A high-frequency continuous-wave Doppler ultrasound system for the detection of blood flow in the microcirculation

Basic ultrasound physics and several clinical and experimental observations suggest that high-frequency Doppler ultrasound (HFD) operating in the frequency range 20–100 MHz holds the promise of detecting blood flow in the microcirculation. This article describes a directional, continuous-wave (CW), 1- to 200-MHz Doppler ultrasound system. The system electronics have a dynamic range of 100 dB, a noise floor of 10 nV and a directional isolation of 50 dB. The development of a 40-MHz Doppler transducer composed of two, 81-μm-thick, lithium niobate crystals that have been air-backed and transmission-line tuned for maximum sensitivity is described. This device is used to test the CW Doppler system using string and capillary phantoms and in vivo tissue. We show that HFD can detect and measure velocities on the order of the blood velocities found in the capillaries (1 mm/s) and arterioles (5 mm/s) with suitable velocity (50–500 μm/s) and temporal (20–250 ms) resolutions. In vivo measurements demonstrate that HFD is sensitive to the detection of blood flow in small vessels.     

A Method to Validate Quantitative High-Frequency Power Doppler Ultrasound With Fluorescence in Vivo Video Microscopy

Flow quantification with high-frequency (>20 MHz) power Doppler ultrasound can be performed objectively using the wall-filter selection curve (WFSC) method to select the cutoff velocity that yields a best-estimate color pixel density (CPD). An in vivo video microscopy system (IVVM) is combined with high-frequency power Doppler ultrasound to provide a method for validation of CPD measurements based on WFSCs in mouse testicular vessels. The ultrasound and IVVM systems are instrumented so that the mouse remains on the same imaging platform when switching between the two modalities. In vivo video microscopy provides gold-standard measurements of vascular diameter to validate power Doppler CPD estimates. Measurements in four image planes from three mice exhibit wide variation in the optimal cutoff velocity and indicate that a predetermined cutoff velocity setting can introduce significant errors in studies intended to quantify vascularity. Consistent with previously published flow-phantom data, in vivo WFSCs exhibited three characteristic regions and detectable plateaus. Selection of a cutoff velocity at the right end of the plateau yielded a CPD close to the gold-standard vascular volume fraction estimated using IVVM. An investigator can implement the WFSC method to help adapt cutoff velocity to current blood flow conditions and thereby improve the accuracy of power Doppler for quantitative microvascular imaging.     

Shunt Flow Evaluation in Congenital Heart Disease Based on Two-Dimensional Speckle Tracking

High-frame-rate ultrasound speckle tracking was used for quantification of peak velocity in shunt flows resulting from septal defects in congenital heart disease. In a duplex acquisition scheme implemented on a research scanner, unfocused transmit beams and full parallel receive beamforming were used to achieve a frame rate of 107 frames/s for full field-of-view flow images with high accuracy, while also ensuring high-quality focused B-mode tissue imaging. The setup was evaluated in vivo for neonates with atrial and ventricular septal defects. The shunt position was automatically tracked in B-mode images and further used in blood speckle tracking to obtain calibrated shunt flow velocities throughout the cardiac cycle. Validation toward color flow imaging and pulsed wave Doppler with manual angle correction indicated that blood speckle tracking could provide accurate estimates of shunt flow velocities. The approach was less biased by clutter filtering compared with color flow imaging and was able to provide velocity estimates beyond the Nyquist range. Possible placements of sample volumes (and angle corrections) for conventional Doppler resulted in a peak shunt velocity variations of 0.49–0.56 m/s for the ventricular septal defect of patient 1 and 0.38–0.58 m/s for the atrial septal defect of patient 2. In comparison, the peak velocities found from speckle tracking were 0.77 and 0.33 m/s for patients 1 and 2, respectively. Results indicated that complex intraventricular flow velocity patterns could be quantified using high-frame-rate speckle tracking of both blood and tissue movement. This could potentially help increase diagnostic accuracy and decrease inter-observer variability when measuring peak velocity in shunt flows.     

