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Biomedical subjects

Elisa E Konofagou

Publications and source records attributed to Elisa E Konofagou.

10 recordsLinked to original sources

Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice.

The feasibility of blood-brain barrier (BBB) opening in the hippocampus of wild-type mice using focused ultrasound (FUS) through the intact skull and skin was investigated. Needle hydrophone measurements through ex vivo skulls revealed minimal attenuation ( approximately 18% of the pressure amplitude), a well-focused beam pattern and minute focus displacement through the parietal bone. In experiments in vivo, the brains of three mice were sonicated transcranially. Pulsed ultrasound sonications at 1.5 MHz and acoustic pressures ranging from 0.8 to 2.7 MPa were used at 20% duty cycle. Before sonication, a bolus of 10 microL of an ultrasound contrast agents (Optison) was injected intravenously. Contrast-enhanced high-resolution magnetic resonance imaging (9.4 T) revealed BBB opening and allowed for the monitoring of the slow permeation of gadolinium in the hippocampus. The region of the brain where BBB opening occurred increased with the pressure amplitude. These findings thus demonstrated the feasibility of locally opening the BBB in mice using FUS through intact skull and skin and serve as the first step in determining and assessing feasibility of drug delivery to specific regions in the mouse brain using FUS.

Animals↗

Elastographic imaging of strain distribution in the anterior cruciate ligament and at the ligament-bone insertions.

The anterior cruciate ligament (ACL) functions as a mechanical stabilizer in the tibiofemoral joint, and is the most commonly injured knee ligament. To improve the clinical outcome of tendon grafts used for ACL reconstructions, our long-term goal is to promote graft-bone integration via the regeneration of the native ligament-bone interface. An understanding of strain distribution at this interface is crucial for functional scaffold design and clinical evaluation. Experimental determination, however, has been difficult due to the small length scale of the insertion sites. This study utilizes ultrasound elastography to characterize the response of the ACL and ACL-bone interface under tension. Specifically, bovine tibiofemoral joints were mounted on a material testing system and loaded in tension while radiofrequency (RF) data were acquired at 5 MHz. Axial strain elastograms between RF frames and a reference frame were generated using crosscorrelation and recorrelation techniques. Elastographic analyses revealed that when the joint was loaded in tension, complex strains with both compressive and tensile components occurred at the tibial insertion, with higher strains found at the insertion sites. In addition, the displacement was greatest at the ACL proper and decreased in value gradually from ligament to bone, likely a reflection of the matrix organization at the ligament-bone interface. Our results indicate that elastography is a novel method that can be readily used to characterize the mechanical properties of the ACL and its insertions into bone.

Animals↗

Single-element focused ultrasound transducer method for harmonic motion imaging.

The harmonic motion imaging (HMI) technique for simultaneous monitoring and generation of ultrasound therapy using two separate focused ultrasound transducer elements was previously demonstrated. In this study, a new HMI technique is described that images tissue displacement induced by a harmonic radiation force using a single focused-ultrasound element. A wave propagation simulation model first indicated that, unlike in the two-beam configuration, the amplitude-modulated beam produced a stable focal zone for the applied harmonic radiation force. The AM beam thus offered the unique advantage of sustaining the application of the spatially-invariant radiation force. Experiments were performed on gelatin phantoms and ex vivo tissues. The radiation force was generated by a 4.68 MHz focused ultrasound (FUS) transducer using a 50 Hz amplitude-modulated wave. A 7.5 MHz pulse-echo transducer was used to acquire rf echoes during the application of the harmonic radiation force. Consecutive rf echoes were acquired with a pulse repetition frequency (PRF) of 6.5 kHz and 1D cross-correlation was performed to estimate the resulting axial tissue displacement. The HMI technique was shown capable of estimating stiffness-dependent displacement amplitudes. Finally, taking advantage of the real-time capability of the HMI technique, temperature-dependent measurements enabled monitoring ofHIFU sonication in ex vivo tissues. The new HMI method may thus enable a highly-localized force and stiffness-dependent measurements as well as real-time and low-cost HIFU monitoring.

