The number and width of CT detector rows determine the

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1 Iodinated Contast Opacification s in Nomal Coonay Ateies Imaged With Pospectively ECG-Gated Single Heat Beat 320-Detecto Row Computed Tomogaphy Michael L. Steigne, MD; Dimitios Mitsouas, PhD; Amanda G. Whitmoe, BA; Hansel J. Oteo, MD; Chunliang Wang, MD; Ola Buckley, MD; Noah A. Levit, BS; Alia Z. Hussain, MD; Tianxi Cai, PhD; Richad T. Mathe, PhD; Öjan Smedby, MD; Macelo F. DiCali, MD; Fank J. Rybicki, MD, PhD Backgound To define and evaluate coonay contast opacification gadients using pospectively ECG-gated single heat beat 320-detecto ow coonay angiogaphy (CTA). Methods and Results Thity-six patients with nomal coonay ateies detemined by mm detecto ow coonay CTA wee etospectively evaluated with customized image postpocessing softwae to measue Hounsfield Units at 1-mm intevals othogonal to the atey cente line. Linea egession detemined coelation between mean Hounsfield Units and distance fom the coonay ostium (egession slope defined as the distance gadient G d ), lumen coss-sectional aea (G a ), and lumen shot-axis diamete (G s ). Fo each gadient, diffeences between the 3 coonay ateies wee analyzed with ANOVA. Linea egession detemined coelations between measued gadients, heat ate, body mass index, and cadiac phase. To detemine feasibility in lesions, all 3 gadients wee evaluated in 22 consecutive patients with left anteio descending atey lesions 50% stenosis. Fo all 3 coonay ateies in all patients, the gadients G a and G s wee significantly diffeent fom zeo (P ), highly linea (Peason values, 0.77 to 0.84), and had no significant diffeence between the left anteio descending, left cicumflex, and ight coonay ateies (P 0.503). The distance gadient G d demonstated nonlineaities in a small numbe of vessels and was significantly smalle in the ight coonay atey when compaed with the left coonay system (P 0.001). vaiations between cadiac phases, heat ates, body mass index, and eades wee low. s in patients with lesions wee significantly diffeent (P 0.021) than in patients consideed nomal by CTA. Conclusions Measuement of contast opacification gadients fom tempoally unifom coonay CTA demonstates feasibility and epoducibility in patients with nomal coonay ateies. Fo all patients, the gadients defined with espect to the coonay lumen coss-sectional aea and shot-axis diametes ae highly linea, not significantly influenced by the coonay atey (left anteio descending atey vesus left cicumflex vesus ight coonay atey), and have only small vaiation with espect to patient paametes. Peliminay evaluation of gadients acoss coonay atey lesions is pomising but equies additional study. (Cic Cadiovasc Imaging. 2010;3: ) Key Wods: computed tomogaphy coonay vessels imaging atheoscleosis The numbe and width of CT detecto ows detemine the caniocaudal coveage pe ganty otation. Coonay CT angiogaphy (CTA) with 64 detecto ows, each 0.5 mm wide, simultaneously ecods 32 mm ( mm) of image data pe ganty otation. Thus, multiple ganty otations ae combined fo image intepetation; each otation contibutes a cadiac subvolume. Spatial misalignment between subvolumes is temed stai-step o slab atifact. Tempoal misalignment between subvolumes fo coonay contast opacification efes to diffeences in attenuation induced by time diffeences between acquisitions of the supeio vesus infeio subvolumes. Clinical Pespective on p 186 Wide aea detecto CT povides up to 160-mm ( mm detecto ows) caniocaudal coveage, eliminating spatial and tempoal misalignment in coonay CTA. Whole volume acquisition enables quantification of the spatial vaiation in Hounsfield units (HU) ove the entie coonay at a single point in time. We define the tem Received Febuay 2, 2009; accepted Decembe 2, Fom Applied Imaging Science Laboatoy, Depatment of Radiology, (M.L.S., D.M., A.G.W., H.J.O., O.B., N.A.L., A.Z.H., F.J.R.) and Noninvasive Cadiovascula Imaging, (M.F.C.), Bigham and Women s Hospital and Havad Medical School, Boston, MA; Depatment of Radiology (C.W., O.S.) and the Cente fo Medical Image Science and Visualization, Linköping Univesity, Linköping, Sweden; the Depatment of Biostatistics, Havad School of Public Health, Boston, MA (T.C.); Toshiba Ameica Medical Systems, Tustin, CA (R.T.M.). Guest Edito fo this aticle was David Bluemke, MD, PhD. Coespondence to Fank J. Rybicki, MD, Applied Imaging Science Laboatoy, Depatment of Radiology, Noninvasive Cadiovascula Imaging Pogam, Bigham and Women s Hospital and Havad Medical School, 75 Fancis St, Boston, MA fybicki@patnes.og 2010 Ameican Heat Association, Inc. Cic Cadiovasc Imaging is available at DOI: /CIRCIMAGING

