In Situ Monitoring and Assessment of Ischemic Skin Flap by High-Frequency Ultrasound and Quantitative Parameters.

Skin flap surgery is a critical procedure for treating severe skin injury in which post-surgery lesions must well monitored and cared for noninvasively. In the present study, attempts using high-frequency ultrasound imaging, quantitative parameters, and statistical analysis were made to extensively assess variations in the skin flap. Experiments were arranged by incising the dorsal skin of rats to create a skin flap using the chamber model. Measurements, including photographs, 30 MHz ultrasound B-mode images, skin thickness, echogenicity, Nakagami statistics, and histological analysis of post-surgery skin flap, were performed. Photograph results showed that color variations in different parts of the skin flap may readily correspond to ischemic states of local tissues. Compared to post-surgery skin flap on day 7, both integrated backscatter (IB) and Nakagami parameter (m) of the distal part of tissues were increased, and those of the skin thickness were decreased. Overall, relative skin thickness, IB, and m of the distal part of post-surgery skin flap varied from 100 to 67%, -66 to -61 dB, and 0.48 to 0.36, respectively. These results demonstrate that this modality and quantitative parameters can be feasibly applied for long-term and in situ assessment of skin flap tissues.

Window-Modulated Compounding Nakagami Parameter Ratio Approach for Assessing Muscle Perfusion with Contrast-Enhanced Ultrasound Imaging.

The assessment of microvascular perfusion is essential for the diagnosis of a specific muscle disease. In comparison with the current available medical modalities, the contrast-enhanced ultrasound imaging is the simplest and fastest means for probing the tissue perfusion. Specifically, the perfusion parameters estimated from the ultrasound time-intensity curve (TIC) and statistics-based time-Nakagami parameter curve (TNC) approaches were found able to quantify the perfusion. However, due to insufficient tolerance on tissue clutters and subresolvable effects, these approaches remain short of reproducibility and robustness. Consequently, the window-modulated compounding (WMC) Nakagami parameter ratio imaging was proposed to alleviate these effects, by taking the ratio of WMC Nakagami parameters corresponding to the incidence of two different acoustic pressures from an employed transducer. The time-Nakagami parameter ratio curve (TNRC) approach was also developed to estimate perfusion parameters. Measurements for the assessment of muscle perfusion were performed from the flow phantom and animal subjects administrated with a bolus of ultrasound contrast agents. The TNRC approach demonstrated better sensitivity and tolerance of tissue clutters than those of TIC and TNC. The fusion image with the WMC Nakagami parameter ratio and B-mode images indicated that both the tissue structures and perfusion properties of ultrasound contrast agents may be better discerned.

Interval Type-2 Neural Fuzzy Controller-Based Navigation of Cooperative Load-Carrying Mobile Robots in Unknown Environments.

In this paper, a navigation method is proposed for cooperative load-carrying mobile robots. The behavior mode manager is used efficaciously in the navigation control method to switch between two behavior modes, wall-following mode (WFM) and goal-oriented mode (GOM), according to various environmental conditions. Additionally, an interval type-2 neural fuzzy controller based on dynamic group artificial bee colony (DGABC) is proposed in this paper. Reinforcement learning was used to develop the WFM adaptively. First, a single robot is trained to learn the WFM. Then, this control method is implemented for cooperative load-carrying mobile robots. In WFM learning, the proposed DGABC performs better than the original artificial bee colony algorithm and other improved algorithms. Furthermore, the results of cooperative load-carrying navigation control tests demonstrate that the proposed cooperative load-carrying method and the navigation method can enable the robots to carry the task item to the goal and complete the navigation mission efficiently.

Quantitative Assessment of First Annular Pulley and Adjacent Tissues Using High-Frequency Ultrasound.

