Journal of Cardiovascular Computed Tomography (2009) 3, 312 320

Original Research Article

Reproducibility of coronary artery plaque volumeand composition quantification by 64-detector rowcoronary computed tomographic angiography:An intraobserver, interobserver, and interscanvariability study

Victor Y. Cheng, MDa,b*, Ryo Nakazato, MDb, Damini Dey, PhDa,Swaminatha Gurudevan, MDa, Joshua Tabakc, Matthew J. Budoff, MDd,Ronald P. Karlsberg, MDa,e, James Min, MDf, Daniel S. Berman, MDa,b

aDepartment of Medicine, 8700 Beverly Boulevard, Taper Building Room 1258, Cedars-Sinai Medical Center, Los Angeles, CA90048, USA; bDepartment of Imaging, 8700 Beverly Boulevard, Taper Building Room 1258, Cedars-Sinai Medical Center,Los Angeles, CA 90048, USA; cJohns Hopkins University, Baltimore, MD, USA; dLos Angeles Biomedical Research Instituteat Harbor University of California, Los Angeles, Torrance, CA, USA; eCardiovascular Medical Group of Beverly Hills,Beverly Hills, CA, USA and fGreenberg Division of Cardiology, Weill Medical College of Cornell University, New YorkPresbyterian Hospital, New York, NY, USA

KEYWORDS:Computed tomography;Coronary artery plaque;Reproducibility;Serial examination

Conflict of interest: The authors re

This study was supported by a gr

Beverly Hills, CA.

1934 5925/$ see front matter � 2009

doi:10.1016/j.jcct.2009.07.001

BACKGROUND: Interscan variability of coronary arterial plaque volume and composition quantification with coronary computed tomographic angiography (CCTA), an important attribute when considering CCTA as a serial modality, has not been examined.

OBJECTIVE: We sought to systematically determine intraobserver and interobserver interscanreproducibility of these measures.

METHODS: Two blinded, experienced readers independently evaluated proximal coronary segmentson CCTAs from 30 patients who underwent 2 scans within 200 days (median, 124 days; interquartilerange, 49 155 days) without experiencing an interim acute coronary event. Readers recorded numberof plaques and, in plaques that met a preset minimal length criterion, quantified total, calcified plaque(CP), and noncalcified plaque (NCP) volumes and percentage of total plaque volume occupied by NCP.

RESULTS: Of 89 total segments studied, 36 contained detectable plaque, and 26 met criterion forquantification. Intraobserver, interobserver, and interscan agreements for normal segments were100%. Intraobserver interscan correlations of total, CP, and NCP volumes and percentage of NCPwere excellent (r 5 0.93 0.97, P values , 0.001). Interobserver interscan correlations for all measureswere also very good (r 5 0.81 0.96, P values , 0.001). Variability in plaque volume quantification wassignificant, exceeding 60% of the averaged paired plaque volumes in the best case scenario

port no conflicts of interest.

ant from the Lincy Foundation,

* Corresponding author.

E mail address: victor.cheng@cshs.org

Submitted April 2, 2009. Accepted for publication July 20, 2009.

Society of Cardiovascular Computed Tomography. All rights reserved.

Cheng et al Interscan coronary plaque quantification with CT 313

(interobserver interscan CP volume). Quantification of percentage of NCP composition by volume wasmore consistent, with ,24% variation in the worst case scenario (interobserver interscan).

CONCLUSION: CCTA shows promise for quantifying serial coronary plaque change. Currently, themost robust measure seems to be percentage of plaque composition, rather than plaque volume. Forsmaller plaques, volume quantification remains challenging.� 2009 Society of Cardiovascular Computed Tomography. All rights reserved.

