Nico R Mollet, Filippo Cademartiri, Pim J de Feyter

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1 BASICS See end of artile for authors affiliations Correspondene to: Pim J de Feyter, MD, PhD, Erasmus Medial Center, Department of Cardiology and Radiology, Thoraxenter Bd 410, PO Box 2040, 3000 CA Rotterdam, The Netherlands; p.j.defeyter@erasmusm.nl Imaging tehniques NON-INVASIVE MULTISLICE CT CORONARY IMAGING M Nio R Mollet, Filippo Cademartiri, Pim J de Feyter Heart 2005; 91: doi: /hrt ultislie spiral omputed tomography (MSCT) oronary angiography is a promising noninvasive tehnique for the detetion of oronary stenoses. 1 4 The advent of the tehnially improved 16 row MSCT sanner, with higher spatial and temporal resolution, has permitted more reliable detetion of oronary plaques and signifiant obstrutive oronary lesions. 5 It appears likely that MSCT oronary angiography will mature into a non-invasive diagnosti tool that will beome integrated into the management of patients with known or suspeted oronary atheroslerosis. This review will fous on the basis of the sanner, the diagnosti performane, and potential future appliations. OF MSCT CORONARY ANGIOGRAPHY What is omputed tomography? A CT sanner onsists of an x ray tube and a row of detetors, whih rotate around the patient who is positioned in the entre. The tube produes a fan shaped x ray beam, whih passes through the patient and hits the detetor on the other side (fig 1). The atomi density of a tissue that an x ray beam enounters determines its attenuation with a higher atomi tissue density resulting in a higher attenuation. The various tissues in a ross setion an be distinguished beause they have differenes in atomi density and attenuation. The attenuation of the x ray beam is expressed as an absolute value measured in Hounsfield units (HU). The rotation of the x ray tube allows alulation of the attenuation at every single point of the slie, whih is used to produe a ross setional image of the body. The first generation CT sanners used a sequential aquisition pattern, also known as stepand-shoot. These sanners produed an axial image while the table remained motionless and for eah other slie the table moved to a different position. This sequene of events was repeated throughout the san range (fig 2A). Sequential CT sanning was both time onsuming and extremely sensitive to respiratory movements and was therefore not suitable for ardia imaging. To what do the terms spiral CT and multi-slie spiral CT refer? The total san time was signifiantly redued with the introdution of spiral CT sanners. The san is performed while the patient is ontinuously moving at a pre-defined speed through the sanner. The resulting trajetory of the x ray tube rotating around the patient an be plotted as a helix or spiral (fig 2B). These sanners aquire volumetri data and ross setional images an be reonstruted later for any anatomi region. This onfiguration signifiantly redued the total san time, but still was not fast enough for ardia sanning. Multislie spiral CT (MSCT) is a reent development in spiral CT. MSCT sanners are equipped with multiple and thinner detetor rows, and have a faster x ray tube rotation speed. These tehnial advanes have an important impat on image quality and will be disussed in detail. What does the term retrospetive ECG gating mean? The ontration of the heart an ause severe motion artefats on MSCT. To overome this problem, only data obtained during the diastoli phase of the ardia yle (when ardia motion is redued) is used for image reonstrution. The ECG trae of the patient is ontinuously monitored during the san proedure, and retrospetive ECG gating is used to generate images in the diastoli phase of the ardia yle. This retrospetive gating tehnique is based on data aquisition during the whole ardia yle. After data aquisition, retrospetively, the optimal reonstrution window is hosen among all available time positions during the diastoli phase to ensure the least ardia motion artefats (fig 3). The retrospetive gating tehnique allows flexibility in the position of reonstrution windows to diminish artefats related to rapid oronary motion and extrasystoles. However, this flexibility is obtained at the ost of a high radiation exposure. 401

