Doppler hemisphere. In part B, six observers were instructed to measure hemisphere radius rh and (on a second viewing) urchinoid distance (du) in 11 clinical PISA datasets; 6 established experts also measured PISA distance as the gold standard. rh measurements, generated using the hemisphere instruction significantly underestimated expert values (-28%, p<0.0005), meaning r(h)(2) was underestimated by approximately 2-fold. du measurements, generated using the non-hemisphere instruction were less biased (+7%, p=0.03). Finally, frame-to-frame variability in PISA distance was found to have a coefficient of variation (CV) of 25% in patients and 9% in in-vitro data. Beat-to-beat variability had a CV of 15% in patients.Doppler-visualized PISA shells are not hemispherical: we should avoid advising observers to measure a hemispherical radius because it encourages underestimation of orifice area by approximately two-fold. If precision is needed (e.g. to detect changes reliably) multi-frame averaging is essential.
Project description:BACKGROUND:Neonatal mortality is a global challenge, with an estimated 1.3 million intrapartum stillbirths in 2015. The majority of these were found in low resource settings with limited options to intrapartum fetal heart monitoring devices. This trial compared frequency of abnormal fetal heart rate (FHR) detection and adverse perinatal outcomes (i.e. fresh stillbirths, 24-h neonatal deaths, admission to neonatal care unit) among women intermittently assessed by Doppler or fetoscope in a rural low-resource setting. METHODS:This was an open-label randomized controlled trial conducted at Haydom Lutheran Hospital from March 2013 through August 2015. Inclusion criteria were; women in labor, singleton, cephalic presentation, normal FHR on admission (120-160 beats/minute), and cervical dilatation ≤7 cm. Verbal consent was obtained. RESULTS:A total of 2684 women were recruited, 1309 in the Doppler and 1375 in the fetoscope arms, respectively. Abnormal FHR was detected in 55 (4.2%) vs 42 (3.1%). (RR = 1.38; 95%CI: 0.93, 2.04) in the Doppler and fetoscope arms, respectively. Bag mask ventilation was performed in 80 (6.1%) vs 82 (6.0%). (RR = 1.03; 95%CI: 0.76, 1.38) of neonates, and adverse perinatal outcome was comparable 32(2.4%) vs 35(2.5%). (RR = 0.9; 95%CI: 0.59, 1.54), in the Doppler and fetoscope arms, respectively. CONCLUSION:This trial failed to demonstrate a statistically significant difference in the detection of abnormal FHR between intermittently used Doppler and fetoscope and adverse perinatal outcomes. However, FHR measurements were not performed as often as recommended by international guidelines. Conducting a randomized controlled study in rural settings with limited resources is associated with major challenges. TRIAL REGISTRATION:This clinical trial was registered on April 2013 with registration number NCT01869582 .
Project description:<b>Background: </b>Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength (?) determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration and conduction velocity determine ?=action potential duration×conduction velocity. We aimed to determine the role of anisotropic wavelength in inducibility of VF in explanted human left ventricular preparations. We tested the hypothesis that 3-dimensional cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity, can accurately predict VF sustainability.<br><br><b>Methods: </b>We conducted panoramic optical mapping of coronary perfused human left ventricular wedge preparations subjected to pharmacologically induced shortening and prolongation of action potential duration, by I<sub>K,ATP</sub> agonist pinacidil and antagonist glybenclamide, respectively. This measured action potential duration, conduction velocity, and thus determined pacing cycle length-dependent wavelengths in longitudinal (?<sub>L</sub>), transverse (?<sub>TV</sub>), and transmural (?<sub>TM</sub>) directions using S1S1 pacing protocol, from which wavelength volume (V<sub>?</sub>) was determined, as V<sub>?</sub>=?<sub>L</sub>×?<sub>TV</sub>×?<sub>TM</sub>, and compared with tissue volume<sub>.</sub> We tested a hypothesis that tissue volume/V<sub>?</sub> ratio can predict VF sustainability.<br><br><b>Results: </b>At baseline, at pacing rate of 240 beats per minute, the wavelengths were ?<sub>L</sub>=9.6±0.6 cm, ?<sub>TV</sub>=4.2±0.3 cm, and ?<sub>TM</sub>=5.8±0.2 cm, respectively (n=7), and thus V<sub>?</sub>=246.4±42.1 cm<sup>3</sup>. Administration of pinacidil at escalating concentrations progressively decreased V<sub>?</sub>, and VF became sustained, when tissue volume/V<sub>?</sub> was above safety factor ?=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased V<sub>T</sub>/V<sub>?</sub> below ? at any pacing rate and prevented VF sustainability.<br><br><b>Conclusions: </b>Sustained VF was only sustained in ventricular volume exceeding critical V<sub>?</sub>=?<sub>L</sub>×?<sub>TV</sub>×?<sub>TM</sub>.