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Biomedical subjects

George R Sutherland

Publications and source records attributed to George R Sutherland.

At least 19 recordsLinked to original sources

The potential clinical role of ultrasonic strain and strain rate imaging in diagnosing acute rejection after heart transplantation.

BACKGROUND: There has been a continued search for a more sensitive noninvasive technique for detecting sub-clinical acute rejection in heart transplant recipients. Ultrasonic deformation imaging (strain/strain rate) is sensitive in detecting sub-clinical abnormalities in regional systolic function and could potentially be sufficiently sensitive to detect changes in deformation induced by graft rejection. AIM: To assess the use of strain (S) and strain rate (SR) imaging as a noninvasive method for monitoring and diagnosing acute rejection in heart transplant recipients. METHODS AND RESULTS: A prospective preliminary study was carried out involving 31 consecutive heart transplant patients who underwent a total of 106 routine follow up endomyocardial biopsy with correlative cardiac ultrasound data. To assess regional longitudinal deformation, ultrasonic S and SR data were acquired from the intraventricular septum, left ventricular (LV) lateral and right ventricular free walls (RVFW). For radial deformation, data were obtained from the LV posterior wall (LVPW). According to the International Society of Heart and Lung Transplantation criteria, 88 biopsies (Group 1) had grade 0 or IA rejection, and 18 biopsies (Group 2) had > or =grade IB rejection. Longitudinal peak systolic S and SR were decreased (p<0.05) in Group 2, compared to Group 1 in the RVFW basal and apical segments and the basal and mid segments of the LV lateral wall. Radial peak systolic S and SR were significantly lower (p<0.001) in Group 2, compared to Group 1. CONCLUSIONS: S/SR imaging might be a good technique and an additional tool for detecting > or =IB grade of acute rejection. The myocardial deformation, as assessed by S/SR imaging could be of clinical value in monitoring and diagnosing acute rejection in heart transplant recipients and could improve patients' management by reducing the number of biopsies performed.

Acute Disease↗

Sequential changes of myocardial function during acute myocardial infarction, in the early and chronic phase after coronary intervention described by ultrasonic strain rate imaging.

OBJECTIVE: The aim of this prospective clinical study was to follow up patients with acute myocardial infarction from the ischemic event, over the primary coronary intervention (PCI), up to the chronic phase after survived myocardial infarction by noninvasive strain rate (SR) imaging and to determine its role in the assessment of transmurality of infarction. METHODS: In all, 41 patients with acute S-T elevation infarction were examined immediately before, 3 days after, and 5 months after PCI. Regional myocardial function was assessed by the use of ultrasonic SR imaging and peak systolic SR and systolic strain were extracted. In addition, late-enhancement (LE) imaging with magnetic resonance imaging was done after 5 months to assess the transmurality of residual scar distribution. RESULTS: Magnetic resonance imaging showed that 8 patients had no LE (complete recovery = no-scar group), 16 patients had subendocardial LE (nontransmural infarction = NT group), and 17 patients had a transmural LE (transmural infarction = T group) in the region of interest. Before PCI both SR and strain were markedly reduced in the ischemic segments compared with the nonischemic remote region in all 3 groups (SR: ischemia = -0.6 +/- 0.3 s(-1); remote = -1.3 +/- 0.4 s(-1), P < .001). Three days after PCI, systolic SR only increased significantly in the regions that were not transmurally infarcted. After 5 months the measurement of systolic strain could accurately distinguish the different groups. (no-scar group = -24 +/- 5%, NT group = -13 +/- 4%, T group = -1 +/- 3%). CONCLUSIONS: This clinical study shows that with SR imaging: (1) the ischemic segment can be precisely detected; (2) the absence of transmurality early after coronary intervention can be predicted; and (3) in the chronic phase the transmurality of scar distribution can be assessed.

Angioplasty, Balloon, Coronary↗

How to distinguish between ischemic and nonischemic postsystolic thickening: a strain rate imaging study.