2 180 Cic Cadiovasc Imaging Mach 2010 coonay contast opacification gadient to descibe these changes. If these paametes could be apidly and epoducibly computed, they would have the potential to extend the ole of cadiac CT beyond coonay atey mophology alone. One advantage could be ealized in patients with diffuse coonay atey disease (CAD) whee the lumen aea is diffusely smalle than nomal 1,2 and thus thee is no nomal efeence segment fo quantitative measues. Moeove, lesions with 50% naowing in these patients ae consideed a substate fo plaque uptue and acute coonay syndome. 3 5 An initial expeiment of nomal coonay ateies imaged by CT in a single R-R measued the diffeence of the mean HU between the ostium and the point whee the nomal vessel tapeed to 2.5-mm diamete. This wok showed a small but consistent decease in contast opacification fom the poximal to distal coonay atey. 6 This poject extends the quantitative assessment of nomal coonay contast attenuation by sampling coonay HU evey 1 mm along the atey. This high ate of sampling enables evaluation of opacification gadients as opposed to diffeence measuements. Although coonay segmentation is available fo seveal postpocessing softwae packages, customized softwae is equied to extact the mean HU othogonal to the cente line at 1-mm intevals. Using a customized softwae package developed fo coonay contast opacification gadients, the pimay pupose of this study was to demonstate that 3 opacification gadients can be noninvasively measued using single heat beat 320-detecto ow CT in patients with nomal ateies. The fist gadient, the distance gadient (denoted G d ), is defined as the change in HU pe centimete of coonay atey. The second and thid gadients ae defined as the change in HU with espect to the coonay atey lumen aea (G a ) and shot-axis diamete (G s ) othogonal to the cente line, espectively. The second pupose of this study was to evaluate the popeties of the 3 gadients, including goodness-of-fit of the espective linea model, potential diffeences between the thee main coonay ateies, and the influence of patient heat ate (HR) and body mass index (BMI). Methods Patients The institutional human eseach committee appoved this etospective study and waived the need fo witten infomed consent. All patients had clinical indications fo coonay CTA. We etospectively evaluated 36 consecutive single R-R mm detecto configuation (Toshiba AquilionOne Dynamic Volume CT, Tochigiken, Japan) pospectively ECG-gated coonay CTA patients with nomal coonay ateies (Table 1). The diagnosis of nomal coonay ateies was obtained fom the CT imaging epots at ou institution. The phase window included 25% (60% to 85%) of the R-R inteval; this potocol has an estimated adiation dose of 5 to 6 msv, depending on body habitus. Two patients wee used to study cadiac phase vaiation. One was in the 36-patient cohot descibed above. The second was an additional patient with no CT evidence of CAD but who undewent etospective ECG gating without tube cuent modulation. Twenty-five consecutive patients with 50% stenosis in the left anteio descending coonay atey (LAD) wee used to test feasibility of computing gadients fom pospectively ECG gated single R-R coonay CTA (Table 1). Thee of these Table 1. Clinical Indications, Patient Demogaphics, and Cadiac Risk Factos fo the 36 Patients Without CAD and 22 Patients With CAD Imaged With Pospective Single R-R 320-Detecto Row CT Acquisition Patients Without CAD Patients With CAD Total No. of patients Indication Chest pain Pesugical evaluation Othe* Asymptomatic Demogaphics Male Mean age, 48.7 (30 66) 59.3 (35 78) 52.7 (30 78) y (ange) BMI, kg/m ( ) 27.5 ( ) 27.7 ( ) (ange) Risk factos Dyslipidemia Hypetension Obesity Diabetes Smoking blockade None mg mg mg HR Mean beats pe 58.2 (45 75) 58.3 (48 70) 58.3 (45 75) minute (ange) 65 beats pe minute 65 beats pe minute *Othe includes dyspnea and/o am numbness/tingling. patients wee excluded because of eos in coonay segmentation: 2 fom dense calcification and 1 fom a coonay stent. Of the emaining 22 patients included in the study, all 7 who undewent conventional coonay angiogaphy had confimation of the LAD disease. Thee hunded twenty detecto-ow CT images wee acquied with 350-ms ganty otation time and 120 kv tube voltage. Among the total 58 patients, 43 wee acquied at 400 ma (standad); 15 patients wee imaged at 580 ma because of a lage body habitus. All patients eceived 80 ml iopamidol 370 mg I/mL (Isovue-370, Bacco Diagnostics, Pinceton, NJ) and 40 ml saline, both at 6 ml/s, injected with a dual injecto (EZEM Empowe CTA DUAL Injecto, EZEM Inc, Lake Success, NY). Bolus tacking in the descending aota was pefomed using a 200-HU theshold. The taget HR fo -blockade (intavenous metopolol, 5-mg incements to a maximum of 20 mg) was 65 beats pe minute. Thee wee no patients with containdication to -blockade, and thee wee no obseved o epoted side effects fom the -blockes. All 58 patients eceived 0.4 mg sublingual nitoglyceine befoe imaging.

