INTRODUCTION:

Carotid artery stenosis (CAS), a narrowing caused by atherosclerosis, is a major contributor to ischemic stroke and death¹. A global study estimates that roughly 21% of people aged 30-79 have carotid plaque, translating to approximately 816 million people worldwide. This condition is more prevalent in men and individuals over 65 years old².

Plaque in the carotid arteries, specifically when it narrows the vessel (ipsilateral carotid stenosis), can be a source of blood clots that cause a significant portion of ischemic strokes³. Extra cranial internal CAS is the most important cause of large artery stroke. Carotid endarterectomy (CEA), a surgical procedure, has been shown to be effective in reducing stroke risk in patients with severe or moderate CAS⁴.

Latest acute stroke management guidelines recommend carotid imaging as soon as possible, preferably within 24 hours, for patients with ischemic strokes/transient ischemic attacks who might be candidates for carotid intervention. However, the applicability of these recommendations depends on factors like the prevalence of CAS and risk associations in different populations⁴.

In India, with increasing life expectancy leading to a rise in age-related diseases like stroke, there is a need for reliable and accessible diagnostic methods for carotid artery disease. Stroke is now India's fourth leading cause of death and a significant cause of disability³. However, data on carotid artery stenosis in India is limited, and existing studies lack uniformity in methods.

Accurately determining stenosis severity is crucial for selecting the appropriate treatment for symptomatic plaques. Plaque composition also plays a role, as it can indicate the risk of plaque rupture and symptom development. Therefore, a reliable, preferably non-invasive method for assessing both carotid artery stenosis and plaque morphology is valuable for managing and preventing strokes and other complications.

This study aimed to evaluate DS as a diagnostic tool for carotid stenosis and plaque morphology. DS is a relatively cheap, widely available, and bedside procedure that allows for continuous monitoring of cerebral blood flow velocity compared to MRI. This investigation may help determine the most appropriate diagnostic approach for patients with suspected carotid artery stenosis, facilitating diagnosis and treatment decisions.

MATERIALS AND METHODS:

This study investigated the diagnostic efficacy of DS in evaluating carotid stenosis and plaque morphology. It was a hospital-based observational study conducted over five years, from January 2019 to December 2023, enrolling 150 patients with suspected CAS.

Inclusion criteria: All patients (in the inpatient and outpatient departments) with clinical suspicion of CAS, such as patients with ischemic strokes, transient ischemic attacks (TIA), drop attacks, syncope, episodic dizziness, carotid bruits, and amaurosis fugax, were evaluated irrespective of age and sex.

Exclusion criteria:

· Contraindications for MRI include incompatible implants.

· Patients with claustrophobia

· Critically ill patients

Internal carotid artery (ICA) stenosis was assessed using high-resolution DS with a linear superficial high-frequency (5–12 MHz) probe on a WIPRO GE Voluson E6 machine. A 1.5-Tesla (T) MRI scanner (GE HDXt) was also used. During DS, B-mode, color Doppler, and spectral Doppler imaging were employed. MRI included TOF angiograms, T1-weighted (T1W), and T2-weighted (T2W) images for stenosis evaluation. The Consensus Panel of Ultrasound and Doppler Criteria for the Diagnosis of Internal Carotid Stenosis guided ICA stenosis grading on DS images. MRI stenosis measurements followed North American Symptomatic Trial Collaborators (NASCET) criteria and were classified using the same grading system as DS^5,6.

DS evaluated plaque morphology based on echogenicity and heterogeneity. MRI, on the other hand, classified plaque composition (fibrous, fatty, hemorrhagic, calcific, or combinations) based on signal intensity in T1-weighted (T1W) and T2-weighted (T2W) images. Researchers then compared parameters from both modalities for correlation and agreement. Sensitivity and specificity of DS in detecting plaques and significant stenosis were calculated, using MRI as the gold standard. Additionally, plaque morphology evaluation by DS was further compared with MRI findings.

This study was conducted after getting approval from the institutional ethics committee. All safety and screening measures adhered to the American College of Radiology practice guidelines for MRI procedures.

RESULTS:

Out of the 150 cases, the majority of patients were in the elderly age group, with a male to female ratio of 3:1. Age and sex distribution are shown in (Table 1).

Table 1: Age and sex distribution.

