Biomedical subjects

James F Greenleaf

Publications and source records attributed to James F Greenleaf.

At least 37 records · Page 2Linked to original sources

PubMed2004

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 (epsilon(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 (epsilon(A)) and rates of deformation during early (E(SR)) and late (A(SR)) diastole were comparable between stunned and remote walls (epsilon(A): 7.3+/-1.6% versus 7.9+/-1.9%; E(SR): -2.7+/-0.4 s(-1) versus -2.6+/-0.5 s(-1); A(SR): -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 (epsilon(A): 1.1+/-0.2% versus 11.4+/-1.9%; E(SR): -0.3+/-0.1 s(-1) versus -2.4+/-0.4 s(-1); A(SR): -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.

Animals↗

PubMed2004

Distinctive changes in end-diastolic wall thickness and postsystolic thickening in viable and infarcted myocardium.

OBJECTIVES: In this study, we sought to compare the magnitude of changes in end-diastolic wall thickness (WT(ed)) and postsystolic thickening (PST) in a swine model of stunning and reperfused acute myocardial infarction, and to explore the relationship between WT(ed) and PST. METHODS: Twenty-six pigs were subjected to left anterior descending coronary artery occlusion followed by reperfusion to induce stunning (n = 6), nontransmural (n = 8), or transmural (n = 12) myocardial infarction. Myocardial wall thickness was measured using intracardiac echocardiography. Transmural extent of necrosis (TEN) was quantified by triphenyltetrazolium chloride technique. RESULTS: During the first minutes of reperfusion, a marked increase in WT(ed) occurred in the myocardial walls with nontransmural and transmural infarct (42% and 102%, respectively) but less in those with stunning (19%). PST persisted at reperfusion in walls with stunning and nontransmural infarct (23% and 26%, respectively). In transmurally infarcted walls, PST progressively decreased either during occlusion (5/12 pigs) or shortly after reperfusion (7/12 pigs). PST at reperfusion was virtually absent when TEN was >70%. Both PST and the increase in WT(ed) at reperfusion correlated well with TEN (P <.0001 for both). Changes in PST at reperfusion were weakly correlated with changes in WT(ed). CONCLUSIONS: A marked increase in WT(ed) after reperfusion and absence of PST indicate transmural myocardial infarction. Presence of PST at reperfusion indicates viable tissue in more than 30% of wall thickness. The results suggest that amplitude of PST is modulated predominantely by factors related to the severity of ischemia and, to a smaller extent, by changes in wall thickness.

Analysis of Variance↗

PubMed2004

Nitric oxide and prostacyclin in ultrasonic vasodilatation of the canine internal mammary artery.

BACKGROUND: Investigators recently demonstrated increased free blood flow from radial artery free grafts harvested using ultrasonic technology. We investigated the mechanism underlying this phenomenon. METHODS: Canine internal mammary artery segments (with and without intact endothelium) were precontracted with norepinephrine and sonicated 3 seconds in organ chambers with ultrasonic coagulating shears (Harmonic Scalpel; Ethicon Endo-Surgery, Cincinnati, OH) functioning at level 2. Vessel tension was continuously measured to examine vasoactivity in response to sonication alone (control) or with N(ù)-Nitro-l-arginine (l-NNA) and indomethacin added to the chamber medium individually or in combination. Tissue heating, acoustic pressure, and endothelial damage as detected by scanning electron micrography were also assessed. RESULTS: In vitro sonication with the Harmonic Scalpel induced predominately endothelium-dependent internal mammary artery vasorelaxation but a small endothelium-independent contribution was also observed. Early vasorelaxation (1 minute after stimulus) was maximally inhibited by l-NNA alone and in combination with indomethacin. Relaxation during this period was insignificantly affected by indomethacin alone. Only the combination of l-NNA and indomethacin maximally inhibited late vasorelaxation (5 minutes after stimulus), whereas inhibitory effects of l-NNA diminished during this time period. Indomethacin inhibited relaxation substantially during this phase, although significantly less than did l-NNA alone. The Harmonic Scalpel minimally heated the tissue surface (0.3 +/- 0.03 degrees C) and did not disrupt endothelial cell integrity while operating at 50 mW/cm(2) intensity (acoustic pressure 40 kPa). CONCLUSIONS: Sonication induces vasorelaxation almost completely by time-dependent endothelial nitric oxide and prostacyclin release, which appears unrelated to tissue heating or endothelial architectural disruption.