3 Steigne et al Nomal Coonay CT Contast s 181 Figue 1. Linea fit of the distance (A), shot-axis diamete (B), and coss-sectional aea (C) gadients in the LAD fo a patient without and a patient with CT evidence of CAD, with esults of linea egession. Coonay Vessel Segmentation Fo each patient, at least 1 phase was identified to have excellent image quality fo the LAD, left cicumflex atey (LCx), and ight coonay atey (RCA). DICOM images fom this phase wee efomatted with a customized plug-in fo OsiiX 3.0.2, based on a 3D vitual contast injection method. 7 The following data wee obtained fom the egion of inteest defined as the entie segmented lumen at evey millimete othogonal to the coonay cente line beginning at the ostium and ending whee each vessel had adequate segmentation, typically when the diamete tapeed to oughly 1.5 mm: the mean and maximum attenuation (in HU), the cosssectional aea (in millimetes squaed), and the shotest diamete of the coss-section o the shot axis (in millimetes). Fo each vessel, a cadiovascula image with 6 yeas of expeience manually detemined the distal point and coected the lumen egions of inteest geneated by the vessel segmentation softwae when equied, fo example at banch points. Definition of Coonay Opacification s The 3 opacification gadients wee computed using linea egession fom the segmented data. The distance gadient, denoted G d, has units of HU pe centimete of coonay atey and is defined as the slope of the egession model, measued HU location G d c, whee the location is the distance distal to ostium in centimetes, and c is a constant detemined fom the linea egession. Note that G d is inheently less than zeo because HU measuements decease distally in a nomal coonay atey imaged with 320-detecto ow CT. 6 The aea gadient, denoted G a, has units of HU pe millimete squaed and is defined as the measued HU aea G a c, whee aea efes to the coss-sectional lumen aea othogonal to the cente line. The shot-axis diamete gadient, denoted G s, has units of HU pe millimete and is defined as measued HU shot-axis diamete G s c. As with the distance gadient, the slopes and constants fo the linea equations epesenting the coss-sectional aea and shot-axis diamete gadients wee obtained using linea egession. Coonay opacification gadients fo nomal patients wee computed fo both the mean and maximum HU values fom the vessel segmentation. Detailed analyses of contast opacification uses the mean HU ove the entie lumen. The maximum HU gadients wee used fo validation in nomal vessels; fo nomal ateies, the maximum HU gives an assessment elatively independent of patial volume effects. Statistical Analyses Fo egession models, the Peason coelation coefficient () was used to detemine the stength of coelation, that is, the goodnessof-fit. A magnitude of 0.25 indicates low coelation, modeate, stong, and 0.75 excellent. We consideed P 0.05 (2-sided t test) to define a egession coefficient (slope) significantly diffeent fom zeo. Geneal Popeties of s The Peason coelation coefficient and coesponding pobability value wee used to detemine whethe the gadient models defined wee appopiate fo each nomal coonay atey, that is, if the coelation was at least modeate ( 0.25) and the coesponding gadient (slope) was nonzeo (P 0.05). Only gadients meeting these citeia wee futhe evaluated.

