1

ABSTRACT
INTRODUCTION:
Coronary artery disease (CAD) is the leading cause of death in adults in many western countries, and nowadays in Asian countries also. Atherosclerotic coronary artery calcifications are most frequently found as calcium (Ca) lumps in advanced atherosclerotic lesions (AHA: American Heart Association) plaque type Vb), but may occur as small deposits of calcium in earlier lesions. Quantifying the amount of coronary artery calcium with unenhanced CT calcium score has been shown to be a reliable noninvasive technique for screening risk of future cardiac events and can be quantified by using the Agatston score.

OBJECTIVES:
The objective of the study was to: To determine the percentage of patients who show agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis

STUDY DESIGN:
Cross sectional survey

SETTING
Radiology Department, Shaukat Khanum Memorial Cancer

Hospital and Research Centre, Lahore. Heart and Body Scan Centre, Lahore.

DURATION OF STUDY:
Six months after approval of synopsis (From JULY 22,2011 to JAN,22,2012)

RESULTS:

Majority of the patients were recorded between 46-55 years i.e. 36%(n=36), 27%(n=27) were between 36-45 years, 17%(n=17) were recorded between 25-35 years and 56-65 years of age, only 3%(n=3) were recorded between 66-75 years of age, mean and SD was 38.65+5.72, 72%(n=72) were male and 28%(n=28) females, frequency of agreement of low CACS and insignificant coronary stenosis was

calculated resulting in agreement with 78%(n=78) while 22%(n=22) had no agreement, kappa test shows 0.0005 value. Relation between CACS and significant stenosis in positive patients was 50%(n=11) with 0 CACS, 27.27%(n=6) was between 1-30 CACS, 13.63%(n=3) between 31-60 CACS, 4.55%(n=1) between 61-90 and 91-99 CACS.

CONCLUSION:
o The result of the study reveals that percentage of patients

who show agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis was much higher.However, a significant number of patients does show disagreement questioning the value of calcium score as gate-keeper

KEY WORDS:
o Coronary artery calcium score, Coronary CT Angiography,

significant stenosis

INTRODUCTION
Coronary Artery Disease (CAD) is a major cause of morbidity and mortality all over the world including Pakistan and is usually attributable to atherosclerotic obstruction.1 Coronary Artery Calcium (CAC) is

characteristic of atherosclerotic disease2 and is associated with future cardiac events3 and coronary luminal stenosis.4 The amount of coronary calcium correlates moderately closely to overall atherosclerotic plaque burden.4,5 On the other hand, not every plaque is calcified, particularly in younger patients below forty. Multidetector Coronary Computed Tomography (MDCCT) has emerged as a promising minimally invasive method for detection and exclusion of obstruction in coronary artery disease. MDCCT both detects CAC and allows direct assessment of stenosis with high degree of accuracy.6,7 In several trials, absence of coronary artery calcium ruled out the presence of significant CAD with high predictive value.8 CACS <100 are thought to be associated without obstruction on cardiac

catheterization.6 It however, has been challenged in few studies.9 Shabestari et al10 reported that 50 percent of their patients having calcium

score less than 100, had significant stenosis i.e. agreement between calcium score <100 and CT Angiography is 50%. The current study is designed to evaluate the level of agreement between severity of stenosis on CT Angiography and calcium burden as measured by dedicated CT protocols for calcium scoring, comparing their results. The relevant prognostic information obtained may be useful in initiating, modulating or intensification of appropriate treatment and diagnostic strategies.

REVIEW OF LITERATURE
CORONARY ARTERY DISEASE
Coronary artery disease (CAD) remains the most common cause of death in the United States and presents a common diagnostic dilemma for primary care physicians. In the past two decades, investigators have identied trends toward both a reduction in the incidence of myocardial infarction and in the case fatality rate.11 These observations provide concrete evidence of improvements in both the primary and secondary prevention of CAD. There have been advances in the understanding of the pathophysiology of CAD and the acute coronary syndrome, the types of treatments for them, and the availability of such treatments. Commensurate with these advances has been the development of new testing modalities and strategies for both screening and diagnosis of CAD.

EPIDEMIOLOGY OF CORONARY ATHEROSCLEROSIS

In many patients, unheralded myocardial infarction associated with a mortality of approximately 20% is the first manifestation of coronary artery disease (CAD). The risk of an event strongly depends on risk

factors, such as hypertension, hypercholesterolemia, smoking, family history, age, and gender. Based of these risk factors, the Framingham12 and Prospective Cardiovascular Munster Study (PROCAM)13 algorithms provide an estimation of the midterm (10-year) risk for an individual to experience a cardiac event. According to international guidelines, subjects who have a midterm risk of less than 10% are considered to be at low risk and usually do not require any specific therapy. Patients who have a midterm risk of more than 20% are considered to be at high risk and therefore may be considered as subjects with a CAD equivalent. Similar to patients who have established CAD, these asymptomatic subjects may require intensive therapy such as lifestyle changes and lifetime medical treatment. Approximately 40% of the population is considered to have a moderate midterm risk of 10% to 20%. Any of the stratification schemes suffers from a lack of accuracy to correctly determine the risk, and uncertainty exists as to how to treat subjects who have been identified to be at intermediate risk. Other tools providing information about the necessity to either reassure or to treat these subjects are warranted.

Currently, the assessment of the atherosclerotic plaque burden by CT may be able provide valid information for this cohort.14

PATHOPHYSIOLOGY OF CORONARY ARTERY CALCIUM

The process of vascular calcification is almost exclusively related to atherosclerosis, barring rare cases of hypervitaminosis D, Monckeberg sclerosis, and infantile calcifications. The calcification of the

atherosclerotic lesion begins at the stage of fatty streak formation as early as in the second decade of life.15 The quantity of coronary artery calcium correlates with the burden of atherosclerosis in different individuals, and to some extent also with different segments of the coronary artery tree in the same individual.15 In theory, as a lesion becomes more uniformly calcified its vulnerability to rupture decreases.16 It may seem paradoxic that coronary calcium exerts a protective influence when numerous studies have shown worsened prognosis and an increased prevalence of cardiovascular disease with increasing coronary calcium. This contradiction may simply indicate that while the calcified plaque itself may not be the cause of an acute event, the extent of coronary arterial calcium is a marker of

atherosclerosis and signifies higher burden of atherosclerosis in the coronary vasculature. DISTRIBUTION OF CORONARY ARTERY CALCIUM The distribution of CAC occurs closer to the origin of the coronary artery and can progress even as the atherosclerotic plaque itself regresses. Mautner and colleagues17 showed that most calcific deposits were present within 5 cm of the aortic ostium of the right coronary artery (RCA) and within 3 cm of the left anterior descending artery (LAD) and left circumflex artery (LCxA) origins. The LAD (86%) was the most heavily calcified coronary artery, followed by RCA (62%) and LCxA (60%).18 CORONARY CALCIUM SCORING Coronary calcium scoring (CS) using MSCT has been validated as a useful imaging tool for risk stratification and reclassification of the risk of CAD.19 Coronary atherosclerotic lesions often contain calcified

components which used to be accurately measured using electron beam CT, but are currently being replaced with MSCT by the Agatston scoring method.20,21 Recent guidelines from the American Heart Association reviewed the scientific data for cardiac MSCT imaging of CAD and atherosclerosis

10

in symptomatic and asymptomatic patients, and approved screening using CS as a method to reclassify risk in patients with an intermediate risk based on traditional scores such as the Framingham and Procam algorithms. 22 CS is usually performed as a screening method with the use of low radiation dose scanning techniques. The purpose of the scan is to detect and calculate the calcium density, volume or mass. The total coronary calcium is used as a way of prognosticating and stratifying the risk of CAD. The rationale behind it is that coronary artery calcification is part of the atherosclerotic degeneration of the arterial vessel wall, and coronary atherosclerosis is the only disease associated with calcium in the coronary arteries. Thus, measurement of the amount of calcium allows for an accurate estimation of the amount of coronary atherosclerosis and therefore, the risk of CAD. The total CS is calculated by adding up the volume of calcium in all coronary arteries by a weighting factor, dependent on the density of each calcified plaque. CS is regarded as a good predictor of cardiac events and adds incremental prognostic value to risk factors in intermediate risk populations. Patients with a normal or zero CS fall into the lowest risk category, and are thus associated with a low risk of cardiac events, or

11

considered to be clinically absent of any major atherosclerosis. The predictive value of CS is further supported by a recent study with the aim of identifying the incidence and predictors of conversion for a normal to abnormal coronary artery calcium over a period of five years.23 In a prospective study, Min et al provided insight into the warranty period relative to a normal CS scan over time. They concluded that the rate of conversion to an abnormal CS scan was non-linear and occurred at a low frequency before four years of follow-up. Their data suggests that repeat CS should not be performed for a minimum of four years in individuals with a normal CS of zero.23 Although most data regarding coronary calcium were derived by use of electron beam CT, multidetector CT has supplanted electron beam scanning. Coronary calcium is detected by a standardized protocol that should result in acceptably low levels of radiation exposure (1 to 2 mSv) and potentially lower levels with the evolution of lower 100-kVp imaging protocols.24 CT quantification methods primarily involve the measurement of the area and density of all foci of calcification (defined by a Hounsfield unit threshold of 130 units) (Fig. 1). The sum of the area and density

12

weightings across the coronary arteries is the unitless calcium score originally defined by Agatston and colleagues. Other quantification methods are available, including a calcium volume determination and mass score. Although specific advantages may include increased reproducibility of these techniques, the clinical data available for coronary calcium quantification are derived by the area-density scoring method and are the clinical standard. Calcium score reproducibility is modest, with interscan variability of 10% to 20%, being more reproducible at low heart rates and for higher calcium scores.

