Walter J. Rogers

Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging.

It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio-frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400-500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short-axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines.

Background Efficient early diastolic filling is essential for normal cardiac function. Diastolic suction, as evidenced by a decreasing left ventricular pressure during early filling, could result from restoring forces (the release of potential energy stored during systolic deformation) dependent on myofilament relaxation. Although these restoring forces have been envisioned within individual myofibers, recent studies suggest that gross fiber rearrangement involving the connective tissue network occurs early in diastole. This may lead to the release of potential energy stored during systole and suction-aided filling. Methods and Results To establish precisely the timing and extent of restoration of the systolic torsional deformation of the left ventricle with respect to early filling at baseline and with enhanced relaxation, we studied untwisting during control conditions and with catecholamine stimulation. Using noninvasive and nondestructive magnetic resonance tagging, torsional deformation of the left ventricle was measured at 20-msec intervals in 10 open-chest, atrially paced dogs, starting at aortic valve closure. Eight equiangular tags intersected the epicardium and endocardium in three short-axis imaging planes (base, mid, and apex). From the intersection points, epicardial and endocardial circumferential chord and arc lengths were measured and angular twist of mid and apical levels with respect to the base (maximal torsion and its reversal, untwisting) was calculated. Echo-Doppler provided timing of aortic valve closure and of mitral valve opening. Zero torsion was defined at end diastole. Torsion at the apical level reversed rapidly between its maximum and the time immediately after mitral valve opening: from 7.0±5.80 to 3.2±5.40 and 12.0±8.50 to 6.9±7.80 (mean±SD, both p < 0.01) at the epicardium and endocardium, respectively. During the same period, no significant circumferential segment length changes occurred. As expected, after mitral valve opening, filling resulted in significant circumferential segment lengthening, whereas further reversal of torsion was small and nonsignificant. During dobutamine infusion, torsion at end systole was greater and reversal during isovolumic relaxation was much more rapid and greater in extent (p < 0.01). Torsion reversed from 11.5±4.3° to 5.7±4.8° and 17.4±6.4° to 6.9±7.7° at epicardium and endocardium. Conclusions Untwisting occurs principally during isovolumic relaxation before filling and is markedly enhanced in speed and magnitude by catecholamines. This partial return of the left ventricle to its preejection configuration before mitral valve opening could represent an important mechanism for the release of potential energy stored in elastic elements during the systolic deformation. These myocardial restoring forces would be markedly enhanced by physiological changes consequent to catecholamines such as during exercise, offsetting the concomitant shortening of the filling period.

Technology insight: in vivo cell tracking by use of MRI.

Animal studies have shown some success in the use of stem cells of diverse origins to treat heart failure and ventricular dysfunction secondary to ischemic injury. The clinical use of these cells is, therefore, promising. In order to develop effective cell therapies, the location, distribution and long-term viability of these cells must be evaluated in a noninvasive manner. MRI of cells labeled with magnetically visible contrast agents after either direct injection or local or intravenous infusion has the potential to fulfill this goal. In this Review, techniques for labeling and imaging a variety of cells will be discussed. Particular attention will be given to the advantages and limitations of various contrast agents and passive and facilitated cell-labeling methods, as well as to imaging techniques that produce negative and positive contrast, and the effect on image quantification of compartmentalization of contrast agents within the cell.

Determination of left ventricular mass by magnetic resonance imaging in hearts deformed by acute infarction.

Measurement of left ventricular (LV) mass by magnetic resonance imaging (MRI) is accurate in normal hearts. Because determination of mass by MRI does not require assumptions about ventricular shape, this method may be well suited for evaluating hearts distorted by infarction. To test this hypothesis, gated MRI was performed in 15 dogs before and after acute myocardial infarction. The LV mass of each dog was calculated from five short-axis images acquired at end systole, when shape distortion is greatest, at end diastole, and also from slices at varying phases of the cycle with a multiphase mode that required only one acquisition. Correlation was excellent between actual mass and end-systolic mass before infarction (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after infarction (p less than 0.001, r = 0.97, and SEE = 6.6 g). Likewise, values correlated closely at end diastole before (p less than 0.001, r = 0.96, and SEE = 6.7 g) and after infarction (p less than 0.001, r = 0.94, and SEE = 8.7 g). Surprisingly, measurements of mass by a multiphase mode were also very accurate before (p less than 0.001, r = 0.98, and SEE = 5.1 g) and after (p less than 0.001, r = 0.95, and SEE = 6.49 g) infarction. Therefore, at the same phase and at multiphases of the cardiac cycle, MRI permits accurate determination of LV mass in distorted hearts.

Quantification of and correction for left ventricular systolic long-axis shortening by magnetic resonance tissue tagging and slice isolation.