4 182 Cic Cadiovasc Imaging Mach 2010 s in patients with no CT evidence of CAD undewent 1-way ANOVA to test the hypothesis that thee is no significant diffeence of the mean gadient between the 3 majo coonay ateies (LAD, LCx, and RCA). Ageement between gadients detemined fom the mean vesus maximum HU measuements in nomal vessels was assessed using the Peason coelation coefficient (). Vaiability and Repoducibility of Measued s HR and BMI Fo the 36 nomal patients, linea egession models wee used to detemine whethe each of the 3 gadients was coelated to patient HR and BMI fo each vessel. The egession coefficients wee used to estimate the influence of HR vaiations between 55 and 65 beats pe minute and patients with a BMI between 20 and 30 kg/m 2. Dift Ove Cadiac Phases Linea egession models wee used to evaluate fo dift (ie, a statistically significant tend) in gadient magnitude duing the cadiac cycle fo the LAD in the patient who undewent etospective ECG gating (5% to 95%) plus 1 of the 36 nomal patients fo whom segmentation was pefomed in all 3 ateies at all 1% intevals between 60% to 85%. Inteobseve Ageement In the patient fo whom segmentation was pefomed at all 1% intevals between 60% to 85%, a second cadiovascula image independently segmented and coected all 3 ateies at 9 phases (3% intevals). Inteobseve ageement was assessed using the Peason coelation coefficient between gadient magnitudes esulting fom the individual segmentations. Peliminay Evaluation of s in Patients With CAD Fo the CAD cohot, all 22 patients had 50% LAD stenosis as detemined by CT. s in the LAD wee computed using the same method as patients with nomal coonay ateies. A 2-sided t test was used to assess whethe each of the 3 gadients was the same in vessels without vesus in vessels with lesions. In this case, P 0.05 indicated that the mean gadient was significantly diffeent between the 2 goups of patients. Phantom Expeiment to Detemine Potential HU Changes Ove the Coonay Atey Field of View To assess potential attenuation dift inheent to the CT scanne, HU diffeences wee evaluated via a Delin cylinde phantom (TOS phantom, Toshiba Medical Systems Copoation, Otawaa, Japan), chosen because the popeties (330 HU, density 1.42 g/cm 3 ) oughly match a nomal contast enhanced coonay lumen. The phantom was scanned with one 0.5-second axial mm detecto ow ganty otation, 120 kv, 300 ma otation, and 5-mm econstuction thickness. The Delin CT numbe was measued via placement of a 330 mm 2 cicula egion of inteest evey 5 mm ove the cental 13 cm of the ganty, coesponding to the location of the coonay ateies fom which the 3 gadients ae computed. Results Geneal Popeties of s The coss-sectional aea (G a ) and shot-axis diamete (G s ) opacification gadients (Figue 1) ae significantly diffeent fom zeo (P ) in all 3 vessels fo all 36 patients with no CT evidence of CAD. Among these nomal vessels, the distance gadient was not significant in the RCA fo 2 patients and in the LAD in 1 patient. These wee the only 3 vessels, that is, 1% among a total of 324 gadients measued in 108 vessels (36 patients multiplied by 3 vessels pe Table 2. Distance Fom the Coonay Ostium, Shot-Axis Diamete, and Coss-Sectional Aea Opacification s, With Mean Values, Significance P Related to a Nonzeo Slope, and Peason Coelation Coefficient Related to Linea Goodness-of-Fit Vessel Mean SD Maximum P Value Peason Mean SD G d, distance fom ostium, HU/cm RCA LAD No CAD CAD * LCx G s, shot axis diamete, HU/mm RCA LAD No CAD CAD * LCx G a, aea, HU/mm 2 RCA LAD No CAD CAD * LCx Data ove all 36 patients with no CT evidence of CAD ae shown fo the shot-axis diamete and coss-sectional aea gadients. As noted in text, 3 vessels in patients with no CT evidence of CAD had a nonlinea ( 0.25) elationship between mean HU and distance fom the ostium (2 RCA plus 1 LAD); these 3 vessels ae excluded fom the distance gadient computations. *All 22 patients with lesions yielded P values All 36 patients with no CT evidence of CAD yielded P values patient, multiplied by 3 gadients pe vessel), with a Peason 0.25, indicating a nonlinea association of HU and distance fom the ostium. Table 2 consides the linea model fits in the emaining 105 vessels fo the distance gadient and all 108 vessels fo the othe 2 models. Regading goodness-of-fit, the mean Peason values fo G s and G a indicated excellent coelation, anging fom 0.79 (RCA) to 0.84 (LAD) and 0.77 (RCA) to 0.82 (LAD), espectively. The mean Peason values fo G d wee slightly lowe, anging fom 0.68 in the RCA to 0.80 in the LAD. Diffeences in significance, P, and coelation,, between G a and G s wee vey small, pobably eflecting the fact that coss-sectional aea and shot-axis diamete ae stongly elated in nomal coonay ateies. Compaing the gadient between the thee coonay ateies in all 36 patients (Figue 2), thee was no significant diffeence fo G a (ANOVA P 0.503) and G s (ANOVA P 0.625). Howeve, the magnitude of G d fo the RCA was significantly smalle than in the LAD and LCx (ANOVA P 0.001).