2 A B X ray tube 402 Patient X ray beam Gantry Detetors Figure 1 sanner. Frontal (A) and side (B) view of a omputed tomography (CT) What are the tehnial requirements for MSCT oronary angiography? Non-invasive visualisation of the oronary arteries is hallenging. High temporal and high spatial resolution are both prerequisites to visualise the small, tortuous, and rapidly moving oronary arteries. Moreover, the san must be performed within a single breath hold to diminish artefats related to breathing. The spatial resolution in the x/y axis of urrent MSCT sanners is mm. The spatial resolution in the z axis is determined by the minimum slie thikness, whih varies from mm depending on the manufaturer. These features permit reonstrution of high quality images with a sub-millimetre, nearly isotropi (same size in every dimension) voxel size. This high spatial resolution redues partial volume effets and also allows visualisation of oronary segments down to diameters of mm. A high temporal resolution is needed to minimise artefats related to oronary motion. The temporal resolution is dependent on the rotation speed of the x ray tube and the detetor. Usually a reonstrution algorithm is applied whih uses data obtained over half the rotation time of the x ray tube. The temporal resolution using this algorithm urrently ranges from ms, depending on the manufaturer. In linial pratie, a temporal resolution within this range is suffiient for reliable visualisation of the oronary arteries in patients with a heart rate below 70 beats/min. Current state-of-the-art MSCT sanners are equipped with 16 detetor rows. This feature, ombined with the inreased rotation speed of the x ray, allows sanning of the heart (generally m in the ranio-audal axis) in a single breath hold of less than 20 seonds, whih is a manageable breath hold for pratially all patients. What are the limitations and pitfalls of MSCT oronary angiography? MSCT oronary angiography is feasible in patients with a stable heart rhythm, able to breath-hold for 20 seonds. The image quality is degraded by artefats in patients with irregular heart rhythms; atrial fibrillation is a ontraindiation for MSCT imaging while frequent extra-systoles an severely degrade image quality, although in the ase of oasional extra-systoles this an be overome by sometimes lengthy manual reonstrution of the images. Breathing during the san an also severely degrade image quality. Other limitations of CT angiography in general are ontraindiations to x ray exposure (for example, pregnany) or to Heart: first published as /hrt on 14 February Downloa Figure 2 Sequential (A) and spiral (B) CT sanning. the administration of intravenous iodinated ontrast material (for example, allergy, renal failure, or hyperthyroidisms). Well known pitfalls of MSCT oronary angiography inlude motion artefats and severe oronary alifiation. The temporal resolution of urrent 16 row MSCT sanners allows reliable evaluation of the oronary arteries at stable heart rates below 70 beats/min. Oral or intravenous b blokers Figure 3 Sanning during the entire ardia yle allows retrospetive gating. Different reonstrution windows during the diastoli phase an be explored to obtain images with the least motion artefats. Two methods an be used to adjust reonstrution windows. One method selets different perentages of the ardia yle (A). Another method selets different positions based on an absolute time interval before the next R wave (B). No data are urrently available to prove the superiority of either method and both methods are ommonly used.

3 Figure 4 Influene of spatial resolution, temporal resolution, and overage on the diagnosti performane of MSCT oronary angiography. COPD, hroni obstrutive pulmonary disease. should be administered to patients with higher resting heart rates to redue the frequeny of motion artefats. The most rapidly moving oronary segment is the mid part of the right oronary artery where motion artefats are most frequently observed. Adequate image quality at this level is usually a guarantee of good image quality in the rest of the oronary tree. Large deposits of alium in the oronary wall also influene image quality. Coronary alifiations are high Table 1 Detetion of signifiant (>50%) oronary lesions with MSCT oronary angiography n Exl Sens Spe PPV NPV A 4 row MSCT Nieman et al Ahenbah et al Knez et al Vogl et al row MSCT Nieman et al Ropers et al Mollet et al Exl, exluded; Sens, sensitivity; Spe, speifiity; PPV, positive preditive value; NPV, negative preditive value; A, auray. density strutures ausing beam hardening and partial volume artefats. These artefats result in over-projetion (blooming) of the alifiations on the oronary lumen hampering assessment of oronary lesions (fig 4). Therefore, assessment of both the presene and severity of oronary lesions is ompromised in heavily alified vessels. The radiation exposure during MSCT oronary angiography, generally between msv, remains a soure of onern. 6 9 Prospetive x ray tube modulation an be applied to redue radiation exposure. This setting redues radiation output during systole and dereases the alulated effetive radiation exposure by up to 50% at low heart rates. The resultant alulated effetive radiation exposure (4.3 msv) is of the same order of magnitude as that of an invasive diagnosti oronary angiogram (2 6 msv). 9 CLINICAL APPLICATIONS Detetion of signifiant obstrutive oronary lesions: historial perspetives The linial appliation of MSCT oronary angiography using the previous generation four row MSCT sanners was limited for several reasons. A signifiant number of vessels were nonassessable beause of the relatively low temporal and spatial resolution. Furthermore, the long san time (,40 s) frequently resulted in breathing artefats during the latter part 403

