Digitalimaginggroup.caEur Radiol (2012) 22:39–50DOI 10.1007/s00330-011-2260-x Non-invasive assessment of functionally relevant coronaryartery stenoses with quantitative CT perfusion: preliminaryclinical experiences Aaron So & Gerald Wisenberg & Ali Islam & Justin Amann & Walter Romano &James Brown & Dennis Humen & George Jablonsky & Jian-Ying Li & Jiang Hsieh &Ting-Yim Lee Received: 4 April 2011 / Revised: 23 August 2011 / Accepted: 25 August 2011 / Published online: 21 September 2011 # European Society of Radiology 2011 Non-Stenosed (NS, angiographically normal or mildly Objectives We developed a quantitative Dynamic Contrast- irregular), Moderately Stenosed (MS, 50–80% reduction Enhanced CT (DCE-CT) technique for measuring Myo- in luminal diameter), Severely Stenosed (SS, >80%) and SS cardial Perfusion Reserve (MPR) and Volume Reserve with Collaterals (SSC). DCE-CT at rest and after dipyr- (MVR) and studied their relationship with coronary idamole infusion was performed using 64-slice CT. Mid- diastolic heart images were corrected for beam hardening Methods Twenty-six patients with Coronary Artery Disease and analyzed using proprietary software to calculate (CAD) were recruited. Degree of stenosis in each coronary Myocardial Blood Flow (MBF, in mL min-1 100 g-1) and artery was classified from catheter-based angiograms as Blood Volume (MBV, in mL 100 g-1) parametric maps.
MPR and MVR in each coronary territory were calculatedby dividing MBF and MBV after pharmacological stress by A. So : G. Wisenberg : T.-Y. Lee their respective baseline values.
Imaging Program, Lawson Health Research Institute,London, Ontario, Canada Results MPR and MVR in MS and SS territories weresignificantly lower than those of NS territories (p<0.05 for A. So (*) : T.-Y. Lee all). Logistic regression analysis identified MPR MVR as Imaging Research Laboratories, Robarts Research Institute, the best predictor of ≥50% coronary lesion than MPR or 100 Perth Drive,London, Ontario, N6A 5K8, Canada Conclusions DCE-CT imaging with quantitative CT perfu-sion analysis could be useful for detecting coronary A. So G. Wisenberg T.-Y. Lee stenoses that are functionally significant.
Medical Biophysics, University of Western Ontario, London, Ontario, Canada • A new quantitative CT technique for measuring myocardial G. Wisenberg A. Islam J. Amann W. Romano T.-Y. Lee function has been developed Medical Imaging, University of Western Ontario, • This new technique provides data about myocardial London, Ontario, Canada perfusion and volume reserve G. Wisenberg J. Brown D. Humen G. Jablonsky • It demonstrates the important relationship between Cardiology, London Health Sciences Centre, myocardial reserve and coronary stenosis.
London, Ontario, Canada • This single test can identify which coronary stenoses are functionally significant A. Islam : J. Amann : W. RomanoRadiology, St. Joseph's Health Care,London, Ontario, Canada Keywords Coronary artery disease . Quantitativemyocardial blood flow and blood volume measurement .
J.-Y. Li : J. Hsieh Dynamic contrast-enhanced CT . Beam hardening CT Engineering, GE Healthcare,Waukesha, Wisconsin, USA correction, CT perfusion Eur Radiol (2012) 22:39–50 patients had surgical revascularization between the coronaryangiography and CT perfusion studies.
Myocardial Perfusion Reserve (MPR), defined as theratio of Myocardial Blood Flow (MBF) during maximal coronary vasodilation induced by exercise or pharmaco-logic stress as compared to its resting value, has been All patients had ECG stress testing and thirteen had used to assess the residual vasodilator reserve in patients additional SPECT MIBI stress imaging as part of their with advanced Coronary Artery Disease (CAD) [ normal care before the research DCE-CT perfusion study.
Coronary stenoses that limit MBF during exercise or Stress tests were interpreted by cardiologists or nuclear pharmacologically induced vasodilation are considered medicine physicians who were unrelated to the research functionally significant because of the attenuation of study and were blinded to its results. A stress test was vascular reserve ].
classified as positive if the physical or pharmacological The intrinsic vasodilation in arterioles in the ischemic stress induced abnormal changes in ECG or a fixed or myocardium in compensation for the impeded flow from reversible perfusion defect in SPECT stress imaging. The the upstream stenosed artery would suggest that Myo- presence of Myocardial Infarction (MI), defined as (a) cardial Volume Reserve (MVR), defined similarly as decreased uptake of MIBI in both the rest and stress MIBI MPR but with respect to Myocardial Blood Volume imaging (fixed perfusion defect) or (b) the presence of Q (MBV), could be an additional marker of stenoses that waves on the resting ECG, was also assessed.
