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To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals.In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI.In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p0.001), gray matter (p0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output.Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated.

Background Pixel-wise T2* maps based on breath-held segmented image acquisition are prone to ghost artifacts in instances of poor breath-holding or cardiac arrhythmia. Single shot imaging is inherently immune to ghost type artifacts. We propose a free-breathing method based on respiratory motion corrected single shot imaging with averaging to improve the signal to noise ratio. Methods Images were acquired using a multi-echo gradient recalled echo sequence and T2* maps were calculated at each pixel by exponential fitting. For 40 subjects (2 cohorts), two acquisition protocols were compared: (1) a breath-held, segmented acquisition, and (2) a free-breathing, single-shot multiple repetition respiratory motion corrected average. T2* measurements in the interventricular septum and liver were compared for the 2-methods in all studies with diagnostic image quality. Results In cohort 1 (N = 28) with age 51.4 ± 17.6 (m ± SD) including 1 subject with severe myocardial iron overload, there were 8 non-diagnostic breath-held studies due to poor image quality resulting from ghost artifacts caused by respiratory motion or arrhythmias. In cohort 2 (N = 12) with age 30.9 ± 7.5 (m ± SD), including 7 subjects with severe myocardial iron overload and 4 subjects with mild iron overload, a single subject was unable to breath-hold. Free-breathing motion corrected T2* maps were of diagnostic quality in all 40 subjects. T2* measurements were in excellent agreement (In cohort #1, T2*FB = 0.95 x T2*BH + 0.41, r2 = 0.93, N = 39 measurements, and in cohort #2, T2*FB = 0.98 x T2*BH + 0.05, r2 > 0.99, N = 22 measurements). Conclusions A free-breathing approach to T2* mapping is demonstrated to produce consistently good quality maps in the presence of respiratory motion and arrhythmias.

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.

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.

ObjectivesCytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia.BackgroundPatients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects.MethodsGranulocyte colony-stimulating factor (G-CSF), 10 μg/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.ResultsGranulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 ± 0.2 μl to 52.4 ± 10.4 μl (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 ± 12.6 μl, 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.ConclusionsGranulocyte 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.

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.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.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).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.

The mechanisms underlying reduced exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy (NHCM) could include perturbations of ventricular relaxation, diastolic compliance, or compensatory atrial systolic function. We hypothesized that a loss of atrial contractility in NHCM patients leads to reduced functional capacity. To test this hypothesis, we compared resting noninvasive left atrial ejection phase indices in 49 consecutive patients with NHCM (ages 36+/-10 years; 41% female) and normal left ventricular ejection fraction (mean, 68%+/-8%) with objective metabolic exercise parameters. Left atrial active emptying fraction, ejection force, and kinetic energy failed to predict exercise capacity. Only left atrial total and active emptying volumes correlated weakly with minute volume/CO2 production slope (r=0.31 and r=0.33; p0.05 for both). Furthermore, when subjects were stratified by New York Heart Association symptomatology, exercise parameters--but not atrial contractility--differed between groups. These data, obtained at rest, fail to suggest that NHCM-related heart failure symptoms are due to an atrial myopathy.

To test whether manganese-enhanced magnetic resonance (MR) imaging can safely depict the myocardial area at risk both during coronary artery occlusion and for at least 2 hours after reperfusion in dogs.All procedures were performed in accordance with the animal care and use committee of the National Institutes of Health. In eight dogs, the left anterior descending (LAD) coronary artery was occluded for 90 minutes, and 15 micromol of MnCl2 per kilogram of body weight was intravenously infused for 12 minutes. Phase-sensitive inversion-recovery MR imaging of the LAD arterial territory was performed before occlusion, during MnCl2 infusion, and for at least 2 hours after reperfusion. Hemodynamic responses were monitored continuously. Fluorescent microsphere enhancement was used as the reference standard for determining the area at risk ex vivo. Results are reported as percentages of left ventricular area. Correlation, Bland-Altman, and t test analyses were performed.Significant differences in manganese-induced contrast enhancement of the area at risk, the normal myocardium, and the blood (P.01) were measured during LAD artery occlusion and at least 2 hours after reperfusion. No significant changes in heart rate or blood pressure were detected during or after MnCl2 infusion. Measurements of the area at risk obtained with manganese-enhanced MR imaging during LAD artery occlusion and 2 hours after reperfusion correlated well with the size of the at-risk area demarcated by the fluorescent microspheres (during occlusion: y = 0.81x, R = 0.90; during reperfusion: y = 0.83x, R = 0.89). Bland-Altman analysis revealed small systematic errors in measurements at both occlusion and reperfusion.Manganese-enhanced MR imaging can depict the area at risk during LAD artery occlusion and at least 2 hours after reperfusion without hemodynamic compromise.

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.

Pulmonary vein imaging is integral for planning atrial fibrillation ablation procedures. We tested the feasibility of quantifying pulmonary vein ostial diameter using two-dimensional cine cardiac magnetic resonance (2D cine CMR) and three-dimensional magnetic resonance angiography (3D MRA). Nine patients with a history of atrial fibrillation and 20 normal volunteers underwent 2D cine CMR and contrast-enhanced 3D MRA of pulmonary veins on a 1.5 T scanner. Pulmonary vein ostial diameters were measured and pulmonary vein vessel border sharpness was graded qualitatively. Both techniques provided excellent pulmonary vein imaging; however, 3D MRA was faster to perform. The average difference between the systolic and diastolic pulmonary vein diameter was 2.5 mm (23.2%, p < 0.0001) in normal volunteers and 2.2 mm (16.9%, p < 0.0001) in atrial fibrillation patients. The ostial diameter measurements by 3D MRA were significantly larger than on 2D cine CMR. Additionally, the pulmonary vein borders appeared sharper with 2D cine CMR compared to 3D MRA. In conclusion, the 2D images can resolve differences in diameter across the cardiac cycle, while the 3D images provide high quality anatomical depiction but blur borders due to pulsatile motion. We suggest a protocol combining 2D cine CMR and 3D MRA for comprehensive evaluation of pulmonary veins.

