[Show abstract][Hide abstract] ABSTRACT: Purpose: Atherosclerotic plaques progress in a highly individual manner. Plaque eccentricity has been associated with a rupture-prone phenotype and adverse coronary events in humans. Endothelial shear stress (ESS) critically determines plaque growth and low ESS leads to high-risk lesions. However, the factors responsible for rapid disease progression with increasing plaque eccentricity have not been studied. We investigated in vivo the effect of local hemodynamic and plaque characteristics on progressive luminal narrowing with increasing plaque eccentricity in humans.
Methods: Three-dimensional coronary artery reconstruction using angiographic and intravascular ultrasound data was performed in 374 patients at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Trial. A total of 874 coronary arteries were divided into consecutive 3-mm segments. We identified 408 BL discrete luminal narrowings with a throat in the middle surrounded by gradual narrowing proximal and distal to the throat. Local BL ESS was assessed by computational fluid dynamics. The eccentricity index (EI) at BL and FU was computed as the ratio of max to min plaque thickness at the throat. Mixed-effects logistic regression was used to investigate the effect of BL variables on the combined endpoint of substantial worsening of luminal narrowing (decrease in lumen area >1.8 mm2 or >20%) with an increase in plaque EI.
Results: Lumen worsening with an increase in plaque EI was evident in 73 luminal narrowings (18%). Independent predictors of worsening lumen narrowing with plaque EI increase were low BL ESS (<1 Pa) distal to the throat (odds ratio [OR] =2.2 [95% CI: 1.3-3.7]; p=0.003) and large BL plaque burden (>51%) at the throat (OR=1.7 [95% CI: 1.0-2.8]; p=0.051). The incidence of worsening lumen narrowing with increasing plaque eccentricity was 30% in the presence of both predictors versus 15% in luminal narrowings without this combination of characteristics (OR=2.4 [95% CI: 1.4-4.3]; p=0.002).
Conclusions: Low local ESS independently predicts areas with rapidly progressive luminal narrowing and increasing plaque eccentricity. Coronary regions manifesting an abrupt anatomic change, i.e., at highest risk to cause an adverse event, can be identified early by assessment of ESS and plaque burden.
[Show abstract][Hide abstract] ABSTRACT: To compare two semiautomated methods for measurement of infarcted myocardium area on delayed contrast enhanced magnetic resonance imaging, with histopathology findings as standard of reference.
Percentage area of myocardial infarction was measured in 10 Yorkshire landrace pigs manually and using two semiautomated methods. The first (standard deviation method) used two operator-selected regions of interest (ROIs) and nine different cutoff values (one to nine times the standard deviation of signal intensity in normal myocardium) to identify infarction. The second (threshold method) used threshold values based on percentages of maximum signal intensity to identify infarction. Results were compared with histopathology findings.
Difference between percentage area of infarction obtained with standard deviation method and autopsy specimens was in the range: -13.5% to +13.2%. With threshold method (thresholds from 30% to 90% of signal intensity), difference was -15% to +23%. Manual contouring underestimated infarcted area by 2% comparing to autopsy results. The best agreement between histopathology and semi-automated software was achieved for 4 standard deviations with standard deviation method: difference -0.45%, and for a percentage threshold of 70% (difference +0.67%) with threshold method. However, with standard deviation method, there was statistically significant difference between ROIs based on their location in viable myocardium: mean difference 1.7 ± 4%, P < .0001.
Semiautomated measurement of myocardial infarcted area on delayed enhanced magnetic resonance images performs well compared to autopsy. The threshold method, based on percentages of maximum signal intensity is preferable over standard deviation method, which is more susceptible to variability from location of ROIs within viable myocardium.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. METHODS: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (<30%), intermediate (30-70%) or high risk (>70%). Angiographic obstructive CAD (>50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. RESULTS: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p<0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p<0.001). CONCLUSIONS: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients.
International journal of cardiology 06/2011; 163(2). DOI:10.1016/j.ijcard.2011.06.002 · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the impact of tube current (mAs) in delayed-enhancement computed tomography (CT) imaging for assessing acute reperfused myocardial infarction in a porcine model.
