European Journal of Vascular & Endovascular Surgery
Volume 39, Issue 2 , Pages 125-133, February 2010

Advanced Carotid Plaque Imaging☆

  • L. Hermus

      Affiliations

    • Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • ,
  • G.M. van Dam

      Affiliations

    • Department of Surgery, Division of Abdominal Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • ,
  • C.J. Zeebregts

      Affiliations

    • Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • Corresponding Author InformationCorresponding author. Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Tel.: +31 503613382; fax: +31 503611745.

Received 18 September 2009; accepted 17 November 2009. published online 23 December 2009.

Article Outline

Abstract 

Treatment of carotid artery stenosis by endarterectomy or stenting can significantly reduce stroke risk. In clinical practice, indication for surgery or stenting is primarily based on the degree of stenosis, but there is growing awareness that pathophysiological features within a vulnerable plaque play a key role in predicting stroke risk. Important molecular processes associated with plaque vulnerability are inflammation, lipid accumulation, proteolysis, apoptosis, angiogenesis and thrombosis. The rapidly emerging field of molecular and functional imaging strategies allows identification of pathophysiological processes in carotid artery stenosis.

We aimed to review the literature regarding the current most promising advanced imaging techniques in carotid artery disease.

Various advanced imaging methods are available, such as high-resolution magnetic resonance imaging (HR-MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET) and near-infrared fluorescence (NIRF). Radionuclide and fluorescent tracers that identify inflammation, apoptosis and proteolysis, such as FDG, MMP probes and Annexin A5, are promising. A combination of activity of molecular processes and detailed anatomic information can be obtained, providing a powerful tool in the identification of the vulnerable plaque. With these developments, we are entering a new era of imaging techniques in the selection of patients for carotid surgery.

Keywords: Atherosclerosis, Carotid artery, Vulnerable plaque, Molecular imaging, Near-infrared fluorescence

Abbreviations: AMA-MoAB, amino malonic acid monoclonal antibody, CCP, cathepsin cysteine protease, CTA, computed tomography angiography, FDG, 18fluorodeoxyglucose, GSM, grey scale median, HR-MRI, high-resolution magnetic resonance imaging, 125I-MCP-1, 125I-monocyte chemotactic protein-1, MNP, magnetic nanoparticle, MMP, matrix metalloproteinases, MRI, magnetic resonance imaging, NIRF, near-infrared fluorescence, PET, positron emission tomography, PS, phosphatidyl serine, PDA, pixel distribution analysis, SPECT, single photon emission computed tomography, 99mTc-IL-2, 99mtechnetium-interleukin-2, TIA, transient ischaemic attack

 

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Carotid artery stenosis 

Stroke is the third leading cause of death after ischaemic heart disease and cancer.1 About 80% of all strokes are ischaemic and approximately 25–50% of these are caused by an unstable carotid artery plaque.2 However, not all plaques become symptomatic and result in a stroke or a transient ischaemic attack (TIA). Treatment of carotid artery stenosis by surgical endarterectomy or stenting can significantly reduce stroke risk. On the other hand, about 3–9% of patients undergoing interventional treatment are expected to suffer stroke or death as a complication from such a treatment, with stenting having a higher risk for major complications than carotid endarterectomy.3

Current selection criteria for intervention are predominantly determined by the grade of stenosis and symptomatology. It is generally accepted to be more aggressive in a high-grade symptomatic carotid stenosis, but invasive interventions in lower-grade stenosis are still a matter of debate. Further, there is growing awareness that stenosis severity alone has limited value in predicting plaque stability and various molecular processes have, independently of degree of stenosis, shown to be importantly associated with plaque vulnerability.

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Current imaging of carotid artery stenosis 

Traditional imaging methods of carotid artery disease include angiography, duplex ultrasound and computed tomography angiography (CTA). These methods mainly focus on anatomic features of the plaque; however, some techniques are also able to detect morphologic characteristics of plaque vulnerability such as ulceration, a large lipid or necrotic core and a thin fibrous cap.