Cardiovascular disease is the leading cause of mortality for women in the United States. Coronary heart disease, which includes coronary atherosclerotic disease, myocardial infarction, acute coronary syndromes, and angina, is the largest subset of this mortality, with >240 000 women dying annually from the disease. Atherosclerotic coronary artery disease (CAD) is the focus of this consensus statement. Research continues to report underrecognition and underdiagnosis of CAD as contributory to high mortality rates in women. Timely and accurate diagnosis can significantly reduce CAD mortality for women; indeed, once the diagnosis is made, it does appear that current treatments are equally effective at reducing risk in both women and men. As such, noninvasive diagnostic and prognostic testing offers the potential to identify women at increased CAD risk as the basis for instituting preventive and therapeutic interventions. Nevertheless, the recent evidence-based practice program report from the Agency for Healthcare Research and Quality noted the paucity of women enrolled in diagnostic research studies. Consequently, much of the evidence supporting contemporary recommendations for noninvasive diagnostic studies in women is extrapolated from studies conducted predominantly in cohorts of middle-aged men. The majority of diagnostic and prognostic evidence in cardiac imaging in women and men has been derived from observational registries and referral populations that are affected by selection and other biases. Thus, a better understanding of the potential impact of sex differences on noninvasive cardiac testing in women may greatly improve clinical decision making. This consensus statement provides a synopsis of available evidence on the role of the exercise ECG and cardiac imaging modalities, both those in common use as well as developing technologies that may add clinical value to the diagnosis and risk assessment of the symptomatic and asymptomatic woman with suspected CAD.

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 mol) was infused over a period of 3 min. Signal intensity increased linearly with MnCl2 dose. At 113 mol (10 mol/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 mol, 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. Magn Reson Med 54:196 –200, 2005. Published 2005 Wiley-Liss, Inc. †

Managing patients with chest pain in the Emergency Department (ED) remains a challenge where advanced imaging technology may play a role. Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging (MRI) was studied in 161 consecutive chest pain patients in a prospective observational study. Patients with ST elevation myocardial infarction were excluded from study participation. All patients underwent MRI study when hemodynamically stable, free of ongoing chest pain, and within 12 hours of symptoms onset. The MRI study takes an average of 38 +/- 12 minutes and included global and regional left ventricular function, myocardial perfusion, and gadolinium-enhanced myocardial infarction detection. The sensitivity and specificity for detecting acute coronary syndrome was 84% and 85% by MRI. The MRI was more sensitive than strict electrocardiogram (ECG) criteria for ischemia (P < 0.001) and peak troponin-I (P < 0.001). The MRI was more specific than an abnormal ECG (P < 0.001). Multivariate logistic regression analysis showed MRI was the strongest predictor of acute coronary syndrome and added diagnostic value over clinical parameters (P < 0.001). A nonstress cardiac MRI performed in this urgent clinical setting is safe and exhibited diagnostic operating characteristics suitable for triage of patients with chest pain in the emergency department. MRI accurately detected a high fraction of patients with acute coronary syndrome including patients with enzyme negative unstable angina.

Alternate inversion recovery spatial modulation of magnetization (AIR-SPAMM) can be used either for doubling the number of tags for a given tagging encoding gradient strength or for improving tagging contrast ratio. AIR-SPAMM requires only a single acquisition and utilizes inversion pulses spaced throughout the gradient recalled echo (GRE) cine acquisition to “lock” the recovering magnetization at a desired level. The theory of AIR-SPAMM is presented along with simulations and results from phantoms. AIR-SPAMM can be used either for imaging systole as demonstrated by initial in vivo results or potentially for imaging the entire cardiac cycle in a slice-interleaved manner.

Segmented cine MRI generally requires breath-holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free-breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self-gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self-gating technique uses interleaved radial k-space sampling to provide low-resolution images in real time during the free-breathing acquisition that are compared to target expiration images. Only the raw data-producing images with high correlation to the target images are included in the final high-resolution reconstruction. The self-gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath-held techniques. Because of the difficulties associated with breath-holding, the respiratory self-gating technique represents an important practical advance for cardiac MRI. Published 2004 Wiley-Liss, Inc.†

