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European Journal of Echocardiography 2004 5(1):41-50; doi:10.1016/j.euje.2003.08.005
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Copyright © 2003, The European Society of Cardiology

Quantitative evaluation of myocardial perfusion in patients with revascularized myocardial infarction: comparison between intravenous myocardial contrast echocardiography and 99mTc-sestamibi single photon emission computed tomography

Gertjan Tj Sieswerdaa,*, Lucas J Kleina, Otto Kampa, Eric A Aiaziana, Wolfgang Lepperb, Frans C Vissera, Peter Hanrathb and Cees A Vissera

aDepartment of Cardiology, VU University Medical Center, Amsterdam, The Netherlands
bDepartment of Cardiology, University Hospital RWTH, Aachen, Germany

Received 7 April 2003; received in revised form 11 August 2003; accepted after revision 13 August 2003.

* Corresponding author. Department of Cardiology, 6N-120, VU University Medical Center, P.O. Box 7057, NL-1007 MB Amsterdam, The Netherlands. Tel.: +31-20-4442244; fax: +31-20-4442446. gtj.sieswerda{at}vumc.nl


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Aims: This two-center study compared quantitative segmental perfusion mapping by intravenous myocardial contrast echocardiography (ivMCE) and scintigraphy (SPECT) in patients in the subacute phase of myocardial infarction (AMI).

Methods and results: Sixteen patients underwent ivMCE using 1:1 intermittent harmonic imaging 24 h after first AMI treated with PTCA and stenting. Apical contrast echocardiograms were obtained after the injections of SonazoidTM. Baseline-corrected peak myocardial videointensity (bcPMVI) was determined automatically in 16 segments. Resting 99mTc-sestamibi SPECT was performed within one day after ivMCE. SPECT images were reoriented matching the ivMCE views, and divided into the same segments as in ivMCE, from which mean count rate values were obtained. After exclusion due to artifacts or attenuation, 208/256 (82%) segments remained for analysis. Normalized SPECT count rate and bcPMVI correlated linearly: bcPMVI=1.237xSPECT–35; r = 0.74, p<0.0001. The relation remained identical in subgroup analysis based on participating center, echocardiographic view, perfusion territory, infarct zone, or function. Using SPECT as reference, mean bcPMVI was 77±19% in normal segments, 53±29% in mild–moderate defects and 25±18% in severe defects (p<0.001 for all comparisons).

Conclusion: The videointensity increase observed in quantitative ivMCE clearly correlated with SPECT tracer uptake. This further substantiates the use of ivMCE as a valid technique for myocardial perfusion imaging.

Keywords: AMI Acute Myocardial Infarction; ASE American Society of Echocardiography; LV Left Ventricle/Ventricular; TIMI Thrombolysis in Myocardial Infarction; (iv)MCE (intravenous) Myocardial Contrast Echocardiography; PTCA Percutaneous Transluminal Coronary Angioplasty; SPECT Single Photon Emission Computed Tomography


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Reliable regional myocardial perfusion assessment is crucial to diagnosis, management, and risk stratification of patients with ischemic heart disease. Although myocardial perfusion imaging by 99mTc-labeled agents and SPECT is the current clinical standard, its clinical utility is limited by a relatively low spatial resolution and the need to inject radioisotopes, while it cannot be performed at the bedside. Intravenous MCE offers an increasingly realistic alternative for perfusion scintigraphy, as advances in ultrasound contrast agent formulation and imaging technology have significantly increased performance of this technique. Although the majority of studies evaluating the accuracy of ivMCE to assess myocardial perfusion report a significant and strong correlation between ivMCE contrast effect and SPECT count rate, results are conflicting.1–10 Also, these studies largely use qualitative visual evaluation, focus on a selected part rather than on the entire LV myocardium, and originate from expert single centers.