are functionally significant. Nuclear medicine perfusionimaging has been used to measure regional MPR in Coronary angiography clinical settings [, ] but to our best knowledgemeasurement of MVR in CAD patients has not been The angiograms, performed within two weeks of DCE-CT reported before.
imaging of the heart, were qualitatively interpreted by We have previously shown that Dynamic Contrast cardiologists blinded to the imaging results. The degree of Enhanced CT (DCE-CT) with deconvolution analysis stenosis and collateral flow to the Left Circumflex (LCx), based on a distributed parameter model of the DCE-CT Left Anterior Descending (LAD) and Right Coronary (RC) images (CT Perfusion, GE Healthcare, Waukesha, USA) arteries were classified as: (1) Non-Stenosed (NS), in which is a robust technique for measuring absolute tissue the coronary artery was either normal angiographically or blood flow (in mL min-1 g-1) and blood volume (mL g-1) mildly irregular; (2) Moderately Stenosed (MS), where the [, More recently, we have developed an image-based artery was 50 to 80% narrowed in luminal diameter; (3) algorithm for reducing beam hardening artifacts in cardiac Severely Stenosed (SS), where the artery was over 80% DCE-CT images . In this paper, we investigated narrowed and (4) SS but the jeopardized vascular bed was whether quantitative CT perfusion, with correction of fed by collaterals from an adjacent coronary artery (SSC).
beam hardening in the DCE-CT images of the heart, couldbe used to measure MPR and MVR in patients with DCE-CT imaging of the heart known CAD, and the relationship of these measurementswith the stenotic severity of the coronary arteries as This study used a 64-slice CT (LightSpeed VCT, GE determined by invasive coronary angiography. DCE-CT Healthcare, Waukesha, USA) system in which the detector measurement of MPR was also compared with SPECT width was 4 cm. Eight consecutive 5-mm-thick slices stress / rest imaging with 99mTc-sestamibi (MIBI) covering the largest cross-sectional area of the LV in an performed in a subgroup of patients to further illustrate approximate Horizontal Long-Axis (HLA) view were the usefulness of quantitative CT perfusion for assessing selected for DCE-CT imaging. To measure MBF at functionally significant coronary lesions.
baseline, a 30 s cine CT data acquisition using 140 kVpand 50 mA with breath-hold was initiated at 4–5 s intointravenous injections of contrast (Omnipaque 300, GE Healthcare, Waukesha, USA, 50 mL at 4 mL s-1) and saline(40 mL at 4 mL s-1). The gantry speed was 0.5 s per Patient population rotation. Five min after the baseline CT data acquisition,dipyridamole (DIP) at 0.56 mg kg-1 was infused intrave- Twenty-six patients with known CAD based on prior non- nously over 4 min and the cine CT data acquisition was invasive stress testing were recruited. The study protocol repeated at 3 min after the infusion to measure hyperaemic was approved by the institutional research ethics board. All MBF. Aminophylline was given as required at the end of patients gave informed consent for the study. None of the the hyperaemic DCE-CT by an attending cardiologist.
Eur Radiol (2012) 22:39–50 CT functional maps DCE-CT images at Mid-Diastole (MD) from all cardiaccycles were manually selected for analysis to minimize theeffect of cardiac motion. A semi-automatic registrationprogram was applied to the selected MD images to ensureany residual lung or cardiac motion was minimized. TheMD images were also corrected for beam hardening usingan algorithm developed in our lab [. With thesecorrections, we were able to calculate MBF and MBVmaps from cine images with minimal motion and beamhardening artifacts using the CT Perfusion softwaredeveloped in our lab. The theoretical basis of CT Perfusionhas previously been discussed [, ] (Fig. Data and statistical analysis MPR and MVR calculations Myocardium in each CT section was divided into sixsegments according to the AHA schema for the HLA viewof the LV  (Fig. The supply artery to each segment,according to published reports, were also shown , ].
The basal lateral and/or basal septal segments might beabsent in the more superior slices within the 4 cm coverage.
MPR and MVR in each segment were calculated bynormalizing MBF and MBV respectively after DIP chal-lenge to its baseline value. Mean MPR and MVR in LCx,LAD, and RC coronary territory were determined by firstfinding the average of the involved segments in each slicebefore averaging over all slices.
Baseline MBF and MBV, MPR, and MVR corresponding Fig. 1 a–d DCE-CT images of the heart at different MDs acquired to the four levels of stenotic severity defined above after a bolus injection of contrast. e Aortic and myocardial time- were analyzed for significant differences using a one- density curves measured from all the MD images from DCE-CT wereanalyzed using CT Perfusion (GE Healthcare) from which the MBF way ANOVA omnibus test (SPSS Inc). Post-hoc t-tests and MBV maps were calculated with Tukey correction were used to determine whichgroup differed from the NS group at the level ofp < 0.05. All measurements were reported as mean ±standard deviation.
predictor for differentiating stenosis ≥ 50% from NSwas defined as the value at the cutoff probability of 0.5.