In five domestic pigs (mean weight 24 kg), the circumflex coronary artery was balloon-occluded for 2 h and then reperfused. After 5 days, CT imaging was performed following administration of iodinated contrast material. A 64-slice CT system was used to perform first-pass coronary angiography with a tube current of 15 mAs/kg [Arterial Phase (ART)] followed by two delayed-enhancement (DE) scans 15 min after contrast material administration, with a tube current of 15 mAs/kg and 37.5 mAs/kg, respectively (DE(1) and DE(2)). The mean heart rate decreased to 51±9 beats/min after administration of zatebradine (10 mg/kg IV). The data set was reconstructed during the end-diastolic phase of the cardiac cycle. Areas with DE, no reflow and remote myocardium [remote left ventricular (LV)] were calculated. CT values expressed in Hounsfield units (HU) were measured using five regions of interest (ROI): DE, no reflow, remote LV, LV cavity (LV lumen) and in air, respectively. Differences, correlations, image quality [signal-to-noise ratio (SNR)] and contrast resolution [contrast-to-noise ratio (CNR)] were calculated.
Significant differences were found between attenuation of areas of DE, no reflow and remote LV (p<0.001) within the different scans. There was a fair correlation between DE and no-reflow attenuation (r=0.6; p<0.001). In DE(1) vs. DE(2), areas of DE and no reflow were not significantly different (p>0.05). The SNR and CNR were not significantly different in DE(1) vs. DE(2) (p>0.05).
Tube current does not significantly affect infarction area, image quality or contrast resolution of DE imaging with CT.
La radiologia medica 03/2010; 115(7):1003-14. DOI:10.1007/s11547-010-0541-0 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose in this study was to compare the impact of contrast material volume in delayed-enhancement computer tomography (CT) imaging for assessing acute reperfused myocardial infarction.
In five domestic pigs (20-30 kg), the circumflex coronary artery (CX) was balloon-occluded for 2 h followed by reperfusion. After 5 days, CT imaging was performed after intravenous administration of iodinated contrast material (Iomeprol 400 mgI/ml; Bracco, Italy). A 64-slice multidetector CT (MDCT) (Sensation 64, Siemens) scanner was used for imaging, with standard angiography characteristics. Three scans were performed: first, coronary angiography at first pass with 1.25 gI/kg of contrast material (ART); and remaining delayed-enhancement (DE(1)-DE(2)) 15 min after administration of 1.25 (DE(1)) and 15 min after additional administration of 2.50 gI/kg (=total 3.75 gI/kg - DE(2)). Mean heart rate decreased to 51+/-9 bpm after intravenous administration of Zatebradine (10 mg/kg). Data sets were reconstructed during the end-diastolic phase of the cardiac cycle. Areas of infarction-enhanced (DE), no-reflow (no-reflow) and remote myocardial [remote left ventricle (LV)] were manually contoured. CT attenuation values (Hounsfield units) were measured using five regions of interest: DE, no-reflow, remote LV, left ventricular cavity (lumen LV) and in air. Differences, correlations, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated.
We found significant differences between the attenuation of DE, no-reflow and remote LV (p<0.001). DE and no-reflow size were assessed accurately with DEMDCT. In particular, SNR and CNR showed higher values in DE(2) (approximately 6.0 and 3.5, respectively; r(2)=0.90) vs. DE(1) (approximately 4.0 and 2.2, respectively; r(2)=0.85).
The increase of contrast material volume determines a significant improvement in myocardial infarction image quality with DE-MDCT.
La radiologia medica 12/2009; 115(1):22-35. DOI:10.1007/s11547-009-0481-8 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Through labelling of cells with magnetic contrast agents it is possible to follow the fate of transplanted cells in vivo with magnetic resonance imaging (MRI) as has been demonstrated in animal studies as well as in a clinical setting. A large variety of labelling strategies are available that allow for prolonged and sensitive detection of the labelled cells with MRI. The various protocols each harbour specific advantages and disadvantages. In choosing a particular labelling strategy it is also important to ascertain that the labelling procedure does not negatively influence cell functionality, for which a large variety of assays are available. In order to overcome the challenges still faced in fully exploiting the benefits of in vivo cell tracking by MRI a good understanding and standardisation of the procedures and assays used will be crucial.