High-Frequency Ex vivo Ultrasound Imaging of the Auditory System

A 50 MHz array-based imaging system was used to obtain high-resolution images of the ear and auditory system. This previously described custom built imaging system (3, 4 and 2) is capable of 50 μm axial resolution, and lateral resolution varying from 80 μm to 130 μm over a 5.12 mm scan depth. The imaging system is based on a 2 mm diameter, seven-element equal-area annular array, and a digital beamformer that uses high-speed field programmable gate arrays (FPGAs). The images produced by this system have shown far superior depth of field compared with commercially available single-element systems. Ex vivo, three-dimensional (3-D) images were obtained of human cadaveric tissues including the ossicles (stapes, incus, malleus) and the tympanic membrane. In addition, two-dimensional (2-D) images were obtained of an intact cochlea by imaging through the round window membrane. The basilar membrane inside the cochlea could clearly be visualized. These images demonstrate that high-frequency ultrasound imaging of the middle and inner ear can provide valuable diagnostic information using minimally invasive techniques that could potentially be implemented in vivo. (E-mail: J.Brown@dal.ca)     

Detectability of Small Blood Vessels with High-Frequency Power Doppler and Selection of Wall Filter Cut-Off Velocity for Microvascular Imaging

Power Doppler imaging of physiologic and pathologic angiogenesis is widely used in preclinical studies to track normal development, disease progression and treatment efficacy but can be challenging given the presence of small blood vessels and slow flow velocities. Power Doppler images can be plagued with false-positive color pixels or undetected vessels, thereby complicating the interpretation of vascularity metrics such as color pixel density (CPD). As an initial step toward improved microvascular quantification, flow-phantom experiments were performed to establish relationships between vessel detection and various combinations of vessel size (160, 200, 250, 300 and 360 μm), flow velocity (4, 3, 2, 1 and 0.5 mm/s) and transducer frequency (30 and 40 MHz) while varying the wall filter cut-off velocity. Receiver operating characteristic (ROC) curves and areas under ROC curves indicate that good vessel detection performance can be achieved with a 40-MHz transducer for flow velocities ≥2 mm/s and with a 30-MHz transducer for flow velocities ≥1 mm/s. In the second part of the analysis, CPD was plotted as a function of wall filter cut-off velocity for each flow-phantom data set. Three distinct regions were observed: overestimation of CPD at low cut-offs, underestimation of CPD at high cut-offs and a plateau at intermediate cut-offs. The CPD at the plateau closely matched the phantom's vascular volume fraction and the length of the plateau corresponded with the flow-detection performance of the Doppler system assessed using ROC analysis. Color pixel density vs. wall filter cut-off curves from analogous in vivo experiments exhibited the same shape, including a distinct CPD plateau. The similar shape of the flow-phantom and in vivo curves suggests that the presence of a plateau in vivo can be used to identify the best-estimate CPD value that can be treated as a quantitative vascularity metric. The ability to identify the best CPD estimate is expected to improve quantification of angiogenesis and anti-vascular treatment responses with power Doppler. (E-mail: jlacefield@eng.uwo.ca)     

Blood-Brain Barrier (BBB) Disruption Using a Diagnostic Ultrasound Scanner and Definity® in Mice