13

Fig. No. 1 Example of coronary artery calcium scoring in which calcified foci are identified within the left anterior descending (orange) and left circumflex (pink outlined in blue) coronary arteries. The regions area (R-Ar) and its average density in Hounsfield units (R-Av) are displayed and used in the area-density calcium scoring calculation

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Coronary calcium presence and extent are dependent on age, gender, ethnicity, and standard cardiac risk factors. Calcium scores are higher for age and gender among whites. It is well established that the detection of coronary calcium indicates an increased risk of incident CHD above that predicted by standard risk factors, from 2-fold for scores of up to 100 and increasing to 11-fold for scores above 1000. 25 Recent data indicate that the spatial distribution of coronary calcium may provide further risk stratification beyond the total calcium score. A coronary calcium coverage score was devised from the Multi-Ethnic Study of Atherosclerosis and showed greater predictive accuracy than the area density scoring system for future CHD events.26 This finding is in line with other observations that multivessel coronary calcium,27 the number of calcified lesions,28 and diffuse spotty pattern (small foci <3 mm)
29

are associated with a higher clinical risk

(Fig. 2). Conversely, data from 13 studies involving 75,000 patients during 4 years show that a calcium score of 0 is associated with a very high event-free probability (99.9% per year). Based on the consistency of studies showing independent prediction of CHD risk, appropriate use criteria support the use of coronary

15

calcium scanning as a risk stratification tool when an initial evaluation of clinical risk with risk prediction tools indicates an intermediate level of CHD risk (10% to 20% during 10 years) or in the setting of low-risk patients with a family history of premature CHD. Areas of uncertainty include patients with low to intermediate risk (6% to 10% risk), particularly among women and younger men in whom relative risk and lifetime CHD risk may be unacceptably increased. However, community-based screening cohorts have shown up to threefold greater use of aspirin, statin cholesterol medications, and other cardiovascular risk reduction interventions in the setting of coronary calcium. Beyond recommendations for the provision of and adherence to risk-reducing therapies, an abnormal coronary calcium scan in an asymptomatic patient can be associated with an increased likelihood of silent ischemia by stress myocardial perfusion imaging, and the absence of myocardial ischemia may moderate the risk associated with a very high calcium score. 30 However, such testing is not recommended without specific clinical trial evidence showing benefit for the patient from such an approach. The use of serial testing to define progression of coronary calcium has been

16

suggested as a method of further defining evolving CHD risk. Once it is present, coronary calcium tends to progress at a rate of approximately 20%/year.31 Middle-aged individuals with a calcium score of 0 have an approximately 5%/year conversion rate from a zero to non-zero score. Although observational data from referred populations suggest that individuals with clinically significant coronary calcium progression (>15%/year) may have substantially higher clinical event risk for a given calcium score, 32 data show that risk-reducing interventions do not retard coronary calcium progression, indicating that calcium progression is a complex phenomenon likely to involve a mixture of both plaque healing and plaque progression. Because of concerns about radiation exposure, intertest variability, and undefined management implications, present guidelines do not support the performance of serial calcium testing.

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Fig. No. 2 Distributions of coronary calcium. A, No detectable coronary calcium. B, Coronary calcium in all three epicardial coronary arteries including (clockwise) the right coronary artery (arrow) and the left anterior descending and left circumflex coronary arteries. C, A spotty or diffuse pattern of coronary calcium with multiple small (<3 mm) foci of coronary calcium. D, A large calcified lesion in the left anterior descending coronary artery

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AGATSON CALCIUM SCORING

Calcium Score
0-1

Int erpretation
No identifiable atherosclerotic plaque; very low cardiovascular disease; less than 5% chance of presence of coronary artery disease A negative examination Minimal plaque burden Significant coronary artery disease very unlikely Mild plaque burden Likely mild or minimal coronary stenosis Moderate plaque burden Moderate nonobstructive coronary artery disease highly likely Extensive plaque burden High likelihood of at least one significant coronary stenosis (>50% diameter)

1 - 10 11 - 100 101 400

Over 400

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INDICATIONS OF CORONARY CTA A 2008 scientific statement from the American Heart Association (AHA)33 indicates that the potential benefit of noninvasive coronary angiography is likely to be the greatest for symptomatic patients who are at intermediate risk for coronary artery disease (CAD) after initial risk stratification, including patients with equivocal stress tests. CCTA is recommended over coronary magnetic resonance angiography (MRA) because of superior diagnostic accuracy. Neither coronary CTA nor MRA is recommended to screen for CAD in patients who have no signs or symptoms suggestive of CAD. Appropriateness criteria were published in 2006 from 8 specialty societies, including the American College of Cardiology and American College of Radiology.34 The following indications were rated as

appropriate for coronary CT angiography:

Evaluation of chest pain syndrome in patients with intermediate pretest probability of CAD and uninterpretable electrocardiogram (ECG) or inability to exercise

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Evaluation of chest pain syndrome in patients with uninterpretable or equivocal stress test (exercise, perfusion, or stress

echocardiogram)

Evaluation of acute chest pain in patients with intermediate pretest probability of CAD and no ECG changes and serial enzymes negative

Evaluation of coronary arteries in patients with new-onset heart failure to assess etiology

Evaluation of suspected coronary anomalies Little data exist as to the cost-effectiveness of CCTA. A 2008 health technology assessment35 suggested that CCTA may be a cost-effective alternative to myocardial perfusion scintigraphy and thought to be a potentially cost-effective method of avoiding unnecessary conventional coronary angiography.

Accuracy The majority of studies (with the exception of the Coronary Evaluation Using Multidetector Spiral Computed Tomography

Angiography using 64 Detectors [CORE 64] study) indicate that a negative CCTA can effectively rule out obstructive coronary artery disease. In a 2008 meta-analysis,35 64-slice CCTA had a sensitivity of

21

99% and negative predictive value (NPV) of 100% for patient-based detection of significant CAD. However the specificity has been lower than the sensitivity in most studies, and false-positive results are possible, particularly in patients with high calcium scores. In the ACCURACY prospective multicenter trial of patients with chest pain without known CAD and intermediate disease prevalence, 64slice CCTA had a patient-based sensitivity of 94% and a specificity of 83% in detecting stenosis of 70% or greater (comparable values were seen at a 50% stenosis level). Patients with high calcium scores were not excluded from the study. Calcium scores greater than 400 reduced specificity significantly. The NPV of CCTA was 99%.36 In the CORE 64 prospective multicenter trial of patients with suspected symptomatic CAD referred for conventional coronary

angiography, 64-slice CCTA had a patientbased sensitivity of 85% and specificity of 90% (excluding patients with a calcium score greater than 600) for detecting stenoses 50% or greater. However, the NPV of 83% in this study was lower than in other studies.37 In a 2008 meta-analysis, the sensitivity was highest in the left main artery and lowest (85%) in the circumflex artery.35

22

The ACCURACY trial suggested that, compared with other noninvasive modalities such as stress echocardiography and stress nuclear testing, CCTA has comparable specificity but superior sensitivity and NPV.36

Understanding the Physics of Cardiac Imaging

To better demonstrate and understand the necessity for high temporal resolution in cardiac imaging, Fig. No.3 shows how the length (in time) of the diastolic phase changes with heart rates. The least amount of cardiac motion is observed during the diastolic phase; however, the diastolic phase narrows with increasing heart rate. With rapid heart rates, the diastolic phase narrows to such an extent that the temporal resolution needed to image such subjects is less than 100 msec. The desired temporal resolution for motion-free cardiac imaging is 250 msec for heart rates up to 70 beats per minute and up to 150 msec for heart rates greater than 100 beats per minute. Ideally, motion-free imaging for all phases requires temporal resolution to be around 50 msec. The standard of reference for comparing the temporal resolution obtained with multiple-row detector CT is fluoroscopy, wherein the heart motion is frozen during dynamic imaging to a few milliseconds (110 msec).

