Cristina Pislaru

Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity

Characterization of tissue elasticity (stiffness) and viscosity has important medical applications because these properties are closely related to pathological changes. Quantitative measurement is more suitable than qualitative measurement (i.e., mapping with a relative scale) of tissue viscoelasticity for diagnosis of diffuse diseases where abnormality is not confined to a local region and there is no normal background tissue to provide contrast. Shearwave dispersion ultrasound vibrometry (SDUV) uses shear wave propagation speed measured in tissue at multiple frequencies (typically in the range of hundreds of Hertz) to solve quantitatively for both tissue elasticity and viscosity. A shear wave is stimulated within the tissue by an ultrasound push beam and monitored by a separate ultrasound detect beam. The phase difference of the shear wave between 2 locations along its propagation path is used to calculate shear wave speed within the tissue. In vitro SDUV measurements along and across bovine striated muscle fibers show results of tissue elasticity and viscosity close to literature values. An intermittent pulse sequence is developed to allow one array transducer for both push and detect function. Feasibility of this pulse sequence is demonstrated by in vivo SDUV measurements in swine liver using a dual transducer prototype simulating the operation of a single array transducer.

Strain and strain rate echocardiography

Strain and strain rate echocardiography is an emerging technique for assessing myocardial systolic and diastolic function. It is envisioned that this modality could change the quantitative assessment of regional wall motion and improve the accuracy and reproducibility of test readings. Myocardial strain and strain rate can detect inducible ischemia and at earlier stages than visual estimation of wall motion or wall thickening parameters. Changes in systolic strain rate and strain have potential to discriminate between different myocardial viability states. Measurement of diastolic rate of deformation can differentiate physiologic from pathologic hypertrophy, and restrictive from constrictive cardiomyopathy. This article reviews basic principles and current experimental and clinical applications of strain and strain rate echocardiography.

Regional asynchrony during acute myocardial ischemia quantified by ultrasound strain rate imaging.

OBJECTIVES We propose a new method to easily quantify asynchronous wall motion due to postsystolic shortening (PSS). We also studied the relationship of the spatial and temporal extent of PSS to the extent of myocardium at ischemic risk after variable duration of ischemia. BACKGROUND Postsystolic shortening is a sensitive marker of asynchrony during ischemia. Current techniques for detection of asynchrony are either subjective, or invasive and time-consuming. Strain rate imaging (SRI) can noninvasively depict PSS as prolonged compression/expansion crossover. METHODS Nineteen open-chest pigs were scanned from apical views, before and after left anterior descending coronary artery occlusion. Strain rates were derived offline from tissue Doppler velocity cineloops. The time from electrocardiographic R-wave to the occurrence of compression/expansion crossover (TCEC) was calculated. Prolonged TCEC during ischemia was identified using a standardized analysis and both spatial (% of left ventricle) and temporal extent were quantified. The extent of myocardium at risk was measured in seven animals from dye-stained specimens. RESULTS Prolonged TCEC was found in all ischemic segments. There was a good correlation (r = 0.91; p < 0.001) and good agreement between the spatial distributions of prolonged TCEC and myocardium at risk. The extent of myocardium at risk was better approximated by TCEC measurement (36 +/- 7% vs. 39 +/- 8%, respectively; p = NS) than by wall motion analysis (47 +/- 17%, p < 0.05). The duration of occlusion did not prolong TCEC. CONCLUSIONS Prolonged TCEC consistently occurs in ischemic myocardium and is apparently not affected by the duration of ischemia. Standardized analysis of TCEC in SRI closely quantifies the extent of ischemic myocardium. This new method may be a useful tool in other cardiac conditions associated with regional diastolic asynchrony.

Optimization of ultrasound-mediated gene transfer: comparison of contrast agents and ultrasound modalities

AIMS Ultrasound (US)-enhanced gene transfer for cardiovascular disease is an emerging technique with translational relevance. Prior to pre-clinical applications, optimization of gene transfer using various US contrast agents and parameters is required. In order to do so, two clinically relevant contrast agents (Optison and PESDA), and two US modalities (dedicated continuous wave system and diagnostic scanner) were tested in vitro and in vivo. METHODS AND RESULTS In vitro, luciferase activity was measured after exposure of primary vascular cells to combinations of luciferase plasmid, contrast agents, and US exposures. US gene transfer was consistently superior to controls. PESDA was better than Optison; there was no significant difference between US modalities. In vivo, luciferase activity in skeletal muscle of rats was measured after injection of plasmid or adenovirus, expressing luciferase with or without US exposure. Diagnostic US was superior to continuous wave. US plasmid gene transfer was highly localized, and was superior to all controls except adenovirus which lacked spatial specificity. To deliver a secreted transgene product, US gene transfer of a plasmid expressing tissue factor pathway inhibitor (TFPI) to skeletal muscle resulted in a dose-related increase in plasma activity for up to 5 days after delivery. CONCLUSION US-enhanced plasmid gene transfer is capable of transducing skeletal muscle in vivo either directly or via an intravascular route. This enhanced nonviral method is an alternative to plasmid DNA alone or viral vectors.

