Clinical and technical background

Atherosclerosis or hardening of arteries is a systemic disease of the vessel wall that occurs in the aorta, carotid, coronary and peripheral arteries (Fuster et al., 1999). It is characterised by the deposition of plaques on the innermost layer of the arterial wall. Factors that may lead to plaque instability are lipid content and iron deposits. The iron deposits in the plaque can be seen as a marker of prior hemorrhagic, or bleeding events that put a person at risk for plaque eruption (Bornstein et al., 1990; Starry et al., 1995). The challenge is to diagnose a vulnerable plaque by the presence of these components and treat or remove it.

A review of the available literature on atherosclerosis shows that lumen size (the inner open space of a blood vessel) is not sufficient to predict the occurrence of clinical events. The information on plaque morphology and composition are more valuable in the vulnerability assessment than lumen size (Glagov et al., 1995; Pasterkamp et al., 2000; Libby, 2009). Many imaging modalities have been investigated in atherosclerotic plaque characterisation. The details about atherosclerosis imaging techniques with regard to their ability to identify unstable lesions at risk of rupture are covered more thoroughly in Chapter 6.

Many efforts have been made recently to extract meaningful information from CT scans, especially the identification of tissues or material being imaged, by using the characteristic energy-dependent attenuation of x-rays (Hounsfield et al., 1973). Furthermore, the use of CT in the hospitals has grown exponentially during the last 25 years, with similar trending of data from regions across the world (Thomas, 2011). The Organisation for Economic Co-operation

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and Development (OECD) records the availability of medical equipment in all health care facilities, including the hospital and ambulatory sectors.

In New Zealand, the total CT scanners per million population have increased by more than 345% while the total MRI unit per million population has increased by 288% in the last two decades (OECD, 2011). This data shows that the availability of CT scans has significantly increased. It has also been reported that there is a remarkable growth in CT utilisation particularly in emergency departments (Gamble, 2010; RSNA, 2010; Guidera, 2010; Manos, 2011). It is worthwhile noting that the rates of CT imaging have risen because of various technological improvements that make them more useful in the diagnosis of many types of diseases and enable provide excellent care to be provided cost-effectively.

A large number of studies have been performed over the last few years to investigate the ability to characterise ex vivo atherosclerotic plaque composition by dual-energy CT imaging. Using synchrotron-based micro-CT (with voxel size of (2 µm)3 and beam energies of 16 keV and 20 keV), synchrotron based fluorescence microscopy and histology, Langheinrich et al. (2007) demonstrated the ability to detect and discriminate iron and calcium deposits in the wall of aorta by virtue of the size of the opacities (the area of individual iron deposits within a single CT slice being <(100 µm)2). The distribution of iron deposits within the plaques showed evidence of prior intraplaque hemorrhage in the mouse model of advanced atherosclerosis. Iron deposit is a marker of intraplaque hemorrhage that accumulates in the arterial wall.

A major challenge to using iron deposits as an imaging marker of plaque vulnerability is the concurrent presence of calcium, which is indistinguishable from iron in conventional imaging modalities. In 2009, Langheinrich et al. demonstrated the influence of voxel size on its ability

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to discriminate iron and calcium deposits in ex vivo coronary arteries. At a voxel size of (20 µm)3 or smaller, iron deposits could be identified based on the CT grey scale value. Voxels of (100 µm)3 or larger cannot resolve nor distinguish iron deposits from calcifications by virtue of their CT grey scale values. The iron and calcium deposits cannot be differentiated at low resolution due to the partial volume effect. The partial volume effect is the loss of information in small objects or regions because of the limited resolution of the imaging system. The resulting CT value represents the average attenuation properties of the structure and the surroundings instead of the attenuation values to be determined.

On the other hand, a recent simulation study by Wang and his colleagues (Wang et al., 2010) demonstrated that iron and calcium deposits can be differentiated using their morphological features at voxel sizes up to (200 µm)3 using dual-energy CT. Wang et al. performed the simulation phantom of human arterial wall with iron and calcium deposits using voxel sizes from 4 to 600 microns at 80 kVp and 140 kVp. The dual-energy ratio map of iron and calcium was computed to distinguish material composition by taking the ratio of low and high energy images. The dual-energy ratio map of iron and calcium remain visually different at a voxel size of (200 µm)3. The ability to use larger voxels sizes makes clinical implementation easier, reduces image noise and decreases patient dose requirements. This study shows that the use of multiple energies might improve material separation.

Multi-energy CT, often known as spectral CT, yields valuable quantitative information about elemental and molecular composition of materials. It enables the identification of materials by decomposing the total attenuation of the material into the various physical contributions for each voxel (Schlomka et al., 2008). Feuerlein et al. (2008) used a preclinical spectral CT scanner with a single-line photon-counting cadmium telluride array detector (MEXC; Gamma

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Medica Ideas, Northridge, Calif). It improved luminal depiction by differentiating among intravascular gadolinium-based contrast agent, calcified plaque and stent material in an artery phantom. Feuerlein et al. used the measurements of the six energy bins of the photon-counting detector to estimate the contributions to the total attenuation of the photoelectric effect, the Compton effect and the k-edge of gadolinium.

Cormode et al. (2010) performed a spectral CT study with contrast agents to characterise the macrophage burden, calcification and stenosis in atherosclerotic plaque. They used apolipoprotein E-knockout (Apo E-KO) mice as the model for atherosclerosis. The gold particles were absorbed by macrophages that cause inflammation in the arterial wall at the places of atherosclerotic plaques. Spectral CT enables differentiation of gold-based contrast agent (K-edge energy, 80 keV) from an iodinated contrast agent (K-edge energy, 33.2 keV) with the use K-edge of the materials. The advantages of the spectral CT method compared to other methods such as Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) include the lack of a need for pre-contrast scans, increased resolution and faster imaging.