Table 1 Clinical information of study patients (n 5 30)

n (%)Median(25%, 75%)

Age (y) 67 (57,76)Male 22 (73) —History of

Diabetes 2 (7) —Hypertension 19 (63) —

Introduction

In addition to stenosis severity, certain coronary arteryplaque features, including plaque volume and plaque compo-sition, possess clinical significance in the development of acutecoronary plaque rupture.1–5 Coronary computed tomographicangiography (CCTA), in comparison with intracoronary ultra-sound,6–9 appears capable of noninvasively characterizingthese features. So far, limited studies have used CCTA to assessserial changes in noncalcified plaque volume.10,11

Successful imaging of coronary arterial plaque with CT ischallenging and limited by the temporal and spatial resolu-tions of current generation scanners, as evidenced by thewide interscan variability associated with coronary arterycalcium scoring12,13 and limited discrimination of stenosisseverity from coronary artery plaque.14 Serial coronaryartery plaque characterization by CCTA is further compli-cated by numerous scan-dependent factors, such as contrasttiming, adequacy of coronary artery enhancement, heartrate, and heart rate variability. To date, interscan reproduci-bility of coronary plaque evaluation by CCTA has not beenevaluated. We thus sought to systematically examine thereproducibility of the detection, quantification, and composi-tion characterization of coronary artery plaques by CCTA.

Dyslipidemia 21 (70) —Any smoking 5 (17) —Family coronary artery disease 8 (27) —

Have CCS 26 (87) 178 (35,525)Time between CCTAs (d) — 124 (43,155)Primary indication for first CCTA

Symptoms 18 (60) —Abnormal stress test 2 (7) —Preoperative 4 (13) —Assess stent 1 (3) —Screening 3 (10) —Other 2 (7) —

Primary indication for second CCTASymptoms 15 (50) —Abnormal stress test 0 (0) —Preoperative 1 (3) —Assess stent 5 (17) —First CCTA unsatisfactory 3 (10) —Other 6 (20) —

On statin at first CCTA 15 (50) —On statin at second CCTA 24 (80) —Heart rate at first CCTA — 57 (50,62)Heart rate at second CCTA — 57 (51,64)Interscan heart rate difference — 0 (-6, 5)

CCS, coronary calcium score.

Methods

Study population

We identified 30 consecutive patients (22 men; medianage, 67 years) without prior coronary artery bypass graftingwho underwent 2 CCTAs within 200 days (median, 124days; interquartile range, 49 155 days) at either Cedars-Sinai Medical Center or the Cardiovascular Medical Groupof Beverly Hills (both serving Los Angeles, CA). Patientsunderwent CCTA primarily for suspected or known coro-nary artery disease. No patient experienced acute coronarysyndrome, surgical coronary revascularization, or signifi-cant ventricular dysrhythmia from myocardial ischemiabetween scans. Study population characteristics and CCTAindications are shown in Table 1.

CCTA image acquisition

Eight patients (27%) underwent CCTA on a Siemensdual-source scanner (Forchheim, Germany). Twenty-two

patients (73%) underwent CCTA on a GE Healthcare VCT64-slice single-source scanner (Princeton, NJ). In allpatients, the first and second CCTAs were performed onthe same scanner.

Dual-source CTPatients with heart rates R 70 beats/min and no contrain-

dications were administered oral (up to 100 mg) or intrave-nous metoprolol (5-mg injections up to 30 mg) to attain aheart rate , 70 beats/min. Imaging proceeded even if heartrate remained R70 beats/min after maximal b-blockade.An initial non contrast coronary calcium scan was per-formed, with electrocardiogram (ECG) triggering at a heartrate that depended on the percentage of the R-R interval,

314 Journal of Cardiovascular Computed Tomography, Vol 3, No 5, September/October 2009

350-mm field of view, and a scan protocol of 2.5-mm slicethickness, 120-kVp tube voltage, and 42-mAs tube current.Sublingual nitroglycerin spray (0.4 mg; Sciele Pharma, Al-pharetta, GA) was then given, followed by power injectionof 92 mL intravenous contrast (Omnipaque with crea-tinine , 1.5 g/dL or Visipaque with creatinine R 1.5 g/dL;GE Healthcare) and 80 mL saline chaser into the antecubitalvein. Once R100 Hounsfield units (HUs) was detected in theascending aorta, ECG-gated helical scanning was performedfrom 1 cm below the tracheal bifurcation to the diaphragmduring a 10-second breathhold. Scan parameters includedheart rate dependent pitch (range, 0.2 0.45), 330-ms gantryrotation time, 120-kVp tube voltage, 600-mA tube current,and ECG-based dose modulation whenever possible.