Two-dimensional fourier transform (FT) (Cartesian) breath-held electrocardiogram (ECG)-gated cardiac function imaging with MRI is an accurate and reliable method for cardiac function evaluation (1,2). However, many breath holds are required to obtain multiple two-dimensional (2D) slices covering the entire apical–basal extent of the heart. Three-dimensional (3D) methods could improve patient examination by reducing the 10–12 breath holds required for complete assessment of cardiac function to a single breath hold, thereby decreasing exam time, improving patient tolerance, and simplifying the cardiac exam. Furthermore, slice-misregistration caused by variability in breath-holding may lead to errors in measurement of left ventricular (LV) volumes; this is not a concern for 3D breath-hold imaging. 3D multiphase imaging of the heart has recently been achieved using contrast agents (3,4). More recently, preliminary studies have investigated the use of 3D balanced steady state free precession (SSFP) imaging of LV function using short TRs (5), the variable sampling in time (VAST) technique (6), sensitivity encoding (SENSE) (7), broad-use linear acquisition speed-up technique (k-t BLAST) (8), and using our approach of undersampled projection reconstruction (PR) (radial imaging) (9). Due to the requirements of short scan times for breath-hold cardiac imaging, these techniques employed unique k-space acquisition strategies, provided low spatial and/or temporal resolution, and required long breath-holds, sometimes with limited slab coverage. For these reasons, and due to lack of validation studies, the methods are not yet routinely used for clinical cardiac MR exams. Undersampled PR is promising since it provides images with spatial resolution that is roughly independent of the number of projections (and therefore scan time), although streak artifacts appear when the number of projections is reduced (10). Approximately 32 to 64 projections are required for relatively artifact-free cardiac images (11-14). Using 3D PR with projections in the x-y plane and partitions in the z direction, breath-held, segmented, ECG-gated SSFP acquisitions can provide whole heart coverage in a feasible breath hold, good through-plane spatial resolution, a temporal resolution of 70–80 msec, and higher in-plane spatial resolution than has been achieved with other 3D single breath-hold approaches. The goal of this study was to validate the 3D PR single breath hold cardiac function technique as a suitable alternative to standard multi-breath hold 2D Fourier transform (FT) techniques for characterizing LV ejection fraction (LVEF), end diastolic volume (LVEDV), end systolic volume (LVESV), and myocardial mass (LVEDM).

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. Published 2004 Wiley-Liss, Inc.†

Regions of the body with long T1, such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium-hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T1 may cause ghosts, with the number of ghosts being equal to the number of segments. B1-weighted phased-array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B1-weighted phased-array combining of multiple receiver coils.

Norlund et al. 1 from Lund University addressed two distinctly different aims in this edition of the European Heart Journal Cardiovascular Imaging. Their primary aim was to compare the diagnostic accuracy and image quality of T 2-STIR ( T 2-weighted Short Tau Inversion Recovery) oedema imaging and CE-SSFP (contrast enhanced steady-state free precession cine MRI) with respect to determining myocardium at risk (MaR). Their second aim was to determine whether there is a bimodal temporal response to oedema or MaR imaging in humans as recently described in swine and possibly also present in dogs. They used data from three separate studies to have multi-centre and multi-vendor representation of CMR MaR methodologies. They picked two clinical trials that used CMR to determine myocardial salvage: the CHILL-MI trial2 and the MITOCARE study.3 These studies provided real world experience in clinical trials aimed at measuring myocardial salvage. To address the second aim of the study, they also included patients from a third study4 to ensure that they had data on Day 1 after myocardial infarction. With respect to their first aim on image quality, Norlund et al. 1 found that T 2-STIR performs poorly for imaging MaR; only 65% of T 2-STIR datasets were considered of diagnostic …

Diastolic and systolic left ventricular (LV) dysfunction often significantly contribute to disabling symptoms in familial hypertrophic cardiomyopathy (FHC). This study compares regional LV function (midwall circumferential strain) during systole and diastole in eight FHC patients and six normal volunteers (NVs) using MR tagging. A prospectively-gated fast gradient-echo sequence with an echo-train readout was modified to support complementary spatial modulation of magnetization (CSPAMM) tagging and full cardiac cycle data acquisition using the cardiac phase to order reconstruction (CAPTOR), thus providing tag persistence and data acquisition during the entire cardiac cycle. Total systolic strains in FHC patients were significantly reduced in septal and inferior regions (both P < 0.01). Early-diastolic strain rates were reduced in all regions of the FHC group (all P < 0.03). The combination of CSPAMM and CAPTOR allows regional indices of myocardial function to be quantified throughout the cardiac cycle. This technique reveals regional differences in systolic and diastolic impairment in FHC patients.

To simultaneously differentiate stunned, infarcted, and normal myocardial regions by using gadolinium-enhanced cine magnetic resonance (MR) imaging with magnetization transfer contrast.Twelve dogs were imaged on days 1 and 8 after transient 90-minute coronary artery occlusion. A magnetization transfer contrast with echo-train readout (MTET) MR sequence was performed before and 30 minutes after gadolinium contrast enhancement. Ex vivo analysis consisted of MR imaging, microsphere blood flow analysis, and triphenyltetrazolium chloride (TTC) staining. A paired two-tailed t test was used to compare wall thickening from day 1 to day 8. Linear regression and Bland-Altman analyses were used to compare infarct size depicted with MTET imaging with that seen on TTC-stained tissue.Severe wall motion abnormalities were detected in all dogs. At TTC analysis, seven dogs had evidence of myocardial infarction and five had evidence of stunned myocardium. The mean percentages of left ventricular wall thickening in infarcted, stunned, and remote myocardial regions were 2% +/- 4 (SD), 4% +/- 8, and 33% +/- 5, respectively. Wall thickening did not improve in the infarcted zones, but it improved to nearly normal levels in the stunned region 1 week after induced occlusion (mean, 40% +/- 8; P.02). MTET images clearly depicted infarcted myocardium as brighter than both the normal and stunned myocardial regions but darker than the blood pool. In vivo MTET infarct volume correlated with ex vivo TTC analysis data (y = 1.01x + 0.00, R = 0.98, standard error of the estimate = 0.019).One day after myocardial ischemia, MTET during one MR imaging examination enabled simultaneous differentiation of infarcted, stunned, and normal myocardial regions on the basis of gadolinium enhancement and regional function.