Due to a lack of appropriate image resolution, most ultrasound scanners are unable to sensitively discern the pulley tissues. To extensively investigate the properties of the A1 pulley system and the surrounding tissues for assessing trigger finger, a 30 MHz ultrasound system was implemented to perform in vitro experiments using the hypodermis, A1 pulley, and superficial digital flexor tendon (SDFT) dissected from cadavers. Ultrasound signals were acquired from both the transverse and sagittal planes of each tissue sample. The quantitative ultrasonic parameters, including sound speed, attenuation coefficient, integrated backscatter (IB) and Nakagami parameter (m), were subsequently estimated to characterize the tissue properties. The results demonstrated that the acquired ultrasound images have high resolution and are able to sufficiently differentiate the variations of tissue textures. Moreover, the attenuation slope of the hypodermis is larger than those of the A1 pulley and SDFT. The IB of A1 pulley is about the same as that of the hypodermis, and is very different from SDFT. The m parameter of the A1 pulley is also very different from those of hypodermis and SDFT. This study demonstrated that high-frequency ultrasound images in conjunction with ultrasonic parameters are capable of characterizing the A1 pulley system and surrounding tissues.

Cross-Sectional Nakagami Images in Passive Stretches Reveal Damage of Injured Muscles.

Muscle strain is still awanting a noninvasive quantitatively diagnosis tool. High frequency ultrasound (HFU) improves image resolution for monitoring changes of tissue structures, but the biomechanical factors may influence ultrasonography during injury detection. We aim to illustrate the ultrasonic parameters to present the histological damage of overstretched muscle with the consideration of biomechanical factors. Gastrocnemius muscles from mice were assembled and ex vivo passive stretching was performed before or after injury. After injury, the muscle significantly decreased mechanical strength. Ultrasonic images were obtained by HFU at different deformations to scan in cross and longitudinal orientations of muscle. The ultrasonography was quantified by echogenicity and Nakagami parameters (NP) for structural evaluation and correlated with histological results. The injured muscle at its original length exhibited decreased echogenicity and NP from HFU images. Cross-sectional ultrasonography revealed a loss of correlation between NP and passive muscle stretching that suggested a special scatterer pattern in the cross section of injured muscle. The independence of NP during passive stretching of injured muscle was confirmed by histological findings in ruptured collagen fibers, decreased muscle density, and increased intermuscular fiber space. Thus, HFU analysis of NP in cross section represents muscle injury that may benefit the clinical diagnosis.

Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention.

Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.

Identification of the Position and Thickness of the First Annular Pulley in Sonographic Images.

The purpose was to identify the A1 pulley's exact location and thickness by comparing measurements from a clinical high-frequency ultrasound scanner system (CHUS), a customized high-frequency ultrasound imaging research system (HURS) and a digital caliper. Ten cadaveric hands were used. We explored the pulley by layers, inserted guide pins and scanned it with the CHUS. After identifying the pulley, we measured each long finger's thickness using the CHUS and excised the pulley to measure its thickness with a digital caliper and the HURS. The thin hypo-echoic layer was revealed to be the synovial fluid space, and the pulley appears hyper-echoic regardless of scan direction. We also defined the pulley's boundaries. Moreover, the CHUS provided a significantly lower measurement of the pulley's thickness than the digital caliper and HURS. Likewise, based on the digital caliper's measurement, the HURS had significantly lower mean absolute and relative errors than the CHUS.

Assessment of the kinetic trajectory of the median nerve in the wrist by high-frequency ultrasound.

Carpal tunnel syndrome (CTS) is typically diagnosed by physical examination or nerve conduction measurements. With these diagnostics however it is difficult to obtain anatomical information in the carpal tunnel. To further improve the diagnosis of CTS, an attempt using 30 MHz high-frequency ultrasound to noninvasively detect the local anatomical structures and the kinetic trajectory of the median nerve (MN) in the wrist was explored. Measurements were performed on the right wrist of 14 asymptomatic volunteers. The kinetic trajectory of the MN corresponding to flexion (from 0° to 90°) and extension (from 90° to 0°) movements of the fingers were detected by a cross correlation-based motion tracking technique. The average displacements of the MN according to finger movements were measured to be 3.74 and 2.04 mm for male and female subjects, respectively. Moreover, the kinetic trajectory of the MN in both the ulnar-palmar and total directions generally follows a sigmoidal curve tendency. This study has verified that the use of high-frequency ultrasound imaging and a motion tracking technique to sensitively detect the displacement and kinetic trajectory of the MN for the assessment of CTS patients is feasible.

Monitoring tissue inflammation and responses to drug treatments in early stages of mice bone fracture using 50 MHz ultrasound.