Ongoing myocardial thickening after aortic valve closure (postsystolic thickening = epsilonPST) is an established marker for the presence of segmental ischemia. However, epsilonPST may also be present in late activated segments and can be induced by pharmacological interventions or left ventricular pressure overload. The aim of this study was to determine if it is possible to distinguish between ischemic and nonischemic epsilonPST. In an experimental pig-model (n = 11) regional radial deformation was measured in the inferolateral wall during either normal perfusion or regional ischemia using ultrasonic strain rate imaging. Ischemia was induced by active hypoperfusion of the circumflex coronary artery territory. Measurements were made at 1. baseline, and during 2. theodrenalin infusion, 3. dobutamine infusion 4. esmolol infusion and 5. during a preload increase induced by saline infusion. In all segments where thickening was ongoing after aortic valve closure, the amount of epsilonPST was calculated as the difference of maximal strain minus systolic strain. In addition, peak strain rate during the isovolumetric relaxation period was extracted. During normal coronary perfusion, 73% of all segments (n = 40) developed epsilonPST. This physiological epsilonPST averaged 5 +/- 2% and was most frequently induced during the esmolol infusion (n = 11). Peak isovolumetric strain rate averaged -2.1 +/- 0.5 s(-1) in segments with physiological epsilonPST. During coronary hypoperfusion, 96% of the "at risk" segments developed epsilonPST. EpsilonPST in the ischemic segments averaged 14 +/- 3%, and was highest during the dobutamine infusion (25 +/- 4%) and lowest during the esmolol infusion (5 +/- 1%). In contrast to normally perfused segments, peak isovolumetric strain rate was positive in the ischemic segments and averaged 2.0 +/- 0.5 s(-1) in these pathologic segments with postsystolic strain. Using a cut-off value of > or = 0 s(-1) for isovolumetric strain rate, pathologic epsilonPST was detected with a sensitivity of 100% and a specificity of 87%. These experimental findings were confirmed by a subsequent clinical study with 6 patients with acute myocardial infarction (ischemic group) and 6 patients with arterial hypertension or aortic stenosis (nonischemic group). Ischemic and nonischemic postsystolic thickening can be precisely differentiated by extracting the polarity of the peak isovolumetric strain curve.

Adrenergic beta-Antagonists↗

Experimental assessment of a new research tool for the estimation of two-dimensional myocardial strain.

One-dimensional strain imaging has been shown to be angle dependent. To address this problem, a new methodology, 2D-strain, has become available. The aim of this study was to validate this methodology in an in vivo set-up against sonomicrometry. In five open chest sheep, ultrasound gray-scale images were acquired of the inferolateral wall from two different angles. The longitudinal and radial strain components were simultaneously extracted using the novel 2D-strain methodology. The extracted values were compared with sonomicrometry using Bland-Altman statistics and correlation coefficients. A good agreement was found for the longitudinal strain component, while, for the radial strain estimates, the accuracy was less. 2D-strain is a fast and accurate tool to assess longitudinal strain from apical views. Further improvements are needed for the method to be sufficiently accurate in estimating the deformation perpendicular or close to perpendicular to the ultrasound beam.

Animals↗

Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle.

BACKGROUND: Strain and strain rate have been proposed as tools to quantify regional myocardial function. One of the major pitfalls of the current methodology is its angle dependency. To overcome this problem, we have developed a new method for the estimation of strain, independent of angle. The aim of this study was to validate this new methodology in an experimental setting using sonomicrometry. METHODS AND RESULTS: In 5 open-chest sheep, ultrasound data were acquired. The new methodology was used to perform simultaneous measurements of radial and longitudinal strain in the inferolateral wall. Segment-length sonomicrometry crystals were used as the reference. After baseline acquisitions, deformation was modulated by pharmacologically changing the inotropic state of the myocardium and by inducing ischemia. Ultrasonically estimated radial and longitudinal strain were validated against sonomicrometry by means of Bland-Altman analysis and the intraclass correlation coefficient. For both strain components, good agreements were found between the ultrasound and the sonomicrometry measurements as shown by Bland-Altman statistics. The intraclass correlation coefficients were found to be 0.72 and 0.80 for the radial and longitudinal components, respectively. CONCLUSIONS: A new technique for the estimation of myocardial deformation was validated. It was shown that the current problem of angle dependency was solved and that 2 deformation components could be estimated simultaneously and accurately. Furthermore, the technique was less time-consuming, because anatomic tracking was performed automatically. This approach could potentially accelerate the clinical acceptance of ultrasound deformation imaging in cardiology.

Animals↗

The evaluation of pulmonary hypertension using right ventricular myocardial isovolumic relaxation time.