1. Auricchio A, Sommariva L, Salo RW, Scafuri A, Chiariello L. Improvement of cardiac function in patients with severe congestive heart failure and coronary artery disease by dual chamber pacing with shortened AV delay. Pacing Clin Electrophysiol 1993;16:2034–2043. 2. Hochleitner M, Hortnagl H, Hortnagl H, Fridrich L, Gschnitzer F. Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol 1992;70:1320–1325. 3. Innes D, Leitch JW, Fletcher PJ. VDD pacing at short atrioventricular intervals does not improve cardiac output in patients with dilated heart failure. Pacing Clin Electrophysiol 1994;17:959–965. 4. Gold MR, Feliciano Z, Gottlieb SS, Fisher ML. Dual-chamber pacing with a short atrioventricular delay in congestive heart failure: a randomized study. J Am Coll Cardiol 1995;26:967–973. 5. Linde C, Gadler F, Edner M, Nordlander R, Rosenqvist M, Ryden L. Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure. J Am Coll Cardiol 1995;75:919–923. 6. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2001;38: 2101–2113. 7. Karpawich PP, Mital S. Comparative left ventricular function following atrial, septal, and apical single chamber heart pacing in the young. Pacing Clin Electrophysiol 1997;20:1983–1988. 8. Owen CH, Esposito DJ, Davis JW, Glower DD. The effects of ventricular pacing on left ventricular geometry, function, myocardial oxygen consumption, and efficiency of contraction in conscious dogs. Pacing Clin Electrophysiol 1998;21:1417–1429. 9. Zile MR, Blaustein AS, Shimizu G, Gaasch WH. Right ventricular pacing reduces the rate of left ventricular relaxation and filling. J Am Coll Cardiol 1987;10:702–709. 10. Blanc JJ, Etienne Y, Gilard M, Mansourati J, Munier S, Boschat J, Benditt DG, Lurie KG. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997; 96:3273–3277. 11. Tantengco MV, Thomas RL, Karpawich PP. Left ventricular dysfunction after long-term right ventricular apical pacing in the young. J Am Coll Cardiol 2001;37:2093–2100. 12. Hamdan MH, Zagrodzky JD, Joglar JA, Sheehan CJ, Ramaswamy K, Erdner JF, Page RL, Smith M. Biventricular pacing decreases sympathetic activity compared with right ventricular pacing in patients with depressed ejection fraction. Circulation 2000;102:1027–1032.

In nine subjects with carotid atherosclerosis, double-oblique, contrast material–enhanced, double inversion-recovery, fast spin-echo magnetic resonance (MR) images were acquired through atheroma in the proximal internal carotid artery. Fibrocellular tissue within atheroma selectively enhanced 29% after administration of gadolinium-based contrast agent. Contrast enhancement helped discriminate fibrous cap from lipid core with a contrast-to-noise ratio as good as or better than that with T2-weighted MR images but with approximately twice the signal-to-noise ratio (postcontrast images, 36.6 ± 3.6; T2-weighted images, 17.5 ± 2.1; P < .001). © RSNA, 2002

Gadolinium-based extracellular contrast agents have enabled cardiac magnetic resonance (CMR) to assess viability and fibrosis at higher resolution than alternative technologies.(Kim, Fieno et al. 1999) In this issue of JACC Cardiovascular Imaging, Hidenari Matsumoto et al from Rakuwakai Otowa Hospital, in Kyoto, Japan present convincing data that early contrast enhancement approximately 2 minutes after administration of gadolinium depicts the area at risk associated with acute myocardial infarction. The convenience of imaging both area at risk and infarct size from the same bolus of gadolinium proffers to be a huge convenience factor in expediting the assessment of myocardial salvage but this “two-for-one” benefit is accompanied by the need to understand the kinetics of gadolinium in the infarct and the peri-infarct zone.

Background T1-mapping has the potential to detect and quantify diffuse processes such as interstitial fibrosis. Detection of disease at an early stage by measurement of subtle changes requires a high degree of reproducibility. Initial implementation of saturation recovery (SR) T1-mapping employed 3-parameter fitting which was highly accurate but was quite sensitive to noise; 2-parameter fitting greatly reduced the sensitivity to noise at the expense of a small degree of systematic bias. A recently introduced implementation that uses a variable readout flip angle greatly reduces systematic errors in T1-measurement thereby making it feasible to use SR methods with 2-parameter fitting with improved accuracy and precision. SR T1 mapping techniques with multi-heartbeat recovery times have been proposed to better sample the T1 recovery curve, but have not been evaluated for 2-parameter fitting. Methods An analytic formulation for calculating the standard deviation (SD) for SR T1-mapping with 2-parameter fitting is developed and validated using Monte-Carlo simulation. The coefficient of variation is compared for a brute force optimization of sampling and for several previously described sampling schemes for T1 measurement over several uncertainty ranges. Experimental validation is performed in phantoms over a range of T1, and in-vivo both native and post-contrast. Pixel-wise SD maps are calculated for SR T1-mapping. Results Sampling schemes that use a non-saturated anchor image and multiple (N) measurements at a single fixed saturation delay are found to be near optimum for the case of known T1 and are close to the brute force optimized solution over wide ranges of native and post-contrast T1 values. The fixed delay sampling scheme is simple to implement and provides an improvement over uniformly distributed schemes. Conclusions Sampling strategies for saturation recovery methods for myocardial T1-mapping have been optimized and validated experimentally. Reduced SD, or improved precision, may be achieved by using fixed saturation delays when considering native myocardium and post-contrast T1 ranges. Pixel-wise estimates of T1 mapping errors have been formulated and validated for SR fitting methods.

