New interpretation of arterial stiffening due to cigarette smoking using a structurally motivated constitutive model.

Cigarette smoking is the leading self-inflicted risk factor for cardiovascular diseases; it causes arterial stiffening with serious sequelea including atherosclerosis and abdominal aortic aneurysms. This work presents a new interpretation of arterial stiffening caused by smoking based on data published for rat pulmonary arteries. A structurally motivated "four fiber family" constitutive relation was used to fit the available biaxial data and associated best-fit values of material parameters were estimated using multivariate nonlinear regression. Results suggested that arterial stiffening caused by smoking was reflected by consistent increase in an elastin-associated parameter and moreover by marked increase in the collagen-associated parameters. That is, we suggest that arterial stiffening due to cigarette smoking appears to be isotropic, which may allow simpler phenomenological models to capture these effects using a single stiffening parameter similar to the approach in isotropic continuum damage mechanics. There is a pressing need, however, for more detailed histological information coupled with more complete biaxial mechanical data for a broader range of systemic arteries.

In-vivo validation of fast spectral velocity estimation techniques.

Spectrograms in medical ultrasound are usually estimated with Welch's method (WM). WM is dependent on an observation window (OW) of up to 256 emissions per estimate to achieve sufficient spectral resolution and contrast. Two adaptive filterbank methods have been suggested to reduce the OW: Blood spectral Power Capon (BPC) and the Blood Amplitude and Phase EStimation method (BAPES). Ten volunteers were scanned over the carotid artery. From each data set, 28 spectrograms were produced by combining four approaches (WM with a Hanning window (W.HAN), WM with a boxcar window (W.BOX), BPC and BAPES) and seven OWs (128, 64, 32, 16, 8, 4, 2). The full-width-at-half-maximum (FWHM) and the ratio between main and side-lobe levels were calculated at end-diastole for each spectrogram. Furthermore, all 280 spectrograms were randomized and presented to nine radiologists for visual evaluation: useful/not useful. BAPES and BPC compared to WM had better resolution (lower FWHM) for all OW<128 while only BAPES compared to WM had improved contrast (higher ratio). According to the scores given by the radiologists, BAPES, BPC and W.HAN performed equally well (p>0.05) at OW 128 and 64, while W.BOX scored less (p<0.05). At OW 32, BAPES and BPC performed better than WM (p<0.0001) and BAPES was significantly superior to BPC at OW 16 (p=0.0002) and 8 (p<0.0001). BPC at OW 32 performed as well as BPC at OW 128 (p=0.29) and BAPES at OW 16 as BAPES at OW 128 (p=0.55). WM at OW 16 and 8 failed as all four methods at OW 4 and 2. The intra-observer variability tested for three radiologist showed on average good agreement (90%, kappa=0.79) and inter-observer variability showed moderate agreement (78%, kappa=0.56). The results indicated that BPC and BAPES had better resolution and BAPES better contrast than WM, and that OW can be reduced to 32 using BPC and 16 using BAPES without reducing the usefulness of the spectrogram. This could potentially increase the temporal resolution of the spectrogram or the frame-rate of the interleaved B-mode images.

In-vivo examples of flow patterns with the fast vector velocity ultrasound method.

PURPOSE: Conventional ultrasound methods for acquiring color flow images of the blood motion are limited by a relatively low frame rate and are restricted to only giving velocity estimates along the ultrasound beam direction. To circumvent these limitations, the Plane Wave Excitation (PWE) method has been proposed. MATERIAL AND METHODS: The PWE method can estimate the 2D vector velocity of the blood with a high frame rate. Vector velocity estimates are acquired by using the following approach: The ultrasound is not focused during the ultrasound transmission, and a full speckle image of the blood can be acquired for each pulse emission. The pulse is a 13 bit Barker code transmitted simultaneously from each transducer element. The 2D vector velocity of the blood is found using 2D speckle tracking between segments in consecutive speckle images. Implemented on the experimental scanner RASMUS and using a 100 CPU linux cluster for post processing, PWE can achieve a frame of 100 Hz where one vector velocity sequence of approximately 3 sec, takes 10 h to store and 48 h to process. In this paper a case study is presented of in-vivo vector velocity estimates in different complex vessel geometries. RESULTS: The flow patterns of six bifurcations and two veins were investigated. It was shown: 1. that a stable vortex in the carotid bulb was present opposed to other examined bifurcations, 2. that retrograde flow was present in the superficial branch of the femoral artery during diastole, 3. that retrograde flow was present in the subclavian artery and antegrade in the common carotid artery during diastole, 4. that vortices were formed in the sinus pockets behind the venous valves in both antegrade and retrograde flow, and 5. that secondary flow was present in various vessels. CONCLUSION: Using a fast vector velocity ultrasound method, in-vivo scans have been recorded where complex flow patterns were visualized in greater detail than previously visualized by conventional color flow imaging techniques.