Animals↗

PubMed2004

Performance of vibro-acoustography in detecting microcalcifications in excised human breast tissue: a study of 74 tissue samples.

X-ray mammography is the principal modality used today for detection of breast microcalcifications and breast lesions associated with breast cancer. X-ray mammography, however, is ionizing and its sensitivity is greatly reduced in dense breasts. Hence, alternative noninvasive and nonionizing breast imaging tools that can aid physicians to better diagnose early-stage breast lesions are of great interest. Vibro-acoustography is a novel noninvasive imaging technique that uses ultrasound in a fundamentally new way. This method uses the radiation force of ultrasound to vibrate the tissue at low (kilohertz) frequency and records the resulting response to produce images that are related to the mechanical properties of the tissue. The goal of this study is to evaluate the performance of vibro-acoustography in detecting breast microcalcifications by conducting vibro-acoustography on 74 fixed breast tissue samples with known microcalcifications based on their radiographs. The results indicate that in most cases micro-calcifications can be detected by vibro-acoustography. Further development of vibro-acoustography may lead to a novel-imaging tool for in vivo detection of microcalcifications.

Acoustics↗

PubMed2004

Imaging mass lesions by vibro-acoustography: modeling and experiments.

Vibro-acoustography is a recently developed imaging method based on the dynamic response of to low-frequency vibration produced by of ultrasound radiation force. The main differentiating feature of this method is that the image includes information about the dynamic properties of the object at the frequency of the vibration, which is normally much lower than the ultrasound frequency. Such information is not available from conventional ultrasound imaging. The purpose of this study is to evaluate the performance of vibro-acoustography in imaging mass lesions in soft tissue. Such lesions normally have elastic properties that are different from the surrounding tissue. Here, we first present a brief formulation of image formation in vibro-acoustography. Then we study vibro-acoustography of solid masses through computer simulation and in vitro experiments. Experiments are conducted on excised fixed liver tissues. Resulting images show lesions with enhanced boundary and often with distinctive textures relative to their background. The results suggest that vibro-acoustography maybe a clinically useful imaging modality for detection of mass lesions.

Algorithms↗

PubMed2004

Quantifying elasticity and viscosity from measurement of shear wave speed dispersion.

The propagation speed of shear waves is related to frequency and the complex stiffness (shear elasticity and viscosity) of the medium. A method is presented to solve for shear elasticity and viscosity of a homogeneous medium by measuring shear wave speed dispersion. Harmonic radiation force, introduced by modulating the energy density of incident ultrasound, is used to generate cylindrical shear waves of various frequencies in a homogeneous medium. The speed of shear waves is measured from phase shift detected over the distance propagated. Measurements of shear wave speed at multiple frequencies are fit with the theoretical model to solve for the complex stiffness of the medium. Experiments in gelatin phantoms show promising results validated by an independent method. Practical considerations and challenges in possible medical applications are discussed.

Adipose Tissue↗

PubMed2004

Linear arrays for vibro-acoustography: a numerical simulation study.

In this work, we study linear array beamforming for vibro-acoustography systems. The goal of this research is to assess the feasibility of vibro-acoustography imaging systems based on linear arrays for clinical applications. The vibro-acoustography transducer is designed with two arrays driven by two continuous-wave or tone-burst signals at slightly different frequencies. The system beamforming is modeled in a homogeneous and lossless fluid. In this model, the point-spread function (psf) of the system is obtained as the product of the spatial impulse function of each linear array. Three linear array configurations are analyzed for vibro-acoustography systems. Simulations considering 64 elements in each array are performed. Aspects related to clinical applications ofvibro-acoustography, such as system spatial resolution, sidelobes, grating lobes and image frame-rate are discussed. It is concluded that linear array transducers can produce acceptable spatial resolution for clinical applications.