Bone fracture induces moderate inflammatory responses that are regulated by cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) for initiating tissue repair and bone formation. Only a handful of non-invasive techniques focus on monitoring acute inflammation of injured bone currently exists. In the current study, we monitored in vivo inflammation levels during the initial 2 weeks of the inflammatory stage after mouse bone fracture utilizing 50 MHz ultrasound. The acquired ultrasonic images were correlated well with histological examinations. After the bone fracture in the tibia, dynamic changes in the soft tissue at the medial-posterior compartment near the fracture site were monitored by ultrasound on the days of 0, 2, 4, 7, and 14. The corresponding echogenicity increased on the 2nd, 4th, and 7th day, and subsequently declined to basal levels after the 14th day. An increase of cell death was identified by the positive staining of deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and was consistent with ultrasound measurements. The increases of both COX-2 and Leukotriene B4 receptor 1 (BLT1, 5-LO-relative receptor), which are regulators for tissue inflammation, in the immunohistochemistry staining revealed their involvement in bone fracture injury. Monitoring the inflammatory response to various non-steroidal anti-inflammatory drugs (NSAIDs) treatments was investigated by treating injured mice with a daily oral intake of aspirin (Asp), indomethacin (IND), and a selective COX-2 inhibitor (SC-236). The Asp treatment significantly reduced fracture-increased echogenicity (hyperechogenicity, p<0.05) in ultrasound images as well as inhibited cell death, and expression of COX-2 and BLT1. In contrast, treatment with IND or SC-236 did not reduce the hyperechogenicity, as confirmed by cell death (TUNEL) and expression levels of COX-2 or BLT1. Taken together, the current study reports the feasibility of a non-invasive ultrasound method capable of monitoring post-fracture tissue inflammation that positively correlates with histological findings. Results of this study also suggest that this approach may be further applied to elucidate the underlying mechanisms of inflammatory processes and to develop therapeutic strategies for facilitating fracture healing.

Distribution and deposition of organic fouling on the microfiltration membrane evaluated by high-frequency ultrasound.

A 50 MHz high-frequency ultrasound and analysis method were developed to further improve the in situ assessment of deposition and distribution of organic fouling on the polyvinylidene fluoride (PVDF) membranes. Measurements of fouling depositions were performed from PVDF membranes filtrated with aqueous humic acid solutions (HAS) of 2 and 4 ppm concentrations in a flat-sheet module. Ultrasound signals reflected from the PVDF membranes, following filtrations at various durations including 0, 5, 15, 30, 60, and 100 min, were acquired. The thickness and distribution of fouling estimated and assessed by peak-to-peak echo voltage (Vpp) and C-mode images were found to be non-homogeneously deposited on the membranes. Following the filtrations with 2 and 4 ppm HAS for 100 min, the corresponding thickness of fouling deposition increased from 1.81±9 to 2.4571.57 mm, respectively; those average Vpp decreased from 2.05±07 to 1.13±16 V and from 2.11±08 to 0.94±15 V. These results demonstrated that the deposition and distribution of organic fouling could be sensitively and rapidly evaluated by high-frequency ultrasound image incorporated with the analysis method.

Quantitative assessment on the orientation and distribution of carbon fibers in a conductive polymer composite using high-frequency ultrasound.