P2-076 THE LINK BETWEEN SERUM NT-PROBNP AND MEMORY FUNCTION IN COMMUNITYDWELLING OLDER ADULTS Behnam Sabayan, Mark van Buchem, Sigurdur Sigurdsson, Qiane Zhang, Vilmundur Gudnason, Andrew Arai, Lenore Launer, Leiden University Medical Center, Leiden, Netherlands; Icelandic Heart Association, Kopavagur, Iceland; National Institute on Aging, Bethesda, Maryland, United States; Icelandic Heart Association, Kopavogur, Iceland; National Institutes of Health, Bethesda, Maryland, United States. Contact e-mail: b.sabayan@lumc.nl

Aims To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). Methods and results We conducted a multicentre study to evaluate the accuracy of integrated CTA–CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA–CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA–SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA–CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84–0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87–0.94) and in patients without prior CAD the AUC for combined CTA–CTP was 0.93 (95% CI: 0.89–0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72–86), 74% (68–80), 65% (58–72), and 86% (80–90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. Conclusions The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Aim Area-at-risk (AAR) measurements often rely on T2-weighted images, but subtle differences in T2 may be overlooked with this method. To determine the differences in oedema between salvaged and infarcted myocardium, we performed quantitative T2 mapping of the AAR. We also aimed to determine the impact of reperfusion time on T2 in the AAR. Methods Twenty-two dogs underwent 2 h of coronary occlusion followed by 4 or 48 h of reperfusion before cardiac magnetic resonance imaging at 1.5 T. Late gadolinium enhancement images were used to define the infarcted, salvaged, and remote myocardium. T2 values from T2 maps and signal intensities on T2-weighted images were measured in the corresponding areas. Results At both imaging time points, the T2 of the salvaged myocardium was longer than of remote (66.0 ± 6.9 vs. 51.4 ± 3.5 ms, P < 0.001 at 4 h, and 56.7 ± 7.3 vs. 48.1 ± 3.5 ms, P < 0.001 at 48 h). The T2 was also longer in the infarcted myocardium compared with remote at both 4 and 48 h (71.4 ± 7.6 ms, P < 0.01 vs. salvage and 64.0 ± 6.9 ms, P = 0.03 vs. salvage, both P < 0.001 vs. remote). The increase in T2 in the salvaged myocardium compared with remote was greater after 4 h than after 48 h (14.7 ± 5.6 vs. 8.7 ± 5.1 ms, P = 0.02). Conclusions T2 relaxation parameters are different in the infarcted and salvaged myocardium, and both are significantly longer than remote. Furthermore, the magnitude of increase in T2 was less in the salvaged myocardium after longer reperfusion, indicating partial resolution of oedema in the first 48 h after reperfusion.

Background: Hypertrophic cardiomyopathy (HCM) with midventricular hypertrophy is an uncommon phenotypic variant of the disease. Midventricular hypertrophy predisposes to intracavitary obstruction and downstream hemodynamic sequelae. Case report: We present a case of HCM with midventricular hypertrophy and obstruction diagnosed after a CT scan of the abdomen incidentally revealed a filling defect in the left ventricular apex. Transthoracic echocardiography demonstrated mid left ventricular hypertrophy and obstruction, as well as an aneurysmal apex containing a large thrombus. Cardiovascular MRI showed a spade-shaped left ventricle with midcavitary obliteration, an infarcted apex and regions of myocardial fibrosis. Due to the risk of embolization and a relative contraindication to anticoagulation, the patient underwent surgery including thrombectomy, septal myectomy and aneurysmal ligation. Conclusions: Hypertrophic cardiomyopathy with midventricular hypertrophy leads to cavity obstruction, increased apical wall tension, ischemia and ultimately fibrosis. Over time, patchy apical fibrosis can develop into a confluent scar resembling a transmural myocardial infarction in the left anterior descending coronary artery distribution. Aneurysmal remodeling of the left ventricular apex potentiates thrombus formation and risk of cardioembolism. For these reasons, hypertrophic cardiomyopathy with midventricular obstruction portends a particularly poor prognosis and should be recognized early in the disease process.

Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Aims Knowledge of adverse events associated with regadenoson perfusion cardiac magnetic resonance (CMR) and patient tolerability has implications for patient safety and staff training. We sought to assess the safety and tolerability of regadenoson stress CMR. Materials and methods A group of 728 consecutive patients (median age 58, 44% female) and 25 normal volunteers (median age 21, 24% female) were recruited from August 2009 to March 2012 using a prospective, cross-sectional study design. Subjects were stressed using fixed-dose regadenoson and imaged using a 1.5T MRI scanner. Symptoms and adverse events including death, myocardial infarction (MI), ventricular tachycardia (VT)/ventricular fibrillation (VF), hospitalization, arrhythmias, and haemodynamic stability were assessed. Results There were no occurrences of death, MI, VT/VF, high-grade atrioventricular block, or stress-induced atrial fibrillation. Notable adverse events included one case of bronchospasm and one case of heart failure exacerbation resulting in hospitalization. The most common symptoms in patients were dyspnoea (30%, n = 217), chest discomfort (27%, n = 200), and headache (15%, n = 111). There was minimal change between baseline and peak systolic and diastolic blood pressure in both patients and volunteers ( P > 0.05). A blunted heart rate response to regadenoson was noted in patients with body mass index (BMI) ≥30 kg/m2 ( P < 0.001), and diabetes ( P = 0.001). Conclusions Regadenoson CMR is well tolerated and can be performed safely with few adverse events.

