Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging

In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid(?) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.     

Clinical application of sonographic elasticity imaging for aging of deep venous thrombosis: preliminary findings.

OBJECTIVE: Aging of deep venous thrombosis is an important and difficult clinical problem. Because it is known that thrombi harden as they mature, we have preliminarily tested sonographic elasticity imaging, a technique that estimates tissue hardness, to age venous thrombi. METHODS: Two adult patients with lower extremity thrombi were studied. One had a clinically chronic thrombus (at least 3 years old), whereas the other patient's thrombus was clinically subacute (25 days old). We performed freehand compression sonographic scans using a 5-MHz linear array transducer. Phase-sensitive B-scan frames were processed offline by a two-dimensional complex correlation-based adaptive speckle-tracking technique. The distribution of internal strains in the wall of the vein, thrombus, and surrounding tissue was analyzed. Clot hardness was normalized to the venous wall. RESULTS: The chronic clot was homogeneous, and the strain in the chronic clot was at least 10 times smaller than that in the vessel wall. The subacute clot was much more heterogeneous, and, on average, the strain magnitude in the clot was 3 to 4 times greater than that in the vessel wall. CONCLUSIONS: In this preliminary work, the 2 thrombi appeared very different, and these results suggest that elasticity imaging may be able to age deep venous thrombosis.     

Spatial characterization of corneal biomechanical properties with optical coherence elastography after UV cross-linking

Corneal collagen cross-linking (CXL) is a clinical treatment for keratoconus that structurally reinforces degenerating ocular tissue, thereby limiting disease progression. Clinical outcomes would benefit from noninvasive methods to assess tissue material properties in affected individuals. Regional variations in tissue properties were quantified before and after CXL in rabbit eyes using optical coherence elastography (OCE) imaging. Low-amplitude (<1µm) elastic waves were generated using micro air-pulse stimulation and the resulting wave amplitude and speed were measured using phase-stabilized swept-source OCE. OCE imaging following CXL treatment demonstrates increased corneal stiffness through faster elastic wave propagation speeds and lower wave amplitudes.OCIS codes: (170.0170) Medical optics and biotechnology, (110.4500) Optical coherence tomography, (170.4580) Optical diagnostics for medicine, (170.6935) Tissue characterization     

α-(Ac)AKRHRKV,a model of the histone H4 amino terminus,uses an unprotonated histidine in phosphate binding

The ¹H NMR spectrum of the title peptide at pH 3.3 in 90% H₂O was assigned by HOHAHA and NOESY 2D methods. Titration studies in D₂O at 300 MHz indicated a histidine side-chain pKa of 6.3. Peptide backbone NH resonances were studied in 90% H₂O at 500 MHz as a function of pH and added phosphate. In acidic solution the peptide was free from conventional secondary structural elements, but near neutrality the valine amide proton resonance remained a sharp doublet, which suggests that it may form a hydrogen bond with some backbone carbonyl group. The other amide resonances broadened and showed significant saturation transfer from the water signal indicating that they exchange with solvent although not all to the same extent. Marked changes in the chemical shift of the histidine aromatic protons in the presence of phosphate and a 70-fold increase in the ³¹P line width of inorganic phosphate in the presence of peptide only at pH values above the pKa (6.3) of the histidine imidazole side-chain implied that the unprotonated imidazole group is specifically involved in phosphate binding. The peptide binds inorganic phosphate with a dissociation constant of 1.6 × 10^?5 M^?1 at pH 7.4.     

Elasticity reconstructive imaging by means of stimulated echo MRI

A method is introduced to measure internal mechanical displacement and strain by means of MRI. Such measurements are needed to reconstruct an image of the elastic Young's modulus. A stimulated echo acquisition sequence with additional gradient pulses encodes internal displacements in response to an externally applied differential deformation. The sequence provides an accurate measure of static displacement by limiting the mechanical transitions to the mixing period of the simulated echo. Elasticity reconstruction involves definition of a region of interest having uniform Young's modulus along its boundary and subsequent solution of the discretized elasticity equilibrium equations. Data acquisition and reconstruction were performed on a urethane rubber phantom of known elastic properties and an ex vivo canine kidney phantom using <2% differential deformation. Regional elastic properties are well represented on Young's modulus images. The long-term objective of this work is to provide a means for remote palpation and elasticity quantitation in deep tissues otherwise inaccessible to manual palpation.     

Loss of nitric oxide release in passively sensitized guinea-pig aorta with purified immunoglobulin Gl

Background Vascular hyperresponsiveness can be reproduced by in vitro passive sensitization of isolated aorta with immunoglobulin G1 (IgGl) taken from ovalbumen-sensitized BFA guinea-pig. Objective The aim of the present work was to investigate the role of nitric oxide in the sensitization-induced alteration of the contractile and relaxant responses of guinea-pig aorta to noradrenaline (NA) and acetylcholine (ACh). respectively. Methods Cumulative concentration-response curves to NA or ACh were established before and after IgG₁ sensitization and then after successive treatments. Results IgG_l in vitro passive sensitization of aorta caused a significant hyperreactivity to NA and completely inhibited the relaxation to ACh. After sensitization. the addition of an intact aortic ring (with endothelium) in the organ chamber restored the maximal response to NA and ACh close to control but was ineffective in the presence of hemoglobin. The restoration of the control reactivity to NA was also inhibited in the presence of L-NAME or when the added aortic ring was endothelium-denuded. Moreover. L-arginine. a nitric oxide (NO) precursor, was able to restore the control reactivity to NA. Conclusion The present results show that IgG| in vitro sensitization induced a loss of NO release from the vascular endothelium. This loss of NO probably plays a great role in vascular hyperreactivity by increasing the contractile response and decreasing the relaxant response to mediators and would be a component of allergic diseases pathogenesis.     