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Therefore, the demand for high temporal resolution implies decreased scan time required to obtain data needed for image reconstruction and is usually expressed in milliseconds. The demand for high spatial resolution that enables the visualization of various coronary segments (such as the right coronary artery, left anterior descending artery, and circumflex artery) that run in all directions around the heart with decreasing diameter is high. These coronary segments range from a few millimeters in diameter (at the apex of the aorta) and decrease to a few submillimeters in diameter as they traverse away from the aorta in all directions. The need to image such small coronary segments requires small voxels, and this is key to cardiac imaging with multiple-row detector CT. Spatial resolution is generally expressed in line pairs per centimeter or line pairs per millimeter. Like temporal resolution, the standard of reference for comparing spatial resolution is the resolution obtained during fluoroscopy. However, one of the major goals of multiple-row detector CT technology development has been to obtain similar spatial resolution in all directions, also expressed as isotropic spatial resolution.38 In addition, a sufficient contrast-to-noise ratio is required to resolve small and low-contrast structures such as plaques. In CT, low-contrast

24

resolution is typically excellent. However, it can degrade with the increasing number of CT detectors in the z direction due to increased scattered radiation that can reach detectors in the z direction. It is important to achieve adequate low-contrast resolution with minimum radiation exposure. The need to keep radiation dose as low as reasonably possible is essential for any imaging modality that uses ionizing radiation. Overall, cardiac imaging is a very demanding application for multiple-row detector CT. Temporal, spatial, and contrast resolution must all be optimized with an emphasis on minimizing radiation exposure during cardiac CT imaging.

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Figure 3. Diagram shows the range of diastolic regions for varying heart rates. The desired temporal resolution for cardiac CT is approximately 250 msec for average heart rates of less than 70 beats per minute; for higher heart rates, the desired temporal resolution is approximately 100 msec.

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Temporal Resolution
There are a number of factors that influence the temporal resolution achieved with multiple-row detector CT scanners. Among them, the key factors are the gantry rotation time, acquisition mode, type of image reconstruction, and pitch. Gantry Rotation Time Gantry rotation time is defined as the amount of time required to complete one full rotation (360) of the x-ray tube and detector around the subject. The advances in technology have considerably decreased the gantry rotation time to as low as 330370 msec. The optimal temporal resolution during cardiac imaging is limited by the gantry rotation time. The faster the gantry rotation, the greater the temporal resolution achieved. However, with increasing gantry rotation speed, there is also an increase in the stresses on the gantry structure, since rapid movement of heavy mechanical components inside the CT gantry results in higher G forces, making it harder to achieve a further reduction in gantry rotation time. In fact, even a small incremental gain in the gantry rotation time requires great effort in the engineering design.

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In the past, the minimum rotation time was as high as 2 seconds; in the past few years, gantry rotation time has decreased steadily to less than 400 msec. As the currently available gantry rotation time is not in the desired range for obtaining reasonable temporal resolution, various methods have been developed to compensate, such as different types of scan acquisitions or image reconstructions to further improve temporal resolution. Acquisition Mode For imaging the rapidly moving heart, projection data must be acquired as fast as possible in order to freeze the heart motion. This is achieved in multiple-row detector CT either by prospective ECG triggering or by retrospective ECG gating.39 Prospective ECG Triggering: This is similar to the conventional CT step and shoot method. The patients cardiac functions are monitored through ECG signals continuously during the scan. The CT technologist sets up the subject with ECG monitors and starts the scan. Instructions are built into the protocol to start the x-rays at a desired distance from the R-R peak, for example at 60% or 70% of the R-R interval. The scanner, in congruence with the patients ECG pulse, starts the scan at the preset point in the R-R

28

internal period (Fig. No. 4). The projection data are acquired for only part of the complete gantry rotation (ie, a partial scan). Hence, the scan acquisition time depends on the gantry rotation time. The best temporal resolution that can be achieved in the partial scan mode of acquisition is slightly greater than half of the gantry rotation time. Once the desired data are acquired, the table is translated to the next bed position and, after a suitable and steady heart rate is achieved, the scanner acquires more projections. This cycle repeats until the entire scan length is covered, typically 1215 cm (depending on the size of the heart). With multiple-row detector CT, the increasing number of detectors in the z direction allows a larger volume of the heart to be covered per gantry rotation. For example, using a multiple-row detector CT scanner capable of obtaining 16 axial sections (16 rows of detectors with 16 data acquisition system channels in the z direction) and with each detector width of 0.625 mm, one can scan a 10-mm (16 0.625-mm) length per gantry rotation. Similarly, with a 64-section multiple-row detector CT scanner (64 rows of detectors with 64 data acquisition system channels) and each detector 0.625 mm wide, one can scan about 40 mm per gantry rotation. Typically, the cardiac region ranges from 120 to 150 mm, which

29

can be covered in three to four gantry rotations with a 64-row detector CT scanner. This has a major advantage in terms of the decreased time required for breath holding to minimize motion artifacts (critical when scanning sick patients). One of the advantages of the prospective triggering approach is reduced radiation exposure, because the projection data are acquired for short periods and not throughout the heart cycle. Temporal resolution with this type of acquisition can range from 200 to 250 msec. Prospective triggering is the mode of data acquisition used for calcium scoring studies, since calcium scoring analysis is typically performed in axial scan mode. The scan technique such as tube current (milliamperes) for a calcium scoring protocol can be quite low, yielding low radiation dose, since calcium has a high CT number and is easily visible even with a noisier background. Also, each data set is obtained during the most optimal ECG signal to reduce motion artifacts.

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Figure 4. During the prospective ECG-triggered scan mode, the patients ECG is continuously monitored but the x-rays are turned on at predetermined R-R intervals to acquire sufficient scan data for image reconstruction. The table is then moved to the next location for further data acquisition. These types of scans are always sequential and not helical and result in a lower patient dose because the x-rays are on for a limited period. Calcium scoring scans are typically performed in this scan mode.

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Fig. No. 5 During the retrospective ECG-gated scan mode, the patients ECG is continuously monitored and the patient table moves through the gantry. The x-rays are on continuously, and the scan data are collected throughout the heart cycle. Retrospectively, projection data from select points within the R-R interval are selected for image reconstruction. Radiation dose is higher in this type of scan mode compared with that in the prospective triggering mode. Pos = position.

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Retrospective ECG Gating: Retrospective gating is the main choice of data acquisition in cardiac coronary artery imaging with multiple-row detector CT. In this mode, the subjects ECG signals are monitored continuously and the CT scan is acquired continuously (simultaneously) in helical mode (Fig. 6). Both the scan projection data and the ECG signals are recorded. The information about the subjects heart cycle is then used during image reconstruction, which is performed retrospectively, hence the

name retrospective gating. The image reconstruction is performed either with data corresponding to partial scan data or with segmented reconstruction. In segmented reconstruction, data from different parts of the heart cycle are chosen, so that the sum of the segments equates to the minimal partial scan data required for image reconstruction. This results in further improvements in temporal resolution. Temporal resolution with this type of acquisition can range from 80 to 250 msec. The disadvantage of the retrospective gating mode of acquisition is the increased radiation dose, because the data are acquired throughout the heart cycle, even though partial data are actually used in the final image reconstruction. Also, since this scan is performed helically, the

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tissue overlap specified by the pitch factor is quite low, indicating excessive tissue overlap during scanning, which also increases radiation dose to the patients. The need for low pitch values or excessive overlap is determined by the need to have minimal data gaps in the scan projection data required for image reconstruction. The need for low pitch values is discussed in detail in the section on pitch.

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Fig. No. 6 Effect of temporal resolution on reconstructed images from the same patient. (a) Partial scan reconstruction with temporal resolution of approximately 250 msec. (b) Multiplesegment reconstruction (two segments) yields a temporal resolution of approximately 105 msec. The stair-step artifacts are less visible and the structures in the sagittal plane have a smooth edge compared with the appearance of partial scan reconstruction.