Age in year	Gender				Total
	Male		Female		Total
	No.	%	No.	%	No.	%
≤50	48	42.1	3	8.3	51	34
51-60	36	31.6	24	66.7	60	40
>60	30	26.3	9	25	39	26
Total	114	100	36	100	150	100

The Intima-media thickness (IMT) in the majority of cases was 0.61-0.79mm. Among the cases, 81% had normal IMT, i.e., ≤ 1mm, and 19% had abnormally high IMT of > 1 mm. The ratio of normal IMT to abnormal IMT is 81:19 (p = 0.0003). There was a significant association between increased IMT and significant ICA stenosis (>50% stenosiss) with (p = 0.0007 with 47.4% of abnormal IMT in CCA having significant stenosis in ICA. Plaques were most commonly found in the carotid bulb, followed by the carotid bulb extending to the ICA in both procedures. A total of 15 plaques in the ICA not detected by DS were detected on MRI (Table 2).

Table 2: The distribution of Location of plaques/ thrombus as evaluated on Doppler Sonography and MRI.

Location of plaques/ thrombus	DS		MRI
Location of plaques/ thrombus	No.	%	No.	%
No plaque	111	37	111	37
CCA	18	6	3	1
Carotid bulb	69	23	66	22
Carotid bulb extending to ICA	39	13	33	11
ICA origin extending distally	6	2	6	2
CCA extending to carotid bulb	3	1	3	1
1-Carotid bulb extending to ICA 2- ICA	3	1	9	3
1-Carotid bulb extending to ICA 2-CCA	30	10	30	10
1-Carotid bulb 2- ICA origin extending distally	6	2	6	2
1-Carotid bulb 2-CCA 3- ICA origin extending distally	6	2	6	2
1-CCA extending to carotid bulb 2-ICA origin extending distally	6	2	6	2
1-Carotid bulb extending to ICA 2-CCA 3- ICA origin extending distally	3	1	3	1
1-Carotid bulb 2-CCA	0	0	3	1
1-CCA 2- ICA	0	0	15	5
Total	150	100	150	100

Figure 1: DS showing (A) Increased IMT in right CCA.(B) Homogeneously hypoechoic plaque causing 50-69 % stenosis of right ICA.(C) Heterogeneously isoechoic plaque causing near complete occlusion of right ICA.(D) Heterogeneously isoechoic plaque showing variable velocity corresponding to near complete occlusion of right ICA.(E)Heterogeneously isoechoic plaque with calcification with posterior acoustic shadowing in right ICA. (F) Heterogeneously isoechoic plaque with calcification of right ICA showing PSV=216cm/sec corresponding to 50-69% stenosis.

Table 3: Correspondence of plaque Morphology on DS and MRI.

Plaque morphology on DS	No	Plaque morphology on MRI	No
Isoechoic	102	Fibrous	99
Isoechoic	102	Fibrous with atheromatous core	3
Isoechoic with calcification	45	Fibrocalcific	39
Isoechoic with calcification	45	Fibrocalcific with hemorrhage	9
Heterogeneously isoechoic	60	Fibrous	51
Heterogeneously isoechoic	60	Hemorrhagic	9
Heterogeneously isoechoic with calcification	15	Fibrocalcific	6
		Fibrocalcific with hemorrhage	6
		Fibrous with atheroma and calcification	3
Heterogenously hypoechoic	3	Hemorrhagic	3
Heterogenously hypoechoic with calcification	3	Fatty with calcification	3
Thrombus	18	Recent thrombus	18

Table 4: Comparison of ICA stenosis on DS and MRI.

Stenosis	Estimated ICA stenosis in DS		ICA stenosis in MRI
Stenosis	No.	%	No.	%
No stenosis	192	64	180	60
<50%	63	21	78	26
50-69%	24	8	21	7
>70% but less than near occlusion	3	1	3	1
Near occlusion	6	2	3	1
Complete occlusion	12	4	15	5
Total	300	100	300	100

Table 5: Agreement of ICA stenosis between DS and MRI.

Estimated stenosis in ICA by DS	ICA stenosis : MRI													Total		Kappa ‘K’ & 'p' value
	No stenosis		<50%		50-69%		>70% but less than near occlusion		Near occlusion		Complete occlusion			Total		Kappa ‘K’ & 'p' value
	No.	%	No	%	No	%	No.	%	No.	%	No.	%	No.		%
No stenosis	177	98	18	23	0	0	0	0	0	0	0	0	195		65	K=0.799 p=0.000
<50%	3	1.7	54	69	3	14	0	0	0	0	3	20	63		21
50-69%	0	0	3	4	18	85	0	0	0	0	0	0	21		7
>70% but less than near occlusion	0	0	0	0	0	0	3	100	0	0	0	0	3		1
Near occlusion	0	0	3	4	0	0	0	0	3	100	0	0	6		2
Complete occlusion	0	0	0	0	0	0	0	0	0	0	12	80	12		4
Total	180	100	78	100	21	100	3	100	3	100	15	100	300		100

In this study, among an effective sample size of 300 carotid arteries, the most common location of plaques was the carotid bulb, followed by plaques extending from the carotid bulb to the internal carotid artery (ICA) in both procedures. Our findings regarding plaque location are consistent with previous reports, which found the carotid bulb to be the most common site¹². However, unlike their study where the second most common location was the common carotid artery (CCA), our study observed plaques extending from the carotid bulb to the ICA as the second most prevalent location. It is believed that carotid plaques originate from endothelial damage caused by local blood flow disturbances, influenced by the bifurcation anatomy, which explains the high prevalence in the carotid bulb¹³.

