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Multiple acoustic wave mode method has been proposed as a new modality in axial bone QUS. The new method is based on measurement of ultrasound velocity at different ratio of wavelength to the bone thickness, and taking into account both bulk and guided waves. It allows assessment of changes in both the material properties related to porosity and mineralization as well as the cortical thickness influenced by resorption from inner layers, which are equally important in diagnostics of osteoporosis and other bone osteopenia. Developed method was validated in model studies using a dual-frequency (100 and 500 kHz) ultrasound device. Three types of bone phantoms for long bones were developed and tested: (1) tubular specimens from polymer materials to model combined changes of material stiffness and cortical wall thickness; (2) layered specimens to model porosity in compact bone progressing from endosteum towards periosteum; (3) animal bone specimens with both cortical and trabecular components. Observed changes of the ultrasound velocity of guided waves at 100 kHz followed gradual changes in the thickness of the intact cortical layer. On the other hand, the bulk velocity at 500 kHz remained nearly constant at the different cortical layer thickness but was affected by the material stiffness. Similar trends were observed in phantoms and in fragments of animal bones.

INTRODUCTION Palpation Imaging (PI) of the breast is based on the principles of tactile imaging, a method for measuring the elasticity lesions using a tactile sensor array. PI provides objective data beyond subjective manual palpation by quantifying the shape and hardness of a lesion as well as creating a permanent digital image. PI is also known as "Tactile Imaging", "Mechanical Imaging", "Stress Imaging" or "Computerized Palpation". It quantitatively evaluates mechanical and structural properties of a breast lesion that is altered by tumor growth, and provides a quantitative characterization of the detected lesion. PI is a radiation-free and an inexpensive in comparison to other imaging devices. The purpose of this paper is to evaluate the clinical efficacy of PI by summarizing all clinical studies conducted to date with this technology. METHODS The two step process to identify the clinical presence of a breast cancer include identifying the presence of an abnormality and secondarily to determine if that abnormality is malignant. Not all studies examined each portion of this two-step process. There have been 9 clinical studies involving 1,155 symptomatic patients using PI in the U.S., China, and UK. To examine the ability of PI to detect an abnormal breast mass, we reviewed the sensitivity comparisons with CBE. To determine whether a breast lesion was malignant, we reviewed the analysis of the sensitivity, specificity and accuracy for the standard imaging modalities; mammography, breast ultrasound, clinical breast examinations (CBE) and MRI using pathology as the gold standard. Calcifications were not included because they represent DCIS which does not present clinically and is the subject of over diagnosis. RESULTS All studies included in this initial meta-analysis were on symptomatic patients. To identify the presence of an abnormality, the sensitivity of PI to detect breast masses was 89% in comparison with CBE which was 83%. To identify the presence of breast cancer, • The sensitivity of PI in detecting breast cancer was 85%, in comparison to CBE (59%), mammography (76%) and ultrasound (90%). • The specificity of PI in detecting breast cancer was 79% in comparison to CBE (78%), mammography (71%) and ultrasound (79%). • The Accuracy of PI in detecting breast cancer was 82% comparison with CBE (67%), mammography (74%) and ultrasound (84%). Breast Cancer Detection Comparision Palpation ImagingCBEMammogramUltrasoundSensitivity for Cancer Detection85597690Specificity for Cancer Detection79787179Accuracy for Cancer Detection82677484 CONCLUSIONS A summary of clinical studies conducted on symptomatic patients to date suggest that PI is (a) sensitive in the detection of breast masses and b) identifies breast cancer with similar sensitivity and specificity compared with other standard imaging modalities while being cost effective. PI may fill a gap in developing countries where little breast screening infrastructure exists. Ongoing clinical research with PI is warranted to evaluate its potential in the early diagnosis and screening for breast cancer in the U.S. Citation Format: Cary S Kaufman, Jae S Son, Eli Yered, Armen Sarvazyan. Clinical studies of palpation imaging of the breast on over 1000 patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-09.

In this talk, an overview of history and physical basis of biomedical applications of acoustic radiation force with a further look into new developments in this field will be presented. In 1902, Lord Rayleigh published his classical work on the theory of sound, introducing the concept of acoustic radiation pressure. Experimental demonstration of radiation force acting on particles in the standing wave field was made by August Kundt (1874). Much later, Wood and Loomis built radiation force balance (1927). Detailed analysis of ultrasound radiation force related to biomedical applications was made in numerous reviews and original articles of Wes Nyborg in the 1960s and 1970s. In spite of over century-old history, most of the significant biomedical applications of acoustic radiation force became known and were extensively studied only during last couple of decades. We will present and discuss recent progress in numerous applications such as the elasticity imaging, assessing viscoelastic properties of biologic...

