Noninvasive ultrasound image guided surface wave method for measuring the wave speed and estimating the elasticity of lungs: A feasibility study.

Lung diseases, such as acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), are closely associated with altered lung elastic properties. Pulmonary function testing and imaging are routinely performed for evaluating lung diseases. However, lung compliance, a measure of lung elastic properties, is rarely used in clinic, because it is invasive and provides only a global and arguably biased estimate of lung elastic properties. Current ultrasound methods also cannot be used for imaging lungs because ultrasound cannot penetrate the lung tissue. In this paper, an ultrasound image guided and surface wave based method is proposed to measure regional lung surface wave speed and estimate lung elasticity noninvasively. The method described here was not explored before to the best knowledge of the authors. Experiments in an ex vivo pig lung and an in vivo human lung pilot study are reported. The surface wave speed is measured to be 1.83±0.02m/s at 100Hz by ultrasound for the ex vivo pig lung at 3mmHg pressure, which is validated by an optical measurement. An in vivo human lung pilot experiment measures the surface wave speed to be 2.41±0.33m/s for the 100Hz sinusoidal wave at total lung capacity (TLC) and 0.99±0.09m/s at functional residual capacity (FRC). These values of wave speed fall well within the range of available literature.

Shear wave dispersion ultrasonic vibrometry for measuring prostate shear stiffness and viscosity: an in vitro pilot study.

This paper reports shear stiffness and viscosity "virtual biopsy" measurements of the three excised noncancerous human prostates using a new tool known as shear wave dispersion ultrasound vibrometry (SDUV) in vitro. Improved methods for prostate guided-biopsy are required to effectively guide needle biopsy to the suspected site. In addition, tissue stiffness measurement helps in identifying a suspected site to perform biopsy because stiffness has been shown to correlate with pathologies, such as cancerous tissue. More importantly, early detection of prostate cancer may guide minimally invasive therapy and eliminate insidious procedures. In this paper, "virtual biopsies" were taken in multiple locations in three excised prostates; SDUV shear elasticity and viscosity measurements were performed at the selected "suspicious" locations within the prostates. SDUV measurements of prostate elasticity and viscosity are generally in agreement with preliminary values previously reported in the literature. It is, however, important to emphasize here that the obtained viscoelastic parameters values are local, and not a mean value for the whole prostate.

A Kramers-Kronig-based quality factor for shear wave propagation in soft tissue.

Shear wave propagation techniques have been introduced for measuring the viscoelastic material properties of tissue, but assessing the accuracy of these measurements is difficult for in vivo measurements in tissue. We propose using the Kramers-Kronig relationships to assess the consistency and quality of the measurements of shear wave attenuation and phase velocity. In ex vivo skeletal muscle we measured the wave attenuation at different frequencies, and then applied finite bandwidth Kramers-Kronig equations to predict the phase velocities. We compared these predictions with the measured phase velocities and assessed the mean square error (MSE) as a quality factor. An algorithm was derived for computing a quality factor using the Kramers-Kronig relationships.

In vitro comparative study of vibro-acoustography versus pulse-echo ultrasound in imaging permanent prostate brachytherapy seeds.

BACKGROUND: Permanent prostate brachytherapy (PPB) is a common treatment for early stage prostate cancer. While the modern approach using trans-rectal ultrasound guidance has demonstrated excellent outcome, the efficacy of PPB depends on achieving complete radiation dose coverage of the prostate by obtaining a proper radiation source (seed) distribution. Currently, brachytherapy seed placement is guided by trans-rectal ultrasound imaging and fluoroscopy. A significant percentage of seeds are not detected by trans-rectal ultrasound because certain seed orientations are invisible making accurate intra-operative feedback of radiation dosimetry very difficult, if not impossible. Therefore, intra-operative correction of suboptimal seed distributions cannot easily be done with current methods. Vibro-acoustography (VA) is an imaging modality that is capable of imaging solids at any orientation, and the resulting images are speckle free. OBJECTIVE AND METHODS: The purpose of this study is to compare the capabilities of VA and pulse-echo ultrasound in imaging PPB seeds at various angles and show the sensitivity of detection to seed orientation. In the VA experiment, two intersecting ultrasound beams driven at f(1)=3.00 MHz and f(2)=3.020 MHz respectively were focused on the seeds attached to a latex membrane while the amplitude of the acoustic emission produced at the difference frequency 20 kHz was detected by a low frequency hydrophone. RESULTS: Finite element simulations and results of experiments conducted under well-controlled conditions in a water tank on a series of seeds indicate that the seeds can be detected at any orientation with VA, whereas pulse-echo ultrasound is very sensitive to the seed orientation. CONCLUSION: It is concluded that vibro-acoustography is superior to pulse-echo ultrasound for detection of PPB seeds.