35

Reconstruction Method Cardiac data acquired with either prospective ECG triggering or retrospective ECG gating are used in reconstructing images. High temporal resolution images are obtained by reconstructing the data either with partial scan reconstruction or with multiple-segment reconstruction. Spatial Resolution There are a number of factors that influence the spatial resolution achieved with multiple-row detector CT scanners. Among them are the detector size in the longitudinal direction, reconstruction algorithms, and patient motion. Effect of Detector Size The effect of detector size in the z direction or out-of-plane spatial resolution is very significant and has become one of the driving forces in the advancement of multiple-row detector CT technology. Also, larger volume coverage in combination with a larger number of thin images requires more detectors in the z direction, which is the hallmark of technological advance in multiple-row detector CT. On the other hand, scan plane or axial spatial resolution has been very high from the beginning and is dependent on the scan field of view (SFOV) and image

36

reconstruction matrix. Axial pixel size is the ratio of SFOV to image matrix; for example, for a conventional 512 512 matrix, the transverse pixel size for a 25-cm SFOV is 0.49 mm. On the other hand, the longitudinal or z-axis resolution mainly depends on the image thickness. The z-axis spatial resolution (image thickness) ranges from 1 to 10 mm in conventional (nonhelical) and in helical single-row detector CT. With multiple-row detector CT, the z-axis detector size is further reduced to submillimeter size. Initially, with the introduction of multiple-row detector CT technology, the thinnest detector size was 0.5 mm and there were only two such detectors. However, within a few years, the technology improved to provide 16 of these thin detectors, ranging from 0.625 to 0.5 mm. With 64-section multiple-row detector CT scanners, the detector array designs are 64 thin detectors (0.625 mm) are currently available, resulting in z-axis coverage of up to 40 mm per gantry rotation.40 Cardiac CT images can be comparable in delineating details of the coronary vessels to the cardiac images obtained with fluoroscopy.41 Reconstruction Interval The reconstruction interval defines the degree of overlap between reconstructed axial images. It is independent of x-ray beam collimation or

37

image thickness and has no effect on scan time or patient exposure. The reason for decreased reconstruction interval (or increased overlap) is to improve z-axis resolution, especially for three-dimensional (3D) and multiplanar reformation (MPR) images. If the reader is making a diagnosis based on only axial images, reconstruction interval is not an issue. But frequently, physicians are also reading MPR and 3D images; this is especially true for cardiac CT. Pitch The concept of pitch was introduced with the advent of spiral CT and is defined as the ratio of table increment per gantry rotation to the total x-ray beam width.42-43. Pitch values less than 1 imply overlapping of the x-ray beam and higher patient dose; pitch values greater than 1 imply a gapped x-ray beam and reduced patient dose.42 Cardiac imaging demands low pitch values because higher pitch values result in data gaps, which are detrimental to image reconstruction. Also, low pitch values help minimize motion artifacts, and certain reconstruction algorithms work best at certain pitch values, which are lower than 0.5 in cardiac imaging. Typical multiple-row detector CT pitch factors used for cardiac imaging range from 0.2 to 0.4.

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The pitch factor plays a significant role in improving both the temporal and spatial resolution but at the same time has a dramatic effect on the overall radiation dose delivered during a cardiac CT examination. Because radiation dose is inversely proportional to the pitch, the low pitch values characteristic of cardiac CT protocols substantially increase radiation dose to patients undergoing cardiac imaging with multiple-row detector CT. In cardiac CT imaging, the need for high spatial and temporal resolution in turn requires the pitch values to be as low as 0.20.4. This results in a radiation beam overlap of nearly 80%60%, respectively, and an increase in radiation dose of up to a factor of five times compared to a pitch of 1. Hence, proper choice and optimization of pitch factor is critical in cardiac imaging. In fact, the demand for reducing radiation dose and faster scans is driving the technology to introduce either an even higher number of thin detectors in the z direction (256 rows) or flat panel technology so that the entire cardiac area can be covered in a single gantry rotation without the necessity for tissue overlap (low pitch values).

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RECENT TECHNOLOGY
The 2 major recent advancements in multidetector CT technology are dual-source 64-slice CT and single-source 256- and 320-slice CT. Both of these techniques offer the possibility of reduced radiation dose compared with single-source 64-slice CT. Dual-source CT allows coronary CT angiography (CCTA) to be performed at higher heart rates. Currently, there is little published literature on 256- or 320-slice CCTA.

Dual-source CT
The primary advantage of dual-source CT is greater temporal resolution. A dual-source CT contains 2 tube/detector sets, arranged at 90 angles to each other. In CCTA, the data are typically reconstructed from a 180 rotation (partial scan reconstruction) to maximize temporal resolution. If the gantry rotation time is 330 msec, a single-source CT performing CCTA with partial scan reconstruction has a temporal resolution of 165 msec. With 2 tubes, only a quarter rotation is needed for data collection, and the temporal resolution is 83 msec. The higher temporal resolution of dual-source CT allows CCTA to be performed at higher heart rates without the use of beta blockers.

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Although the tube current is doubled with 2 tubes, the scan time is halved, and the tube current-time product (mAs) is unchanged as compared with single-source CT.44 However, radiation dose can usually be lower than that with single-source CT. Because of higher temporal resolution, the pitch can be increased at higher heart rates, which will decrease dose (see Radiation Dose). In addition, other dose-reduction techniques, such as ECG-dependent tube current modulation and prospectively triggered sequential scanning (see Radiation Dose), can be optimally used with the increased temporal resolution of a dual-source scanner. In addition, simultaneous data acquisition can be performed with the tubes operating at different voltages (80 kV and 140 kV).44 This offers the possibility of improved tissue differentiation, but it is unclear what impact this will have on CCTA.

256-slice CT and 320-slice CT

The primary advantage of 256- and 320-slice CT is the increased craniocaudal coverage. The 256- and 320-slice CT scanners have a craniocaudal coverage of approximately 12 and 16 cm, respectively. This potentially allows the heart to be scanned in one tube rotation and one heartbeat, without table movement. This technique is ideal for the

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prospectively triggered sequential scan technique,45 which substantially reduces radiation dose compared with retrospectively gated helical techniques. If the prospectively triggered technique is used, heart rate control is useful, as a slower heart rate allows a narrower phase window to be used,46 further decreasing radiation dose. Another advantage is that if the data can be acquired in one heartbeat, phase misregistration artifacts arising from irregular heartbeats are not an issue

Radiation Dose
Attention has been drawn to the risk of cancer from computed tomography. In these discussions, coronary CT angiography (CCTA) is often cited for its high radiation dose. For example, in a review by SmithBindman et al,47 it was estimated that 1 in 270 women, and 1 in 600 men, who underwent CCTA at age 40 would develop cancer from that scan. However, these figures do not take into account recent technological developments that can greatly decrease the radiation dose from CCTA. There are several things that are important to note. First, the radiation dose from CCTA is highly variable and is largely dependent upon the specific equipment and techniques used. For example, one study suggests that use of a prospectively triggered technique reduced

42

the risk of cancer by 87%, compared to a retrospectively gated technique.48 Therefore, it is very important for the practitioner to understand ways of reducing the radiation dose to the patient. Other examinations that might be used instead of CCTA, such as cardiac nuclear medicine studies, have relatively high radiation doses. In addition, noninvasive examinations such as CCTA have the potential to reduce the use of coronary catheterization, which is invasive and involves relatively high radiation doses. In a study of 398,978 patients who underwent elective coronary catherization,49 only 37.6% had obstructive coronary disease. Examinations that do not utilize ionizing radiation, such as stress echocardiography, could also be considered. A decision analytic model suggests that stress echocardiography followed by CCTA if needed is most appropriate for evaluation of patients with a pretest probability for coronary artery disease of less than 20%, while CCTA alone is more appropriate for intermediate-risk patients.50 Radiation doses for CCTA studies, if performed with retrospective gating in helical mode, are typically relatively high. Radiation doses are high because data are acquired throughout the cardiac cycle, and with the fast gantry rotation required for high temporal resolution in CCTA, a

43

low pitch (table travel per gantry rotation/collimation) is required in order to avoid gaps in the data. If data are acquired throughout the cardiac cycle, the table should not move more than the beam width during one cardiac cycle. In particular, slow movement is required with fast gantry rotation; otherwise, all phases of the heart at a specific location will not be seen by the detector. As pitch is inversely related to radiation dose, a low pitch results in a high radiation dose.51 The reported radiation doses for CCTA vary depending on the specific technology and techniques employed. With retrospectively gated single-source 64-slice CT, the reported effective radiation doses have ranged from 9.5 to 21.4 mSv.52 However, using many of the technologies and techniques discussed below, it is possible to lower the dose to less than 5 mSv, and doses less than 1 mSv are currently possible in some patients. For comparison, the average yearly background radiation dose is around 3 mSv, and a chest x-ray dose is 0.05 mSv. 33 Depending on the technique, CCTA may have a higher or lower effective dose than conventional coronary angiography (3.1-9.4 mSv). However, the dose from a cardiac single-photon emission computed tomography (SPECT) scan performed using technetium-99m is typically high (8 -17.5 mSv).