A new modality termed mechanical imaging has recently been developed. We determined whether mechanical imaging could be used to detect prostate cancer in radical prostatectomy specimens.Stress patterns on the surface of excised prostates were evaluated using the data obtained from a planar piezoelectric resistive force sensor array. Seven radical prostatectomy and 2 cystoprostatectomy specimens were manually palpated and evaluated by the mechanical imager. The prostates were histopathologically analyzed for the presence of cancer. The results of the manual palpation, mechanical imaging and pathological analysis were correlated.Mechanical imaging correlated closely with nodules palpated in all specimens and in 1 it revealed a suspicious area undetected by palpation, which on subsequent histological analysis demonstrated carcinoma.Mechanical imaging can detect areas of heterogeneity in prostate tissue which correlate with cancer. Our findings provide the basis for the development of a transrectal mechanical imaging probe for prostate cancer detection.

Regulator of G protein-signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits and are thought to be responsible for rapid deactivation of enzymes and ion channels controlled by G proteins. We wanted to identify and characterize Gi-family alpha subunits that were insensitive to RGS action. Based on a glycine to serine mutation in the yeast Galpha subunit Gpa1(sst) that prevents deactivation by Sst2 (DiBello, P. R., Garrison, T. R., Apanovitch, D. M., Hoffman, G., Shuey, D. J., Mason, K., Cockett, M. I., and Dohlman, H. G. (1998) J. Biol. Chem. 273, 5780-5784), site-directed mutagenesis of alphao and alphai1 was done. G184S alphao and G183S alphai1 show kinetics of GDP release and GTP hydrolysis similar to wild type. In contrast, GTP hydrolysis by the G --> S mutant proteins is not stimulated by RGS4 or by a truncated RGS7. Quantitative flow cytometry binding studies show IC50 values of 30 and 96 nM, respectively, for aluminum fluoride-activated wild type alphao and alphai1 to compete with fluorescein isothiocyanate-alphao binding to glutathione S-transferase-RGS4. The G --> S mutant proteins showed a greater than 30-100-fold lower affinity for RGS4. Thus, we have defined the mechanism of a point mutation in alphao and alphai1 that prevents RGS binding and GTPase activating activity. These mutant subunits should be useful in biochemical or expression studies to evaluate the role of endogenous RGS proteins in Gi function.

Mechanical imaging (MI) is a newly developed modality of medical diagnostics based on reconstruction of tissue structure and viscoelastic properties using mechanical sensors. The essence of MI is the solution to an inverse problem using the data of stress patterns on the surface of tissue compressed by a pressure sensor array. Imaged tissue structures are presented in terms of their viscoelastic properties. Evaluation of tissue 'hardness' (shear elasticity modulus) provides a means for characterizing the tissue, differentiating normal and diseased conditions and detecting tumors and other lesions. In contrast to the other existing methods of medical imaging which use sophisticated hardware such as superconductive magnets, expensive X-ray equipment and complex ultrasonic phased arrays, MI hardware consists of inexpensive mechanical sensors and a positioning system connected to a PC. A key feature of MI is 'knowledge-based imaging'. To produce a three-dimensional image, the computer uses both the measured parameters of an individual examined object and a general database on anatomy and pathology of the object. Two applications of MI are currently being developed: MI for mass screening and detection of breast cancer and MI for imaging the prostate and diagnosing prostate diseases. A prototype of the device for mechanical imaging of the prostate has been developed and is being tested clinically at the Robert Wood Johnson Medical School, New Jersey. The device is comprised of a transrectal probe with a position sensor and a pressure sensor array mounted on the articulated tip, an electronic unit and a PC. Results of extensive laboratory studies with rubber prostate models and initial data obtained in clinical trials strongly suggests that for certain applications the MI technology, as a new modality of imaging, has a diagnostic potential comparable to that of conventional diagnostic technologies. Mechanical imaging of the prostate appeared to be an efficient means of objectively evaluating and imaging the prostate and detecting prostate cancer.

