Henrik Engblom

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.

A Pilot Study of Rapid Cooling by Cold Saline and Endovascular Cooling Before Reperfusion in Patients With ST-Elevation Myocardial Infarction

Background—Experimental studies have shown that induction of hypothermia before reperfusion of acute coronary occlusion reduces infarct size. Previous clinical studies, however, have not been able to show this effect, which is believed to be mainly because therapeutic temperature was not reached before reperfusion in the majority of the patients. We aimed to evaluate the safety and feasibility of rapidly induced hypothermia by infusion of cold saline and endovascular cooling catheter before reperfusion in patients with acute myocardial infarction. Methods and Results—Twenty patients with acute myocardial infarction scheduled to undergo primary percutaneous coronary intervention were enrolled in this prospective, randomized study. After 4±2 days, myocardium at risk and infarct size were assessed by cardiac magnetic resonance using T2-weighted imaging and late gadolinium enhancement imaging, respectively. A core body temperature of <35°C (34.7±0.3°C) was achieved before reperfusion without significant delay in door-to-balloon time (43±7 minutes versus 40±6 minutes, hypothermia versus control, P=0.12). Despite similar duration of ischemia (174±51 minutes versus 174±62 minutes, hypothermia versus control, P=1.00), infarct size normalized to myocardium at risk was reduced by 38% in the hypothermia group compared with the control group (29.8±12.6% versus 48.0±21.6%, P=0.041). This was supported by a significant decrease in both peak and cumulative release of Troponin T in the hypothermia group (P=0.01 and P=0.03, respectively). Conclusions—The protocol demonstrates the ability to reach a core body temperature of <35°C before reperfusion in all patients without delaying primary percutaneous coronary intervention and that combination hypothermia as an adjunct therapy in acute myocardial infarction may reduce infarct size at 3 days as measured by MRI. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00417638.

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.

Relation between cardiac dimensions and peak oxygen uptake

BackgroundLong term endurance training is known to increase peak oxygen uptake () and induce morphological changes of the heart such as increased left ventricular mass (LVM). However, the relationship between and the total heart volume (THV), considering both the left and right ventricular dimensions in both males and females, is not completely described. Therefore, the aim of this study was to test the hypothesis that THV is an independent predictor of and to determine if the left and right ventricles enlarge in the same order of magnitude in males and females with a presumed wide range of THV.Methods and ResultsThe study population consisted of 131 subjects of whom 71 were athletes (30 female) and 60 healthy controls (20 female). All subjects underwent cardiovascular MR and maximal incremental exercise test. Total heart volume, LVM and left- and right ventricular end-diastolic volumes (LVEDV, RVEDV) were calculated from short-axis images. was significantly correlated to THV, LVM, LVEDV and RVEDV in both males and females. Multivariable analysis showed that THV was a strong, independent predictor of (R2 = 0.74, p < 0.001). As LVEDV increased, RVEDV increased in the same order of magnitude in both males and females (R2 = 0.87, p < 0.001).ConclusionTotal heart volume is a strong, independent predictor of maximal work capacity for both males and females. Long term endurance training is associated with a physiologically enlarged heart with a balance between the left and right ventricular dimensions in both genders.

Rationale and Design of the 'MITOCARE' Study: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of TRO40303 for the Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction

Treatment of acute ST-elevation myocardial infarction (STEMI) by reperfusion using percutaneous coronary intervention (PCI) or thrombolysis has provided clinical benefits; however, it also induces considerable cell death. This process is called reperfusion injury. The continuing high rates of mortality and heart failure after acute myocardial infarction (AMI) emphasize the need for improved strategies to limit reperfusion injury and improve clinical outcomes. The objective of this study is to assess safety and efficacy of TRO40303 in limiting reperfusion injury in patients treated for STEMI. TRO40303 targets the mitochondrial permeability transition pore, a promising target for the prevention of reperfusion injury. This multicenter, double-blind study will randomize patients with STEMI to TRO40303 or placebo administered just before balloon inflation or thromboaspiration during PCI. The primary outcome measure will be reduction in infarct size (assessed as plasma creatine kinase and troponin I area under the curve over 3 days). The main secondary endpoint will be infarct size normalized to the myocardium at risk (expressed by the myocardial salvage index assessed by cardiac magnetic resonance). The study is being financed under an EU-FP7 grant and conducted under the auspices of the MITOCARE research consortium, which includes experts from clinical and basic research centers, as well as commercial enterprises, throughout Europe. Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present paper describes the rationale, design and the methods of the trial.Treatment of acute ST-elevation myocardial infarction (STEMI) by reperfusion using percutaneous coronary intervention (PCI) or thrombolysis has provided clinical benefits; however, it also induces considerable cell death. This process is called reperfusion injury. The continuing high rates of mortality and heart failure after acute myocardial infarction (AMI) emphasize the need for improved strategies to limit reperfusion injury and improve clinical outcomes. The objective of this study is to assess safety and efficacy of TRO40303 in limiting reperfusion injury in patients treated for STEMI. TRO40303 targets the mitochondrial permeability transition pore, a promising target for the prevention of reperfusion injury. This multicenter, double-blind study will randomize patients with STEMI to TRO40303 or placebo administered just before balloon inflation or thromboaspiration during PCI. The primary outcome measure will be reduction in infarct size (assessed as plasma creatine kinase and troponin I area under the curve over 3 days). The main secondary endpoint will be infarct size normalized to the myocardium at risk (expressed by the myocardial salvage index assessed by cardiac magnetic resonance). The study is being financed under an EU-FP7 grant and conducted under the auspices of the MITOCARE research consortium, which includes experts from clinical and basic research centers, as well as commercial enterprises, throughout Europe. Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present paper describes the rationale, design and the methods of the trial. Copyright (c) 2012 S. Karger AG, Basel (Less)

