Key Points
Introduction: Why Atherosclerosis Imaging Matters
Understanding the Biology of Atherosclerosis
Anatomical Imaging: Looking at Structure and Narrowing
Intravascular Imaging: Cameras Inside the Artery
Non-Invasive Imaging: Ultrasound, CT, and MRI
Molecular Imaging: Tracking Disease Activity
Clinical Implications: What This Means for Patients
Limitations: What These Techniques Cannot Yet Do
Recommendations for Patients
Frequently Asked Questions
Source Information

Key Points

Atherosclerosis is a chronic immune-driven disease causing heart attacks and strokes.
Vulnerable plaques have thin fibrous caps, large lipid cores, and inflammation.
OCT, IVUS, CT, MRI, and PET can image plaque structure and biological activity.
Molecular imaging can detect microcalcification and inflammation to identify high-risk plaques.
Patients should control risk factors and take medications to stabilize plaque.

Introduction: Why Atherosclerosis Imaging Matters

Atherosclerosis is a chronic, immune-modulated disease that affects multiple vascular beds—meaning it can strike arteries throughout the body—and it remains a leading cause of death and disability worldwide. For many years, the disease progresses silently without any symptoms. In later stages, it may cause chest pain or leg pain during exercise as arteries narrow, or it may suddenly trigger a heart attack or stroke when plaque ruptures.

Traditional imaging methods have focused on measuring the degree of stenosis (the percentage of narrowing) caused by a plaque. But narrowing alone doesn't tell the whole story. Modern CT, MRI, and positron emission tomography (PET) scanners now offer faster image acquisition and sharper resolution, expanding what doctors can see. By combining multiple imaging methods—an approach called multimodality imaging—clinicians can look at the constituency and metabolic processes within the vessel wall itself, potentially improving cardiovascular risk prediction.

This review provides an overview of current imaging techniques for atherosclerosis and explains how different modalities provide information that goes beyond basic morphology. The goal is to help doctors identify biologically active plaques that are at high risk of rupturing, allowing earlier and more targeted treatment.

Understanding the Biology of Atherosclerosis

Atherosclerosis is a multifocal immunoinflammatory condition of medium and large-sized arteries. Established risk factors—including hypertension (high blood pressure), hypercholesterolaemia (high cholesterol), and smoking—create a harmful environment throughout the body that encourages endothelial dysfunction (damage to the artery lining), oxidation of lipoproteins (the fat-carrying proteins in blood), production of free oxygen radicals, and migration of leukocytes (white blood cells) into the artery wall.

Here's what happens step by step:

Oxidized lipoproteins accumulate within the vessel wall, forming fatty streaks
Macrophages (a type of immune cell) migrate across the endothelium to engulf these lipid-rich proteins
The high cholesterol content inside macrophages triggers cell death pathways
The resulting debris, along with dead endothelial and smooth muscle cells, forms the lipid-rich necrotic core

Atherosclerotic plaques consist of necrotic debris contained by outward remodelling and a fibrous cap on the inner surface of the artery. Plaques that are prone to rupture—called vulnerable plaques—have distinctive features: large lipid-rich necrotic cores, a thin fibrous cap measuring less than 65 micrometres (µm), dense macrophage infiltration, and microcalcification. In metabolically active plaques, macrophages accumulate in the fibrous cap and degrade the extracellular matrix produced by vascular smooth muscle cells. The necrotic core also creates a microenvironment of hypoxia (low oxygen) that stimulates angiogenesis (growth of new, fragile blood vessels).

Calcification in atherosclerosis is not a passive process; it is active and controlled. Early microcalcification involves the deposition of hydroxyapatite crystals (calcium and phosphate crystals) at a microscopic level that is beyond the resolution of conventional imaging. This early stage signals intense biological activity and is associated with increased plaque vulnerability. In contrast, larger, established deposits of macroscopic calcification are associated with plaque stability and a more quiescent phase of disease.

When a thin fibrous cap ruptures, the lipid-rich necrotic core is exposed to flowing blood, triggering rapid and aggressive thrombosis (blood clotting) that can block the artery completely. However, plaque rupture is frequently silent and subclinical. Over time, the vessel remodels around the exposed thrombus, and the degree of stenosis may worsen. If arterial disruption occurs rapidly, the body's compensatory angiogenesis doesn't have time to develop, making the resulting ischaemia (blood shortage) more severe. Prompt therapeutic reperfusion (restoring blood flow) is critical to minimize irreversible tissue loss in this highly time-dependent process.