G protein heterocomplex undergoes dissociation and association during its functional cycle. Quantitative measurements of α and βγ subunit binding have been difficult due to a very high affinity. We used fluorescence flow cytometry to quantitate binding of fluorescein-labeled Gi1α (F-α) to picomolar concentrations of biotinylated Gβγ. Association in Lubrol solution was rapid (k on = 0.7 × 106 m −1 s−1), and equilibrium binding revealed a K d of 2.9 ± 0.8 nm. The binding showed a complex dependence on magnesium concentration, but activation of F-α with either GDP/aluminum fluoride or guanosine 5′-O-(3-thiotriphosphate) completely prevented formation of the heterocomplex (K d > 100 nm). The binding was also influenced by the detergent or lipid environment. Unlabeled βγ reconstituted in biotinylated phospholipid vesicles (pure phosphatidylcholine or mixed brain lipids) bound F-α ∼2–3-fold less tightly (K d = 6–9 nm) than in Lubrol. In contrast, βγ in ionic detergents such as cholate and 3-[(cholamidopropyl)diethylammonio]-1-propanesulfonate exhibited substantially lower affinities for F-α. Dissociation of F-α from βγ reconstituted in lipid vesicles was observed upon addition of aluminum fluoride or excess unlabeled α subunit, indicating that myristoylated α subunit has only a weak interaction with lipids without the βγ subunit. The kinetics of aluminum fluoride-stimulated dissociation were slower than those of the α subunit conformational change detected by intrinsic fluorescence. These results quantitatively demonstrate G protein subunit dissociation upon activation and provide a simple but powerful new approach for studying high affinity protein/protein interactions in solution or in a lipid environment.

An increasing number of studies use calcium-sensitive fluorescent dyes to address the relationship between elevated levels of intracellular calcium and free-radical-mediated damage in a variety of pathophysiological phenomena. The present study evaluates the effects of reactive oxygen species on the spectral properties of widely used calcium probes such as Fura-2 and Fluo-3. We found that both Fura-2 and Fluo-3 are rapidly inactivated by hydroxyl radicals and enzymatically inactivated by peroxidase/H2O2. This results in a decrease in the dynamic range of sensitivity of both dyes to Ca2+, as well as in a decrease in the affinity of Fluo-3 for Ca2+. The data suggest that oxidation of the calcium probes affects the measurement of calcium in vitro and may alter the interpretation of in vivo data since the absence of or small changes in the calcium fluorescence signal can be the result of probe deactivation by free oxygen radicals rather than the lack of actual Ca2+ changes.

Objective:to develop a computerized procedure to obtain the percentage of rod-shaped cells in preparations of isolated adult cardiomyocytes.Methods:(1) isolated adult rat myocytes were either pretreated with a fixative (0.2% glutaraldehyde, 0.25% Triton X-100 and 0.1% trypan blue) or monitored via phase-contrast optics without fixation; (2) an image field with several hundred cells was captured by a microscope-mounted video camera, which was connected to a frame grabber, and saved as a TIFF file; (3) the image was processed using Mocha software. Analysis consisted of setting the image threshold, an object count, automatic measurements of objects and their classification.Results:though the software could measure many geometrical characteristics, a combination of two parameters, object size and shape factor, was found to be the most efficient. With these parameters, four classes of sample objects were constructed including rod-shaped myocytes, round damaged cells, overlapping cell clusters, and small debris. Test objects were classified automatically based on which sample object their parameters matched the most. Excellent correlation was obtained between manual counts and computer analysis of cell viability (r=0.98).Conclusion:a more efficient method, based on computer-assisted classification of objects, has been developed to assess the viability of isolated adult cardiomyocytes.

An extensively trypsin-digested Na+/K+-ATPase, which retains the ability to bind Na+, K+, and ouabain, consists of four fragments of the alpha-subunit that contain all 10 transmembrane alpha domains, and the beta-subunit, a fraction of which is cleaved at Arg142-Gly143. In previous studies, we solubilized this preparation with a detergent and mapped the relative positions of several transmembrane helices of the subunits by chemical cross-linking. To determine if these detected helix-helix proximities were representative of those existing in the bilayer prior to solubilization, we have now done similar studies on the membrane-bound preparation of the same digested enzyme. After oxidative sulfhydryl cross-linking catalyzed by Cu2+-phenanthroline, two prominent products were identified by their mobilities and the analyses of their N termini. One was a dimer of a 11-kDa alpha-fragment containing the H1-H2 helices and a 22-kDa alpha-fragment containing the H7-H10 helices. This dimer seemed to be the same as that obtained in the solubilized preparation. The other product was a trimer of the above two alpha-fragments and that fraction of beta whose extracellular domain was cleaved at Arg142-Gly143. This product was different from a similar one of the solubilized preparation in that the latter contained the predominant fraction of beta without the extracellular cleavage. The cross-linking reactions of the membrane preparation, but not those of the solubilized one, were hindered specifically by Na+, K+, and ouabain. These findings indicate that (a) the H1-H2 transmembrane helices of alpha are adjacent to some of its H7-H10 helices both in solubilized and membrane-bound states, (b) the alignment of the residues of the single transmembrane helix of beta with the interacting H1-H2 and H7-H10 helices of alpha is altered by detergent solubilization and by structural changes in the extracellular domain of beta, and (c) the three-dimensional packing of the interacting transmembrane helices of alpha and beta are regulated by the specific ligands of the enzyme.