Logistic regression analysis In the multivariate analysis, both MPR and MVR and theirinteraction term were considered by the regression model. A Both univariate and multivariate logistic regression likelihood ratio test was applied to identify the most analyses were used to identify predictors of stenosis significant predictor of ≥ 50% stenosis, and the less significant ≥50% or NS. In the univariate analysis, only one predictors were excluded from the regression model.
potential predictor (either MPR or MVR or their Sensitivity, specificity, PPV, and NPV of the most interaction term) was included in the logistic regression important predictor were calculated as in the univariate model. Sensitivity, specificity, positive predictive value analysis. The results from the multivariate and univariate (PPV), and negative predictive value (NPV) of the tests were compared. All the logistic regression analyses tested predictor were calculated. The threshold of each were performed using SPSS for Windows (SPSS Inc.).
Eur Radiol (2012) 22:39–50 Fig. 2 a and b Averaged mapsin approximate HLA view of theLV in two different slices. c Thecorresponding distribution ofcoronary territories in the LVmyocardium. The basal septalsegment was not seen in theaveraged map shown in (a). dApproximate position of theHLA slices of a DCE-CTperfusion study with respect tothe short-axis orientation of cor-onary territories. The slices cor-respond to (a) and (b) arehighlighted in deep yellow ROC curve analysis The diagnostic performance of either MPR or MVR to distinguish NS lesions from ≥50% stenoses was alsoevaluated using Receiver Operating Characteristic There were 23 male and 3 female patients in this study; (ROC) curve analysis. Diagnostic performance was their mean age was 62±9 years. All had stress ECG and 13 estimated from the Area Under the ROC Curve (AUC) had additional MIBI SPECT (Table Among the twenty- and its 95% Confident Interval (CI) estimated. All ROC six patients, 25 had positive stress tests and 1 had a curve analyses were performed using SPSS for Windows negative test. Thirteen patients had MI while 13 patients showed no evidence of MI. Among the patients whounderwent MIBI SPECT, all showed perfusion defects (1 Comparison with SPECT stress results fixed, 2 partially reversible and 10 reversible).
In patients who had prior SPECT MIBI studies, mean MPRs Coronary angiography in the coronary territories with and without SPECT defectwere compared. Corresponding coronary territories in the There were 6 patients with single-vessel, 8 with double- approximate HLA MBF maps and short-axis SPECT maps vessel, 12 with triple-vessel CAD, and 10 had collateral were identified with the help of the AHA model of coronary supply to the stenosed coronary arteries (Table ). Table territories for the respective tomographic planes. Differences also lists the number of coronary territories in each patient in MPR between territories with and without SPECT defects assigned to subgroups of NS, MS, SS, and SSC according were evaluated by unpaired t-test.
to the angiographic results.
DCE-CT perfusion measurements Effective dose of a CT perfusion study was estimated as the Figure illustrates the MBF maps obtained before and after product of the Dose Length Product (DLP) reported by the CT DIP stress in selected patients. Four out of a total of 78 system and the conversion factor (0.014 mSv mGy-1 cm-1) for coronary territories from 26 patients (3 territories per patient) were excluded for analysis due to significant misalignment Eur Radiol (2012) 22:39–50 Table 1 Summary of stresstesting (SPECT or ECG) results Post-stress perfusion on study patients Y present; N absent; ex. exertional; (+) positive result; (−) negativeresult; (/) MIBI test not per- formed; n/a data not available; MIBI defects: r reversible; pr partially reversible; f fixed between the two DCE-CT studies. Of the remaining 74 Logistic regression analysis coronary territories, 17 were assigned as NS, 22 as MS, 25 asSS, and 10 as SSC from the results of coronary angiography.
