Assessment of an ultrasound bladder scanner in prostate radiotherapy: A validation study and analysis of bladder filling variability.

INTRODUCTION: During prostate radiotherapy treatment, it is important to ensure the position of the bladder and prostate is consistent between treatments. The aim of this study was to provide a quantitative basis for incorporating ultrasound bladder volume estimates into local practice for prostate radiotherapy. METHODS: Agreement between bladder volume estimates obtained using computed tomography (CT) and ultrasound was assessed. Analysis of bladder volumes between planning and treatment scans was used to quantify expected variations in bladder volume over the course of radiotherapy. Dose-volume statistics were estimated and compared to planned dose constraints to propose a target bladder volume and tolerance. RESULTS: Bladder volume measurements were obtained from 19 radiotherapy patients using ultrasound and CT. Ultrasound underestimated bladder volume compared to CT with a mean bias of -28 ± 30 ml. Pre-treatment (planning) bladder volumes varied from 71 to 383 ml with a mean of 200 ml. Treatment bladder volumes reduced by more than half in 9% of patients during the course of their treatment, potentially leading to a 30% increase in mean bladder dose. Patients with pre-treatment bladder volumes < 200 ml were most likely to exhibit differences in bladder volume, resulting in 'out of tolerance' increases in dose. CONCLUSIONS: A pragmatic individualised drinking protocol, aimed at achieving a minimum ultrasound bladder volume of 200 ml at planning CT, may be beneficial to reproducibility in radiotherapy treatment. Ultrasound measurements prior to treatment should ideally confirm that bladder volume is at least half the volume measured at planning.

A standard test phantom for the performance assessment of magnetic resonance guided high intensity focused ultrasound (MRgHIFU) thermal therapy devices.

Purpose: Test objects for High Intensity Focused Ultrasound (HIFU) are required for the standardization and definition of treatment, Quality Assurance (QA), comparison of results between centers and calibration of devices. This study describes a HIFU test object which provides temperature measurement as a function of time, in a reference material compatible with Magnetic Resonance (MR) and ultrasound.Materials and methods: T-Type fine wire thermocouples were used as sensors and 5 correction methods for viscous heating artifacts were assessed. The phantom was tested in a MR-HIFU Philips Sonalleve device over a period of 12 months, demonstrating stability and validity to evaluate the performance of the device.Results: The study furnished useful information regarding the MR-HIFU sessions and highlighted potential limitations of the existing QA and monitoring methods. The importance of temperature monitoring along the whole acoustic path was demonstrated as MR Thermometry readings differed in the three MR plane views (coronal, sagittal, transverse), in particular when the focus was near a soft-tissue/bone interface, where there can be an MR signal loss with significant temperature and thermal dose underestimation (138% variation between the three plane views).Conclusions: The test object was easy to use and has potential as a valid tool for training, QA, research and development for MR guided HIFU and potentially ultrasound guided devices.

Shear Wave Elastography May Be Superior to Greyscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology.

PURPOSE: There is a need to develop methods that reliably quantify characteristics associated with vulnerable carotid plaque. Greyscale median (GSM) and shear wave elastography (SWE) are two techniques that may improve individual plaque risk stratification. SWE, which quantifies Young's Modulus (YM) to estimate tissue stiffness, has been researched in the liver, breast, thyroid and prostate, but its use in carotid plaques is novel. MATERIALS AND METHODS: The aim of this study was to quantify YM and GSM of plaques and compare to histology. 25 patients (64% male) with a mean age of 76 underwent both clinical and SWE imaging. The mean GSM was quantified over a cardiac cycle. The mean YM was quantified in multiple regions within the plaque over 5 frames. Histological features were assessed following carotid endarterectomy. RESULTS: The mean YM of unstable plaques was significantly lower than that of stable plaques (50.0 kPa vs. 79.1 kPa; p = 0.027). The presence of intra-plaque hemorrhage, thrombus and increasing numbers of foam cells was also associated with a significantly lower YM. Plaque YM did not correlate well with plaque GSM (r =  .12). The mean plaque GSM was the same in both unstable and stable plaques. Fibrous plaques had a significantly higher GSM (p = 0.036). CONCLUSION: In conclusion, SWE provides additional information on plaque stiffness which may be of clinical benefit to help identify vulnerable plaque, and warrants further study.