VCT 64Prescan b-blockade protocol was identical to that at

Cedars-Sinai Medical Center, with the exception that ,60beats/min was used as the target heart rate. Sublingualnitroglycerin spray (0.4 mg) was given before any imaging.Non contrast coronary calcium CT was then performed,with ECG triggering at a heart rate dependent percentageof the R-R interval, 350-mm field of view, and a scan protocolof 2.5-mm slice thickness, 120-kVp tube voltage, and 150-mAs tube current. Subsequently, 100 mL Omnipaque (GEHealthcare) followed by 50 60 mL saline chaser werepower-injected into the antecubital vein. On the basis ofexperience at the center, manual inspection at the level ofthe pulmonary artery bifurcation was used to trigger scan-ning: When signal in the contrast-filled ascending aorta visu-ally appeared to have matched that in the pulmonary trunk,ECG-gated helical scanning was initiated from 1 to 2 cmbelow the tracheal bifurcation to just below the costophrenicangles during a 10- to 20-second breathhold. Scan parametersincluded heart rate dependent pitch, 350-ms gantry rotationtime, 120-kVp tube voltage, 320- to 740-mA tube current,and ECG-based dose modulation whenever possible.

CCTA image reconstruction

Dual-source CTRetrospectively gated reconstruction of contrast-en-

hanced data was performed at end systole and in diastolewith the use of the following parameters: 0.6-mm slicethickness (0.75 mm with body mass index . 35 kg/m2),0.3-mm slice increment, 250-mm field of view,512 ! 512 matrix, and a ‘‘medium smooth’’ kernel. A‘‘sharp’’ kernel was also used in patients with coronarystents or coronary calcium score . 100.

VCT 64Retrospectively gated reconstruction of contrast-

enhanced data was performed at end systole and in diastolewith the use of the following parameters: 0.6-mm slicethickness, 0.3-mm slice increment, 250-mm field of view,and 512 ! 512 matrix.

All reconstructed images were transferred to a Hewlett-Packard workstation (Palo Alto, CA), where coronaryanalysis was done with the use of the Vitrea 2 software(Vital Images, Minnetonka, MN).

CCTA image evaluation

Reconstructed CCTA studies were anonymized andpresented to 2 level III verified readers (reader 1, V.C.;reader 2, R.N.) in random order. Reader 1 first determinedthe optimal phase for visual analysis. Then both readers,blinded to patient clinical status, ICA results, and eachother, independently used data from this phase to assess allproximal coronary segments by evaluating standard axialimages, oblique long- and short-axis multiplanar reforma-tions, and oblique long- and short-axis maximum intensityprojections. Every patient had 4 proximal segments: leftmain, proximal left anterior descending (distal end markedby the first diagonal or first septal branch, whichever wasmore distal), proximal left circumflex (distal end marked bythe first obtuse marginal branch), and proximal rightcoronary artery (pRCA; distal end marked by the firstacute marginal branch), yielding a total of 120 segments.Image quality of each segment was scored on a qualitative5-point scale (5 5 excellent contrast, no artifact, and mini-mal noise; 4 5 adequate contrast or mild artifact or noisenot interfering with assessment; 3 5 definite artifact, bor-derline contrast, or noise that mildly impaired assessment;2 5 definite artifact, significant contrast underenhance-ment, or significant noise that greatly impaired assessment;1 5 unable to assess segment). Twenty segments containingstents or in which percutaneous coronary intervention wasperformed between scans were excluded from analysis.An additional 11 segments with quality scores of 1 or 2were excluded; all such cases were due to artifact: 7 frommisregistration, 3 from motion, and 1 from pacer leadstreaking. The remaining 89 segments with qualityscores R 3 on CCTAs 1 and 2 were analyzed.