44

A variety of methods exist for decreasing radiation dose from cardiac CT.53 In general, radiation dose from a CT scan can be reduced by reducing tube current, reducing tube voltage, or increasing pitch.
ECG-dependent tube current modulation

Anatomic-based tube current modulation can be performed where the tube current is adjusted for patient size and shape. However, a more effective method of dose reduction is ECG-dependent tube current modulation. As the best image quality for CCTA is typically obtained at the specific phase of the R-R interval (usually mid- to end-diastole), the tube current (and thus dose) can be reduced in the phases where image quality is not optimal.53 This is the most common method to reduce radiation dose. The primary disadvantage of this technique is that optimal functional imaging is not possible because of poor image quality in the portions of the cardiac cycle where lower tube current was used. The use of ECG-dependent dose modulation can result in a 20-50% decrease in radiation dose.52 This technique can be optimally used with dual-source CT, as the time requiring the highest tube current is shorter. Slow and steady heart rates are necessary for effective ECGdependent dose modulation. At high heart rates, the period of reduced tube output (diastolic duration) becomes shorter relative to the cardiac

45

cycle. With irregular heart rates, the optimal time point in the cardiac cycle to apply the full tube current is less predictable.
Reduced tube voltage

Reducing the tube voltage (from 120 kV to 100 or 80 kV) will reduce the radiation dose. Another advantage is that opacification of the blood vessels may increase at lower kV because of an increase in the photoelectric effect.52 The primary disadvantage is increased image noise. As image noise increases with patient weight, Hausleiter recommends reducing the kV to 100 in patients weighing less than 85-90 kg or with a body mass index less than 30 k/m2.53

Increased pitch
With dual-source scanners, the pitch can be increased at high heart rates to reduce radiation dose. Increasing the pitch will decrease the radiation dose, as the patient is exposed to radiation for a shorter period of time. The pitch can be increased at higher heart rates, because the time necessary to collect data throughout the cardiac cycle is decreased when the R-R interval is shorter. However, single-source scanners typically do not allow pitch to be increased at high heart rates. Single-source scanners usually need to utilize multisegment

46

reconstruction to increase temporal resolution at high heart rates, and multisegment reconstruction requires a low pitch. In this technique, the data required for image reconstruction are selected from multiple sequential heart cycles. This technique requires retrospective gating and a regular heart rate.54 For data from several cardiac cycles to be used for image reconstruction, the same position has to be covered by the detector during consecutive cardiac cycles. Thus, the pitch must be lowered, which will increase radiation dose. Multisegment reconstruction is effective in improving temporal resolution only at specific heart rates (the heart rate and gantry rotation time need to be desynchronized). A dual-source scanner has greater temporal resolution, and multisegment reconstruction is not necessary at high heart rates. This allows the pitch to be increased, and dose decreased, at higher heart rates.

Prospective ECG triggering and sequential scanning

Coronary CT angiography is usually performed with retrospective ECG gating, where scanning occurs throughout the cardiac cycle and simultaneously acquired ECG data are used retrospectively during image reconstruction. The acquisition of data throughout the cardiac cycle increases radiation dose. In addition, the scan is performed helically with

47

a low pitch, resulting in substantial tissue overlap during scanning, as well as increasing radiation dose.54 With prospective ECG triggering, the data are acquired at a specific point in the R-R interval. The scanner acquires data sequentially ("step and shoot") rather than in helical mode. Radiation dose is decreased, as data are not acquired throughout the cardiac cycle, and there is minimal tissue overlap with a sequential scan technique. This technique is standard for coronary artery calcium scoring but can be used to reduce radiation dose substantially during CCTA. Using a prospectively triggered sequential scan technique, Earls et al achieved an 83% reduction in dose as compared to the retrospective gated technique.52 The primary disadvantage of this technique is the lack of functional data. In addition, as data are only available from predefined phases of the R-R interval, reconstructions from additional phases to improve image quality are not possible. This technique is optimal in patients with a low and stable heart rate.55-56 High heart rates are not optimal for this technique, as reconstructions at multiple phases during the R-R cycle are sometimes

48

needed. With irregular heart rates, the acquisitions may be triggered at different points in the R-R interval. Prospective ECG triggering is optimal for 256- or 320-slice CT, where the entire heart could potentially be scanned in one tube rotation and one heartbeat. This obviates the issue of phase misregistration in patients with irregular heart rates. In one study, the median effective radiation dose of 320-slice CT was 4.2 mSv,57 which was lower than an 8.5 mSv median dose from catheter angiography performed in the same patients. Prospective ECG triggering is also well suited for use with dualsource CT, as the increased temporal resolution may allow the technique to be used at a higher heart rate threshold.55

Iterative reconstruction
Iterative reconstruction is a new CT reconstruction technique that reduces image noise, which then allows radiation dose to be decreased. This technique has not yet been extensively studied for CCTA, but in one report, a CCTA exam was performed using iterative reconstruction that had a dose of less than 1 mSv.58

49

How low can radiation dose be?

In one study, many of the techniques above were used in conjunction to lower radiation dose.59 In non-obese patients with a low and stable heart rate, dual-source CT with high pitch, lower tube voltage (100 kV), and prospective ECG triggering yielded studies with excellent image quality and doses consistently less than 1 mSv. For comparison, the average yearly background radiation dose is around 3 mSv.

Patient Preparation
At our institution, patients are instructed to avoid caffeine and smoking 12 hours prior to the procedure to avoid cardiac stimulation. They are also instructed to avoid eating solid food 4 hours before the study and to increase fluid intake prior to the study. Standard precautions with regard to contrast allergy history and renal function are taken.

Beta blockers
Beta-blocker administration is often helpful in cardiac CT to lower the heart rate and decrease motion artifact. The level to which the heart rate should be lowered depends on the temporal resolution of the scan. With single-source CT scanners, it is usually helpful to lower heart rate below 65 beats per minute (bpm). Dual-source CT scanners have higher

50

temporal resolution and can be performed at heart rates of up to 90 bpm, obviating the need for beta blockers in many cases. Cardiac MRI has higher temporal resolution than CT and can be performed without beta blockers. However, heart rate variability may be a more important determinant of image quality than absolute heart rate.60 Beta blockers are also helpful in patients with irregular heart rates, supraventricular tachycardias, and arrhythmias. For example, in atrial fibrillation, the negative chronotropic and dromotropic to effects can lengthen

diastole.61Possible

contraindications

beta-blocker

administration

include the following:61

Heart rate < 60 bpm Systolic blood pressure < 100 mm Hg Asthma or chronic obstructive pulmonary disease (COPD) on beta2 -agonist inhaler

Active bronchospasm Second- or third-degree atrioventricular block Sick sinus syndrome Decompensated cardiac failure

51

Pheochromocytoma (can be given in combination with an alpha blocker if the alpha blocker has been initiated beforehand)

Allergy to beta blockers Beta blockers should be used with caution in patients with

severe peripheral vascular disease and in patients taking calcium channel blockers. Metoprolol is a frequently used beta blocker for CCTA. The effects of an oral dose are seen within 1 hour after administration, with peak plasma concentration at 90 minutes.61 IV-push metoprolol has a peak effect 5-10 minutes after administration. There are many different protocols for metoprolol administration. An oral dose of 50-100 mg can be administered 60-90 minutes before the study.61 If this does not lower the heart rate to the desired level, 5-mg doses of IV metoprolol can be administered at 3- to 5-minute intervals, up to a total dose of 15-30 mg.61 Atenolol and esmolol have also been successfully used. Diltiazem or verapamil can also be used in patients in whom beta blockade is contraindicated, although these are less effective and result in more hypotension.62 These drugs can also be used in combination with a very low dose of metoprolol.

52

Nitroglycerin The administration of sublingual nitroglycerin dilates the coronary arteries and increases side branch visualization.63 Nitroglycerin is contraindicated in patients who are allergic to it and in patients who are taking phosphodiesterase inhibitors for erectile dysfunction. Patients should not have taken a phosphodiesterase inhibitor for at least 48 hours before the exam. The concomitant use of phosphodiesterase inhibitors can cause severe hypotension. Nitroglycerin can cause orthostatic hypotension and should be used with caution in patients who have low systolic blood pressure (eg, < 90 mm Hg) and who are volume depleted from diuretic therapy. Angina caused by hypertrophic cardiomyopathy can also be aggravated.

