Panel-reactive screening and treatment practices following bridge to transplantation ventricular assist device placement.

The use of left ventricular assist devices (LVAD) as a bridge to transplantation is associated with the development of circulating antibodies. We conducted a survey of all adult cardiac transplantation programs in the United States in an attempt to define current practices with regard to LVAD implantation, monitoring panel-reactive antibody (PRA) levels, treatment options, and peritransplantation management. Pretransplantation sensitization with the use of LVAD is a concern to the majority of transplantation professionals and there is no consensus on the need or mode of treatment.

Successful treatment of Nocardia nova bacteremia and multilobar pneumonia with clarithromycin in a heart transplant patient.

Nocardia is an opportunistic pathogen in solid organ transplantation for which long-term sulfonamide therapy is considered the treatment of choice. We report a patient 7 months status post-orthotopic heart transplantation with Nocardia nova bacteremia and pneumonia. Initial treatment consisted of intravenous trimethoprim-sulfamethoxazole, which cleared blood cultures, but the patient subsequently went into renal failure and required alternative therapy. This report describes the first case of N nova bacteremia after orthotopic heart transplantation successfully treated with clarithromycin. All therapy should be guided by antibiotic sensitivity, and combination therapy should be considered in acutely ill patients and cases where in vitro synergy has been documented. This case suggests that clarithromycin can be an alternative treatment in cases of sulfonamide resistance, intolerance, or allergy.

In vivo magnetic resonance evaluation of atherosclerotic plaques in the human thoracic aorta: a comparison with transesophageal echocardiography.

BACKGROUND: The structure and composition of aortic atherosclerotic plaques are associated with the risk of future cardiovascular events. Magnetic resonance (MR) imaging may allow accurate visualization and characterization of aortic plaques. METHODS AND RESULTS: We developed a noninvasive MR method, free of motion and blood flow artifacts, for submillimeter imaging of the thoracic aortic wall. MR imaging was performed on a clinical MR system in 10 patients with aortic plaques identified by transesophageal echocardiography (TEE). Plaque composition, extent, and size were assessed from T1-, proton density-, and T2- weighted images. Comparison of 25 matched MR and TEE cross-sectional aortic plaque images showed a strong correlation for plaque composition (chi(2) = 43.5, P<0.0001; 80% overall agreement; n = 25) and mean maximum plaque thickness (r = 0.88, n = 25; 4.56+/-0.21 mm by MR and 4.62+/-0.31 mm by TEE). Overall aortic plaque extent as assessed by TEE and MR was also statistically significant (chi(2) = 61.77, P<0.0001; 80% overall agreement; n = 30 regions). CONCLUSIONS: This study demonstrates that noninvasive MR evaluation of the aorta compares well with TEE imaging for the assessment of atherosclerotic plaque thickness, extent, and composition. This MR method may prove useful for the in vivo study of aortic atherosclerosis.

High resolution ex vivo magnetic resonance imaging of in situ coronary and aortic atherosclerotic plaque in a porcine model.

Atherosclerotic plaque composition is central to the pathogenesis of plaque disruption and acute thrombosis. Thus, there is a need for accurate imaging and characterization of atherosclerotic lesions. Even though there is no ideal animal model of atherosclerosis, the porcine model is considered to most closely resemble human atherosclerosis. We report the feasibility of MR imaging and characterizing of atherosclerotic lesions from in situ coronary arteries and aortas in an ex vivo setting and validate this with histopathology. Coronary and aortic atherosclerosis was induced in Yucatan mini-swine (n=4) by a combination of atherogenic diet (6 months) and balloon injury. All coronary arteries were imaged ex vivo on the intact heart, preserving the curvature of their course. The aorta also underwent MR imaging. The MR images were correlated with the matched histopathology sections for both the coronary arteries (n=54) and the aortas (n=43). MR imaging accurately characterized complex atherosclerotic lesions, including calcified, lipid rich, fibrocellular and hemorrhagic regions. Mean wall thickness for the coronary arteries (r=0.94, slope: 0.81) and aortas (r=0.94, slope: 0.81) as well as aortic plaque area (r=0.97, slope: 0.90) was accurately determined by MR imaging (P<0.0001). Coronary artery MR imaging is not limited by the curvature of the coronary arteries in the heart. MR imaging accurately quantifies and characterizes coronary and aortic atherosclerotic lesions, including the vessel wall, in this experimental porcine model of complex atherosclerosis. This model may be useful for future study of MR imaging of atherosclerosis in vivo.

The diagnostic accuracy of ex vivo MRI for human atherosclerotic plaque characterization.

