IVUS Tales: From Research to its Clinical application in Contemporary Interventions. Presenter: Islam Bolad Attending: Jos...
<ul><li>Visual interpretation of coronary angiography exhibits </li></ul><ul><li>intraobserver and interobserver variabili...
Am J Cardiol 2002;89(suppl):24B-31B
IVUS <ul><li>Vessel wall vs. lumen. </li></ul><ul><li>Internal electronic distance scale </li></ul>
IVUS Technology <ul><li>Real time high resolution imaging. </li></ul><ul><li>2D tomographic assessments of vessels </li></...
<ul><li>Two main IVUS systems are currently in use: </li></ul><ul><li>1- A mechanical system that contains a flexible </li...
<ul><li>IVUS catheters max. diameter 2.6-3 Fr (0.89-1mm) </li></ul><ul><li>Motorized pull back of transducer (0.25-1mm/sec...
<ul><li>Recently, more advanced IVUS plaque  </li></ul><ul><li>characterization has been introduced. </li></ul><ul><li>1- ...
<ul><li>2- Intravascular elastography. </li></ul><ul><li>IVUS radiofrequency acquired at different levels  </li></ul><ul><...
Technical Aspects <ul><li>Transducers with US frequencies ranging between </li></ul><ul><li>20-50 MHz are used (usually 30...
Resolutions
Perivascular Landmarks. <ul><li>A well defined imaging protocol is vital for proper </li></ul><ul><li>IVUS interpretation ...
 
 
LAD <ul><li>Diagonals </li></ul><ul><li>Anterior Interventricular Vein. </li></ul><ul><li>- Left of proximal and mid LAD i...
 
In its distal portion, the anterior interventricular vein (AIV) may branch into  two vessels accompanying the LAD on both ...
The elliptic shape of the AIV can be appreciated at 3 o'clock in this cross section from the mid LAD
LAD/LCx bifurcation, LCx, GCV triangle. Triangle of Brocq & Mouchet
LCx <ul><li>Distally, Cx is accompanied by posterior LV vein </li></ul><ul><li>Proximally, Cx is accompained and crossed b...
 
The great cardiac vein is seen best from the proximal Cx as a large, almost clear structure filled with fine blood speckle...
RCA <ul><li>Translational effect (like CX) as it is an AV groove  </li></ul><ul><li>artery. </li></ul><ul><li>The marginal...
Veins are associated with RV marginal branches and are characterized by an  arching pattern around the RCA.
The Endovascular Anatomy.  The arterial wall.
Different echogenic qualities is due to the relative amount of  collagen (1000x reflectance than smooth muscles) and elastin
Blood <ul><li>Speckled pattern that is constantly changing with  </li></ul><ul><li>systolic and diastolic blood flow alter...
 
 
Calcific Plaque <ul><li>Calcific plaque is the simplest tissue type to identify </li></ul><ul><li>Bright reflection of int...
 
<ul><li>Sometimes, shadowing with no bright reflections  </li></ul><ul><li>occurs in calcified lesions. </li></ul><ul><li>...
Fibrous Plaque <ul><li>Plaques with echogenicity that is < bright than  </li></ul><ul><li>than calcium, but higher than th...
 
Fatty Plaque <ul><li>Radiolucent, and has a soft grey-scale appearance </li></ul><ul><li>on IVUS. </li></ul><ul><li>Radiol...
 
Plaque distribution and remodeling <ul><li>Significant plaque burden (30-40%) & normal  </li></ul><ul><li>arteries by angi...
RCA: IVUS from segments 5mm apart without vessel branching between them. A- Small vessel with some element of focal calcif...
<ul><li>Negative remodeling / de-remodeling. </li></ul><ul><li>Commonly seen as part of restenosis process  </li></ul><ul>...
 
Endovascular Entities.  Thrombus. One of the most difficult tissue types to identify by IVUS <ul><li>Sparkling pattern on ...
Thrombus after stent deployment.
Post PTCA and Reopro
False Lumen <ul><li>Recognition of 3 layered appearance (true lumen), </li></ul><ul><li>observation of slower and more ech...
 
Aneurysms <ul><li>Useful in discriminating between true and false  </li></ul><ul><li>aneurysms. </li></ul><ul><li>Histolog...
 
Black Holes <ul><li>Initially described following brachytherapy. </li></ul><ul><li>Thought to represent tissue is acellula...
 