Right ventricular (RV) blood pool-derived isovolumic relaxation time (IVRT) correlates well with systolic pulmonary arterial pressure (PAP). However, because of complex parameter derivation, the method is rarely used. The aim of this study was to validate the measurement of myocardial velocity imaging-derived RV IVRT (IVRT') against invasively measured PAP. Transthoracic echocardiography with myocardial velocity imaging and right heart catheterization were performed in 33 patients with pulmonary hypertension. Blood pool IVRT and myocardial IVRTs for the tricuspid valve annulus ring, basal and apical RV free wall segments were measured and compared with data from 33 age- and sex-matched control subjects. Measured IVRTs were significantly longer in patients with pulmonary hypertension than in control subjects. The strongest correlation (R = 0.74, P < .0001) was found between systolic PAP and the heart rate-corrected IVRT' derived from the basal RV free wall segment. The basal segment IVRT' corrected for heart rate correlates well with the invasive PAP measurement and, therefore, can be used to predict systolic PAP. It can even be considered as an alternative to tricuspid regurgitation-derived PAP systolic when tricuspid regurgitation is nonrecordable. A proposed method to derive systolic PAP should be used while screening the patients at risk for pulmonary hypertension, monitoring the disease progression and the effect of treatment.

Adult↗

Ultrasonic strain/strain rate imaging--a new clinical tool to evaluate the transplanted heart.

OBJECTIVE: The aim of this study was to investigate the clinical applicability of strain and strain rate imaging (epsilon/SRI) in heart transplantation (Htx) patients and to establish "normal" post-Htx regional systolic deformation values. BACKGROUND: Epsilon/SR indices have been shown to be a more sensitive measure of regional systolic function than standard echo measurements. Thus, they might provide a new tool to better define both normal cardiac graft function and detect changes due to post-Htx complications. However, prior to investigating the role of epsilon/SRI in detecting abnormalities, "normal" post-Htx regional deformation values must be established as graft regional function can be altered by a number of factors such as ischemic time, surgical technique or accelerated graft ageing. METHODS: A total of 57 Htx patients (age 36+/-12 years; post-Htx 5.5+/-3 years) without any documented complication were studied. Epsilon/SRI data were acquired from the septum, left ventricular (LV) free walls and right ventricular free wall (RVFW). A total of 29 age-matched healthy subjects served as controls. RESULTS: Htx longitudinal peak systolic velocities (Vsys) were lower in inferior, septal and RVFW segments compared to controls. Peak systolic epsilon/SR (epsilonsys/SRsys)) did not differ from controls except in septum and RVFW in which the values were significantly reduced. Radial Vsys) in the Htx group were higher than controls while epsilonsys/SRsys were reduced. There was a significant decrease in SR(sys) in apical LV segments with increasing time post-Htx, whereas those measured in RVFW showed an increase by that time. CONCLUSION: Epsilon/SRI demonstrated that "healthy" Htx hearts have normal global systolic function but altered regional systolic deformation indices compared to normal hearts. Post-Htx time has a diminishing effect on the regional systolic deformation indices in LV segments but an improving effect in RVFW. These "normal" Htx values should provide the basis for subsequent studies into the role of epsilon/SRI in the non-invasive detection of post-Htx complications.

Adult↗

Cellular mechanisms of contractile dysfunction in hibernating myocardium.

Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca2+]i transient was not significantly reduced, but reducing [Ca2+]o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca2+]i. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca2+]i transient was significantly smaller in ISCH, as was the Ca2+ current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca2+ currents and Ca2+ release are decreased. The steep [Ca2+]i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.

Actin Cytoskeleton↗

Strain and strain rate imaging: a new clinical approach to quantifying regional myocardial function.

On the basis of color Doppler myocardial motion data, 1-dimensional regional natural strain rate and strain curves can now be calculated by comparing local myocardial velocity profiles. Such deformation data sets may be an important, new, and more sensitive approach to quantifying both regional radial and long-axis function of the left or right ventricle in both acquired and congenital heart disease. The normal ranges of regional velocity, strain rate, and strain values have already been determined in both adults and children. This review will focus both on the potential clinical applications of these new ultrasound-based deformation parameters and the current limitations inherent in implementing the technique in everyday practice.

Cardiomyopathies↗

The sequential changes in myocardial thickness and thickening which occur during acute transmural infarction, infarct reperfusion and the resultant expression of reperfusion injury.