The aim of the present two-center study was to quantitatively evaluate the relation between the segmental ivMCE contrast effect and 99mTc-sestamibi SPECT count rate in patients in the subacute phase of AMI, covering the entire LV myocardium.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1 Patient population and study protocol
This study included 16 unselected patients with first AMI undergoing revascularization by primary PTCA and stent implantation within 6 h after the onset of the symptom. Patients were eligible if they presented with typical anginal chest pain lasting <30 min and ST-segment elevation of ≥0.2 mV in ≥2 contiguous leads. Patients were part of a multicenter phase II study.11 MCE was performed 12–24 h after successful PTCA and stent delivery. Myocardial perfusion scintigraphy using 99mTc-sestamibi SPECT was scheduled within a day after ivMCE. The study complies with the Declaration of Helsinki. The research protocol was approved by the ethics committees of both participating hospitals, and all patients provided written informed consent.

2.2 Coronary angiography and angioplasty
Before angiography, all patients received 10.000 U of heparin and 500 mg of acetylsalicylic acid intravenously. PTCA was performed with standard techniques and included stent implantation in all patients. After the interventional procedure, intravenous heparin was continued for ≥24 h (activated partial thromboplastin time 60–80 s). All patients received acetylsalicylic acid (100 mg/day) and ticlopidine (250 mg BID). Flow in the infarct-related artery was graded by means of TIMI flow classification.12 Collateral flow was graded according to Rentrop et al.13

2.3 Intravenous myocardial contrast echocardiography
MCE was performed using SonazoidTM (Nycomed–Amersham, Amersham, England), an ultrasound contrast agent consisting of stabilized perfluorocarbon microbubbles with a mean diameter of 2.4–3.5 m. Three intravenous injections at a dose of 0.030 µl microbubbles/kg body weight followed by a slow (1 ml/s) 10 ml 0.9% saline flush were given per MCE examination. Echocardiography was performed using a digital ultrasound system (Sonos 2500LE or Sonos 5500, Hewlett Packard, Andover, MA, USA) capable of harmonic imaging with mean transmit and receive frequencies of 1.8 MHz and 3.6 MHz, respectively. The imaging mode was intermittent harmonic with one image per cardiac cycle gated at end-systole. A dynamic range of ~80% was chosen. Transmitted power was adjusted to result in a mechanical index of 0.5–0.7. The focus was set at two-thirds of the image depth or deeper. A linear post-processing curve was used. Time and lateral gain compensation were adjusted to achieve a homogeneous myocardial brightness in the non-enhanced image, resulting in a myocardium that was dark gray, without any black or white in any part. After optimization at its onset, instrument settings were held constant throughout each study. Prior to contrast injection, a sequence of images from the standard parasternal and apical positions was recorded to allow evaluation of segmental wall motion. MCE image acquisition in the apical four-, two-, and three-chamber views was started 5–10 beats before contrast injection by switching from the continuous to the intermittent harmonic imaging mode, and continued until a minimum of 30 contrast-enhanced cycles were acquired. All images were stored on S-VHS videotape for off-line analysis.

2.4 Single photon emission computed tomography
Resting perfusion scintigraphy was performed after an injection of 250 MBq 99mTc-sestamibi. Imaging was performed with a large field-of-view gamma camera equipped with low-energy, high-resolution collimators. Sixty-four images of a duration of 40 s were acquired over a 360° orbit. The data were reconstructed by backprojection using a Hanning filter with a cut-off frequency of 0.9 cycles/s.

2.5 Image analysis and comparison
Analysis of ivMCE and SPECT images was performed independently by single observers, who were unaware of clinical data and of the analysis of the other modality. To optimize comparison between SPECT and MCE derived data, a similar approach was applied to both imaging modalities.

2.5.1 Analysis of myocardial contrast intensity
Videodensitometry was used to evaluate the myocardial ultrasound contrast effect. The videotaped consecutive end-systolic frames of each imaging sequence were digitized with a resolution of 360x288 pixels by 256 gray-scale levels, using a dedicated analysis system (Axle International, The Hague, The Netherlands). Frame grabbing started five cardiac cycles before the appearance of LV cavity opacification, and continued until complete resolution of cavity opacification was observed. In each view, regions of interest (ROIs) were defined corresponding to the ASE 16-segment model14 (see Fig. 1). Frame-to-frame drift as well as translation and rotation of the heart were manually corrected using motion correction software incorporated in the system. The mean pixel value of each segment was computed frame-by-frame, and time–intensity curves were generated. As reported previously, the intra-observer agreement of this approach is excellent.15 Subsequently, the baseline-corrected peak myocardial videointensity (bcPMVI) was calculated by subtracting the mean intensity value of the five precontrast frames from the mean value of the contrast-enhanced frame with the highest intensity value and its two neighboring frames. Based on the segmental bcPMVI values, a color-coded 3-D LV map was constructed. A representative example is shown in Fig. 2.


