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Biomedical subjects

Christopher M Kramer

Publications and source records attributed to Christopher M Kramer.

At least 37 records · Page 2Linked to original sources

Meeting highlights of the 8th Annual Scientific Sessions of the Society For Cardiovascular Magnetic Resonance, January 21 to 23, 2005.

Parallel tracks for clinical scientists, basic scientists, and pediatric imagers was the novel approach taken for the highly successful 8th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance, held in San Francisco, California, January 21 to 23, 2005. Attendees were immersed in information on the latest scientific advances in cardiovascular magnetic resonance (CMR) from mice to man and technological advances from systems with field strengths from 0.5 T to 11.7 T. State-of-the-art applications were reviewed, spanning a wide range from molecular imaging to predicting outcome with CMR in large patient populations.

Adult↗

Black blood gradient echo cine magnetic resonance imaging of the mouse heart.

A black blood gradient echo sequence for multiphase cardiac MRI of the mouse heart was implemented on a 4.7-T scanner and compared to a conventional bright blood sequence. Black blood was achieved using the double inversion recovery technique. Ten mice were imaged using both the bright and the black blood sequences, and 2 of the mice were additionally imaged using bright and black blood sequences modified to perform myocardial tagging. Manual planimetry of the images was performed by two independent observers to detect the endocardial and epicardial borders and subsequently to compute chamber volumes and myocardial mass. Weight of the excised left ventricle was used as a gold standard for myocardial mass. Bland-Altman analysis demonstrated reduced interobserver variability for the measurement of cardiac volumes using the black blood sequence compared to the bright blood sequence (95% confidence interval was -0.89-0.73 microL for black blood versus -1.86-1.28 microL for bright blood). Also, Bland-Altman analysis showed that the black blood sequence provides improved accuracy for the measurement of myocardial mass compared to the bright blood sequence (average difference between MRI versus weight was 0.9 microg for black blood and -11.2 microg for bright blood, P < 0.01). For myocardial tagging, qualitative assessment demonstrated improved endocardial border definition using the black blood sequence. Black blood cine MRI in mice provides reduced interobserver variability and improved accuracy for the measurement of myocardial volumes and mass compared to the conventional bright blood technique.

Animals↗

The angiotensin II type 2 receptor and improved adjacent region function post-MI.

Angiotensin II type 2 receptor (AT2-R) overexpression in the mouse heart preserves left ventricular (LV) size and global LV function during post-MI remodeling. We hypothesized that CMR tagging would localize regional improvements in myocardial function during post-MI remodeling in AT2-R cardiac overexpressed transgenic mice (TG), which could explain the preservation of global LV function post-MI. Six male wild-type (WT) C57BL/6 mice and 10 TG mice were studied by CMR at baseline (day 0) and days 1, 7, and 28 post-MI. MI was induced by 1 hour occlusion of the LAD followed by reperfusion. On day 1 post-MI, gadolinium-DTPA was injected to assess infarct size. LV size and function was assessed by cine CMR. Mean % circumferential shortening (%CS) was calculated within infarcted, adjacent, and remote regions at each time point in WT and TG mice. Quantitative interstitial collagen and mean myocyte cross-sectional area was measured postmortem at day 28 post-MI. LV end-systolic volume was lower and ejection fraction higher at baseline in the TG group and these differences were maintained post-MI. Within infarcted and remote zones, although %CS was higher in TG mice at day 0, there was no difference by day 28 between groups. Within adjacent regions, while there was no difference at day 0 or 1 in TG vs. WT, %CS was significantly higher in TG mice by day 7, and these changes persisted out to day 28 post-MI. Regional interstitial collagen and myocyte size were similar between groups. Thus, myocardial tagging can detect regional differences in contractile function post-MI in TG mice, and AT2-R overexpression is associated with improved contractile function in adjacent noninfarcted myocardium.

Angiotensin II↗

Chagas myocarditis and syncope.

This case report describes the diagnosis of Chagas myocarditis in a patient from Honduras who presented with syncope. The discussion summarizes the pathophysiology of cardiac Chagas disease. Acute, latent, and chronic Chagas myocarditis are described. The role of CMR in diagnosing Chagas myocarditis is discussed.

Adult↗

Calcified carotid atherosclerotic plaque is associated less with ischemic symptoms than is noncalcified plaque on MDCT.

