Detection and Detection and Management of Management of

Vulnerable PlaqueVulnerable PlaqueDept of Cadiology Dept of Cadiology

Beijing Anzhen HospitalBeijing Anzhen Hospital Capital University of Medical SciencesCapital University of Medical Sciences

QuanMingQuanMing ZhaoZhao M.D, Ph.D.M.D, Ph.D.

Part onePart one

ConceptConcept

Definition Definition

ReviewReview

Definition of Vulnerable PlaqueDefinition of Vulnerable Plaque

The term “vulnerable plaque” refers to a subgroup of often modestly stenotic plaques that are prone to rupture or erosion, often resulting in acute coronary syndromes and sudden cardiac death.

Postmortem evaluation has shown that rupture-prone plaques have certain characteristics: a thin, fibrous cap (65 um); a large, lipid-rich pool; and increased macrophage activity .

Cellular mechanisms thought to predispose to plaque vulnerability include reduced collagen synthesis, local overexpression of collagenase, and smooth muscle cell apoptosis.

It has been suggested that disruption in cap integrity releases procoagulant factors, particularly tissue factor, creating a nidus for thrombus formation and the potential for an acute coronary event.

Major criteria • Active inflammation (monocyte/macrophage and sometimes T-cell infiltration) • Thin cap with large lipid core • Endothelial denudation with superficial platelet gregation • Fissured plaque • Stenosis 90%Minor criteria • Superficial calcified nodule • Glistening yellow • Intraplaque hemorrhage • Endothelial dysfunction • Outward (positive) remodeling

Criteria for Defining Vulnerable Plaque, Based on the Study of Culprit Plaques

Part Two

Detection of Detection of Vulnerable Plaque Vulnerable Plaque

Invasive method AngiographyAngiography （（ Golden standard ）） intravascular unltrasound (intravascular unltrasound (IVUS) Optical Coherence Tomography(Optical Coherence Tomography(OCT)) AngioscopyAngioscopy Intravascular magnetic resonance imaging (Intravascular magnetic resonance imaging (MRI))

Non invasive method Computed tomographyComputed tomography （（ CTCT ）） Magnetic resonance imagingMagnetic resonance imaging （（ MRAMRA ）） Radionuclide imagingRadionuclide imaging

1. Angiography for 1. Angiography for Detection of Vulnerable Detection of Vulnerable PlaquePlaque

There is no clear standard in AngiographyAngiography associated with plaque vulnerabilityassociated with plaque vulnerability

Morphological characteristics are critical in Morphological characteristics are critical in AngiographyAngiography

Angiography has been shown to detect features Angiography has been shown to detect features associated with plaque vulnerability, such as an associated with plaque vulnerability, such as an eccentric pattern ,an irregular surface , filling eccentric pattern ,an irregular surface , filling defect and presence of thrombi defect and presence of thrombi 。。

The lesions are usually divided into two types: The lesions are usually divided into two types: simple lesions and complex lesions.simple lesions and complex lesions.

Lesion Types by AngiographyAngiography

1. concentric (symmetric narrowing); 2 .type I eccentric(asymmetric narrowing with smoothborders and a broad neck)3. type II eccentric (asymmetric with a narrow neck or irregular borders, or both); 4.multiple irregular coronary narrowings in series. Simple Lesions: 1,2 Complex Lesions: 3,4

JACC,1985,5:609-616

Angiographic Morphology and Angina Pectoris

Author Clinical Type(patients number) Complex Lesions References

Ambrose SAP （ 47 ） 18% JACC,1985,5:609-616

UAP （ 63 ） 56%

Taus SAP （ 65 ） 18% Radiology,1985,157(p):67

UAP （ 38 ） 55%

Ambrose SAP （ 25 ） 20% JACC,1985,5:609-616

UAP （ 25 ） 71%

Ambrose SAP （ 12 ） 6% JACC,1985,6:1233-1238

Ambrose UAP （ 12 ） 9%

SAP: Stable angina pectoris UAP: Unstable angina petoris

Postmortem Coronary Angiographic Morphology and Histopathological Results

Simple Lesions

Complex Lesions

Simple Lesions

31 8

Complex Lesions

4 30

Postmortem Coronary Angiographic

His

top

ath

olo

gic

al

Res

ult

s

Circulation. 1982;66:316-320

CAG OF a ACS patient

Limitations:

1.this imaging method does not provide information about the composition of the atherosclerotic plaque such as the vulnerable lipid-rich plaques or other histopathological features. 2.diffuse atherosclerotic disease may narrow the entire lumen of the artery, and as a result underestimate the degree of local stenosis.3.some of the plaques may be displaced outward, the luminal diameter may appear normal despite significant disease.