Figure 1
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  		Fig. 1 Example of an AP4CV end-systolic still frame after administration of SonazoidTM. Regions of interest corresponding to the standard ASE segments (lines) were drawn over the original two-dimensional image. Using consecutive frames, a time–intensity curve was generated for each segment.

 


Figure 2
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  		Fig. 2 Example of a color-coded segmental perfusion map based on bcPMVI in a patient with extensive anterior AMI. Reduced intensity, represented by the darker colors, is seen in the LAD-territory. In contrast, the remote areas show a higher intensity, as indicated by the lighter colors. The segments are numbered according to the ASE guidelines. AW, anterior wall; FW, (lateral) free wall; IVSa, anterior interventricular septum; IVSp, posterior (inferior) interventricular septum; PW, posterior (inferior) wall.

 
2.5.2 SPECT analysis
SPECT transaxial images were scaled linearly on a 0–255 scale, employing NucMed_Image software (http://www.nucmed.slu.edu). Subsequently, the images were reoriented to short-axis images, with both intersections between the right ventricular wall and ventricular septum positioned directly opposite, thus forming a vertical line, which was considered to represent the 0° position. The 0° orientation as well as the 60° clockwise (CW) and 60° counter-clockwise (CCW) orientations were then vertically resliced to obtain orientations analogous to the standard echocardiographic apical four-chamber (60° CW), two-chamber (0°), and three-chamber views (60° CCW), as illustrated in Fig. 3. From these resliced images, the slice with the largest ventricular cavity was selected. ROIs corresponding to the 16 segments used in contrast echocardiography were defined, and mean segmental count rates were obtained.


Figure 3
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  		Fig. 3 Rotation and reslicing of short-axis SPECT images to match the standard echocardiographic views. Vertical reslicing was performed on the 60° clockwise, 0° and 60° counter-clockwise rotated orientations to obtain orientations corresponding to AP4CV, AP2CV, AP3CV, respectively. The images are from the same patient as in Fig. 2, and tracer uptake is in concordance with segmental bcPMVIs, with extensive areas of reduced uptake in the apex, anterior wall, and anterior interventricular septum, while normal uptake is present in the remote areas.

 
2.5.3 Image comparison
Segments with obvious artifacts or attenuation on SPECT or ivMCE were a priori excluded from analysis. Videointensity and count rate values in the remaining segments were normalized to the maximum value as 100% on a per patient basis, regardless of coronary anatomy. Linear regression analysis was performed on these normalized segmental bcPMVI and SPECT values. Subgroup analysis was performed after division of segments based on participating center, echocardiographic imaging plane, perfusion territory, and infarct zone. The 16 myocardial segments were assigned to a specific coronary artery perfusion territory, and anterior and inferior infarct zones were defined.16 Finally, segments were categorized into predefined grades of perfusion based on normalized SPECT values. Tracer uptake of <80% was considered to represent normal perfusion, uptake of 65–80% a mild–moderate perfusion defect, and uptake of <65% a severe perfusion defect.17,18 Within these categories, mean segmental bcPMVI was calculated.

2.6 Statistical analysis
Continuous variables are represented as mean ± SD. F-test was used to evaluate differences in the relation between both techniques in various subgroups. Analysis of variance with Tukey's multiple comparison test was used to evaluate differences in bcPMVI values between grades of perfusion. Receiver operating characteristics (ROC) curve analysis was employed to determine the optimal cut-off values for bcPMVI to differentiate between the different SPECT perfusion grades. Kappa statistics were used to determine agreement between the techniques.19 Statistical significance was set at p<0.05. Statistical analysis was performed with the GraphPad Prism (GraphPad Software Inc., San Diego, CA) software package.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
3.1 Study population
The clinical characteristics of the study population are outlined in Table 1. Following angioplasty and stent implantation, flow in the infarct-related artery was TIMI grade 3 in 12 (75%) patients, grade 2 in 2 (13%) patients, and grade 0–1 in 2 (13%) patients. No clinical events occurred between the MCE and SPECT studies in any of the patients.