5 Steigne et al Nomal Coonay CT Contast s 183 Table 3. Coelations Between Mean and Maximum HU Contast Opacification s in 36 Patients With No CT Evidence of CAD Vessel Regession Coefficient Peason Distance, G d, HU/cm RCA LAD LCx Shot-axis diamete, G s, HU/mm RCA LAD LCx Aea, G a, HU/mm 2 RCA LAD LCx The egession coefficient indicates the elationship between the magnitude of the contast opacification gadient obtained fom maximum HU measuements to that obtained fom mean HU measuements. Ove the ange of standad coonay CTA patients, namely those with HR between 55 and 65 beats pe minute and BMI between 20 and 30 kg/m 2, the coelated gadient change was 1 standad deviation of the coesponding gadient obseved ove the 36-patient cohot with no CAD. Figue 2. Mean and standad deviation of the distance (A), shot-axis diamete (B), and coss-sectional aea (C) gadients fo the 3 majo coonay ateies in 36 nomal RCA, LAD, and LCx ateies, as well as coesponding gadients in 20 patients with LAD disease. Only the distance gadient has a significant diffeence between nomal coonay ateies; the RCA is significantly close to zeo than the LAD and LCx (ANOVA P 0.001). Patients with LAD stenosis have significantly diffeent gadient magnitudes than nomal patients (P 0.21 fo all thee gadient models). Using the maximum HU contast opacification gadients to evaluate the potential influence of volume aveaging, 5% of the 324 gadients had a Peason 0.25, as opposed to 1% fo the mean HU gadient definition, eflecting the fact that the maximum is not a smooth statistic. The maximum HU gadient was highly coelated to the mean HU gadient acoss all patients and gadient models, indicating that volume aveaging does not alte patient-specific diffeences in the measued gadient magnitude (Table 3, 0.9 fo 5 of 9 gadient models). Vaiability and Repoducibility of Measued s HR and BMI s exhibited significant (P 0.05) low to modeate (Peason 0.5) coelations with HR and BMI (Table 4). Dift Ove Cadiac Phases In the single patient with econstuctions at evey 1% intevals in diastole, all 3 gadients exhibited stong coelation with cadiac phase in the RCA and LCx (Table 5). None of Table 4. Coelations and Significance Between the 3 s and Each Atey With Respect to HR and BMI in 36 Patients With No CT Evidence of CAD RCA LAD LC Change Change Change Coelations fo distance gadient HR * 5.91* BMI Coelations fo shot-axis diamete gadient HR * 11.86* 0.40* 13.89* BMI 0.45* 16.35* 0.45* 16.68* 0.47* 17.73* Coelations fo coss-sectional aea gadient HR * 3.48* 0.43* 4.38* BMI 0.39* 3.37* 0.38* 3.51* 0.37* 4.04* The gadient change fo distance is expessed as HU/cm, fo diamete as HU/mm, and fo aea as HU/mm 2. The gadient change eflects the expected influence on the gadient magnitude of HR (55 to 65 beats pe minute) and BMI (20 to 30 kg/m 2 ) vaiations obseved fo coonay CTA patients, that is, gadient change egession coefficient 10 beats pe minute o kg/m 2 ]. *Significant coelations (P 0.05).