Background Obesity is associated with cardiovascular morbidity and mortality. This quantitative CMR perfusion study aims to examine the contribution of body mass index (BMI) to decreased myocardial perfusion reserve (MPR). Methods 123 patients with no obstructive epicardial coronary artery disease, defined by coronary computed tomographic angiogram demonstrating < 30% stenosis, underwent regadenoson CMR 1st-pass perfusion imaging, using 0.05 mmol/kg gadolinium (Gd) followed by rest perfusion imaging (also 0.05 mmol/kg Gd) performed 20 minutes later. The subjects were categorized into 4 groups: normal BMI (between 18.5-24.9 kg/m2, overweight (BMI 25-29.9 kg/m2), Class I obese (BMI 30-34.9), and Class II and III obese (BMI≥35). Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution.

Methods Quantitative CMR perfusion was performed at 1.5T in 17 healthy volunteers under baseline (rest) and adenosine hyperemia (stress). Median filters with different kernel size were used to estimate MBF at different resolutions (0.07 g, 0.27 g, 0.61 g, 1.1 g of myocardium). MBF heterogeneity was evaluated as the relative dispersion ([RD] = standard deviation/mean) on basal- and mid-ventricular slices for each subject. Paired t-tests and linear mixed-models were used to account for withinsubject effects. Results All normal volunteers had Framingham scores

Background Mitral annular plane systolic excursion (MAPSE) reflects longitudinal left ventricular function, predicts survival in heart failure patients and provides a sensitive marker of early systolic dysfunction in hypertensive patients with normal ejection fraction (EF). Doppler mitral annulus velocity (e’) in early diastole predicts cardiac mortality, differentiates diseases and estimates filling pressures. We present a practical technique that facilitates measuring atrioventricular junction (AVJ) motion throughout the cardiac cycle from cine cardiac magnetic resonance (CMR) and correlate these measurements with EF and echocardiographydetermined e’.

This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation.Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited.Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal.The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to50% of mean epicardial flow, which yielded a sensitivity of 87% and specificity of 93%. The area under the curve for QP was 92%, which was superior to semiquantitative methods: contrast enhancement ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019, p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p0.001 and p0.001 vs. QP, respectively).Fully quantitative stress perfusion CMR has high diagnostic accuracy for detecting obstructive coronary artery disease. QP outperforms semiquantitative measures of perfusion and qualitative methods that incorporate a combination of cine, perfusion, and late gadolinium enhancement imaging. These findings suggest a potential clinical role for quantitative stress perfusion CMR.

Background Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. Methods CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. Results Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P

Individuals with SCD have recurrent episodes of ischemia-reperfusion in vital organs, and abnormal microcirculation is considered a major determinant of end organ damage. Hydroxyurea (HU) treatment has been shown to produce ATP- and nitric oxide-mediated vasodilation, and to improve red cells deformability Few tools are available to quantitatively measure microvascular blood flow in vivo. The purpose of this study was to assess the ability of a novel ECHO based imaging modality to assess the effect of hydroxyurea on cardiac and skeletal muscle perfusion in patients with sickle cell anemia. Methods and Results: Twenty-one HBSS/B0 patients, of whom 15 were treated with HU(average daily dose of 18 ± 8 mg/kg/day), underwent brachial artery ultrasound, echocardiography and contrast enhanced ultrasound (CEU) perfusion imaging of deep flexor muscles of the forearm as well as the myocardium at rest and during vasodilator stress with regadenoson ( ClinicalTrials.gov NCT016028090). Quantitative image analysis was performed to obtain microvascular blood volume and flow velocity measurements. Patients on HU had a lower white blood cell count (6.7±2.1 K/uL vs 10.0±2.1 K/uL, p Conclusions: The beneficial effects of HU therapy in SCD are varied, and clinical effects are often seen prior to a rise in fetal hemoglobin. Other effects, such as lower hemolysis, improved red cell deformability, and inhibition of adhesive properties in the microvasculature have been reported. Some of the beneficial effects of HU may be due to stimulation of nitric oxide synthase, induction of cyclic GMP dependent signaling and improved NO bioavailability. Our study indicates that SCD patients on chronic HU therapy have higher levels of myocardial and skeletal muscle microvascular blood flow. Long term studies are necessary to evaluate whether HU reduces end organ damage in SCA. Skeletal muscle and myocardial microvascular blood flow. Each panel shows blood flow in all SCD patients (red filled diamonds), SCD patients not on HU (red open triangles) and SCD patients on HU (red open inverted triangles). Panel A. Skeletal muscle perfusion normalized to hemoglobin (A x β x hemoglobin) Panel B. Myocardial perfusion normalized to hemoglobin level and total myocardial work. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Background —We report hypertrophic cardiomyopathy (HCM) in a Spanish-American family caused by a novel α-tropomyosin ( TPM1) mutation and examine the pathogenesis of the clinical disease by characterizing functional defects in the purified mutant protein. Methods and Results —HCM was linked to the TPM1 gene (logarithm of the odds [LOD] score 3.17). Sequencing and restriction digestion analysis demonstrated a TPM1 mutation V95A that cosegregated with HCM. The mutation has been associated with 13 deaths in 26 affected members (11 sudden deaths and 2 related to heart failure), with a cumulative survival rate of 73±10% at the age of 40 years. Left ventricular wall thickness (mean 16±6 mm) and disease penetrance (53%) were similar to those for the β-myosin mutations L908V and G256E previously associated with a benign prognosis. Left ventricular hypertrophy was milder than with the β-myosin mutation R403Q, but the prognosis was similarly poor. With the use of recombinant tropomyosins, we identified several functional alterations at the protein level. The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament–myosin subfragment-1 (S1) MgATPase assays, a 20% decrease in MgATPase rates in the presence of saturating calcium, a 5% decrease in unloaded shortening velocity in in vitro motility assays, and no change in cooperative myosin S1 binding to regulated thin filaments. Conclusions —In contrast to other reported TPM1 mutations, V95A-associated HCM exhibits unusual features of mild phenotype but poor prognosis. Both myosin cycling and calcium binding to troponin are abnormal in the presence of the mutant tropomyosin. The genetic diagnosis afforded by this mutation will be valuable in the management of HCM.