2. Intravascular 2. Intravascular Ultrasound(IVUS)Ultrasound(IVUS)for Detection of for Detection of Vulnerable PlaqueVulnerable Plaque

IVUS has been shown to detect features IVUS has been shown to detect features associated with plaque vulnerability, such as associated with plaque vulnerability, such as an eccentric pattern; the presence of an an eccentric pattern; the presence of an echolucent core, probably representing the echolucent core, probably representing the lipid-rich core; positive vessel wall remodeling, lipid-rich core; positive vessel wall remodeling, defined by the expansion of the overall vessel defined by the expansion of the overall vessel without compromising the lumen ; presence of without compromising the lumen ; presence of thrombi ; plaque length ; lumen narrowing ; thrombi ; plaque length ; lumen narrowing ; and a spotty pattern of calcificationsand a spotty pattern of calcifications

Characteristic：

A: Mild concentric

B: Eccentric lesion with an echolucent area (arrow).C: Eccentric lesion

with high echogenic density.

Coronary occlusion occurring 3 months after patient inclusion. The coronary is occluded at the portion (arrow) where the eccentric plaque with echolucent area had been seen by intravascular ultrasound (B).

Representative IVUS Image of Vulnerable Atherosclerotic Plaque

J Am Coll Cardiol 2000;35:106.

Coronary Angiographic Image of Clinically Non-significant Obstructive Disease of the LAD

A: In an area that appeared normal with angiography, a non obstructive plaque is revealed containing a necrotic or lipid core covered by more echogenic tissue (Fib). B: In a section that likewise appeared normal with angiography, a calcified plaque can be seen. C: A severely calcified plaque with a minimum lumen cross-sectional area (CSA) of 4 mm2 (see inset). D: An IVUS cross-section showing a normal distal reference, the pericardium (Peri).

CMAJ. 2006 February 14; 174(4): 487–495

CMAJ. 2006 February 14; 174(4): 487–495

Four Cross-Sectional Images From Proximal to Distal Within the Same Patient Coronary Lesion Obtained by IVUS and VH

Fibrous, fibro-fatty, necrotic core, and dense calcium are labeled green, yellow, red,and white

Eur Heart J 2006;27: 2939–44.

Four Cross-Sectional Images From Proximal to Distal Within the Same Patient Coronary Lesion Obtained by IVUS and VH

Post-mortem vulnerable coronary plaque marked (arrow) in intravascular ultrasound (A), elastogram (B), macrophage staining (C), and collagen staining (D).

In the elastogram,a vulnerable plaque is indicated by a high strain on the surface. In the corresponding histology, a high amount of macrophages (C) is visible with a thin cap (D)and a lipid pool (LP).

Circulation 2003;108:2636–41.

Limitations:

Invasiveness

limited spatial resolution

limited temporal resolution

Therefore, several new methods are being studied , to identify the plaque characteristics more accurately

3. Optical Coherence 3. Optical Coherence Tomography (OCT)Tomography (OCT) for Detection of for Detection of Vulnerable PlaqueVulnerable Plaque

With ultra-high resolution (4 to20 um), which constitutes a definite advantage for vulnerable plaque imaging).

Thanks to its high-resolution capabilities, OCT allows for the recognition of the features associated with TCFA and is more accurate than IVUS and angioscopy to identify plaque ruptures, plaque erosions, and thrombi .

Moreover, it is important to specify that OCT is the only technique able to detect eroded plaques

Characteristic：

OCT images of 3 different types of atherosclerotic plaques.

