In Vivo Measurement of Plaque Neovascularization and Thermal

Heterogeneity in Intermediate Lesions of Human Carotids

Georgios Benetos

, Konstantinos Toutouzas

, Haralampos Grassos

, Maria Drakopoulou

Charalampia Nikolaou

, Ioannis Felekos

, Constantina Aggeli

, Eleftherios Tsiamis

Elias Siores

and Christodoulos Stefanadis

First Department of Cardiology, Athens School of Medicine, Athens, Greece

Center of Materials, Research and Innovation, University of Bolton, Bolton, U.K.

Keywords: Microwave Radiometry, Inflammation, Carotid Artery, Atherosclerosis.

Abstract: Purpose: Both plaque angiogenesis and inflammation contribute to the development and progression of

atherosclerosis. Contrast-enhanced ultrasound (CEUS) allows direct visualization of the adventitia vasa

vasorum. Microwave Radiometry (MWR) is a special technology, which quantifies internal temperature of

tissues, reflecting their inflammatory status. In the present study we aimed to evaluate in human carotid

arteries, whether atherosclerotic plaque temperature, measured by MWR, is associated with plaque

neovascularization assessed by CEUS. Methods: For this purpose, 48 consecutive patients with significant

coronary artery disease and carotid plaques in at least one carotid were included in the analysis .All patients

underwent basic ultrasound carotid imaging, neovascularization evaluation through CEUS and temperature

measurements through MWR. Results: Plaques with vulnerable characteristics showed both higher

temperatures and contrast uptake. There was a positive correlation between temperature and CEUS

measurements. Conclusions: In vivo non-invasive assessment of the functional characteristics of carotid

artery atherosclerotic plaques is feasible, promising and may serve as an additional screening tool to identify

‘high risk’ patients for future cerebrovascular events.

1 INTRODUCTION

Both plaque angiogenesis and inflammation

contribute to the development and progression of

atherosclerosis. Contrast-enhanced ultrasound

(CEUS) provides direct visualization of the

adventitial vasa vasorum and intraplaque

neovascularization. Microwave radiometry (MWR)

is a new non-invasive method, which detects

radiation transmitted from internal tissues in

microwave frequencies and converts these signals

into temperature measurements. It allows this way

the in vivo measurement of internal temperature of

tissues, reflecting inflammatory activation. The aim

of the current study is to assess whether carotid

plaque temperature, measured by MWR, is

associated with plaque neovascularization assessed

by CEUS.

2 METHODS

2.1 Study Population

Consecutive patients undergoing coronary

angiography for stable angina or acute coronary

syndrome were prospective enrolled in the study.

Patients with significant coronary artery disease

(stenosis≥50% in at least one major epicardial

artery) were evaluated with standard carotid

ultrasound. Only patients with carotid plaques in at

least one carotid artery (defined as intima-medial

thickening of at least 1.2mm) were finally included

in the study. Exclusion criteria included previous

cerebrovascular event, vasculitis, intermittent

inflammatory or neoplastic conditions.

2.2 Standard Carotid Ultrasound

Extracranial (common, internal, external) carotid

arteries were examined with a high resolution B-

Benetos G., Toutouzas K., Grassos H., Drakopoulou M., Nikolaou C., Felekos I., Aggeli C., Tsiamis E., Siores E. and Stefanadis C..

In Vivo Measurement of Plaque Neovascularization and Thermal Heterogeneity in Intermediate Lesions of Human Carotids.

 2014 SCITEPRESS (Science and Technology Publications, Lda.)

mode ultrasound unit (Philips iEE33 ultrasound

machine, Philips, Bothell, Washington), using the

7.5-MHz linear probe L9-3. All carotid plaques were

characterized according to their surface contour

(regular, irregular), echogenicity (homogeneous,

heterogeneous) and texture (fatty, mixed, calcified),

according to predefined criteria.

2.3 Contrast Enhanced Ultrasound

(CEUS)

All CEUS examinations were performed with the

commercially available contrast agent, SonoVue

(Bracco Imaging, Milan). The contrast agent was

infused intravenously via an infusion pump at a rate

of 0.8 ml/min. Contrast enhancement (CE) was

quantified using dedicated software. CE was defined

as the percentage of signal intensity difference, prior

and post contrast infusion.

2.4 Microwave Radiometry

Measurements (MWR)

The MWR measurements were performed with the

RTM 01 RES microwave computer based system

(Bolton, UK) that measures temperature from

internal tissues at microwave frequencies. Briefly,

MWR is based on the measurement of the

electromagnetic thermal noise that is emitted by

lossy materials in the microwave frequency range.

All media with absolute temperature T>0

K emit

electromagnetic radiation towards their

surroundings. Microwave radiation is capable of

penetrating human tissue and therefore the emission

provides information related to subcutaneous

conditions within the body. The depth of penetration

of microwave radiation depends on the wavelength,

the dielectric properties, and the water content of the

tissue. The signal which is recorded by the sensor is

given by the equation P=k T ΔF, where K is

Bolzmann coefficient, T absolute temperature and

ΔF the receivers bandwidth.

The sensor of the antenna of the device measures

with an accuracy of 0.20°C the ‘volume under

investigation’ as a rectangular area of 3 cm in width,

2 cm in length, and 3–7 cm in depth depending on

the water content of the body. Temperature

measurements were performed along each carotid

artery over segments 2cm of length. Thermal

heterogeneity (ΔT) was assigned as maximal

temperature along the carotid artery minus

minimum.

3 RESULTS

Eighty-six carotid arteries of 48 patients were

included in the analysis. Fatty plaques (n=9) had

higher CE% compared to mixed (n=55) and calcified

plaques (n=22) (21.4±2.70 versus 17.11±5.23 versus

8.55±2.42%, p<0.01). Heterogeneous plaques (n=9)

had higher CE% compared to homogenous (n=77)

(21.44±2.7 versus 14.66±6.02% p<0.01). Plaques

with irregular surface (n=32) had higher CE%

compared to plaques with regular surfaces (n=54)

(18.29±5.09 versus 13.64±6.06%, p<0.01). Fatty

plaques (n=9) had higher ΔΤ compared to mixed

(n=55) and calcified plaques (n=22) (1.13±0.27

versus 0.96±0.34 versus 0.53±0.26°C p<0.01).

Plaques with irregular surface (n=32) had higher ΔΤ

compared to plaques with regular surfaces (n=54)

(1.05±0.32 versus 0.75±0.36°C, p<0.01).

Heterogeneous plaques (n=9) had higher ΔΤ

compared to homogenous (n=77) (1.13±0.27 versus

0.83±0.37°C p<0.01). There was a positive

correlation between mean ΔΤ and CE (R=0.60,

p<0.001).

4 CONCLUSIONS

In the present study a significant correlation between

two vulnerable plaque characteristics, inflammation

and neoangiogenesis, was shown. The prognostic

significance of the evaluation of those characteristics

in clinical practice warrants further studies.