The objective of this work was to determine whether diagnostic ultrasound and contrast agent could be used to transcranially and nondestructively disrupt the blood-brain barrier (BBB) in mice under ultrasound image guidance and to quantify that disruption using magnetic resonance imaging (MRI) and magnetic resonance (MR) contrast agent. Each mouse was placed under isoflurane anesthesia and the hair on top of its skull was removed before treatment. A diagnostic ultrasound transducer was placed in a water bag coupled with gel on the mouse skull. Definity (ultrasound [US] contrast) and Magnevist (MR contrast) were injected concurrent with the start of a custom ultrasound transmission sequence. The transducer was translated along the rostral-caudal axis to insonify three spatial locations (2 mm apart) along one half of the brain for each sequence. T1-weighted MR images were used to quantify the volume of tissue over which the BBB disruption allowed Magnevist to enter the brain, based upon increases in MR contrast-to-noise ratio (CNR) compared with the noninsonified portions of the brain. Ultrasonic frequency, pressure and pulse duration, as well as Definity dose and injection time were varied. Preliminary results suggest that a threshold exists for BBB opening dependent upon both pressure and pulse duration (consistent with reports in the literature performed at lower frequencies). A range of typical diagnostic frequencies (e.g., 5.0–8.0 MHz) generated BBB disruption. Comparable BBB opening was noted with varied delays between Definity injection and insonification (0–2 min) for a range of Definity concentrations (400-2400 μL/kg). The low-pressure, custom sequences (mechanical index [MI] ≤ 0.65) had minimal blood cell extravasation as determined by histologic evaluation. This study has shown the ability of a diagnostic ultrasound system, in conjunction with Definity, to open the BBB transcranially in a mouse model for molecules approximately 0.5 kDa in size. Opening was achieved at higher frequencies than previously reported and was localized under ultrasound image guidance. A typical, ultrasound imaging mode (pulsed wave [PW] Doppler) with specific settings (transmit frequency = 5.7 MHz, gate size = 15 mm, pulse repetition frequency = 100 Hz, system power = 15%) successfully opened the BBB, which facilitates implementation using the most of commercially available clinical diagnostic scanners. Localized opening of the BBB may have potential clinical utility for the delivery of diagnostic or therapeutic agents to the brain. (Email: kdf2@duke.edu)     

Cardiac Shear Wave Elastography Using a Clinical Ultrasound System

The propagation velocity of shear waves relates to tissue stiffness. We prove that a regular clinical cardiac ultrasound system can determine shear wave velocity with a conventional unmodified tissue Doppler imaging (TDI) application. The investigation was performed on five tissue phantoms with different stiffness using a research platform capable of inducing and tracking shear waves and a clinical cardiac system (Philips iE33, achieving frame rates of 400–700 Hz in TDI by tuning the normal system settings). We also tested the technique in vivo on a normal individual and on typical pathologies modifying the consistency of the left ventricular wall. The research platform scanner was used as reference. Shear wave velocities measured with TDI on the clinical cardiac system were very close to those measured by the research platform scanner. The mean difference between the clinical and research systems was 0.18 ± 0.22 m/s, and the limits of agreement, from ?0.27 to +0.63 m/s. In vivo, the velocity of the wave induced by aortic valve closure in the interventricular septum increased in patients with expected increased wall stiffness.     

Controlled permeation of cell membrane by single bubble acoustic cavitation

Sonoporation is the membrane disruption generated by ultrasound and has been exploited as a non-viral strategy for drug and gene delivery. Acoustic cavitation of microbubbles has been recognized to play an important role in sonoporation. However, due to the lack of adequate techniques for precise control of cavitation activities and real-time assessment of the resulting sub-micron process of sonoporation, limited knowledge has been available regarding the detail processes and correlation of cavitation with membrane disruption at the single cell level. In the current study, we developed a combined approach including optical, acoustical, and electrophysiological techniques to enable synchronized manipulation, imaging, and measurement of cavitation of single bubbles and the resulting cell membrane disruption in real-time. Using a self-focused femtosecond laser and high frequency ultrasound (7.44 MHz) pulses, a single microbubble was generated and positioned at a desired distance from the membrane of a Xenopus oocyte. Cavitation of the bubble was achieved by applying a low frequency (1.5 MHz) ultrasound pulse (duration 13.3 or 40 μs) to induce bubble collapse. Disruption of the cell membrane was assessed by the increase in the transmembrane current (TMC) of the cell under voltage clamp. Simultaneous high-speed bright field imaging of cavitation and measurements of the TMC were obtained to correlate the ultrasound-generated bubble activities with the cell membrane poration. The change in membrane permeability was directly associated with the formation of a sub-micrometer pore from a local membrane rupture generated by bubble collapse or bubble compression depending on ultrasound amplitude and duration. The impact of the bubble collapse on membrane permeation decreased rapidly with increasing distance (D) between the bubble (diameter d) and the cell membrane. The effective range of cavitation impact on membrane poration was determined to be D/d = 0.75. The maximum mean radius of the pores was estimated from the measured TMC to be 0.106 ± 0.032 μm (n = 70) for acoustic pressure of 1.5 MPa (duration 13.3 μs), and increased to 0.171 ± 0.030 μm (n = 125) for acoustic pressure of 1.7 MPa and to 0.182 ± 0.052 μm (n = 112) for a pulse duration of 40 μs (1.5 MPa). These results from controlled cell membrane permeation by cavitation of single bubbles revealed insights and key factors affecting sonoporation at the single cell level.     

Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases

Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7 T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that ¹⁸F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10^− 5 cm/s versus 1.12 × 10^− 5 cm/s). PET imaging further demonstrated tumor permeability to ⁶⁴Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule ¹⁸F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.     

Feasibility of Dual Doppler Velocity Measurements to Estimate Volume Pulsations of an Arterial Segment

If volume flow was measured at each end of an arterial segment with no branches, any instantaneous differences would indicate that volume was increasing or decreasing transiently within the segment. This concept could provide an alternative method to assess the mechanical properties or distensibility of an artery noninvasively using ultrasound. The goal of this study was to determine the feasibility of using Doppler measurements of pulsatile velocity (opposed to flow) at two sites to estimate the volume pulsations of the intervening arterial segment. To test the concept over a wide range of dimensions, we made simultaneous measurements of velocity in a short 5 mm segment of a mouse common carotid artery and in a longer 20 cm segment of a human brachial-radial artery using a two-channel 20 MHz pulsed Doppler and calculated the waveforms and magnitudes of the volume pulsations during the cardiac cycle. We also estimated pulse wave velocity from the velocity upstroke arrival times and measured artery wall motion using tissue Doppler methods for comparison of magnitudes and waveforms. Volume pulsations estimated from Doppler velocity measurements were 16% for the mouse carotid artery and 4% for the human brachial artery. These values are consistent with the measured pulse wave velocities of 4.2 m/s and 10 m/s, respectively, and with the mouse carotid diameter pulsation. In addition, the segmental volume waveforms resemble diameter and pressure waveforms as expected. We conclude that with proper application and further validation, dual Doppler velocity measurements can be used to estimate the magnitude and waveform of volume pulsations of an arterial segment and to provide an alternative noninvasive index of arterial mechanical properties. (E-mail: cjhartley@ieee.org)     

Cerebral Hemodynamics during Coronary Artery Bypass Graft Surgery: The Effect of Carotid Stenosis

Carotid stenosis is a frequent coexisting condition in patients undergoing coronary artery bypass graft (CABG) surgery. The impact of carotid stenosis on cerebral perfusion is not fully understood. The purpose of this study was to determine the impact of carotid stenosis on cerebral blood flow velocity in patients undergoing CABG. Seventy-three patients undergoing CABG were prospectively recruited and underwent preoperative Duplex carotid ultrasound to evaluate the degree of carotid stenosis. Intraoperatively, transcranial Doppler ultrasound was used to record the mean flow velocity (MFV) within the bilateral middle cerebral arteries. In addition, during the period of cardiopulmonary bypass, regulators of cerebral hemodynamics such as hematocrit, partial pressure of carbon dioxide and temperature were recorded. The ipsilateral middle cerebral artery mean flow velocity was compared in arteries with and without carotid stenosis using a repeated measures analysis. Seventy-three patients underwent intraoperative monitoring during CABG and 30% (n = 22) had carotid stenosis. Overall, MFV rose throughout the duration of CABG including when the patient was on cardiopulmonary bypass. However, there was no significant MFV difference between those arteries with and without stenosis (F = 1.2, p = .21). Further analysis during cardiopulmonary bypass, demonstrated that hemodilution and partial pressure of carbon dioxide may play a role in cerebral autoregulation during CABG. Carotid stenosis did not impact mean cerebral blood flow velocity during CABG. The cerebrovascular regulatory process appears to be largely intact during CABG.     