Quantitative Coronary Ultrasound (QCU)
Evaluating Intermediate Coronary Lesions. <ul><li>Abizaid et al compared various IVUS parameters </li></ul><ul><li>with CF...
<ul><li>Nishioka et al compared IVUS parameter with  </li></ul><ul><li>nuclear perfusion imaging. </li></ul><ul><li>They f...
<ul><li>Takagi et al compared IVUS parameters with FFR </li></ul><ul><li>for determining functional significance of modera...
<ul><li>Briguori et al compared IVUS with FFR only in  </li></ul><ul><li>patients with intermediate lesions. </li></ul><ul...
What about the LMS? <ul><li>Jasti et al examined 55 patients with an angiographically  </li></ul><ul><li>ambiguous LMCS, a...
<ul><li>Regression analysis demonstrated strong correlations between  </li></ul><ul><li>FFR and MLD as well as between FFR...
<ul><li>Fassa et al performed IVUS on 121 patients with  </li></ul><ul><li>angiographically normal LMSs to determine the  ...
<ul><li>In the normal LMSs group, LCSA was 16.25 ±4.3 mm 2. </li></ul><ul><li>The lower N value (mean MLA-2SD) was 7.65mm ...
Limitations of IVUS <ul><li>Ring-down artifact. </li></ul><ul><li>Caused by transducer oscillation filling the area  </li>...
<ul><li>NURD </li></ul><ul><li>Occurs when the rotating transducer inside the  </li></ul><ul><li>US catheter is exposed to...
Image Quantification Errors <ul><li>Catheter positioning. </li></ul><ul><li>Catheter angulation, especially in large arter...
Ghost Images <ul><li>Occurs when structures of high echogenicity are </li></ul><ul><li>imaged (eg Calcium, stent struts) <...
Summary <ul><li>Gold standard for vessel visualization. </li></ul><ul><li>Led to new insights into the pathophysiology of ...
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IVUS Tales: From Research to its Clinical application in ...