Animals↗

Autocorrelation-based technique for automated segmentation of endocardial border in 3D echocardiograms.

Left-ventricular (LV) segmentation is essential in the early detection of heart disease, where left-ventricular wall motion is being tracked in order to detect ischemia. In this paper, a new method for automated segmentation of the left-ventricular chamber is described. An autocorrelation-based technique isolates the LV cavity from the myocardial wall on 2-D slices of 3D short-axis echocardiograms. A morphological closing function and median filtering are used to generate a uniform border. The proposed segmentation technique is designed to be used in identifying the endocardial border and estimating the motion of the endocardial wall over a cardiac cycle. To this purpose, the proposed technique is particularly successful in border delineation by tracing around structures like papillary muscles and the mitral valve, which constitute the typical obstacle in LV segmentation techniques. The results using this new technique are compared to the manual detection results in short-axis views obtained at the papillary muscle level from 3D datasets in human and canine experiments in vivo. Qualitatively, the automatically-detected borders are highly comparable to the manually-detected borders enclosing regions in the left-ventricular cavity with a relative error within the range of 4.2%-6%. Thus, the new technique constitutes a robust segmentation method for automated segmentation of endocardial borders and is suitable for wall motion tracking for automated detection of ischemia in vivo.

Algorithms↗

Estimation of material elastic moduli in elastography: a local method, and an investigation of Poisson's ratio sensitivity.

The local material stiffness of tissues is a well-known indicator of pathology, with locally stiffer tissue related to the possible presence of an abnormal growth in otherwise compliant tissue. Elastography is a non-invasive technique for measuring displacement distributions in loaded tissues within a medical imaging context. From these measured displacement fields, estimated for local strain have been made using well-studied techniques, but the calculation of elastic modulus has been difficult. In this study we show a method for estimating local tissue elastic modulus that gives numerically stable and robust results in test cases, and that is numerically efficient. The method assumes the tissue is isotropic and it requires an independent estimate of tissue Poisson's ratio, but the method reaches a stable result when the estimated Poisson's ratio is in error, and the resulting estimates are not very sensitive to the assumed value.

Algorithms↗

Tissue displacements during acupuncture using ultrasound elastography techniques.

Acupuncture needle manipulation has been previously shown to result in measurable changes in connective tissue architecture in animal experiments. In this study, we used a novel in vivo ultrasound (US)-based technique to quantify tissue displacement during acupuncture manipulation in humans. B-scan ultrasonic imaging was performed on the thighs of 12 human subjects at different stages of needle motion, including varying amounts of rotation, downward and upward movement performed with a computer-controlled acupuncture needling instrument. Tissue displacements, estimated using cross-correlation techniques, provided successful mapping and quantitative analysis of spatial and temporal tissue behavior during acupuncture needle manipulation. Increasing amounts of rotation had a significant linear effect on tissue displacement during downward and upward needle motion, as well as on rebound tissue displacement after downward needle movement. In addition to being a valuable tool for studies of acupuncture's mechanism of action, this technique may have applications to other types of needling including biopsies.

Acupuncture Therapy↗

Localized harmonic motion imaging: theory, simulations and experiments.