Acoustics↗

PubMed2004

Spectral normalization for ultrasonic contrast microbubble detection.

Ultrasonic contrast agents consisting of microbubbles are used to assess tissue perfusion. The microbubbles are highly reflective and nonlinear and thus produce harmonics that are stronger than those from tissues. However, the magnitude of harmonic signals resulting from a region with microbubbles also depends on the acoustic pressure of incident ultrasound and the attenuation of intervening tissues in the ultrasound path. Therefore, the harmonic magnitude, as used in traditional harmonic imaging, may not be a reliable indicator of the presence or absence of microbubbles, and hence, tissue perfusion. To compensate for these effects, we present two parameters defined as the ratio of the harmonic to the fundamental component (HFR) and the ratio of the harmonic to squared fundamental (HSFR). A simplified model is used to illustrate the usefulness of these two parameters. Experiments show that both parameters improve detection of microbubbles and that HSFR performs better than HFR.

Contrast Media↗

PubMed2004

Application of vibro-acoustography for detection of calcified arteries in breast tissue.

OBJECTIVE: The relationship between breast arterial calcification and coronary artery calcification and stenosis is currently an area of active research. It has been suggested in the literature that calcified arteries in the breast may be positively correlated with coronary artery disease. The sensitivity of x-ray mammography, the main breast imaging method, is reduced in radiologically dense breasts. In a recent study, we showed that vibro-acoustography, a novel noninvasive imaging technique that is based on the dynamic response of the object to a vibrating force, can detect microcalcifications in the breast regardless of breast density. In this study, we examined the application of vibro-acoustography in detecting calcified arteries in breast tissue. METHODS: Experiments were conducted on 207 postsurgical excised human breast tissue samples. Tissues specimens were imaged with a high-resolution x-ray mammography unit. Each sample with confirmed arterial calcification was then scanned by the vibro-acoustography system, and the resulting image was compared with the corresponding mammogram. We also studied the histologic characteristics of each sample to positively identify the disease and the presence of arterial calcification. RESULTS: Initial mammograms clearly showed 14 calcified arteries. The corresponding vibro-acoustographic images showed all calcified arteries as fragmented linear structures. The vibro-acoustographic appearance of the arteries was highly correlated with their distinctive radiographic appearance, which allowed us to identify all the calcified arteries in the vibro-acoustographic images. CONCLUSIONS: Vibro-acoustography can be used to detect calcified arteries in excised breast tissue. This method may eventually play a role in identifying individuals with an increased risk of coronary artery disease.

Arteries↗

PubMed2004

Comparison of stress field forming methods for vibro-acoustography.

Vibro-acoustography is a method that produces images of the acoustic response of a material to a localized harmonic motion generated by ultrasound radiation force. The low-frequency, oscillatory radiation force (e.g., 10 kHz) is produced by amplitude modulating a single ultrasound beam, or by interfering two beams of slightly different frequencies. Proper beam forming for the stress field of the probing ultrasound is very important because it determines the resolution of the imaging system. Three beam-forming geometries are studied: amplitude modulation, confocal, and x-focal. The amplitude of radiation force on a unit point target is calculated from the ultrasound energy density averaged over a short period of time. The profiles of radiation stress amplitude on the focal plane and on the beam axis are derived. The theory is validated by experiments using a small sphere as a point target. A laser vibrometer is used to measure the velocity of the sphere, which is proportional to the radiation stress exerted on the target as the transducer is scanned over the focal plane or along the beam axis. The measured velocity profiles match the theory. The theory and experimental technique may be useful in future transducer design for vibro-acoustography.