Evaluation of the Sensitivity of an in vitro High Frequency Ultrasound Device to Monitor the Coagulation Process: Study of the Effects of Heparin Treatment in a Murine Model

This study evaluates the sensitivity of a new in vitro high frequency ultrasound test of the whole blood coagulation process. A rat model of anticoagulant treatment is reported. Many recent studies of the role of red blood cells in the whole blood coagulation process have revealed an increasing demand for global tests of the coagulation process performed on whole blood instead of plasma samples. In contrast to existing optical tests, high frequency ultrasound presents the advantages of characterizing the mechanical properties of whole blood clotting. Ultrasound longitudinal wave velocity and integrated attenuation coefficient (IAC) were simultaneously assessed in a 10 to 30 MHz frequency range during the whole blood coagulation process in vitro in rats under anticoagulant therapy. Differences between humans and rats were also clearly emphasized in non-clotting blood and in clotting blood using specific criteria deduced from acoustic parameters (ultrasound velocity for non-clotting blood: = 1574 ± 2 m/s for rats and 1583 ± 3 m/s for humans and IAC = 2.25 ± 0.14 dB/cm for rats and 1.5 ± 0.23 dB/cm for humans). We also measured the coagulation time t₀ from the acoustic velocity (t₀ = 11.15 ± 7 min for control rat blood and 43.3 ± 11.4 min for human blood). Different doses of heparin were administered to rats. The sensitivity of the ultrasound device to the effects of heparin was evaluated. Differences between non-treated rats and chronically and acutely treated rats were recorded and quantified. We particularly noted that the slope S and the amplitude I of the variations in acoustic velocity were linked to clot retraction, which is a good indicator of the platelet function. The amplitude of the variations in S was between (20 ± 8) × 10^–3 m/s² for control group rats, and (0.92 ± 0.35) × 10^–3 m/s² for chronic heparin-treated group rats. The values of I were 15 times higher for control group rats than for chronic heparin-treated group rats. (E-mail: rachel.libgot@univ-tours.fr)     

A laboratory-scale device for the straightforward production of uniform, small sized cell microcapsules with long-term cell viability

Microencapsulated and genetically engineered cells may be used for prolonged delivery of therapeutically active proteins. The objective of this study was to develop a simple, inexpensive and flexible laboratory-scale device for the production of cell microcapsules, especially capsules of small diameter (<300 μm). Many microencapsulation devices are expensive, difficult to assemble and to use, and often more suitable for large-scale experiments. However, the simplicity and low price of the encapsulation system should not limit the quality of capsules and reproducibility of the process: for successful in vitro and in vivo experiments it is important to be able to produce uniform, spherical microcapsules without deformities with high reproducibility. In addition, an advantage of the present procedure compared to other similar, co-axial laminar gas flow systems is the possibility to produce also small microcapsules, less than 200 μm in diameter, with narrow size distribution. First, design, optimization and reproducibility testing of this custom-built device were carried out. Second, microencapsulated retinal pigment epithelial cells (ARPE-19) capable of secreting soluble vascular endothelial growth factor receptor 1 (sVEGFR1) were engineered. The cells remained viable in alginate-poly-L-lysine-alginate microcapsules and secreted sVEGFR1 for prolonged periods.     