Artifacts
Stairstep artifacts

Stairstep artifacts are associated with heart rate variability.60 With irregular heart rates, phase misregistration can occur when data from different cardiac phases are used for reconstruction. A stairstep appearance results from the data reconstructed from different cardiac phases.

53

Beta blockers are helpful in reducing heart rate variability and avoiding stairstep artifacts. Manual ECG editing can also be helpful. With 256- and 320-slice CT, stairstep artifacts should not be seen if the heart is scanned in one heartbeat.

Coronary artery motion artifacts

Artifacts from motion of the coronary arteries result in image blurring. The right coronary artery is often most affected by motion artifact. General strategies to decrease motion artifact are to increase the time during the cardiac cycle where there is the least motion and to image as quickly as possible (increase temporal resolution). Motion can be minimized by reconstructing the data during a phase where there is minimal motion. Choosing the optimal phase of the R-R cycle to reconstruct the data is discussed in the image reconstruction section, below. Decreasing the heart rate with beta blockers has the advantages of decreasing the motion velocity of the coronary

arteries60 and increasing the relative and absolute duration of the diastolic rest period in the cardiac cycle. Temporal resolution can be increased in 2 ways. Dual-source CT scanners have substantially higher temporal resolution. With a single-

54

source scanner, one way to increase temporal resolution, typically used in patients with higher heart rates, is to use a multiple-segment reconstruction technique. In this technique, the data required for image reconstruction are selected from multiple sequential heart cycles. This technique requires retrospective gating and a regular heart rate. 60 For data from several cardiac cycles to be used for image reconstruction, the same position has to be covered by the detector during consecutive cardiac cycles. Thus, the pitch must be lowered, which will increase radiation dose. Multi-segment reconstruction is only effective in improving temporal resolution at specific heart rates (the heart rate and gantry rotation time need to be desynchronized).

Arrhythmias
Arrhythmias present a challenge for CCTA because of both high and irregular heart rates, and both stairstep and motion artifacts can be seen. Atrial fibrillation has sometimes been considered a relative contraindication to the performance of CCTA. However, in recent studies, CCTA has been successfully performed in patients with atrial fibrillation by using dual-source CT and end-systolic reconstruction and by using single-source reconstruction. 64-slice CT with ECG-editing64 and middiastolic

55

Respiratory motion artifacts

Most patients can breath-hold for the time necessary to complete a CCTA study. A Valsalva maneuver should be avoided, as this can decrease inflow into the right atrium and decrease contrast

enhancement.60 Respiratory motion artifact can be recognized on the lung windows and is most prominent on coronal and sagittal images.

Streak artifacts
Streak artifacts from beam hardening can be seen secondary to metal clips. Streak artifact in the superior vena cava and right atrium from dense contrast can limit evaluation of the right coronary artery. This can be mitigated by the use of a saline bolus chaser. However, a saline bolus chaser can result in poor contrast opacification of the right heart lumen, which may limit morphologic and functional evaluation. Protocols that utilize an admixture of saline and contrast are helpful in maintaining right heart opacification without streak artifact.

Blooming artifacts
Blooming artifacts can cause small high-contrast structures such as stents and calcium to appear larger than they are.60 Edge-enhancing

56

kernel filters can decrease blooming artifacts and may be helpful for evaluating a stent lumen, although image noise is increased.

Image Reconstruction
Reconstruction Window
The coronary arteries are optimally imaged when there is the least cardiac motion. This occurs during so-called rest periods, which is typically in middiastole (diastasis). Coronary motion is also minimal during end-systole (isovolumic relaxation), but this is of shorter duration than diastolic diastasis at low heart rates. With dual-source CT at low heart rates, the optimal reconstruction window is often 7075% of the R-R interval (diastolic) for all of the coronary arteries. A 30-35% systolic window may occasionally be helpful for the right coronary artery.65 As heart rate increases, diastole shortens relative to systole, and diastasis shortens dramatically. The optimal reconstruction window transitions from diastole to systole around 75-85 bpm.40 At high heart rates, the optimal reconstruction windows are 8590% (diastole) and 40-45% (systole). End-systolic reconstruction windows may be helpful in patients with atrial fibrillation, as the systolic rest period will be less variable than the diastolic rest period.

57

Use of a fixed reconstruction window, such as 50 msec rather than a percentage of the R-R interval, is helpful in patients with atrial fibrillation and variable R-R intervals.

Postprocessing Techniques
A variety of postprocessing techniques are useful in CCTA. 66 Many interpreting physicians will start with the axial source images and then utilize multiplanar reconstructions in at least 2 planes.

Axial source images

Axial source images are often the initial images used to review the coronary arteries and are used to evaluate the extracardiac structures.

Multiplanar reconstruction (MPR)

MPRs can be performed at oblique planes to the body or the coronary arteries. For coronary artery imaging, a curved MPR technique is usually used where the reconstruction plane is locked onto the target vessel. This requires a manual or automatic centerline to be drawn along the vessel. Curved MPR images can often be difficult to obtain if the centerline is difficult to trace, for reasons such as motion artifact, poor contrast opacification, or dense calcifications. The curved MPR can be unfolded so that the vessel appears to be straight ("ribbon view"). Note

58

that a single curved MPR may not adequately display eccentric lesions, and correlation with orthogonal MPR views, such as an end-on view perpendicular to the vessel, is necessary.

Maximum intensity projection (MIP)

With the MIP technique, the highest voxel attenuation values from a volume of CT data are used to reconstruct the image. The MIP technique can be used to create "angiographic" images. However, as voxels with lower attenuation values are suppressed, noncalcified plaques can be masked by luminal contrast, and calcified plaque can mask less dense luminal contrast.66 The MIP technique tends to overestimate stenosis.

3D volume rendering
Volume-rendered images are visually appealing, but they usually play little role in primary interpretation. They are helpful for visualizing anomalous vessels and bypass grafts. Generation of volume-rendered images is computationally intensive and often requires manual editing.

59

Anatomy
The left anterior descending artery (LAD) and posterior descending artery (PDA) run in the interventricular groove, while the circumflex and right coronary arteries (RCA) run in the atrioventricular groove.67-69 In general, hypoplasia of one vessel will be accompanied by prominence of another vessel. For example, if the LAD is small and does not extend to the apex, the PDA is typically prominent and extends to the apex. If the circumflex is small, there are typically prominent posterolateral branches arising from the RCA. If there is a large ramus intermedius, the diagonals may be small.67-69

Dominance
Right dominant (80-85%): Both the PDA and the posterolateral (also called posterior ventricular) branches arise from the RCA. Left dominant (15-20%): Both the PDA and the posterolateral branches arise from the circumflex. Codominant (5%): The PDA arises from the RCA. The

posterolateral branches arise from the circumflex.

60

Left main coronary artery The left main coronary artery is variable in length, 11 mm 5 mm.70 If intervention in the left coronary artery system is a possibility, it may be helpful to report the length of the left main artery. The left main coronary artery will usually bifurcate into the LAD and the left circumflex artery. In approximately 30% of cases, the left main artery will trifurcate, with a ramus intermedius artery between the LAD and circumflex. The ramus intermedius artery will supply a lateral wall territory between the first diagonal and the first obtuse marginal branch territories. Rarely, the left main coronary artery will be absent and the LAD and circumflex artery will arise directly from the aorta. Left anterior descending artery The LAD is variable in length and can terminate before the apex, supply the apex, or supply the distal inferior wall. The LAD gives rise to diagonal branches supplying the anterolateral wall and to septal perforators supplying the interventricular septum. Compared with the diagonals, the septal perforators usually are less implicated

in ischemia and are less often targets of intervention.

61

In 1% of cases, there can be dual LADs.71 In these cases, a short LAD terminates high in the interventricular groove. A long LAD originates as an early branch from the LAD proper or, less likely, from the RCA. The proximal LAD courses outside the interventricular groove, with the distal portion returning to the groove. This should be distinguished from a diagonal branch; the diagonal will not enter the interventricular groove distally. Left circumflex artery The left circumflex artery gives off obtuse marginal branches that supply the posterolateral wall. There is often a prominent first obtuse marginal branch with a relatively small circumflex artery in the atrioventricular groove distal to this branch. The left circumflex artery usually terminates in the atrioventricular groove. In a left dominant system, the PDA and posterolateral branches arise from the circumflex. In the codominant system, the posterolateral branches arise from the circumflex.