The odds ratio (95% CI) of MPR, MVR, and MPR MVR Baseline MBF in the NS, MS, SS, and SSC segments were determined by independent univariate logistic regression 104.5 ±18.4, 111.4 ± 20.9, 114.0 ±20.1, and 113.1 ± 28.1 analyses were 0.085 (0.02–0.36), 0.007 (0.0–0.16) and mL min-1 (100 g)-1 respectively (Fig. and baseline MBV 0.299 (0.15–0.59) respectively indicating that all three were 8.6±1.2, 8.9±1.5, 9.1±1.4, and 9.0±1.8 mL (100 g)-1 predictors were useful in detecting the presence of ≥50% respectively (Fig. ). Both MBF and MBV were not stenosis but MPR MVR was the best predictor among the significantly different among stenosis groups at baseline. At three candidates investigated. The thresholds of MPR, DIP stress, MBF in the NS, MS, SS, and SSC groups were MVR, and MPR MVR for differentiating NS from ≥50% 230.2 ± 42.2, 195.2 ± 70.3, 196.4 ± 49.8, and 188.4 ± of stenosis were 2.5, 1.4, and 3.5 respectively. Sensitivity, 46.4 mL min-1 (100 g)-1 respectively (Fig. ) and MBV specificity, PPV, and NPV of MPR MVR and MPR for were 11.2±2.2, 9.9±3.0, 9.5±1.9, and 9.7±2.6 mL (100 g)-1 detection of ≥50% of coronary stenosis were 94.7%, 35.3%, respectively (Fig. Both hyperaemic MBF and MBV 83.1%, and 66.7% respectively while those for MVR were were not different among the groups. MPR in the NS, MS, 96.5%, 23.5%, 80.9%, and 66.7% respectively. Fig. a plots SS, and SSC segments were 2.3±0.5, 1.8±0.5, 1.8±0.3, and MVR vs. MPR measurements in all coronary territories of 1.8±0.5 respectively while MVR were 1.3±0.2, 1.1±0.3, the study patients. The threshold MPR MVR, derived from 1.0±0.2, and 1.1±0.3 respectively (Fig. ). MPR of the logistic regression analysis, separating the NS from the MS, SS, and SSC groups were significantly lower than that stenosed groups (i.e., MS, SS, and SSC) is also shown.
of the NS group (p<0.05), while MVR of the MS and SS Univariate analysis agreed with multivariate analysis, groups were lower than that of the NS group (p<0.05).
which also identified MPR MVR as the most significant Eur Radiol (2012) 22:39–50 Table 2 Summary of severity oflesion and collateral supply in Number of territories each coronary artery of the Mean age: 62±9 y; Gender: 23M, 3F; N normal coronary condition; * evaluated as mildly irregular but without stenosis;INT intermediate branch; O occluded; (c) supplied by col- laterals from adjacent coronary artery; / no collaterals predictor of ≥50% stenosis over MPR or MVR alone. The was not properly covered in the post DIP DCE-CT due to odds ratio and CI for MPR MVR reported from the patient movement. Of the remaining 12 patients, SPECT defect univariate analysis were identical to those reported by (including reversible and partial reversible) was observed in 12 out of 35 coronary territories (the RC territory from patient #26was also excluded due to motion). Mean MPRs in the 12/23 ROC curve analysis territories with/out SPECT defect were 1.53±0.41 and 1.96±0.52 (p<0.05, Fig. ). In three patients who had triple-vessel The ROC curve of each predictor is shown in Fig. The disease (#4, 21, and 24), while MPR in all three coronary AUC for MPR MVR was 0.791 and larger than those of territories were depressed relative to the mean MPR in the NS MPR (0.785) and MVR (0.778). The 95% CI of AUC for territories of those who had either a single or double CAD (≤ MPR MVR, MPR and MVR were 0.664 to 0.917, 0.662 to 1.9 vs. 2.3), the SPECT of each patient showed a perfusion 0.909, and 0.650 to 0.906 respectively. All the AUCs were defect in only one territory: LAD in patient #4; RC in patient significantly different from 0.5 (no-discrimination).
#21 and 24. Fig. shows the MIBI SPECT findings forpatient #21 at stress (Fig. and following redistribution at Comparison with SPECT stress test rest (Fig. The SPECT defect at stress was seen mostly inthe territory supplied by the RC. In patient #17 who had a Of the 13 patients who had defects (1 fixed, 2 partially partially reversible MIBI defect in the inferior wall perfused reversible, and 10 reversible) on SPECT, comparison of MPR by a MS RC artery, the DCE-CT MBF maps showed that in and SPECT results was not possible in the only patient with the RC territory the subepicardium in the basal septal wall of fixed defect because the basal septal wall (i.e., RC territory) the LV responded normally to hyperaemic DIP stress (MPR≈
Eur Radiol (2012) 22:39–50 Fig. 3 Averaged map at DIP stress, MBF map at baseline and DIP collateral supply. During DIP stress, a coronary steal also occurred in a stress are shown in each column from left to right. The range of MBF discrete region within but not the entire LCx territory (yellow arrow) value (in mL min-1 100 g-1) represented by the pseudo rainbow colour while the LAD territory, which was perfused by a normal LAD, scale is specified in each MBF map. a–c Patient #8 (in Tables and exhibited an over two times increase in MBF. g–i Patient # 21 with who had a normal LCx and an occluded LAD whose territory was fed moderate to severe stenoses in all three coronary arteries. Resting by collaterals. Following DIP administration, MBF in the LCx MBF was uniform and not different from the other two patients [100± territory increased by over two-fold; in contrast, a coronary steal 15 mL⋅min-1⋅(100 g)-1]. However, there were discrete regions in each occurred in the LAD territory (yellow arrow). d–f Patient #11 whose of the three vascular territories that demonstrated the lack of flow LCx was sub-totally occluded but without angiographic evidence of reserve (yellow arrows) 2.5) while MBF in the subendocardium remained relatively and 9.7 mSv respectively. For the rest and stress protocol (i.e., unchanged after the DIP challenge (MPR≈1, white dotted 2 cardiac DCE-CT perfusion studies), the total effective dose circle in Figs. d–i).
was 19.4 mSv.