  1. 1. IVUS Tales: From Research to its Clinical application in Contemporary Interventions. Presenter: Islam Bolad Attending: Jose Diez
  2. 2. <ul><li>Visual interpretation of coronary angiography exhibits </li></ul><ul><li>intraobserver and interobserver variability </li></ul><ul><li>( < 50%) </li></ul><ul><li>Angiography & postmortem histology. </li></ul><ul><li>QCA </li></ul><ul><li>Glagov phenomenon </li></ul>Coronary Angiography
  3. 3. Am J Cardiol 2002;89(suppl):24B-31B
  4. 4. IVUS <ul><li>Vessel wall vs. lumen. </li></ul><ul><li>Internal electronic distance scale </li></ul>
  5. 5. IVUS Technology <ul><li>Real time high resolution imaging. </li></ul><ul><li>2D tomographic assessments of vessels </li></ul><ul><li>Also longitudinal and 3D computer asssited </li></ul><ul><li>reconstruction. </li></ul><ul><li>Allows assessment of total vessel lumen and </li></ul><ul><li>plaque dimension in vivo. </li></ul>
  6. 6. <ul><li>Two main IVUS systems are currently in use: </li></ul><ul><li>1- A mechanical system that contains a flexible </li></ul><ul><li>imaging cable which rotates a single transducer </li></ul><ul><li>at its tip inside an echo-lucent distal sheath. </li></ul><ul><li>2- An electronic solid state catheter system with </li></ul><ul><li>multiple imaging elements at its distal tip, providing </li></ul><ul><li>cross sectional imaging by sequentially activating </li></ul><ul><li>the imaging elements in a circular way. </li></ul><ul><li>1 is usually smaller than 2. </li></ul>
  7. 7. <ul><li>IVUS catheters max. diameter 2.6-3 Fr (0.89-1mm) </li></ul><ul><li>Motorized pull back of transducer (0.25-1mm/sec, </li></ul><ul><li>usually 0.5mm/sec) </li></ul><ul><li>Volumetric measurement. </li></ul><ul><li>Imaging frequencies increased- improved qualitative </li></ul><ul><li>assessment of atherosclerotic plaques. </li></ul><ul><li>- Soft, low echogenecity </li></ul><ul><li>- Fibrous, high echogenicity </li></ul><ul><li>- Calcified, high echogenicity with acoustic </li></ul><ul><li>shadowing/ reverberations. </li></ul>
  8. 8. <ul><li>Recently, more advanced IVUS plaque </li></ul><ul><li>characterization has been introduced. </li></ul><ul><li>1- Analysis of the backscatter IVUS radiofrequency </li></ul><ul><li>data provided a color coded mapping based on </li></ul><ul><li>the different backscatter signals among the tissue </li></ul><ul><li>types (virtual histology). </li></ul><ul><li>- Allows examination of the different plaque </li></ul><ul><li>components in more details (fibrous, fibro-lipidic, </li></ul><ul><li>calcium, lipid core) </li></ul>Nair et al Circulation. 2002 Oct 22;106(17):2200-6.
  9. 9. <ul><li>2- Intravascular elastography. </li></ul><ul><li>IVUS radiofrequency acquired at different levels </li></ul><ul><li>of intravascular pressure can measure tissue strain </li></ul><ul><li>reflecting the mechanical properties of the vessel </li></ul><ul><li>wall. </li></ul><ul><li>- Help identify vulnerable plaque prior to rupture. </li></ul><ul><li>Both techniques require further validation. </li></ul>
  10. 10. Technical Aspects <ul><li>Transducers with US frequencies ranging between </li></ul><ul><li>20-50 MHz are used (usually 30MHz). </li></ul><ul><li>High frequencies provide excellent theoretical </li></ul><ul><li>resolution, as US wavelength which determines </li></ul><ul><li>the maximum resolution is inversely proportional </li></ul><ul><li>to frequency. </li></ul><ul><li>AT 30MHz, the wavelength is ≈50µm, which permits </li></ul><ul><li>an axial resolution of 100 µm. Lateral resolution </li></ul><ul><li>≈ 250µm. </li></ul>Metz JA et al.
  11. 11. Resolutions
  12. 12. Perivascular Landmarks. <ul><li>A well defined imaging protocol is vital for proper </li></ul><ul><li>IVUS interpretation in the coronary tree. </li></ul><ul><li>Slow pullback from distal to proximal vessel. </li></ul><ul><li>Perivascular markings are important reference </li></ul><ul><li>for axial position and tomographic orientation </li></ul><ul><li>within the artery. </li></ul><ul><li>Important for reproducibility of examination within </li></ul><ul><li>same segment. </li></ul>