Window width and level were initially set at 800 900 HUand 250 300 HU. At reader discretion, these settings couldbe modified without limitation as needed to produce the mostrepresentative image of the plaque, defined as a visuallyidentifiable coronary arterial lesion with a radiodensitydistinct from that of the contrast-filled lumen, arterial wall,and surrounding connective tissue. Any plaque componentwith radiodensity significantly greater than that of thecontrast-filled lumen was considered calcified plaque (CP;typical range, .600 HU); with radiodensity greater than thatof the periarterial connective tissue but less than that of thecontrast-filled lumen, noncalcified plaque (NCP; typicalrange, between 50 and 300 HU). After rendering contig-uous transverse views of each plaque with the use of obliquemultiplanar reformations along the longitudinal axis of theaffected segment (Fig. 1), the reader first determined whetherplaque length extended for .5 contiguous 3-dimensionalstep increments in the transverse view. Plaques extending

Cheng et al Interscan coronary plaque quantification with CT 315

for %5 step increments were categorized as ‘‘minimal pla-que’’ and were not quantified given the limitations of CT spa-tial resolution. Plaques extending for .5 step incrementswere categorized as ‘‘measurable plaque’’. The numbers ofminimal plaques and measurable plaques in each segmentwere counted.

Volume of each measurable plaque was obtained bysteps similar to previously described techniques (seeFig. 1).4,5 With the use of oblique multiplanar reformationviews, starting and ending 3-dimensional positions (ie,along the x-, y-, and z-axes) of the plaque were determinedand used to calculate the distance vector along the plaque.Next, the number of contiguous cross-sectional slices thatthe plaque occupied was counted (median and maximumnumber of slices, averaged between readers, were 22 and61, respectively). Dividing the distance vector by the num-ber of cross-sectional slices yielded the length of each stepincrement along the vector (typically between 0.3 and0.45 mm). CP and NCP component areas were then manu-ally traced in each contiguous cross-sectional view andsummed. Total plaque, NCP, and CP volumes were calcu-lated by multiplying the respective plaque area sums withthe step increment. In segments with .1 measurable pla-que, volumes from each measurable plaque were summed,and segmental plaque composition was calculated by divid-ing the summed NCP volume by the summed total plaquevolume.

Figure 1 Technique of plaque volume quantification. The beginning aque are used to determine the distance covered by the plaque. Cross secincrement along the longitudinal axis of the plaque (B). Calcified and noslices; red tracing for calcified plaque, white for noncalcified plaque). Coplaque areas by the step increment.

Statistical analysis

Distributions of continuous variables were described asmedians with 25th and 75th percentile values or means 6

standard deviations, when appropriate. Interobserver, intra-observer-interscan, and interobserver-interscan reproduci-bilities were assessed by calculating Pearson’s correlationcoefficient with 95% confidence intervals and constructingBland-Altman plots with 95% limits of agreement. Differ-ences and variability in volume quantification were ana-lyzed in absolute terms and in relation to the average ofpaired measurements. P values were calculated for correla-tion, with values ,0.05 considered statistically significant.

Results

Interscan heart rate differences in 7 patients (23%) wereR10 (individual differences were 10, 13, 14, 16, 17, 18,and 37). In 25 patients, the same diastolic phase wasselected for optimal plaque assessment for CCTAs 1 and 2(75% phase in 20 patients, 70% phase in 4 patients, and65% phase in 1 patient). In 4 patients, optimal phases forCCTAs 1 and 2 were slightly different parts of diastole(65% phase for CCTA 1 and 70% phase for CCTA 2 in 3patients, 70% phase for CCTA 1 and 80% phase for CCTA2 in 1 patient). In 1 patient, the optimal phase for CCTA

nd ending positions (closed and open yellow circles, A) of the plational tracing to obtain plaque area is then performed at each stepncalcified plaques are traced separately (B1 5 show representativerresponding plaque volumes are calculated by multiplying sums of

316 Journal of Cardiovascular Computed Tomography, Vol 3, No 5, September/October 2009

1 was at end systole (35% phase) and for CCTA 2 was indiastole (75% phase).

At CCTA 1, both readers found the same 54 segments tobe normal and the same 35 segments to contain visibleplaque. At CCTA 2, both readers found 53 segments to benormal and the same 36 segments to contain visible plaque.In one proximal left anterior descending, both readersidentified a new minimal plaque on CCTA 2. Interobserverand interscan agreements for normal segments were 100%.