62

Right coronary artery The branches from the RCA are called acute marginal or right ventricular marginal arteries. The acute marginals usually do not cause significant ischemia and are rarely targets for intervention. There are 3 "named" arteries that can arise from the RCA: o The first branch off the RCA is often the conus artery. In 50% of cases, the conus artery arises from the RCA; in the other 50%, it arises from the aorta. The conus artery heads anteriorly toward the conus (right ventricular outflow tract). o The second branch off the RCA is often the sinoatrial (SA) nodal artery. In 55% of cases, the SA nodal artery arises from the RCA; in the other 45%, it arises from the circumflex. The SA nodal artery heads posteriorly toward the sinoatrial node. The sinoatrial node is located in the superior aspect of crista terminalis of the right atrium (near where the superior vena cava joins the right atrium). The crista terminalis is a vestigial remnant located between the right atrial appendage and the sinus venosus. The crista terminalis can be seen as a right atrial "pseudomass" on CT, MRI, or echocardiography

63

The last named branch off the RCA is the atrioventricular (AV) nodal artery, which arises from the RCA in 8087% of cases. It can also arise from the circumflex or from both the RCA and the circumflex. If it originates from the RCA, it typically arises slightly distal to the PDA origin. It heads superiorly through the septum to the AV node, which is in the inferior aspect of the interatrial septum.

Collateral pathways Collateral pathways are typically better visualized on invasive coronary angiography than on CCTA. There is a large number of potential collateral pathways.72 Two "named" collateral pathways are the following:

Kugel's artery :73 Connects an anterior artery (typically the circumflex) with a posterior artery (typically the RCA) at the crux (junction of the posterior interventricular and AV grooves) of the heart. This may connect with the AV nodal artery and supply the AV node.

Arc of Vieussens'/Vieussens' ring74 : Connects the RCA (typically via the conus artery) with the LAD.

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Anomalies Coronary artery anomalies can be broadly classified as anomalies of origin, anomalies of course, and anomalies of termination.75 Only a few anomalies can be hemodynamically significant. Patients with anomalous origin of the LCA or RCA from the pulmonary artery typically show symptoms early in infancy or during early childhood. The left and right coronary arteries can arise from the noncoronary sinus or the opposite sinus. In these cases, the arteries can take 4 courses: retroaortic, prepulmonic, septal (beneath the right ventricular outflow tract), or interarterial (between the aorta and pulmonary artery). Patients with an interarterial course are at high risk for sudden cardiac death. Myocardial bridging,76 also called tunneled artery, is a congenital anomaly where myocardium encases a segment of coronary artery. It is most common in the mid-LAD. The artery may be compressed in the systolic phase. Although it is usually a benign anomaly, it has been associated with myocardial ischemia. Myocardial bridging is well demonstrated by CCTA. As most diagnostic images are obtained in diastole, it is important to also review systolic images, if available, to

65

evaluate for systolic compression. Atherosclerotic changes are more common proximal to the tunneled artery. Myocardial loops refer to muscle bundles from the atrial myocardium surrounding three quarters of the circumference of an artery. These are of no clinical significance. Congenital coronary artery fistulas can be symptomatic if large. They are well visualized by CCTA. Coronary artery fistulas originate from the RCA in two thirds of cases and the left coronary system in a quarter of cases. More than 90% drain into the right atrium, coronary sinus, or right ventricle.77 On CCTA, contrast opacification of the receiving

chamber/vessel (shunt sign)77 is useful for determining the exact site of entry of the fistula. However, this finding will be obscured if there is a significant amount of preexisting contrast in the receiving chamber/vessel. Other anomalies are not hemodynamically significant but important to describe in detail if intervention is a possibility. For example, a dual LAD can result in diagnostic error during cardiac catheterization or in technical difficulty during revascularization.

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STENOSIS GRADING There are many different methods to grade the degree of stenosis, including visual assessment; manually determined diameter or crosssectional area on multiplanar reformats perpendicular to the median centerline of the vessel ("end-on" view); diameter on maximum intensity projection (MIP) images parallel to the long axis of the vessel; and software calculation78 of diameter or area. Dodd et al found that the crosssectional area technique had the highest correlation with quantitative coronary angiography, and MIP technique had the smallest interobserver variability.79 Grading is less accurate in calcified plaques and in distal coronary vessels. Because the spatial resolution is inadequate for precise grading, coronary stenoses are often graded with semiquantitative descriptors such as normal, mild (< 50%), moderate (5070% stenosis), severe (>70% stenosis), and occluded. Stenosis is typically overestimated in areas where heavily calcified plaques are present. Zhang et al offer the following suggestions to better assess the degree of stenosis when calcified plaques are present80:

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A significant luminal stenosis is unlikely if the plaque thickness measures 50% or less of the diameter of a nearby normal segment and if it is eccentrically positioned on a cross-sectional multiplanar reconstruction (MPR) view or there is visible lumen adjacent to the plaque on a long-axis MPR view,

A significant stenosis is likely if calcified plaque fills the entire central portion of the lumen on a cross-sectional MPR image.

A significant stenosis can be suggested if calcified plaque is 50% or greater than the diameter of a nearby normal segment on cross-sectional MPR images but does not completely fill the lumen; however, the interpreter might add that CCTA may overestimate the degree of stenosis in this situation.

Reporting A consensus report from 2 cardiac CT specialty societies suggests a reporting template for CCTA. A structured approach to reporting can also be used.81 Reporting template The reporting template includes the following: Indication for examination

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Imaging technique:

Contrast agent administered CT technique Vasodilator or beta blocker Workstation methods for image reconstruction Complications

Description of findings:

Overall description of image quality/diagnostic confidence Source of limitations, such as calcification and motion

Coronary anatomy/anomalies:

Anomalies of coronary origin Right or left dominant system Location and size of coronary artery aneurysm/dilatation Coronary artery atherosclerosis:

Calcium score (if performed) Description of atherosclerotic narrowing for vessels 2 mm or less in diameter

Location of atherosclerotic narrowing by anatomic landmarks, or a 15-segment model used for conventional angiography

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Diffuse or focal disease description Description of plaque, such as noncalcified, mixed, or calcified

Ventricular size and function, when requested and available Extracardiac findings Summary/impression and recommendation

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OBJECTIVES OF THE STUDY

o To determine the percentage of patients who show

agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis.

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OPERATIONAL DEFINITIONS
Agatston calcium score is a method for the quantification of calcium in coronary artery atherosclerosis. Low coronary artery calcium score is defined as equal to or less than 100. Significant coronary artery stenosis was considered to be equal or greater than 50 percent luminal narrowing. Agreement If CT Angiography did not show significant coronary artery stenosis, it was labelled as agreement.

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MATERIAL AND METHODS

SETTING:
Radiology Department, Shaukat Khanum Memorial Cancer

Hospital and Research Centre, Lahore. Heart and Body Scan Centre, Lahore.

DURATION OF STUDY:
o 6 months after approval of synopsis.

SAMPLE SIZE:
Sample size of 100 cases was calculated with 95% confidence level, 10 percent margin of error and taking expected percentage of agreement between calcium score less than 100 and coronary stenosis on CT Angiography for the diagnosis of significant coronary artery disease i.e. 50 percent in patients with suspected or known coronary artery disease.

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SAMPLING TECHNIQUE:
Non-probability purposive sampling

SAMPLE SELECTION:
INCLUSION CRITERIA:
Consecutive patients Greater than 25 years of age Both Sexes Suspected or known CAD Coronary Artery Calcium Score 100 or less Sinus Rhythm

EXCLUSION CRITERIA:
Agatston Calcium Score > 100 Previously undergone Coronary Stenting or Bypass Grafts Renal Dysfunction or raised serum creatinine greater than 1.5 mg/dl Allergic to lodine or IV contrast

74

Pregnancy

STUDY DESIGN:
Cross sectional survey

DATA COLLECTION PROCEDURE:

Patients with suspected or known CAD referred by physicians for MDCT, fulfilling inclusion/exclusion criteria were scanned after obtaining informed consent and demographic history. CT Scan was performed on 64-slice Aquillion (Toshiba Medical System, Japan). For Calcification assessment, un-enhanced ECG gated cardiac CT was done. It was followed by CT Angiography using non-ionic intravenous contrast medium (lopromide Ultravist, Schering Germany). Reconstruction and

interpretation of scans was done on workstation Vitrea 2 version 3.0.9.1 (vital images, Minnesota, USA). A radiologist assessed each segment on non-enhanced CT for amount of calcium using Agatston score and also assessed each segment on contrast enhanced CT for stenosis. The most significant stenosis > 50% was noted for each vessel and patients. All this information was recorded in a pre-designed proforma (attached).

