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Biomedical subjects

Andrew E Arai

Publications and source records attributed to Andrew E Arai.

At least 19 recordsLinked to original sources

Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome.

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.

Adult↗

Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations.

BACKGROUND: The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2-weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. METHODS AND RESULTS: Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres (9 animals), was comparable to the size of the hyperintense zone on T2-weighted images 2 days later (43.4+/-3.3% versus 43.0+/-3.4% of the left ventricle; P=NS), and the 2 measures correlated (R=0.84). The infarcted zone was significantly smaller (23.1+/-3.7; both P<0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted images, resolved, and regional radial systolic strain partially improved from 4.9+/-0.7 to 13.1+/-1.5 (P=0.001) over 2 months. CONCLUSIONS: These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction.

Animals↗

Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain.

OBJECTIVES: This study was designed to determine the diagnostic value of adenosine cardiac magnetic resonance (CMR) in troponin-negative patients with chest pain. BACKGROUND: We hypothesized that adenosine CMR could determine which troponin-negative patients with chest pain in an emergency department have coronary artery disease (CAD) or future adverse cardiac events. METHODS: Adenosine stress CMR was performed on 135 patients who presented to the emergency department with chest pain and had acute myocardial infarction (MI) excluded by troponin-I. The main study outcome was detecting any evidence of significant CAD. Patients were contacted at one year to determine the incidence of significant CAD defined as coronary artery stenosis >50% on angiography, abnormal correlative stress test, new MI, or death. RESULTS: Adenosine perfusion abnormalities had 100% sensitivity and 93% specificity as the single most accurate component of the CMR examination. Both cardiac risk factors and CMR were significant in Kaplan-Meier analysis (log-rank test, p = 0.0006 and p < 0.0001, respectively). However, an abnormal CMR added significant prognostic value in predicting future diagnosis of CAD, MI, or death over clinical risk factors. In receiver operator curve analysis, adenosine CMR was a more accurate predictor than cardiac risk factors (p < 0.002). CONCLUSIONS: In patients with chest pain who had MI excluded by troponin-I and non-diagnostic electrocardiograms, an adenosine CMR examination predicted with high sensitivity and specificity which patients had significant CAD during one-year follow-up. Furthermore, no patients with a normal adenosine CMR study had a subsequent diagnosis of CAD or an adverse outcome.

Adenosine↗

Quantitative myocardial infarction on delayed enhancement MRI. Part II: Clinical application of an automated feature analysis and combined thresholding infarct sizing algorithm.

PURPOSE: To compare global and regional myocardial infarction (MI) measurements on clinical gadolinium-enhanced magnetic resonance (MR) images using human manual contouring and a computer algorithm previously validated by histopathology, and to study the degree to which visual assessment and human contouring of infarct extent agreed with the computer algorithm. MATERIALS AND METHODS: Infarct size in 20 patients was measured by human manual contouring and with an automated feature analysis and combined thresholding (FACT) computer algorithm. Short-axis slices were divided into myocardial sectors for regional analysis. Extent of infarction was also graded visually by consensus of expert readers and compared to human and computer contouring. RESULTS: Despite good correlations (R = 0.93-0.95) between human contouring and the FACT algorithm, human contouring overestimated infarct size by 3.8% of the left ventricle (23.8% of the MI) area (P < 0.001). Human contouring also overestimated the circumferential extent, transmural extent, and extent of infarction within a sector by 7.1%, 18.2%, and 27.9%, respectively (all P < 0.001). Both consensus reading and human contouring overestimated infarct grades compared with the FACT algorithm (P = 0.002 and P < 0.001). CONCLUSION: Clinically relevant overestimation of MI can occur in visual interpretation and in human manual contouring, particularly with respect to extent of infarction on a regional basis.

Adult↗

Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm.

