Einar Heiberg

Design and validation of Segment - freely available software for cardiovascular image analysis

BackgroundCommercially available software for cardiovascular image analysis often has limited functionality and frequently lacks the careful validation that is required for clinical studies. We have already implemented a cardiovascular image analysis software package and released it as freeware for the research community. However, it was distributed as a stand-alone application and other researchers could not extend it by writing their own custom image analysis algorithms. We believe that the work required to make a clinically applicable prototype can be reduced by making the software extensible, so that researchers can develop their own modules or improvements. Such an initiative might then serve as a bridge between image analysis research and cardiovascular research. The aim of this article is therefore to present the design and validation of a cardiovascular image analysis software package (Segment) and to announce its release in a source code format.ResultsSegment can be used for image analysis in magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET). Some of its main features include loading of DICOM images from all major scanner vendors, simultaneous display of multiple image stacks and plane intersections, automated segmentation of the left ventricle, quantification of MRI flow, tools for manual and general object segmentation, quantitative regional wall motion analysis, myocardial viability analysis and image fusion tools. Here we present an overview of the validation results and validation procedures for the functionality of the software. We describe a technique to ensure continued accuracy and validity of the software by implementing and using a test script that tests the functionality of the software and validates the output. The software has been made freely available for research purposes in a source code format on the project home page http://segment.heiberg.se.ConclusionsSegment is a well-validated comprehensive software package for cardiovascular image analysis. It is freely available for research purposes provided that relevant original research publications related to the software are cited.

Myocardium at risk after acute infarction in humans on cardiac magnetic resonance: quantitative assessment during follow-up and validation with single-photon emission computed tomography.

OBJECTIVES Our goal was to validate myocardium at risk on T2-weighted short tau inversion recovery (T2-STIR) cardiac magnetic resonance (CMR) over time, compared with that seen with perfusion single-photon emission computed tomography (SPECT) in patients with ST-segment elevation myocardial infarction, and to assess the amount of salvaged myocardium after 1 week. BACKGROUND To assess reperfusion therapy, it is necessary to determine how much myocardium is salvaged by measuring the final infarct size in relation to the initial myocardium at risk of the left ventricle (LV). METHODS Sixteen patients with first-time ST-segment elevation myocardial infarction received (99m)Tc tetrofosmin before primary percutaneous coronary intervention. SPECT was performed within 4 h and T2-STIR CMR within 1 day, 1 week, 6 weeks, and 6 months. At 1 week, patients were injected with a gadolinium-based contrast agent for quantification of infarct size. RESULTS Myocardium at risk at occlusion on SPECT was 33 +/- 10% of the LV. Myocardium at risk on T2-STIR did not differ from SPECT, at day 1 (29 +/- 7%, p = 0.49) or week 1 (31 +/- 6%, p = 0.16) but declined at week 6 (10 +/- 12%, p = 0.0096 vs. 1 week) and month 6 (4 +/- 11%, p = 0.0013 vs. 1 week). There was a correlation between myocardium at risk demonstrated by T2-STIR at week 1 and myocardium at risk by SPECT (r(2) = 0.70, p < 0.001), and the difference between the methods on Bland-Altman analysis was not significant (-2.3 +/- 5.7%, p = 0.16). Both modalities identified myocardium at risk in the same perfusion territory and in concordance with angiography. Final infarct size was 8 +/- 7%, and salvage was 75 +/- 19% of myocardium at risk. CONCLUSIONS This study demonstrates that T2-STIR performed up to 1 week after reperfusion can accurately determine myocardium at risk as it was before opening of the occluded artery. CMR can also quantify salvaged myocardium as myocardium at risk minus final infarct size.

Transit of Blood Flow Through the Human Left Ventricle Mapped by Cardiovascular Magnetic Resonance

BACKGROUND The transit of blood through the beating heart is a basic aspect of cardiovascular physiology which remains incompletely studied. Quantification of the components of multidirectional flow in the normal left ventricle (LV) is lacking, making it difficult to put the changes observed with LV dysfunction and cardiac surgery into context. METHODS Three dimensional, three directional, time resolved magnetic resonance phase-contrast velocity mapping was performed at 1.5 Tesla in 17 normal subjects, 6 female, aged 44+/-14 years (mean+/-SD). We visualized and measured the relative volumes of LV flow components and the diastolic changes in inflowing kinetic energy (KE). Of total diastolic inflow volume, 44+/-11% followed a direct, albeit curved route to systolic ejection (videos 1 and 2), in contrast to 11% in a subject with mildly dilated cardiomyopathy (DCM), who was included for preliminary comparison (video 3). In normals, 16+/-8% of the KE of inflow was conserved to the end of diastole, compared with 5% in the DCM patient. Blood following the direct route lost or transferred less of its KE during diastole than blood that was retained until the next beat (1.6+/-1.0 millijoules vs 8.2+/-1.9 millijoules, p<0.05); whereas, in the DCM patient, the reduction in KE of retained inflow was 18-fold greater than that of the blood tracing the direct route. CONCLUSION Multidimensional flow mapping can measure the paths, compartmentalization and kinetic energy changes of blood flowing into the LV, demonstrating differences of KE loss between compartments, and potentially between the flows in normal and dilated left ventricles.

Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results

AIM The MITOCARE study evaluated the efficacy and safety of TRO40303 for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). METHODS Patients presenting with STEMI within 6 h of the onset of pain randomly received TRO40303 (n = 83) or placebo (n = 80) via i.v. bolus injection prior to balloon inflation during primary percutaneous coronary intervention in a double-blind manner. The primary endpoint was infarct size expressed as area under the curve (AUC) for creatine kinase (CK) and for troponin I (TnI) over 3 days. Secondary endpoints included measures of infarct size using cardiac magnetic resonance (CMR) and safety outcomes. RESULTS The median pain-to-balloon time was 180 min for both groups, and the median (mean) door-to-balloon time was 60 (38) min for all sites. Infarct size, as measured by CK and TnI AUCs at 3 days, was not significantly different between treatment groups. There were no significant differences in the CMR-assessed myocardial salvage index (1-infarct size/myocardium at risk) (mean 52 vs. 58% with placebo, P = 0.1000), mean CMR-assessed infarct size (21.9 g vs. 20.0 g, or 17 vs. 15% of LV-mass) or left ventricular ejection fraction (LVEF) (46 vs. 48%), or in the mean 30-day echocardiographic LVEF (51.5 vs. 52.2%) between TRO40303 and placebo. A greater number of adjudicated safety events occurred in the TRO40303 group for unexplained reasons. CONCLUSION This study in STEMI patients treated with contemporary mechanical revascularization principles did not show any effect of TRO40303 in limiting reperfusion injury of the ischaemic myocardium.

Rapid Initial Reduction of Hyperenhanced Myocardium After Reperfused First Myocardial Infarction Suggests Recovery of the Peri-Infarction Zone One-Year Follow-Up by MRI

Background—The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI. Methods and Results—Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly (P<0.001), although the left ventricular mass remained unchanged. Left ventricular ejection fraction increased gradually, whereas the greater the regional transmural extent of hyperenhancement at day 1, the later the recovery of regional wall thickening. Regional wall thickening decreased progressively with increasing initial transmural extent of hyperenhancement (Ptrend<0.0001). The time course and magnitude of decrease in QRS score corresponded with the reduction of hyperenhanced myocardium. Conclusions—The early reduction of hyperenhanced myocardium may reflect recovery of hyperenhanced, reversibly injured myocardium, which must be considered when predicting functional recovery from delayed contrast-enhanced MRI findings early after infarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes.

Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

BackgroundThe aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model.MethodsPigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4°C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI.ResultsPre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 ± 8%) compared to post-reperfusion hypothermia (80 ± 6%, p < 0.05) and by 39% compared to normothermia (75 ± 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 ± 5%; p < 0.05), compared to normothermia: (30.2 ± 5%).ConclusionRapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.

Semi-automatic quantification of myocardial infarction from delayed contrast enhanced magnetic resonance imaging.

Objective. Accurate and reproducible assessment of myocardial infarction is important for treatment planning in patients with ischemic heart disease. This study describes a novel method to quantify myocardial infarction by semi-automatic delineation of hyperenhanced myocardium in delayed contrast enhanced (DE) magnetic resonance (MR) images. Design. The proposed method automatically detects the hyperenhanced tissue by first determining the signal intensity of non-enhanced myocardium. A fast level set algorithm was used to limit the heterogeneity of the hyperenhanced regions, and to exclude small regions that constitute noise rather than infarction. The method was evaluated in 40 patients; 20 with acute infarction and 20 with chronic healed infarction using scanners from two different manufacturers. Infarct size measured by the proposed semi-automatic method was compared with manual measurements from three experienced observers. The software used is freely available for research purposes at http://segment.heiberg.se. Results. The difference in infarct size between semi-automatic quantification and the mean of the three observers was 6.1±6.6 ml (mean±SD), and the interobserver variability (SD) was 4.2 ml. Conclusions. The method presented is a highly automated method for analyzing myocardial viability from DE-MR images. The bias of the method is acceptable and the variability is in the same order of magnitude as the interobserver variability for manual delineations.