6 184 Cic Cadiovasc Imaging Mach 2010 Table 5. Coelations of s With Cadiac Phase in All 3 Vessels at 1% Phase Intevals Between 60% and 85% Cadiac Phase in One Patient and in the LAD at 5% Intevals Between 5% and 95% Cadiac Phase in Anothe Patient Phase Range, % P Value Coelation Coefficient, RCA Distance, G d * 0.55* Shot-axis diamete, G s * 0.56* Aea, G a * 0.66* LAD Distance, G d Shot-axis diamete, G s Aea, G a LCx Distance, G d * 0.78* Shot-axis diamete, G s * 0.67* Aea, G a * 0.72* *Significant tends ae obseved fo all 3 gadients in the RCA and LCx but not the LAD. the 3 gadients was coelated to cadiac phase in the LAD (Table 5). The LAD was futhe evaluated thoughout the entie R-R inteval fo the patient with etospective ECGgated acquisition. Fo these econstuctions spaced by 5% of the R-R inteval, none of the 3 gadients was coelated to cadiac phase in the LAD (Table 5). Example coelations in the RCA and LAD fo G a ae povided in Figue 3. The vaiation of the gadient magnitude though the cadiac cycle was smalle than its vaiation in the 36-patient cohot with no CAD (Figue 4). s in the LCx demonstated the lagest vaiation with espect to cadiac phase. Inteobseve Ageement Inteobseve ageement was excellent fo all gadients and ateies (Table 6). In addition to high ageement, the vaiation in gadient magnitudes obseved between eades (Table 6) was significantly smalle than both the entie sample of ateies as well as the obseved cadiac phases in 1 patient (Figue 4). Peliminay Evaluation of s in Patients With CAD All 3 gadients in all 22 patients with the LAD lesions wee significantly diffeent fom zeo (P , Figue 1). Regading goodness-of-fit, the mean Peason values fo G s and G a indicated stong coelation; fo G d thee was excellent coelation (Table 2). The slightly lowe Peason values fo G s and G a pobably eflect the moe challenging segmentation and subsequent impecision in the shot-axis diamete and aea measuements fo vessels with lesions. All 3 gadients in patients with LAD stenosis 50% had mean values significantly diffeent (P 0.021) compaed with Figue 3. Vaiation of aea gadient with espect to cadiac phase in diastole in one RCA (A) and though the entie cadiac cycle in the LAD of a diffeent patient (B). Linea egession esults ae shown fo the RCA, whee the tend was significant (Table 5, P 0.05). the coesponding gadients in patients with no CT evidence of CAD (Figue 1). The diffeence was most consistent fo the shot-axis diamete gadient (Figue 2B). Phantom Expeiment to Detemine Potential HU Changes Ove the Coonay Atey Field of View The mean (ange) HU measuements in the Delin cylinde wee HU (327.8 to HU). The vey small gadient ove the 4.5 HU ange had a slope of HU/cm, with the HU deceasing as measuements appoached the tube anode as detemined by the oientation of the phantom within the scanne. Discussion Wide aea detecto CT enables noninvasive quantitative assessment of coonay contast changes with tempoal unifomity. The cuent data confim that opacification gadients exist in patients with nomal coonay ateies. Customized image segmentation softwae is equied to quantify attenuation diffeences ove shot coonay distances. Until ecently, coonay CTA was pefomed with etospective ECG gating so that cadiac function could be estimated in conjunction with CAD. Because of the lowe adiation dose, pospective ECG gating is used with inceasing fequency 8 ; with this acquisition potocol, data egading cadiac function is not available. State-of-the-at multidetecto CT technology is now moving close to acquiing infomation egading myocadial pefusion. Howeve, pefusion data equie specialized potocols, ideally pefomed at both est and stess. Unlike the assessment of wall motion o pefusion, coonay contast opacification gadients ae simple paametes that only equie postpocessing tools. We defined, computed, and analyzed 3 coonay contast opacification gadients to quantify mean HU changes in