European Radiology 09/2009; 20(2):255-74. DOI:10.1007/s00330-009-1540-1 · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the diagnostic performance of CT angiography (CTA) and exercise electrocardiography (XECG) in a symptomatic population with a low-intermediate prevalence of coronary artery disease (CAD).
Tertiary university hospital.
471 consecutive ambulatory patients with stable chest pain complaints, mean (SD) age 56 (10), female 227 (48%), pre-test probability for significant CAD >5%.
All patients were intended to undergo both 64-slice, dual-source CTA and an XECG. Clinically driven quantitative catheter angiography was performed in 98 patients.
Feasibility and interpretability of, and association between, CTA and XECG, and their diagnostic performance with invasive coronary angiography as reference.
CTA and XECG could not be performed in 16 (3.4%) vs 48 (10.2%, p<0.001), and produced non-diagnostic results in 3 (0.7%) vs 140 (33%, p<0.001). CTA showed > or =1 coronary stenosis (> or =50%) in 140 patients (30%), XECG was abnormal in 93 patients (33%). Results by CTA and XECG matched for 185 patients (68%, p = 0.63). Catheter angiography showed obstructive CAD in 57/98 patients (58%). Sensitivity, specificity, positive and negative predictive value of CTA to identify patients with > or =50% stenosis was 96%, 37%, 67% and 88%, respectively; compared with XECG: 71%, 76%, 80% and 66%, respectively. Quantitative CTA slightly overestimated diameter stenosis: 6 (21)% (R = 0.71), compared with QCA. Of the 312 patients (66%) with a negative CTA, 44 (14%) had a positive XECG, but only 2/17 who underwent catheter angiography had significant CAD.
CTA is feasible and diagnostic in more patients than XECG. For interpretable studies, CTA has a higher sensitivity, but lower specificity for detection of CAD.
[Show abstract][Hide abstract] ABSTRACT: We sought to evaluate the automatic detection of the papillary muscle and to determine its influence on quantitative left ventricular (LV) mass assessment.
Twenty-eight Yorkshire-Landrace swine and 10 volunteers underwent cardiac magnetic resonance imaging (CMR) of the left ventricle. The variability in measurements of LV papillary muscles traced automatically and manually were compared to intra- and interobserver variabilities. CMR-derived LV mass with the papillary muscle included or excluded from LV mass measurements was compared to true mass at autopsy of the Yorkshire-Landrace swine.
Automatic LV papillary muscle mass from all subjects correlated well with manually derived LV papillary muscle mass measurements (r = 0.84) with no significant bias between both measurements (mean difference +/- SD, 0.0 +/- 1.5 g; P = .98). The variability in results related to the contour detection method used was not statistically significant different compared to intra- and interobserver variabilities (P = .08 and P = .97, respectively). LV mass measurements including the papillary muscle showed significantly less underestimation (-10.6 +/- 7.1 g) with the lowest percentage variability (6%) compared to measurements excluding the papillary muscles (mean underestimation, -15.1 +/- 7.4 g percentage variability, 7%).
The automatic algorithm for detecting the papillary muscle was accurate with variabilities comparable to intra- and interobserver variabilities. LV mass is determined most accurately when the papillary muscles are included in the LV mass measurements. Taken together, these observations warrant the inclusion of automatic contour detection of papillary muscle mass in studies that involve the determination of LV mass.
[Show abstract][Hide abstract] ABSTRACT: Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of approximately 10(8) human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92+/-3 mL) and LV mass (75+/-2 g) were larger, while ejection fraction (42+/-2%) was smaller than in healthy control (68+/-3 mL, 66+/-3 g and 55+/-3%, all P<0.05). Regional wall thickening (-7+/-2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20+/-3 g vs. 8+/-2 g, P<0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later.
Journal of Molecular and Cellular Cardiology 05/2007; 42(4):735-45. DOI:10.1016/j.yjmcc.2007.01.005 · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The purpose of this study was to evaluate the utility of delayed enhancement 64-MDCT in the assessment of myocardial infarct size in a porcine model of acute reperfused myocardial infarction. CT can be used for noninvasive assessment of coronary artery stenosis, but to our knowledge, evaluation of myocardial viability in the subacute phase of acute myocardial infarction has not been validated. We performed delayed enhancement imaging on six domestic swine 5 days after reperfused acute myocardial infarction and assessed the relation between delayed enhancement patterns in vivo and the extent of viable and nonviable myocardium at postmortem histochemical analysis. CONCLUSION: Delayed enhancement imaging with 64-MDCT can be used for accurate assessment of the size of reperfused acute myocardial infarcts.