4 404 of the san. 1 4 These limitations resulted in exlusion of up to 32% of the vessels from the analysis beause of insuffiient image quality (table 1). 2 Detetion of signifiant obstrutive oronary lesions: urrent status The sensitivity and speifiity for detetion of signifiant (> 50% lumen narrowing) lesions with the urrent generation of 16 row MSCT sanners, when appropriate measures are taken to ensure an appropriate heart rate (use of b blokers for pre-san heart rates above 60 beats/min), is around 90% (fig 5) More importantly, the number of non-assessable vessels has been signifiantly redued with the 16 row MSCT sanner. Ropers et al exluded only 12% of the vessels and both Nieman et al and Mollet et al did not exlude any vessels for this reason (table 1). This is an important advane beause linial appliation of this tehnique presupposes reliable visualisation of the entire oronary tree. Coronary plaque imaging MSCT oronary alium sore: assessment of the alium burden Coronary alium quantifiation was first reported with eletron beam CT (EBCT) sanners. Histologial studies have shown that attenuation values. 130 HU were losely orrelated with the presene of alified plaque. 13 Agatston proposed a alium sore to lassify alium deposits in the oronary wall. This sore used an area threshold of > 1mm 2 and a density threshold of. 130 HU to identify a alified lesion and the Agatston sore was alulated by multiplying the area of eah alified lesion with the peak density of the plaque. 14 Long term follow up studies have suggested that the Agatston sore has inremental prognosti value in the predition of sudden oronary death or non-fatal myoardial infartion in asymptomati, high risk patients although this is still somewhat ontroversial. The presene of alium is a Figure 5 Conventional angiography image (left panel) showing a subtotal olusion (arrowhead) of the mid part of the right oronary artery, distal to a right ventriular (RV) branh (arrow). Corresponding CT images using different image post-proessing tehniques: volume rendered (middle panel) and maximum intensity projetion (right panel) images showing the subtotal olusion (arrowhead) and RV branh (arrow). surrogate for the presene of atheroslerosis and the extent of oronary alium orrelates with the overall atherosleroti plaque burden. A high alium sore is assoiated with a higher likelihood of an adverse oronary event, but the presene of alium in a plaque annot be onsidered, at present, as an indiator of plaque vulnerability. Furthermore, a negative alium sore is not a guarantee that the vessel is free from atherosleroti lesions, inluding vulnerable plaques, although it renders their presene less likely. 15 Coronary alium is also a funtion of age and sex, and the preditive auray of alium soring is improved when adjusted for these parameters. Several prospetive follow up studies have been published to establish the prognosti value of oronary alium in intermediate to high risk asymptomati subjets (table 2) However, the inremental value, over onventional risk fators, of alium soring for sreening asymptomati, high risk patients is urrently still somewhat ontroversial beause of onfliting data. Large, randomised, prospetive follow up studies are needed to establish the real prognosti value of oronary alium. A good orrelation between alium soring with EBCT and MSCT sanners has been desribed and urrently both tehniques are used for alium soring. 20 Most studies have been performed using EBCT sanners, but nowadays this will gradually be taken over by MSCT sanners, whih are widely available. MSCT oronary angiography: assessment of the total MSCT plaque burden Coronary alium quantifiation with EBCT orrelates with the extent of atheroslerosis, but severely underestimates the total oronary plaque burden. 13 In fat, the amount of alium deteted with EBCT reflets only one fifth of the measured atherosleroti plaque burden. 13 In individual patients, there is wide variation in the extent and severity Table 2 Prognosti value of oronary alium in intermediate and high risk individuals (EBCT studies) Study Subjet (n) Mean age (years) Follow up (months) Adverse events* Cut off valueà Relative risk` Detrano et al Arad et al Raggi et al v 3.01 Kondos et al ô M:50, F: M:5.8, F:1.8 *Adverse events defined as: death and myoardial infartion. ÀCut off value: threshold based on Agatson sore, onsidered as having an inreased risk. `Relative risk is alulated against the patients with a lower risk sore. 1Annual risk. ôfollow up rate only 64%. M, male; F, female.