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  		Table 1 Clinical characteristics of the study population

 
3.2 Overall segment-by-segment comparison
Of the 256 segments, 208 (82%) were suitable for analysis. Of the 45 ivMCE-segments that could not be analyzed, 11 were located in the lateral wall, 17 in the anterior wall, 7 in the inferior wall, 3 in the posterior wall, 1 in the anteroseptum, and 5 in the inferoseptum. In one patient, the four apically localized SPECT-segments could not be analyzed. One segment could not be analyzed by both MCE and SPECT. Regression analysis revealed that normalized bcPMVI and SPECT correlated linearly: bcPMVI=1.237xSPECT–35; r = 0.74, p<0.0001 (see Fig. 4). The relation proved not different between the subpopulation of both centers: r = 0.75 (p<0.0001) for the Amsterdam population (n = 11), and r = 0.71 (p<0.0001) for the Aachen patients (n = 5) (p = NS for both slope and intercept).


Figure 4
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  		Fig. 4 Relation between normalized segmental SPECT count rates and normalized bcPMVI values. Dashed lines indicate 95% prediction interval.

 
3.3 Segmental comparison by echocardiographic imaging plane
The correlation between normalized bcPMVI and SPECT count rate proved not significantly different among the 76 analyzable segments of the apical four-chamber view: r = 0.76 (p<0.0001), the 72 segments of the two-chamber view: r = 0.78 (p<0.0001), and the 60 segments of the three-chamber view: r = 0.70 (p<0.0001) (p = NS between groups for slope and intercept).

3.4 Segmental comparison by coronary territory
In the three coronary perfusion territories, the respective correlations between segmental bcPMVI and SPECT count rate values proved similar: r = 0.73 (p<0.0001) for the LAD-territory, r = 0.76 (p<0.0001) for the LCx-territory, and r = 0.70 (p<0.0001) for the RCA-territory (p = NS between groups for slope and intercept). Also, anterior and inferior perfusion territories did not differ significantly: r = 0.73 (p<0.0001) for both anterior and inferior territories (p = NS for slope and intercept).

3.5 Segmental comparison by wall motion
The correlation between segmental bcPMVI and SPECT count rate value appeared stronger in hypokinetic segments (r = 0.73 [p<0.0001]), than in normokinetic (r = 0.49 [p<0.0001]) or akinetic segments (r = 0.51 [p<0.0001]); however, the difference did not reach significance.

3.6 Analysis by SPECT perfusion grade
3.6.1 Segmental level
Using scintigraphy as clinical standard, normal perfusion was observed in 108 segments, while 53 segments had a mild–moderate, and 47 a severe perfusion defect. Using ROC curve analysis, the optimal cut-off values for bcPMVI to differentiate between the different SPECT perfusion grades were calculated to be 59% and 37%, respectively. Applying these values, the mean bcPMVI was 25±18% in segments with a severe SPECT defect, 53±29% in segments with a moderate defect, and 77±19% in normally perfused segments (p<0.001 between groups), as shown in Fig. 5. When differentiating between either normal or abnormal (i.e. mild–moderate or severe defect) segmental perfusion, the agreement between both techniques was 81%, with a kappa value of 0.59. Intra-patient agreement was 83±11%. SPECT and ivMCE identified 107 and 111 segments as normal, while a perfusion defect was identified in 101 and 97 segments, respectively (see Table 2). The sensitivity and specificity of ivMCE to detect abnormal segmental tracer uptake at rest were 78% and 83%, with positive and negative predictive values at 81% and 80%, and positive and negative likelihood ratios at 4.6 and 3.8, respectively.


Figure 5
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  		Fig. 5 Mean bcPMVI values in segments with severe perfusion defects, moderate defects and normal perfusion on SPECT. Error bars indicate one SD.