Anatomical Imaging: Looking at Structure and Narrowing

Anatomical imaging aims to detect luminal narrowing and characterize the features of atherosclerotic plaque. It also allows doctors to assess the total burden of atherosclerosis throughout an entire vascular territory—information that helps stratify a patient's risk of future adverse events.

Catheter-based contrast angiography remains the most frequently used method to image the coronary arteries, largely because of its high spatial and temporal resolution and its role as a platform for intervention. However, catheter angiography alone provides only a "lumenogram" of the coronary circulation—a picture of the space where blood flows—without showing the arterial wall itself. Plaque characterization is possible but requires specialist equipment. Intravascular optical and ultrasound imaging can assess plaque morphology in remarkable detail, making these techniques excellent choices for high-risk patients who may require simultaneous intervention.

There is a growing need to identify adverse plaque features using non-invasive imaging techniques, particularly for low- and medium-risk patient groups. CT and MRI angiography are safe and reliable alternatives to catheter angiography. They can simultaneously image the vessel wall and any surrounding atherosclerosis. Ultrasound can also measure blood flow across a lesion to quantify stenosis, and spectral analysis plus specialized contrast agents can characterize plaque at the same time. Non-invasive imaging improves clinical decision making by separating diagnosis from intervention, allowing a multidisciplinary team to make rational treatment decisions.

Intravascular Imaging: Cameras Inside the Artery

Optical Coherence Tomography (OCT)

Optical coherence tomography (OCT) provides exceptionally detailed images of the fibrous cap using near-infrared light delivered through a fibre-optic wire. The OCT catheter is positioned over a guidewire, and a blood-free pool is created by injecting saline or contrast media. Using fast frequency domain analysis, OCT captures detailed images of the thin fibrous cap. These findings correlate well with histological features. High signals within the fibrous cap indicate macrophage adherence and thrombus (clot) formation.

These high-resolution benefits must be balanced against reduced tissue penetration, which limits assessment of deeper plaque constituents. OCT is already used clinically to detect vulnerable plaques and guide therapy in the coronary arteries. It is now being applied to carotid artery stenosis (narrowing of the neck arteries) and peripheral vascular disease as well.

Near Infrared Spectroscopy / Intravascular Ultrasound (NIRS/IVUS)

Near infrared spectroscopy (NIRS) is another catheter-based invasive technique that does not require a blood-free field. It uses wave scatter to produce a gradient map corresponding to the probability of adjacent lipid. The resulting lipid-core burden index (LCBI) describes the ratio of high lipid content in adjacent structures against the total area studied. Modern probes combine NIRS with intravascular ultrasound (IVUS) to provide structural context to the morphological data.

IVUS is a more established and, consequently, more cost-effective technique than OCT and NIRS. It packages a high-frequency ultrasound probe inside a catheter that directly visualizes adjacent atherosclerotic plaque from within the artery lumen. High-resolution greyscale images show the structure of the plaque and the adjacent vessel wall. By analyzing backscatter signals, doctors can reliably identify the lipid-rich necrotic core, calcification, and fibrofatty plaque. Despite reasonable tissue penetration, IVUS lacks the spatial resolution to measure the thickness of the fibrous cap. Like conventional ultrasound, mineralized calcium deposits cast acoustic shadows that obscure underlying tissue detail.

NIRS/IVUS is well established for detecting and treating coronary disease, and its use has been validated in the carotid arteries and lower limb arteries as well.

Non-Invasive Imaging: Ultrasound, CT, and MRI

Ultrasound

In superficial vessels such as the carotid and limb arteries, duplex ultrasound combines structural and functional data to quantify the degree of stenosis caused by atherosclerotic plaque. The ratio of peak systolic velocity proximal (before) and distal (after) a suspected lesion is used to estimate stenosis severity. Ultrasound can measure total plaque area, and the greyscale pixel intensity of plaque images corresponds well with histological features.

Ultrasound is non-invasive, radiation-free, and portable, making it the first-line imaging modality to quantify stenoses throughout the peripheral vascular tree. High-resolution ultrasound can also differentiate components of the arterial wall. Pathological thickening of the intimal-medial layer (the inner two layers of the artery wall) is an early sign of subclinical plaque formation. This intima-media thickness (IMT) measurement serves as a "window" to an individual's global cardiovascular health—increased IMT is associated with significantly increased risk of myocardial infarction (heart attack), stroke, and death.

Contrast agents containing a homogeneous suspension of inert gas microbubbles (such as sulphur hexafluoride, SF6) can be injected intravenously to highlight specific features of arterial plaque. In the carotid arteries, microbubbles identify neovascularization in culprit lesions with a sensitivity and specificity greater than 80%. In patients with abdominal aortic aneurysms, contrast-enhanced ultrasound provides real-time characterization of luminal flow and can visualize complications after endovascular repair, such as endoleaks (leaks of blood into the aneurysm sac). The lack of ionizing radiation makes contrast-enhanced ultrasound ideal for situations requiring repetitive imaging.