OBJECTIVE: Risk assessment based on plaque vulnerability would be valuable in the management of asymptomatic carotid stenosis. The purpose of this study was to compare plaque morphology in symptomatic and asymptomatic patients with significant extracranial carotid artery stenosis using MDCT angiography. MATERIALS AND METHODS: We identified 31 patients with greater than 60% carotid artery stenosis on MDCT angiography using the criteria of the North American Symptomatic Carotid Endarterectomy Trial Collaborators. We analyzed plaque density by blinded review in Hounsfield units in the atherosclerotic plaques of 15 symptomatic and 21 asymptomatic stenotic vessels for classification as soft, intermediate, or calcified. Data were analyzed using multiple logistic regression. RESULTS: Even with age, traditional cardiovascular risk factors, and treatment taken into account, we found that calcified plaques were 21 times less likely to be symptomatic than noncalcified plaques (95% confidence interval for odds ratio, 0.003, 0.749; p = 0.030). No significant predictive value was found between soft (p = 0.23) or intermediate (p = 0.18) plaque morphology for the occurrence of symptoms. CONCLUSION: MDCT angiography may help risk-stratify patients with asymptomatic carotid artery stenosis. Extracranial carotid artery calcified plaques causing stenosis are significantly less likely to be symptomatic and thus may be more stable than noncalcified plaques. This finding may have implications for the interpretation of calcification of atherosclerotic plaque in other vascular beds.

Aged↗

Electromechanical mapping identifies improvement in function and retention of contractile reserve after revascularization in ischemic cardiomyopathy.

BACKGROUND: We hypothesized that (1) a significant proportion of ischemic dysfunctional segments that do not improve function will demonstrate postrevascularization contractile reserve and (2) electromechanical mapping (EMM) can identify segments that improve function as well as those with postrevascularization contractile reserve, a potential indicator of delayed functional improvement. METHODS AND RESULTS: Eighteen patients with severe ischemic left ventricular dysfunction underwent EMM and dobutamine (D) cardiac magnetic resonance imaging (CMR) followed by revascularization. Four months after revascularization, all patients underwent a repeated D-CMR, and at 35 months, a subgroup (n=6) underwent a third CMR. Of 120 dysfunctional segments, 60 segments had improved rest function (IRF) and 60 did not. Twenty-eight of 60 segments (47%) that did not improve RF demonstrated postrevascularization contractile reserve (CR), and 32 of 60 segments (53%) that demonstrated neither IRF nor CR were persistently dysfunctional (PD). CR segments recovered significantly greater late function compared with IRF or PD: 14+/-12% vs 2+/-5% and 4+/-7%, respectively; P<0.05. EMM ratio, defined as the unipolar voltage divided by linear shortening, was significantly higher in IRF segments compared with segments that did not improve RF: 2.4+/-4.5 vs 0.7+/-3.5, P<0.05. Unipolar voltage was stepwise lower in normal, IRF, CR, and PD segments (10.5+/-4.7, 9.3+/-3.9, 8.8+/-3.2, and 7.4+/-2.3 mV, respectively; P<0.01 for trend). CONCLUSIONS: Almost half of dysfunctional myocardial segments in chronic ischemic heart disease that do not improve RF early after revascularization demonstrate early CR and delayed functional recovery. EMM parameters can identify segments that improve RF and retain CR early after revascularization.

Adult↗

Magnetic resonance imaging identifies the fibrous cap in atherosclerotic abdominal aortic aneurysm.

BACKGROUND: MRI can distinguish components of atherosclerotic plaque. We hypothesized that contrast enhancement with gadolinium-DTPA (Gd-DTPA) could aid in the differentiation of plaque components in abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Twenty-three patients (19 males, age 70+/-8 years) with AAA underwent MRI on a 1.5-T clinical scanner 3+/-3 days before surgical grafting. T1- and T2-weighted (W) black blood spin echo imaging was performed in 1 axial slice, and the T1-W imaging was repeated after a Gd-DTPA-enhanced 3D magnetic resonance angiogram. A section of the aorta at the site of imaging was resected at surgery for histopathologic examination of tissue components and inflammatory cells. Signal-to-noise and contrast-to-noise ratios (CNR) were measured in visualized plaque components from multispectral MRI, and percent enhancement after contrast on T1-W imaging was calculated. The kappa value for agreement between pathology and MRI for the number of tissue components was 0.785. T2-W imaging identified thrombus as regions of high signal and lipid core as low signal, with a CNR of 6.43+/-3.41. Nine patients had a fibrous cap pathologically, which was visualized as a discrete area of uniform increased signal on T2-W imaging with a CNR of 4.52+/-1.93 compared with lipid core. Within the cap, the percent enhancement after Gd-DTPA on T1-W imaging was 91+/-63%. CONCLUSIONS: Higher signal on T2-W MRI identifies the fibrous cap and thrombus within AAA. Contrast enhancement improves delineation of the fibrous cap. The addition of contrast to MRI plaque imaging may enhance identification of vulnerable plaque.