7 Steigne et al Nomal Coonay CT Contast s 185 Figue 4. Standad deviations of the magnitude fo all 3 gadients fo the 36 patients with no CT evidence of CAD (blue bas), 60% to 85% cadiac phase in 1 patient (ed bas), 5% to 95% cadiac phase at 5% intevals in a single LAD in 1 patient (puple bas), and between cadiovascula images pefoming the segmentation fo 9 cadiac phases in 1 patient (geen bas). Table 6. Diffeence in Analyzed by 2 Independent Cadiovascula Images (R1 and R2) fo 9 Diastolic Cadiac Phases Equally Spaced Between 60% and 85% in 1 Patient and Coesponding Inteobseve Ageement (Peason Coelation ) Vessel R1-R2 Diffeence (Mean SD) Peason Distance, G d, HU/cm RCA LAD LCx Shot-axis diamete, G s, HU/mm RCA LAD LCx Aea, G a, HU/mm 2 RCA LAD LCx nomal coonay ateies. The distance gadient G d is the linea fit that most esembles ealie wok that quantifies the decease in HU between 2 points in a coonay atey. 6 When compaed with the coss-sectional aea and shot-axis diamete gadients, the distance gadients may be consideed easie to intepet but in a small numbe of cases demonstate nonlineaities that may limit potential clinical use. One possible eason fo the slightly lowe goodness-of-fit fo G d compaed with G s and G a is the pesence of banching vessels. Those linea fits inheently measue changes in HU with espect to coonay lumen size and thus ae expected to be less sensitive to highly vaiable coonay banching pattens, a potential cause of nonlineaity in G d. Consideing only significance and coelation, the shot-axis diamete gadient slightly outpefomed the coss-sectional aea gadient. Neithe of those gadients demonstated a significant diffeence between the 3 majo coonay ateies. Howeve, the distance gadient was significantly diffeent in the RCA than in the left coonay system. In vessels with no wall calcification, gadients computed using maximum HU values ae insensitive to patial volume aveaging because the voxel with maximum HU fo evey coss section is expected to contain only contast-enhanced blood. In the 108 nomal vessels, the maximum HU gadients had excellent coelation with the mean HU gadients. Although small wall calcium (below visual theshold fo detection) could not be definitively excluded, the excellent coelation fo all vessels agues that patial volume effects and impefect segmentation do not skew gadient magnitude diffeences between patients. The potential utility of gadients in coonay CTA will depend on the ease and epoducibility of the measuements as well as sepaation between vessels with and without CAD. Regading gadient measuements, the equied customized softwae can be used on cuent DICOM coonay CTA data. Regading epoducibility, fo the patients with no CAD, we obseved limited impact of vaying HR, BMI, cadiac phases, and diffeent cadiovascula eades in compaison to vaiations in the patient population. In fact, many coelations such as those fo HR and BMI wee no moe than modeate and may be ielevant in lage populations. Regadless, the ensemble of esults well chaacteizes the distibution of all gadients in patients with no CAD, the pimay pupose of the study. Ou undestanding of gadients in diseased vessels is vey spase. Howeve, the peliminay evaluation in 22 patients with LAD disease suggests a consistent diffeence with nomal patients. Additional studies will be equied to confim the diffeences between patients with and without CAD fo diffeent lesion types. Initial studies will focus on patients with both focal lesions and diffuse CAD, as the latte goup is expected to have diffeences ove long segments of the coonay ateies and have a gaded, continuous pessue decease along the length of the atey. 9 Nomal coonay ateies do not have a measuable dop in pessue along thei couse. Howeve, the epoducibility of the gadient data agues that diffeences in opacification ae linked to flow. Regading coonay lesions, the most impotant facto to detemine esistance is the minimum cosssectional aea, 10 incopoated into the definition of G a. If 1 o moe gadients can be eliably measued acoss lesions o in patients with diffuse CAD, and if those gadients diffe fom the nomal coonay gadients established in this wok, these paametes could potentially be incopoated into the evaluation of CAD. It is impotant to acknowledge that the confimation of clinical utility will ultimately equie measues of clinical outcome fom multiple centes, and thus the study of contast opacification gadients is only in its infancy. Howeve, the low level of HU dift fo the scanne and the ease in computing the gadients makes it amenable fo futue wok.