Cardiovascular magnetic resonance of the myocardium at risk in acute reperfused myocardial infarction: comparison of T2-weighted imaging versus the circumferential endocardial extent of late gadolinium enhancement with transmural projection

BackgroundIn the situation of acute coronary occlusion, the myocardium supplied by the occluded vessel is subject to ischemia and is referred to as the myocardium at risk (MaR). Single photon emission computed tomography has previously been used for quantitative assessment of the MaR. It is, however, associated with considerable logistic challenges for employment in clinical routine. Recently, T2-weighted cardiovascular magnetic resonance (CMR) has been introduced as a new method for assessing MaR several days after the acute event. Furthermore, it has been suggested that the endocardial extent of infarction as assessed by late gadolinium enhanced (LGE) CMR can also be used to quantify the MaR. Hence, we sought to assess the ability of endocardial extent of infarction by LGE CMR to predict MaR as compared to T2-weighted imaging.MethodsThirty-seven patients with early reperfused first-time ST-segment elevation myocardial infarction underwent CMR imaging within the first week after percutaneous coronary intervention. The ability of endocardial extent of infarction by LGE CMR to assess MaR was evaluated using T2-weighted imaging as the reference method.ResultsMaR determined with T2-weighted imaging (34 ± 10%) was significantly higher (p < 0.001) compared to the MaR determined with endocardial extent of infarction (23 ± 12%). There was a weak correlation between the two methods (r2 = 0.17, p = 0.002) with a bias of -11 ± 12%. Myocardial salvage determined with T2-weighted imaging (58 ± 22%) was significantly higher (p < 0.001) compared to myocardial salvage determined with endocardial extent of infarction (45 ± 23%). No MaR could be determined by endocardial extent of infarction in two patients with aborted myocardial infarction.ConclusionsThis study demonstrated that the endocardial extent of infarction as assessed by LGE CMR underestimates MaR in comparison to T2-weighted imaging, especially in patients with early reperfusion and aborted myocardial infarction.

Preventing heart injury during negative pressure wound therapy in cardiac surgery: assessment using real-time magnetic resonance imaging.

OBJECTIVE Heart rupture is a devastating complication to negative pressure wound therapy in cardiac surgery. Also, reduced cardiac output during negative pressure wound therapy has been reported. The present study aimed to examine the effects of negative pressure wound therapy on the position of the heart in relation to the thoracic wall using magnetic resonance imaging in a porcine sternotomy wound model. METHODS Six pigs had median sternotomy followed by negative pressure wound therapy at -75, -125, and -175 mm Hg. Real-time magnetic resonance imaging movies (10 images/s) were acquired in a midventricular transverse plane or a midsagittal plane during the application of negative pressure wound therapy. RESULTS Similar finding were observed at all different negative pressures studied. Negative pressure wound therapy caused the heart to be displaced toward the thoracic wall, and in some cases, the right ventricular free wall bulged into the space between the sternal edges, and the sharp edges of the sternum jutted into and deformed the anterior surface of the right ventricular free wall. These events were not affected by the interposition of 4 layers of paraffin gauze dressing but were hindered by the placement of a rigid barrier between the anterior portion of the heart and the inside of the thoracic wall. CONCLUSION The results show altered position of the heart in relation to the sternum during negative pressure wound therapy. This may explain 2 potentially hazardous events associated with negative pressure wound therapy, namely, risk for heart rupture and reduced cardiac output. Inserting a rigid barrier over the heart may be a protective measure that is clinically practicable.