BackgroundMeasurement of regional left ventricular (LV) function is predicated on the ability to compare equivalent LV segments at different time points during the cardiac cycle. Standard techniques of short-axis acquisition in two-dimensional echocardiography, cine computed tomography, and standard magnetic resonance imaging (MRI) acquire images from a fixed plane and fail to compensate for through-plane motion. The shortening of the left ventricle along its long axis during systole results in planar images of two different levels of the ventricle, leading to error in any derived functional measurements. LV systolic long-axis motion was measured in 19 normal volunteers using MRI. Methods and ResultsWith a selective radio frequency (RF) tissue-tagging technique, three short-axis planes were labeled at end diastole and standard spin-echo images were acquired at end systole in the two- and four-chamber orientations. Persistence of the tags through systole allowed visualization of the intersecting short-axis tags in the long-axis images and allowed precise quantification of long-axis motion of the septum, lateral, anterior, and inferior walls at the base, mid, and apical LV levels. The total change in position along the long axis between end diastole and end systole was greatest at the base, which moved toward the apex 12.8 ± 3.8 mm. The mid left ventricle moved 6.9 ± 2.6 mm, and the apex was nearly stationary, moving only 1.6 ± 2.2 mm (p < 0.001). Having quantified the normal range of long-axis shortening, we developed a technique that isolates a slice of tissue between selective RF saturation planes at end diastole. Combining this with a wide end-systolic image slice, end-systolic images were acquired without contamination of signal from adjacent tissue moving into the imaging plane. This technique was validated in a moving phantom and in normal volunteers. ConclusionsSignificant LV systolic long-axis shortening exists, and this effect is seen the most at the base and the least at the apex. At a given ventricular level, shortening varied significantly according to location. A method using selective saturation pulses and gated spin-echo MRI automatically corrects for this motion and thus eliminates misregistration artifact from regional function analysis.

Quantification and validation of left ventricular wall thickening by a three-dimensional volume element magnetic resonance imaging approach.

We have developed a method to quantify and map regional wall thickening throughout the left ventricle (LV) with magnetic resonance imaging. In contrast to methods that measure planar wall thickness and thickening, this method uses the three-dimensional (3D) geometry of the left ventricle to calculate the perpendicular thickness of the wall. We tested this method at three levels of increasing complexity using 1) phantom studies, 2) in vivo experiments in dogs with normal cardiac function, and 3) in vivo studies in dogs during acute ischemia. Experiments were conducted in 15 open-chest dogs imaged by a 0.38 T iron core magnet. Five short-axis images at end diastole and end systole were obtained with the spin echo technique by use of the QRS as a trigger for end diastole and the second heart sound, S2, to time end systole. After acquisition of preischemic images, acute ischemia was induced by either coronary artery ligation (n = 5) or intracoronary dental rubber injection (n = 5), which produced severe transmural ischemia. By use of computer-aided contouring of the endocardial and epicardial borders, each image was divided into 16 segments with radial lines originating from the midwall centroid. A 3D volume element was defined as that generated by connecting two matched planar segments in two adjacent image planes. This defined 64 volume elements comprising the entire left ventricle. Thickness and thickening before and during ischemia were then calculated by using the planar segments and the 3D volume elements. In phantom studies, the 3D method was accurate, independent of the angle of inclination of the image plane to the phantom wall, whereas the planar method showed considerable overestimation of thickness when the image plane was oblique to the phantom wall. In the dogs before induction of ischemia, the 3D method demonstrated the well-established normal taper in end-diastolic wall thickness from 1.10 +/- 0.02 cm at the base to 1.05 +/- 0.11 cm at the apex (p less than 0.01). By contrast, the planar method did not detect the decrease in thickness toward the apex (1.13 +/- 0.07 cm at the base vs. 1.16 +/- 0.14 cm at the apex, p = NS). During acute ischemia, thickening was calculated by both methods at the center of the ischemic zone defined by Monastral blue nonstaining and compared with the preischemic values.(ABSTRACT TRUNCATED AT 400 WORDS)

Magnetic Resonance Imaging of Carotid Atherosclerotic Plaque in Clinically Suspected Acute Transient Ischemic Attack and Acute Ischemic Stroke