Acoustics↗

PubMed2003

Measurement of the ultrasound backscatter signal from three seed types as a function of incidence angle: application to permanent prostate brachytherapy.

PURPOSE: To measure the relative ultrasound backscatter of different seed types as a function of seed orientation and to evaluate the corresponding images of these seeds. METHODS AND MATERIALS: Three seed types were evaluated: OncoSeed (standard), EchoSeed (corrugated), and RAPID Strand(RS). Ultrasound images for angles of incidence varying from 90 degrees (perpendicular) to 20 degrees at 5MHz and 7.5MHz were produced by raster scanning the seeds in a degassed water bath. Seed images were visually inspected and analyzed using the integrated-optical-density (IOD) method. RESULTS: Corrugated seeds appear as contiguous objects over the range of frequencies and orientations examined, whereas standard seeds appear as contiguous objects from 90 degrees to 80 degrees only. The ranges and means of the backscattered IOD ratio of the seeds from 85 degrees to 20 degrees were: (corrugated vs. standard) 1.48 to 3.72 (2.32 +/- 0.62) for 5 MHz and 1.26 to 3.77 (2.19 +/- 0.84) for 7.5 MHz and (corrugated vs. RS) 1.21 to 9.53 (2.98 +/- 2.48) for 5 MHz and 1.008 to 10.86 (2.79 +/- 3.08) for 7.5 MHz. Backscattered signal increase ranged from 1.66 dB to 20.7 dB for the corrugated seed as compared to the other seeds. CONCLUSIONS: Corrugated seeds produce greater backscatter signal and a more readily identifiable seed image over a large range of seed orientation as compared with standard brachytherapy seeds.

Brachytherapy↗

PubMed2003

Myocardial contractility by strain echocardiography: comparison with physiological measurements in an in vitro model.

Strain echocardiography (SE) provides the rate and extent of myocardial segment shortening and lengthening. Thus we hypothesized that SE will noninvasively provide estimates of shortening velocity (SV) and length change (delta L). We compared SE-derived strain rate (SR) and strain (epsilon) to force/length transducer-derived SV and percent delta L in isolated muscle strips at multiple load levels and under varying conditions. Electrically stimulated contractions in left ventricular muscle strips (n = 20) were simultaneously recorded with a force/length transducer (to measure SV and percent delta L) and an ultrasound transducer (to measure SR and epsilon). Measurements were made at baseline, after inotropic stimulation, and during hypoxia at multiple load clamp levels (simulating multiple levels of afterload). Despite a difference in absolute numbers, there was a close correlation between SR and SV at baseline (R2 = 0.95), with dobutamine treatment (R2 = 0.99), and during hypoxia (R2 = 0.99). SR was load dependent at baseline (r = 0.98), with dobutamine treatment (r = 0.99), and during hypoxia (r = 0.92). Similarly, there was a close correlation between epsilon and delta L at baseline (R2 = 0.99), with dobutamine treatment (R2 = 0.96), and during hypoxia (R2 = 0.87). Percent epsilon was load dependent at baseline (r = 0.98), with dobutamine treatment (r = 0.98), and during hypoxia (r = 0.94). Bland-Altman analysis revealed a systematic overestimation of SV by SE-derived SR at baseline and with dobutamine treatment. There was no bias with SR measurements during hypoxia or with epsilon measurements. SE closely tracks standard physiological parameters of regional contractile function, such as SV and delta L, under conditions of varying afterload.

Animals↗

PubMed2003

Selected methods for imaging elastic properties of biological tissues.

For millennia, physicians have used palpation as a part of the physical examination to detect pathology. The ubiquitous presence of "stiffer" tissue associated with pathology often represents an early warning sign for disease, as in the cases of breast or prostate cancer. Very often tumors are found at surgery that were occult even with modern imaging instruments. This implies that methods for estimating "hardness" of tissues would add a weapon to the medical armamentarium. To this end, this review discusses several methods of estimating tissue hardness using internal or external means of applying stress (force per unit area) and several associated methods of detecting the resulting strain (fractional length change) in an effort to image a tissue mechanical property, such as Young's modulus (ratio of stress to strain). Some investigators have developed methods of estimating stiffness or modulus, but most methods result in qualitative images of stiffness. Nevertheless, such estimates may add a great deal of information not currently available to the current field of medical imaging.