Aged↗

Myocardial tissue tracking with two-dimensional cine displacement-encoded MR imaging: development and initial evaluation.

A breath-hold two-dimensional cine magnetic resonance (MR) pulse sequence based on displacement encoding with stimulated echoes (DENSE) for quantitative myocardial motion tracking was developed and evaluated. In the sequence, complementary spatial modulation of magnetization was used for time-independent artifact suppression, and echo-planar imaging was used for rapid data sampling. Twelve healthy volunteers underwent cine DENSE MR imaging, and six of them also underwent conventional MR imaging myocardial tagging. The circumferential shortening component of strain (E(cc)) was measured on cine DENSE MR images and conventional tagged MR images. With complementary spatial modulation of magnetization, 10% or less of the total cine DENSE MR image energy was attributed to an artifact-generating echo during systolic imaging. Two-dimensional intramyocardial displacement and strain were measured at cine DENSE MR imaging with spatial resolution and temporal resolution of 2.7 x 2.7 mm and 60 msec, respectively. E(cc) measured at cine DENSE MR imaging correlated well with that measured at conventional MR imaging tagging (slope = 0.88, intercept = 0.00, R = 0.87).

Adult↗

Nitric oxide mediates benefits of angiotensin II type 2 receptor overexpression during post-infarct remodeling.

We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT(2)-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT(2)-R overexpression were studied by cardiac magnetic resonance imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior descending artery occlusion and reperfusion. Sixteen TG mice were treated from day 1 through 28 post-MI with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI), wall thickness, percent thickening, and ejection fraction (EF) were measured. Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen was quantified in noninfarcted regions. At baseline, heart rate (HR), blood pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41+/-0.18 microL/g versus 2.53+/-0.14 microL/g in WT; 2.17+/-0.14 microL/g in TG-Rx; P<0.008 for both). At day 28, EF was higher in TG (46.3%+/-2.9%) compared with WT and TG-Rx (32.7+/-2.3% and 33.7+/-2.3, respectively; P<0.003 for both). Wall thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and TG-Rx. Noninfarcted region interstitial collagen was similar between groups. Thus, the NO pathway may mediate much of the benefits of cardiac AT(2)-R overexpression during post-MI remodeling.

Animals↗

Infarct involution and improved function during healing of acute myocardial infarction: the role of microvascular obstruction.

Delayed contrast-enhanced cardiac magnetic resonance imaging (ceCMR) delineates infarct size. The presence of hypoenhancement consistent with microvascular obstruction (MO) signifies larger infarcts with a worse prognosis. We hypothesized that the size of the contrast defect (CD) on ceCMR in acutely infarcted myocardium may change during infarct healing and depend upon the presence of MO. Twenty-five patients underwent CMR on weeks 1 and 8 after reperfused myocardial infarction. After short-axis cine CMR was performed, gadolinium was infused and ceCMR images and matched tagged cine MR images were obtained in the three most dysfunctional short-axis slices on cine CMR. The area and transmural extent of hyperenhancement (HE) with or without MO representing total CD size were planimetered. Between week 1 and week 8, the CD area fell from 1729+/-970 mm2 at week 1 to 1270+/-706 mm2 (p<0.001), as did the transmural extent of infarction (71+/-22% to 63+/-24%, p<0.001). The decline in CD trended to be higher in patients with MO (840+/-807 mm2) than in HE (312+/-485 mm2, p<0.07). In the patient group as a whole, ejection fraction (EF) improved (56+/-9% to 60+/-10%, p=0.002) between weeks 1 and 8, but patients with MO showed no increase in EF. Segments with some HE demonstrated partial functional improvement whereas no improvement was seen in HE+MO segments. In patients 8 weeks after reperfused myocardial infarction (MI), the size of infarction by ceCMR decreases compared to week 1 post-MI, especially in those with microvascular obstruction in whom there is little improvement in regional or global function.