Three-dimensional flow characterization using vector pattern matching

This paper describes a novel method for regional characterization of three-dimensional vector fields using a pattern matching approach. Given a three-dimensional vector field, the goal is to automatically locate, identify, and visualize a selected set of classes of structures or features. Rather than analytically defining the properties that must be fulfilled in a region in order to be classified as a specific structure, a set of idealized patterns for each structure type is constructed. Similarity to these patterns is then defined and calculated. Examples of structures of interest include vortices, swirling flow, diverging or converging flow, and parallel flow. Both medical and aerodynamic applications are presented in this paper.

Quantification of left and right ventricular kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements

We aimed to quantify kinetic energy (KE) during the entire cardiac cycle of the left ventricle (LV) and right ventricle (RV) using four-dimensional phase-contrast magnetic resonance imaging (MRI). KE was quantified in healthy volunteers (n = 9) using an in-house developed software. Mean KE through the cardiac cycle of the LV and the RV were highly correlated (r(2) = 0.96). Mean KE was related to end-diastolic volume (r(2) = 0.66 for LV and r(2) = 0.74 for RV), end-systolic volume (r(2) = 0.59 and 0.68), and stroke volume (r(2) = 0.55 and 0.60), but not to ejection fraction (r(2) < 0.01, P = not significant for both). Three KE peaks were found in both ventricles, in systole, early diastole, and late diastole. In systole, peak KE in the LV was lower (4.9 ± 0.4 mJ, P = 0.004) compared with the RV (7.5 ± 0.8 mJ). In contrast, KE during early diastole was higher in the LV (6.0 ± 0.6 mJ, P = 0.004) compared with the RV (3.6 ± 0.4 mJ). The late diastolic peaks were smaller than the systolic and early diastolic peaks (1.3 ± 0.2 and 1.2 ± 0.2 mJ). Modeling estimated the proportion of KE to total external work, which comprised ∼0.3% of LV external work and 3% of RV energy at rest and 3 vs. 24% during peak exercise. The higher early diastolic KE in the LV indicates that LV filling is more dependent on ventricular suction compared with the RV. RV early diastolic filling, on the other hand, may be caused to a higher degree of the return of the atrioventricular plane toward the base of the heart. The difference in ventricular geometry with a longer outflow tract in the RV compared with the LV explains the higher systolic KE in the RV.

Quantification and visualization of cardiovascular 4D velocity mapping accelerated with parallel imaging or k-t BLAST: head to head comparison and validation at 1.5 T and 3 T.

BackgroundThree-dimensional time-resolved (4D) phase-contrast (PC) CMR can visualize and quantify cardiovascular flow but is hampered by long acquisition times. Acceleration with SENSE or k-t BLAST are two possibilities but results on validation are lacking, especially at 3 T. The aim of this study was therefore to validate quantitative in vivo cardiac 4D-acquisitions accelerated with parallel imaging and k-t BLAST at 1.5 T and 3 T with 2D-flow as the reference and to investigate if field strengths and type of acceleration have major effects on intracardiac flow visualization.MethodsThe local ethical committee approved the study. 13 healthy volunteers were scanned at both 1.5 T and 3 T in random order with 2D-flow of the aorta and main pulmonary artery and two 4D-flow sequences of the heart accelerated with SENSE and k-t BLAST respectively. 2D-image planes were reconstructed at the aortic and pulmonary outflow. Flow curves were calculated and peak flows and stroke volumes (SV) compared to the results from 2D-flow acquisitions. Intra-cardiac flow was visualized using particle tracing and image quality based on the flow patterns of the particles was graded using a four-point scale.ResultsGood accuracy of SV quantification was found using 3 T 4D-SENSE (r2 = 0.86, -0.7 ± 7.6%) and although a larger bias was found on 1.5 T (r2 = 0.71, -3.6 ± 14.8%), the difference was not significant (p = 0.46). Accuracy of 4D k-t BLAST for SV was lower (p < 0.01) on 1.5 T (r2 = 0.65, -15.6 ± 13.7%) compared to 3 T (r2 = 0.64, -4.6 ± 10.0%). Peak flow was lower with 4D-SENSE at both 3 T and 1.5 T compared to 2D-flow (p < 0.01) and even lower with 4D k-t BLAST at both scanners (p < 0.01). Intracardiac flow visualization did not differ between 1.5 T and 3 T (p = 0.09) or between 4D-SENSE or 4D k-t BLAST (p = 0.85).ConclusionsThe present study showed that quantitative 4D flow accelerated with SENSE has good accuracy at 3 T and compares favourably to 1.5 T. 4D flow accelerated with k-t BLAST underestimate flow velocities and thereby yield too high bias for intra-cardiac quantitative in vivo use at the present time. For intra-cardiac 4D-flow visualization, however, 1.5 T and 3 T as well as SENSE or k-t BLAST can be used with similar quality.