For the 36 segments with coronary plaque noted by atleast 1 reader in either CCTA 1 or CCTA 2, completeinterobserver plaque count agreement occurred in 33 seg-ments (92%) for CCTA 1 and 30 segments (83%) for CCTA2. Complete interscan plaque count agreement occurred in 33segments (92%) for reader 1 and 32 segments (89%) forreader 2. Measurable plaque was found by at least 1 reader onCCTA 1 or CCTA 2 in 26 segments. In these cases, mean andmedian segmental total plaque volumes, averaged betweenreaders, were 40.6 6 73.2 mm3 and 27.6 mm3 for CCTA1 and 45.5 6 83.7 mm3 and 26.6 mm3 for CCTA 2. Meansegmental total plaque volume was ,50 mm3 in 20 segments(77%) and ,80 mm3 in 25 segments (96%).

We removed 2 segments from quantitative correlationand agreement analysis for the following reasons. OnepRCA was an extreme outlier compared with all othersegments; averaged total plaque volume for this segmentwas 384.8 mm3 for CCTA 1 and 436.9 mm3 for CCTA 2(Fig. 2), markedly higher than any other measurement inour study population (all other total plaque volumes were,80 mm3). A separate pRCA exhibited clear plaque con-tent change over time (Fig. 2); both readers detected amarked increase in the percentage of NCP compositionfrom CCTA 1 to CCTA 2 (reader 1, 16% 71%; reader 2,

Figure 2 Representative images of the 2 pRCA segments that were epanels show the pRCA segment that showed clear increase in noncalcifiewhose plaque volume was markedly higher than all other study segmen

10% 75%), and this was confirmed through independentreview by a third blinded observer (D.B.). In 2 segmentswhere measurable plaque was identified in only 1 scan by1 reader, interobserver and interscan quantitative compari-sons were made by setting corresponding total plaque,CP, and NCP volumes from the 3 other evaluations to 0.

Reproducibility of coronary plaque volumeand composition quantification

Interobserver quantificationCorrelations were very good for total plaque volume

(r 5 0.82 and 0.83, P values , 0.001) and excellent for CPvolume, NCP volume, and percentage of NCP (r valuesranged from 0.89 to 0.99, all P values , 0.001). Bland-Alt-man limits of agreement were within 25 mm3 for total pla-que volume, 23 mm3 for CP volume, and 13 mm3 for NCPvolume. In comparison to the average of paired values,these limits were wide, exceeding 90% of segmental plaquevolume in all Bland-Altman analyses. Limits of agreementin the percentage of NCP composition were within 623%.

Intraobserver-interscan quantificationCorrelations for plaque volume and percentage of plaque

composition were excellent (r values ranged from 0.93 to0.97, all P values , 0.001). Limits of agreement werewithin 15 mm3 for total plaque volume, 13 mm3 for CP vol-ume, and 9 mm3 for NCP volume. In comparison to the av-erage of paired values, these limits were wide, exceeding70% of segmental plaque volume in all Bland-Altman anal-yses. Limits of agreement in the percentage of NCP compo-sition were within 617%.

xcluded from correlation and agreement analyses. Left and middled plaque over 188 days (arrows). The right panels show the pRCAts. This segment was excluded to reduce data skewing.

Figure 3 Correlation plots for interobserver interscan agreement showing very good to excellent correlations for all quantitative measures (r values ranged from 0.81 to 0.96).

Cheng et al Interscan coronary plaque quantification with CT 317

Interobserver-interscan quantificationWhen results from reader 1 CCTA 1 were compared

with reader 2 CCTA 2 and results from reader 2 CCTA1 were compared with reader 1 CCTA 2, correlationsremained high (r values ranged from 0.81 to 0.96, all P val-ues , 0.001; Fig. 3), particularly with the percentage ofplaque composition (r R 0.95, P , 0.001). Limits of agree-ment were within 27 mm3 for total plaque volume, 27 mm3

for CP volume, and 19 mm3 for NCP volume. In compari-son to the average of paired values, these limits were wide,exceeding 60% of segmental plaque volume in all Bland-Altman analyses (Fig. 4). Limits of agreement in the per-centage of NCP composition were within 624%.

Figure 4 Bland Altman plots for interobserver interscan agreement. Lumes are shown in parentheses.