Mechanical Imaging (MI) is a branch of Elastography. MI differs from conventional ultrasonic and MR elastography in that it evaluates soft tissue mechanical structure using stress data rather than dynamic or static strain data. MI closely mimics manual palpation because the MI probe with a force sensor array attached to its tip acts as a palpating finger. MI is intrinsically a three-dimensional imaging modality because the surface stress patterns obtained at different levels of tissue compression are defined by three-dimensional mechanical structure of the tissue. This review presents the biomechanical basis of MI and its applications for breast cancer screening, and the differentiation of benign and malignant lesions, the visualization and evaluation of prostate conditions, and for the characterization of vaginal wall elasticity.

Colonoscopy is the most sensitive and specific means for detection of colon cancers and polyps. To make colonoscopy more effective several problems must be overcome including: pain associated with the procedure, the risk of perforation, and incomplete intubation colonoscopy. Technically, these problems are the result of loop formation during colonoscopy. Although, several solutions such as modifying the stiffness of the colonoscope, using an overtube and developing image-guided instruments have been introduced to resolve the looping problem, the results of these systems are not completely satisfactory. A new paradigm to overcome loop formation is proposed that is doctor-assistive colonoscopy. In this approach, the endoscopists performance is enhanced by providing using a kinetic model that provides information such as the shape of the scope, direction of the colon and forces exerted within certain sections. It is expected that with the help of this model, the endoscopist would be able to adjust the manipulation to avoid loop formation. In the present studies, the kinetic model is developed and validated using an ex vivo colonoscopy test-bed with a comprehensive kinematic and kinetic data collection. The model utilizes an established colon model based on animal tissue with position tracking sensors, contact force sensors for the intraluminal portion of the scope and a Colonoscopy Force Monitor for the external insertion tube.

Findings from a pilot clinical study of a novel Infant Hydration Monitor (IHM) are presented. IHM is a portable device measuring ultrasound velocity (USV) through the leg muscles in young infants to monitor changes of their hydration status. Study in newborns revealed that USV in their muscles is lower than in adults, indicating higher water content in the tissue by an average of 12%. Observed cases of short term changes of USV can be explained by hydration changes during applied hydration therapy or water detention regiments.

Time Reversal Acoustic (TRA) system provides effective focusing in inhomogeneous media that can be used in various biomedical applications including high intensity ultrasound treatment, ultrasound-assisted drug delivery, ultrasonic battery charging of implants, etc. In many cases the temporal variation of propagating media properties leads to a degradation of the focusing. The in situ adjustment of radiated TRA signal is required in order to restore focusing. We present the feedback algorithm with Tikhonov regularization that enables the refocusing of acoustic field based on the changes in the focused signal received by a beacon. Temporal and spatial quality of the feedback refocusing was characterized experimentally using hydrophone and compared with standard TRA focusing. Algorithm is applicable for power delivery to implantable wireless cardiac pacemakers, percutaneous devices and neuro-stimulators.

The paper presents high-resolution fluorescence images obtained using laser-scanning confocal microscopy. Isolated cells from adult rat hearts were preloaded with 2',7'-dichlorofluorescin (an oxidant-sensitive fluorescent probe) and exposed to doxo- rubicin, an important anticancer drug with prominent cardioxicity. Fluorescence images were collected from live cells simultaneously on two channels: 1) 515-530 nm emission range was used to monitor an increase in dichlorofluorescein, the oxidized product of dichlorofluorescein, and 2) emission > 610 nm was used to visualize the intracellular distribution of doxorubicin. The images reveal intracellular oxidation close to the mitochondria after only 20 min of exposure of isolated cardiomyocytes to 40-160 microM doxorubicin. The data confirm an oxidative mechanism of doxorubicin cardiotoxicity and demonstrate the capability of a new technique to monitor intracellular oxidation in living cardiomyocytes.