Angiography was the gold standard in the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial to determine degree of stenosis. Duplex ultrasonography and CTA are also being used to determine the degree of stenosis in carotid artery disease. With regard to plaque morphology, several studies have compared the imaging results to histopathological findings as the gold standard. Angiography was able to detect ulceration with a sensitivity and specificity of approximately 45% and 75%, respectively.4, 5 Calcification and ulceration could be determined by ultrasound grey-scale appearance. Computer-assisted duplex ultrasound image analyses by using grey-scale median (GSM) showed correlations between GSM values and histopathological findings varying from 46%6 to 75%.7

CTA has also shown to identify plaque ulceration, calcification and lipid cores with an overall agreement of about 75% between CTA findings and histology.8, 9

Among the current clinically available imaging modalities, MRI seems the most accurate method to image plaque morphology in carotid artery disease. High-resolution MRI (HR-MRI) can detect differences in morphologic plaque characteristics between symptomatic and asymptomatic carotid plaques. U-King-Im et al. prospectively evaluated differences in carotid plaque characteristics in 20 symptomatic and 20 asymptomatic patients using HR-MRI. Symptomatic patients were more likely to have a thin fibrous cap, intra-plaque haemorrhage, a large lipid core and a complex morphology.10 In another group of 60 patients, HR-MRI was able to detect fibrous cap thickness, intra-plaque haemorrhage, and other components associated with an increased risk of thrombo-embolic events.11

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Future imaging of carotid artery stenosis 

Although limited morphological plaque features may be detected by current imaging methods, information about molecular processes is only available at postoperative or post-mortem examination of the plaque. There is growing awareness that molecular processes such as inflammation, lipid accumulation, proteolysis, apoptosis, angiogenesis and thrombosis are highly related with plaque vulnerability. In vivo identification of these processes would be of great advantage in the selection for vascular intervention.

New techniques have been developed to image cellular and molecular processes and provide biological and pathological information regarding the plaque. These advanced molecular imaging methods may play a central role in determination of the unstable plaque and also provide a powerful tool for selection of individual therapeutic strategies and monitoring the effect of interventions.

In this review, we aim to summarise innovative functional imaging methods in carotid artery disease. In the next part, we discuss the processes and related cellular and molecular targets associated with plaque instability and the corresponding advanced imaging methods.

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Search strategy 

A Medline search from January 1966 to August 2009 was carried out to identify publications reporting experience with innovative functional imaging techniques in atherosclerotic disease, and carotid stenotic disease in particular. Search terms used were ‘atherosclerosis’, ‘plaque’, ‘carotid’, ‘imaging’, ‘magnetic resonance imaging’, ‘positron emission tomography’, ‘single photon emission computed tomography’, ‘near-infrared fluorescence’, ‘inflammation’, ‘lipid accumulation’, ‘proteolysis’, ‘angiogenesis’ and ‘apoptosis’, in various combinations with the Boolean operators AND, OR and NOT (Table 1). Only publications in English language were included. Manual cross-referencing was also performed. The final reference list was selected on the basis of relevance to the topics in this review article.

Table 1. Search results.
Search termsResults
1. “Carotid plaque” AND imaging226
2. #1 AND inflammation18
3. #1 AND lipids74
4. #1 AND angiogenesis4
5. #1 AND PET9
6. #1 AND MRI117
7. #1 AND SPECT4
8. Atherosclerosis AND NIRF7
9. Atherosclerosis AND PET167
10. Atherosclerosis AND SPECT163
11. Atherosclerosis AND HR-MRI2

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Functional carotid plaque imaging 

Inflammation 

Inflammation plays a key role in early atherosclerotic lesions and in atherosclerotic plaque destabilisation. Especially, macrophages play a central role in plaque pathogenesis. By ingesting lipids, they transform into foam cells and produce a large array of pro- and anti-inflammatory cytokines. The highly inflammatory vulnerable plaque is typified by an abundance of inflammatory cells and proteins that are all potential targets for molecular imaging tracers. Therefore, molecular imaging of inflammatory activity in the plaque may predict vulnerability and stroke risk.

The most widely studied imaging method to identify inflammatory processes in carotid artery plaques is radionuclide scintigraphic imaging by positron emission tomography (PET). Radionuclide tracers for macrophage metabolism, macrophage recruitment and inflammatory markers have also been developed and have potential to image inflammatory activity.12 18Fluorodeoxyglucose (FDG) is a glucose analogue that is taken up by glucose-using cells and accumulates in proportion to metabolic activity. FDG-PET has extensively been used in cancer patients. Some cancer patients undergoing FDG-PET showed uptake of FDG in the large arteries and they were retrospectively identified as having risk factors for atherosclerosis.13 This suggested that atherosclerotic plaques may be suitable for FDG-PET imaging. In atherosclerosis, FDG-PET is thought to identify only those plaques that are most actively inflamed and at highest risk for instability and is a potential method for non-invasive identification of an unstable carotid plaque (Fig. 1).

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  • Figure 1 

    Coronal view of a 50–70% symptomatic stenosis of the internal carotid artery on the left side in a 77-year-old male patient as shown by FDG-PET-CT imaging. No FDG uptake was noted at the level of the asymptomatic stenosis of the internal carotid artery on the contralateral side.

The first clinical study using FDG-PET in carotid artery plaques was performed in 2002, showing more accumulation of FDG in unstable plaques.14 FDG-PET signals have also shown to correlate with histological macrophage staining or macrophage markers in human atherosclerotic plaques.15, 16 In another clinical study, 12 patients with a recent TIA underwent FDG-PET and high-resolution MRI. FDG uptake was high in 83% of patients with lesions that were compatible with the patients' presenting symptoms.17

FDG uptake within an arterial wall or plaque can be quantified in several ways, but there is always a partial volume error (PVE), depending on the spatial resolution of the imaging technique that is being used.18 PET has an advantage over SPECT in having a 2–3 times better spatial resolution.19 Izquierdo-Garcia et al.20 recently studied the reproducibility of methods of quantification by MR-guided FDG-PET in symptomatic carotid artery plaques and compared quantification methods to a gold standard technique using the Patlak analysis.21 MR-guided FDG-PET showed to be a highly reproducible technique.

Another radionuclide tracer that has been used in carotid artery patients is 99mTechnetium-Interleukin-2 (99mTc-IL-2). Annovazzi et al. showed that in human carotid artery disease there is 99mTc-IL-2 uptake corresponding with histological findings of IL-2-receptor positive cells. However, there was no correlation between 99mTc-IL-2 uptake and ultrasound classification by means of echostructure or luminal surface aspects.22 Other promising radionuclide tracers used to image inflammation in atherosclerosis are 125I-monocyte chemotactic protein-1 (125I-MCP-1)23 and 131amino malonic acid monoclonal antibody (131AMA-MoAB)24 but they have not been studied in vivo yet. Therefore, of all radionuclide tracers, 18FDG has currently the most clinical potential to identify inflamed plaques in patients with carotid artery disease.

In addition to radionuclide tracers, a variety of magnetic nanoparticles (MNPs) have been developed to detect aspects of inflammation in the atherosclerotic plaque. Nanoparticles are digested by macrophages and accumulate in macrophages that are present in the carotid artery plaque. MNPs are detectable in vivo by high-resolution MRI as explained earlier or, as in case of fluorescent MNPs, by near-infrared fluorescence (NIRF). For example, the inflammatory molecule vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 expression could be imaged in vivo in a murine model of atherosclerosis with MRI and fluorescence imaging using multimodal nanoparticles (NPs).25 In humans, VCAM-1 could potentially be detected by MRI and NIRF non-invasively in carotid artery plaques but its value is unknown.26

Lipid accumulation 

Lipid accumulation not only plays a role in the initial phases of atherogenesis, but is also important in the stability of the atherosclerotic plaque. Unstable lesions have shown to have a much greater area occupied by lipid. In addition, elevated oxidised low-density lipoprotein (LDL) levels play a role in the transition from stable to unstable plaques and are associated with higher risk for atherosclerotic complications. In carotid artery disease, technetium-99m labelled LDL (99mTc-LDL) was used for identification of plaque and appeared to accumulate depending on plaque composition.27 Another study in carotid artery plaques compared 99mTc-oxLDL uptake between normal carotid arteries and patients with a carotid artery stenosis. They found significantly higher uptake of 99mTc-oxLDL in carotid plaques compared with normal carotid arteries. However, relationship between 99mTc-oxLDL uptake and plaque vulnerability by comparison among stable and unstable plaques was not assessed.28 Although clinical experience in imaging lipid accumulation is limited, some results suggest that at-risk plaques with high lipid content may be detected by non-invasive imaging in the future.

Proteolysis 

Release of proteolytic enzymes such as matrix metalloproteinases (MMPs) and cathepsin cystein proteases (CCPs) has been suggested as a mechanism of cap erosion and thus plaque destabilisation. Several studies in atherosclerotic plaques have shown proteolytic activity in relation to plaque instability.29, 30 Therefore, non-invasive visualisation and quantification of MMP and CCP activity is of great potential in risk assessment of carotid artery stenosis. Radiolabelled molecules designed to specifically target proteolytic activity have been developed for scintigraphic techniques such as SPECT and PET. For example, radiolabelled MMP inhibitors that bind to a broad spectrum of MMPs have been studied in mice and showed higher uptake in carotid artery stenosis compared to normal arteries.31 Histological analysis showed co-localisation of the specific tracer and MMP-9. In rabbits, MMP activity could be detected by non-invasive SPECT imaging and correlated well with immunohistochemically verified macrophage infiltration and presence of MMP-2 and MMP-9 in the atherosclerotic plaque. In addition, statin therapy and dietary modification showed to decrease MMP activity as visualised by SPECT and again immunohistochemical correlations were high.32 This indicates that SPECT may be an important tool for monitoring of effect of new therapy strategies. However, most of the tracers have only been validated in animal studies and only 111In-DTPA-N-TIMP-2 has been used in humans.33 The development of new tracers in atherosclerotic plaques is complicated by a so-called poor target-to-background ratio, which means that background activity makes it hard to distinguish plaque uptake from surrounding healthy tissue (Fig. 2).

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  • Figure 2 

    Multispectral near-infrared fluorescence imaging within IVIS Spectrum camera (Caliper Life Sciences, Hopkinton, MA, USA) of a resected left-sided symptomatic >70% carotid stenosis in a 74-year-old woman. Ex vivo plaque in white light (left), near-infrared fluorescence signal before (autofluorescence, middle) and after incubation with MMP-sensitive activatable fluorescent probe (MMPSense, VisEn Medical, Boston, MA, USA; right). After incubation with MMPSense clear hotspots (yellow areas) were identified both at the intraluminal and extraluminal sides, most present in the origin of the internal carotid artery and at the level of the common carotid bulb. (With kind permission of Niels Harlaar and Johannes de Jong, University Medical Center Groningen, Groningen, The Netherlands)

Another new and promising technique to image proteolytic activity in atherosclerotic plaques is NIRF molecular imaging. This technique operates in the near-infrared spectrum of light and uses activatable probes that provide fluorescent images to detect enzymatic action of proteolytic enzymes such as MMPs and CCPs. Probes, such as gelatinase-activated probes34 or cathepsin-B-sensitive probes35 are conjugated with NIRF fluorochromes. These probes produce very low background fluorescence and after activation produce a profound amplification of fluorescence. This way, vulnerable plaques with high proteolytic activity can be identified – at this stage only ex vivo or in animal studies. The first NIRF application in human carotid artery plaques was recently reported by Wallis de Vries et al. who detected MMP-2 and MMP-9 in a carotid endarterectomy specimen (Fig. 2).36 However, it will take technical developments and preclinical toxicity testing before in vivo studies in humans can be performed with NIRF. Furthermore, the reporter capabilities and specific cellular distribution in vivo needs to be understood and technical aspects, such as dose-finding studies of a fluorescent tracer and timing of imaging, need to be improved to obtain optimal fluorescence signals of a plaque in situ.

Angiogenesis 

In atherosclerotic plaques, the formation of microvessels has been studied as a possible contributing factor to plaque destabilisation and rupture. Neo-vessels in carotid artery plaques are fragile and prone to rupture and may cause plaque growth and intra-plaque haemorrhage, resulting in a high-risk plaque.37 Several angiogenic cytokines, such as vascular endothelium growth factor (VEGF), integrins or angiotensin may be potential targets for molecular imaging of angiogenesis in plaque formation.38, 39 Angiotensin 1 receptor40 and VEGF radionuclide tracers41 have already been used in other diseases in which angiogenesis plays an important role, but not in atherosclerosis. For example, non-invasive imaging of angiogenesis by radionuclide VEGF tracers42 or fluorescent VEGF tracers43 has been performed.

In mice models for atherosclerosis, angiogenesis imaging has been performed by NIRF using fluorescently labelled antibodies targeting extra-domain B (ED-B), a molecule that is also involved in angiogenesis.44

Apoptosis 

Finally, apoptosis plays an important role as a feature of complex human atherosclerotic plaques. The risk of plaque rupture depends in part upon the presence of a necrotic core, containing lipids, dead cells and debris with a thin fibrous cap.45 Carotid artery plaques with an increased necrotic core and a thin fibrous cap due to apoptosis of macrophages or smooth muscle cells are known to be instable and are at high risk for rupture.

Imaging of apoptosis in carotid artery plaques has mainly been studied in animal models by targeting markers of apoptosis such as annexin A5. In a rabbit model, Technetium-99m labelled annexin A5 showed a higher uptake in atherosclerotic lesions compared with controls.46 In another rabbit study, Annexin A5 (111In-labelled Annexin A5) was imaged in combination with MMP activity (99mTc-labelled matrix metalloproteinase inhibitor (MPI)) using SPECT-CT (Fig. 3).47 Annexin A5 and MPI uptake were both visualised in atherosclerotic animals and were interrelated.

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  • Figure 3 

    Non-invasive radionuclide imaging of proteolytic (MMP) activity and apoptosis by using 99mTc-labelled matrix metalloproteinase inhibitor (MPI) and 111In-labelled Annexin A5 in atherosclerosis. Micro-SPECT (top), and micro-SPECT-CT fusion images (bottom) of atherosclerotic rabbit on uninterrupted high-cholesterol diet using Tc-MPI (A) and In-AA5 (B). The left sets in A and B display images immediately (0h) after radiotracer administration, which reveal blood pool activity in the aorta (arrows) in front of vertebral column. The right sets in A and B show target localisation 4h after radiotracer administration. The radiotracer uptake in the atherosclerotic lesions of the abdominal aorta is observed (arrows). (With kind permission of A. Petrov, PhD, University of California, Irvine, USA.)

In a clinical pilot study in four patients with a history of TIA caused by symptomatic carotid artery stenosis, annexin A5 uptake corresponded well with histopathological characterisation of vulnerability of the endarterectomy specimens.48 Unstable plaques showed higher uptake of annexin A5 while in stable plaques no uptake of annexin A5 was seen after SPECT imaging.

Although obviously more clinical studies in apoptotic markers are needed, so far 99mTc-Annexin A5 is one of the few tracers that have been used in the clinical setting of acute vascular disease.

Thrombosis 

In carotid artery plaques, thrombotic activity is associated with stroke and TIAs.49 Unstable carotid artery plaques express a wide array of thrombomodulatory factors and expression of these factors is higher in unstable plaques compared to stable plaques.50 In a large series of carotid endarterectomy specimens, thrombotic activity was seen in 74% and 35% of patients with ischaemic stroke and TIAs, respectively, and only in 14% of asymptomatic patients. In stroke patients, thrombotic activity was seen until several months after the first cerebrovascular event.49 These findings suggest that thrombotic activity plays a crucial role in plaque rupture and the pathogenesis of stroke.

HR-MRI has been used to identify thrombus formation and intra-plaque haemorrhage in the carotid artery plaque.51 MRI showed a sensitivity and specificity of 84% in detecting complex plaques, defined as that with surface rupture or intra-plaque haemorrhage.52 Other studies have shown similar sensitivity and specificity values (Table 2).53

Table 2. Molecular imaging in atherosclerosis.
Author (year)Molecular targetTechniquenStudy subjectsResults
Tawakol (2006)FDG
PET

19
9 Atherosclerotic rabbits

10 Control rabbits


FDG uptake: atherosclerotic>control

Rudd (2002)FDG
PET

8
8 Symptomatic carotid artery plaques (human), contralateral side was used as control group


FDG uptake: symptomatic side>asymptomatic side

Davies (2005)FDG
PET

12
12 Patients with carotid artery stenosis and symptoms


High FDG uptake in 58% of target lesion, in 83% in lesions corresponding with symptoms

Tawakol (2006)FDG
PET

17
17 Carotid artery plaques (human)


Correlation FDG uptake and CD68 expression

Graebe (2009)FDG
PET

10
10 Symptomatic carotid artery plaques (human)


Correlation FDG uptake and CD68 expression

Annovazzi (2006)IL-2
SPECT

23
14 Patients carotid artery stenosis

9 Patients carotid artery stenosis and statin treatment


Correlation IL-2 uptake and IL-2R+ cells

IL-2 uptake decreased after statin treatment

Ohtsuki (2001)MCP-1
Radiolabeled autoradiography

10
Atherosclerotic rabbits


MCP-1 uptake: atherosclerotic vessel wall>normal vessel wall

Correlation MCP-1 uptake and macrophages

Chakrabarti (1995)AMA-MoAB
Radiolabeled autoradiography

8
4 Atherosclerotic rabbits

4 Control rabbits


AMA-MoAB uptake: atherosclerotic>controls

Jaffer (2006)Nano-particles
NIRF

HR-MRI

11
Atherosclerotic mice, saline vs nanoparticles


Plaque enhancement: nanoparticles>saline

Chen (2002)Cathepsin-B
NIRF

20
10 ApoE−/− mice

5 ApoE−/−eNOS−/−

5 Wildtype mice


Cathepsin-B enhancement: high in atherosclerotic lesions compared to control mice