AIM: Successful primary PTCA (with TIMI 3 reflow) in patients with acute transmural infarction has been observed to result in an immediate abnormal increase in wall thickness associated with persisting abnormal post-systolic thickening. To understand the sequential changes in regional deformation during: (i) the development of acute transmural infarction, (ii) upon TIMI grade 3 infarct reperfusion and (iii) during the subsequent expression of reperfusion injury the following correlative experimental study was performed in a pure animal model in which there was no distal dispersion of thrombotic material causing either no reflow or secondary microvascular obstruction. METHODS: In 10 closed-chest pigs, a 90 min PTCA circumflex occlusion was used to induce a transmural infarction. This was followed by 60 min of TIMI 3 infarct reperfusion. M-mode ultrasound data from the "at risk" posterior wall infarct segment and from a control remote non-ischemic septal segment were acquired at standardized time intervals. Changes in regional deformation (end-diastolic (EDWT), end-systolic (ESWT) and post-systolic (PSWT) wall thickness, end-systolic strain (epsilonES) and post-systolic strain (epsilonps)) were measured. RESULTS: In this pure animal model of acute transmural infarction/infarct reperfusion (with no pre-existing intra-luminal thrombus), the induced changes in wall thickness and thickening were complex. During prolonged occlusion, after an initial acute fall in ESWT, there was no further change in systolic deformation to indicate the progression of ischaemia to infarction. Both transmurally infarcted and reperfused-infarcted myocardium retained post-systolic thickening indicating that this parameter, taken in isolation, is not a consistent marker of segmental viability and, in this regard, should be interpreted only in combination with other indices of segmental function. The most striking abnormality induced by reperfusion was an immediate increase in EDWT which then increased logarithmically over a 60 min period as reperfusion injury was further expressed. PS did not change significantly during reperfusion. Histology confirmed the wall thickness changes on reperfusion to be due to massive extra-cellular oedema. CONCLUSIONS: The identification of an acute increase in regional wall thickness in a reperfused infarct zone by cardiac ultrasound following primary PTCA might be used in patients to both identify successful infarct reperfusion and to monitor the presence, extent and resolution of the oedema associated with reperfusion injury.

Animals↗

Is post-systolic motion the optimal ultrasound parameter to detect induced ischaemia during dobutamine stress echocardiography?

AIMS: Doppler myocardial imaging (DMI) has been suggested as a method of quantifying induced ischaemia during dobutamine stress echocardiography (DSE). The aim of the present study was to investigate both standard systolic and diastolic parameters, but more specifically to address the phenomenon of post-systolic motion (PSM) as a marker of acquired ischaemia during DSE using pulsed-wave DMI. METHODS AND RESULTS: We examined 60 patients without previous myocardial infarction who underwent DSE. Peak systolic, post-systolic, early and late diastolic velocities were measured at rest and during stress. Myocardial segments (n = 908) were divided into ISCHAEMIC and NON-ISCHAEMIC groups according to the presence of significant angiographic coronary stenosis. ISCHAEMIC segments (n = 357) compared with NON-ISCHAEMIC segments (n = 551) demonstrated a reduced increase of systolic velocity (8.0-12.7 vs 9.3-16.4 cm/s, P < 0.05), prominent PSM (5.8-8.3 vs 0.63-2.1 cm/s, P < 0.000001) and reduced early diastolic velocity (6.5-10.2 vs 7.9-13.2 cm/s, P < 0.04) during stress. The peak velocity of PSM was the most accurate index of induced ischaemia (sensitivity 73-100%, specificity 82-97%) compared to systolic and early diastolic velocities (sensitivity 52-77% and 63-68%, specificity 63-77% and 59-81%, respectively). CONCLUSION: PSM derived by pulsed-wave DMI during DSE was the most sensitive index of acquired ischaemia compared to other functional DMI indices.

Blood Flow Velocity↗

Three-directional myocardial motion assessed using 3D phase contrast MRI.