 


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  		Table 2 2x2 Table showing normal vs abnormal segmental myocardial perfusion as determined by ivMCE and SPECT (n = 208)

 
3.6.2 Territory level
Of the 48 perfusion territories (three in each patient), 15 were considered abnormal by MCE, 16 by SPECT and 15 by both (concordance 94%, kappa 0.69).

3.6.3 Patient level
The mean extent of the perfusion defects was 6.3±3.0 segments by MCE and 6.2±2.7 segments by SPECT (p = NS). Intra-patient agreement for presence, location (anteroapical or inferoposterior), and extent of a perfusion defect was 100%, 88%, and 80%, respectively.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
The principal finding of the present study is that quantitatively measured segmental myocardial contrast enhancement obtained during triggered harmonic imaging had a significant and strong linear correlation with the segmental SPECT count rate. The relation between quantitated segmental ivMCE and SPECT was similar in subgroup analysis based on participating center, echocardiographic view, coronary perfusion territory, infarct zone, or function. Furthermore, bcPMVI values were reduced in accordance with SPECT perfusion grade.

The major strength of this study is that the comparison of ivMCE and SPECT is based on quantitative measurements, rather than on intrinsically qualitative visual interpretation. Also, we reoriented the SPECT images to closely match the standard apical echocardiographic image planes, and subsequently applied a similar method of image analysis to both techniques. We feel that quantification and reorientation significantly optimize the comparison of ivMCE with other methods for perfusion imaging, and deserve incorporation into future studies.

4.1 Myocardial contrast intensity and myocardial perfusion
Transpulmonary ultrasound contrast agents reach the left ventricular cavity and subsequently the coronary arteries and myocardium after intravenous injection. Unlike other agents used in perfusion imaging, they remain entirely intravascular, and possess an intravascular rheology similar to that of erythrocytes.20 When distributed in the myocardial microvasculature, microbubbles enhance scattering echoes originating from the capillary bloodpool by a factor of 10,000.21 Following complete destruction by high energy ultrasound during continuous infusion of microbubbles, myocardial opacification is known to gradually increase to a plateau value over the next several cardiac cycles. This plateau intensity value is related to the microvascular volume of the interrogated area, while the rate of rise (beta-term) is related to flow velocity.22

Although the present study used 1:1 triggering, employment of a medium-range mechanical index in conjunction with a microbubble that is relatively unsusceptible to ultrasound-induced destruction23 implies incomplete destruction after each imaging pulse. Thus, compared to triggering at higher intervals, the same plateau intensity value will be reached, albeit at a lower rate of rise. Therefore, it is inferred that the observed differences in segmental bcPMVI predominantly reflect differences in microvascular volume, the major determinant of perfusion. As the observed rate of rise is determined by the opposing forces of ultrasound-induced bubble destruction and flow velocity, we could not incorporate this parameter into our model.

4.2 Interpretation of the study results
The relation between normalized segmental SPECT count rate and bcPMVI values as observed in the present study (bcPMVI=1.237xSPECT–35; r = 0.74, p<0.0001) is characterized by a negative elevation and a slope greater than 1, suggesting systematic underestimation of perfusion by ivMCE compared with SPECT. However, several phenomena may serve as alternative explanation for the observed relationship. The negative elevation may primarily result from SPECT background noise (mainly due to scatter and reconstruction algorithms24), with additional influence from echocardiographic thresholding and dynamic range limitations. The slope of <1 may reflect presence of the partial volume effect: relatively low SPECT values in areas with normal bcPMVI, typically occurring in stunned segments. Indeed, as illustrated in Fig. 4, several datapoints with such properties are present at the upper end of the spectrum. Also, in areas with very low perfusion, 1:1 triggering may have had more profound influence on the replenishment than in areas with less disturbed perfusion, thus resulting in lower bcPMVI values and underdetection of perfusion by ivMCE. This may be illustrated by the somewhat lower correlation coefficient in akinetic than in hypokinetic segments.