Fast gradient-echo sequences that use an echo-train readout are becoming more widely used, particularly for imaging the heart. An important issue for these sequences involves determining the optimal duration for the echo-train readout. In normal volunteer scans and theoretically the echo-train readout duration was varied from 2.4 to 32.8 msec. Myocardial signal-to-noise ratio (SNR), myocardium-tag signal difference-to-noise ratio (SDNR), flow artifact-to-noise ratio (FNR), and geometric distortion were measured and/or calculated. Our results showed that to obtain high SNR, SDNR, and data acquisition efficiency while minimizing FNR and geometric distortion, the readout duration should be 10-15 msec at 1.5 T.

Although magnetic resonance imaging (MRI) is capable of imaging various physiological parameters associated with the heart valves, it has generally been difficult to visualize the valve leaflets directly. The aortic valve was imaged in 120 patients referred for cardiac MRI to assess myocardial volumes or mass. The average patient age was 37 and ranged from 9 to 75 years. Heart rate ranged from 43 to 100 bpm. Imaging was performed on a 1.5 T scanner equipped with enhanced gradients and a cardiac phased-array coil. A double inversion recovery fast spin-echo sequence was used to acquire short-axis images of the aortic valve in a breath-hold (15 +/- 3 seconds). All three leaflets of the aortic valve were seen in 102 of 120 studies (85%). Two leaflets were detected in another 15 subjects. No leaflets were seen in three individuals. Seven cases of a bicuspid or thickened aortic valves were clearly distinguished from normal valves. The signal-to-noise ratio of aortic leaflets (14 +/- 5) was significantly higher than that of the residual blood signal in the aortic root (7 +/- 4, P < 0.001). MR images showed the aortic valve leaflets in a high fraction of people with suspected normal aortic valves and detected seven cases of abnormal aortic valves. The potential of MRI to study both the anatomic and functional consequences of valvular heart disease warrants further study. J. Magn. Reson. Imaging 1999;10:771-777.

Empirical data between 510 and 590 nm of diffuse reflected light from the pig heart in vivo have shown that myoglobin and cytochrome c absorption peaks with little apparent contribution of red blood cell (RBC) Hb. Monte Carlo simulations of photon migration in tissue were performed to compare the effects of myoglobin and cytochromes with those of blood Hb on photon pathlengths and diffuse reflectance of visible wavelengths (450–600 nm) from the pig heart in vivo. Wavelength dependence of the input parameters, including the transport-corrected scattering coefficients (1.1–1.2 mm−1) and the absorption coefficients of blood-free solubilized heart tissue (0.43–1.47 mm−1), as well as the absorption coefficients of Hb, were determined by an integrating sphere method and standard spectrophotometry, respectively. The Monte Carlo simulations indicate that in the 510- to 590-nm range the mean path length within the myocardium for diffusely reflected light varies from 1.4 to 1.2 mm, whereas their mean penetration depth within the epicardium is only 330–400 μm for blood-free heart tissue. Analysis shows that the blood Hb absorption extrema are only observable between 510 and 590 nm when RBC concentration in tissue is >0.5%. Blood within vessels much larger than capillaries does not contribute significantly to the spectral features, because virtually all light in this spectral range is absorbed during transit through large vessels (>100 μm). This analysis suggests that diffuse reflected light in the 510- to 590-nm region will show spectral features uniquely associated with myoglobin and cytochrome c oxygenation states within 400 μm of the surface of the heart in situ as long as the capillary RBC concentration remains

The oxygenation state of myoglobin and the redox state of cytochrome c provide information on the[Formula: see text] in the cytosol and mitochondria, respectively. An optical “window” from ∼540 to 585 nm was found in the pig heart in vivo that permitted the monitoring of myoglobin and cytochrome c without interference from Hb oxygenation or blood volume. Scanning reflectance spectroscopy was performed on the surgically exposed left ventricle of pigs. Difference spectra between control and a total left anterior descending coronary artery occlusion revealed maxima and minima in this spectral region consistent with myoglobin deoxygenation and cytochrome c and b reduction. Comparison of in vivo data with in vitro fractions of the heart, including Hb-free tissue whole heart and homogenates, mitochondria, myoglobin, and pig red blood cells, reveals minimal contributions of Hb in vivo. This conclusion was confirmed by expanding the blood volume of the myocardium and increasing mean Hb O2saturation with an intracoronary infusion of adenosine (20 μg ⋅ kg−1⋅ min−1), which had no significant effect on the 540- to 585-nm region. These results also suggested that myoglobin O2saturation was not blood flow limited under these conditions in vivo. Work jump studies with phenylephrine also failed to change cytochrome c redox state or myoglobin oxygenation. Computer simulations using recent physical data are consistent with the notion that myoglobin O2saturation is >92% under basal conditions and does not change significantly with moderate workloads. These studies show that reflectance spectroscopy can assess myocardial oxygenation in vivo. Myoglobin O2saturation is very high and is not labile to moderate changes in cardiac workload in the open-chest pig model. These findings indicate that myoglobin does not contribute significantly to O2transport via facilitated diffusion under these conditions.