Conductive polymer composites, typically fabricated from a mix of conductive fillers and a polymer substrate, are commonly applied as bipolar plates in a fuel cell stack. Electrical conductivity is a crucial property that greatly depends on the distribution and orientation of the fillers. In this study, a 50-MHz ultrasound imaging system and analysis techniques capable of nondestructively assessing the properties of carbon fibers (CFs) in conductive polymer composites were developed. Composite materials containing a mix of polycarbonate substrates and 0 to 0.3 wt% of CFs were prepared using an injection molding technique. Ultrasonic A-line signals and C-scan images were acquired from each composite sample in regions at a depth of 0.15 mm beneath the sample surface (region A) and those at a depth of 0.3 mm (region B). The integrated backscatter (IB) and the Nakagami statistical parameter were calculated to quantitatively assess the samples. The area ratio, defined as the percentage of areas composed of CF images normalized by that of the whole C-scan image, was applied to further quantify the orientation of CFs perpendicular to the sample surface. Corresponding to the increase in CF concentrations from 0.1 to 0.3 wt%, the average IB and Nakagami parameter (m) of the composite samples increased from -78.10 ± 2.20 (mean ± standard deviation) to -72.66 ± 1.40 dB and from 0.024 ± 0.012 to 0.048 ± 0.011, respectively. The corresponding area ratios were respectively estimated to be 0.78 ± 0.35%, 2.33 ± 0.66%, and 2.20 ± 0.60% in region A of the samples; those of CFs with a perpendicular orientation were 0.04 ± 0.03%, 0.08 ± 0.02%, and 0.12 ± 0.05%. The area ratios in region B of the samples were calculated to be 1.19 ± 0.54%, 2.81 ± 0.42%, and 2.64 ± 0.76%, and those of CFs with a perpendicular orientation were 0.07 ± 0.04%, 0.12 ± 0.04%, and 0.14 ± 0.03%. According to the results of the orientations and ultrasonic images, CFs tended to distribute more uniformly in the deeper regions of the samples. This study validates that the distribution and orientation of CFs in conductive polymer composites could be sensitively and quantitatively assessed by high-frequency ultrasound in conjunction with current analysis methods.

Quantitative assessments of burn degree by high-frequency ultrasonic backscattering and statistical model.

An accurate and quantitative modality to assess the burn degree is crucial for determining further treatments to be properly applied to burn injury patients. Ultrasounds with frequencies higher than 20 MHz have been applied to dermatological diagnosis due to its high resolution and noninvasive capability. Yet, it is still lacking a substantial means to sensitively correlate the burn degree and ultrasonic measurements quantitatively. Thus, a 50 MHz ultrasound system was developed and implemented to measure ultrasonic signals backscattered from the burned skin tissues. Various burn degrees were achieved by placing a 100 °C brass plate onto the dorsal skins of anesthetized rats for various durations ranged from 5 to 20 s. The burn degrees were correlated with ultrasonic parameters, including integrated backscatter (IB) and Nakagami parameter (m) calculated from ultrasonic signals acquired from the burned tissues of a 5 × 1.4 mm (width × depth) area. Results demonstrated that both IB and m decreased exponentially with the increase of burn degree. Specifically, an IB of -79.0 ± 2.4 (mean ± standard deviation) dB for normal skin tissues tended to decrease to -94.0 ± 1.3 dB for those burned for 20 s, while the corresponding Nakagami parameters tended to decrease from 0.76 ± 0.08 to 0.45 ± 0.04. The variation of both IB and m was partially associated with the change of properties of collagen fibers from the burned tissues verified by samples of tissue histological sections. Particularly, the m parameter may be more sensitive to differentiate burned skin due to the fact that it has a greater rate of change with respect to different burn durations. These ultrasonic parameters in conjunction with high-frequency B-mode and Nakagami images could have the potential to assess the burn degree quantitatively.

Assessment of blood coagulation under various flow conditions with ultrasound backscattering.

Several in vitro studies have employed ultrasonic techniques to detect varying properties of coagulating blood under static or stirred conditions. Most of those studies mainly addressed on the development and feasibility of modalities and however were not fully considering the effect of blood flow. To better elucidate this issue, ultrasonic backscattering were measured from the coagulating porcine blood circulated in a mock flow loop with various steady laminar flows at mean shear rates from 10 to 100 s(-1). A 3 ml of 0.5 M CaCl2 solution for inducing blood coagulation was added to that of 30 ml blood circulated in the conduit. For each measurement carried out with a 10-MHz transducer, backscattered signals digitized at 100-MHz sampling frequency were acquired for a total of 20 min at temporal resolution of 50 A-lines per s. The integrated backscatter (IB) was calculated for assessing backscattering properties of coagulating blood. The results show that blood coagulation tended to be increased corresponding to the addition of CaCl2 solution: the IB was increased approximately 6.1 +/- 0.6 (mean +/- standard deviation), 5.4 +/- 0.9, and 4.5 +/- 1.2 dB at 310 +/- 62, 420 +/- 88, and 610 +/- 102 s associated with mean shear rates of 10, 40, and 100 s(-1), respectively. The rate of increasing IB for evaluating the growth of clot was estimated to be 0.075 +/- 0.017, 0.052 +/- 0.027, and 0.038 +/- 0.012 delta dB delta s(-1) corresponding to the increase of mean shear rates. These results consistently demonstrate that higher shear rate tends to prolong the duration for the flowing blood to be coagulated and to decrease the rate of IB. Moreover, the laminar flow was changed to turbulent flow during that the blood was clotting discerned by spatial variations of ultrasound backscattering in the conduit. All these results validate that ultrasound backscattering is feasible to be utilized for detecting and assessing blood coagulation under dynamic conditions.