Results from all reproducibility analyses are summa-rized in Table 2.

Discussion

Among a group of patients who underwent 2 CCTAswithin 200 days (median, 124 days) for clinical reasons, wefound excellent interobserver and interscan agreements inplaque counting and qualitative plaque size assessment (ie,differentiating between minimal plaque and measurableplaque). Complete agreement was 100% in normal seg-ments and ranged from 83% to 92% in diseased segments.

imits of agreement as a percentage of the average of paired vol

Table 2 Summary of interobserver, interscan, and interobserver-interscan agreement measures of coronary plaque volumequantification

Correlation 95% Limits of agreement

r 95% CI Range in absolute value, mm3Range as percentage ofaveraged volume, %

InterobserverCCTA 1

Total plaque volume 0.83 0.64–0.92 21.8 to 21.2 96 to 94Calcified plaque volume 0.90 0.79–0.96 14.2 to 19.4 106 to 108Noncalcified plaque volume 0.93 0.84–0.97 12.8 to 8.0 226 to 96Noncalcified plaque, % 0.96 0.90–0.98 22.5 to 12.6 —

CCTA 2Total plaque volume 0.82 0.61–0.92 23.0 to 25.0 104 to 125Calcified plaque volume 0.89 0.75–0.95 16.3 to 22.5 87 to 124Noncalcified plaque volume 0.95 0.88–0.98 12.6 to 8.6 257 to 130Noncalcified plaque, % 0.99 0.97–0.99 13.4 to 8.0 —

InterscanReader 1

Total plaque volume 0.97 0.93–0.99 8.4 to 11.1 96 to 84Calcified plaque volume 0.97 0.92–0.99 8.0 to 10.0 101 to 89Noncalcified plaque volume 0.96 0.91–0.98 7.9 to 8.5 216 to 164Noncalcified plaque, % 0.96 0.91–0.98 19.6 to 15.9 —

Reader 2Total plaque volume 0.96 0.91–0.98 9.7 to 14.1 77 to 103Calcified plaque volume 0.96 0.90–0.98 10.0 to 13.0 84 to 107Noncalcified plaque volume 0.93 0.84–0.97 7.3 to 8.7 210 to 154Noncalcified plaque, % 0.97 0.93–0.99 14.7 to 15.3 —

Interobserver-interscanReader 1 CCTA 1 to reader 2 CCTA 2

Total plaque volume 0.82 0.62–0.92 21.5 to 26.3 134 to 143Calcified plaque volume 0.87 0.72–0.94 18.1 to 26.3 127 to 150Noncalcified plaque volume 0.96 0.91–0.98 9.2 to 5.7 269 to 118Noncalcified plaque, % 0.96 0.90–0.98 22.6 to 13.4 —

Reader 2 CCTA 1 to reader 1 CCTA 2Total plaque volume 0.81 0.60–0.91 21.5 to 23.8 69 to 76Calcified plaque volume 0.88 0.73–0.95 18.9 to 15.8 77 to 63Noncalcified plaque volume 0.87 0.73–0.94 12.6 to 18.1 128 to 223Noncalcified plaque, % 0.95 0.89–0.98 16.9 to 223.1 —

CI, confidence interval.

318 Journal of Cardiovascular Computed Tomography, Vol 3, No 5, September/October 2009

Visual determination of plaque presence on CCTA is highlyreproducible. Previously, the shortest reported time be-tween scans allotted for detecting serial plaque change withcoronary calcium scanning is 12 months.15–17 On the basisof this information, we believe the 200-day span specifiedin our study adequately ensured no major coronary plaquechange in patients without interscan coronary artery events.Our CCTA results supported this important assumption, de-tecting a small absolute increase in mean total plaque vol-ume (40.6 45.5 mm3) and minimal intraobserver bias in allmeasurements between serial scans. The 12% increase isconsistent with data from Schmid et al,11 who estimatedthe annualized rate of plaque progression at 22%.