It is noteworthy that despite the time delay between the ivMCE and SPECT studies, reactive hyperaemia seems to have abated at the time of the ivMCE, as its presence would have resulted in overestimation of perfusion by ivMCE, while the present study observed the opposite. This observation is in line with previous studies suggesting that the influence of a preceding ischemic insult on the (micro)circulation has largely ended 24 h after the event,25,26 and with the absence of clinical events in any of our patients.

The observed correlation (r = 0.74) between segmental bcPMVI and SPECT count rate was significant and strong, and remained unchanged in various subgroup analyses. However robust, the agreement was not perfect. First, this may reflect inherent differences between both techniques, as microbubbles remain entirely intravascular, while scintigraphic tracer uptake by myocytes is proportional to flow, but also depends on sarcolemmal and mitochondrial integrity. Second, although image alignment between ivMCE and SPECT was optimized by reorienting the SPECT images, it may not have been perfect because the exact orientation of the ivMCE images is not known precisely. This may have contributed to the relatively wide distribution of datapoints, thus negatively influencing the correlation coefficient. Third, the correlation between contrast intensity and myocardial blood flow may be closest in the setting of exogenous hyperaemia.27 However, the setting of subacute MI precluded the use of coronary vasodilators. Finally, we speculate that the correlation coefficient may have been better if we had not been confined to a rigid phase II protocol, which prohibited contrast administration or image acquisition regimens other than bolus injections and intermittent harmonic imaging, rendering incorporation of the beta-term a priori unattainable. Suggestions to improve clinical performance include the use of continuous infusions of contrast agent and imaging protocols employing incremental triggering intervals,22 or real-time low-destruction imaging10 and subsequently assessing refill kinetics following a destruction burst.

4.3 Comparison with previous clinical studies
To our knowledge, this is the first study comparing ivMCE and SPECT to discriminate normal from abnormal segmental myocardial perfusion in the subacute phase of AMI. Previous studies comparing MCE and SPECT in chronic ischemic heart disease report conflicting results, with agreement varying between 43 and 93%, and correlation coefficients ranging from r = 0.24 to r = 0.84.1–10 Comparison with the result of this study requires scrutiny, as significant methodological differences that inherently influence study outcome need to be taken into account. For instance, the results of the one intra-arterial MCE study1 are difficult to interpret, as myocardial intensity dynamics after intra-arterial injection inherently differ from those following intravenous injection. Furthermore, most studies use less and larger segments than the standard 16-segment ASE-model,1–3,7–10 while several other exclude patients with suboptimal echogenicity,1,3,7,8 pre-select echocardiographic views depending on the location of SPECT perfusion abnormalities,7,8 pre-select myocardial segments based on the presence of resting wall motion abnormalities,4,6 employ extensively post-processed ivMCE images,3,7 or use qualitative rather than quantitative image comparison,1,3–6,8–10 all of which significantly lower the challenge for MCE to agree with SPECT.

Interestingly, agreement in the studies employing incremental triggering intervals or real-time ivMCE is in the same order of magnitude as in the present study, only if MCE images at higher intervals (1:5–8) were used.2,8–10 Thus, although the present clinical study covered the entire LV myocardium using the 16 standard ASE segments, did not select patients for acoustic window, did not use pre-selected views or segments, and was performed by investigators at two different centers, the observed correlation between normalized segmental bcPMVI and SPECT count rate was robust and relatively high (r = 0.74; p<0.0001) compared with most previous studies, particularly compared to those with similar ivMCE protocols.

4.4 Clinical implications
Although not the primary aim of the present study, the clinical potential of ivMCE is suggested by its promise to predict presence of abnormal SPECT segmental perfusion with a positive likelihood ratio of 4.6. At a patient level, the technique accurately identified SPECT segmental perfusion defects with respect to location, severity and extent. However, quantitative studies specifically using clinical end-points are yet to be performed.