Effect of low intensity ultrasounds on the growth of osteoblasts.

Previous studies have indicated that low intensity ultrasounds could accelerate the repair of fibula fracture and facilitate the proliferation of osteoblasts. To further investigate the effect of low intensity ultrasounds, two different frequency of ultrasound, 1 MHz and 3 MHz, were applied to osteoblasts. The cells were stimulated for a typical 20% duty cycle of ultrasound with various intensities ranged from 50 to 150 mW/cm2 (ISATA) for 3 minutes once daily for 6 days. The cellular responses, in terms of cell number and morphological change, associated with ultrasound stimulations were estimated using a hemocytometer and microscopic morphology in which cells were stained with trypan blue. Results showed that the proliferation rates of osteoblasts for particular stimulated group are larger than those of control groups. The largest proliferation rate corresponds to those cells culture at 24 hours after seeding. Ultrasound increased approximately the cell proliferation proportional to ultrasonic intensity at which the exposure of 100 mW/cm2 intensity of 1 MHz ultrasound 1.1 fold, and 50 mW/cm2 intensity of 3 MHz ultrasound 1.2 fold than that of the control group. These finding suggest that the growth of cell may be controlled by appropriate ultrasonic mechanical stress.

Effect of ultrasound doses on the amyloid-beta 25-35 induced PC12 apoptosis.

Previous studies have shown that Amyloid-beta (A beta) may induce the apoptosis of neuronal cells leading to the syndrome of Alzheimer's disease (AD). The stimulation by optical energy was found able to greatly inhibit A beta induced apoptosis. This study aims to further explore the effect of different doses of ultrasonic insonification on neuronal cells. Experiments were carried out using PC12 cells added with A beta 25-35 of a 20 microM during pre-cultured preparation. These cells were respectively stimulated by a single and multiple insonification for three minutes with a 20% duty cycle ultrasound of the intensity of 150 mW/cm2 (SATA). The cellular response was assessed, using the microscopic morphology, cell death measured by the typical MTT assay, and annexin V/PI double stain assay, for 8 times within 72 hours after that cells were stimulated. Results showed that both stimulations by single and multiple does ultrasound may diminish A beta induced neuronal cells apoptosis. The diminish effects tend to be time dependent corresponding to 72 and 12 hours after ultrasound exposure by single and multiple insonification, respectively. Fluorescence stain results indicated that those cells stimulated by a single dose ultrasound tended to slightly inhibit A beta-induced PC12 to apoptosis. This study demonstrated that the effect of diminishing neuronal cells from apoptosis could be regulated with the insonation of appropriate ultrasonic doses.

High frequency ultrasonic characterization of human vocal fold tissue.

Recently, endolaryngeal sonography at frequencies ranging from 10 to 30 MHz has been found to be useful in diagnosing diseases of the vocal folds (VFs). However, image resolution can be further improved by ultrasound at higher frequencies, necessitating the measurement of high-frequency acoustic properties of VF tissue. The ultrasonic parameters of integrated backscatter, sound velocity, and frequency-dependent attenuation coefficient were measured in both the lamina propria (LP) and vocalis muscle (VM) of human VFs using a 47 MHz high-frequency ultrasonic transducer. The integrated backscatter was -173.44+/-6.14 (mean+/-s.d.) and -195.13+/-3.58 dB in the LP and VM, respectively, the sound velocity was 1667.68+/-44.9 and 1595.07+/-39.33 ms, and the attenuation coefficient at 47 MHz was 8.28+/-1.72 and 7.17+/-1.30 dBmm. The difference between these ultrasonic parameters may be attributed to variations in the structure and fiber concentrations in VF tissue. These results could serve as a useful clinical reference for the further development of high-frequency ultrasound devices for endolarynx sonography applications.

Feasibility study of using high-frequency ultrasonic Nakagami imaging for characterizing the cataract lens in vitro.

A cataract is a clouding of the crystalline lens that reduces the amount of incoming light and impairs visual perception. Phacoemulsification is the most common surgical method for treating advanced cataracts, and determining the optimal phacoemulsification energy is dependent on measuring the hardness of the lens. This study explored the feasibility of using an ultrasonic parametric image based on the Nakagami distribution to quantify the lens hardness. Young's modulus was measured in porcine lenses in which cataracts had been artificially induced. High-frequency ultrasound at 35 MHz was used to obtain the B-mode and Nakagami images of the cataract lenses. The averaged integrated backscatter and Nakagami parameters were also estimated in the region of interest. The experimental results show that the conventional B-scan and integrated backscatter are inadequate for quantifying the lens hardness, whereas Nakagami imaging allows different degrees of lens hardening to be distinguished both globally and locally based on the concentration of fiber coemption therein.

Determining the acoustic properties of the lens using a high-frequency ultrasonic needle transducer.

Ultrasonic parameters including sound velocity and attenuation coefficient have recently been found to be useful in characterizing the cataract lens noninvasively. However, the regional changes of these acoustic parameters in the lens cannot be detected directly by those ultrasonic measurements. This prompted us to fabricate a 46-MHz needle transducer (lead magnesium niobate-lead titanate [PMN-PT] single crystal) with an aperture size of 0.4 mm and a diameter of 0.9 mm for directly measuring the sound velocity and frequency-dependent attenuation coefficient in lenses. These parameters have been shown to be related to the hardness of a cataract, and hence this technique may allow surgeons to detect the acoustic properties of the cataract via a small incision on the cornea before/during phacoemulsification surgery. To verify the performance of the needle transducer, experiments were performed on porcine lenses in which two types of cataracts (nucleus and cortical) were induced artificially. The needle transducer was mounted on a positioning system and its tip was inserted into the lens, allowing the anterior-to-posterior profiles of acoustic parameters along the lens axis to be obtained immediately. The experimental results show that the acoustic parameters are not constant within a single normal lens. The sound velocity and ultrasound attenuation coefficient (at 46 MHz) were 1701.2 +/- 8.4 m/s (mean +/- SD) and 9.42 +/- 0.57 dB/mm, respectively, at the nucleus, and 1597.2 +/- 9.6, 1589.3 +/- 6.1 m/s and 0.42 +/- 0.26 and 0.40 +/- 0.33 dB/mm close to the anterior and posterior capsules, respectively. Finally, the data obtained demonstrate that regional variations in the acoustic properties of lenses corresponding to the hardness of different types of cataract can be detected sensitively by a needle transducer.

Statistical variations of ultrasound signals backscattered from flowing blood.

The statistical distributions of ultrasonic signals backscattered from blood have recently been used to characterize hemodynamic properties, such as red blood cell (RBC) aggregation and blood coagulation. However, a thorough understanding of the relationship between blood properties and the statistical behavior of signals backscattered from flowing blood is still lacking. This prompted us to use the statistical parameter to characterize signals backscattered from both whole blood and RBC suspensions at different flow velocities (from 10 to 60 cm/s) and hematocrits (from 20% to 50%) under a steady laminar flow condition. The Nakagami parameter, scaling parameter, backscatter amplitude profile and flow velocity profile across a flow tube were acquired using a 10 MHz focused ultrasonic transducer. The backscattered signal peaked approximately at the centerline of the flow tube due to the effects of RBC aggregation, with the peak value increasing as the flow velocity of whole blood decreased. The Nakagami parameter increased from 0.45 to 0.78 as the flow velocity increased from 10 to 60 cm/s. The probability density function (PDF) of signals backscattered from flowing whole blood conformed with a pre-Rayleigh distribution. The Nakagami parameter was close to 1 for signals backscattered from RBC suspensions at all the flow velocities and hematocrits tested, for which the PDF was Rayleigh distributed. These differences in the statistical distributions of backscattered signals between whole blood and RBC suspensions suggest that variations in the size of dynamic scatterers in the flow affect the shape of the backscattered signal envelope, which should be considered in future statistical models used to characterize blood properties.