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DATA ANALYSIS PROCEDURE:

Collected data was entered and analyzed using the statistical software (SPSS) version 12. Quantitative variable like age was presented in the form of mean + SD. Qualitative variable like gender were in the form of frequency and percentages. Agreement between coronary artery calcium score less than 100 and CT Angiography for the diagnosis of the significant stenosis > 50% was calculated as frequency and percentages. Kappa statistics were used to determine the strength of agreement between calcium score less than 100 and CT Angiography for the diagnosis of significant stenosis.

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RESULTS
In this study, a total of 100 patients were recruited after fulfilling the inclusion/exclusion criteria to determine the percentage of patients who show agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis. AGE DISTRIBUTION Age distribution of the patients was done in Table No. 1, where majority of the patients were recorded between 46-55 years i.e. 36% (n=36), 27%(n=27) were between 36-45 years, 17%(n=17) were recorded between 25-35 years and 56-65 years of age, only 3%(n=3) were recorded between 66-75 years of age, mean and SD was calculated as 38.65+5.72. GENDER DISTRIBUTION Gender distribution of the subjects shows 72%(n=72) male and 28%(n=28) females. (Table No. 2) FREQUENCY OF AGREEMENT OF LOW CACS AND INSIGNIFICANT CORONARY STENOSIS Frequency of agreement of low CACS and insignificant coronary stenosis was calculated and it was found 78%(n=78) while 22%(n=22)

77

had no agreement, kappa test was applied, p value was recorded. 0.0005. (Table No. 3) RELATION BETWEEN CACS AND SIGNIFICANT STENOSIS Relation between CACS and significant stenosis in positive patients was 50%(n=11) with 0 CACS, 27.27%(n=6) was between 1-30 CACS, 13.63%(n=3) between 31-60 CACS, 4.55%(n=1) between 61-90 and 91-99 CACS. (Table No. 4)

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TABLE No. 1: AGE DISTRIBUTION OF THE SUBJECTS (n=100)

Age (in years) 25 35 36 - 45 46 55 56 65 66 75 Total Mean and SD No. of cases 17 27 36 17 3 100 Percentage 17 27 36 17 3 100 38.65+5.72

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TABLE No. 2: GENDER DISTRIBUTION OF THE SUBJECTS (n=100)

Gender Male Female Total No. of cases 72 28 100 Percentage 72 28 100

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TABLE No. 3: FREQUENCY OF AGREEMENT OF LOW CACS AND INSIGNIFICANT CORONARY STENOSIS (n=100)
Agreement Yes No Total No. of cases 78 22 100 Percentage 78 22 100

k: 0.0005

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TABLE No. 4:
RELATION BETWEEN CACS AND SIGNIFICANT STENOSIS IN POSITIVE PATIENTS
(n = 22)

CACS 0 1 - 30 31 60 61 - 90 91 - 99 Total

No. of patients 11 6 3 1 1 22

% 50 27.27 13.63 4.55 4.55 100

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DISCUSSION
Coronary artery disease (CAD) is the leading cause of death in adults in many western countries, and nowadays in Asian countries also.82-83 Atherosclerotic coronary artery calcifications are most frequently found as calcium (Ca) lumps in advanced atherosclerotic lesions (AHA: American Heart Association) plaque type Vb), but may occur as small deposits of calcium in earlier lesions.84 Quantifying the amount of coronary artery calcium with

unenhanced CT calcium score has been shown to be a reliable noninvasive technique for screening risk of future cardiac events85,86 and can be quantified by using the Agatston score. 87 Large patient studies have shown that the amount of coronary artery calcium based on the Agatston score is a strong predictor for risk of myocardial infarction and sudden cardiac death, independently of conventional coronary risk factors.88-90 Computed tomographic coronary angiography (CTCA) using 4and 16-slice scanners lacked sufficient robustness to be useful in clinical practice.91,92 The 64-slice CT technology featuring increased spatial and temporal resolution has improved the clinical reliability and permits evaluation of all clinically relevant branches of the coronary tree.93-94

83

CT angiography and CS can be used to predict the presence or absence of coronary artery disease. Few studies, however, have addressed the ability of CT angiography and CS (assessed with multi section CT) to demonstrate lesions in individual coronary arteries and the potential limitations of such evaluation. In several trials, absence of coronary artery calcium ruled out the presence of significant CAD with high predictive value.8 CACS <100 are thought to be associated without obstruction on cardiac catheterization.6 It however, has been challenged in few studies.9 We designed to evaluate the level of agreement between severity of stenosis on CT Angiography and calcium burden as measured by dedicated CT protocols for calcium scoring, comparing their results. The relevant prognostic information obtained may be useful in initiating, modulating or intensification of appropriate treatment and diagnostic strategies. We recorded majority of the patients between 46-55 years i.e. 36%, 27% were between 36-45 years, 17% between 25-35 years and 56-65 years of age, only 3% were between 66-75 years of age, mean age was 38.65+5.72 years, 72% male and 28% were females, frequency of

84

agreement of low CACS and insignificant coronary stenosis was 78% while 22%(n=22) had no agreement, kappa test showed a significant value (p value 0.0005). Of 22 patients having relation between CACS and significant stenosis 50% were with 0 CACS, 27.27% between 1-30, 13.63% between 31-60, 4.55% between 61-90 and 91-99 CACS.

Kelly et al reported a population of 325 patients (high risk for CAD or atypical symptoms or abnormal stress test results) with zero CACS undergoing CT-CA and CAG.95 The authors found 167 patients with noncalcified plaques and 18 (5.5%) patients with obstructive CAD.95 They concluded that an atherosclerotic burden and obstructive CAD may be present in patients with zero CACS and that imaging the vessel wall directly may be helpful to identify noncalcified plaque and guide therapy. Another study by Akram et al. explored the impact of symptoms in a population of patients with zero CACS.96 They used CT-CA as the reference standard for CACS in detecting obstructive CAD (CAG was not performed extensively). They found that 8.2% of the symptomatic patients with zero CACS had an obstructive coronary artery stenosis. In the asymptomatic patients with zero CACS, there were no obstructive coronary lesions.96 They concluded that CT-CA is better than CACS in

85

symptomatic patients, and CACS is better than CT-CA in asymptomatic patients. Another study from Choi et al. studied a very large (n= 1,000) asymptomatic population with CT-CA.97 The mean CACS was very low (Agatston=18), and the prevalence of obstructive CAD was 7.3%. In the subgroup of patients with zero CACS, 4% (40/825) of the patients had non-calcified plaques, with 1.8% (15/825) having significant or severe obstructive CAD. They concluded that the presence of occult CAD is not negligible in the asymptomatic population. Another study extrapolate that there is a not negligible obstructive burden of disease in populations with zero CACS and that this prevalence is very much affected by clinical presentation (symptomatic vs. asymptomatic). They found that the noninvasive assessment of arterial segments at CT angiography is useful and results in few

misclassifications, but that CS is best used to identify patients with disease rather than to exclude disease or to localize stenoses to particular arteries or segments. Therefore, CT angiography is likely to be better suited to the detection of new obstructive coronary lesions than is CS.98

86

The results of our study in determination of patients who show agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis by using CT Scan on 64-slice Aquilion (Toshiba Medical System, Japan) shows a significant relation with calcium level <100 for stenosis.However value of CACS as gatekeeper to conventional coronary angiography has been questioned. A significant strength of our study was its prospective nature and thorough analysis of calcium score and coronary artery stenosis.Our limitations were that we couldnot evaluate prognostic value of calcium score and stenosis due to short time period and most of our patients were referred from far places.Also,we could not correlate all our findings with conventional coronary angiography,still regarded as gold standard.The reporting physician was also aware of patients calcium score at the time of assessing stenosis. We recommend that absence of calcium or low calcium does not exclude significant coronary stenosis.Depending on presentation ,it is

recommended to get calcium score and coronary CT angiography done in the same setting.

87

CONCLUSION
o The result of the study reveals that percentage of patients

who show agreement between low coronary artery calcium score and Coronary CT Angiography for the exclusion of significant stenosis was significantly higher. However ,absence of coronary calcium or low calcium score does not exclude obstructive stenosis or the need for revascularization in patients with high enough suspicion of coronary artery disease.

88

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PROFORMA
DETERMINATION OF AGREEMENT BETWEEN LOW AGATSON CALCIUM SCORE AND 64-SLICE CT SCANNER FOR EXCLUSION OF SIGNIFICANT CORONARY STENOSIS . Serial No.___________ Name______________ MS LAD LCX
____

Reg. No____________ Age: ______________ RI

____

Date.___________ Sex.____________ Others2

____

RCA
____

Others1
____

Others3
___

CACS ____ ____

Stenosis

____ ____

____

____

____

____

____

____

On CTA > 50% or 50%

Final Assessment Agreement:

Yes

No