Background— Carotid atherosclerotic plaque rupture is thought to cause transient ischemic attack (TIA) and ischemic stroke (IS). Pathological hallmarks of these plaques have been identified through observational studies. Although generally accepted, the relationship between cerebral thromboembolism and in situ atherosclerotic plaque morphology has never been directly observed noninvasively in the acute setting. Methods and Results— Consecutive acutely symptomatic patients referred for stroke protocol magnetic resonance imaging/angiography underwent additional T1- and T2-weighted carotid bifurcation imaging with the use of a 3-dimensional technique with blood signal suppression. Two blinded reviewers performed plaque gradings according to the American Heart Association classification system. Discharge outcomes and brain magnetic resonance imaging results were obtained. Image quality for plaque characterization was adequate in 86 of 106 patients (81%). Eight TIA/IS patients with noncarotid pathogenesis were excluded, yielding 78 study patients (38 men and 40 women with a mean age of 64.3 years, SD 14.7) with 156 paired watershed vessel/cerebral hemisphere observations. Thirty-seven patients had 40 TIA/IS events. There was a significant association between type VI plaque (demonstrating cap rupture, hemorrhage, and/or thrombosis) and ipsilateral TIA/IS (P<0.001). A multiple logistic regression model including standard Framingham risk factors and type VI plaque was constructed. Type VI plaque was the dominant outcome-associated observation achieving significance (P<0.0001; odds ratio, 11.66; 95% confidence interval, 5.31 to 25.60). Conclusions— In situ type VI carotid bifurcation region plaque identified by magnetic resonance imaging is associated with ipsilateral acute TIA/IS as an independent identifier of events, thereby supporting the dominant disease pathophysiology.

Perfluoro-t-butyl-containing compounds for use in fluorine-19 nmr and/or mri

The present invention is directed to biological compounds derivatized so as to contain at least one perfluoro-t-butyl moiety for use in fluorine-19 NMR and/or MRI studies. The perfluoro-t-butyl (PFTB) moiety, ##STR1## is an excellent reporter group for fluorine-19 NMR/MRI. It is a source of nine magnetically equivalent fluorine nuclei which generate a single intense resonance for easy detection in spectroscopy or imaging. This signal is a sharp singlet, not split by neighboring nuclei or spread over a wide frequency range and eliminates any chance of ghost images which might arise from multiple resonances. These spectral properties ensure a maximum signal-to-noise ratio (S/N) for readily detecting this moiety. The foregoing allows either reduction in the concentration of the derivatized compound, ability to use MRI instruments with lower field strengths, a reduction in imaging times, or a combination of the foregoing as a result of this moiety producing a single, sharp, intense resonance. Additionally, the PFTB moiety-containing compounds may be utilized to determine oxygen concentration in aqueous solutions present in animate and inanimate objects.

Effects of afterload on regional left ventricular torsion

OBJECTIVE To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.

Regional myocardial strain before and after mitral valve repair for severe mitral regurgitation.

Magnetic resonance tagging (MRI) can be used to study intramyocardial trains in human in vivo. We wished to determine whether patients with severe mitral regurgitation demonstrate subtle myocardial contractile dysfunction despite normal left ventricular (LV) ejection fraction (EF) and how, mitral valve repair (MVR) may preserve EF in such patients. MRI was performed on seven patients with severe mitral regurgitation (mean age +/- SD, 65+/-13 years) and normal EF day 1 (range, 0-8 days) before (Pre) and week 8+/-3 after (Post) MVR and on nine normal volunteers (mean age, 32+/-4). LV mass index (LVMI), end-diastolic and end systolic volume, mass/volume ratio, EF, and sphericity index were measured Pre and Post. Two-dimensional strain analysis of MR tagged images was performed and expressed as L1 (greatest systolic lengthening, radial in normal subjects), L2 (greatest systolic shortening, circumferential in normals), and beta (angular deviation of L1 from the radial direction). LVMI fell from 142+/-38 g/m2 Pre to 117+/-44 g/m2 Post (p < or = 0.008) as did LV end-diastolic volume (117+/-26 to 69+/-12 ml, p < or = 0.003), whereas EF remained unchanged (59+/-7% at both time points). LV mass/volume ratio increasedfrom 2.2+/-0.3 g/ml Pre to 3.1+/-0.4 g/ml Post (p < or = 0.02) and sphericity index fell from 0.86+/-0.10 to 0.71+/-0.13 (p = 0.02). In the short axis, L1 was greater in patients with mitral regurgitation than normal subjects (19+/-9% vs 16+/-6%, p < or = 0.003) and tended to increase further after MVR (21+/-8%, p < or = 0.06 vs. Pre). Beta was abnormal in mitral regurgitation (19+/-8 vs. 12+/-8 degrees in control subjects, p < 0.0001) and remained abnormal after MVR (19+/-9 degrees). L2 in the short axis was depressed in mitral regurgitation compared with control subjects (12+/-6% vs. 21+/-6%, p < or = 0.001) and was further depressed after MVR (9+/-7%, p < 0.001 vs. Pre). As detected by MRI, regional myocardial strains are abnormal in severe mitral regurgitation despite normal EF, characterized by increased short-axis systolic lengthening that is abnormally directed and by reduced shortening. After MVR, the further increase in short-axis lengthening may preserve EF despite its abnormal direction and a fall in shortening. The increase in short-axis lengthening may be due in part to the reduction in LV sphericity after MVR.