In vivo comparison of three ultrasound vector velocity techniques to MR phase contrast angiography.

The objective of this paper is to validate angle independent vector velocity methods for blood velocity estimation. Conventional Doppler ultrasound (US) only estimates the blood velocity along the US beam direction where the estimate is angle corrected assuming laminar flow parallel to vessel boundaries. This results in incorrect blood velocity estimates, when angle of insonation approaches 90 degrees or when blood flow is non-laminar. Three angle independent vector velocity methods are evaluated in this paper: directional beamforming (DB), synthetic aperture flow imaging (STA) and transverse oscillation (TO). The performances of the three methods were investigated by measuring the stroke volume in the right common carotid artery of 11 healthy volunteers with magnetic resonance phase contrast angiography (MRA) as reference. The correlation with confidence intervals (CI) between the three vector velocity methods and MRA were: DB vs. MRA: R=0.84 (p<0.01, 95% CI: 0.49-0.96); STA vs. MRA: R=0.71 (p<0.05, 95% CI: 0.19-0.92) and TO vs. MRA: R=0.91 (p<0.01, 95% CI: 0.69-0.98). No significant differences were observed for any of the three comparisons (DB vs. MRA: p=0.65; STA vs. MRA: p=0.24; TO vs. MRA: p=0.36). Bland-Altman plots were additionally constructed, and mean differences with limits of agreements (LoA) for the three comparisons were: DB vs. MRA=0.17 ml (95% CI: -0.61-0.95) with LoA=-2.11-2.44 ml; STA vs. MRA=-0.55 ml (95% CI: -1.54-0.43) with LoA=-3.42-2.32 ml; TO vs. MRA=0.24 ml (95% CI: -0.32-0.81) with LoA=-1.41-1.90 ml. According to the results, reliable volume flow estimates can be obtained with all three methods. The three US vector velocity techniques can yield quantitative insight into flow dynamics and visualize complex flow patterns, which potentially can give the clinician a novel tool for cardiovascular disease assessment.

Simulation of RF data with tissue motion for optimizing stationary echo canceling filters.

Blood velocity estimation is complicated by the strong echoes received from tissue surrounding the vessel under investigation. Proper blood velocity estimation necessitates use of a filter for separation of the different signal components. Development of these filters and new estimators requires RF-data, where the tissue component is known. In vivo RF-data does not have this property. Instead simulated data incorporating all relevant features of the measurement situation can be employed. One feature is the motion in the surrounding tissue induced by pulsation, heartbeat, and breathing. This study has developed models for the motions and incorporated them into the RF simulation program Field II, thereby obtaining realistic simulated data. A powerful tool for evaluation of different filters and estimators is then available. The model parameters can be varied according to the physical situation with respect to scan-site and the individual to be scanned. The nature of pulsation is discussed, and a relation between the pressure in the carotid artery and the experienced vessel wall motion is derived.

A new estimator for vector velocity estimation.

A new estimator for determining the two-dimensional velocity vector using a pulsed ultrasound field is derived. The estimator uses a transversely modulated ultrasound field for probing the moving medium under investigation. A modified autocorrelation approach is used in the velocity estimation. The new estimator automatically compensates for the axial velocity when determining the transverse velocity. The estimation is optimized by using a lag different from one in the estimation process, and noise artifacts are reduced by averaging RF samples. Further, compensation for the axial velocity can be introduced, and the velocity estimation is done at a fixed depth in tissue to reduce the influence of a spatial velocity spread. Examples for different velocity vectors and field conditions are shown using both simple and more complex field simulations. A relative accuracy of 10.1% is obtained for the transverse velocity estimates for a parabolic velocity profile for flow transverse to the ultrasound beam and a SNR of 20 dB using 20 pulse-echo lines. The overall bias in the estimates was -4.3%.