A Novel Ultrasound-Based Carotid Plaque Risk Index Associated with the Presence of Cerebrovascular Symptoms.

PURPOSE: The purpose of this study was to determine the efficacy of a novel ultrasound-based carotid plaque risk index (CPRI) in predicting the presence of cerebrovascular symptoms in patients with carotid artery stenosis. MATERIALS AND METHODS: This was a cross-sectional, observational study involving 56 patients (mean age 76.6 years, 62.5 % male). Plaque grayscale median (GSM) and surface irregularity indices (SII) were measured in 82 stenosed carotid arteries (range 10 - 95 %) and combined with the degree of stenosis (DOS) in the form of (DOS*SII)/(1 + GSM). A reduced index DOS/(1 + GSM) not incorporating plaque surface irregularities was also investigated. Receiver operating characteristic curves (ROC) were used to study the diagnostic efficacy of CPRI, comparing against DOS and an equivalent risk index constructed using a conventional logistic regression based method with model parameters optimized to the dataset (CPRIlogistic). RESULTS: There were 42 stenosed carotid arteries with cerebrovascular symptoms, and 40 without symptoms. The presence of symptoms significantly correlated with DOS, GSM and SII (p < 0.01). The median CPRI of the symptomatic (asymptomatic) groups were 23.2 (9.2) compared with 0.71 (0.30) for CPRIlogistic (p < 0.01). The diagnostic performance of CPRI exceeded that of CPRIlogistic and DOS, and demonstrated a better separation of the symptomatic and asymptomatic groups. CONCLUSION: Our novel risk index combines quantitative measures of carotid plaque echogenicity and surface irregularities with the degree of stenosis. It is a better predictor of cerebrovascular symptoms than the degree of stenosis and could be valuable in studies and clinical trials aimed at identifying vulnerable carotid artery stenoses.

Evaluation of the effect of machine settings on quantitative three-dimensional power Doppler angiography: an in-vitro flow phantom experiment.

OBJECTIVES: Three-dimensional (3D) ultrasound is being used increasingly to acquire and subsequently quantify power Doppler data within the clinical setting. One proprietary software package calculates three 3D vascular indices: the vascularization index (VI), the flow index (FI), and the vascularization flow index (VFI). Our aim was to evaluate how different settings affect the Doppler signal in terms of its quantification by these three indices within a 3D dataset. METHODS: A computer-driven 'flow phantom' was used to continuously pump a nylon particle-based blood mimic (Orgasol(trade mark)) around a closed system through a C-flex(trade mark) tube embedded in an agar-based tissue mimic. The test tanks were insonated with a modified 3D transvaginal 4-8-MHz ultrasound transducer (V530D) and power Doppler data were acquired over a series of different settings. Each experiment involved the manipulation of just one Doppler setting in order to study it in isolation. RESULTS: As expected, all of the power Doppler settings, when altered, were found to effect significant changes (P < 0.05) in the VI, FI and VFI. The gain and signal power had the greatest effect, producing no Doppler signals at the lowest settings and the highest recordable indices at the maximum settings. The pulse repetition frequency (PRF) was the next most influential setting but a Doppler signal was seen and measurable at all of the different settings. The other Doppler settings had a much less profound effect on the vascular indices, with subtle but significantly different measures across the full range of settings. The speed of data acquisition was also found to affect the vascular indices, all of which were reduced when the fast mode was used although the only significant effect was on the VFI. CONCLUSIONS: The VI, FI and VFI are all affected significantly by variations in power Doppler settings and by the speed of acquisition. The gain and signal power have the greatest effect on the power Doppler signal, followed closely by the PRF. The other settings and speed of acquisition also influence the signal, but to a much lesser degree. It is essential to maintain Doppler settings if any meaningful comparisons are to be made within and between subjects.

Determining the relationship between three-dimensional power Doppler data and true blood flow characteristics: an in-vitro flow phantom experiment.

OBJECTIVES: Three-dimensional (3D) ultrasound can be used to acquire power Doppler data which can be quantified to give an objective impression about blood flow within a tissue or organ. Proprietary software can be used to calculate three indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Although these indices appear to have a predictive value in the clinical setting and can be shown to vary between different patient populations and over time within the same population, their relationship with true in-vivo blood flow characteristics has not been established. The objective was to examine the effect of flow rate, vessel number, attenuation and erythrocyte density on these indices. METHODS: A computer-driven flow phantom was used to continuously pump a nylon particle-based blood mimic (Orgasol(trade mark)) around a closed system through three different ultrasound test tanks. These tanks were designed specifically for these experiments and contained C-Flex(trade mark) tubing, in a variety of arrangements, encased in an agar-based tissue mimic. The test tanks were insonated with a modified 3D transvaginal 4-8-MHz ultrasound transducer and 3D power Doppler data were then acquired over a graduated series of flow rates, depths and blood mimic concentrations. Regression analysis was used to determine the resulting relationships. RESULTS: The VI increased linearly with an increase in flow rate (P < 0.05), whereas the FI increased in a cubic manner with a more rapid initial increase (P < 0.05). The VI demonstrated a similar linear increase with an increase in the erythrocyte mimic density (P < 0.05), whereas the FI increased markedly with a small change in erythrocyte mimic density and then plateaued (P < 0.01). There was a significant reduction in each index as the distance between the transducer and vessel increased (P < 0.05). Patterns similar to those seen in relation to the change in flow rate were evident, with a more linear relationship between depth and the VI and VFI than between depth and the FI, although the FI remained relatively constant and was not significantly affected by distance from the transducer until a depth of 55 mm was reached. Although a positive linear relationship was seen between vessel number and VI and VFI (P < 0.05) the FI demonstrated a very different and complex, cubic relationship (P < 0.001), increasing linearly until a maximum of three vessels were present when it decreased, and no overall correlation was seen (P > 0.05). CONCLUSIONS: The VI, FI and VFI are all significantly affected by volume flow, attenuation, vessel number and erythrocyte density, but in different ways. The VI and VFI seem to have a more predictable relationship, whereas the FI often demonstrates a more complex cubic relationship that is not always logical. Further work is required to establish the effect of other confounding parameters before valid conclusions may be made and a better understanding of 3D power Doppler ultrasound imaging achieved.

Anatomical flow phantoms of the nonplanar carotid bifurcation, part I: computer-aided design and fabrication.

Doppler ultrasound is widely used in the diagnosis and monitoring of arterial disease. Current clinical measurement systems make use of continuous and pulsed ultrasound to measure blood flow velocity; however, the uncertainty associated with these measurements is great, which has serious implications for the screening of patients for treatment. Because local blood flow dynamics depend to a great extent on the geometry of the affected vessels, there is a need to develop anatomically accurate arterial flow phantoms with which to assess the accuracy of Doppler blood flow measurements made in diseased vessels. In this paper, we describe the computer-aided design and manufacturing (CAD-CAM) techniques that we used to fabricate anatomical flow phantoms based on images acquired by time-of-flight magnetic resonance imaging (TOF-MRI). Three-dimensional CAD models of the carotid bifurcation were generated from data acquired from sequential MRI slice scans, from which solid master patterns were made by means of stereolithography. Thereafter, an investment casting procedure was used to fabricate identical flow phantoms for use in parallel experiments involving both laser and Doppler ultrasound measurement techniques.

Anatomical flow phantoms of the nonplanar carotid bifurcation, part II: experimental validation with Doppler ultrasound.