  13. 15. LAD <ul><li>Diagonals </li></ul><ul><li>Anterior Interventricular Vein. </li></ul><ul><li>- Left of proximal and mid LAD in 85%. D1 & D2 </li></ul><ul><li>emerge from LAD on same side of vein. </li></ul><ul><li>- Right of LAD in 15% and crosses it near bifurcation </li></ul><ul><li>of the LCx. </li></ul><ul><li>- In 30%, the AIV branches into 2 beyond D2. </li></ul>
  14. 17. In its distal portion, the anterior interventricular vein (AIV) may branch into two vessels accompanying the LAD on both sides
  15. 18. The elliptic shape of the AIV can be appreciated at 3 o'clock in this cross section from the mid LAD
  16. 19. LAD/LCx bifurcation, LCx, GCV triangle. Triangle of Brocq & Mouchet
  17. 20. LCx <ul><li>Distally, Cx is accompanied by posterior LV vein </li></ul><ul><li>Proximally, Cx is accompained and crossed by </li></ul><ul><li>great cardiac vein. </li></ul><ul><li>GCV & posterior LV vein form coronary sinus, </li></ul><ul><li>best visualized from distal RCA. </li></ul><ul><li>GCV runs superior to Cx , just inferior to LA </li></ul><ul><li>appendage. </li></ul>
  18. 22. The great cardiac vein is seen best from the proximal Cx as a large, almost clear structure filled with fine blood speckle.
  19. 23. RCA <ul><li>Translational effect (like CX) as it is an AV groove </li></ul><ul><li>artery. </li></ul><ul><li>The marginal veins (in contrast to LAD) cross over </li></ul><ul><li>artery in an arcing pattern. </li></ul><ul><li>Usually, small amount of fluid near the crux. </li></ul>
  20. 24. Veins are associated with RV marginal branches and are characterized by an arching pattern around the RCA.
  21. 25. The Endovascular Anatomy. The arterial wall.
  22. 26. Different echogenic qualities is due to the relative amount of collagen (1000x reflectance than smooth muscles) and elastin
  23. 27. Blood <ul><li>Speckled pattern that is constantly changing with </li></ul><ul><li>systolic and diastolic blood flow alterations </li></ul><ul><li>( > echogenic in systole). </li></ul><ul><li>In real-time imaging, lumen/ intima has distinct </li></ul><ul><li>appearance; in still frames blood speckle can have </li></ul><ul><li>a pattern similar to plaque. </li></ul><ul><li>Blood stagnation proximal to a stenosis may have </li></ul><ul><li>a similar effect. Saline flush can clear the lumen </li></ul><ul><li>temporarily. </li></ul>
  24. 30. Calcific Plaque <ul><li>Calcific plaque is the simplest tissue type to identify </li></ul><ul><li>Bright reflection of intense signal attenuation. </li></ul><ul><li>“ Ghost Arcsor” reverbrations. </li></ul><ul><li>Calcification is seen in 60-80% of target lesions </li></ul><ul><li>using IVUS compared to 30-40% by angiography. </li></ul><ul><li>180 degrees of vascular circumference must be </li></ul><ul><li>calcified before it can be visualized by angiography. </li></ul>
  25. 32. <ul><li>Sometimes, shadowing with no bright reflections </li></ul><ul><li>occurs in calcified lesions. </li></ul><ul><li>IVUS imaging of calcium is angle dependent, and the </li></ul><ul><li>calcific plaque itself is imaged only when the beam is </li></ul><ul><li>perpendicular </li></ul><ul><li>Acosutic shadowing can occur in the absence of </li></ul><ul><li>calcium in the presence of dense fibrous tissue. </li></ul><ul><li>Therefore it is correct to refer to lesions with </li></ul><ul><li>shadowing on IVUS as fibrocalcific. This distinction </li></ul><ul><li>does not have major clinical implication. </li></ul>
  26. 33. Fibrous Plaque <ul><li>Plaques with echogenicity that is < bright than </li></ul><ul><li>than calcium, but higher than that from muscle or </li></ul><ul><li>fat tissue. </li></ul><ul><li>In general, brightness of fibrous tissue is similar </li></ul><ul><li>to that of adventitia. </li></ul><ul><li>No reverebrations. </li></ul>
  27. 35. Fatty Plaque <ul><li>Radiolucent, and has a soft grey-scale appearance </li></ul><ul><li>on IVUS. </li></ul><ul><li>Radiolucent areas within fibrous plaques reflect </li></ul><ul><li>accumulation of lipid. </li></ul><ul><li>Shadowing from a heavily fibrotic plaque can be </li></ul><ul><li>mistaken for lipid. </li></ul>
  28. 37. Plaque distribution and remodeling <ul><li>Significant plaque burden (30-40%) & normal </li></ul><ul><li>arteries by angiography. </li></ul><ul><li>Positive remodeling. </li></ul><ul><li>Concentric / focal remodeling. </li></ul><ul><li>Positive remodeling is exhausted when 50% of the </li></ul><ul><li>lumen is occupied by plaque, and further growth </li></ul><ul><li>results in lumen encroachment. </li></ul>