However, ultrasound has limitations. Densely calcified plaque can obscure vessel assessment, and bone or gas overlying the target vessel prevents adequate visualization. This restricts its use to easily accessible arteries, and standardization is needed to reduce interobserver variability.

Computed Tomography (CT)

CT angiography (CTA) is well established for assessing the cardiovascular system. It is non-invasive, accessible, and can visualize the entire vessel from its origin to the target structure, even in tortuous (twisted) vessels. CTA has the spatial resolution to detect focal luminal stenoses and provides a global assessment of vascular disease. Thanks to short acquisition times with new-generation scanners, it is now possible to image the coronary vessels in great detail.

CTA is highly accurate in determining coronary stenosis severity and has been incorporated into many clinical guidelines as the first-line imaging modality for individuals with suspected cardiac chest pain. In the carotid arteries, CTA has a reported sensitivity approaching 100% and a specificity of 63% (95% confidence interval 25–88%) for detecting a stenosis greater than 70%.

Beyond measuring stenosis, CT can characterize plaque morphology. Several high-risk plaque features can be identified:

Positive remodelling (outward bulging of the artery wall)
Spotty calcification
High-attenuation fibrous plaques
Low-attenuation lipid-rich necrotic plaques

The napkin-ring sign, seen on centreline reconstruction of the coronary vessels, represents differentiation between the fibrous plaque and necrotic core. It appears as a crescentic high-attenuation pattern surrounding a low-attenuation atheromatous lesion distinct from the vessel lumen—a morphological pattern that mirrors plaque histology.

CT is particularly well suited to visualize vessel calcification. However, beam hardening from densely calcified plaque causes "blooming" that exaggerates plaque size and obscures the lumen, especially in small vessels with heavy calcification. In acute disease, CT cannot differentiate soft-tissue components of a plaque—for example, it is not possible to distinguish a stable fibroatheromatous lesion from acute plaque haemorrhage or thrombosis. Identifying the culprit plaque relies on a combination of radiological features, clinical presentation, and the pattern of end-organ damage.

Magnetic Resonance Imaging (MRI)

MRI angiography is best suited to imaging large, stable vessels such as the carotid arteries. Multicontrast MRI (T1-weighted, T2-weighted, proton density) offers excellent soft tissue characterization, allowing plaque constituents to be investigated without ionizing radiation. These properties make MRI particularly useful for longitudinal studies of chronic cardiovascular diseases.

Administration of gadolinium (Gd)-based contrast media improves image acquisition times and provides further structural information, outlining differences between the blood pool and vessel wall. Motion artefact near the heart has historically made imaging small vessels challenging, but advances have addressed this limitation. Accelerated image acquisition reduces motion artefacts and noise. Bright-blood techniques use blood itself as an intrinsic contrast agent, reducing the need for gadolinium. A 1.5 Tesla (T) MRI machine can now detect significant left main stem or three-vessel coronary disease in up to 94% of patients.

While image quality remains inferior to CT coronary angiogram, MRA is useful for assessing coronary aneurysms and aberrant coronary ostia (unusual origins of the coronary arteries). Additionally, T1-weighted imaging can be applied to the coronary arteries to detect intraluminal thrombus or intraplaque haemorrhage. MRI has the added benefit of assessing cardiac dynamics, myocardial perfusion, and viability. In the carotid arteries, MRI's superior soft tissue discrimination allows measurement of fibrous cap thickness and visualization of the necrotic core. The sensitivity to detect lipid-rich cores is further improved with gadolinium-based contrast media. Following an acute event such as a transient ischaemic attack (a "mini-stroke") from internal carotid artery plaque rupture, T1-weighted MRI can detect intraplaque haemorrhage and thrombus—findings that correlate with the risk of future ischaemic events. Higher magnetic field strengths reduce background noise and artefact.

"Smart" Contrast Agent MRI

Ultrasmall paramagnetic particles of iron oxide (USPIOs) are 30 nanometre (nm) iron oxide nanoparticles stabilized with low-molecular-weight dextran. After injection, USPIOs are taken up by macrophages through phagocytosis (a cellular "eating" process) and remain in the circulation for extended periods. Areas rich in USPIO-positive macrophages show low signal intensity on T2 and T2* weighted MRI.