Ultrasound Dynamic Micro-Elastography Applied to the Viscoelastic Characterization of Soft Tissues and Arterial Walls

Quantitative noninvasive methods that provide in vivo assessment of mechanical characterization of living tissues, organs and artery walls are of interest because information on their viscoelastic properties in the presence of disease can affect diagnosis and treatment options. This article proposes the dynamic micro-elastography (DME) method to characterize viscoelasticity of small homogeneous soft tissues, as well as the adaptation of the method for vascular applications [vascular dynamic micro-elastography (VDME)]. The technique is based on the generation of relatively high-frequency (240–1100 Hz) monochromatic or transient plane shear waves within the medium and the tracking of these waves from radio-frequency (RF) echoes acquired at 25 MHz with an ultrasound biomicroscope (Vevo 770, Visualsonics). By employing a dedicated shear wave gated strategy during signal acquisition, postprocessed RF sequences could achieve a very high frame rate (16,000 images per s). The proposed technique successfully reconstructed shear wave displacement maps at very high axial (60 μm) and lateral (250 μm) spatial resolutions for motions as low as a few μm. An inverse problem formulated as a least-square minimization, involving analytical simulations (for homogenous and vascular geometries) and experimental measurements were performed to retrieve storage (G′) and loss (G″) moduli as a function of the shearing frequency. Viscoelasticity measurements of agar-gelatin materials and of a small rat liver were proven feasible. Results on a very thin wall (3 mm thickness) mimicking artery enabled to validate the feasibility and the reliability of the vascular inverse problem formulation. Subsequently, the G′ and G″ of a porcine aorta showed that both parameters are strongly dependent on frequency, suggesting that the vascular wall is mechanically governed by complex viscoelastic laws. (E-mail: guy.cloutier@umontreal.ca)     

High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: quantitative imaging and correlation with iron

We report R₂ and R₂* in human hippocampus from five unfixed post-mortem Alzheimer's disease (AD) and three age-matched control cases. Formalin-fixed tissues from opposing hemispheres in a matched AD and control were included for comparison. Imaging was performed in a 600 MHz (14 T) vertical bore magnet at MR microscopy resolution to obtain R₂ and R₂* (62 μm × 62 μm in-plane, 80 μm slice thickness), and R₁ at 250 μm isotropic resolution. R₁, R₂ and R₂* maps were computed for individual slices in each case, and used to compare subfields between AD and controls. The magnitudes of R₂ and R₂* changed very little between AD and control, but their variances in the Cornu Ammonis and dentate gyrus were significantly higher in AD compared for controls (p < 0.001). To investigate the relationship between tissue iron and MRI parameters, each tissue block was cryosectioned at 30 μm in the imaging plane, and iron distribution was mapped using synchrotron microfocus X-ray fluorescence spectroscopy. A positive correlation of R₂ and R₂* with iron was demonstrated. While studies with fixed tissues are more straightforward to conduct, fixation can alter iron status in tissues, making measurement of unfixed tissue relevant. To our knowledge, these data represent an advance in quantitative imaging of hippocampal subfields in unfixed tissue, and the methods facilitate direct analysis of the relationship between MRI parameters and iron. The significantly increased variance in AD compared for controls warrants investigation at lower fields and in-vivo, to determine if this parameter is clinically relevant.     

A wall-less vessel phantom for Doppler ultrasound studies

Doppler ultrasound flow measurement techniques are often validated using phantoms that simulate the vasculature, surrounding tissue and blood. Many researchers use rubber tubing to mimic blood vessels because of the realistic acoustic impedance, robust physical properties and wide range of available sizes. However, rubber tubing has a very high acoustic attenuation, which may introduce artefacts into the Doppler measurements. We describe the construction of a wall-less vessel phantom that eliminates the highly attenuating wall and reduces impedance mismatches between the vessel lumen and tissue mimic. An agar-based tissue mimic and a blood mimic are described and their acoustic attenuation coefficients and velocities are characterised. The high attenuation of the latex rubber tubing resulted in pronounced shadowing in B-mode images; however, an image of a wall-less vessel phantom did not show any shadowing. We show that the effects of the highly attenuating latex rubber vessels on Doppler amplitude spectra depend on the vessel diameter and ultrasound beam width. In this study, only small differences were observed in spectra obtained from 0.6 cm inside diameter thin-wall latex, thick-wall latex and wall-less vessel phantoms. However, a computer model predicted that the spectrum obtained from a 0.3-cm inside diameter latex-wall vessel would be significantly different than the spectrum obtained from a wall-less vessel phantom, thus resulting in an overestimation of the average fluid velocity. These results suggest that care must be taken to ensure that the Doppler measurements are not distorted by the highly attenuating wall material. In addition, the results show that a wall-less vessel phantom is preferable when measuring flow in small vessels.     