Adult↗

Electromechanical mapping for detecting myocardial viability and ischemia in patients with severe ischemic cardiomyopathy.

This study was designed to evaluate several electromechanical mapping parameters for assessment of myocardial viability and inducible ischemia as defined by dipyridamole single-photon emission computed tomographic (SPECT) imaging at rest in patients with severe ischemic cardiomyopathy. Unipolar voltage, normalized unipolar voltage, bipolar voltage, and fragmentation were compared with tracer uptake at rest and reversibility on stress or rest quantitative technetium-99m sestamibi SPECT imaging in 32 patients with severe ischemic cardiomyopathy (left ventricular ejection fraction 0.24 +/- 0.08). In dysfunctional myocardial segments, logistic regression showed unipolar voltage, normalized unipolar voltage, and bipolar voltage to be predictive of viable myocardium (> or = 60% tracer uptake at rest) and was significantly higher in viable than in nonviable segments (p <0.01). A unipolar voltage of > or = 7.1 mV was the best predictor of viable myocardium. In dysfunctional viable segments, unipolar voltage was significantly higher in reversible than in fixed segments (p <0.001), and a unipolar voltage of > or = 8.5 mV had optimal power for identifying reversibility on dipyridamole SPECT imaging. We conclude that in patients with severe ischemic cardiomyopathy, unipolar voltage can identify viable from nonviable myocardium and reversible from fixed viable defects as defined by dipyridamole technetium-99m sestamibi SPECT imaging.

Aged↗

Importance of k-space trajectory in echo-planar myocardial tagging at rest and during dobutamine stress.

Hybrid fast gradient echo/echo-planar imaging (FGRE-EPI) can be used to increase temporal resolution, enhance tag contrast, and/or decrease scan time for breathhold myocardial tagging. However, off-resonance effects and motion can lead to local phase discontinuities in FGRE-EPI raw data when a conventional interleaved bottom-up k-space trajectory is used. These discontinuities can be particularly problematic for myocardial tagging, where the image energy is not only concentrated near the k-space origin, but is also concentrated in multiple spectral peaks centered throughout k-space. In this study, tag distortion artifacts in FGRE-EPI tagging due to off-resonance and velocity-induced phase discontinuities were characterized at rest and dobutamine stress, and the flyback and gradient moment smoothing (GMS) methods were shown to reduce these artifacts. For the specific parameters used in this study, flyback and GMS resulted in improved image quality at rest and stress, increased myocardium-tag contrast-to-noise ratio (11.4 +/- 2.1 vs. 10.0 +/- 2.9, P < 0.01 at rest; 11.1 +/- 1.8 vs. 8.1 +/- 2.4, P < 0.01 at stress), and reduced full width at half maximum of the tag profile (3.6 vs. 3.8 pixels at rest; 4.0 vs. 5.1 pixels at stress) compared to the conventional trajectory. A limitation of the improved trajectory is a parameter-dependent decrease in data acquisition efficiency. For the specific imaging protocol used, the repetition time of the improved trajectory increased by 36% compared to the conventional trajectory.

Artifacts↗

Imaging of cardiopulmonary diseases.

Clear physiologic adaptations to endurance and resistance training occur in the myocardium. These morphologic changes have been identified primarily by echocardiography. In the evaluation of the symptomatic athlete, imaging is a valuable tool. To differentiate athletic hypertrophy from hypertrophic cardiomyopathy, echocardiography, or MRI may be used, although the latter may be superior in the accurate assessment of wall thickness. Either imaging modality may be used to differentiate athletic dilatation from dilated cardiomyopathy in which systolic dysfunction always accompanies the dilatation. To exclude anomalous coronary arteries, either MRI or CT is a reasonable examination, although the latter requires x-ray exposure and iodinated contrast dye. Chest radiograph continues to be the standard imaging modality for athletic lung disease, whereas fluoroscopy and laryngoscopy are useful for identifying vocal cord dysfunction. Knowledge of the utility of these different imaging modalities is crucial to the practitioner of sports medicine.

Diagnostic Imaging↗

Adding angiotensin II type 1 receptor blockade to angiotensin-converting enzyme inhibition limits myocyte remodeling after myocardial infarction.