Ultrasound Strain Imaging of Altered Myocardial Stiffness Stunned Versus Infarcted Reperfused Myocardium

Background—In this study we evaluate the diastolic deformation of ischemic/reperfused myocardium and relate this deformation to tissue elastic properties. Methods and Results—Farm pigs were subjected to left anterior descending coronary artery occlusion followed by reperfusion to create either stunning (n=12) or transmural myocardial infarction (n=12). Ultrasound-derived radial strain rates (SR) and strain were measured in the ischemic and remote walls. Myocardial stiffness was estimated from diastolic pressure–wall thickness relationship obtained from preload alterations. At reperfusion, end-systolic strain (∈sys) was significantly reduced in both stunned and infarcted walls compared with their remote walls (3±3% versus 26±2% and 1±0% versus 33±5%, respectively; P< 0.0001) or baseline values. Diastolic passive deformation (∈A) and rates of deformation during early (ESR) and late (ASR) diastole were comparable between stunned and remote walls (∈A: 7.3±1.6% versus 7.9±1.9%; ESR: −2.7±0.4 s−1 versus −2.6±0.5 s−1; ASR: −1.8±0.2 s−1 versus −1.9±0.3 s−1; P= NS for all) but were of significantly lower magnitude in infarcted walls versus remote walls (∈A: 1.1±0.2% versus 11.4±1.9%; ESR: −0.3±0.1 s−1 versus −2.4±0.4 s−1; ASR: −0.3±0.1 s−1 versus −2.5±0.4 s−1; P< 0.0001 for all). Stiffness coefficient of exponential diastolic pressure–wall thickness relation was higher for infarcted (P< 0.05) but not for stunned walls (P= NS) compared with their remote walls. Conclusions—Early after postischemic reperfusion and in the presence of severely reduced systolic deformation, diastolic passive deformation (and rates of deformation) can distinguish stiff, noncompliant, transmurally infarcted myocardial walls from those more compliant walls containing viable but stunned myocardium.

Noninvasive Measurements of Infarct Size After Thrombolysis With a Necrosis-Avid MRI Contrast Agent

BACKGROUND Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.

Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging With a Phased Array Transducer

Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode imaging quality thanks to its effectiveness in suppressing imaging artifacts associated with ultrasound reverberation, phase aberration, and clutter noise. In ultrasound shear wave elastography (SWE), because the shear wave motion signal is extracted from the ultrasound signal, these noise sources can significantly deteriorate the shear wave motion tracking process and consequently result in noisy and biased shear wave motion detection. This situation is exacerbated in in vivo SWE applications such as heart, liver, and kidney. This paper, therefore, investigated the possibility of implementing harmonic imaging, specifically pulse-inversion harmonic imaging, in shear wave tracking, with the hypothesis that harmonic imaging can improve shear wave motion detection based on the same principles that apply to general harmonic B-mode imaging. We first designed an experiment with a gelatin phantom covered by an excised piece of pork belly and show that harmonic imaging can significantly improve shear wave motion detection by producing less underestimated shear wave motion and more consistent shear wave speed measurements than fundamental imaging. Then, a transthoracic heart experiment on a freshly sacrificed pig showed that harmonic imaging could robustly track the shear wave motion and give consistent shear wave speed measurements of the left ventricular myocardium while fundamental imaging could not. Finally, an in vivo transthoracic study of seven healthy volunteers showed that the proposed harmonic imaging tracking sequence could provide consistent estimates of the left ventricular myocardium stiffness in end-diastole with a general success rate of 80% and a success rate of 93.3% when excluding the subject with Body Mass Index higher than 25. These promising results indicate that pulse-inversion harmonic imaging can significantly improve shear wave motion tracking and thus potentially facilitate more robust assessment of tissue elasticity by SWE.

Higher myocardial strain rates during isovolumic relaxation phase than during ejection characterize acutely ischemic myocardium.

