Comparison of Iodixanol and Ioxaglate for Coronary Optical Coherence Tomography Imaging

Abstract: Background. The impact of contrast type on coronary imaging using optical coherence tomography (OCT) has received limited study. We compared OCT imaging obtained using the non-ionic, iso-osmolar iodixanol with the ionic, low-osmolar ioxaglate. Methods. Twenty-two vessels in 20 patients were imaged twice using manual injection of iodixanol and ioxaglate in random order. OCT images were analyzed at 1 mm intervals to determine lumen area, artifact diameter and area, as well as stent strut coverage and malapposition in OCT pullbacks that included stents. Results. There were no complications related to OCT imaging or to contrast administration. A total of 2184 cross-sections (1092 with iodixanol and 1092 with ioxaglate) were analyzed. Compared with iodixanol, imaging using ioxaglate provided similar mean lumen area (6.21 ± 2.83 mm² vs 6.27 ± 2.83 mm²; Spearman’s rho, 0.982), mean minimum lumen diameter (2.47 ± 0.59 mm vs 2.50 ± 0.58 mm; Spearman’s rho, 0.939), and mean maximum lumen diameter (2.99 ± 0.71 mm vs 3.01 ± 0.70 mm; Spearman’s rho, 0.964), but lower mean artifact area per cross-section (0.099 ± 0.325 mm² vs 0.068 ± 0.329 mm²; P<.001). Analyses of 3303 stent struts in 388 cross-sections (194 with iodixanol and 194 with ioxaglate) demonstrated similar strut malapposition rates (11.82% vs 13.90%; P=.10) and strut coverage (41.92% vs 40.33%; P=.35). Conclusions. Compared with iodixanol, OCT imaging using ioxaglate provided similar lumen and diameter measurements and stent strut characterization, but smaller area of artifact.   

 J INVASIVE CARDIOL 2015;27(12):E287-E290. Epub 2015 September 15.

Key words: coronary artery disease, cardiac imaging, radiographic contrast, iodixanol, ioxaglate

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Optical coherence tomography (OCT) is a high-resolution (15-20 µm), catheter-based coronary imaging technique that can reliably identify various anatomic substrates, such as lipid-rich plaques, fibrous plaques, calcium, and thrombus.^1,2 In addition, due to its higher resolution, OCT has been shown to be superior to intravascular ultrasonography for determining plaque rupture, fibrous cap erosion, stent apposition, dissection, and extent of intimal hyperplasia.^3-5 These qualities make OCT a powerful tool in assessing coronary plaque morphology and optimizing the outcomes of percutaneous coronary intervention.^3,6 

OCT requires displacement of the red blood cells from the vessel lumen during image acquisition.⁷ This is usually accomplished using radiographic contrast, although low-molecular-weight dextran can provide similar results.⁸ Several contrast types are currently available for clinical use that can be broadly categorized as low-osmolar and iso-osmolar, with the latter being more viscous. No study has evaluated the impact of contrast type on OCT imaging. Hence, we compared the non-ionic, iso-osmolar iodixanol with the ionic, low-osmolar ioxaglate for coronary OCT imaging. 

Methods

Patients. Patients undergoing clinically indicated coronary angiography with OCT imaging between January 2014 and April 2014 were enrolled. Exclusion criteria included hemodynamic instability, severe coronary tortuosity, severe coronary calcification, and creatinine ≥2.5 mg/dL. The study was approved by the review board of our institution and all patients provided written informed consent. 

Coronary angiography. Coronary angiography was performed using femoral or radial access with 6 Fr guide catheters and conventional 0.014˝ coronary guidewires. All lesions were imaged using at least two orthogonal views. Selection of anticoagulation, other adjunctive pharmacotherapy, and percutaneous coronary intervention technique and equipment were at the discretion of the operator. 

Optical coherence tomography. OCT imaging of the same target coronary artery segment was sequentially performed using the 2.7 Fr C7 Dragonfly intravascular imaging catheter (St. Jude Medical) during manual intracoronary administration of iodixanol and ioxaglate at room temperature. Administration of the two different contrast agents was performed in random order. The catheter was advanced distally to the target lesion, and automated mechanical pullback was performed at a speed of 20 mm/s during contrast injection, until 54 mm were imaged. The catheter position was not changed during imaging with each contrast agent.

OCT analysis was performed using the Ilumien Optis system (St. Jude Medical), with calibration before each measurement. OCT images were analyzed at 1 mm intervals, measuring lumen area and diameter as well as area of residual blood artifact, which was defined as high attenuation areas within the lumen with no connection to the coronary vessel wall. Care was taken to avoid mistakenly labeling residual blood artifact as thrombus or some other specific intravascular finding.

Measurements were performed every third frame. Co-registration of the pullbacks obtained using the two different contrast types was ascertained using fiduciary landmarks, such as side branches and location of the target coronary lesion. Clear image segments were defined as a visible lumen border >270°.⁹ Images acquired using both iodixanol and ioxaglate were analyzed using the 100% contrast setting of the imaging analysis software.