  29. 38. RCA: IVUS from segments 5mm apart without vessel branching between them. A- Small vessel with some element of focal calcification. B- Dramatic vessel remodeling in a fibrofatty lesion.
  30. 39. <ul><li>Negative remodeling / de-remodeling. </li></ul><ul><li>Commonly seen as part of restenosis process </li></ul><ul><li>following PCI. </li></ul><ul><li>Vessel scarring & shrinkage may in some caces </li></ul><ul><li>contribute significantly to late lumen loss after PTCA </li></ul>
  31. 41. Endovascular Entities. Thrombus. One of the most difficult tissue types to identify by IVUS <ul><li>Sparkling pattern on real time IVUS imaging. </li></ul><ul><li>Presence of microchannels, echodensity < 50% </li></ul><ul><li>of the surrounding adventitia and deep Ca are </li></ul><ul><li>clues to the correct diagnosis of thrombus. </li></ul><ul><li>Sometimes, lobular or cauliflower-like appearance. </li></ul><ul><li>Identification of thrombus after stenting may </li></ul><ul><li>sometimes be vital. </li></ul>
  32. 42. Thrombus after stent deployment.
  33. 43. Post PTCA and Reopro
  34. 44. False Lumen <ul><li>Recognition of 3 layered appearance (true lumen), </li></ul><ul><li>observation of slower and more echogenic blood </li></ul><ul><li>reflectance (commonly in false lumen) and </li></ul><ul><li>identification of branches taking off from true lumen </li></ul><ul><li>provide clues to discriminate the 2 lumina. </li></ul><ul><li>Contrast material injection can sometimes be </li></ul><ul><li>helpful because the echogenic patterns from </li></ul><ul><li>contrast hung-up and takes longer to evacuate </li></ul><ul><li>a false lumen. </li></ul>
  35. 46. Aneurysms <ul><li>Useful in discriminating between true and false </li></ul><ul><li>aneurysms. </li></ul><ul><li>Histologically, presence of media differentiates </li></ul><ul><li>true from false aneurysms. </li></ul><ul><li>In true aneurysms, the media is thinned and </li></ul><ul><li>expanded but fully encompasses the perimeter </li></ul><ul><li>of the aneurysm. </li></ul>
  36. 48. Black Holes <ul><li>Initially described following brachytherapy. </li></ul><ul><li>Thought to represent tissue is acellular and necrotic </li></ul><ul><li>and lacks connective tissue elements 1 . </li></ul><ul><li>Kay et al 2 showed that it is tissue rich in </li></ul><ul><li>proteoglycans while poor in mature collagen &elastin </li></ul><ul><li>Now seen with DES. </li></ul><ul><li>1- Circulation. 2001 Feb 6;103(5):778. </li></ul><ul><li>2- Int J Cardiovasc Intervent. 2003;5(3):137-42. </li></ul>
  37. 50. Quantitative Coronary Ultrasound (QCU)
  38. 51. Evaluating Intermediate Coronary Lesions. <ul><li>Abizaid et al compared various IVUS parameters </li></ul><ul><li>with CFR. </li></ul><ul><li>Linear relation between CFR and minimum LCSA. </li></ul><ul><li>They defined minimum LCSA as ≤4mm 2 and </li></ul><ul><li>demonstrated concordance of 89% with CFR </li></ul><ul><li>(abnormal CFR <2). </li></ul>Am J Cardiol. 1998 Aug 15;82(4):423-8.
  39. 52. <ul><li>Nishioka et al compared IVUS parameter with </li></ul><ul><li>nuclear perfusion imaging. </li></ul><ul><li>They found that minimum LCSA ≤4mm 2 had </li></ul><ul><li>sensitivity of 88% and specificity of 90% for predicting </li></ul><ul><li>reversible perfusion defect. </li></ul><ul><li>Other IVUS parameters (eg % area stenosis) </li></ul><ul><li>performed less well. </li></ul>J Am Coll Cardiol. 1999 Jun;33(7):1870-8
  40. 53. <ul><li>Takagi et al compared IVUS parameters with FFR </li></ul><ul><li>for determining functional significance of moderate </li></ul><ul><li>lesions. </li></ul><ul><li>Strong correlation between minimum LCSA and FFR </li></ul><ul><li>Using cutoff of ≤3mm 2 to define abnormal minimum </li></ul><ul><li>LCSA and < 0.75 to define abnormal FFR, the </li></ul><ul><li>investigators found IVUS had a sensitivity of 83% </li></ul><ul><li>and specificity of 92% for detecting ischemia </li></ul><ul><li>producing lesions based on FFR. </li></ul>Circulation. 1999 Jul 20;100(3):250-5.