Continuous-wave ultrasound reflectometry for surface roughness imaging applications.

BACKGROUND: Measurement of surface roughness irregularities that result from various sources such as manufacturing processes, surface damage, and corrosion, is an important indicator of product quality for many nondestructive testing (NDT) industries. Many techniques exist, however because of their qualitative, time-consuming and direct-contact modes, it is of some importance to work out new experimental methods and efficient tools for quantitative estimation of surface roughness. OBJECTIVE AND METHOD: Here we present continuous-wave ultrasound reflectometry (CWUR) as a novel nondestructive modality for imaging and measuring surface roughness in a non-contact mode. In CWUR, voltage variations due to phase shifts in the reflected ultrasound waves are recorded and processed to form an image of surface roughness. RESULTS: An acrylic test block with surface irregularities ranging from 4.22 microm to 19.05 microm as measured by a coordinate measuring machine (CMM), is scanned by an ultrasound transducer having a diameter of 45 mm, a focal distance of 70 mm, and a central frequency of 3 MHz. It is shown that CWUR technique gives very good agreement with the results obtained through CMM inasmuch as the maximum average percent error is around 11.5%. CONCLUSION: Images obtained here demonstrate that CWUR may be used as a powerful non-contact and quantitative tool for nondestructive inspection and imaging of surface irregularities at the micron-size level with an average error of less than 11.5%.

Vibro-acoustography imaging of permanent prostate brachytherapy seeds in an excised human prostate--preliminary results and technical feasibility.

OBJECTIVE: The objective in this work is to investigate the feasibility of using a new imaging tool called vibro-acoustography (VA) as a means of permanent prostate brachytherapy (PPB) seed localization to facilitate post-implant dosimetry (PID). METHODS AND MATERIALS: Twelve OncoSeed (standard) and eleven EchoSeed (echogenic) dummy seeds were implanted in a human cadaver prostate. Seventeen seeds remained after radical retropubic prostatectomy. VA imaging was conducted on the prostate that was cast in a gel phantom and placed in a tank of degassed water. 2-D magnitude and phase VA image slices were obtained at different depths within the prostate showing location and orientation of the seeds. RESULTS: VA demonstrates that twelve of seventeen (71%) seeds implanted were visible in the VA image, and the remainder were obscured by intra-prostatic calcifications. Moreover, it is shown here that VA is capable of imaging and locating PPB seeds within the prostate independent of seed orientation, and the resulting images are speckle free. CONCLUSION: The results presented in this research show that VA allows seed detection within a human prostate regardless of their orientation, as well as imaging intra-prostatic calcifications.

A combined parabolic-integral equation approach to the acoustic simulation of vibro-acoustic imaging.

This paper aims to model ultrasound vibro-acoustography to improve our understanding of the underlying physics of the technique thus facilitating the collection of better images. Ultrasound vibro-acoustography is a novel imaging technique combining the resolution of high-frequency imaging with the clean (speckle-free) images obtained with lower frequency techniques. The challenge in modeling such an experiment is in the variety of scales important to the final image. In contrast to other approaches for modeling such problems, we break the experiment into three parts: high-frequency propagation, non-linear interaction and the propagation of the low-frequency acoustic emission. We then apply different modeling strategies to each part. For the high-frequency propagation we choose a parabolic approximation as the field has a strong preferred direction and small propagation angles. The non-linear interaction is calculated directly with Fourier methods for computing derivatives. Because of the low-frequency omnidirectional nature of the acoustic emission field and the piecewise constant medium we model the low-frequency field with a surface integral approach. We use our model to compare with experimental data and to visualize the relevant fields at points in the experiment where laboratory data is difficult to collect, in particular the source of the low-frequency field. To simulate experimental conditions we perform the simulations with the two frequencies 3 and 3.05 MHz with an inclusion of varying velocity submerged in water.