PURPOSE: To develop a computer algorithm to measure myocardial infarct size in gadolinium-enhanced magnetic resonance (MR) imaging and to validate this method using a canine histopathological reference. MATERIALS AND METHODS: Delayed enhancement MR was performed in 11 dogs with myocardial infarction (MI) determined by triphenyltetrazolium chloride (TTC). Infarct size on in vivo and ex vivo images was measured by a computer algorithm based on automated feature analysis and combined thresholding (FACT). For comparison, infarct size by human manual contouring and simple intensity thresholding (based on two standard deviation [2SD] and full width at half maximum [FWHM]) were studied. RESULTS: Both in vivo and ex vivo MR infarct size measured by the FACT algorithm correlated well with TTC (R = 0.95-0.97) and showed no significant bias on Bland Altman analysis (P = not significant). Despite similar correlations (R = 0.91-0.97), human manual contouring overestimated in vivo MR infarct size by 5.4% of the left ventricular (LV) area (equivalent to 55.1% of the MI area) vs. TTC (P < 0.001). Infarct size measured by simple intensity thresholdings was less accurate than the proposed algorithm (P < 0.001 and P = 0.007). CONCLUSION: The FACT algorithm accurately measured MI size on delayed enhancement MR imaging in vivo and ex vivo. The FACT algorithm was also more accurate than human manual contouring and simple intensity thresholding approaches.

Algorithms↗

Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans.

PURPOSE: To compare fully quantitative and semiquantitative analysis of rest and stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a dual-bolus first-pass perfusion MRI method in humans. MATERIALS AND METHODS: Rest and dipyridamole stress perfusion imaging was performed on 10 healthy humans by administering gadolinium contrast using a dual-bolus protocol. Ventricular and myocardial time-signal intensity curves were generated from a series of T1-weighted images and adjusted for surface-coil intensity variations. Corrected signal intensity curves were then fitted using fully quantitative model constrained deconvolution (MCD) to quantify MBF (mL/min/g) and MPR. The results were compared with semiquantitative contrast enhancement ratio (CER) and upslope index (SLP) measurements. RESULTS: MBF (mL/min/g) estimated with MCD averaged 1.02 +/- 0.22 at rest and 3.39 +/- 0.59 for stress with no overlap in measures. MPR was 3.43 +/- 0.71, 1.91 +/- 0.65, and 1.16 +/- 0.19 using MCD, SLP, and CER. Both semiquantitative parameters (SLP and CER) significantly underestimated MPR (P < 0.001) and failed to completely discriminate rest and stress perfusion. CONCLUSION: Rest and stress MBF (mL/min/g) and MPR estimated by dual-bolus perfusion MRI fit within published ranges. Semiquantitative methods (SLP and CER) significantly underestimated MPR.

Adult↗

Long-term safety of cardiac magnetic resonance imaging performed in the first few days after bare-metal stent implantation.

PURPOSE: To investigate the long-term safety of cardiac magnetic resonance imaging (CMR) performed one to seven days after coronary artery stent (bare metal) implantation. MATERIALS AND METHODS: We analyzed 119 consecutive patients with acute myocardial infarction (MI) who underwent emergency coronary stent implantation with a bare-metal stent. CMR using a 1.5T scanner was performed on 51 patients (42.9%) at a mean of 2.7+/-3.1 days after stent implantation (CMR+ group), and the remaining 68 patients (57.1%) served as controls (CMR- group). The patients were followed up to six months for major adverse cardiac events. RESULTS: The average stent size was 3.3+/-0.5x18.4+/-6.7 mm, and 86% of the stents were made of 316L stainless steel. There were no significant differences between the CMR+ and CMR- groups in terms of infarct features, angiographic findings, or stent characteristics. Over a mean follow-up of 4.4+/-2.1 months, 12 patients (10.1%) had 16 events (13.4%). Two patients had adverse events after early MRI scan (4.3%), a rate that is lower than the event rate in the patients who did not undergo MRI (16%, P=0.04), and one of the two events was clearly not MRI related. CONCLUSION: CMR on a 1.5T scanner can be safely performed within one to seven days after coronary bare-metal stent implantation and is not associated with an increased risk of adverse clinical cardiac outcomes. In the light of accumulating data, the guidelines by stent manufacturers should be revised.