Regional myocardial function is a complex entity consisting of motion in three dimensions (3D). Besides magnetic resonance imaging (MRI), no other noninvasive technique can give a true 3D description of cardiac motion. Using a time-resolved 3D phase contrast technique, three-dimensional image volumes containing myocardial velocity data in six normal volunteers were acquired. Coordinates and velocity information were extracted from nine points placed in different myocardial segments in the left ventricle (LV), and decomposed into longitudinal (V(L)), radial (V(R)), and circumferential (V(C)) velocity components. Our findings confirm a longitudinal apex-to-base gradient for the LV, with only a small motion of the apex. The mean velocity for V(L) for all the basal segments was higher compared to the midsegments during systole [3.5+/-1.2 vs. 2.5+/-1.7 cm/s (p<0.01)], early filling [-6.9+/-1.8 vs. -4.9+/-1.8 cm/s (p<0.001)], and during atrial contraction [-2.2+/-1.4 vs. -1.6+/-1.3 cm/s (p<0.05)]. A similar pattern was observed when comparing velocities from the midsegments to the apex. Radial velocity was higher during early filling in the midportion of the lateral [-4.9+/-2.7 vs. -3.2+/-1.6 cm/s (p<0.05)] wall compared to the basal segments, no difference was observed for the septal [-2.0+/-1.5 vs. -0.3+/-2.5 cm/s (p=0.15)], anterior [-5.8+/-3.3 vs. -4.0+/-1.7 cm/s (p=0.17)], and posterior [-2.3+/-2.1 vs. -2.5+/-1.0 cm/s (p=0.78)] walls. When observing the myocardial velocity in a single point and visualizing the movement of the main direction of the velocities in this point as vectors in velocity vector plots like planes, it is clear that myocardial movement is by no means one dimensional. In conclusion, our time-resolved 3D, phase contrast MRI technique makes it feasible to extract myocardial velocities from anywhere in the myocardium, including all three velocity components without the need for positioning any slices at the time of acquisition.

Adult↗

RF-based two-dimensional cardiac strain estimation: a validation study in a tissue-mimicking phantom.

Strain and strain rate imaging have been shown to be useful techniques for the assessment of cardiac function. However, one of the major problems of these techniques is their angle dependency. In order to overcome this problem, a new method for estimating the strain (rate) tensor had previously been proposed by our lab. The aim of this study was to validate this methodology in a phantom setup. A tubular thick-walled tissue-mimicking phantom was fixed in a water tank. Varying the intraluminal pressure resulted in a cyclic radial deformation. The 2D strain was calculated from the 2D velocity estimates, obtained from 2D radio frequency (RF) tracking using a 1D kernel. Additionally, ultrasonic microcrystals were implanted on the outer and inner walls of the tube in order to give an independent measurement of the instantaneous wall thickness. The two methods were compared by means of linear regression, the correlation coefficient, and Bland-Altman statistics. As expected, the strain estimates dominated by the azimuth velocity component were less accurate than the ones dominated by the axial velocity component. Correlation coefficients were found to be r = 0.78 for the former estimates and r = 0.83 was found for the latter. Given that the overall shape and timing of the 2D deformation were very accurate (r = 0.95 and r = 0.84), these results were within acceptable limits for clinical applications. The 2D RF-tracking using a 1D kernel thus allows for 2D, and therefore angle-independent, strain estimation.

Algorithms↗

Cardiac resynchronization therapy can reverse abnormal myocardial strain distribution in patients with heart failure and left bundle branch block.

OBJECTIVES: We studied the effects of cardiac resynchronization therapy (CRT) on regional myocardial strain distribution, as determined by echocardiographic strain rate (SR) imaging. BACKGROUND: Dilated hearts with left bundle branch block (LBBB) have an abnormal redistribution of myocardial fiber strain. The effects of CRT on such abnormal strain patterns are unknown. METHODS: We studied 18 patients (12 males and 6 females; mean age 65 +/- 11 years [range 33 to 76 years]) with symptomatic systolic heart failure and LBBB. Doppler myocardial imaging studies were performed to acquire regional longitudinal systolic velocity (cm/s), systolic SR (s(-1)), and systolic strain (%) data from the basal and mid-segments of the septum and lateral wall before and after CRT. By convention, negative SR and strain values indicate longitudinal shortening. RESULTS: Before CRT, mid-septal peak SR and peak strain were lower than in the mid-lateral wall (peak SR: -0.79 +/- 0.5 [septum] vs. -1.35 +/- 0.8 [lateral wall], p < 0.05; peak strain: -7 +/- 5 [septum] vs. -11 +/- 5 [lateral wall], p < 0.05). This relationship was reversed during CRT (peak SR: -1.35 +/- 0.8 [septum] vs. -0.93 +/- 0.6 [lateral wall], p < 0.05; peak strain: -11 +/- 6 [septum] vs. -7 +/- 6 [lateral wall], p < 0.05). Cardiac resynchronization therapy reversed the septal-lateral difference in mid-segmental peak strain from -46 +/- 94 ms (LBBB) to 17 +/- 92 ms (CRT; p < 0.05). CONCLUSIONS: Left bundle branch block can lead to a significant redistribution of abnormal myocardial fiber strains. These abnormal changes in the extent and timing of septal-lateral strain relationships can be reversed by CRT. The noninvasive identification of specific abnormal but reversible strain patterns should help to improve patient selection for CRT.

Adult↗