Combined Vector Velocity and Spectral Doppler Imaging for Improved Imaging of Complex Blood Flow in the Carotid Arteries

Color flow imaging and pulsed wave (PW) Doppler are important diagnostic tools in the examination of patients with carotid artery disease. However, measurement of the true peak systolic velocity is dependent on sample volume placement and the operator's ability to provide an educated guess of the flow direction. Using plane wave transmissions and a duplex imaging scheme, we present an all-in-one modality that provides both vector velocity and spectral Doppler imaging from one acquisition, in addition to separate B-mode images of sufficient quality. The vector Doppler information was used to provide automatically calibrated (angle-corrected) PW Doppler spectra at every image point. It was demonstrated that the combined information can be used to generate spatial maps of the peak systolic velocity, highlighting regions of high velocity and the extent of the stenotic region, which could be used to automate work flow as well as improve the accuracy of measurement of true peak systolic velocity. The modality was tested in a small group (N = 12) of patients with carotid artery disease. PW Doppler, vector velocity and B-mode images could successfully be obtained from a single recording for all patients with a body mass index ranging from 21 to 31 and a carotid depth ranging from 16 to 28 mm.     

Listening to the Cochlea With High-Frequency Ultrasound

We have developed a high-frequency pulsed-wave Doppler ultrasound probe as a promising minimally-invasive technique for measuring intracochlear mechanics without damaging the cochlea. Using a custom high-frequency ultrasound system, we have measured dynamic motion of intracochlear structures by recording the pulsed-wave Doppler signal resulting from the vibration of the basilar and round window membranes. A 45 MHz needle-mounted Doppler probe was fabricated and placed against the round window membranes of eight different fresh human temporal bones. Pulsed-wave ultrasonic Doppler measurements were performed on the basilar membrane and round window membrane during the application of pure tones to the external ear canal. Doppler vibrational information for acoustic input frequencies ranging from 100–2000 Hz was collected and normalized to the sound pressure in the ear canal. The middle ear resonance, located at approximately 1000 Hz, could be characterized from the membrane velocities, which agreed well with literature values. The maximum normalized mean velocity of the round window and the basilar membrane were 180 μm/s/Pa and 27 μm/s/Pa at 800 Hz. The mean phase difference between the membrane displacements and the applied ear canal sound pressure showed a flat response almost up to 500 Hz where it began to accumulate. This is the first study that reports the application of high frequency pulsed wave Doppler ultrasound for measuring the vibration of basilar membrane through the round window. Since it is not required to open or damage the cochlea, this technique might be applicable for investigating cochlear dynamics, in vivo.     

A Rotating Cylinder Phantom for Flow and Tissue Color Doppler Testing

Ultrasound Doppler using two-dimensional (2D) techniques is commonly used to study blood flow and myocardial tissue motion. This use includes measurement of velocity and time intervals, often in relation to the electrocardiogram (ECG) signal. 2D Doppler is frequently considered a real-time technique but in reality the acquisition time can be as long as 200 ms per image. We have developed a test-phantom using a rotating cylinder to simulate blood flow and tissue motion in a whole sector or space angle to evaluate velocity and timing characteristics. The phantom can produce constant velocities for velocity testing, as well as accelerating movement for testing the timing characteristics of ultrasound systems. Our investigation shows that the cylinder phantom is especially suitable for timing measurements in 2D Doppler imaging and that time delays between the Doppler signals and the ECG signal exist in the tested ultrasound system. (E-mail: andrew.walker@ltv.se)