Aged↗

T2* measurement during first-pass contrast-enhanced cardiac perfusion imaging.

First-pass contrast-enhanced (CE) myocardial perfusion imaging will experience T(2) (*) effects at peak concentrations of contrast agent. A reduction in the signal intensity of left ventricular (LV) blood due to T(2) (*) losses may effect estimates of the arterial input function (AIF) used for quantitative perfusion measurement. Imaging artifacts may also result from T(2) (*) losses as well as off-resonance due to the bolus susceptibility. We hypothesized that T(2) (*) losses would not be significant for measurement of the AIF in full-dose studies using a short echo time (TE = 0.6 ms). The purpose of this study was to directly measure T(2) (*) in the LV cavity during first-pass perfusion. For single-dose Gd-DTPA (0.1 mmol/kg at 5 ml/s), the LV blood pool T(2) (*) had a mean value of 9 ms (N = 10) at peak enhancement. Distortion of the AIF due to T(2) (*) signal intensity loss will be less than 10% using TE = 0.6 ms.

Algorithms↗

Myocardial strain decreases with increasing transmurality of infarction: a Doppler echocardiographic and magnetic resonance correlation study.

BACKGROUND: Regional abnormalities in myocardial systolic function can be detected with myocardial strain measurements derived from Doppler tissue echocardiography. We studied longitudinal strain measurements in patients with evidence of myocardial infarction by cardiac magnetic resonance imaging to determine whether end-systolic strain could identify the severity of the infarction. METHODS: A total of 20 patients with chronic myocardial infarctions and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac magnetic resonance with delayed gadolinium (Gd) gadopentetate dimeglumine (DTPA) contrast hyperenhancement. Delayed Gd hyperenhancement was graded using the following scale: 0 = none, 1 = less than 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = greater than 75%. RESULTS: There was a progressive decrease in peak systolic strain in the infarct segments as the transmural extent of infarction increased. When compared with the peak systolic strain in remote segments without evidence of infarction (-19.7 +/- 0.9), the strain was significantly lower in segments with greater than 25% Gd hyperenhancement (grade 2, -14.8 +/- 1.1, P = .001; grade 3, -12.9 +/- 2.1, P = .001; grade 4, -9.1 +/- 2.0, P < .001). CONCLUSIONS: In patients with chronic myocardial infarctions, strain measurements with echocardiography show a graded response of decreasing regional strain in segments with increasing transmural extent of infarction defined by Gd hyperenhancement.

Echocardiography, Doppler↗

Cardiac magnetic resonance appearance of myocarditis caused by high dose IL-2: similarities to community-acquired myocarditis.

The purpose of this study was to describe and compare the cardiac magnetic resonance (CMR) characteristics of myocarditis caused by high dose interleukin-2 (7 patients) with community-acquired myocarditis (14 patients). A total of 21 patients with suspected myocarditis and elevated cardiac enzymes underwent cine CMR followed by delayed enhancement. The mean ejection fraction was mildly decreased in both groups. The location, pattern, and extent of DE were similar in both groups of patients. The CMR similarities between these two populations suggest that cytokine-mediated cytotoxicity may play an important role in community-acquired myocarditis.

Aged↗

Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease.

OBJECTIVES: Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. BACKGROUND: Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects. METHODS: Granulocyte colony-stimulating factor (G-CSF), 10 microg/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging. RESULTS: Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 microl to 52.4 +/- 10.4 microl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 microl, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline. CONCLUSIONS: Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients.

Aged↗

Wash-in kinetics for gadolinium-enhanced magnetic resonance imaging of carotid atheroma.