In the carotid arteries, USPIO accumulation within atherosclerotic lesions coincides with active plaque disease—these plaques exhibit intense macrophage infiltration. USPIOs also accumulate with high affinity in areas of macrophage infiltration within abdominal aortic aneurysms. Using "smart" MRI contrast agents to detect cellular activity within the vascular bed carries immense promise. These techniques may ultimately allow detection of active plaques at risk of imminent events and enable preventative therapy.

Magnetic Resonance Spectroscopy (MRS)

MR spectroscopy (MRS) combines the spatial imaging of MRI with spectral analysis to detect the chemical composition and metabolic state of cardiovascular tissue. MRS can detect a range of atoms, including 1-Hydrogen (1H), 31-Phosphorus (31P), and 13-Carbon (13C). In vivo carotid studies using MRS have successfully quantified cholesteryl esters within atherosclerotic plaque—the major class of lipids found in the lipid-rich necrotic core of vulnerable plaques.

The chemical composition of structures is obtained using a chemical shift imaging sequence to acquire spectra over and around the plaque. MRS amplitudes for specific metabolites, such as lipids, are interpreted as a ratio to the amplitude of intrinsic water. The final analysis allows detection and quantification of the lipid content of atherosclerotic plaque.

Molecular Imaging: Tracking Disease Activity

Biologically active atherosclerotic lesions are inherently unstable and prone to rupture. Targeted biological tracers enable positron emission tomography (PET) and single photon emission computed tomography (SPECT) to detect increased activity of specific disease processes, such as increased glycolytic activity or microcalcification.

Biological radiotracer molecules typically consist of two components: a ligand that targets specific sites of disease activity, and a radioisotope that PET and SPECT scanners can detect. The intensity and distribution of tracer activity reveal where disease processes are most active.

Key Tracers in Atherosclerosis Imaging

18F-Fluorodeoxyglucose (18F-FDG) is a well-known tracer that detects increased glucose metabolism, a hallmark of inflammatory cells. However, its use in coronary imaging has limitations due to background uptake in heart muscle. 18F-Sodium fluoride (18F-NaF) binds to microcalcification—an early marker of active, vulnerable plaque—and has been shown to detect areas of greatest vascular injury and activity.

Advances in radiotracer development using DOTA- (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid) or NOTA- (1,4,7-Tricarboxymethyl-1,4,7-triazacyclononane) based "cage" structures have produced various tracers. The cage houses a positron-emitting isotope such as Gallium-68 (68Ga) or Copper-64 (64Cu). PET studies show these agents exhibit preferential vascular uptake in patients with established cardiovascular risk factors and adverse Framingham risk scores.

Histological comparison of carotid plaque with high 68Ga-DOTA-TATE uptake reveals selective binding of the radiotracer to CD68-positive macrophage-rich lesions. In a pilot study, 68Ga-DOTA-TATE correctly identified metabolically active coronary and carotid lesions with good reproducibility and higher sensitivity than 18F-FDG.

Other tracers targeting macrophage activity include:

Vascular cell adhesion molecule-1 (VCAM-1)—targets inflamed endothelium
11C-choline—detects cell membrane synthesis
18F-fluorothymidine—measures cellular proliferation
Translocator protein (TSPO)—a marker of activated macrophages

Clinical Implications: What This Means for Patients

These emerging imaging techniques represent a fundamental shift in how doctors think about atherosclerosis. Instead of asking only "how blocked is this artery?", clinicians can now ask "how dangerous is this plaque?" This distinction matters because many heart attacks are caused by plaques that were not severely narrowed before they ruptured.

For patients with established cardiovascular risk factors—such as high blood pressure, high cholesterol, or smoking—these advanced imaging tools may one day provide a personalized picture of arterial health. A patient with a high burden of biologically active plaque might be offered more aggressive medication, closer monitoring, or earlier intervention, while a patient with quiescent (inactive) plaque and good risk factor control might safely avoid unnecessary procedures.

Specifically, the ability of 18F-NaF PET to detect microcalcification may help identify patients at highest risk of imminent heart attack. This is especially important because vulnerable plaques are not always the most narrowed ones, and a strategy focused only on stenting tight blockages misses many dangerous lesions. Additionally, the use of USPIO-enhanced MRI to detect macrophage activity could help doctors monitor whether anti-inflammatory treatments are working and guide modification of therapy to achieve maximum stabilization of high-risk plaque.