Recent evidence indicates that the type of atherosclerotic plaque, rather than the degree of obstruction to flow, is an important determinant of the risk of cardiovascular complications. In previous work, the feasibility of using MRI for the characterization of plaque components was shown. This study extends the previous work to all the plaque components and shows the accuracy of this method. Twenty-two human carotid endarterectomy specimens underwent ex vivo MRI and histopathological examination. Sixty-six cross sections were matched between MRI and histopathology. In each cross section, the presence or absence of plaque components were prospectively identified on the MRI images. The overall sensitivity and specificity for each tissue component were very high. Calcification and fibrocellular tissue were readily identified. Lipid core was also identifiable. However, thrombus was the plaque component for which MRI had the lowest sensitivity. A semiautomated algorithm was created to identify all major atherosclerotic plaque components. MRI can characterize carotid artery plaques with a high level of sensitivity and specificity. Application of these results in the clinical setting may be feasible in the near future.

Noninvasive In vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice.

BACKGROUND: The pathogenesis of atherosclerosis is currently being investigated in genetically engineered small animals. Methods to follow the time course of the developing pathology and/or the responses to therapy in vivo are limited. METHODS AND RESULTS: To address this problem, we developed a noninvasive MR microscopy technique to study in vivo atherosclerotic lesions (without a priori knowledge of the lesion location or lesion type) in live apolipoprotein E knockout (apoE-KO) mice. The spatial resolution was 0.0012 to 0.005 mm3. The lumen and wall of the abdominal aorta and iliac arteries were identified on all images in apoE-KO (n=8) and wild-type (n=5) mice on chow diet. Images obtained with MR were compared with corresponding cross-sectional histopathology (n=58). MR accurately determined wall area in comparison to histopathology (slope=1.0, r=0.86). In addition, atherosclerotic lesions were characterized in terms of lesion shape and type. Lesion type was graded by MR according to morphological appearance/severity and by histopathology according to the AHA classification. There was excellent agreement between MR and histopathology in grading of lesion shape and type (slope=0.97, r=0.91 for lesion shape; slope=0. 64, r=0.90 for lesion type). CONCLUSIONS: The combination of high-resolution MR microscopy and genetically engineered animals is a powerful tool to investigate serially and noninvasively the progression and regression of atherosclerotic lesions in an intact animal model and should greatly enhance basic studies of atherosclerotic disease.

Detection of residual quadrupolar interaction in human skeletal muscle and brain in vivo via multiple quantum filtered sodium NMR spectra.

Using sodium multiple quantum filtered methods, we have, for the first time, demonstrated the presence of residual quadrupolar interaction in human skeletal muscle and brain in vivo. Surface coils were used in both skeletal muscle and brain studies on healthy human volunteers. Theoretical analysis shows that even with arbitrary flip angles the double quantum filter retains filtering capability; it passes even rank two quantum coherence more efficiently than odd rank two quantum coherence. Multiple quantum filtered spectra were obtained from the gastrocnemius muscle in the leg and from the parietal lobe region of the brain. In double quantum filtered spectra, we observed different proportions of narrow and broad components with preparation time, while the line shape of triple quantum filtered spectra remained similar to the one observed in isotropic environment. These results suggest that, in human skeletal muscle and brain, sodium ions are bound to some ordered structures.

Reduced power selective excitation radio frequency pulses.

A pulse synthesis algorithm is described that allows for the synthesis of selective radio frequency pulses requiring less peak power. The pulses thus synthesized have the same duration, total energy, and frequency response as those synthesized by the standard algorithm. Their phase function is, however, different. The power reduction is typically on the order of 60-70%. This modification will increase the utility of optimized selective pulses.

Multiple-quantum filters of spin-3/2 with pulses of arbitrary flip angle.

The influence of inhomogeneous RF fields on the double- and triple-quantum filtering of spin-3/2 nuclei in the presence of biexponential relaxation is analyzed. In this analysis, spherical tensor operators have been used for density-matrix calculations. In the presence of inhomogeneous RF fields, it is shown that the three-pulse triple-quantum filter (TQF) without a refocusing 2 theta pulse (with delta omega = 0) is on average about 100% more sensitive than the corresponding double-quantum filter (DQF), and in the case of four-pulse DQF and TQF with a refocusing 2 theta pulse (with delta omega not equal to 0), two relaxation coefficients f(1)11(tau) and f(1)33(tau) also contribute to the observed DQ and TQ coherences. It is also shown that the three-pulse filters are more sensitive than the corresponding four-pulse filters. In both three- and four-pulse cases, when used with surface coils, these filters act as depth pulses and thus yield spatial localization. The experimental results obtained with homogeneous RF coils are in excellent agreement with the theoretical results.

The synthesis of pulse sequences yielding arbitrary magnetization vectors.