Velocity-encoded phase contrast magnetic resonance imaging (MRI) has the potential to quantify regional myocardial contractile function with a sensitivity to motion comparable to implanted ultrasonic crystals. An MRI sequence and post-processing algorithm were developed to measure myocardial velocity gradients on a 1.5 T MRI scanner. These methods were validated on a rotating phantom and applied to dogs before (n = 11) and during prolonged coronary occlusion (n = 5). In phantom validation studies, the average absolute error corresponded to motion equivalent to 0.03 ± 0.04 mm (mean ± SD) during the repetition time of the experiment. Rigid body corrections during post-processing significantly simplified the interpretation of myocardial velocity vectors. In vivo, rigid body motion contributes substantially to the recorded myocardial velocities in systole and diastole and can give the false impression of regional wall motion abnormalities. After rigid body correction, normal systolic and diastolic velocity vectors in short-axis views of the left ventricle were primarily directed toward the center of the left ventricle. Transmural radial strain rate was 2.0 ± 0.6 sec−1 during systole and −3.6 ± 1.1 sec−1 during early diastole in normal canine hearts. Ischemic myocardium was easily discriminated from normal left ventricle by velocity-encoded phase contrast MRI both qualitatively and quantitatively (P < 0.01 in systole and P < 0.05 in early diastole). Although the myocardial velocity images have a spatial resolution on the order of a millimeter, the velocity encoding describes the mechanical consequences of focal myocardial ischemia with sensitivity to submillimeter displacement of the pixels. The three-dimensional nature of velocity-encoded MRI is particularly well suited to the study of the complex motion of the heart in vivo. Magn Reson Med 42:98–109, 1999. © 1999 Wiley-Liss, Inc.

A segmented k-space fast gradient-echo pulse sequence with an echo-train readout (FGRE-ET) was developed for high-quality cine imaging of the heart in reduced scan times. Using segmented FGRE-ET, cine images of the heart can be acquired in as few as 1-5 heart beats and do not display the geometric distortion and flow-related artifacts typically associated with cardiac echoplanar imaging (EPI). Segmented FGRE-ET was compared with conventional segmented FGRE and with conventional multi-phase EPI in normal volunteers. Segmented FGRE-ET was found to have reduced temporal blurring compared with segmented FGRE for cine imaging in 4 heart beats (P < 0.05). Also, segmented FGRE-ET did not display geometric distortion characteristic of conventional EPI (P < 0.05). Segmented FGRE-ET may be particularly applicable to functional cardiac stress testing because it allows versatile cine imaging in very short breath-holds.

Cardiac magnetic resonance imaging (MRI), particularly when enhanced with commonly available gadolinium-based contrast agents, is a powerful clinical tool for characterizing myocardial abnormalities. One of the best-known applications of this relatively new technology has been the detection of myocardial infarction. It is also possible to image myocardial scarring or fibrosis in other disease states such as myocarditis and infiltrative cardiomyopathies. Assomull et al. 1 from the Royal Brompton Hospital document the adjunctive diagnostic value of late gadolinium enhancement imaging in patients who present with chest pain, elevated troponin but unexpectedly ‘normal’ appearing coronary angiograms. The introduction of troponin assays revolutionized the diagnosis of acute myocardial infarction. This was largely based on the high sensitivity and specificity for acute myocardial injury. Elevated troponin was associated with adverse prognosis before we came to a consensus that it must be a marker of cardiac necrosis. On the basis of this work and a much wider range of literature than can be quoted in this brief article, the very definition of myocardial infarction was revised in 2000.2 The revised definition of myocardial infarction required either pathological evidence of acute myocardial infarction or a new set of clinical criteria based largely on serum markers of myocardial necrosis. Acute myocardial infarction can be diagnosed by a typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: (i) ischaemic symptoms, (ii) development of pathological q-waves on ECG, (iii) ECG changes indicative of ischaemia (ST-elevation or ST-depression), or (iv) percutaneous coronary intervention.2 Although overall a substantial advance in our understanding … Corresponding author. Tel: +1 301 496 3658; fax: +1 301 402 2389. E-mail address : araia{at}nih.gov

A method is proposed to reconstruct multiphase images that accurately depicts the entire cardiac cycle. A segmented, gradient-recalled-echo sequence (FASTCARD) was modified to acquire data continuously. Images were reconstructed retrospectively by selecting views from each heartbeat based on cardiac phase rather than the time elapsed from the QRS complex. Cardiac phase was calculated using a model that compensates for beat-to-beat heart rate changes. Images collected using cardiac phase to order reconstruction (CAPTOR) depict the entire cardiac cycle and lack the temporal gap that is characteristic of prospectively reconstructed sequences. Time-volume curves of the left ventricle capture the contribution of atrial contraction to end-diastolic volume (EDV). Transmitral phase-contrast flow measurements show a second peak inflow (alpha wave) that is absent in the standard sequence. Because atrial contraction contributes to ventricular EDV, images using CAPTOR potentially may provide a more reliable measure of EDV, stroke volume, and ejection fraction than standard techniques.

It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P(i)-driven heart mitochondrial respiratory rate (MV(O2 mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha1 alpha3 (cytochrome oxidase; Cyt a) content. To extrapolate this rate to the intact heart, the Cyt a content of the myocardium (nmol Cyt a/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P(i)-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O2 x min(-1) x nmol Cyt a(-1) in the dog and pig, respectively. The Cyt a content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt a/g wet wt, respectively. With these values, the MV(O2 mito) was calculated to be 29.5 (dog) and 24.3 (pig) micromol O2 x min(-1) x g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart.