Fig. 12.1
Components of a flow phantom. The phantom mimics the cardiovascular geometry and is connected to a pump by tubing. A pump controller, usually a computer, enables programming of specific flow waveforms. An imaging system is used to record information on blood mimic velocities within the phantom
There are various terms used in the literature including ‘experimental flow system’, ‘phantom’ and ‘flow phantom’. In this chapter, the term ‘phantom’ will be used to describe the central cardiovascular construct, and ‘flow phantom’ used to describe the entire apparatus consisting of pump, pump controller, tubing, reservoirs and the phantom. The phantom consists of components which mainly mimic 2 tissues; the blood (blood mimic) and the soft tissue (tissue mimic). For phantoms mimicking flow in vessels the soft tissue may be further divided into the artery or vein (vessel mimic) and the surrounding soft tissue consisting of fat, muscle, liver, kidney, etc. (tissue mimic).
The advantages of using a flow phantom over an in vivo experiment are:
Control. High degree of control over experimental conditions including vessel geometry and flow rates.
Reproducibility. Ability to undertake repeated experiments with identical experimental conditions.
Licensing and safety. Avoidance of the use of biological material (e.g. blood, arteries, animal models) which may be difficult to obtain, require specialist biological facilities and use-licenses and which may be hazardous.
Optical transparency. Ability to create phantoms which can be used with imaging systems with high temporal and spatial resolution (i.e. optical imaging systems).
The main disadvantage of using a flow phantom over an in vivo experiment is
Inadequate mimicking. The phantom may not adequately mimic the characteristics of the cardiovascular system (e.g. vascular geometry, arterial wall properties, haemodynamics) hence conclusions from experiments may not be applicable in vivo.
The flow phantom replicates or mimics key aspects of the cardiovascular system. The flow phantom cannot mimic in detail all aspects of the cardiovascular system. One might then ask: how complicated does the flow phantom need to be? As with computational models discussed earlier (Chap. 10), the flow phantom needs to be sufficiently complex to allow a specific research question to be answered. This rationale then dictates that the research question comes first, and the flow phantom design follows the research question. If the research question changes then this may require redesign of aspects of the flow phantom. Another way of expressing this rationale is that the flow phantom is a simplified version of reality. The design of the flow phantom needs to be as complicated as necessary and no more complicated than that. An overcomplicated flow phantom will mean unnecessary effort in construction. It is noted that a similar rationale was discussed in Chap. 10 on the complexity of the computational model.
There are three main uses of flow phantoms:
Investigation of flow–field velocity data and associated phenomena. Optical imaging systems such as PIV (particle image velocimetry) and LDA (laser Doppler anemometry) have high spatial and temporal resolution and have been mostly used for measurement of flow-field velocity data and associated phenomena.
Validation of flow–field data obtained using medical imaging. Medical imaging systems such as MRI and ultrasound can be used to measure blood velocity and associated quantities. Validation of measured velocity is commonly undertaken using flow phantoms.
Investigation of the relationship between flow and aspects of biological function of the vessel wall. These flow phantoms are mostly concerned with endothelium which is cultured on the walls of a flow chamber where the relationship between wall shear rate and endothelial function is of interest.
12.2 Optically Transparent Phantoms
The use of an optically transparent phantom allows direct visualisation of flow patterns and measurement using optical techniques. This section will describe phantom construction and the associated optical imaging techniques. Further reading of optical techniques with respect to use in medical applications is given in the reviews by Hoskins (2008) and Vennemann et al. (2007).
12.2.1 Flow Visualisation
This is the simplest method for investigating flow patterns. The flow is seeded with a material which ideally is neutrally buoyant and can be visualised. Materials which have been used include injected dyes and inks, hydrogen bubbles, hollow glass spheres and a variety of solid particles. The seeded material will follow the flow-streamlines allowing the observer to visualise flow patterns. A video camera can be used to record the progress of the seeded material. In Fig. 1.18 a simple straight tube phantom with dye injection illustrated the difference between laminar flow and turbulence. Phantoms with anatomical geometry provided early evidence of complex flow patterns in bifurcations, including flow recirculation and helical flow (Ku and Giddens 1983; Zarins et al. 1983) (Fig. 12.2). Flow visualisation as its name implies is only concerned with qualitative visualisation of flow patterns, not quantitative measurement of velocities.
Fig. 12.2
Flow visualisation in a model of the carotid bifurcation. From;Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS, Mabon RF, Glagov S; Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress; Circulation Research 1983;53(4):502–514; reprinted with permission by Wolters Kluwer Health, Inc. Circulation Research is an official journal of the American Heart Association
12.2.2 Particle Image Velocimetry (PIV) and Particle Tracking Velocimetry (PTV)
Quantitative measurement of the velocity field may be undertaken using particle image velocimetry (PIV). In PIV the fluid is seeded with particles at low concentration of typically less than 1 % by volume. A pulsed laser is used to illuminate a single plane within the flow. A video camera is used to record sequential images of the illuminated particles. Between images the particles move a small distance. Image processing algorithms applied to groups of particles are used to estimate the distance the particles have moved; this distance is divided by the time between images to obtain the local velocity. Figure 12.3 shows an example of PIV data taken in a stenosis phantom. A related technique is particle tracking velocimetry (PTV) in which individual particles are tracked rather than groups of particles. Further details of PIV and PTV technology are provided by Adrian (1991), Westerweel (1997) and Prasad (2000).
Fig. 12.3
PIV in a stenosis model. a The interrogation region is shown as shaded in the schematic. b A typical PIV image; each bright dot represents a particle or group of particles. c Estimated velocity field
PIV provides high accuracy high resolution data on the velocity field. Due to its simplicity, accuracy and robustness it is regarded as providing gold-standard data, which is useful in validation of flow-field data obtained from CFD or from medical imaging.
12.2.3 Laser Doppler Anemometry (LDA)
Quantitative measurement of velocity may also be undertaken using laser Doppler anemometry (LDA). Two laser beams of the same frequency overlap producing a set of interference fringes within the overlap region. Particles moving through the interference fringes scatter light. The scattered light is detected by a photodetector. The frequency of the scattered light is dependent on the velocity of the particle and also on the angle between the direction of motion and the laser interference wave direction. This is very similar to Doppler ultrasound in that the motion of a particle produces a Doppler frequency shift. Common positions for the detector are on the opposite side to the laser or on the same side. Use of a single detector enables measurement of one velocity component whereas use of multiple detectors allows measurement of two or three velocity components. Information is gathered at a single point, however 3D information may be obtained by scanning the interrogation region through the flow field. Information is gathered continuously so that LDA may be used to study high frequency changes in the flow field associated with turbulence. Further details of LDA technology are provided by Tropea (1995); Liepsch et al. (1998) reviews the use of LDA in carotid artery phantoms.
12.2.4 Phantom Construction
Materials which are optically transparent and which have been used for phantom manufacture include glass, acrylic, polyester and silicone elastomers. The use of glass is challenging requiring phantom manufacture using glass-blowing. Most optically transparent phantoms with complex vascular geometries are manufactured using polyester, acrylic or silicone elastomers using a casting technique involving pouring and setting of the liquid. A simple straight tube model may be manufactured using metal rods which are joined together. These rods are positioned in a box and the liquid is poured into the box, allowed to set and the rods removed (Fig. 12.4).
Fig. 12.4
Straight-tube stenosis phantom for use in PIV. The metal rods used in construction are shown positioned within the phantom
3D cardiovascular geometries such as bifurcations require a more complicated manufacturing approach. Phantom manufacture is increasingly dominated by recent developments in rapid-prototyping (3D printing). Figure 12.5 summarises the steps which have been taken in published studies and are described below.