A nonplanar wall-less anatomical flow phantom of a healthy human carotid artery is described, the construction of which is based on a lost-core technique described in the companion paper (Part I) by . The core was made by rapid prototyping of an idealized three-dimensional computer model of the carotid artery. Flow phantoms were built using these idealized non planar carotid artery bifurcations. Physiologically realistic flow waveforms were produced with resistance index values of 0.75, 0.72 and 0.63 in the common, external and internal carotid artery branches, respectively. Distension of the common carotid using M-mode imaging was found to be at 10% of diameter. Although differences in vessel diameter between the phantom and that of the original computer model were statistically significant (p < 0.05), there was no difference (p > 0.05) in measurements made on the lost-cores and those obtained by B-mode ultrasound on the resulting flow phantoms. In conclusion, it was possible to reliably reproduce geometrically similar anatomical flow phantoms that are capable of producing realistic physiological flow patterns and distensions.

Angle-dependence and reproducibility of dual-beam vector doppler ultrasound in the common carotid arteries of normal volunteers.

Dual-beam vector Doppler has the potential to improve peak systolic blood velocity measurement accuracy by automatically correcting for the beam-flow Doppler angle. Using a modified linear-array system with a split receive aperture, we have assessed the angle-dependence over Doppler angles of 40 degrees -70 degrees and the reproducibility of the dual-beam blood maximum velocity estimate measured in the common carotid arteries (CCA) 1 to 2 cm prior to the bifurcation of 9 presumed-healthy volunteers. The velocity magnitude estimate was reduced by approximately 7.9% as the angle between the transmit beam and the vessel axis was increased from 40 degrees to 70 degrees. With repeat measurements made, on average, approximately 6 weeks apart, the 95% velocity magnitude limits of agreement were as follows: Intraobserver -41.3 to +45.2 cm/s; interobserver -29.6 to +46.8 cm/s. There was an 8.6 cm/s interobserver bias in velocity magnitude. We conclude that the dual-beam vector Doppler system can measure blood velocity within its scan plane with low dependence on angle and with similar reproducibility to that of single-beam systems.

Assessment of the acoustic properties of common tissue-mimicking test phantoms.

Ultrasound (US) test phantoms incorporating tissue-mimicking materials (TMMs) play an important role in the quality control (QC) and performance testing of US equipment. Three commercially available TMMs (Zerdine from CIRS Inc.; condensed-milk-based gel from Gammex RMI; urethane-rubber-based from ATS Labs) and a noncommercial agar-based TMM, were investigated. Acoustic properties were measured over the frequency range 2.25 to 15 MHz at a range of ambient temperatures (10 to 35 degrees C). The acoustic velocity of the TMMs remained relatively constant with increasing frequency. Only the agar-based TMM had a linear increase of attenuation with frequency, with the other materials exhibiting nonlinear responses to varying degrees (f(1.08) to f(1.83)). The acoustic velocity and attenuation coefficient of all the TMMs varied with temperature, with the urethane-rubber TMM showing the greatest variation of +/- 1.2% for acoustic velocity and +/- 12% for attenuation coefficient. The data obtained in this study highlight the importance of greater knowledge of the acoustic behavior of TMMs to variations in both frequency and temperature, to ensure that accurate and precise measurements are obtained during QC and performance testing.

Understanding the limitations of ultrasonic backscatter measurements from microbubble populations.

Despite over ten years of in vitro investigations of ultrasound contrast agents, the level of understanding of their behaviour in ultrasound fields is limited. Several problems associated with these investigations, particular to the nature of contrast agents, are discussed. Using a commercial scanner the RF normalized backscatter of two different contrast agents (Definity and Quantison) was measured at different suspension concentrations and acoustic pressures. Both contrast agents scattered ultrasound nonlinearly and the backscatter showed a dependence on acoustic pressure. In order to assess the average behaviour of the agents across the range of acoustic pressures and microbubble concentrations the experimental data were fitted to a theoretically acceptable model using nonlinear regression analysis. The analysis showed that both the backscatter and the attenuation of the Quantison suspensions displayed a higher order of dependence on acoustic pressure than the Definity suspensions. It was also discovered that Quantison microbubbles did not demonstrate uniform behaviour across the acoustic pressure range. At lower acoustic pressures the behaviour could not follow a model similar to that which predicted the behaviour at higher acoustic pressures, which was mainly due to the fact that free bubbles were released in a fashion dependent on acoustic pressure. The fact that two different populations of scatterers exist in the same suspensions makes the assessment of the behaviour of the particular agent impossible with the high concentrations that are commonly used. Very low concentration suspensions whereby single scattering events can be monitored should be more useful. In conclusion, the approach of using high microbubble concentrations in order to investigate the properties of ultrasonic contrast agents is limited in that the results of such studies cannot be used to understand the behaviour of single microbubbles.

Numerical investigation of physiologically realistic pulsatile flow through arterial stenosis.

Numerical simulations of pulsatile blood flow in straight tube stenosis models were performed to investigate the poststenotic flow phenomena. In this study, three axisymmetrical and three asymmetrical stenosis models with area reduction of 25%, 50% and 75% were constructed. A measured human common carotid artery blood flow waveform was used as the upstream flow condition which has a mean Reynold's number of 300. All calculations were performed with high spatial and temporal resolutions. Flow features such as velocity profiles, flow separation zone (FSZ), and wall shear stress (WSS) distributions in the poststenotic region for all models are presented. The results have demonstrated that the formation and development of FSZs in the poststenotic region are very complex, especially in the flow deceleration phase. In axisymmetric stenoses the poststenotic flow is more sensitive to changes in the degree of stenosis than in asymmetric models. For severe stenoses, the stenosis influence length is shorter in asymmetrical models than in axisymmetrical cases. WSS oscillations (between positive and negative values) have been observed at various downstream locations in some models. The amplitude of the oscillation depends strongly on the axial location and the degree of stenosis.

Construction and geometric stability of physiological flow rate wall-less stenosis phantoms.

Wall-less flow phantoms are preferred for ultrasound (US) because tissue-mimicking material (TMM) with good acoustical properties can be made and cast to form anatomical models. The construction and geometrical stability of wall-less TMM flow phantoms is described using a novel method of sealing to prevent leakage of the blood-mimicking fluid (BMF). Wall-less stenosis flow models were constructed using a robust agar-based TMM and sealed using reticulated foam at the inlet and outlet tubes. There was no BMF leakage at the highest flow rate of 2.8 L/min in 0%, 35% and 57% diameter reduction stenoses models. Failure of the 75% stenosis model, due to TMM fracture, occurred at maximum flow rate of 2 L/min (mean velocity 10 m/s within the stenosis). No change of stenosis geometry was measured over 4 days. The construction is simple and effective and extends the possibility for high flow rate studies using robust TMM wall-less phantoms.

Improved characterisation of focal liver tumours: dynamic power Doppler imaging using NC100100 echo-enhancer.

OBJECTIVE: To assess the vascularisation of focal hepatic tumours using NC100100, enhanced power Doppler imaging. METHODS: Twenty-two patients with focal liver tumours (12 metastases and ten hemangiomas) were studied. Using standardised settings, power Doppler imaging with ATL HDI3000 was performed before and after intravenous administration of NC100100 contrast agent. The video-recorded examinations were digitised for off-line analysis on a personal computer. Regions of interest were defined over the entire tumour and a neighbouring area of the normal liver parenchyma. The temporal changes of the mean power Doppler signal intensity (PDSI) was quantified to provide contrast agent wash-in (PDSI-time) curves for the initial 40 s. RESULTS: Liver metastases were characterised by a rapid increase in PDSI, while the PDSI-time curves within hemangiomas were flat. The PDSI within the tumour increased significantly in ten subjects with liver metastases and only one subject with hemangioma. An enhanced rim around hemangiomas was seen in four subjects. There was no clear relationship between the contrast agent dose and the peak PDSI within metastases. CONCLUSIONS: Power Doppler imaging with NC100100 contrast agent enhances tumour visualisation and may aid differential diagnosis of focal liver lesions.