Investigating the absolute phase information in acoustic wave resonance scattering.

The aim of this work is to investigate the absolute phase information in resonance acoustic scattering by spheres and cylinders and place this work in the broader context of scattering in which the properties of the magnitude and (processed) phase have been examined in a more general way than in the classical resonance scattering theory (RST). Here, comparisons are made between the classical and modified RST formalisms of acoustic resonance scattering. Experimental and theoretical backscattering form functions are obtained and discussed. It is shown that the magnitude and processed (unwrapped) phase can be correctly obtained through the classical RST, suggesting that the modified RST formalism offers little new practical advantage. Furthermore, the absolute phase is shown to be very sensitive to object's resonances, suggesting that the unwrapped phase may be considered as an efficient tool, along with the magnitude information, to carry out remote (active) classification of targets in underwater acoustics applications. The combination of absolute phase information with the magnitude data offers a complementary advantage in the identification of resonances from cylinders and spheres.

A proposed method for assessing plasma hypertonicity in vivo.

Indices of plasma hypertonicity, elevated plasma concentrations of solutes that draw fluid out of cells by osmosis, are needed to pursue hypertonicity as a possible risk factor for obesity and chronic disease. This paper proposes a new index that may be more sensitive to mild hypertonicity in vivo at a point in time than traditional measures. The index compares mean corpuscular volume (MCV) estimates from diluted (in solution by automated cell counter) and nondiluted blood (calculated from manual hematocrit, MCV=Hct/RBC*10(6)). A larger Auto vs Manual MCV (>2 fl) in vitro indicates hypertonicity in vivo if the cell counter diluent is isotonic with the threshold for plasma vasopressin (PVP) release and PVP is detectable in plasma (>0.5 pg/ml). To evaluate this principle of concept, hypertonicity was induced by 24-h fluid restriction after a 20 ml/kg water load in four healthy men (20-46 years). Unlike serum and urine indices, the MCV difference-&-PVP index detected hypertonicity in all participants.

Chirp imaging vibro-acoustography for removing the ultrasound standing wave artifact.

Vibro-acoustography (VA) is an imaging technique that uses the dynamic (oscillatory) radiation force of two continuous-wave (CW) ultrasound to image objects at low frequency (within the kHz range). In this technique, the dynamic radiation force is created by means of a confocused transducer emitting two ultrasound beams at slightly-shifted frequencies f1 and f2 = f1 + deltaf. It has been demonstrated previously that high-resolution images of various types of inclusions and tissues can be obtained using this technique. However, if the targeted object reflects ultrasound directly back to the transducer, standing waves are produced that result in an artifact in the VA image. The goal of this study is to remove the standing wave artifact and improve VA images by means of a new process called chirp imaging. The procedure consists of sweeping the frequencies of the primary ultrasound beams in a selected bandwidth while keeping deltaf constant during the sweep. The chirp image is produced by averaging the amplitude of the acoustic emission produced during the sweep. Vibro-acoustography chirp imaging experiments are performed on a stainless-steel sphere attached to a latex sheet in a tank of degassed water. The resulting chirp images demonstrate remarkable reduction of the standing wave artifact compared to the "fixed frequency" VA images.

Exercise training and 3-day head down bed rest deconditioning: exercise thermoregulation.