Fig. 12.5
Steps in the manufacture of 3D phantoms using 3D printing. a Mould and lost core. b Lost core. c Direct 3D printing
Mould and lost core. This method is exemplified by Watts et al. (2007). A 3D dataset of the carotid bifurcation is obtained from a volunteer using MRI. This is used to generate an idealised CAD (computer-aided design file) in which surfaces are smoothed and some arterial segments straightened (Fig. 12.6a). A solid model of the bifurcation is 3D printed. This is used to make a mould consisting of silicone. A low melting point alloy is poured into the mould. After cooling, the metal core is removed (Fig. 12.6b) and incorporated into a container with suitable inlet and outlet connections. Liquid silicone elastomer is poured into the box and allowed to set. Once set the container is heated resulting in melting of the metal core which can then be poured out leaving the final phantom containing the anatomical geometry (Fig. 12.6c). Doyle et al. (2008) also describes this process step by step for use in creating abdominal aortic aneurysm phantoms.
Fig. 12.6
Bifurcation phantom for use in optical studies manufactured using the ‘mould and lost core’ approach. a CAD image. b Lost core. c Final phantom. See Watts et al. (2007) for more detail
Lost core. This method is exemplified by Geoghegan et al. (2012). The procedure is similar to that described above except the steps involving the mould are missing. The lost core is 3D printed directly. The lost core is composed of water-dissoluble plaster powder. This is coated with PVA which provides smoothness, strength and acts to prevent ingress of the liquid silicone elastomer. After the elastomer has set the core is removed through a combination of water and physical erosion with a soft scraper, producing the final phantom (Fig. 12.7).
Fig. 12.7
Carotid artery bifurcation rigid flow phantom. The phantom is for use in optical studies manufactured using the ‘lost core’ approach. From; Experiments in Fluids; Fabrication of rigid and flexible refractive-index-matched flow phantoms for flow visualisation and optical flow measurements; Vol. 52, 2012, pp. 1331–1347, Geoghegan P, Buchmann N, Spence C, Moore S, Jermy M; © Springer-Verlag 2012, with permission of Springer
Direct 3D printing. This represents one of the goals in phantom manufacture as the number of steps is reduced to the minimum; direct 3D printing of the phantom in final form. Cloonan et al. (2014) describes the use of 3D printing for phantom manufacture.
Other methods have been used to acquire 3D geometries and create phantoms:
Corrosion casting of arteries involves injection of a liquid into autopsy or excised tissues. The liquid hardens in the artery and the tissues are chemically removed. Early studies on anatomical optical phantoms used injected silicone rubber which then formed the lost core in a phantom consisting of transparent plastic (Friedman et al. 1987; Friedman 1993). Resin-based corrosion casting is commonly used producing a high-resolution stiff model of the vascular system. Whilst this could not be removed using a lost core method, the model geometry could be scanned using a laser scanning system to provide a 3D CAD file suitable for 3D printing. 3D geometry data obtained from corrosion casting of arteries is extremely high quality.
Mould manufacture from milling. Planar anatomical phantoms have been manufactured based on the lost core method (Smith et al. 1999) which have been used in flow visualisation (Steinman et al. 2000). An idealised planar carotid bifurcation was used from which a mould was made in aluminium using a milling machine. The mould was used to produce a lost core in low melting point alloy from which the phantom was produced in silicone.
Once the phantom has been produced, the blood mimic must be designed to match the refractive index of the material of the phantom (Nguyen et al. 2004; Miller et al. 2006; Yousif et al. 2011) otherwise there will be visualisation artefacts (Fig. 12.8) and velocity measurement errors.
Fig. 12.8
Visual monitoring of the match in optical refractive index based on distortion of grid lines beneath a carotid bifurcation phantom fabricated from polydimethylsiloxane (PDMS) polymer. The phantom is filled with a air, showing high distortion, b nearly matched fluid (n = 1.4112 ± 0.0001), still showing minor distortion as indicated by the arrows, and c optimally matched fluid (n = 1.4140 ± 0.0001) with no distortion, as indicated by the arrows. Note the vertical white markers, denoting the flow lumen, and the unintentional stain at the bifurcation apex, which provides a convenient landmark here. From Yousif et al. (2011); © Springer-Verlag 2010, with permission of Springer. Image kindly provided by Prof. Tamie Poepping
12.3 Flow Phantoms for Medical Imaging
12.3.1 Medical Imaging Flow Phantom Design Requirements
Flow phantoms for medical imaging should mimic key features of the cardiovascular system which, as discussed above will depend on the application. Features might include cardiovascular geometry, blood viscous behaviour, wall stiffness and wall motion. In addition flow phantoms should mimic key properties of tissue relevant to the imaging modality. This ensures that images produced from the phantom are a good representation of images from the cardiovascular system in vivo. Tissue-mimicking also enables conclusions (e.g. on quantification of measurement errors) to be applicable in vivo. Construction of flow phantoms for medical imaging therefore requires choice or formulation of materials with the correct physical properties.