5 of oronary plaques. Sixteen row MSCT oronary angiography not only permits reliable detetion of signifiant obstrutive lesions, but also detetion and lassifiation of oronary plaques into alified or non-alified plaques (fig 6) The total MSCT plaque burden provides additional information about the extent, distribution, and loation of oronary atheroslerosis, and might orrelate more losely with the total plaque burden found on histology. It has been suggested that the attenuation, in Hounsfield units, of the omponents of non-alified plaques ould reliably identify the presene of lipid or of fibrous tissue. This might help to identify potentially vulnerable plaques More extensive studies are needed to establish the full potential of MSCT oronary angiography in plaque detetion and haraterisation. An important limitation is the absene of dediated software able to quantify aurately the amount of alified as well as non-alified plaques on a ontrast enhaned san. Left ventrile funtion with MSCT oronary angiography Information of left ventriular funtion (LVF) an be derived from the san data obtained during MSCT oronary angiography. Reonstrution of datasets during different phases of the ardia yle enables alulation of end diastoli Figure 6 Maximum intensity projeted CT image of the left main and left anterior desending oronary artery showing mixed (inlays), alified (B), and non-alified (C) plaques. Ca, alified; LAD, left anterior desending oronary artery; NC, non-alified. Figure 8 Contrast is well visualised inside the stent allowing assessment of stent pateny. This is also shown on the ross setional image loated between the two arrowheads. and end systoli volumes of the left ventrile, stroke volume, and ejetion fration (fig 7). A good orrelation between ejetion fration measured with MSCT and either magneti resonane imaging (MRI) or onventional biplane ventriulography has been demonstrated. MSCT is a less suitable tehnique for the assessment of wall motion abnormalities beause of its lower temporal resolution when ompared with MRI or ehoardiography. However, the primary aim of Figure 7 Reonstrution of datasets at end diastole (left) and end systole (right) allow alulation of ejetion fration and volumes. Reonstrution of additional datasets during the ardia yle is required for assessment of wall motion abnormalities. This patient has an impaired ejetion fration due to a previous inferoseptal infartion, whih is visualised by redued thikening of the septal myoardium. MSCT angiography is a potential alternative for patients who annot undergo MRI for example, patients with paemakers (in the present ase, a paemaker lead is visualised in the right ventrile; arrowhead). EDV, end diastoli volume; ESV, end systoli volume; lv, left ventrile; rv, right ventrile. 405

6 406 Non-invasive multislie CT: key points Multislie spiral omputed tomography (MSCT) oronary angiography is a non-invasive tehnique that an visualise both the lumen and the wall of the oronary arteries A low dose non-enhaned MSCT san an be used for alium soring The latest MSCT sanners allow reliable detetion of signifiant obstrutive lesions in native oronary arteries in seleted patients Improvements in MSCT tehnology are required for reliable evaluation of less seleted patient groups The linial value of MSCT oronary angiography needs to be established in multi-entre studies, evaluating populations with differing prevalene and presentations of oronary atheroslerosis MSCT is non-invasive evaluation of the oronary arteries and the provision of funtional information is a bonus. Other appliations of ardia MSCT The use of a higher tube urrent and edge enhaning reonstrution filters allows assessment of stent pateny (fig 8). However, beam hardening artefats related to high density stent materials hamper reliable visualisation of the oronary lumen in stents and do not permit aurate assessment of non-obstrutive intima hyperplasia. MSCT angiography is not restrited to native oronary arteries. It provides morphologi information about oronary veins and ardia hambers, whih an be useful for venous mapping or detetion of intraardia thrombi. This tehnique an also be used to evaluate venous or arterial bypass grafts (fig 9). Preliminary studies, using four row MSCT sanners, showed a high sensitivity and speifiity for the detetion of oluded venous grafts (97 100% and 98%, respetively). Diagnosti auray for the detetion of non-olusive Figure 9 This maximum intensity projetion image shows a patent arterial graft (left internal mammary artery, LIMA) inserted on an oluded left anterior desending artery (LAD). The anastomosis is learly visualised and antegrade filling of the distal part of the LAD (A) as well as retrograde filling of the mid part of the LAD (B) is shown. stenoses in venous grafts and evaluation of arterial grafts was suboptimal; this finding, in onjuntion with the fat that a signifiant perentage of bypass segments (up to 42% of arterial bypasses) were non-assessable limits urrent linial appliation. FUTURE ROLE OF MSCT CORONARY ANGIOGRAPHY Current 16 row MSCT sanners allow non-invasive evaluation of both the lumen and wall of the oronary artery. In the near future, MSCT oronary angiography might beome an alternative to diagnosti onventional angiography for the detetion of signifiant obstrutive lesions. Further studies are needed to determine the role of MSCT oronary angiography in various patient groups suh as asymptomati high risk individuals, asymptomati patients with known oronary artery disease, or in the evaluation of oronary obstrutions in patients with stable angina or aute oronary syndromes.... Authors affiliations N R Mollet*, P J de Feyter*, Department of Cardiology, Thoraxenter, Erasmus Medial Center, Rotterdam, The Netherlands F Cademartiri, Department of Radiology, Erasmus Medial Center *Also Department of Radiology, Erasmus Medial Center REFERENCES 1 Nieman K, Oudkerk M, Rensing BJ, et al. Coronary angiography with multislie omputed tomography. Lanet 2001;357: First study omparing the results of four row multislie CT oronary angiography with that of onventional angiography for the detetion of signifiant obstrutive stenoses. 2 Ahenbah S, Giesler T, Ropers D, et al. 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