Animals↗

PubMed2003

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.

Animals↗

PubMed2003

Fresnel transform phase retrieval from magnitude.

This report presents a generalized projection method for recovering the phase of a finite support, two-dimensional signal from knowledge of its magnitude in the spatial position and Fresnel transform domains. We establish the uniqueness of sampled monochromatic scalar field phase given Fresnel transform magnitude and finite region of support constraints for complex signals. We derive an optimally relaxed version of the algorithm resulting in a significant reduction in the number of iterations needed to obtain useful results. An advantage of using the Fresnel transform (as opposed to Fourier) for measurement is that the shift-invariance of the transform operator implies retention of object location information in the transformed image magnitude. As a practical application in the context of ultrasound beam measurement we discuss the determination of small optical phase shifts from near field optical intensity distributions. Experimental data are used to reconstruct the phase shape of an optical field immediately after propagating through a wide bandwidth ultrasonic pulse. The phase of each point on the optical wavefront is proportional to the ray sum of pressure through the ultrasound pulse (assuming low ultrasonic intensity). An entire pressure field was reconstructed in three dimensions and compared with a calibrated hydrophone measurement. The comparison is excellent, demonstrating that the phase retrieval is quantitative.

Journal Article↗

PubMed2002

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.

Animals↗

PubMed2002

Calcium signaling is required for ultrasound-stimulated aggrecan synthesis by rat chondrocytes.

Low-intensity ultrasound accelerates fracture healing in humans. In rat femur fracture models, ultrasound advanced healing is associated with increased proteoglycan expression. Here we report that ultrasound stimulation of primary rat chondrocytes elevated the intracellular concentration of calcium [Ca2+]i. The [Ca2+]i increase was rapid and transient at lower pressures (175-320 kPa), but rapid and sustained at higher ultrasound exposures (350-500 kPa). Chelating internal [Ca2+]i with 1,2-bis(2-aminophenoxy) ethane-N-N-N',N'-tetraacetic acid (BAPTA-AM), stopping the Ca2+/ATP-ase induced mitochondrial release of [Ca2+]i with Thapsigargin, or removing [Ca2+]i from the medium with EGTA inhibited the stimulatory effects of ultrasound on proteoglycan synthesis. These results imply that ultrasound-stimulated synthesis of cell matrix proteoglycan, associated with accelerated fracture healing, is mediated by intracellular calcium signaling.

Aggrecans↗

PubMed2002

Rapid quantitative assessment of myocardial perfusion: spectral analysis of myocardial contrast echocardiographic images.

We described a novel rapid spectral analysis technique performed on raw digital in-phase quadrature (IQ) data that quantitatively differentiated perfused from nonperfused myocardium based on the simultaneous comparison of local fundamental and harmonic frequency band intensity levels. In open-chest pigs after ligation of the left anterior descending coronary artery (LAD) and continuous venous contrast infusion, the fundamental-to-harmonic intensity ratio (FHIR) for samples placed within the left ventricular (LV) cavity (10.8 +/- 1.7 dB) and perfused myocardium (13.7 +/- 1.6 dB) were significantly (P <.001) lower than for nonperfused myocardium (27.1 +/- 2.9 dB). In attenuated images, the FHIR for the LV cavity and perfused myocardium were also significantly (P <.05) lower than for the nonperfused myocardium (21.4 +/- 3.0 dB, 34.4 +/- 3.2 dB, and 40.2 +/- 4.4 dB, respectively). Spectral properties of contrast microbubbles, as characterized by the FHIR, allow for rapid quantitative assessment of myocardial perfusion from data contained in a single-image frame, without requiring background image subtraction and image averaging.

Acute Disease↗