  41. 54. <ul><li>Briguori et al compared IVUS with FFR only in </li></ul><ul><li>patients with intermediate lesions. </li></ul><ul><li>IVUS minimum LCSA was significantly related to </li></ul><ul><li>FFR (r=0.41, p<0.004). </li></ul><ul><li>The sensitivity and specificity of minimum IVUS </li></ul><ul><li>LCSA of ≤ 4mm 2 for predicting FFR ≤0.75 were </li></ul><ul><li>92% and 56%. </li></ul>Am J Cardiol. 2001 Jan 15;87(2):136-41.
  42. 55. What about the LMS? <ul><li>Jasti et al examined 55 patients with an angiographically </li></ul><ul><li>ambiguous LMCS, a pressure guidewire was used to calculate </li></ul><ul><li>FFR, and IVUS parameters were calculated after automatic </li></ul><ul><li>pullback. </li></ul><ul><li>IVUS MLD = 3.8±0.61 mm, MLA = 7.65±2.9 mm2, cross- </li></ul><ul><li>sectional narrowing (CSN) = 59±13%, , and area stenosis (AS) </li></ul><ul><li>= 47±19%. </li></ul>Circulation. 2004;110:2831-2836
  43. 56. <ul><li>Regression analysis demonstrated strong correlations between </li></ul><ul><li>FFR and MLD as well as between FFR and MLA. </li></ul><ul><li>Compared with FFR as the &quot;gold standard,&quot; an MLD of 2.8 </li></ul><ul><li>mm had the highest sensitivity and specificity (93% and 98%, </li></ul><ul><li>respectively) for determining the significance of an LMCS, </li></ul><ul><li>followed by an MLA of 5.9 mm 2 (93% and 95%, respectively). </li></ul>
  44. 57. <ul><li>Fassa et al performed IVUS on 121 patients with </li></ul><ul><li>angiographically normal LMSs to determine the </li></ul><ul><li>lower range of normal minimum lumen area (MLA), </li></ul><ul><li>defined as the mean - 2 SD. </li></ul><ul><li>They also conducted IVUS studies on 214 patients </li></ul><ul><li>with angiographically indeterminate LMS lesions, and </li></ul><ul><li>deferral of revascularization was recommended when </li></ul><ul><li>the MLA was larger than this predetermined value. </li></ul>J Am Coll Cardiol. 2005 Jan 18;45(2):204-11
  45. 58. <ul><li>In the normal LMSs group, LCSA was 16.25 ±4.3 mm 2. </li></ul><ul><li>The lower N value (mean MLA-2SD) was 7.65mm 2. </li></ul><ul><li>7.5mm 2 was used as the lower range of normal. </li></ul><ul><li>The majority of patients < 7.5 underwent revasc. </li></ul><ul><li>Follow-up (mean 3.3 ± 2.0 yrs) showed no significant </li></ul><ul><li>difference in MACE between patients with an MLA </li></ul><ul><li><7.5 mm 2 who underwent revascularization and </li></ul><ul><li>those with an MLA ≥ 7.5 mm 2 deferred for </li></ul><ul><li>revascularization (p = 0.28). </li></ul><ul><li>Based on outcome, the best cut-off MLA by ROC </li></ul><ul><li>was 9.6 mm 2 . </li></ul>
  46. 59. Limitations of IVUS <ul><li>Ring-down artifact. </li></ul><ul><li>Caused by transducer oscillation filling the area </li></ul><ul><li>immediately adjacent to the catheter with noise, </li></ul><ul><li>making this area unavailable for imaging. </li></ul><ul><li>Seen as bright halo of variable thickness surrounding </li></ul><ul><li>the catheter. </li></ul>
  47. 60. <ul><li>NURD </li></ul><ul><li>Occurs when the rotating transducer inside the </li></ul><ul><li>US catheter is exposed to frictional forces </li></ul><ul><li>(eg catheter bending, hemostatic valve too tight) </li></ul><ul><li>Portions of the images are stretched or compacted </li></ul><ul><li>Catheter manipulation eliminates artifact. </li></ul><ul><li>Can be a problem in calcific arteries. </li></ul><ul><li>NURD does not occur in solid state design </li></ul><ul><li>(advantage over mechanical design). </li></ul>
  48. 61. Image Quantification Errors <ul><li>Catheter positioning. </li></ul><ul><li>Catheter angulation, especially in large arteries. </li></ul><ul><li>Can alter vessel geometry. </li></ul>
  49. 62. Ghost Images <ul><li>Occurs when structures of high echogenicity are </li></ul><ul><li>imaged (eg Calcium, stent struts) </li></ul><ul><li>Appear of the side of the transducer that is opposite </li></ul><ul><li>the bright structure being imaged. </li></ul>
  50. 63. Summary <ul><li>Gold standard for vessel visualization. </li></ul><ul><li>Led to new insights into the pathophysiology of </li></ul><ul><li>coronary plaque accumulation. </li></ul><ul><li>Advances in technology will certainly revolutionalize </li></ul><ul><li>this imaging modality. </li></ul>

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