4.5 Limitations
The study population is limited. However, the number of segments is sufficient to address the primary goals of the study adequately. Several segments had to be excluded as a result of overlying lung and ivMCE attenuation artifacts, but both the number (~18%) and their location in the basal lateral and anterior wall are comparable to similar ivMCE studies, and they did not prohibit correct identification of abnormally perfused coronary territories. Although purely quantitative, videodensitometry was performed on inherently distorted data resulting from non-linear transformation of the original backscattered signal in the ultrasound imaging chain. This may lower the agreement with quantitated SPECT, where such distortion is not an issue. Applying acoustic densitometry, based on data obtained more ‘upstream’ in the imaging chain, may overcome this limitation. The observed correlation between bcPMVI and SPECT count rate was obtained without normalization of SPECT values to a normal database. Commercially available normal database profiles are based on studies of ‘normal’ patients with a low likelihood of ischemic heart disease. Also, comparison to normal database profiles does not account for the significant patient-to-patient variability of attenuation factors, and is thus prone to false-positive results.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
In conclusion, this clinical two-center study in patients in the subacute phase of AMI shows that the segmental videointensity increase observed in quantitative intravenous myocardial contrast echocardiography is linearly and strongly correlated with SPECT tracer uptake. The relation between both techniques remained unchanged in various subgroups based on participating center, echocardiographic imaging plane, perfusion territory, infarct zone, or function. Also, myocardial videointensity increase was reduced in accordance with the grade of SPECT perfusion, and quantitative ivMCE accurately identified segmental perfusion defects with respect to location, severity and extent. These findings further substantiate the use of ivMCE as a valid tool for the non-invasive evaluation of myocardial perfusion.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 