A new acoustic approach to medical imaging and diagnostics based on the remote evaluation of shear elasticity modulus of soft tissues is considered. The new method, called shear wave elasticity imaging, is based on the detection of shear waves remotely generated in tissues by radiation pressure of amplitude‐modulated focused ultrasound. Remotely induced shear wave is fully attenuated within a short distance and the induced strain in the tissue can be extremely localized. By choosing appropriate temporal characteristics of the amplitude‐modulated ultrasonic pulse, the volume of tissue involved in the mechanical excitation can be kept on the order of 1=A0 cm3, in contrast to other methods of elasticity imaging where the complete organ is subjected to shear stress. Consequently, evaluation of viscoelastic properties of tissue is greatly simplified since trivial boundary conditions can be assumed and an infinite medium model can be used to reconstruct the mechanical properties of tissue. Analytical equations ...

Most of the biomedical applications of ultrasound are based on the use of focused ultrasound with a high concentration of energy in the focal region and, respectively, with significant contribution of nonlinear phenomena in ultrasonic bioeffects. The main objective of the current paper is to provide a clear understanding of basic phenomena in nonlinear acoustic fields of focused ultrasound, and to derive simplified equations that would enable physicists and engineers to optimize parameters of biomedical devices for particular applications. Special attention is paid to the contribution of acoustic nonlinearity to the second‐order quantities, such as radiation pressure and temperature rise in ultrasonic fields in tissues. Based on asymptotic methods recently developed in nonlinear acoustics, analytical solutions of the equations for the radiation force induced in a dissipative medium are considered. The relationships between parameters of acoustic field and characteristics of biological tissues are quantita...

This paper describes development of mechanical models of breast and prostate mimicking tissue hardness, an important tissue characterization parameter capable of differentiating normal and diseased conditions, revealing tumors and other lesions. Various materials are analyzed and the technique for fabricating mechanical models of soft biological tissue is developed. The models of breast and prostate having Young's moduli varying from 1 to 20 kPa, with and without inclusions mimicking cancer lumps are fabricated. The models are used in testing mechanical imaging devices, a new technology of medical diagnostics in which internal structures are visualized by sensing patterns of mechanical stresses on the surface of an organ.

The relative success of manual palpation in the detection of breast cancer would suggest that a method for remote palpation resulting in a measurement of tissue elasticity could provide a diagnostic tool for detecting cancerous lesions deeper within the breast. This presumption is based in part on the excellent contrast between neoplastic and normal tissue due to the large (orders of magnitude) relative variation in the shear elastic modulus. By comparison, the bulk deformational modulus maintains the same value to within 20% for most soft tissues. A specific method of magnetic-resonance imaging (MRI) which measures tissue displacements has been used in experiments with a phantom containing regions of increased Young's modulus as a demonstration. The spatial modulation of magnetization technique uses the displacement of a spatial grid pattern caused by spin saturation to track regional motion. Mathematical reconstruction of the distribution of elastic moduli is shown for select examples. Any modality, e.g., MRI, ultrasound, etc., which can detect local tissue motion with sufficient spatial resolution can be used and therefore the results presented here should give an indication of the utility of such motion tracking techniques to future measurement of tissue elasticity.

Background Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures. Objective To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions. Methods Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated and unablated spectra to each pixel was then displayed. Results of spectral unmixing were compared to lesion pathology. Results RF ablation caused significant changes in the tissue autofluorescence profile. The magnitude of these spectral changes in human left atrium was relatively small (< 10% of peak fluorescence value), yet highly significant. Spectral unmixing of hyperspectral datasets enabled high spatial resolution, in-situ delineation of radiofrequency lesion boundaries without the need for exogenous markers. Lesion dimensions derived from hyperspectral imaging approach strongly correlated with histological outcomes. Presence of blood within the myocardium decreased the amplitude of the autofluorescence spectra while having minimal effect on their overall shapes. As a result, the ability of hyperspectral imaging to delineate ablation lesions in vivo was not affected. Conclusions Hyperspectral imaging greatly increases the contrast between ablated and unablated tissue enabling visualization of viability gaps at clinically relevant locations. Data supports the possibility for developing percutaneous hyperspectral catheters for high-resolution ablation guidance.

Highly purified preparations of duck salt gland and canine kidney Na + /K + -ATPases with comparable specific activities were used to clarify the causes of previously reported differences between the substrate-velocity curves of these enzymes, When assays were done under identical conditions (pH 7.4; 37°C), and a wide range of closely spaced ATP concentrations were used, the curves of both enzymes exhibited intermediary plateaus, as noted before for the salt gland enzyme. The two enzymes also had the same numbers of phosphorylation and ouabain binding sites, and their catalytic subunits were of the α 1 isoform type as revealed by immunostaining with specific antibodies, The findings suggest that the substrate-velocity curves of all widely used Na + /K + -ATPases may contain an intermediary plateau which is diagnostic of reaction mechanisms that generate rate equations containing powers of substrate concentration greater than two, e.g., a mechanism involving an oligomer with more than two protomers.