The CTDIvol of a cardiac DCE-CT perfusion study (rest orstress) reported from our CT system was 173.43 mGy. The This initial study demonstrated a non-linear inverse corresponding DLP and effective dose were 693.71 mGy cm relationship between the mean MPR and MVR values
Eur Radiol (2012) 22:39–50 Fig. 5 a Scatter plot of MVR vs. MPR of all coronary territories in allpatients. The dash line represents the threshold, MPR MVR=3.5,determined by logic regression analysis for maximal separationbetween the NS and stenosed territories (MS, SS, and SSC). b ROCcurve of MPR MVR in comparison with those of other potentialpredictors (MPR and MVR) for distinguishing NS from ≥50%stenosed coronary lesions Fig. 4 a MBF and b MBV at rest and DIP stress in territories suppliedby coronary arteries at different degrees of stenosis. c MPR and MVR were significantly lower than those in region supplied by in response to DIP stimuli as a function of degree of stenosis in NS arteries. In patients who also had MIBI SPECT coronary arteries. Error bars in each graph represent standard perfusion assessment, MPR in territories with reversible deviation of the mean values SPECT defect was significantly attenuated compared withthat in region without SPECT defect.
The inverse non-linear relationship of MPR and coro- nary stenotic severity determined by CT perfusion (Fig. measured by DCE-CT imaging with CT perfusion analysis was similar to results obtained using gold standard 13N- and the average degree of luminal narrowing in coronary ammonia or 15O-water myocardial perfusion imaging with arteries as determined by coronary angiography. MPR and PET [, ]. The considerable scatter of the MPR measure- MVR in myocardium perfused by ≥50% stenosed arteries ment in each group, also analogous to those shown in
Eur Radiol (2012) 22:39–50 * p < 0.05 from MIBI defect group than that of the NS segments (Fig. ), although thedifferences did not reach significance in this relatively smallsample.
Coronary steal, a phenomenon in which MBF drops below its baseline value after pharmacologic challenge (i.e.,MPR < 1), occurred in some but not all SSC and SSsegments (Figs. ). As a result, the overall MPRand MVR for both groups remained greater than one. Asshown in Fig. coronary steal can occur in a limitedregion within a jeopardized territory, and partial volumeaveraging of MPR would result in the normalization of Fig. 6 Comparison of mean MPR in territories with MIBI defect (10 MPR in those territories depending on the size of the reversible and 2 partially reversible) and without MIBI defect in coronary steal defect relative to the whole territory.
SPECT. Error bars denote standard deviation of the mean MPR values Coronary steal appears to occur exclusively in collateral-ized myocardium [and the technique described heremay be useful in the assessment of CAD patients byrevealing functioning collaterals in ischemic myocardium ], was probably contributed by the variability of the (Fig. ) potentially even below the limit of detection by hyperaemic response to DIP stimulation, as well as differ- invasive angiography (i.e., < 300 μm [ ences in the resting MBF level which is dependent on the DCE-CT Perfusion demonstrated an excellent sensitivity patient's age [The morphological complexities of to detect 50% or greater luminal narrowing in coronary stenosis such as shape, eccentricity, length and stenotic arteries. However, in the absence of healthy volunteers in inflow/outflow angles were not considered, all of which our study, the use of NS segments in CAD patients is a poor could affect the flow resistance differently and account for alternative because MPR and MVR measured in this group some of the variability in MPR at a given percentage of could be lower than those in patients without CAD [ stenosis. Increase in MBV in all territories after DIP because of diffuse disease not detected angiographically, challenge regardless of their angiographic status (i.e., mean resulting in more overlap with the stenosed groups (i.e., MVR >1.0 in Fig. ) suggests that the observed MPR ≥50 % lumen narrowing) as shown in Figs. and a and response was generated through coronary vasodilation of ultimately a poor specificity for detecting stenosis. The the microvasculature, possibly mediated through increased lowering of MPR and MVR could also be a direct result of local interstitial adenosine levels [Increases in MBV including both normal and mildly irregular coronary after DIP stress was significantly reduced in the MS and SS arteries in the NS group. Segments supplied by arteries territories compared with NS. This indicates that the that were mildly irregular and without angiographically vasodilatory effect of DIP on MBV was inversely related significant obstructive stenosis might have a lower MPR to the degree of luminal narrowing in the coronary arteries.
and MVR than those that were supplied by arteries truly Furthermore, it suggests that vessels downstream of the MS completely free of disease ].