Limitations: What These Techniques Cannot Yet Do

Despite significant promise, these techniques have important limitations:

Catheter-based angiography, OCT, and IVUS are invasive and are typically reserved for patients already undergoing intervention
OCT's high resolution comes at the cost of limited tissue penetration, so it cannot assess deeper components of the plaque
IVUS cannot measure fibrous cap thickness due to limited spatial resolution, and heavy calcification creates acoustic shadows that obscure detail
Ultrasound is limited to easily accessible arteries and can be obstructed by bone, gas, or dense calcification
CT has difficulty distinguishing soft-tissue components of plaques in acute disease and cannot differentiate stable fibrous lesions from acute haemorrhage or thrombosis
Beam hardening and "blooming" from calcification obscure the lumen in heavily calcified small vessels
MRI images of the coronary arteries are still inferior to CT and remain susceptible to motion artefact near the heart
Many molecular imaging tracers are still in the research or pilot-study phase and require further validation before entering routine clinical practice
Some tracers, such as 18F-FDG, have limited application in coronary imaging due to background uptake in surrounding structures

Recommendations for Patients

While advanced imaging techniques continue to evolve, established strategies for protecting arterial health remain crucial:

Control blood pressure, cholesterol, and blood sugar through regular check-ups and prescribed medications
Quit smoking—this is among the most powerful steps to reduce endothelial dysfunction and plaque progression
Maintain a heart-healthy diet low in saturated fats and high in fruits, vegetables, and whole grains
Engage in regular physical activity to improve vascular function and reduce inflammation
Discuss your individual cardiovascular risk profile with your doctor, including whether advanced imaging such as CT calcium scoring or carotid ultrasound might be appropriate for your situation
If you have experienced a heart attack or stroke, ask your cardiologist whether emerging imaging approaches—such as 18F-NaF PET or USPIO-enhanced MRI—might be available through research studies to better understand your plaque risk
Take your prescribed medications consistently, including statins, antiplatelet agents, and blood pressure medications, as these have been shown to stabilize plaque and reduce rupture risk

Frequently Asked Questions

What is atherosclerosis and why is it dangerous?

Atherosclerosis is a chronic, immune-driven disease where arteries narrow due to plaque buildup. It often progresses silently and can suddenly cause heart attacks or strokes when a plaque ruptures and triggers a blood clot. Advanced imaging can help identify dangerous plaques before they cause harm.

What makes a plaque vulnerable or high-risk?

A vulnerable plaque has a large lipid-rich necrotic core, a thin fibrous cap less than 65 micrometres, dense macrophage infiltration, and microcalcification. These features make it prone to rupture, exposing the contents to blood and causing rapid clot formation that can block the artery.

What imaging techniques can look inside artery walls?

Modern techniques include optical coherence tomography (OCT) and intravascular ultrasound (IVUS), which are invasive catheter-based methods, and non-invasive CT, MRI, and PET scans. These can assess plaque structure and biological activity, such as inflammation or microcalcification, beyond just measuring narrowing.

What is the difference between anatomical and molecular imaging of atherosclerosis?

Anatomical imaging, like CT or MRI angiography, shows the structure, narrowing, and plaque size. Molecular imaging, such as PET with targeted tracers, tracks disease activity like inflammation or microcalcification. This helps doctors determine not just how blocked an artery is, but how dangerous the plaque is.

How can advanced imaging help in treating heart attack or stroke risk?

Advanced imaging can identify biologically active, high-risk plaques even when they are not severely narrowed. This allows doctors to offer more aggressive medication, closer monitoring, or earlier intervention to patients at highest risk, while avoiding unnecessary procedures in those with stable plaque.

What are the limitations of these advanced imaging techniques?

Some techniques are invasive, like OCT and IVUS. OCT has limited tissue penetration; IVUS cannot measure fibrous cap thickness and is affected by calcium shadows. CT can be obscured by dense calcification, MRI is susceptible to motion near the heart, and many molecular tracers are still in research.

What should patients do to protect their arteries?

Control blood pressure, cholesterol, and blood sugar, quit smoking, maintain a heart-healthy diet, exercise regularly, and take prescribed medications like statins. Discuss your risk profile with your doctor to see if advanced imaging, like CT calcium scoring or carotid ultrasound, might be appropriate for you.

Source Information

This patient-friendly article is based on peer-reviewed research.

Original article title: Edinburgh Emerging techniques in atherosclerosis imaging

Authors: Maaz BJ Syed, Alexander J Fletcher, Rachael O Forsythe, Jakub Kaczynski, David E Newby, Marc R Dweck, and Edwin JR van Beek

Journal: British Journal of Radiology, 2019; Volume 92: 20180309

DOI: 10.1259/bjr.20180309

Author affiliations: British Heart Foundation Centre of Cardiovascular Science and Edinburgh Imaging Facility QMRI, University of Edinburgh

Seeing Inside Your Arteries: A Patient's Guide to Advanced Atherosclerosis Imaging

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