American Journal of Roentgenology 03/2007; 188(2):W135-7. DOI:10.2214/AJR.05.1176 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stem cell therapy after myocardial infarction (MI) has been studied in models of permanent coronary occlusion. We studied the effect of intracoronary administration of unselected bone marrow (BM) and mononuclear cells (MNC) in a porcine model of reperfused MI.
In 34 swine, the left circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. Ten swine without MI served as controls. All swine underwent magnetic resonance imaging (MRI) 1 week post-MI. The next day, 10 of the 30 surviving MI swine received BM, 10 other MI swine received MNC, and the remaining MI swine received medium intracoronary. Four weeks later, all swine underwent a follow-up MRI. One week after MI, end-diastolic volume (92+/-16 mL) and left ventricular (LV) weight (78+/-12 g) were greater, whereas ejection fraction (40+/-8%) was lower than in controls (69+/-11 mL, 62+/-13 g, and 53+/-6%). Injection of BM or MNC had no effect on the MI-induced changes in global or regional LV-function. However, there was a significant reduction in infarct size 4 weeks after MNC injection (-6+/-3%) compared with the medium (-3+/-5%).
Intracoronary injection of BM or MNC in swine does not improve regional or global LV-function 4 weeks after injection. However, a reduction in infarct-size was noted after MNC injection.
European Heart Journal 01/2007; 27(24):3057-64. DOI:10.1093/eurheartj/ehl401 · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the accuracy of in vivo delayed-enhancement multislice computed tomography (DE-MSCT) and delayed-enhancement magnetic resonance imaging (DE-MRI) for the assessment of myocardial infarct size using postmortem triphenyltetrazolium chloride (TTC) pathology as standard of reference.
The diagnostic value of DE-MSCT for the assessment of acute reperfused myocardial infarction is currently unclear.
In 10 domestic pigs (25 to 30 kg), the circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. After 5 days (3 to 7 days), DE-MRI (1.5-T) was performed 15 min after administration of 0.2 mmol/kg gadolinium-DTPA using an inversion recovery gradient echo technique. On the same day, DE-MSCT (64-slice) was performed 15 min after administration of 1 gI/kg of iodinated contrast material. One day after imaging, hearts were excised, sectioned in 8 mm short-axis slices, and stained with TTC. Infarct size was defined as the hyperenhanced area on DE-MSCT and DE-MRI images and the TTC-negative area on TTC pathology slices. Infarct size was expressed as percentage of total slice area.
Infarct size determined by DE-MSCT and DE-MRI showed a good correlation with infarct size assessed with TTC pathology (R2 = 0.96 [p < 0.001] and R(2) = 0.93 [p < 0.001], respectively). The correlation between DE-MSCT and DE-MRI was also good (R2 = 0.96; p < 0.001). The relative difference in CT attenuation value of infarcted myocardium compared to remote myocardium was 191 +/- 18%. The relative MR signal intensity between infarcted myocardium and remote myocardium was 554 +/- 156%.
We demonstrated that DE-MSCT can assess acute reperfused myocardial infarction in good agreement with in vivo DE-MRI and TTC pathology.
Journal of the American College of Cardiology 08/2006; 48(1):144-52. DOI:10.1016/j.jacc.2006.02.059 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance imaging (MRI) has been proposed as a tool to track iron oxide-labelled cells within myocardial infarction (MI). However, infarct reperfusion aggravates microvascular obstruction (MO) and causes haemorrhage. We hypothesized that haemorrhagic MI causes magnetic susceptibility-induced signal voids that may interfere with iron oxide-labelled cell detection.