Exposure to cadmium and conventional and ambulatory blood pressures in a prospective population study. Public Health and Environmental Exposure to Cadmium Study Group

This prospective population study investigated in a random sample of 692 subjects (age 20-83 years) how changing environmental exposure to cadmium influenced blood pressure (BP) and the incidence of hypertension. At baseline (1985 to 1989; participation rate, 78%) and follow-up (1991 to 1995; re-examination rate, 81%), blood pressure was measured by conventional sphygmomanometry (CBP; 15 readings in total) and, at follow-up, also by 24-h ambulatory blood pressure monitoring (ABP). Systolic/diastolic CBP at baseline averaged 128.4/77.3 mm Hg. At baseline, blood cadmium concentration (B-Cd) and urinary cadmium excretion (U-Cd) averaged (geometric means) 11.1 nmol/L and 10.2 nmol/24 h. Over 5.2 years (median follow-up), B-Cd fell by 29.6% and U-Cd by 15.2%. B-Cd fell less in subjects living closer to three zinc smelters and in premenopausal women. During follow-up, systolic CBP decreased by 2.2 mm Hg in men and remained unchanged in women, and diastolic CBP increased by 1.8 mm Hg in both sexes. No relationship could be demonstrated between the secular trends in CBP and B-Cd or U-Cd or between B-Cd or U-Cd at baseline and the incidence of hypertension. In addition, in cross-sectional analyses involving the average of all available CBP measurements in each participant or 24-h ABP at follow-up (mean, 119.1/71.4 mm Hg), blood pressure was not correlated with B-Cd or U-Cd. In conclusion, environmental exposure to cadmium was not associated with higher CBP or 24-h ABP or with increased risk for hypertension. The lesser fall in B-Cd in the residents living closer to the zinc smelters or in premenopausal women underscores the necessity to sanitize cadmium-polluted areas and to systematically reinforce the preventive measures to be adopted by exposed communities to reduce cadmium uptake.     

Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics

Shear wave elasticity imaging (SWEI) is a new approach to imaging and characterizing tissue structures based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. SWEI provides the physician with a virtual “finger” to probe the elasticity of the internal regions of the body. In SWEI, compared to other approaches in elasticity imaging, the induced strain in the tissue can be highly localized, because the remotely induced shear waves are attenuated fully within a very limited area of tissue in the vicinity of the focal point of a focused ultrasound beam. SWEI may add a new quality to conventional ultrasonic imaging or magnetic resonance imaging. Adding shear elasticity data (“palpation information”) by superimposing color-coded elasticity data over ultrasonic or magnetic resonance images may enable better differentiation of tissues and further enhance diagnosis. This article presents a physical and mathematical basis of SWEI with some experimental results of pilot studies proving feasibility of this new ultrasonic technology. A theoretical model of shear oscillations in soft biological tissue remotely induced by the radiation force of focused ultrasound is described. Experimental studies based on optical and magnetic resonance imaging detection of these shear waves are presented. Recorded spatial and temporal profiles of propagating shear waves fully confirm the results of mathematical modeling. Finally, the safety of the SWEI method is discussed, and it is shown that typical ultrasonic exposure of SWEI is significantly below the threshold of damaging effects of focused ultrasound.     

Reconstructive ultrasound elasticity imaging for renal transplant diagnosis: kidney ex vivo results

It may be possible to diagnose and monitor scarring, inflammation and edema in transplant kidney using reconstructive ultrasound elasticity imaging. Kidney elasticity is expected to change dramatically with scar, and to a lesser degree, with acute inflammation and edema. The hypothesis that changes in kidney elasticity can be imaged using a clinical ultrasound scanner was experimentally tested with an ex vivo canine kidney model, and results on a single pair of kidneys are reported in this paper. A cross-linking agent affected kidney elasticity both globally and locally. Elasticity changes were monitored with accurate estimates of internal displacement and strain followed by Young's modulus reconstruction. The results of this study strongly suggest that ultrasound elasticity imaging can detect elasticity changes in complex structures such as the kidney. Moreover, it has the potential to become an important clinical tool for renal transplant diagnosis.     

Strain imaging of corneal tissue with an ultrasound elasticity microscope.

PURPOSE: We hypothesize that high-resolution elasticity measurements can guide corrective refractive surgery of the cornea. Elasticity measurements would improve surgical outcomes by adding biomechanical information not used in existing clinical nomograms. As an initial investigation, we determined the usefulness and evaluated the ability of our ultrasound elasticity microscope by measuring strain ex vivo in an intact porcine eye globe. METHODS: Strain was predicted with a finite element model guided by direct mechanical measurements of corneal elasticity. Next, a porcine cornea was deformed with a slitted plate while being imaged with ultrasound. For high spatial resolution, the ultrasound elasticity microscope uses a 50 MHz transducer with a 1.4 f/number. It produces high-quality conventional ultrasonic B-scans over large thicknesses by confocal processing. Strain was calculated from tracking speckle in these images after deformation. This technique is compatible with in vivo measurements. RESULTS: Compressional and expansional deformations were the same order of magnitude from -3.5% to as great as +3.5%. Strain imaging indicated the stroma expanded into the slit of the deformation plate while Bowman's layer compressed. This bipolar variation within a specimen is unusual. Within the stroma, a variation of strain with depth was measured suggesting a distribution of elasticity. Results compared favorably with the finite element model. CONCLUSION: An ultrasound elasticity microscope can produce high-resolution strain images throughout the corneal depth. Various layers with different elastic properties appeared as different strains in the images.