BACKGROUND: Adding angiotensin II type 1 receptor blockade (ARB) to angiotensin-converting enzyme inhibition (ACEI) further attenuates left ventricular (LV) remodeling in an ovine model of myocardial infarction (MI). We hypothesized that combined therapy with ACEI and ARB (CT) would be additive in the limitation of the myocyte hypertrophy and dysfunction that occurs in untreated adjacent noninfarcted regions during remodeling. METHODS AND RESULTS: Nineteen sheep underwent coronary ligation to create a moderate-sized anteroapical infarction. Post-MI day 2, sheep were randomized to therapy with ramipril (ACEI, n = 5) or ramipril plus losartan (CT, n = 6) or none (untreated, n = 8). Infarct size was similar between groups. At 8 weeks post-MI, myocytes were isolated from regions adjacent to and remote from the infarct to measure morphometric indices (cell volume, length, cross-sectional area, width) and parameters of contraction (% shortening and -dL/dt, rate of shortening) and relaxation (+dL/dt [rate of relengthening] and TR 70% [time for 70% relengthening]). Volume % collagen was measured from adjacent and remote regions. Adjacent myocyte volume was different between groups (2.5 +/- 0.1 x 10(4) microm(3) in CT, 3.0 +/- 0.4 x 10(4) microm(3) in ACEI, 3.5 +/- 0.2 x 10(4) microm(3) in untreated, analysis of variance [ANOVA] P =.001) as was length (158 +/- 4 microm, 161 +/- 9 microm, 189 +/- 8 microm, respectively, ANOVA P <.001). Adjacent cell volume and length in CT were lower than untreated (P <.05). Percent shortening and -dL/dt of isolated adjacent myocytes were improved with both ACEI (7.9 +/- 0.3%, -131 +/- 6 microm/sec, P <.05) and CT (7.7 +/- 0.3%, -144 +/- 8 microm/sec, P <.05) compared with no therapy (6.4 +/- 0.4%, -104 +/- 7 microm/sec), as was both +dL/dt and TR 70%. No between-group difference in volume % collagen was found in adjacent or remote regions. CONCLUSION: Compared with ACEI alone, the addition of ARB further limits adjacent noninfarcted myocyte hypertrophy during post-MI LV remodeling. Both ACEI alone and CT preserve isolated unloaded myocyte function, but neither significantly reduce interstitial collagen. The additional benefit of ARB on regional and global function in vivo may also be due to other factors including regional load.

Angiotensin Receptor Antagonists↗

MRI for the diagnosis of myocardial ischemia and viability.

Assessment of myocardial ischemia and viability plays a crucial role in the clinical management of patients with coronary artery disease. Recently, cardiovascular MRI has emerged as an important noninvasive diagnostic modality in the assessment of coronary artery disease. MRI is able to evaluate both myocardial perfusion as well as myocardial contractile reserve. Because of its superior spatial resolution, integration of qualitative and quantitative methodology, and excellent reproducibility, MRI has advantages over conventional noninvasive modalities currently used in the evaluation of myocardial ischemia and viability, and may well emerge as the premier noninvasive technique in the assessment of patients with coronary artery disease. The authors review the rapidly expanding recent literature that has now established cardiovascular MRI (including dobutamine cine MRI and vasodilator perfusion MRI techniques) as an ideal choice in the evaluation of myocardial ischemia and delayed contrast-enhanced MRI and low-dose dobutamine cine MRI for evaluation of viability. Comparisons with more established techniques such as dobutamine stress echocardiography, single photon emission computed tomography perfusion imaging, and positron emission tomography are reviewed.

Acute Disease↗

Magnetic resonance imaging to identify the high-risk plaque.

Atherosclerotic plaque stability depends on 3 factors: (1) lipid core, (2) fibrous cap and its thickness, and (3) inflammation within the cap. Magnetic resonance imaging (MRI) is a noninvasive technique that can provide information on these plaque components using a variety of pulse sequences. Assessment of plaque volume and tissue components and the efficacy of lipid-lowering therapy has been performed in human aorta and carotid arteries. Imaging the coronary wall for plaque burden is a novel application of MRI. Newer approaches also include intravascular and transesophageal MRI techniques. Several emerging MR contrast agents being tested in animal models hold promise for targeted imaging of plaque. MRI is a powerful noninvasive imaging tool with high spatial resolution that continues to prove its value in determining atherosclerotic plaque volume and tissue components.

Aorta↗