PURPOSE: To determine the wash-in kinetics of intravenous gadolinium into the fibrous cap and lipid core of carotid atheroma, and identify the time following gadolinium administration that maximizes contrast between the cap and core. MATERIALS AND METHODS: Seven subjects with carotid artery stenosis were studied. Magnetic resonance (MR) images of the atheroma were acquired using a single-inversion-recovery fast-spin-echo (IR FSE) sequence, which was serially repeated during the first 30 minutes following intravenous gadolinium administration. Postcontrast time was divided into three intervals: <10, 11-20, and >21 minutes. Adjusted signal intensity (SI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) values for postcontrast images were compared to adjusted precontrast values. RESULTS: The mean SNRs of the cap and core were significantly elevated in each postcontrast interval compared with mean precontrast values. The CNRs of the cap vs. the core increased by 19.8% (3.03 to 4.14, P = 0.03) in the first 10 minutes following gadolinium administration, and remained elevated over the next two intervals with a slight decrease in the final interval. CONCLUSION: Increased signal and contrast between the cap and core can be achieved by imaging up to 30 minutes following gadolinium administration, with peak enhancement occurring in the first 10 minutes.

Aged↗

Multi-contrast delayed enhancement provides improved contrast between myocardial infarction and blood pool.

PURPOSE: To develop and test a delayed-enhancement imaging method for improving the contrast between myocardial infarction (MI) and blood pool. MATERIALS AND METHODS: The T(2) of blood is significantly longer than that of acute or chronic MI. The proposed multi-contrast delayed-enhancement (MCODE) imaging method produces a series of images with both T(1) and T(2) weightings, which provides both excellent contrast between normal and infarcted myocardium, and between blood and MI. RESULTS: The subendocardial border between MI and blood pool was easily discriminated in the T(2)-weighted image. The measured MI-to-blood contrast-to-noise ratio (CNR) was better in the T(2)-weighted image than in the T(1)-weighted image (22.5+/-8.7 vs. 2.9+/-3.1, mean+/-SD, N=11, P<0.001, for True FISP, and 19.4+/-10.8 vs. 3.9+/-2.3, N=11, P<0.001, for Turbo FLASH). CONCLUSION: The MCODE method provides a significant improvement in the ability to easily discriminate subendocardial MI by providing a T(2)-weighted image with high contrast between blood and MI. MCODE should improve both the detection and accurate sizing of MI.

Contrast Media↗

Motion-corrected free-breathing delayed enhancement imaging of myocardial infarction.

Following administration of Gd-DTPA, infarcted myocardium exhibits delayed enhancement and can be imaged using an inversion-recovery sequence. A conventional segmented acquisition requires a number of breath-holds to image the heart. Single-shot phase-sensitive inversion-recovery (PSIR) true-FISP may be combined with parallel imaging using SENSE to achieve high spatial resolution. SNR may be improved by averaging multiple motion-corrected images acquired during free breathing. PSIR techniques have demonstrated a number of benefits including consistent contrast and appearance over a relatively wide range of inversion recovery times (TI), improved contrast-to-noise ratio, and consistent size of the enhanced region. Comparison between images acquired using segmented breath-held turbo-FLASH and averaged, motion-corrected, free-breathing true-FISP show excellent agreement of measured CNR and infarct size. In this study, motion correction was implemented using image registration postprocessing rather than navigator correction of individual frames. Navigator techniques may be incorporated as well.

Algorithms↗

Manganese enhanced magnetic resonance imaging of normal and ischemic canine heart.

The ability of MnCl2 to enhance canine myocardium and to delineate ischemic areas is demonstrated. A dose-response curve was measured using T1 weighted images in 11 dogs. MnCl2 (36, 113, 360, and 3600 micromol) was infused over a period of 3 min. Signal intensity increased linearly with MnCl2 dose. At 113 micromol ( approximately 10 micromol/kg) the steady-state increase in intensity averaged 212 +/- 34%. No significant physiologic effects due to the infused MnCl2 were detected except at the highest dose where there was a cardiac depressive effect. Ischemia was induced by occluding the left anterior descending coronary artery in 5 dogs. At an infused dose of 113 micromol, MnCl2 clearly demarcated the ischemic zone during coronary occlusion. Contrast enhancement in the ischemic zone was less than 30% compared with normal tissue (P < 0.03). In conclusion, the intracellular contrast agent MnCl2 enhances the canine heart and shows promise in detecting ischemia at doses that do not cause adverse cardiac effects.