UNLABELLED: Bed rest (BR) deconditioning causes excessive increase of exercise core body tempera-ture, while aerobic training improves exercise thermoregulation. The study was designed to determine whether 3 days of 6 degrees head-down bed rest (HDBR) affects body temperature and sweating dynamics during exercise and, if so, whether endurance training before HDBR modifies these responses. Twelve healthy men (20.7+/-0.9 yrs, VO2max: 46+/-4 ml x kg(-1) x min(-1) ) underwent HDBR twice: before and after 6 weeks of endurance training. Before and after HDBR, the subjects performed 45 min sitting cycle exercise at the same workload equal to 60% of VO2max determined before training. During exercise the VO2, HR, tympanic (Ttymp) and skin (Tsk) temperatures were recorded; sweating dynamics was assayed from a ventilated capsule on chest. Training increased VO2max by 12.1% (p<0.001). Resting Ttymp increased only after first HDBR (by 0.22 +/- 0.08 degrees C, p<0.05), while exercise equilibrium levels of Ttymp were increased (p<0.05) by 0.21 +/- 0.07 and 0.26 +/- 0.08 degrees C after first and second HDBR, respectively. Exercise mean Tsk tended to be lower after both HDBR periods. Total sweat loss and time-course of sweating responses were similar in all exercise tests. The sweating threshold related to Ttymp was elevated (p<0.05) only after first HDBR. IN CONCLUSION: six-week training regimen prevents HDBR-induced elevation of core temperature (Ttymp) at rest but not during ex-ercise. The post-HDBR increases of Ttymp without changes in sweating rate and the tendency for lower Tsk suggest an early (<3d) influence of BR on skin blood flow.

Intensive exercise training suppresses testosterone during bed rest.

Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P < 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.

Catecholamine responses to environmental stressors in trained and untrained men after 3-day bed rest.

INTRODUCTION: The effect of decreased physical activity with reduced gravitational stress on activity, sensitivity, and reactivity of the sympathetic nervous system (SNS) is not fully recognized. We hypothesized that the effect is most pronounced in physically active subjects. Thus, basal plasma norepinephrine [NE] and epinephrine [E], and catecholamine responses to physiological stimuli were determined after 3 d of horizontal bed rest (BR) in subjects differing in level and kind of habitual activity. METHODS: Before and after BR, 11 untrained students, 8 endurance athletes, and 10 power/strength athletes were submitted to oral glucose tolerance test (OGTT) and orthostatic stand test (OST). Another 32 men (12 untrained, 10 endurance athletes, and 10 power/strength athletes) underwent cold pressor test (CPT) and graded exercise test (GET) performed until volitional exhaustion. RESULTS: After BR, basal [NE] was decreased only in athletes (p < 0.01). Increases in both catecholamines during OGTT were diminished (p < 0.05), particularly in endurance athletes. Plasma [NE] response to standing was not affected by BR in individual groups, but it was diminished in the whole group (p < 0.05). Bed rest did not affect the increases in catecholamines induced by CPT and GET. Heart rate response to OST, and BP responses to OST, CPT, and glucose ingestion were enhanced. CONCLUSIONS: Basal sympathetic activity is diminished after 3 d of BR in physically active men. Although catecholamine responses to glucose load and standing were reduced, the general reactivity and sensitivity of SNS were not attenuated since catecholamine responses to the most (exercise) and least (CPT) powerful stimuli were unchanged.

Noncontact ultrasound stimulated optical vibrometry study of coupled vibration of arterial tubes in fluids.

Coupled vibration of arterial tubes is analyzed with the wave propagation approach and first-order shear deformation theory. Both the interior and exterior fluids are considered as compressible so that acoustic waves can be generated and propagated in the fluids. Results obtained using the theory have been evaluated against those available in the literature and the agreement has been found to be good. The theory can be used for future research on the vibration and acoustics of arterial walls. Vibration experiments were carried out on a silicone rubber tube in a water tank with a novel ultrasound stimulated optical vibrometry system. This system uses the radiation force of ultrasound to vibrate the tube at low frequency and records the resulting response by a laser vibrometer. Both the excitation and measurement are remote and noncontact. The silicone rubber tube was chosen because it has mechanical properties close to those of arteries. The fundamental frequency is well excited by the radiation force and measured with the laser. The measured fundamental frequency is in good agreement with the present theory.

Magnetic resonance elastography: non-invasive mapping of tissue elasticity.