Previous studies have shown that susceptibilities of hepatocytes and endothelial cells to H2O(2)-induced injury are altered by changes in the intracellular activity of Cu,Zn-containing superoxide dismutase (CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in oxidant-induced injury to rat cardiac myocytes, cells with reduced CuZn-SOD activity but normal ATP content were either isolated from the hearts of adult copper-deficient rats or obtained by treatment of normal isolated adult myocytes with diethyldithiocarbamate. These myocytes and controls with normal CuZn-SOD activity were exposed to either reagent H2O2 or oxidants generated by extracellular glucose oxidase plus glucose or xanthine oxidase plus xanthine. It was shown that myocytes with CuZn-SOD activities reduced by 70-90% were equally susceptible to H2O2 and the two oxidant-generating systems as the control myocytes. The findings suggest that in adult cardiac myocytes, in contrast to the situation in some other cells, intracellular CuZn-SOD may not have a significant defensive role against acute H2O(2)-induced injury. The possibility remains, however, that changes in the activity of this enzyme, e.g., in copper deficiency, may be relevant to the ability of myocytes to cope with chronic oxidative stress resulting from imbalance between intracellular oxygen radical-generating and -scavenging systems.

Acoustic radiation force (ARF) has been used for many medical applications, the most notable of which is measuring the stiffness of soft tissues. The ARF used in these applications results from the dissipation of acoustic energy due to scattering and absorption of sound and accordingly may be called dissipative ARF. Another source of ARF, which is not related to dissipation of acoustic energy in medium, is variation in acoustic energy density due to gradients of compressional wave speeds in the medium. The effects of this non-dissipative ARF (nARF) are most pronounced in sonication of medium by short ultrasonic pulses with duration on the order of microseconds. Experiments with tissue-mimicking gelatin blocks and various excised animal tissues demonstrated the possibility of measuring sub-nanometer range displacements induced by nARF acting on interfaces in materials with different compressional wave speeds. A continuous wave Doppler device was used to measure the interface particles velocity. Demonstrate...

There are several physical effects responsible for the generation of acoustic radiation force (ARF) in soft tissue. The first effect, which is widely used in elastographic applications of ARF, is the transfer of momentum from ultrasonic wave in an attenuating medium due to absorption and scattering. Two other effects include reflection of sound wave from the boundaries between tissues differing in the acoustic impedance and second, spatial variations of the energy density of the propagating wave as a result of variations in the sound wave velocity in a medium. The latter mode of ARF can be directed both outward and toward the source of the propagating wave. In this study, relative contributions of various modes of acoustic radiation force are investigated both theoretically and experimentally. Using Green function for the acoustic potential near the boundaries between tissue structures, the expression for the motion of tissue interfaces under the action of short ultrasonic pulses is derived. Theoretical e...

Radiofrequency ablation (RFA) aims to produce lesions that interrupt reentrant circuits or block the spread of electrical activation from sites of abnormal activity. Today, there are limited means for real-time visualization of cardiac muscle tissue injury during RFA procedures. We hypothesized that the fluorescence of endogenous NADH could be used as a marker of cardiac muscle injury during epicardial RFA procedures. Studies were conducted in blood-free and blood-perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits. Radiofrequency was applied to the epicardial surface of the heart using a 4-mm standard blazer ablation catheter. A dual camera optical mapping system was used to monitor NADH fluorescence upon ultraviolet illumination of the epicardial surface and to record optical action potentials using the voltage-sensitive probe RH237. Epicardial lesions were seen as areas of low NADH fluorescence. The lesions appeared immediately after ablation and remained stable for several hours. Real-time monitoring of NADH fluorescence allowed visualization of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked the gaps between lesions to postablation reentries. We found that the fluorescence of endogenous NADH aids the visualization of injured epicardial tissue caused by RFA. This was true for both blood-free and blood-perfused preparations. Gaps between NADH-negative regions revealed unablated tissue, which may promote postablation reentry or provide pathways for the conduction of abnormal electrical activity.