Doppler backscatter properties of a blood-mimicking fluid for Doppler performance assessment.

The Doppler backscatter properties of a blood-mimickig fluid (BMF) were studied to evaluate its suitability for use in a Doppler flow test object. Measurements were performed using a flow rig with C-flex tubing and BMF flow produced by a roller pump or a gear pump. A SciMed Doppler system was used to measure the backscattered Doppler power with a root-mean-square power meter connected to the audio output. Studies investigated the dependence of the backscattered Doppler power of the BMF with: circulation time; batch and operator preparations; storage; sieve size; flow speed; and pump type. A comparison was made with human red blood cells resuspended in saline. The backscatter properties are stable and within International Electrotechnical Commission requirements. The BMF is suitable for use in a test object for Doppler performance assessment.

Development of an example flow test object and comparison of five of these test objects, constructed in various laboratories.

Doppler test objects are used to characterise Doppler systems, both stand-alone systems and the Doppler part of so-called duplex scanners. The aim of the project partially presented here is the development and validation of an example of a Doppler test object fulfilling the requirements of the IEC 1685. The project has been carried out by nine partners of five European countries and has been funded by the European Commission. The flow Doppler test object is composed of: tissue mimicking material (TMM), blood mimicking fluid (BMF), tube (embedded in the TMM and carrying the BMF), tank flow system, including a pump and a flow meter. In the normative part of the IEC 1685, requirements are given for the values of acoustical parameters of TMM and BMF such as sound velocity, attenuation and backscattering. For BMF, requirements are given also for values of density and viscosity. In an informative (but not compulsory) annex, a description is given of a flow test object meeting these requirements as an example. 'example test object' developed during the project is composed of TMM based on agar and including SiC- and Al2O3-powders, BMF based on nylon particles suspended in water and glycerine, and a tube of c-flex, a silicon copolymer. Two tube sizes are used: 4.0 mm ID and 8.0 mm ID. During the project, very precise recipes have been developed for the composition and preparation of both TMM and BMF. Based on these recipes and a description of the construction in a design five flow test objects have been constructed in the laboratories of five participants. The test objects have been compared by measurements of the physical parameters and by Doppler measurements of the five test objects with the Doppler system. The measurements have been carried out by five observers. Inter-test object and inter-observer variabilities are determined, yielding information about usefulness of the parameters.

Effects of pulsed ultrasound on embryonic development: an in vitro study.

Whole-embryo culture was used as the model system to study the effects of pulsed ultrasound on embryonic development. Rat embryos (9.5 days old) were exposed to a wide range of ultrasound levels at ultrasound frequencies between 1-4 MHz for 30 min in vitro. After 48 h in culture, absolute control, sham and treatment embryos were assessed for viability, morphology, growth and development. At an ambient temperature of 37 degrees C, no significant effects were observed for spatial peak temporal average intensities below 4 W/cm2 or peak negative pressures below 1.9 MPa. At higher acoustic levels, there was a significant increase in the number of nonviable embryos and the number of morphological abnormalities in viable embryos increased. Abnormal cephalocaudal flexion and abnormal head development were the most common gross morphological abnormalities. Both thermal and nonthermal bioeffect mechanisms are involved.

Validation of a new blood-mimicking fluid for use in Doppler flow test objects.

A blood-mimicking fluid (BMF) suitable for use in Doppler flow test objects is described and characterised. The BMF consists of 5 microns diameter nylon scattering particles suspended in a fluid base of water, glycerol, dextran and surfactant. The acoustical properties of various BMF preparations were measured under uniform flow to study the effects of particle size, particle concentration, surfactant concentration, flow rate and stability. The physical properties, (density, viscosity and particle size), and acoustical properties (velocity, backscatter and attenuation) of the BMF are within draft International Electrotechnical Commission requirements.