OBJECTIVES The aim of this study was to define an index that can differentiate normal from ischemic myocardial segments that exhibit postsystolic shortening (PSS). BACKGROUND Identification of ischemia based on the reduction of regional systolic function is sometimes challenging because other factors such as normal nonuniformity in contraction between segments, tethering effect, pharmacologic agents, or alterations in loading conditions can also cause reduction in regional systolic deformation. The PSS (contraction after the end of systole) is a sensitive marker of ischemia; however, inconsistent patterns have also been observed in presumed normal myocardium. METHODS Twenty-eight open-chest pigs underwent echocardiographic study before and during acute myocardial ischemia induced by coronary artery occlusion. Ultrasound-derived myocardial longitudinal strain rates were calculated during systole (S(SR)), isovolumic relaxation (IVR(SR)), and rapid filling (E(SR)) phases in both ischemic and normal myocardium. Systolic strain (epsilon(sys)) and postsystolic strain (epsilon(ps)) were calculated by integrating systolic and postsystolic strain rates, respectively. RESULTS During ischemia, S(SR), E(SR), and epsilon(sys) in ischemic segments were significantly lower (in magnitude) than in nonischemic segments or at baseline. However, some overlap occurred between ischemic and normal values for all three parameters. At baseline, 18 of 28 animals had negative IVR(SR) (i.e., PSS) in at least one segment. During coronary artery occlusion, IVR(SR) became negative and larger in magnitude than S(SR) in all ischemic segments. The IVR(SR)/S(SR) and epsilon(ps) best differentiated ischemic from nonischemic segments. CONCLUSIONS In the presence of reduced regional systolic deformation, a higher rate of PSS than systolic shortening identifies acutely ischemic myocardium.

Intracoronary delivery of Gd-DTPA and Gadophrin-2 for determination of myocardial viability with MR imaging

Abstract The aim of this study was to compare intracoronary (i. c.) administration of Gadophrin-2, a necrosis-avid contrast agent (NACA), and nonspecific agent Gd-DTPA for determination of myocardial viability (MV) in acute myocardial infarction (AMI) with MRI. Reperfused AMI was induced in 12 dogs by transcatheter balloon occlusion of coronary artery. In 6 dogs each, Gd-DTPA at 0.1 mmol/kg or Gadophrin-2 at 0.005 mmol/kg was administered into coronary artery by fast bolus (n = 3) or slow infusion (n = 3). Serial ECG-triggered cardiac MRI of T1-weighted segmented turbo fast low-angle shot (FLASH) sequence was conducted and compared with triphenyltetrazolium chloride (TTC) histochemical staining. The contrast ratio and infarct size were quantified and analysed statistically. No cardiovascular side effects were found with local delivery of both agents. After i. c. administration, Gadophrin-2 induced a strong (CR ≥ 1.78) and persistent ( ≥ 10 h) contrast enhancement of infarcted region. The infarct size defined with Gadophrin-2 was almost identical to that with TTC staining throughout the postcontrast period. With a dose 20 times higher, Gd-DTPA also strongly enhanced infarct-to-normal contrast; however, the enhancement diminished with time, i. e. from early strong to later faint enhancement and eventual loss of contrast. The delineated infarct size was also unstable, i. e. from early overestimation to later underestimation and eventual disappearance of the enhanced infarct. In combination with PTCA procedure, i. c. administration of MRI contrast agents may prove useful for post-procedure verification of diagnosis. The NACA-enhanced MRI may serve as an in vivo surrogate of postmortem histochemical staining for determination of MV. Although applicable in clinical setting, cardiac MRI with nonspecific Gd-DTPA is less reliable and should be performed within less than 1 h after contrast.

Infarct Size, Myocardial Hemorrhage, and Recovery of Function After Mechanical Versus Pharmacological Reperfusion Effects of Lytic State and Occlusion Time

BACKGROUND Whether myocardial reperfusion obtained with thrombolysis or primary angioplasty is associated with a similar recovery of function and with the same risk of hemorrhagic infarction is unknown. We evaluated the effects of mechanical and pharmacological reperfusion (with or without a plasma lytic state) on infarct size, myocardial hemorrhage, and left ventricular (LV) function in a canine model. METHODS AND RESULTS Six groups of six dogs were subjected to balloon occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion. The study had a two-by-three factorial design with two occlusion periods (90 and 240 minutes) and three different reperfusion strategies (placebo, 0.4 mg/kg recombinant tissue plasminogen activator, and 40 microg/kg recombinant staphylokinase). In a seventh control group, LAD occlusion was maintained without reperfusion. All dogs received aspirin and heparin. A systemic lytic state was present in staphylokinase-treated dogs. Planimetry of LV slices showed larger infarcts (percent of area at risk) and more hemorrhage (percent of IA) after 240 minutes of occlusion than after 90 minutes of occlusion (54+/-17% versus 37+/-18% and 52+/-27% versus 29+/-27%, respectively; P<.01 for both comparisons), with no significant difference among treatments. Hemorrhage was not observed in the control group without reperfusion. LV angiography showed no differences in global and regional LV function between mechanical and pharmacological reperfusion. CONCLUSIONS In this experimental model, hemorrhagic infarctions of similar extent were observed after both pharmacological and mechanical reperfusion. The extent of hemorrhage was increased by the delay in reperfusion but not by the presence of a lytic state.