Background Colonoscopy is a frequently performed procedure that requires extensive training and a high skill level. Objective Quantification of forces applied to the external portion of the colonoscope insertion tube during the insertion phase of colonoscopy. Design Observational cohort study of 7 expert and 9 trainee endoscopists for analysis of colonic segment force application in 49 patients. Forces were measured by using the colonoscopy force monitor, which is a wireless, handheld device that attaches to the insertion tube of the colonoscope. Setting Academic gastroenterology training programs. Patients Patients undergoing routine screening or diagnostic colonoscopy with complete segment force recordings. Main Outcome Measurements Axial and radial force and examination time. Results Both axial and radial force increased significantly as the colonoscope was advanced from the rectum to the cecum. Analysis of variance demonstrated highly significant operator-independent differences between segments of the colon (zones) in all axial and radial forces except average torque. Expert and trainee endoscopists differed only in the magnitude of counterclockwise force, average push/pull force rate used, and examination time. Limitations Small study, observational design, effect of prototype device on insertion tube manipulation. Conclusion Axial and radial forces used to advance the colonoscope increase through the segments of the colon and are operator independent.

In percutaneous procedures there is often a need to focus therapeutic ultrasound to a predefined area without affecting surrounding tissues. Focusing based on Time Reversal Acoustics (TRA) principles constitutes a promising approach for generating high intensity ultrasound field tailored to the shape of the predefined area. Conventional TRA technique enables ultrasound focusing only at a site, where there is an ultrasound beacon, e.g. piezo-transducer mounted at the tip of a catheter. We developed a method of steering the focus away from the beacon location. The method is based on the measurements of impulse response (IR) in several reference points and calculating virtual IRs for the points outside the reference beacon location. The IR for the point away from the beacon is constructed based on mathematical extrapolation of the measured reference IRs frequency spectra, particularly phases. The effectiveness of extrapolated TRA focusing is explored experimentally and by computer simulation. Potential applications include ultrasounda-ssisted drug delivery, artery recanalization and tumor ablation.

An increasing number of protocols are used to create engineered heart tissue (EHT) constructs, using different progenitors of cardiac cells with various scaffolds and bioreactors. Different laboratories develop their own EHT protocols, which are in most cases highly specialized and involve methods that do not transfer easily from one lab to another. Likewise, the imaging protocols used to evaluate the functional, structural and molecular properties of EHTs are also highly specialized and can involve equipment and methods that do not transfer well between the labs. As a result, it is often necessary to move EHTs between the location where they are engineered to locations where they are used for physiological testing or advanced imaging. In this work, we establish the feasibility of long-distance overnight shipping of EHTs grown in at Columbia University with electrical stimulation to George Washington University for high resolution optical mapping. The EHTs survived overnight shipping in sealed culture media flasks, as evidenced by robust synchronized contractions upon arrival at the destination institution. Calcium transients were readily recordable upon loading of the constructs with Fluo-4. Waves of electrical activity propagating throughout the constructs were imaged using high quantum efficiency back illuminated CCD camera. Due to perfusion limitations, cardiomyocyte-containing layers of EHT are usually restricted to 100-300 microns and the cell density is significantly lower than in intact myocardium. Therefore it was critical to show that the intensity and fidelity of the signals from EHTs stained with the potentiometric dye RH237 are sufficient to record wave propagation throughout the entire 7 mm-wide EHT with 50 micron spatial resolution. The data confirm the feasibility of collaborative arrangements between tissue engineering centers and other laboratories for high resolution fluorescence imaging.

We use high-precision acoustic and densimetric techniques to determine, at 25 degrees C, the changes in volume, delta V, and adiabatic compressibility, delta Ks, that accompany the binding of netropsin to the poly(dAdT).poly(dAdT) and poly(dA).poly(dT) duplexes, as well as to the poly(dT).poly(dA).poly(dT) triplex. We find that netropsin binding to the heteropolymeric poly(dAdT).poly(dAdT) duplex is accompanied by negative changes in volume, delta V, and small positive changes in compressibility, delta Ks. By contrast, netropsin binding to the homopolymeric poly(dA).poly(dT) duplex is accompanied by large positive changes in both volume, delta V, and compressibility, delta Ks. Furthermore, netropsin binding to the poly(dT).poly(dA).poly(dT) triplex causes changes in both volume and compressibility that are nearly twice as large as those observed when netropsin binds to the poly(dA).poly(dT) duplex. We interpret these macroscopic data in terms of binding-induced microscopic changes in the hydration of the DNA structures and the drug. Specifically, we find that netropsin binding induces the release of approximately 22 waters from the hydration shell of the poly(dAdT).poly(dAdT) heteropolymeric duplex, approximately 40 waters from the hydration shell of the poly(dA).poly(dT) homopolymeric duplex, and about 53 waters from the hydration shell of the poly(dA).poly(dT), induces the release of 18 more water molecules than netropsin binding to the heteropolymeric duplex, poly(dAdT).poly(dAdT). On the basis of apparent molar volume, phi V, and apparent molar adiabatic compressibility, phi Ks, values for the initial drug-free and final drug-bound states of the two all-AT duplexes, we propose that the larger dehydration of the poly(dA).poly(dT) duplex reflects, in part, the formation of a less hydrated poly(dA).poly(dT)-netropsin complex compared with the corresponding poly(dAdT).poly(dAdT)-netropsin complex. In conjunction with our previously published entropy data [Marky, L. A., & Breslauer, K. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4359-4363], we calculate that each water of hydration released to the bulk solvent by ligand binding contributes 1.6 cal K-1 mol-1 to the entropy of binding. This value corresponds to the average difference between the partial molar entropy of water in the bulk state and water in the hydration shells of the two all-AT duplexes. When netropsin binds to the poly(dT).poly(dA).poly(dT) triplex, the changes in both volume and compressibility suggest that the binding event induces more dehydration of the triplex than of the duplex state. Specifically, we calculate that netropsin binding to the poly(dT).poly(dA).poly(dT) triplex causes the release of 13 more waters than netropsin binding to the poly(dA).poly(dT) duplex.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of internal displacement and strain distributions in tissue under externally applied forces is a necessary step in elasticity imaging. To obtain a quantitative image of the elastic modulus, strain and displacement fields must be measured with reasonable accuracy and inverted based on an accurate theoretical model of soft tissue mechanics. In this paper, results of measured internal strain and displacement fields from gel-based phantoms are compared with theoretical predictions of a linear elastic model. In addition, some aspects of elasticity reconstruction based on measured displacement and strain fields are discussed. >