Materials which mimic the relevant imaging properties of tissues are referred to as being ‘tissue equivalent’. The relevant imaging properties are summarised in Table 12.1.
Table 12.1
Relevant physical properties of materials relevant to flow phantom design
Imaging system | Physical properties relevant to imaging |
---|---|
MRI | T1, T2, proton density |
Ultrasound | Speed of sound, acoustic attenuation, acoustic backscatter coefficient |
CT | X-ray attenuation coefficient |
PET | Gamma-ray attenuation coefficient |
12.3.2 Tissue and Vessel Mimics
The most commonly used phantoms consist of a length of tubing bought from a laboratory supplier. Stiff tubing includes acrylic, glass, PTFE and polypropylene, whilst softer tubing is mostly based on latex rubber. These simple vessel phantoms may be used to produce idealised flow to validate MRI velocity measurement methods; with the implication that the MR properties of the tube are unimportant as they have little effect on the measurement of velocity. Simple tube models have been used in ultrasound, however the tube has a large effect due to refraction and attenuation of the ultrasound beam within the vessel wall. C-flex tubing (Cole Parmer, Vernon Hills, IL, USA) has been used as its speed of sound (1556 m s−1) is close to the standard speed of 1540 m s−1 (Hoskins 2008).
Off-the-shelf materials can also be used to construct medical imaging phantoms with more complicated geometries. For CT and PET solid materials such as acrylic provide similar X-ray and gamma-ray attenuation characteristics to human tissue. This is convenient as phantoms can easily be constructed by milling or by casting. For MRI solid materials such as polyester, acrylic or silicone have been used to construct phantoms (e.g. Smith et al. 1999). Essentially these phantoms are identical to those used for optical imaging (Sect. 12.1). Figure 12.9 shows bifurcation phantoms and the associated MRI images of flow.
Fig. 12.9
MRI images from bifurcation phantoms. a Normal phantom—MRI intensity. b Normal phantom—MRI velocity. c 30 % stenosis phantom—MRI intensity. d 30 % stenosis phantom—MRI velocity. From; Marshall I. Computational simulations and experimental studies of 3D phase-contrast imaging of fluid flow in carotid bifurcation geometries. Journal of Magnetic Resonance Imaging. 2010;31:928–934; © 2010 Wiley-Liss, Inc., with permission from John Wiley and Sons. Images kindly provided by Prof. Ian Marshall
Solid materials such as polyester do not return an MRI signal which leads to unrealistic image appearance (Smith et al. 1999). This is an issue if the effect of surrounding tissue on velocity measurement is of interest. Solid materials such as acrylic have high speed of sound compared to soft tissue and are unsuitable for use in ultrasound phantoms. Ultrasound phantoms are available commercially based on urethane as the acoustic properties provide a reasonable match for soft tissue (Table 12.2).
Table 12.2
MRI properties of selected tissue mimics, vessel mimics and blood mimics
Mimic/Tissue | Main composition | T1 (ms) @1.5T | T2 (ms) @1.5T | T1 (ms) @3T | T2 (ms) @3T | Reference |
---|---|---|---|---|---|---|
Tissue/Vessel | PVAc (10 %) | 718–1034a | 108–175a | – | – | Surry et al. (2004) |
Tissue | Agar | 1150 | 50 | 1504 | 40 | |
Tissue | Sodium polyacrylate | – | – | 1077–2406 | 74–602 | Hellerbach et al. (2013) |
Tissue | Carrageenan/Agarose | 202–1904 | 38–423 | 395–2601 | 29–334
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