Youseph Yazdi

Elastography: A Quantitative Method for Imaging the Elasticity of Biological Tissues

We describe a new method for quantitative imaging of strain and elastic modulus distributions in soft tissues. The method is based on external tissue compression, with subsequent computation of the strain profile along the transducer axis, which is derived from cross-correlation analysis of pre- and post-compression A-line pairs. The strain profile can then be converted to an elastic modulus profile by measuring the stresses applied by the compressing device and applying certain corrections for the nonuniform stress field. We report initial results of several phantom and excised animal tissue experiments which demonstrate the ability of this technique to quantitatively image strain and elastic modulus distributions with good resolution, sensitivity and with diminished speckle. We discuss several potential clinical uses of this technique.

Resonance Raman spectroscopy at 257 nm excitation of normal and malignant cultured breast and cervical cells

The sensitivity and selectivity of UV-excited resonance Raman spectroscopy indicate that this technique may be useful in studying certain biochemical changes in cells, especially changes in DNA that occur during the development of cancer. To determine whether this technique can distinguish normal from malignant cells, we have measured UV resonance Raman spectra at 257.26 nm excitation of suspensions of normal and malignant cultured breast and cervical cells. Samples were excited with the use of an intracavity doubled argon-ion laser, and the spectra were recorded with a single grating spectrograph and a liquid nitrogen-cooled charge-coupled device. Cell spectra obtained closely resembled that of DNA, with peaks around 1330, 1480, and 1580 cm−1, due to the nucleotide bases. In addition to these, the uracil base in RNA provides a peak at 1230 cm−1. Strong tryptophan and tyrosine contributions appear in the 1520–1670 cm−1 range. The ratios of Raman spectral peaks 1480/1614 cm−1 and 1480/1540 cm−1, which are sensitive to the concentration of nucleic acids relative to cell proteins, were found to be higher in malignant cells than in normal cells. Normal and malignant cells could also be differentiated by using the ratio at 1330/1480 cm−1. This difference may be the result of decreased hypochromism due to changes in stacking of the purine bases. Changes in relative amounts of RNA may also contribute to this ratio. The results of this pilot study indicate that there may be significant differences in the UV resonance Raman spectra of normal and cancerous cells. These differences may be related to changes in nucleotide/protein concentrations in the cell, as well as changes in the vibrational structure of the nucleic acids associated with the malignant cell phenotype.

Combined ultrasound and fluorescence spectroscopy for physico-chemical imaging of atherosclerosis

Describes a combined ultrasonic and spectroscopic system for remotely obtaining physico-chemical images of normal arterial tissue and atherosclerotic plaque. Despite variations in detector-tissue separation, R, fluorescence powers corresponding to pixels in the image are converted to the same set of calibrated units using distance estimations from A-mode ultrasound reflection times. An empirical model, validated by Monte Carlo simulations of light propagation in tissue, is used to describe changes in fluorescence power as a function of R. Fluorescence spectra of normal and atherosclerotic human aorta obtained with this system are presented as a function of R. To compensate for changes in fluorescence power with R, the empirical model was used in each case to calculate the fluorescence power at a constant reference value of R(R/sub ref/=1.67 mm). Prior to compensation, tissue fluorescence power decreased more than a factor of two as R was increased from 2.5 to 5 mm. Following compensation. The fluorescence power varied less than /spl plusmn/10% of the average compensated peak. The chemical composition of each sample was determined by fitting its fluorescence spectrum (in calibrated units) to a model of tissue fluorescence incorporating structural protein and ceroid fluorescence, as well as structural protein and hemoglobin attenuation. Parameters of the fit were used to classify tissue type. Without compensation for distance variation, classification of tissue type was frequently incorrect; however, with compensation, predictive value was high. A 1D chemical image of a section of human aorta containing both normal and atherosclerotic regions obtained with this system is also presented. After compensation for detector-sample separation, tissue classifications along the cross-section closely resemble those obtained from histology. Regions of elevated ceroid concentration and intimal thickening are clearly observable in the resultant chemical image. The potential value of this type of system in the diagnosis and treatment of coronary artery disease is discussed.<<ETX>>

A transaxial compression technique (TACT) for localized pulse-echo estimation of sound speed in biological tissues

We describe a new method for the estimation of the speed of sound in soft tissues in the pulse-echo mode. A transducer imparts an accurate transaxial compression to the tissue, and the corresponding change in the arrival time of an echo feature is measured. The ratio between the compressed depth and the difference in arrival time is taken as the estimate of the speed of sound. A second, noncompressing transducer is used to correct for distal tissue movement. We show theoretically and experimentally that accurate speed of sound estimations can be made in overlying and underlying tissue mimicking layers.