A, Lipid-rich plaque (L) covered by thin fibrous cap (arrow, magnified inset). B, Another type of lipid-rich plaque, but with thick fibrous cap. C, Dense, eccentric fibrous plaque (F) with no lipid component. A signal-rich, homogeneous reflective pattern is typical for fibrous tissue. In regions with no plaque (between 7 and 10 o’clock positions), intima, media, and adventitia are clearly visualized.

circulation 2005 ， 111:1551-1555

Angioscopic and Corresponding OCT Images Obtained in Patients Presenting With Acute Coronary Syndromes

In the angioscopic images, plaque color is graded as white (A-1), light yellow (B-1), yellow (C-1), or intensive yellow (D-1). In the optical coherence tomography (OCT)images, a lipid pool (*) is characterized by a signal-poor region (A-2, B-2, C-2, D-2). The fibrous cap is identified as a signal-rich region between the coronary arterylumen and inner border of lipid pool in the OCT image, and its thickness is measured at the thinnest part (A-3, B-3, C-3, D-3; arrows).

J Am Coll Cardiol Intv 2008;1:74–80.

Frequency of TCFA defined by lipid-rich plaque (2 quadrants) and fibrous cap thickness<65um.

TCFA was observed in 72% of patients with AMI, in 50% of patients with ACS, and in 20% of patients with SAP (P0.012).

circulation 2005 ， 111:1551-1555

OCT Images of Human Atherosclerotic Arterial Segments Obtained at Autopsy

Raw (A) and logarithm base 10 (B) optical coherence tomography (OCT) images of a fibroatheroma with a low density of macrophages within the fibrous cap. (C) Correspondinghistology for A and B (CD68; original magnification 100). Raw (D) and logarithm base 10 (E) OCT images of a fibroatheroma with a high density of macrophageswithin the fibrous cap. (F) Corresponding histology for D and E (CD68; original magnification 100).

Circulation 2003;107:113–9.

Invasiveness

Limited tissue penetration, need for flushing or for occlusion balloon

Limitations：

Finally, OCT-elastography, OCT-Doppler, and polarization-sensitive OCT offer further possibilities to assess plaque characteristics

4.Angioscopy for for

Detection of Detection of

Vulnerable PlaqueVulnerable Plaque

Coronary angioscopy complements angiography by characterizing plaque composition and illuminating the presence of thrombus or endoluminal irregularities, such as ulcerations, fissures, or tears. basis of its angioscopic color as yellow or white. Histologic correlation has demonstrated high concentrations of cholesterol-laden crystals seen through a thin, fibrous cap in yellow plaque and a thick, fibrous cap in smooth white plaques. Platelet-rich thrombus at the site of plaque rupture is characterized as white granular material, and fibrin/erythrocyte-rich thrombus, as an irregular, red structure protruding into the lumen. Furthermore, yellow plaques are seen more commonly at the site of culprit lesions, increase the likelihood of a subsequent coronary event, and demonstrate increased susceptibility to rupture and thrombosiswith increased intensity of yellow color, all supporting the concept that yellow lesions correspond to vulnerable plaque.

Angioscopic color grading of atherosclerotic coronaryplaque, with white plaque representing fibrous plaque (A). Yellow plaque signifies a lipid-rich core seen through a thin, fibrous cap. The intensity of the image increases as the fibrous cap thins and becomes increasingly transparent (B, C, and D). An irregular or complex lipid-rich plaque is seen in E, and a lipidrich plaque with associated thrombus is shown in F. A 0.014-in. wire in D provides a reference of scale.

5.5.MDCT MDCT for Detection of for Detection of Vulnerable PlagueVulnerable Plague

Principles and Applications MDCTMDCT检测易损斑块检测易损斑块

Cardiac CT has recently emerged as a new alternative to invasive angiography. With the rapid technological advances in multiple-slice spiral computed tomography (MSCT), it is now possible to reveal coronary vessels and bypass grafts noninvasively. MSCT coronary angiography is performed during the administration of intravenous contrast. The scan is completed in 10–15 seconds, an easy length of time for the subject to hold his or her breath. The best image quality is obtained when the heart rate is slower than 65 beats/min and the cardiac rhythm is regular. Findings for sensitivity ranged from 82% to 100%; specificity, 78% to 98%. The real strength of cardiac CT was found to be its negative predictive value, which in the most recent studies ranged from 95% to 97% among patients deemed to be at intermediate-to-high risk of CAD 。Recently, 2 studies evaluated the accuracy of 64-slice MSCT angiography in the detection of coronary stenoses in patients with no known CAD. They both found sensitivity, specificity, and positive and negative predictive values of better than 90% 。

MRI, MDCT for identification of calcification

Anterior descending artery calcification sites T2-weighted MRI tomography imaging 

MDCT imaging of the same parts Biopsy revealed calcification site

MDCTMDCT检测易损斑块检测易损斑块

MRI, MDCT identify the lipid-rich lesions  

 T2-weighted MRI imaging of LAD

MDCT imaging of the same parts Biopsy shows extracellular lipid pools

MDCTMDCT检测易损斑块检测易损斑块

Marco A.S. Cordeiro MD, PhD , ‡, a and João A.C. Lima MD, MBA, FACC

, Marco A.S. Cordeiro MD, PhD , ‡, a and João A.C. Lima MD, MBA, FACC

,

Marco A.S. Cordeiro MD, PhD ， et,a.Atherosclerotic Plaque Characterization by Multidetector Row Computed Tomography Angiography.J Am Coll Cardiol,2006,47:C40-C47

Mean Attenuation Densities of Atherosclerotic Plaques by MDCTA

MDCTMDCT检测易损斑块检测易损斑块

reference soft intermediate calcified

500/4 x1.0-MDCTA

Circulation,2005,111:3236-3241

16±26 91±21 419±194

Am J Cardiol,2006,97:1564-1569

42±22 71±21 715±328

420/12 x0.75-MDCTA

J Am Coll Cardiol,2004,43:1241-1247

49±22 91±22 392±156

Circulation,2004,110:1467-1472

51±25 116±27 -----

Hounsfield units

Marco A.S. Cordeiro MD, PhD , ‡, a and João A.C. Lima MD, MBA, FACC

, Marco A.S. Cordeiro MD, PhD , ‡, a and João A.C. Lima MD, MBA, FACC

,

MDCTMDCT检测易损斑块检测易损斑块

Example of Example of vulnerable plaque vulnerable plaque rupture in human:rupture in human:A 66ys, male, AMI A 66ys, male, AMI occurred 20 days occurred 20 days after coronary after coronary CTA. CTA CTA. CTA indicated: an indicated: an irregulete, irregulete, eccentric and low eccentric and low density plaque at density plaque at proxm LAD. proxm LAD.

A B

C Coronary angiogram of the same patient two weeks after AMI ：A: proxm LAD total occluded;

B ： after dilatation;

C ： after stenting.

AdvantagesAdvantages：： Non-invasiveNon-invasive High sensitivity and speciality for diagnozing CAD.High sensitivity and speciality for diagnozing CAD. MDCTA can provide more comprehensive informations.MDCTA can provide more comprehensive informations.

DisadvantagesDisadvantages：： The time resolution is relatively lower.The time resolution is relatively lower. The current level of technology and the technical indicators The current level of technology and the technical indicators

are still to be improved, it can not replace conventional are still to be improved, it can not replace conventional angiography.angiography.

The sensitivity for differentiating plaque composition is low.The sensitivity for differentiating plaque composition is low.

Conclusion: MDCTMDCT检测易损斑块检测易损斑块

6. MRI 6. MRI for detecting for detecting vulnerable plaquevulnerable plaque

Cappendijk VC, Cleutjens KB, Kessels AG,et,al. Assessment of Human Atherosclerotic Carotid Plaque Components with Multisequence MR Imaging : Initial Experience. Radiology , 2005 ,234(2) :487- 492.

C: CalcificationC: CalcificationH: Hemorrhage H: Hemorrhage F: Fibrous F: Fibrous

MRI shows the composition of the leision 磁共振显像检测易损斑块磁共振显像检测易损斑块

Cappendijk VC, Cleutjens KB, Kessels AG,et,al. Assessment of Human Atherosclerotic Carotid Plaque Components with Multisequence MR Imaging : Initial Experience. Radiology , 2005 ,234(2) :487- 492.

磁共振显像检测易损斑块磁共振显像检测易损斑块

means and standard deviations of rSIs for99 regions of atherosclerotic plaque tissue and illustrates differences between rSIs of plaquecomponents for the five MR weightings

C.Yuan,N. Balu,B.C. Chu,T.Hatsukami. MRI of the vulnerable carotid plaque. MedicaMundi ， 2008,52(1):57-65

Multi-contrast weighted high-resolution 3T MR shows the presence of a lipid-rich necrotic core(arrow) at the left carotid bifurcation.The core produces iso-intense signals on TOF, T1W, and a slightly hyper-intense signal on T2W.However, the CE T1W image has a clear demarcation of the core boundary due to the absence of neovasculature or loose matrix into the necrotic core.

Advantages: Advantages:  Non-invasive, no radiation.Non-invasive, no radiation. Can distinguish plaque composition,and evaluate the efficacy Can distinguish plaque composition,and evaluate the efficacy

of lipid-lowering therapy.of lipid-lowering therapy.

Disadvantages Disadvantages ：： As a tool for the detection of unstable plaque is still a lack of As a tool for the detection of unstable plaque is still a lack of

adequate resolution.adequate resolution. Can not accurately measure the thickness and the distinction Can not accurately measure the thickness and the distinction

between the fibrous cap of atherosclerotic lesions. between the fibrous cap of atherosclerotic lesions. 

Conclusion:

7. Radionuclide imaging7. Radionuclide imaging for detection of for detection of vulnerable plaquevulnerable plaque

More recently it has become clear that the vulnerable More recently it has become clear that the vulnerable atherosclerotic plaques responsible for the majority of life-atherosclerotic plaques responsible for the majority of life-threatening syndromes are characterized by high numbers threatening syndromes are characterized by high numbers of infammatory cells and proteins. of infammatory cells and proteins.

This has highlighted the urgent need for suitable imaging This has highlighted the urgent need for suitable imaging techniques that can identify and quantify levels of techniques that can identify and quantify levels of inflammation within atheromatous lesions.inflammation within atheromatous lesions.

Positron emission tomography (Positron emission tomography (PETPET) and single-photon ) and single-photon emission computed tomography (emission computed tomography (SPECTSPECT) imaging hold ) imaging hold promise in this regard. promise in this regard.

Tracer compounds capable of assessing macrophage Tracer compounds capable of assessing macrophage recruitment, foam cell generation, matrixmetalloproteinase recruitment, foam cell generation, matrixmetalloproteinase production, macrophage apoptosis, and Macrophage production, macrophage apoptosis, and Macrophage metabolism have been developed and tested in the carotid metabolism have been developed and tested in the carotid and peripheral circulation. and peripheral circulation.

One of the major advantages of FDG-PET is its ability to quantify the metabolic activity of the investigated physiologic and/or disease states. By quantifying plaque inflammation, it may be possible to predict the natural course of the disease and the risk of plaque rupture, and to also monitor the effect of therapy.

The standardized uptake value(SUV) which is commonly employed for assessing disease activity with PET imaging, can provide quantitative information about the severity of the inflammatory process in the arterial wall even before it is clinically symptomatic or visible by structural imaging techniques.

Maximal standardized uptake value ， SUVmaxmean Mean standardized uptake value ， SUVmean Target-background ratio, TBR

CTA was highly accurate in detecting thrombi and lumen stenosis. Fused image of PET/CT can detect morphorlogical and functional Abnormality of tissues.

(1). PET detection of atherosclerotic plaque

in animal

Tawakol A ， Migrino R, Hoffmann U,et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography.J Nucl Cardiol,2005,12(3):294-301

The rate of aortic 18F-FDG uptake

The relationship between 18F-FDG uptake and inflammation (macrophage density) 

PET成像评价实验性动脉粥样硬化

Before and after using Probucol

Ogawa M, Magata Y, Kato T, et al.Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerableatherosclerotic plaques. J Nucl Med 2006;47:1845–50.

PET成像评价实验性动脉粥样硬化

Typical findings about FDP uptake and atherosclerosis

年份 学者 主要发现

1996 Vallabhajosula S FDG 在斑块中聚集且与斑块中巨噬细胞浓度有关（兔）

2005 Tawakol A FDG 摄取与巨噬细胞浓度的相关性研究（兔）2006 Laitinen I 以小鼠为实验对象发现 FDG 在斑块中聚集

2006 Ogawa M 应用普罗布考降低动脉对 FDG 摄取率（兔）

PET成像评价实验性动脉粥样硬化

OUR STUDYOUR STUDY

分离兔股动脉

股动脉球囊拉伤

In this experiment, using vulnerable plaque formation in the pathophysiological process as an entry point, vulnerable plaques of rabbit models were made through the artery de-endothelialization + intermittent high-fat feeding, and drug-trigger plaques’ rupture.

PET / CT imaging technology that combined functional and morphological imaging, detected and evaluated vulnerable plaques systematically.