The effects of dietary copper deprivation on the activities, immunoreactive protein concentrations, and mRNA abundance of copper/zinc- and manganese-superoxide dismutase (Cu/Zn- and Mn-SOD) were examined in liver, heart, and brain of weanling rats fed a Cu-deficient diet for 4 weeks. Hepatic Cu/Zn-SOD activity, enzyme content, and mRNA abundance were significantly reduced, and, conversely, the activity, protein, and mRNA levels of Mn-SOD were significantly elevated in Cu-deficient rats. In Cu-deficient heart, the activity and protein content for Cu/Zn-SOD were reduced, whereas those for Mn-SOD were increased; the levels of mRNAs for these two enzymes was unaffected. Dietary Cu deficiency was without effect on the activities, enzyme contents, and mRNA abundance of brain Cu/Zn- and Mn-SOD. These results indicate that SODs from liver, heart, and brain exhibit differential sensitivities to dietary Cu deprivation, and that different mechanisms (transcriptional, posttranscriptional, or posttranslational) may be involved in their regulation.

We have determined the partial molar volumes, expansibilities, and adiabatic compressibilities of glycine, diglycine, triglycine, tetraglycine, and pentaglycine over the temperature range 18–55°C. These data were analyzed and interpreted in terms of the hydration of these short oligoglycines and their constituent groups. From our results, we have estimated the contributions of the peptide group to the partial molar volume and the partial molar adiabatic compressibility of these oligoglycines. Based on these data, we propose that each of the polar atomic groups of the peptide bond forms approximately two hydrogen bonds with adjacent water molecules. Furthermore, the temperature dependence of the partial molar volume suggests that water that solvates the polar groups of a peptide linkage behaves more like a “normal” liquid than does bulk water, which exhibits its well-known anomalous liquid properties. © 1994 John Wiley & Sons, Inc.

Using high-precision densitometric and ultrasonic measurements, we have determined, at 25 degrees C, the apparent molar volumes, phi V, and the apparent molar compressibilities, phi KS, of five natural and three synthetic B-form DNA duplexes with varying base compositions and base sequences. We find that phi V ranges from 152.0 to 186.6 cm3 mol-1, while phi KS ranges from -73.0 x 10(-4) to -32.6 x 10(-4) cm3 mol-1 bar-1. We interpret these data in terms of DNA hydration which, by the definition employed in this work, refers to those water molecules whose density and compressibility differ from those of bulk water due to interactions with the DNA solute. This definition implies that hydration depends not just on the quantity but also on the quality of the solvent molecules perturbed by the solute. In fact, we find that the number of water molecules perturbed by the DNA duplexes (the quantity of water in their hydration shells) is approximately the same for all of the B-form double helixes studied, while the quality of this water differs as measured by its density and compressibility, thereby yielding differences in the overall hydration properties. Specifically, we find a linear relationship between the density and the coefficient of adiabatic compressibility, beta Sh, of water in the hydration shell of the DNA duplexes, with the range of values for beta Sh being only 65-80% of the value of bulk water.(ABSTRACT TRUNCATED AT 250 WORDS)