The case for gastrin-releasing peptide acting as a morphogen when it and its receptor are aberrantly expressed in cancer.

Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are frequently expressed by cancers of the gastrointestinal tract, breast, lung, and prostate. Most studies have found that GRP and its amphibian homologue bombesin act to increase tumor cell proliferation, leading to the hypothesis that this peptide hormone is a mitogen important for the growth of various cancers. Yet GRP/GRP-R co-expression in cancer promotes the development of a well-differentiated phenotype; while multiple studies suggest that the presence of these 2 proteins confer a survival advantage. Along with recent reports showing that GRP and its receptor critically regulate aspects of colon and lung organogenesis, we argue that these proteins do not function primarily as mitogens when aberrantly expressed in cancer. Rather, we postulate that GRP/GRP-R are onco-fetal antigens that function as morphogens, with their effect on tumor cell proliferation being a component property of their ability to regulate differentiation. Thus aberrant GRP/GRP-R expression in cancer recapitulates, albeit in a dysfunctional manner, their normal role in development.

A new approach for the estimation of the axial velocity using ultrasound.

The most used estimation method for calculating the blood velocity in commercial scanners is the autocorrelation approach. The calculation of the mean velocity used in this method depends on the center frequency of the interacting ultrasound pulse which downshifts as a function of depth, introducing a bias. A new velocity estimator for the mean axial velocity is presented. The estimation principle is based on the 2D Fourier transform and the Radon transform. The input data are a sequence of RF data forming a 2D data input, one column for each pulse emission. A 2D segment is selected for a specific depth. This data segment is first transformed by a 2D Fourier transform, and the result is then transformed by a Radon transform. The center of gravity for the angles of the lines intersecting the origin of the R-theta coordinate system in the Radon domain gives the mean axial velocity for the data segment. The benefit of this method is an estimate of the mean axial velocity which is independent of the center frequency of the propagating ultrasound pulse. The estimate will only depend on f(s) and f(pr f). Results of the estimation method is presented based on both simple generated RF harmonic data for different signal/noise ratios and simulated acoustic RF responses from a 3D measurement situation with an array transducer and a tube with plug flow. The new method shows improvement with a factor of 1.5-4 on the standard deviation on the estimated mean velocity for the simulated case.

Application of different spatial sampling patterns for sparse array transducer design.

In the last few years, the efforts of many researchers have been focused on developing 3D real-time scanners. The use of 2D phased-array transducers makes it possible to steer the ultrasonic beam in all directions in the scanned volume. An unacceptably large amount of transducer channels (more than 4,000) must be used, if the conventional phased array transducers are extrapolated to the 2D case. To decrease the number of channels, sparse arrays with different aperture apodization functions in transmit and receive apertures have to be designed. The design is usually carried out in 1D, and then transferred to a 2D rectangular grid. In this paper, five different 2D array transducers have been considered and their performance was compared with respect to spatial and contrast resolution. An optimization of the element placement along the diagonals using vernier arrays is suggested. The simulation results of the ultrasound fields show a decrease in the grating-lobe level of 10 dB for the diagonally optimized 2D array transducers compared to the previously designed 2D arrays which did not consider the diagonals.

Potential of coded excitation in medical ultrasound imaging.

Improvement in signal-to-noise ratio (SNR) and/or penetration depth can be achieved in medical ultrasound by using long coded waveforms, in a similar manner as in radars or sonars. However, the time-bandwidth product (TB) improvement, and thereby SNR improvement is considerably lower in medical ultrasound, due to the lower available bandwidth. There is still space for about 20 dB improvement in the SNR, which will yield a penetration depth up to 20 cm at 5 MHz [M. O'Donnell, IEEE Trans. Ultrason. Ferroelectr. Freq. Contr., 39(3) (1992) 341]. The limited TB additionally yields unacceptably high range sidelobes. However, the frequency weighting from the ultrasonic transducer's bandwidth, although suboptimal, can be beneficial in sidelobe reduction. The purpose of this study is an experimental evaluation of the above considerations in a coded excitation ultrasound system. A coded excitation system based on a modified commercial scanner is presented. A predistorted FM signal is proposed in order to keep the resulting range sidelobes at acceptably low levels. The effect of the transducer is taken into account in the design of the compression filter. Intensity levels have been considered and simulations on the expected improvement in SNR are also presented. Images of a wire phantom and clinical images have been taken with the coded system. The images show a significant improvement in penetration depth and they preserve both axial resolution and contrast.