Ex vivo aorta gross examinationEx vivo aorta gross examination

A组

B组

C 组 1

C 组 2.1 C 组 2.2

Control group normal aorta (A)

AS plaque groupAS aorta (B)

thrombosis groupThrombosis aorta (C)

Control group normal aorta (A)

A

B

C

AS plaque groupAS aorta (B)

thrombosis groupThrombosis aorta (C)

PET/CT PET/CT imagingimaging CT PET PET/CT

ItemItem thrombusthrombus Artery segmentsArtery segments Mean±SDMean±SD PP

Cap/core ratioCap/core ratio __ 2929aa 0.3060.306±±00.163.163 P=0.001P=0.001

++ 3636 0.1880.188±±00.110.110TBRTBR __ 2323bb 1.5971.597±±00.489.489 P=0.000P=0.000

++ 2525 2.2992.299±±00.498.498SUVmeanSUVmean __ 1818cc 0.9100.910±±00.260.260 P=0.015P=0.015

++ 2525 1.1151.115±±00.260.260SUVmaxSUVmax __ 1818cc 1.0921.092±±00.295.295 P=0.006P=0.006

++ 2525 1.3721.372±±00.325.325

MacrophageMacrophage __ 1919 46.9546.95±±11.39411.394 P=0.052P=0.052

++ 3131 40.040.0±±11.93611.936

fiber cap fiber cap thicknessthickness （（ uu

mm））

__ 2929aa 74.78774.787±±31.52531.525 P=0.000P=0.000

++ 3636 48.41448.414±±24.61524.615

lipid core thicknelipid core thicknessss(um)(um)

__ 2929aa 279.430279.430±±68.39868.398 P=0.987P=0.987

++ 3636 279.776279.776±±91.97291.972

Seven of the 12 triggered rabbits developed thrombi. Selecting 36 Segments Triggering with thrombosis and 33 Segments triggering without thrombosis do analysis 。

C group:Segments developed C group:Segments developed thrombosis compared with segments thrombosis compared with segments

without thrombosiswithout thrombosis

Segments developed thrombosis compared with segments Segments developed thrombosis compared with segments without thrombosis in Cap/core ratiowithout thrombosis in Cap/core ratio ， ， SUV and TBRSUV and TBR

there were significant differences of 18F-FDG uptake in the control there were significant differences of 18F-FDG uptake in the control

group and plaque group, and peaked with plaque disruption and group and plaque group, and peaked with plaque disruption and

thrombosis group. thrombosis group.

Three groups SUVmean Comparison:0.286 ± 0.060 in control group, 0.709 ± 0.172 in plaque group, and 1.029 ± 0.276 in thrombosis group. The difference among these groups was statistically significan (p=0.000) 。

(2). PET imaging of atherosclerosis

in clinical settings

PET imaging of carotid atherosclerosis

FDG uptake in large arteries detected by PET was noted FDG uptake in large arteries detected by PET was noted as early as 1987 in patients with vasculitis.as early as 1987 in patients with vasculitis.

Tahara et al. recently determined the prevalence of inflammation in carotid Tahara et al. recently determined the prevalence of inflammation in carotid

artery atherosclerosis by FDGPET in 100 consecutive patients who artery atherosclerosis by FDGPET in 100 consecutive patients who underwent carotid artery ultrasonography for screening carotid underwent carotid artery ultrasonography for screening carotid atherosclerosis. FDG-PET revealed inflammation (defined as standardized atherosclerosis. FDG-PET revealed inflammation (defined as standardized uptake value, SUV, ≥1.6) in 12 of 41 patients (29%) with documented uptake value, SUV, ≥1.6) in 12 of 41 patients (29%) with documented carotid atherosclerosis by carotid artery ultrasonography, and in 6 of 59 carotid atherosclerosis by carotid artery ultrasonography, and in 6 of 59 patients (10.2%) without carotid atherosclerosis patients (10.2%) without carotid atherosclerosis （（ p<0.01p<0.01 ）） ..

carotid arteries Ultrasonography

PET\CT

+ -

+ 12 6

- 29 53

sum 41 59

CT (left), 18F-FDG PET (middle), and fused PET/CT (right) images of coronal (upper panel) and sagittal (lower panel) view from 75-y-old man, diagnosed with a right carotid territory stroke 1 mo earlier, with a nearly total occlusion of right common and internal carotid artery and 70% luminal stenosis of left common carotid artery on angiogram. Calcifications are seen in the neck bilaterally, whereas the most intense 18F-FDG uptake was demonstrated over the right carotid artery region (arrows). Highly inflammatory right carotid artery plaque could be the cause of this patient's presenting symptoms.