Animals↗

Left atrial volumetric remodeling is predictive of functional capacity in nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The left atrium is afterload sensitive, responding to immediate changes in left ventricular (LV) diastolic pressure, and left atrial volumetric remodeling has been reported in conditions associated with abnormal diastolic function. We examined the relationship between left atrial volumetric remodeling and objective measures of exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (HCM). METHODS: We compared LA volume indices, other 2-dimensional and Doppler echocardiographic parameters, invasive hemodynamic measures, and magnetic resonance imaging (MRI)-derived LV mass with exercise duration, maximal oxygen uptake (MV* O2), anaerobic threshold (AT), and ventilatory efficiency (VE/V* CO2 slope) in 43 patients with nonobstructive HCM. Patients underwent cardiac catheterization within 48 hours and metabolic stress testing within 1 week of their echocardiogram and MRI examinations. RESULTS: Left atrial volume at end-ventricular systole (LA max) and end-atrial emptying (LA min) correlated with MV* O2 (r = -0.39, P < .01 for both), AT (r = -0.42, r = -0.39, respectively, P < .01 for both), and VE/V* CO2 slope (r = 0.45, P = .003; r = 0.41, P = .008). Patients with an LA max > or =33 mL/m2 had significantly lower MV* O2 (P = .025) and AT levels (P = .017) and higher VE/V* CO2 slope levels (P = .004) as compared with patients with a smaller LA size. In multivariate analysis, MRI-determined LV mass, which was not a univariate correlate of exercise tolerance, provided additional effect when combined with LA volume index. CONCLUSIONS: Left atrial volumetric remodeling predicts exercise capacity in nonobstructive HCM and may reflect chronic LV diastolic burden. This simple noninvasive measure of LA size may provide a long-term indication of the effects of chronically elevated filling pressures in patients with HCM and further studies testing its prognostic value are necessary.

Adult↗

DENSE with SENSE.

Displacement encoding with stimulated echoes (DENSE) with a low encoding strength phase-cycled meta-DENSE readout and a two fold SENSE acceleration (R = 2) is described. This combination reduces total breath-hold times for increased patient comfort during cardiac regional myocardial contractility studies. Images from phantoms, normal volunteers, and a patient are provided to demonstrate the SENSE-DENSE combination of methods. The overall breath-hold time is halved while preserving strain map quality.

Artifacts↗

Reproducibility and inter-observer variability of dobutamine stress CMR in patients with severe coronary disease: implications for clinical research.

PURPOSE: The purpose of this study was to analyze reproducibility and inter-observer variability of dobutamine stress cardiac magnetic resonance imaging (dobutamine CMR) and its implications on serial studies. METHODS: Nineteen consecutive patients underwent two dobutamine CMR each (median 12 days apart), as part of eligibility criteria for phase I/II stem cell therapy trial. These patients had Canadian Cardiovascular Society Class III/IV angina despite maximal therapy. The two studies were compared for reproducibility of stress response. To assess inter-observer variability, 29 randomly selected dobutamine CMR studies were analyzed by three experienced observers and Kappa values were computed to measure the agreement. RESULTS: Dobutamine CMR studies were completed without any major complications. The left ventricular function, dobutamine and atropine dose, hemodynamic response, symptomatic response and the results of wall motion and perfusion abnormalities were highly reproducible between the two studies (p = .91). Sample size calculations suggested that a clinical trial using dobutamine CMR to detect an endpoint of resolution of two ischemic segments would require a sample size of 20 subjects and to detect an improvement in perfusion of two segments would require a sample size of 8 subjects. Inter-observer variability between individual and consensus interpretation of dobutamine CMR was good to very good (kappa = 0.81 for wall motion and 0.70 for perfusion). CONCLUSION: Dobutamine CMR is a highly reproducible technique with very good inter-observer variability and could be used as a specific endpoint in a relatively small clinical trial.

Adrenergic beta-Agonists↗