Algorithms for estimating blood velocities using ultrasound.

Ultrasound has been used intensively for the last 15 years for studying the hemodynamics of the human body. Systems for determining both the velocity distribution at one point of interest (spectral systems) and for displaying a map of velocity in real time have been constructed. A number of schemes have been developed for performing the estimation, and the various approaches are described. The current systems only display the velocity along the ultrasound beam direction and a velocity transverse to the beam is not detected. This is a major problem in these systems, since most blood vessels are parallel to the skin surface. Angling the transducer will often disturb the flow, and new techniques for finding transverse velocities are needed. The various approaches for determining transverse velocities will be explained. This includes techniques using two-dimensional correlation (speckle tracking), multiple beams, and the new transverse modulation technique. The different advantages and disadvantages of the approaches are explained.

Quantitation of urinary metabolites of a tobacco-specific lung carcinogen after smoking cessation.

We quantified urinary levels of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in people who had stopped smoking: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide, 4-[(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). Twenty-seven people completed the study. Thirteen used the nicotine patch starting at the quit date, whereas the others used no patch. Two 24-h urine samples were collected on 2 consecutive days before smoking cessation; blood was also obtained. Beginning at their quit date, subjects provided 24-h urine samples on days 7, 21, 42, 70, 98, and 126, and some subjects also provided samples at later times. The urine was analyzed for NNAL, NNAL-Gluc, nicotine plus nicotine-N-glucuronide, and cotinine plus cotinine-N-glucuronide. Some blood samples were also analyzed for NNAL. The decline of urinary NNAL and NNAL-Gluc after smoking cessation was much slower than expected. This was clearly demonstrated by comparison with cotinine and nicotine levels in urine. One week after smoking cessation, 34.5% of baseline NNAL plus NNAL-Gluc was detected in urine, whereas the corresponding values for cotinine and nicotine were 1.1 and 0.5%, respectively. Even 6 weeks after cessation, 7.6% of the original levels of NNAL plus NNAL-Gluc remained. In some subjects, NNAL plus NNAL-Gluc were detected 281 days after cessation. The distribution half-life for NNAL and NNAL-Gluc was 3-4 days, whereas the elimination half-life was 40-45 days. Total body clearance of NNAL was estimated to be 61.4 +/- 35.4 ml/min, and volume of distribution in the beta-phase was estimated to be 3800 +/- 2100 liters, indicating substantial distribution into the tissues. Parallel studies in rats treated chronically or acutely with NNK in the drinking water support the conclusion that NNAL has a large volume of distribution. There was no effect of the nicotine patch on levels of NNAL plus NNAL-Gluc, indicating that NNK is not formed endogenously from nicotine. The results of this study demonstrate that NNAL and NNAL-Gluc are slowly cleared from the body after smoking cessation, indicating the presence of a high-affinity compartment where NNK, NNAL, and/or NNAL-Gluc are retained or sequestered and slowly released.

A new method for estimation of velocity vectors.

The paper describes a new method for determining the velocity vector of a remotely sensed object using either sound or electromagnetic radiation. The movement of the object is determined from a field with spatial oscillations in both the axial direction of the transducer and in one or two directions transverse to the axial direction. By using a number of pulse emissions, the inter-pulse movement can be estimated and the velocity found from the estimated movement and the time between pulses. The method is based on the principle of using transverse spatial modulation for making the received signal influenced by transverse motion. Such a transverse modulation can be generated by using apodization on individual transducer array elements together with a special focusing scheme. A method for making such a field is presented along with a suitable two-dimensional velocity estimator. An implementation usable in medical ultrasound is described, and simulated results are presented. Simulation results for a flow of 1 m/s in a tube rotated in the image plane at specific angles (0, 15, 35, 55, 75, and 90 degrees) are made and characterized by the estimated mean value, estimated angle, and the standard deviation in the lateral and longitudinal direction. The average performance of the estimates for all angles is: mean velocity 0.99 m/s, longitudinal S.D. 0.015 m/s, and lateral S.D. 0.196 m/s. For flow parallel to the transducer the results are: mean velocity 0.95 m/s, angle 0.10, longitudinal S.D. 0.020 m/s, and lateral S.D. 0.172 m/s.