Among the patientsAmong the patients with carotid stenosis, with carotid stenosis, the MMP-1 values were significantly the MMP-1 values were significantly higherhigher in patients with a higher SUVmax in patients with a higher SUVmax (>2.0) on the target lesions.(>2.0) on the target lesions. Of the 19 Of the 19 patients who underwent successful patients who underwent successful stenting, postproceduralstenting, postprocedural MMP-1 levels MMP-1 levels were also significantly higher in those with were also significantly higher in those with higherhigher SUVmax values on the target SUVmax values on the target lesions .The change inlesions .The change in MMP-1 levels MMP-1 levels tended to be greater among the subjects tended to be greater among the subjects with SUVmaxwith SUVmax values > 2.0 on target values > 2.0 on target lesions, compared with those withlesions, compared with those with the the SUVmax values 2.0. However, the SUVmax values 2.0. However, the difference did not reachdifference did not reach statistical statistical significance (5.8 ± 3.0 vs. 4.7 ±significance (5.8 ± 3.0 vs. 4.7 ± 0.3 ng/mL, 0.3 ng/mL, PP = 0.3), probably due to the small sample = 0.3), probably due to the small sample sizesize..

Baseline and postprocedural MMP-1 levels in patients with target lesion SUVmax > 2 (left) and 2 (right). *P < 0.05.

Wu et al. demonstrated that increasedFDG uptake in carotid Wu et al. demonstrated that increasedFDG uptake in carotid atherosclerosis is related to serum matrix metalloproteinase-1 atherosclerosis is related to serum matrix metalloproteinase-1 levels [f1]. High tissue matrix metalloproteinase activity has been levels [f1]. High tissue matrix metalloproteinase activity has been associated with advanced atherosclerosis and plaque rupture.associated with advanced atherosclerosis and plaque rupture.

the relationship between FDG uptake and the Application of Simvastatin

After 3 months with simvastatin,  plaque FDG uptake was significantly reduced 

Tahara N, Kai H, Ishibashi M, et al.Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006;48:1825–31.

Vascular FDG uptake and cerebro-cardiovascular events

Several studies have linked vascular FDG uptake to cardiovascular events. with a recent transient ischemic attack and severe carotid artery stenosis in

the ipsilateral carotid artery who were awaiting endarterectomy of the most severely stenotic lesions. Of the 12 patients, 7 had high FDG uptake in the lesion which was targeted for endarterectomy, and 3 of the remaining 5 patients had FDG uptake in the nonstenotic lesions located in the vascular territory that was considered likely to be associated with the presenting symptoms

A, HRMRI and FDG-PET images from patient 7, who suffered a right carotid territory stroke. The HRMRI image shows a large stenotic right internal carotid artery plaque (green arrow), which was subsequently excised surgically. The plaque demonstrated a high level of FDG uptake (blue and red arrows).B, HRMRI and FDG-PET scans from patient 6, who had suffered a recent stroke and was due to undergo carotid endarterectomy. Despite the presence of a highly stenotic left internal carotid artery caused by the presence of concentric atheroma (yellow arrow), there is no discernable FDG uptake (white and black arrows), suggesting a low level of inflammatory activity within this plaque.

In another pilot study inIn another pilot study in 13 13 patients with symptomatic patients with symptomatic carotid atherosclerosis, PET images revealed FDG carotid atherosclerosis, PET images revealed FDG accumulation at the site of the symptomatic plaque in accumulation at the site of the symptomatic plaque in all patients, all patients, 11 (85%)11 (85%) of whom exhibited significant of whom exhibited significant uptake (SUV ≥2.7). uptake (SUV ≥2.7). 66 patients patients (54%)(54%) with intense FDG with intense FDG uptake suffered from one of the primary end-points: uptake suffered from one of the primary end-points: two two died during follow-up; died during follow-up; threethree had recurrent nonfatal had recurrent nonfatal ipsilateral ischemic stroke, and ipsilateral ischemic stroke, and oneone had restenosis after had restenosis after stenting.stenting.