and SS coronary arteries were already dilated to maintain In comparison with SPECT, we showed that MPR in resting MBF and their "reserve" to respond to the vaso- territories with MIBI defect was more attenuated than that dilatory DIP stimulus was limited. The presence of such in territories without the defect. As such, DCE-CT autoregulatory vasodilation to maintain normal MBF in perfusion could be as effective as SPECT to assess resting myocardium is supported further by the finding that functionally significant coronary stenosis. A potential MBV at baseline in these affected territories trended higher limitation of SPECT is that relative rather than absolute Fig. 7 MIBI SPECT images ofpatient #21, a during maximalstress and b at rest. c A schemato illustrate the distribution ofcoronary territories in the polarmaps of (a) and (b). Thecorresponding MBF maps gen-erated by CT Perfusion for thispatient are shown in Figs. (stress) and 3 h (rest)
Eur Radiol (2012) 22:39–50 Fig. 8 Averaged maps at rest a–c, MBF maps at rest d–f and during consecutive slices suggested a non-transmural MI (dotted circles) in DIP stress g–i of a patient (#17 in Tables and who had a partially the same coronary territory, originated from the inferior wall to reversible perfusion defect in the inferior wall of the LV myocardium inferoseptal wall (basal-septal wall in the HLA view) (RC territory) identified by MIBI SPECT. CT perfusion MBF maps in regional MBF is assessed. In patients with left main or Fig. This discrepancy is particularly problematic in triple-vessel CAD, relatively balanced global hypoperfu- patients with tripe-vessel CAD, in whom stress perfusion in sion of the LV may lead to underestimation of both the all territories of the myocardium are abnormal. This extent and severity of ischemia ]. In this study there suggests that DCE-CT perfusion may better detect func- were twelve patients who had moderate to severe triple- tionally significant triple-vessel or left main CAD, the vessel CAD (Table ). MPR measured with DCE-CT group that is at the highest risk for cardiac events, than Perfusion in all three coronary territories of these patients SPECT. The effectiveness of DCE-CT perfusion for CAD were depressed relative to the values found in NS (as management is further enhanced by its ability to assess non- discussed above there were no truly normal territories in transmural ischemia/MI, as demonstrated in a patient who this study) territories (<1.9 vs. 2.3). In contrast, SPECT, had partially reversible defect in the MIBI scan (Fig. which normalizes perfusion throughout the myocardium to The superior spatial resolution of CT outlines the extent of the region with maximal perfusion, may underestimate the injured tissue after heart attack better than SPECT, which true extent of severe triple-vessel CAD as demonstrated in would better inform decision on the appropriate treatment Eur Radiol (2012) 22:39–50 (s) for the patient. The interesting findings from this initial reduced with 1) the prospective ECG gating method, which study in which DCE-CT perfusion and SPECT MIBI turns on X-rays only at MDs, and 2) novel CT reconstruction measurements could only be compared in half of the algorithms which maintain image quality at a lower X-ray patients, would warrant further investigations on the tube current These radiation dose saving techniques effectiveness of DCE-CT perfusion versus MIBI SPECT would facilitate future cardiac DCE-CT perfusion trials to be which is frequently used for MBF assessment to detect performed with the inclusion of healthy volunteers as functionally significant CAD in clinical settings.
control, and/or with the conjunctional use of coronary CTA DCE-CT perfusion provides additional information on for a more precise comparison between coronary stenosis the change in MBV induced by coronary lesions which may and the downstream MBF/MBV physiology. Another limi- provide insights into the physiology distal to a coronary tation is that current 64-slice CT systems cannot measure stenosis above and beyond that provided by the measure- perfusion of the entire LV. Newer 256/320 slice CT systems ment of MBF alone. The advantage of measuring both with their extended coverage, up to 16 cm, resolve the above MBF and MBV by DCE-CT perfusion is reflected by the problem adequately (though the most outer slices in 320- logistic regression finding that MPR MVR was a more slice CT may not be useful for quantitative perfusion significant predictor of functionally relevant stenosis than measurement due to cone beam artifact). Another solution either MPR or MVR alone. The logistic regression finding for existing 64-slice systems is to ‘toggle' the table between was echoed by the ROC curve analysis which depicted a two adjacent 4 cm wide locations during DCE-CT data higher accuracy (ROC AUC) of MPR MVR for distin- acquisition to increase the coverage from 4 to 8 cm at the guishing NS from stenosed coronary lesions compared with expense of time sampling frequency.