Deguchi (2006)MMP-2 MMP-9
NIRF

28
19 ApoE−/− mice

9 ApoE+/+ mice


MMP-2 and MMP-9 enhancement in aorta: ApoE−/−>controls

Wallis de Vries (2009)MMP-9
NIRF

1
Symptomatic carotid artery plaque (human)


MMP-signal corresponds with MMP-9 and MMP-2 values

Haider (2009)
MPI

Annexin A5


SPECT

12
6 High-cholesterol diet rabbits

6 Control rabbits


Annexin A5 and MPI uptake: HC>controls

Correlation MPI and Annexin A5

Kolodgie (2003)Annexin A5
Radiolabelled autoradiography

10
5 Atherosclerotic rabbits

5 Control rabbits


Annexin A5 uptake: atherosclerotic lesions>normal arteries

Kietselaar (2004)Annexin A5
SPECT

4
2 Recently symptomatic carotid artery plaques (human)

2 Symptomatic carotid artery plaques >3 months earlier (human)


Annexin A5 uptake: recently symptoms>not recently symptoms

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Discussion and conclusion 

Traditional imaging techniques for atherosclerosis focus primarily on defining anatomic features of the atherosclerotic plaque rather than pathophysiological processes. However, the emerging knowledge of plaque biology emphasises that other characteristics than the degree of stenosis are important in risk assessment, namely stroke in carotid artery disease.

Currently, we are entering a new era with the development of state-of-the-art functional molecular imaging techniques to identify cellular processes in vulnerable carotid plaques. Radiographic scintigraphic techniques such as PET and SPECT and fluorescent molecular imaging techniques such as NIRF are the most promising techniques currently available. Especially when functional molecular imaging methods are combined with detailed anatomical imaging by HR-MRI or CT and used in a multimodal setting, these techniques seem to be able to accurately identify processes in vulnerable carotid plaques. In addition, these techniques may be useful for the evaluation of individual therapeutic strategies and monitoring the effect of therapeutic interventions (Table 3).

Table 3. The advantages and disadvantages of the various molecular imaging techniques.
Imaging techniqueAdvantagesDisadvantages
PET
Non-invasive

Spatial resolution 2–3 times better than SPECT

More specific than SPECT

Reproducible

Has been used in vivo in humans


Radio-active probes

Partial volume effect

Target-to-background ratio


SPECT
Non-invasive

Has been used in vivo in humans

Better availability than PET


Radio-active probes

Partial volume effect

Target-to-background ratio

Poor spatial resolution


NIRF
Non-invasive

No radio-activity


Partial volume effect

Target-to-background ratio

Has only been used in animal studies or ex vivo in carotid artery plaques

Poor spatial resolution


HR-MRI
Non-invasive

No radio-activity

Has been used in vivo in humans

High spatial resolution

Identifies morphologic characteristics


No information on molecular processes


HR-MRI using nanoparticles
Non-invasive

No radio-activity

High spatial resolution


Provides only information on inflammation (macrophages)

Target-to-background ratio

Has only been used in animal studies

Although the above-described approaches are promising, no large clinical prospective trials have been carried out so far. Whereas multiple candidate targets have been evaluated in preclinical molecular imaging studies, only a few radionuclide or fluorescent targets have been recently used in the clinical setting of carotid artery stenosis. Additional research is needed, in part focussed on the identification of additional and specific target molecules of vulnerable carotid artery plaques and, on the other hand, pharmacokinetic and toxicity testing prior to clinical trials for validation of new imaging techniques.

In conclusion, it is clear that advanced molecular imaging methods are an important development in atherosclerotic research. The pathophysiological information of plaque vulnerability that can be obtained by these imaging techniques is of great potential for usage in clinical practice and in future may improve the selection criteria for vascular intervention. However, further research is warranted before there will be clinical applicability.

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Conflict of interest 

None.

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Funding 

None.

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☆ This paper was presented at the XXIII Annual Meeting 3–6 September, 2009, European Society for Vascular Surgery, Oslo, Norway.

PII: S1078-5884(09)00589-9

doi:10.1016/j.ejvs.2009.11.020

European Journal of Vascular & Endovascular Surgery
Volume 39, Issue 2 , Pages 125-133, February 2010

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