Optimization of speed-of-sound estimation from noisy ultrasonic signals

The effects of prefiltering and the choice of time-delay estimators and statistical data reduction techniques on the precision of speed-of-sound estimation were investigated using the beam-tracking technique. It was found that prefiltering the data with an ideal 50-kHz low-pass filter improved the precision of the estimation in all cases. Echo cross-correlation had an advantage over peak detection for low signal-to-noise ratio (SNR) levels, but its advantage diminished as the signal-to-noise level improved due to filtering. The linear regression method was superior to the paired-point analysis technique under all conditions. Using the optimal set of parameters, precision on the order of 0.1% was achieved in a tissue-mimicking phantom when one beam was tracking along 75 mm in 1-mm increments.<<ETX>>

Correlation artifacts in speed of sound estimation in scattering media

A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the second order statistical properties of the stairstep artifact are derived.

Voluntary medical male circumcision in resource-constrained settings

Throughout East and Southern Africa, the WHO recommends voluntary medical male circumcision (VMMC) to reduce heterosexual HIV acquisition. Evidence has informed policy and the implementation of VMMC programmes in these countries. VMMC has been incorporated into the HIV prevention portfolio and more than 9 million VMMCs have been performed. Conventional surgical procedures consist of forceps-guided, dorsal slit or sleeve resection techniques. Devices are also becoming available that might help to accelerate the scale-up of adult VMMC. The ideal device should make VMMC easier, safer, faster, sutureless, inexpensive, less painful, require less infrastructure, be more acceptable to patients and should not require follow-up visits. Elastic collar compression devices cause vascular obstruction and necrosis of foreskin tissue and do not require sutures or injectable anaesthesia. Collar clamp devices compress the proximal part of the foreskin to reach haemostasis; the distal foreskin is removed, but the device remains and therefore no sutures are required. Newer techniques and designs, such as tissue adhesives and a circular cutter with stapled anastomosis, are improvements, but none of these methods have achieved all desirable characteristics. Further research, design and development are needed to address this gap to enable the expansion of the already successful VMMC programmes for HIV prevention.

Dual imaging of arterial walls: intravascular ultrasound and fluorescence spectroscopy

This paper describes a combined ultrasonic and spectroscopic system for imaging both the structure and chemical composition of atherosclerotic plaque. Using this system, ultrasound pulse echo distance estimations can be used to accurately compensate detected tissue fluorescence intensities for a wide range of tissue-detector separations, D. Compensation is achieved using an empirical model, wherein fluorescence intensity decreases as 1/Dn with n equals 1.1 for tissue detector separations from 2.5 to 5 mm and 1.4 for separations of 5 to 15 mm. This behavior indicates that fluorescence exiting the tissue surface is not isotropic.

Correction of refraction and other angle errors in beam tracking speed of sound estimations using multiple tracking transducers.

The beam tracking approach to the estimation of the speed of sound has shown potential for making unbiased estimates in tissues. The speed of sound in a medium can be found from the arrival times of echoes as a function of the position of a tracking transducer. There is a problem in this approach if the angle between the direction of tracked beam and the direction of tracking translation is not zero due to refraction or other effects. An angle error as small as 1 degree would result in an error that is too large for diagnostic applications. A modified technique using three or more tracking transducers is described. This yields a corrected speed of sound estimate, and calculates the angle error. A simulation program has shown that this modified technique could indeed correct for the angle errors.

Design improvements for personal protective equipment used in Ebola and other epidemic outbreaks

We redesigned the personal protective equipment ensemble widely used during the 2014 Ebola outbreak into a relatively simpler and more versatile coverall and hood, to improve protection and usability for frontline workers treating patients in infectious disease outbreaks around the world. We redesigned the personal protective equipment ensemble widely used during the 2014 Ebola outbreak into a relatively simpler and more versatile coverall and hood, to improve protection and usability for frontline workers treating patients in infectious disease outbreaks around the world.