MPR or MVR alone. Measurements of MBV with DCE-CT In conclusion, the findings from this study with small perfusion also agree with findings from studies using number of patients suggest that DCE-CT imaging with beam myocardial contrast echocardiography. These findings hardening correction and quantitative CT perfusion analysis demonstrated vasodilation of microvasculature distal to a could be a useful technique to evaluate the functional stenosis resulting in an increase in resting MBV  and significance of coronary stenosis in CAD patients through significant attenuation of MVR in ischemic myocardium measurements of MPR and MVR. This technique could play subtended by stenotic coronary arteries ]. The superior an important role in the evaluation of the likelihood of future spatial resolution of CT allows for more precise localization cardiac events in patients with intermediate to advanced risk of the extent of vulnerable myocardium through delineation of CAD, allowing timely and appropriate management for of all the areas with abnormal perfusion (volume) reserve those who are more susceptible to acute MI. Prospective (Figs. ) than echocardiography, thus improving randomized control trials of this technique are warranted.
the targeting of revascularization.
There are several limitations of the proposed DCE-CT The authors thank Anna MacDonald, Karen Betteridge and Lynn Bender for their help on the patient studies. This perfusion method. One limitation is the relatively high work was supported in part by the Canadian Institutes of Health effective dose from a rest and stress protocol: 19.4 mSv for Research (Ottawa, ON, Canada), Canadian Foundation of Innovation 4 cm coverage of the heart, estimated using the DLP reported (Ottawa, ON, Canada), Ontario Research Fund (Toronto, ON, by the CT system and the chest conversion factor proposed by Canada), Ontario Innovation Trust (Toronto, ON, Canada), and GEHealthcare (Waukesha, WI, USA). T.-Y. Lee is a grant recipient of and European Commissions in 2004 (0.014 mSv mGy-1 cm-1) consultant to GE Healthcare on the CT Perfusion software. J. Hsieh This estimated effective dose can be 2 times higher and J.-Y. Li are employees of GE Healthcare.
(38.8 mSv) if a recently proposed conversion factor specificfor cardiac CT (0.028 mSv mGy-1 cm-1) is used instead .
Compared to the traditional chest conversion factor, thecardiac conversion factor takes into account: 1) cardiac CT scans typically irradiate only the lower chest that contains themajority of the radiosensitive breast tissue, rather than the 1. Uren NG, Melin JA, De Bruyne B, Wijns W, Baudhuin T, Camici whole chest which includes the relatively radio-resistant PG (1994) Relation between myocardial blood flow and the upper chest tissue; 2) The recent ICRP Publication 103 severity of coronary-artery stenosis. N Engl J Med 330:1782–1788 increased the tissue weighting factor of the breast by 240% 2. Di Carli M, Czernin J, Hoh CK, Gerbaudo VH, Brunken RC, compared to the previously proposed value (0.12 vs. 0.05 Huang SC, Phelps ME, Schelbert HR (1995) Relation among from ICRP 60) ]. Thus, it is necessary to employ stenosis severity, myocardial blood flow, and flow reserve in vigorous radiation dose reduction techniques with CT patients with coronary artery disease. Circulation 91:1944–1951 3. Gould KL, Lipscomb K, Hamilton GW (1974) Physiologic basis perfusion for its application in clinical settings. With the for assessing critical coronary stenosis. Instantaneous flow recent advances of CT technology, radiation exposure of a response and regional distribution during coronary hyperemia as cardiac DCE-CT perfusion study can be significantly measures of coronary flow reserve. Am J Cardiol 33:87–94 Eur Radiol (2012) 22:39–50 4. Cenic A, Nabavi DG, Craen RA, Gelb AW, Lee TY (2000) A CT 17. Bluemke DA, Achenbach S, Budoff M, Gerber TC, Gersh B, method to measure hemodynamics in brain tumors: validation and Hillis LD, Hundley WG, Manning WJ, Printz BF, Stuber M, application of cerebral blood flow maps. AJNR Am J Neuroradiol Woodard PK (2008) Noninvasive coronary artery imaging.
Magnetic resonance angiography and multidetector computed 5. Murphy BD, Fox AJ, Lee DH, Sahlas DJ, Black SE, Hogan MJ, tomography angiography. A scientific statement from the American Coutts SB, Demchuk AM, Goyal M, Aviv RI, Symons S, Gulka heart association committee on cardiovascular imaging and interven- IB, Beletsky V, Pelz D, Chan RK, Lee TY (2008) White matter tion of the council on cardiovascular radiology and intervention, and thresholds for ischemic penumbra and infarct core in patients with the councils on clinical cardiology and cardiovascular disease in the acute stroke: CT perfusion study. Radiology 247:818–825 young. Circulation 118:586–606 6. So A, Hsieh J, Li JY, Lee TY (2009) Beam hardening correction in 18. Uren NG, Marraccini P, Gistri R, de Silva R, Camici PG (1993) CT myocardial perfusion measurement. Phys Med Biol 54:3031– Altered coronary vasodilator reserve and metabolism in myocar- dium subtended by normal arteries in patients with coronary artery 7. Lee TY (2002) Functional CT: physiological models. Trends disease. J Am Coll Cardiol 22:650–658 19. Gould KL, Nakagawa Y, Nakagawa K, Sdringola S, Hess MJ, 8. Lee TY, Purdie TG, Stewart E (2003) CT imaging of angiogenesis. Q Haynie M, Parker N, Mullani N, Kirkeeide R (2000) Frequency J Nucl Med 47:171–187 and clinical implications of fluid dynamically significant diffuse 9. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, coronary artery disease manifest as graded, longitudinal, base-to- Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS apex myocardial perfusion abnormalities by noninvasive positron (2002) Standardized myocardial segmentation and nomenclature emission tomography. Circulation 101:1931–1939 for tomographic imaging of the heart: a statement for healthcare 20. Christian TF, Miller TD, Bailey KR, Gibbons RJ (1992) professionals from the Cardiac Imaging Committee of the Council Noninvasive identification of severe coronary artery disease on Clinical Cardiology of the American Heart Association.