8 186 Cic Cadiovasc Imaging Mach 2010 Limitations All patients eceived sublingual nitoglycein fo coonay vasodilation, inceasing coonay blood flow. It is not possible to detemine the influence on the calculated gadients, but the point could be elatively moot because essentially all coonay CTA is pefomed afte nitoglycein administation. All patients had identical iodinated contast injection and bolus tacking potocols. Howeve, the influence of contast media volume, ate of injection, and iodine concentation will also equie futhe evaluation. All patients wee evaluated on a single CT platfom that offes tempoal unifomity; that is, data fom the entie coonay tee was acquied at a single phase of opacification. Futue wok will evaluate if and how the gadients change when the image data ae acquied on diffeent CT platfoms. Anothe limitation is that thee is no coonay catheteization confimation that the patients pesumed to have no CAD ae in fact nomal. This evaluation was pefomed etospectively, and because of the high negative pedictive value of CT, patients with a nomal study typically equie no additional imaging. Futue wok using patients with and without CAD will confim the pesence of opacification gadients in patients with no CAD confimed with coonay catheteization. Finally, efinements in the postpocessing softwae will advance ou ability to apidly detemine the gadients with little use input. The pesent softwae equies manual coection nea banch vessels. The time fo a complex coonay system (all vessels) is 45 minutes (standad deviation 10 minutes). Futhe efinements to the softwae ae expected to educe the time buden to levels compatible with clinical wokflow. Conclusion The mean HU changes along the couse of a coonay atey ae temed contast opacification gadients and can be epoducibly evaluated with a 320-detecto ow CT acquisition. In nomal coonay ateies, the gadients computed with espect to coss-sectional lumen shot-axis diamete and aea othogonal to the coonay centeline ae significant, linea, and not significantly influenced by the coonay atey (LAD vesus LCx vesus RCA). The modeate influence fom BMI, HR, and cadiac phase vaiations ae pobably compatible with changes in motion atifact and signal-to-noise atio cuently obseved in clinical coonay CTA. Studying changes between coonay ateies in the same patient and changes within individual coonay ateies may povide insight with espect to coonay physiology not peviously accessible noninvasively. Ealy expeience in vessels with lesions demonstates feasibility and futhe studies ae waanted. The clinical utility of these measuements will ely on potential diffeences when these new paametes ae studied in patients with CAD. Souces of Funding This study was funded in pat by National Institutes of Health gant (NIH K23-EB00882; Rybicki), as well as funded, in pat, by a eseach gant fom Toshiba Medical Systems Copoation and the Bacco Diagnostics. Disclosues D. Rybicki seved as speake fo and eceived honoaia fom the Toshiba Copoation and seved on the advisoy boad fo Toshiba Copoation, Bacco Goup, and Vital Images, Inc. Refeences 1. Robets WC, Jones AA. Quantitation of coonay ateial naowing at necopsy in sudden coonay death: analysis of 31 patients and compaison with 25 contol subjects. Am J Cadiol. 1979;44: Macus ML, Haison DG, White CW, McPheson DD, Wilson RF, Kebe RE. Assessing the physiologic significance of coonay obstuctions in patients: impotance of diffuse undetected atheoscleosis. Pog Cadiovasc Dis. 1988;31: Libby P. Molecula bases of the acute coonay syndomes. Ciculation. 1995;91: Falk E, Shah PK, Fuste V. Coonay plaque disuption. Ciculation. 1995;92: Fab A, Tang AL, Buke AP, Sessums L, Liang Y, Vimani R. Sudden coonay death: fequency of active coonay lesions, inactive coonay lesions, and myocadial infaction. Ciculation. 1995;92: Rybicki FJ, Oteo HJ, Steigne ML, Voobiof G, Nallamshetty L, Mitsouas D, Esoy E, Mathe RT, Judy PF, Cai T, Coyne K, Schultz K, Whitmoe AG, Di Cali MF. Initial evaluation of coonay images fom 320-detecto ow computed tomogaphy. Int J Cadiovasc Imaging. 2008; 24: Wang C, Smedby Ö. Coonay atey segmentation and skeletonization based on competing fuzzy connectedness tee. Med Image Comput Assist Intev. 2007;10(Pt 1): Steigne ML, Oteo HJ, Cai T, Mitsouas D, Nallamshetty L, Whitmoe AG, Esoy H, Levit NA, Di Cali MF, Rybicki FJ. Naowing the phase window width in pospectively ECG-gated single heat beat 320-detecto ow coonay CT angiogaphy. Int J Cadiovasc Imaging. 2009;25: De Buyne B, Hesbach F, Pijls NH, Batunek J, Bech JW, Heyndickx GR, Gould KL, Wijns W. Abnomal epicadial coonay esistance in patients with diffuse atheoscleosis but nomal coonay angiogaphy. Ciculation. 2001;104: Klocke FJ. Measuements of coonay blood flow and degee of stenosis: cuent clinical implications and continuing uncetainties. J Am Coll Cadiol. 1983;1: CLINICAL PERSPECTIVE Coonay computed tomogaphy angiogaphy pefomed at a single phase in the cadiac cycle ove one heat beat enables noninvasive quantitative assessment of coonay contast changes with tempoal unifomity. These contast opacification gadients exist and ae epoducible in patients with nomal coonay ateies. The clinical impact of this finding is that gadients can be measued in both nomal and abnomal coonay ateies, and gadients have the potential to futhe contibute to the noninvasive evaluation of coonay lesions. These analyses equie customized image segmentation softwae to measue attenuation diffeences ove shot coonay distances. Futhe wok is needed to chaacteize gadients acoss diffeent lesion subtypes.