A new procedure and algorithm are presented to allow the synthesis of a pulse sequence which will generate an arbitrary frequency-dependent spin excitation. This procedure is a generalization of our previous paper, where this was done subject to the restriction that the spin excitation was symmetric about zero offset frequency, and pulses were restricted to being about a fixed axis. The required final z-magnetization vector (Mz) is expressed as a function of the off-resonance frequency as an Nth order complex Fourier series. We then form a consistent Fourier series for (Mxy). As many as 2(2)N different pulse sequences may be directly generated all of which produce a different Mxy(f), but the same Mz(f). A pulse sequence is then generated which will yield the desired Mz(f) and Mxy(f). This is done by an analytic inversion of the Bloch equation, not by the classical Fourier approximation. This technique enables us to generate any Mz which is potentially realizable by a pulse sequence.

The use of finite impulse response filters in pulse design.

We develop a new way of synthesizing pulse sequences with desirable frequency characteristics. By combining our previous results with techniques from the theory of finite impulse response filters, we can specify (1) the total duration of the pulse sequence, (2) the frequency ranges it is desired to perturb, (3) the desired perturbation, and (4) the frequency range it is desired not to perturb. We can then synthesize a hard pulse sequence which will yield that desired perturbation with the minimal possible error. The minimum error is global, in the sense that no pulse sequence can do better at achieving the specifications, and is not just a local minimum, around the pulse sequences close to the derived pulse.

The synthesis of soft pulses with a specified frequency response.

We propose a new approach to synthesizing shaped pulses, by first synthesizing a hard pulse sequence and then converting it to a soft pulse. In previous papers, we developed a new approach to synthesizing hard pulse sequences by exactly inverting the Bloch equation, which yields the optimal frequency response. These results can now be applied to shaped pulses. Specifically, one can specify (1) the total duration of the pulse, (2) the frequency range it is desired to perturb, (3) the perturbation desired and, (4) the frequency range it is desired not to perturb. One can then synthesize a shaped pulse which has the desired effect with the least possible error. This enables us to obtain very sharp inversion and pi/2 pulses.

The application of spinors to pulse synthesis and analysis.

We show how spinors may be used to solve many problems in pulse synthesis and analysis. They provide an elegant simple notation for many problems. We show how one can specify the component of a spinor and then, by exactly solving the Bloch equations, synthesize a hard pulse sequence or a soft pulse which will yield the desired spinor. This is done by generalizing our previous approach to inverting the Bloch equations. This can be applied to synthesizing refocusing pulses. Finally, some simple consequences about symmetric pulses are derived. It is shown that given a symmetric inversion pulse, one can always synthesize an asymmetric inverting pulse of the same duration, which, as an inversion, is better.

Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium.

We developed a computer model of the interaction of impulse propagation with anatomic barriers in uniformly anisotropic tissue. Its predictions were confirmed experimentally by using an in vitro cut to create a 6 X 1-mm anatomic barrier in 12 canine epicardial strips. The model predicted that long, thin barriers located parallel to the direction of impulse propagation would have little effect in delaying conduction regardless of the arrangement of cardiac fibers. In this situation, the mean experimental ratio of postcut to control conduction times across the barrier was 1.05:1.00 in 10 tissues. When impulses were proceeding perpendicular to an anatomic barrier, significant distal conduction delay was predicted and found to occur only when the conduction from pacing to recording sites was initially longitudinal to fiber orientation (mean experimental ratio, 2.34:1.00 in five tissues) but not transverse to fiber orientation (ratio, 1.08:1.00 in five tissues). We conclude that the direction of initial impulse propagation and the orientation of myocardial fibers have large effects on the degree to which anatomic barriers delay activation in cardiac tissue. These findings may have implications for the participation of anatomic barriers in reentrant circuits.

Pathological studies in rectal cancer.

In order to improve our selectivity in treating rectal cancer by local measures alone and to delineate patients most suitable for adjuvant preoperative (abdominoperineal resection) radiation therapy, we have evaluated rectal cancer size, configuration, and grade, and correlated this information with subsequent pathological findings. Data from 247 patients treated by abdominoperineal resection were analyzed. Only 15-20% of exophytic/moderately or well-differentiated tumors had gross transmural invasion, independent of size. Twelve percent of ulcerated/moderately or well-differentiated tumors less than or equal to 4 cm penetrated grossly through the wall, vs. 42% of those greater than 4 cm. Sixty-seven percent of poorly-differentiated or colloid carcinomas greater than 4 cm also had gross transmural penetration. These data suggest patients most likely to benefit from preoperative radiation therapy are those with poorly differentiated or colloid tumors, or with ulcerated lesions greater than 4 cm in size of moderate or well-differentiated histology. All seven exophytic/well-differentiated carcinomas less than or equal to 4 cm, and 4/5 exophytic/moderately differentiated tumors less than or equal to 3 cm had penetration limited to the bowel wall only.