Wound tissue oxygen tension predicts the risk of wound infection in surgical patients.

OBJECTIVE: To test the hypothesis that subcutaneous wound oxygen tension (PsqO2) has a predictive relation to the development of wound infection in surgical patients. DESIGN: A noninterventional, prospective study. SETTING: A university department of surgery. PATIENTS: One hundred thirty operative general surgical patients at notable risk of infection as predicted by an anticipated Study on the Effect of Nosocomial Infection Control (SENIC) score of 1 or greater. OUTCOME MEASURES: PsqO2 was measured perioperatively. Its relation to the subsequent incidence of surgical wound infection was then determined and compared with the SENIC score as a criterion standard. RESULTS: Although the SENIC score and PsqO2 are inversely correlated, PsqO2 is the stronger predictor of infection. Low PsqO2 identified patients at risk and concentrated them in a cohort that was about half the size of that identified by the SENIC score. CONCLUSIONS: Subcutaneous perfusion and oxygenation are important components of immunity to wound infections. The SENIC score identifies systemic physiological variables that are important to the development of wound infection. Nevertheless, PsqO2 is the more powerful predictor of wound infection. Moreover, PsqO2 can be manipulated by available clinical means, and thus may direct interventions to prevent infection.

Breast conservation therapy after augmentation mammaplasty: is it appropriate?

Breast conservation therapy, consisting of lumpectomy, axillary node dissection, whole-breast irradiation, and a boost to the tumor bed, is an increasingly popular option for the treatment of breast cancer. Among patients with stage I and stage II disease, breast conservation therapy yields survival rates equivalent to those for mastectomy. The cosmetic results of radiotherapy are usually good, and this approach preserves an intact, sensate breast. Most studies on breast conservation therapy, however, have been performed in nonaugmented patients. Relatively little has been published regarding breast conservation therapy in the presence of silicone implants. Between 1981 and 1994, we treated 33 augmented patients with breast conservation therapy. Among 26 individuals for whom complete follow-up data were available, 17 (65 percent) developed significant capsular contracture on the irradiated side. Thus far 8 patients with radiation-induced contracture have undergone corrective surgery. In our experience, augmented breast cancer patients treated with breast conservation therapy have less satisfactory cosmetic results than nonaugmented women. In addition, mammographic follow-up, critical for identifying local recurrence, may be impaired by the presence of an implant and capsular contracture. On the basis of these considerations, breast conservation therapy may be less than optimal in augmented cancer patients unless explantation is performed before treatment.

Fine needle aspiration cytology of the oxyphil variant of papillary carcinoma of the thyroid. A report of three cases.

BACKGROUND: A number of histologic variants of papillary carcinoma of the thyroid have been described, including an oxyphil cell subtype (OVPC). Few OVPC cases have been detailed cytologically. CASES: Smears prepared from aspiration biopsies, as well as the corresponding histologic sections and clinical histories, were reviewed for three cases. Two patients had asymptomatic thyroid tumors, and the third developed neck tumors after thyroid cancer surgery. All smears revealed scattered papillary groups and monolayered sheets. The large, neoplastic cells had abundant, granular cytoplasm and eccentrically placed nuclei. Nuclear grooves and intranuclear inclusions were variably present. Psammoma bodies and colloid were not identified. Histologically the tumors consisted predominantly of oxyphil cells arranged in papillary patterns and with nuclear features of usual papillary carcinoma (UPC). CONCLUSION: OVPC can be diagnosed in smears composed predominantly of large oxyphil cells but showing features associated with UPC and can be cytologically distinguished from follicular oxyphilic tumors and UPC.

A patient classification system for ambulatory surgery centers.

A well-developed and operational patient classification system can lessen problems associated with determining and allocating nursing personnel. This article discusses the development of such a tool in a free-standing ambulatory surgery center and includes a tool for facilities that want to develop similar classification systems.