Reproducing plaque volume quantification was less ro-bust. Although correlations of interobserver, intraobserver-

interscan, and interobserver-interscan volumes were excel-lent, differences in agreement remained large compared withunderlying plaque volume. We believe this primarily reflectedthe challenge in quantifying small coronary plaques; totalplaque volume in 77% of study segments was ,50 mm3. Insuch cases, small absolute variations become relatively large.These variations may have arisen from a number of sources:volume averaging, which probably affected each reader’scross-sectional plaque tracing despite the use of the smallestpossible slice thickness; calcium-related artifact (bloomingand beam-hardening), which probably caused windowingand display differences between readers (we allowed window-ing changes to reflect real-life practice); underlying readerbias, found with any manual tracing technique. Because we re-stricted our analyses to segments exhibiting at least adequate

Cheng et al Interscan coronary plaque quantification with CT 319

visual quality, we believe the effect of individual technical fac-tors (such as contrast enhancement, contrast timing, and heartrate) on plaque volume variability was probably small.

Significantly lower intraobserver reproducibility wasnoted when assessing small coronary plaques as previouslydescribed.18 Susceptibility of interscan plaque volume re-producibility to relatively large differences in these situa-tions should caution readers when interpreting resultsfrom serial CCTA studies. When evaluating small plaques,our data suggest that plaque composition is the most repro-ducible parameter, demonstrating ,17% error in intraob-server serial assessment and ,24% error in interobserverserial assessment.

In comparison to other works that assessed nonserialreproducibility of plaque volume quantification withCCTA,18–20 the plaques we studied were significantlysmaller. Our quantification method was similar in address-ing only proximal coronary segments and systematicallytracing coronary plaques along the longitudinal axis of theaffected segment. We were rigorous in adjusting to eachacquired dataset by determining scan-specific 3-dimensionaldistance covered by the plaque and corresponding stepincrements. Overall, our technique was most comparableto that used by Hoffmann et al18 in their evaluation of non-serial observer variability with CCTA. Those investigatorsalso found great variability when performing volumetricmeasurement in their subset of small plaques.

By performing analysis on a per-segment (and in caseswhen the segments contained only 1 visible plaque, per-plaque) basis, we maximized the adverse effects of smallplaques on reproducibility and thus biased our datasettoward high interscan variability. Combining measurementsfrom multiple segments to represent total vessel or totalpatient plaque burden may lead to improved results andshould be studied in larger cohorts. Currently, manualmeasurement of ‘‘total plaque burden’’ is tremendouslylabor intensive and, to the best of our knowledge, availablesoftware-based tools to expedite this process have yet to bevalidated.

CCTA offers the prospect of serial noninvasive coronaryplaque evaluation. The high interscan concordance ofplaque presence found in our study shows that CCTA canindeed ‘‘track’’ plaque, whereas the interscan variability insegmental plaque volume suggests individual plaque quan-tification is currently best reserved for detecting largechanges. We anticipate continued improvement in thisendeavor as techniques emerge to improve spatial resolu-tion, reduce calcium-related artifact, and remove reader-based bias.

Limitations

Our sample size was small, reflecting the unusual clinicaloccurrence of repeating CCTA within a short period of time;nevertheless, it represented the largest cohort of its kind tobe studied to date. Image data acquired from 2 different

scanners were used and may have introduced additionalvariability; however, our sample size was insufficient todetect such a difference. Because of the absence of priorwork in interscan reproducibility with CCTA, we could notverify that some amount of detectable plaque volumeprogression did occur and contributed to the detectedvariability, although, based on prior data,11 we suspect theeffect of this was minor. As noted in ‘‘Results.’’, pla-ques . 80 mm3 were not included in our study population.This may have occurred because of increased clinical ten-dency to revascularize larger plaques. We only evaluatedproximal vessel segments. In mid and distal coronary seg-ments, where plaques are expected to be smaller, segmentalreproducibility may be reduced. Manual quantification ofplaque volume is a time-consuming task unrealistic for clin-ical practice; its principal use remains for research. Invasiveassessment of plaque volume and composition was notavailable.

Conclusion

In summary, CCTA shows promise as a tool for mon-itoring serial coronary plaque change, although more workto reduce interobserver and interscan reproducibility isneeded. At present, highly reproducible measures of plaquedetection and percentage of plaque composition are achiev-able, with lower levels of agreement for absolute plaquevolume.

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