Magnetic resonance elastography (MRE) is a phase-contrast-based MRI imaging technique that can directly visualize and quantitatively measure propagating acoustic strain waves in tissue-like materials subjected to harmonic mechanical excitation. The data acquired allows the calculation of local quantitative values of shear modulus and the generation of images that depict tissue elasticity or stiffness. This is significant because palpation, a physical examination that assesses the stiffness of tissue, can be an effective method of detecting tumors, but is restricted to parts of the body that are accessible to the physician's hand. MRE shows promise as a potential technique for 'palpation by imaging', with possible applications in tumor detection (particularly in breast, liver, kidney and prostate), characterization of disease, and assessment of rehabilitation (particularly in muscle). We describe MRE in the context of other recent techniques for imaging elasticity, discuss the processing algorithms for elasticity reconstruction and the issues and assumptions they involve, and present recent ex vivo and in vivo results.

Intracardiac measurement of pre-ejection myocardial velocities estimates the transmural extent of viable myocardium early after reperfusion in acute myocardial infarction.

OBJECTIVES: We hypothesized that wall motion velocity during pre-ejection is proportional to the regional content of viable myocardium after reperfusion for acute myocardial infarction (AMI). BACKGROUND: Pre-ejection wall motion consists of short and fast inward and outward movement towards and away from the center of the left ventricle (LV) and is altered during regional ischemia. This short-lived event can be accurately quantified by Doppler myocardial imaging (DMI). METHODS: Fourteen open-chest pigs underwent 60 to 120 min of left anterior descending coronary artery occlusion followed by 30 min of reperfusion. The DMI data were collected using a phased-array intracardiac catheter (LV cavity) from ischemic and nonischemic myocardium encompassed within a plane passing through two epicardial bead markers. Peak tissue velocities during isovolumic contraction (IVC) (peak positive and peak negative), ejection (S) and early filling (E) were measured. The cardiac specimen was sliced through the epicardial markers in a plane approximating the ultrasound imaging plane. The transmural extent of necrosis (TEN) (%) was measured by triphenyltetrazolium chloride staining. RESULTS: During ischemia, positive IVC velocity was zero in ischemic walls with TEN >20%. At reperfusion, positive IVC velocity correlated better with TEN (r = -0.94, p < 0.0001) than it did S (r = -0.70, p < 0.01) and E (r = -0.81, p < 0.01). Differential IVC (the difference between peak positive and peak negative velocity) highly correlated with TEN, during ischemia (r = -0.78, p < 0.001) and during reperfusion (r = -0.93, p < 0.0001). CONCLUSIONS: Pre-ejection tissue velocity, as measured by intracardiac ultrasound, allows rapid estimation of the transmural extent of viable myocardium after reperfusion for AMI.

Neural network analysis of EUS images to differentiate between pancreatic malignancy and pancreatitis.

BACKGROUND: The differentiation of focal pancreatitis and pancreatic adenocarcinoma is problematic and often resolved only by pancreaticoduodenectomy. EUS is the most sensitive imaging modality for both conditions, yet ultrasonic criteria for distinguishing the two have not been described and differentiation remains difficult. The aims of this study were to develop a self-learning computer program that can analyze EUS images and differentiate malignancy from pancreatitis, and to compare results obtained with this system with EUS interpretation by experienced endosonographers. METHODS: Twenty-one patients with pancreatic cancer and 14 with focal pancreatitis were included. The diagnosis was confirmed histologically in all cases and each patient had undergone EUS. A single EUS image from each procedure was used for computer analysis. The results were compared with the EUS diagnosis reported at the actual procedure as well that of an endosonographer who reviewed videotapes of the procedures. RESULTS: The software program differentiated focal pancreatitis from malignancy with a maximal 89% accuracy. With sensitivity set at 100% for malignancy, the program was 50% specific and accuracy was 80%. Sensitivity and accuracy of the endosonographer's impression at the time of EUS were, respectively, 89% and 85%. A sensitivity of 73% and accuracy of 83% were achieved with blinded interpretation of EUS videotapes. CONCLUSIONS: Analysis of EUS images with computer software programs is feasible and compares favorably with human interpretation. The application of this technology to EUS and other imaging scenarios could be a useful adjunct to diagnostic endoscopy and warrants further investigation.

Fetal stimulation by pulsed diagnostic ultrasound.