These findings suggest that FDG-PET may be able to assess the degree of inflammation in the stenotic and nonstenotic culprit lesions and could potentially be used to identify lesions that are responsible for embolic events.

(3)Imaging of coronary artery in patients with PET/CT

Imaging of Inflamed and Vulnerable Plaque in Coronary Arteries with 18 F-FDG PET/CT In Patients with Suppression of Myocardial Uptake Using a Low-Carbohydrate, High-Fat Preparation

(J Nucl Med 2009; 50:563-568)

Suppression of myocardial uptake

Poor fair good

PET(A), CT(B), PET/CT, and Coronary angiography (D)

Correlation of coronary 18F-FDG with angiographic disease (per patient

anlasis) CAD by angiography

18F-FDG uptake by coronary tree

Negative Positive

Negative 1 2

Positive 2 15

Conclusion (1)Conclusion (1)

FDG-PET imaging combined with CT FDG-PET imaging combined with CT holds great promise for noninvasive holds great promise for noninvasive assessment of atherosclerosis in large assessment of atherosclerosis in large arteries. Its high sensitivity and the ability arteries. Its high sensitivity and the ability to optimally quantify the disease process to optimally quantify the disease process would allow early diagnosis and accurate would allow early diagnosis and accurate evaluation of response to treatment of this evaluation of response to treatment of this serious and common disease.serious and common disease.

Conclusion (2)Conclusion (2)

18F-FDG PET/CT with myocardial suppression may provide an novel method to image the coronary vasculature and potentially identify vulnerable (inflamed) plaque. Further studies of controls and patients with stable and unstable coronary syndromes are needed; such studies are ongoing. In addition, correlation with traditional markers of inflammation and clinical outcomes are necessary to establish the clinical significance of this imaging modality.

Part three

Management of

vulnerable plaque

1.TOGETHAR trial Circ J. 2010 Sep;74(9):1922-8.

A prospective open-label trial was performed to assess coronary plaque regression and stabilization following 52 weeks of pitavastatin treatment (2 mg/day). Coronary segments of 90 patients determined on angioscopy were analyzed using IVUS.

Yellow grade decreased (2.9+/-0.8 to 2.6+/-0.7, P=0.040) during 52 weeks. The reduction of yellow grade was not correlated with the LDL-C level at 52 weeks or its change. The change of yellow grade was inversely correlated with maximum yellow grade at baseline. Percent atheroma volume on IVUS did not change during 52 weeks, but its change for 52 weeks was significantly correlated with LDL-C level at 52 weeks (Spearman's rank correlation coefficient 0.312, P=0.035).

2. Plaque-stabilizing effect of atorvastatin

The aim of this study was to compare the effect of atorvastatin treatment on high-grade yellow coronary plaques (grade ≥2, group H) vs. low-grade yellow plaques (grade ≤1, group L).

Circ J. 2011 May 25;75(6):1448-54.

The plaque color grade decreased significantly from baseline to weeks 28 and 80 in group H (2.27±0.48, 1.47±0.75, and 1.55±0.86, respectively), but not significantly in group L (0.90±0.31, 0.83±0.61, and 0.89±0.56, respectively).

The plaque-stabilizing effect of atorvastatin was stronger for more vulnerable plaques with a higher color grade, although regression of plaque during atorvastatin therapy was noted irrespective of plaque vulnerability.

3. Comparision of PCI vs conservative treatments for borderline vulnerable

plaque lesion in ACS patients by IVUS(chin j cardiol2011 Feb;39(2):137-41 ）

METHODS: 100 ACS patients undergoing coronary angiography (CAG) with borderline lesion (between 50% - 70%) were enrolled. Randomly divided into PCI group (50 patients) and conservative therapy group (50 patients). Outcomes during hospitalization and after 10 - 12 month follow-up were compared.

IVUS:that MLA increased significantly (P < 0.01), while plaque area (P < 0.05), plaque burden and low echo area were significantly decreased at follow up compared to those as baseline (all P < 0.01). There was one patient in PCI group developed acute in-stent thrombosis in LAD two days after the procedure, and 9 patients in conservative therapy group received PCI due to recurrent angina pectoris during follow-up.

谢谢 Thanks

Mercie Beaucoup

Thank you for Thank you for yous attention!yous attention!