Pigs (n = 23) underwent 2 h occlusion of the left circumflex artery. Cine, T2*-weighted, perfusion, and delayed enhancement MRI scans were performed at 1 and 5 weeks, followed by ex vivo high-resolution scanning. At 1 week, MO was observed in 17 out of 21 animals. Signal voids were observed on T2*-weighted scans in five out of eight animals, comprising 24 +/- 22% of the infarct area. A linear correlation was found between area of MO and signal voids (R2 = 0.87; P = 0.002). At 5 weeks, MO was observed in two out of 13 animals. Signal voids were identified in three out of seven animals. Ex vivo scanning showed signal voids on T2*-weighted scanning in all animals because of the presence of haemorrhage, as confirmed by histology. Signal voids interfered with the detection of iron oxide-labelled cells ex vivo (n = 21 injections).
Haemorrhage in reperfused MI produces MRI signal voids, which may hamper tracking of iron oxide-labelled cells.
European Heart Journal 08/2006; 27(13):1620-6. DOI:10.1093/eurheartj/ehl059 · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: LEARNING OBJECTIVES
1. Describe the scan protocol for 64-slice CT and 1.5 Tesla MRI for the assessment of myocardial infarction in a porcine model of reperfused acute myocardial infarction 2. Describe the correlation between 64-slice CT, 1.5 Tesla MRI and pathology for the assessment of acute myocardial infarction
Non-invasive assessment of myocardial infarct size after acute myocardial infarction offers prognostic information. Infarct size can be assessed with Magnetic Resonance Imaging performed 10-30 minutes after the administration of gadolinium-DTPA since gadolinium-derivates accumulate in the infarcted myocardium and enhance the signal on a gated inversion-recovery gradient echo sequence. The pharmacokinetic behavior of gadolinium-derivates and iodinated contrast material is relatively similar. Therefore, we developed and optimized a delayed enhancement imaging protocol for the 64-slice CT in order to assess acute myocardial infarct size. We used a porcine model of reperfused acute myocardial infarction and performed 64-slice CT and 1.5 Tesla MRI at 5 days after infarction. This exhibit shows the positive correlation between 64 slice-CT imaging, 1.5 Tesla MRI and pathology for the assessment of acute myocardial infarction.
5 Tesla MRI with Pathology Correlation. Radiological Society of North America 2005 Scientific Assembly and Annual Meeting; 11/2005
[Show abstract][Hide abstract] ABSTRACT: PURPOSE/AIM
1. To provide an overview of current applications of MRI in Molecular Imaging. 2. To provide insight into the new developments in the field of Molecular Magnetic Resonance Imaging. 3. To create an appreciation for the versatility of MRI for Molecular Imaging research.
MRI as a single modality imaging tool in Molecular Imaging for: Cell tracking Assessment of cell function Plaque characterization Angiogenesis MRI in multi-modality applications: MRI and Optical Imaging MRI and SPECT MRI and PET MRI and Ultrasound Limitations of and challenges for MRI in Molecular Imaging.
After viewing this exhibit, the viewer will: 1. Have a basic understanding of the wide range of possibilities MRI provides in Molecular Imaging research. 2. Appreciate the versatility of MRI as an imaging tool.
Radiological Society of North America 2008 Scientific Assembly and Annual Meeting;
[Show abstract][Hide abstract] ABSTRACT: PURPOSE/AIM
1. To review the basic needs for stem cell tracking with MRI. 2. To understand the necessary tools and resolution for stem cell tracking in the heart. 3. How to optimize MRI protocols on clinical platforms to provide high spatial/temporal resolution for cardiac imaging. 4. To compare performance on clinical and specialized animal scanners.
Stem cell tracking: *Tools for detection/study cells in small laboratory animals; *examples from our research (cell labeling/tracking of dark, iron-labeled and bright, Gd-labeled stem cells in live and in-vitro myocardium). (Dis)Advantages of using lower magnetic field strengths (1.5/3T) regarding: *signal-to-noise ratio; *spatial resolution; *acquisition time; *contrast; *sensitivity to susceptibility gradients; *contrast agents. Recommendations for: *Optimizing protocols and necessary tools.
After viewing this exhibit, the viewer will: 1. understand the wide range of possibilities present in clinical MRI scanners for stem cell tracking in rodent hearts. 2. Appreciate the benefits of clinical whole body scanning platforms. 3. Know which artifacts and pitfalls to expect from the lower gradient performance of clinical imaging platforms and how to overcome the limitations. 4. Be able to optimize MRI scanning protocols for addressing rodent cardiac imaging.
Radiological Society of North America 2008 Scientific Assembly and Annual Meeting;