OBJECTIVE: To show that pulsed ultrasound from a clinical ultrasonic imaging system can stimulate the fetus. Stimulation is defined mainly as increased fetal gross body movements in response to excitation. METHODS: Fetuses of a group of 9 volunteer women (mean gestational age, 33.37 weeks; range, 25-40 weeks) were evaluated for body movement under 3 different conditions: (1) control, with no ultrasound exposure; (2) ultrasound in continuous wave Doppler mode; and (3) pulsed ultrasound in pulsed Doppler and B modes. A conventional external fetal monitor, with negligible ultrasonic output, was used to monitor fetal gross body motions. After an initial rest period of 3 minutes with 1 or no fetal motion, fetuses were monitored for an additional 3 minutes under the exposure criterion defined for each condition. Resulting fetal motions under the 3 conditions were compared using the Wilcoxon signed rank test. RESULTS: The test showed that fetuses moved significantly more frequently under condition 3 (mean +/- SD, 3.43 +/- 1.93 movements per minute) than under condition 1 (0.40 +/- 7.33 movements per minute) or condition 2 (0.63 +/- 7.67 movements per minute); P = .004 and .016, respectively. Fetal movements under conditions 1 and 2 did not differ significantly. CONCLUSION: Diagnostic ultrasound may stimulate fetal body motion.

Radiofrequency spectral analysis of attenuated ultrasound signals in experiments with echo contrast microbubbles.

Conventional gray-scale myocardial contrast echocardiography cannot distinguish perfused but attenuated from nonperfused myocardium because both may appear similar at low image intensity. We hypothesized that with radiofrequency spectral analysis of attenuated ultrasound signals, the harmonic-to-fundamental frequency ratio of the peak power spectrum (HFR(P)) could determine the presence of contrast microbubbles. We measured frequency responses of Optison microbubbles at defined degrees of ultrasound signal attenuation with different formulations of silicone (55D, 80A, and 3M); gray-scale intensities of Optison plus water compared with degassed water were analyzed at different attenuation settings (-25, -32, and -44 dB, respectively). HFR(P) values of Optison plus water were significantly higher than reference values of degassed water at each attenuation setting (55D, -14 +/- 2 dB versus -30 +/- 2 dB, P <.001; 80A, -19 +/- 2 dB versus -30 +/- 3 dB, P <.01; 3M, -22 +/- 2 dB versus -30 +/- 3 dB, P <.05), even though conventional videodensitometric analysis could not distinguish them. HFR(P) analysis objectively detects microbubbles in clinically relevant conditions of attenuation.

Plasma sodium-osmotic dissociation and hormonal interaction with drinking-induced hypervolemia at 2800 m altitude.

PURPOSE: To study hormonal factors that may account for the dissociation between beverage-induced plasma sodium p[Na+] and osmotic p[Osm] concentrations that appear to refute the high theoretical correlation between p[Na+] and p[Osm]. METHODS: Ten men (24 +/- SD 3 yr of age) sat reclining (head up) for 12 h in a chamber (21-23 degrees C dry bulb, 25-33% relative humidity) at 2800 m (9184 ft, 539 mm Hg) altitude (ALT), and at 321 m (1053 ft, 732 mm Hg) on the ground (GND). During 1000-1030 hours they consumed 3 fluids (12 ml x kg(-1),X = 948 ml x d(-1)) with large differences in sodium and osmotic contents: AstroAde (AA) with 185 mEq x L(-1) Na+ and 283 mOsm x kg(-1), Performance 1 (Shaklee) (P1) with 22 mEq x L(-1) Na+ and 365 mOsm kg(-1), or H2O at ALT; and only H2O on the GND. RESULTS: After drinking: plasma volume (PV) increased at 1200 hours by 8.3% (p < 0.05) with AA but was not significantly (NS) changed in the other sessions (Xdelta = +0.9%, range -0.9 to 2.8%); p[Na+] and p[Osm] were unchanged. Urinary rates and free-water clearances were attenuated with AA and P1 vs. those with H2O. Correlations between and among p[Na+] and p[Osm] suggest that the pNa+ ion is more tightly controlled than pOsm; and that there was no clear hormonal response that could account for this dissociation from theoretical considerations. CONCLUSIONS: There is significant dissociation between plasma sodium and osmotic concentrations after fluid intake. Induction and maintenance of hypervolemia requires increased (near isotonic) drink Na+ osmols rather than increased non-ionic osmols.