Several techniques have been developed in an effort to estimate mechanical properties of tissues. These techniques typically estimate static or harmonic motion resulting from an externally or internally applied mechanical stimulus. In this paper, we discuss the advantages of utilizing a new technique that performs radiofrequency (RF) signal tracking to estimate the localized oscillatory motion resulting from the harmonic radiation force produced by two focused ultrasound (US) transducer elements with overlapping beams oscillating at distinct frequencies. Finite-element and Monte-Carlo simulations were performed to characterize the range of oscillatory displacements produced by a harmonic radiation force. In the experimental verification, three transducers were used: two single-element focused transducers and one lead zirconate-titanate (PZT) composite 16-element probe. Four agar gels were utilized to determine the effect of stiffness on the motion amplitude. Estimates of the displacement relative to the initial position (i.e., at the onset of the application of the radiation force) were obtained during the application of the radiation force that oscillated at frequencies ranging between 200 Hz and 800 Hz. In the simulations, the estimated oscillatory displacement spanned from -800 to 600 microm and the frequencies of excitation could easily be estimated from the temporal variation of the displacement. In addition, a frequency upshift (on the order of tens of Hz) was estimated with stiffness increase. Furthermore, an exponential decrease of the displacement amplitude with stiffness was observed at all frequencies investigated. An M-mode version to depict both the spatial and temporal variations of the locally induced displacement was used. In experiments with gels of different stiffness, the resulting amplitude of the harmonic displacement estimated oscillated at the same frequencies and ranged from -300 to 250 microm. An exponential decrease of the displacement amplitude with the gel stiffness was also observed. In tissue experiments, the results showed that the method is feasible in tissues and that focused US surgery (FUS) ablation can be detected. These preliminary results demonstrate the feasibility of imaging localized harmonic motion as induced by an oscillatory US radiation force. Due to the highly localized and harmonic nature of the estimated response, this technique may be proven to be highly suitable for simple and accurate estimation of the elastic modulus variation in tissues due to disease.

Agar↗

The temperature dependence of ultrasound-stimulated acoustic emission.

Given the high variability of tissue properties during sonication, temperature monitoring is one of the most crucial components for accurate thermal treatment of tissues with focused ultrasound and other thermotherapy devices. Recently, the method of ultrasound-stimulated acoustic emission (USAE) has been introduced as a potential method for measurements of mechanical properties of tissues. In this paper, the dependence of USAE on tissue temperature is determined. Because USAE depends on the acoustic and mechanical properties, both of which vary with temperature, it is hypothesized that the USAE signal is also temperature-dependent and in such a way that it can be used to guide thermal therapy. In a series of experiments, ex vivo porcine muscle and fat samples were exposed to ultrasound at power levels that induce temperature elevation. In both tissue types, below the coagulation threshold, the USAE amplitude was found to vary linearly with temperature. However, at higher powers, the correlation with temperature was lost due mainly to the irreversible nature of the changes in the tissue properties. Theoretical simulations were used to interpret the USAE response change with temperature involving both reversible and irreversible changes and during both heating and cooling. These results indicate that USAE may have important promise as a potential method for localizing temperature elevation and, thus, thermal surgery monitoring, as well as detection of irreversible changes in tissues.

Adipose Tissue↗

Myocardial elastography--a feasibility study in vivo.

Early detection of cardiovascular diseases has been a very active research area in the medical imaging field. Assessment of the local and global mechanical functions is one of the major goals of accurate diagnosis. In this study, we investigated the feasibility of elastography for estimation and imaging of the local cardiac muscle displacement and strain in a human heart in vivo. In its noninvasive applications, elastography has been typically used to determine local tissue strain through the use of externally applied compression. For our study, we utilized the cardiac muscle motion during a cardiac cycle as the mechanical stimulus, and acquired successive radiofrequency (RF) data frames of the septal and posterior walls over a few cardiac cycles in parasternal and apical views, respectively. High-quality ciné-loop elastograms were obtained due to high frame rates and the resulting low decorrelation noise. Furthermore, the strain contrast was higher in the parasternal case, when only the posterior wall was imaged, and strain estimation was more robust in the apical view. High repeatability of the results was observed through elastographic measurements over several cardiac cycles. Finally, an M-mode version of elastography was used to follow part of the interventricular septum or the posterior wall over the course of two cardiac cycles. Not only do these preliminary results show that elastography is feasible in cardiac applications in vivo, but also that it can provide new information regarding cardiac motion and mechanical function. Future prospects include assessment of the role of elastography in detection of ischemia and infarction.

Adult↗