  1. Meza M.F, Mobarek S, Sonnemaker R, Shuler S, Ramee S.R, Collins T.J, et al. Myocardial contrast echocardiography in human beings: correlation of resting perfusion defects to sestamibi single photon emission computed tomography. Am Heart J (1996) 132:528–535.[CrossRef][Web of Science][Medline]
  2. Porter T.R, Li S, Kricsfeld D, Armbuster R.W. Detection of myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles using transient response second harmonic imaging. J Am Coll Cardiol (1997) 29:791–799.[Abstract]
  3. Kaul S, Senior R, Dittrich H, Raval U, Khattar R, Lahiri A. Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography. Circulation (1997) 96:785–792.[Abstract/Free Full Text]
  4. Marwick T.H, Brunken R, Meland N, Brochet E, Baer F.M, Binder T, et al. Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice. Comparison with wall motion and technetium-99m sestamibi single-photon emission computed tomography. J Am Coll Cardiol (1998) 32:1260–1269.[Abstract/Free Full Text]
  5. Binder T, Assayag P, Baer F, Flachskampf F, Kamp O, Nienaber C, et al. NC100100, a new echo contrast agent for the assessment of myocardial perfusion—safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study. Clin Cardiol (1999) 22:273–282.[Web of Science][Medline]
  6. Jucquois I, Nihoyannopoulos P, D'Hondt A.M, Roelants V, Robert A, Melin J.A, et al. Comparison of myocardial contrast echocardiography with NC100100 and 99mTc sestamibi SPECT for the detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction. Heart (2000) 83:518–524.[Abstract/Free Full Text]
  7. Lindner J.R, Villanueva F.S, Dent J.M, Wei K, Sklenar J, Kaul S. Assessment of resting perfusion defects with myocardial contrast echocardiography: theoretical and practical considerations. Am Heart J (2000) 139:231–240.[Web of Science][Medline]
  8. Senior R, Kaul S, Soman P, Lahiri A. Power harmonic Doppler imaging: a feasibility study of a new technique for the assessment of myocardial perfusion. Am Heart J (2000) 139:245–251.[Web of Science][Medline]
  9. Wei K, Crouse L, Weiss J, Villanueva F, Schiller N.B, Naqvi T.Z, et al. Comparison of usefulness of dipyridamole stress myocardial contrast echocardiography to technetium-99m sestamibi single photon emission computed tomography for detection of coronary artery disease (PB127 multicenter phase II trial results). Am J Cardiol (2003) 91:1293–1298.[CrossRef][Web of Science][Medline]
  10. Shimoni S, Zoghbi W.A, Xie F, Kricsfeld D, Iskander S, Gobar L, et al. Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography. J Am Coll Cardiol (2001) 37:741–747.[Abstract/Free Full Text]
  11. Kamp O, Lepper W, Vanoverschelde J.L, Aeschbacher B.C, Rovai D, Assayag P, et al. Serial evaluation of perfusion defects in patients with first acute myocardial infarction referred for primary PTCA using intravenous myocardial contrast echocardiography. Eur Heart J (2001) 22:1485–1495.[Abstract/Free Full Text]
  12. TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial: phase I findings. N Engl J Med (1985) 312:932–936.[Medline]
  13. Rentrop K.P, Cohen M, Blanke H, Phillips R.A. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol (1985) 5:587–592.[Abstract]
  14. Schiller N.B, Shah P.M, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantification of the left ventricle by 2-dimensional echocardiography: American Society of Echocardiography Committee on Standards, Subcommittee on Quantification of 2-Dimensional Echocardiograms. J Am Soc Echocardiogr (1989) 2:358–367.[Medline]
  15. Sieswerda G.T, Kamp O, Van den Ende R, Visser C.A. Intermittent harmonic imaging and videodensitometry significantly enhance the ability of intravenous air-filled ultrasonographic contrast agent to produce ventricular and myocardial opacification. J Am Soc Echocardiogr (2001) 14:20–28.[CrossRef][Web of Science][Medline]
  16. Segar D.S, Brown S.E, Sawada S.G, Ryan T, Feigenbaum H. Dobutamine stress echocardiography: correlation with coronary lesion severity as determined by quantitative angiography. J Am Coll Cardiol (1992) 19:1197–1202.[Abstract]
  17. DePuey E.G. A stepwise approach to myocardial perfusion SPECT interpretation. In: Cardiac nuclear medicine—Gerson M.C, ed. (1997) 3rd ed. New York: McGraw Hill. 81–141.
  18. Cuocolo A, Acampa W, Nicolai E, Pace L, Petretta M, Salvatore M. Quantitative thallium-201 and technetium 99m sestamibi tomography at rest in detection of myocardial viability in patients with chronic ischemic left ventricular dysfunction. J Nucl Cardiol (2000) 7:8–15.[CrossRef][Web of Science][Medline]
  19. Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Measur (1960) 20:37–46.[CrossRef]
  20. Jayaweera A.R, Edwards N, Glasheen W.P, Villanueva F.S, Abbott R.D, Kaul S. In-vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography: comparison with radiolabeled red blood cells. Circ Res (1994) 74:1157–1165.[Abstract/Free Full Text]
  21. de Jong N, Ten Cate F.J, Lancee C.T, Roelandt J, Bom N. Principles and recent developments in ultrasound contrast agents. Ultrasonics (1991) 29:324–330.[CrossRef][Web of Science][Medline]
  22. Wei K, Jayaweera A.R, Firoozan S, Linka A, Skyba D.M, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation (1998) 97:473–483.[Abstract/Free Full Text]
  23. Moran C.M, Anderson T, Pye S.D, Sboros V, McDicken W.N. Quantification of microbubble destruction of three fluorocarbon-filled ultrasonic contrast agents. Ultrasound Med Biol (2000) 26:629–639.[CrossRef][Web of Science][Medline]
  24. Van Train K.F, Gracia E.V, Cooke C.D, Areeda J.S. Quantitative analysis of SPECT myocardial perfusion. In: Cardiac SPECT imaging—DePuey E.G, Garcia E.V, Berman D.S, eds. (2001) 2nd ed. Philadelphia: Lippincott, Williams and Wilkins. 41–64.
  25. Cobb F.R, Bache R.J, Rivas F, Greenfield J.C. Local effects of acute cellular injury on regional myocardial bloodflow. J Clin Invest (1976) 57:1359–1368.[Web of Science][Medline]
  26. Villanueva F.S, Glasheen W, Sklenar J, Kaul S. Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography: implications in determining extent of myocardial salvage. Circulation (1993) 88:2596–2606.[Abstract/Free Full Text]
  27. Skyba D.M, Jayaweera A.R, Goodman N.C, Ismail S, Camarano G, Kaul S. Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection. Circulation (1994) 90:1513–1521.[Abstract/Free Full Text]

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