Strut apposition and coverage. A strut was considered suitable for analysis only if it had both a well-defined bright “blooming” appearance and characteristic shadow perpendicular to the light source. The center of the luminal surface of the strut blooming was determined for each strut, and its distance to the lumen contour was calculated automatically to determine strut-level intimal thickness (SIT). Struts covered by tissue had positive SIT values, whereas uncovered or malapposed struts had negative SIT values. The number of struts without coverage was counted for each frame analyzed, and the total number of frames with uncovered struts was recorded. All study stents were everolimus eluting. Struts were classified as malapposed when the negative SIT value was higher than 108 µm (81 µm strut thickness + 7.8 µm coating thickness + 20 µm resolution threshold for OCT).¹⁰  

Statistical analysis of lumen measurements. Continuous variables were summarized as mean ± standard deviation and compared using the paired-sample t-test. The agreement between measurements obtained with iodixanol and ioxaglate was evaluated using Bland-Altman analysis. Spearman’s rho and linear regression were used to evaluate the correlation between the iodixanol and ioxaglate measurements. Analyses were performed using JMP version 11 and P<.05 was considered statistically significant. 

Results

Patients. Twenty patients who met the criteria were enrolled in our study. A total of 22 target vessels were imaged with OCT using both ioxaglate and iodixanol for blood clearance during imaging. The following vessels were imaged: right coronary artery (30%), left anterior descending coronary artery (40%), saphenous vein graft (15%), and circumflex artery (15%). Mean age was 68.35 ± 8.25 years and all patients were men. There were no complications related to contrast administration or to OCT imaging.

OCT lumen analysis. A total of 2184 cross-sections (1092 obtained using iodixanol and 1092 obtained using ioxaglate) were analyzed. Table 1 provides a detailed comparison of the paired measurements. Nearly all cross-sections were clearly imaged with both agents, and measurements of lumen area and lumen diameter were highly correlated (correlation coefficients ranged between 0.939 and 0.982) (Table 1 and Figure 1). The total artifact area (sum of artifact from all the cross-sections) was 110.1 mm² with iodixanol vs 86.44 mm² with ioxaglate (P<.001), and the mean artifact area per imaged cross-section was also higher with iodixanol (Table 1). 

OCT stent strut analysis. Of the 22 vessels imaged with OCT, 10 included stents (all everolimus eluting). A total of 388 cross-sections (194 obtained using iodixanol and 194 obtained using ioxaglate) with a total of 3303 struts were analyzed. The prevalence of stent strut malapposition and coverage was similar when imaging was performed with iodixanol and ioxaglate (Table 2).

Discussion

To the best of our knowledge, this study was the first to compare two contrast agents for coronary OCT imaging. The main finding was that administration of iodixanol and ioxaglate via manual injection provided similar luminal measurements and stent strut characterization; however, the area of residual blood artifact was slightly larger with iodixanol.

Compared with iodixanol, ioxaglate is less viscous, and hence easier to inject, which could theoretically facilitate vessel filling with contrast and improve the quality of OCT imaging by minimizing the extent of blood artifact. Our study demonstrated that the images obtained with ioxaglate were indeed slightly less likely to have blood artifact; however, the difference was small and its clinical significance remains uncertain. Therefore, both contrast agents appear to be suitable for coronary OCT imaging. 

Saline or low-molecular-weight dextran could be used instead of contrast for OCT imaging. Frick et al demonstrated that dextran provides similar image quality with contrast agents during OCT image acquisition, suggesting that dextran could be substituted for contrast, especially in patients in whom contrast load minimization is desired.⁸ Given et al demonstrated that saline provided similar imaging quality to contrast media in frequency-domain OCT imaging of human carotid atherosclerosis.¹¹ However, the lower viscosity of contrast and low-molecular-weight dextran require higher flow injection to clear injection, which may be challenging to achieve in some patients. Contrast media currently remain the most commonly used agents for OCT imaging. 

Study limitations. This was a single-center study and the number of patients and OCT runs examined was relatively small. Contrast administration was performed using manual injection; if injections were performed using an automated injector, differences in area of artifact could be decreased, as high contrast flow could provide more complete vessel filling. Evaluating the clinical significance of the differences in artifact area would require a much larger study. 

Conclusion

In summary, OCT imaging using iodixanol and ioxaglate through manual injection provides similar luminal measurements and stent strut characterization, but iodixanol is associated with slightly larger area of artifact. 

References

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From the VA North Texas Health Care System, Dallas, Texas and University of Texas Southwestern Medical School, Dallas, Texas. 

Funding: This study was funded through a grant from Guerbet, LLC.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Banerjee reports research grants from Gilead and The Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, Asahi Intecc, Boston Scientific, Elsevier, Somahlution, St. Jude Medical, and Terumo Corporation; research support from Guerbet and InfraRedx; spouse is employee of Medtronic. The remaining authors report no disclosures regarding the content herein.

Manuscript submitted November 21, 2014, provisional acceptance given February 13, 2015, final version accepted April 13, 2015.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, VA North Texas Health Care System, The University of Texas Southwestern Medical Center at Dallas, Division of Cardiology (111A), 4500 S. Lancaster Rd, Dallas, TX 75216. Email: esbrilakis@gmail.com