using exercise tomographic thallium-201 imaging. Am J Cardiol 70:14–20 10. Geleijnse ML, Fioretti PM, Roelandt JR (1997) Methodology, 21. Lindner JR, Skyba DM, Goodman NC, Jayaweera AR, Kaul S feasibility, safety and diagnostic accuracy of dobutamine stress (1997) Changes in myocardial blood volume with graded echocardiography. J Am Coll Cardiol 30:595–606 coronary stenosis. Am J Physiol 272:H567–H575 11. Matsumura Y, Hozumi T, Arai K, Sugioka K, Ujino K, Takemoto Y, 22. Bin JP, Pelberg RA, Wei K, Le E, Goodman NC, Kaul S (2002) Yamagishi H, Yoshiyama M, Yoshikawa J (2005) Non-invasive Dobutamine versus dipyridamole for inducing reversible perfusion assessment of myocardial ischaemia using new real-time three- defects in chronic multivessel coronary artery stenosis. J Am Coll dimensional dobutamine stress echocardiography: comparison with Cardiol 40:167–174 conventional two-dimensional methods. Eur Heart J 26:1625–1632 23. Einstein AJ, Moser KW, Thompson RC, Cerqueira MD, Henzlova 12. Bongartz G, Golding SJ, Jurik AG, Leonardi M, van Meerten EVP, MJ (2007) Radiation dose to patients from cardiac diagnostic Rodriguez R (2004) CT quality criteria. European Commission, imaging. Circulation 116:1290–1305 24. Gosling O, Loader R, Venables P, Rowles N, Morgan-Hughes G, 13. Senneff MJ, Geltman EM, Bergmann SR (1991) Noninvasive Roobottom C (2010) Cardiac CT: are we underestimating the delineation of the effects of moderate aging on myocardial dose? A radiation dose study utilizing the 2007 ICRP tissue perfusion. J Nucl Med 32:2037–2042 weighting factors and a cardiac specific scan volume. Clin Radiol 14. Czernin J, Muller P, Chan S, Brunken RC, Porenta G, Krivokapich J, Chen K, Chan A, Phelps ME, Schelbert HR (1993) Influence of age 25. Gosling O, Loader R, Venables P, Roobottom C, Rowles N, and hemodynamics on myocardial blood flow and flow reserve.
Bellenger N, Morgan-Hughes G (2010) A comparison of radiation Circulation 88:62–69 doses between state-of-the-art multislice CT coronary angiography 15. Fredholm BB, Sollevi A (1986) Cardiovascular effects of with iterative reconstruction, multislice CT coronary angiography adenosine. Clin Physiol 6:1–21 with standard filtered back-projection and invasive diagnostic 16. Demer L, Gould KL, Kirkeeide R (1988) Assessing stenosis severity: coronary angiography. Heart 96:922–926 coronary flow reserve, collateral function, quantitative coronary 26. Thibault JB, Sauer KD, Bouman CA, Hsieh J (2007) A three- arteriography, positron imaging, and digital subtraction angiography.
dimensional statistical approach to improve image quality for A review and analysis. Prog Cardiovasc Dis 30:307–322 multislice helical CT. Med Phys 34:4526–4544
Viharos, Zs. J.; Kis K. B.: Survey on Neuro-Fuzzy Systems and their Applications in Technical Diagnostics and Measurement, Measurement, Vol. 67., 2015., pp. 126-136., (doi: http:// dx.doi.org/10.1016/j.measurement.2015.02.001), SCI, Impact Factor: 1.526. Survey on Neuro-Fuzzy Systems and their Applications in Technical Diagnostics and Measurement
Exotic tendencies: Spa hop around the globe for the ultimate in blissful treatmentsTHERMAE BATH SPA IN BATH, With a name like Bath, this is a city, just a two-hour train trip from London, that understands pampering. In fact, it has oodles of history behind it as the site of 2,000-year-old Roman baths with natural thermal springs. Sur- rounded by Georgian architecture