Although the total number of plaque-free arteries was identical on both DS and MRI (111), MRI detected a total of five plaques in the ICA that were missed by DS. This finding aligns with a previous study which demonstrated superior sensitivity and specificity of MRI compared to DS in identifying plaques and stenosis¹⁴. Therefore, MRI may be a preferable option for patients with a high suspicion of ICA stenosis, even if DS fails to detect any plaques in the ICA.

Our study found that DS, when compared to a reference standard of magnetic resonance imaging (MRI), demonstrated high sensitivity (98.41%) and specificity (100%) for detecting plaques. Similar results were reported by other investigators, showing sensitivity and specificity of 94% and 93% respectively, for plaque detection using ultrasound¹⁵. Additionally, another study reported a sensitivity and specificity of 89% and 87% respectively, for detecting plaques¹⁶. These findings highlight the high sensitivity and specificity of DS for plaque detection, adding to its other important advantages such as lack of ionizing radiation, cost-effectiveness, and minimal patient discomfort, making it a valuable tool for monitoring plaque progression and regression.

In our study, the most common type of plaque identified was isoechoic to the sternocleidomastoid muscle. Similar findings were also reported by Peterson et al., who observed homogeneously isoechoic plaques in the majority of their patients¹⁷.

A study found that patients without symptoms had a preponderance of isoechoic plaques, while symptomatic patients with stenosis exceeding 70% had a preponderance of echolucent plaques. Although plaque assessment by duplex ultrasound (DS) is a straightforward method, concerns have been raised regarding inter-observer variability in plaque category assignment. Several factors contribute to this variability, including intrinsic instrument differences, variation in instrument settings, and sonologist experience. Nevertheless, studies have shown that excellent results can be achieved with visual plaque assessment when proper attention is paid to imaging detail^18,19.

A previous study demonstrated that the echogenicity of plaques varies with their specific tissue composition¹⁶. Fibrous plaques, rich in collagen, appear highly echogenic and uniformly homogeneous in texture. Conversely, as the lipid content within the plaque increases, it becomes more echolucent.

A previous study reported that both hyper echoic and isoechoic materials likely represent fibrous components of plaque⁹. The authors stated that relatively hypo echoic areas corresponded to lipid-rich material, hemorrhage, or smooth muscle cell proliferation, which aligns with our findings. Another study observed that 91% (30 out of 33) of intraplaque hemorrhages occurred in heterogeneous lesions²⁰. This suggests the potential of preoperative ultrasound carotid imaging for identifying plaque's histological characteristics. Zwibel compared homogenous and heterogeneous plaques and found that calcification can contribute to heterogeneity; however, no link between calcification and neurological symptoms has been established¹⁹.

The literature has widely discussed two other types of heterogeneity: focal areas and scattered areas of low echogenicity. Clinicians are particularly interested in reports linking heterogeneous plaque to a higher prevalence of hemispheric neurological symptoms, such as transient ischemia and stroke, compared to patients with homogeneous, isoechoic (fibrous) plaque.

In theory, focal or diffuse plaque heterogeneity is associated with complex plaque histology and potentially with degeneration of the fibrous cap and endothelium. This heterogeneity is thus linked with an increased potential for embolization¹⁹. Studies have observed that MRI has better sensitivity and specificity for detecting internal carotid artery (ICA) stenosis compared to digital subtraction angiography (DSA)¹⁵. A systematic review by Nederkoorn et al. demonstrated that the pooled sensitivity and specificity of MRI are superior to DSA, with digital subtraction angiography serving as the reference standard²¹.

Our study found that DS has high sensitivity (92.89%) and specificity (97.67%) for diagnosing significant stenosis (>50%). Other investigators have reported similar findings, with a peak systolic velocity of 130 cm/s demonstrating a sensitivity of 98% and a specificity of 88% in detecting 50% angiographic stenosis²². Additionally, DS shows sensitivity of 90% and specificity of 94% for diagnosing 70% angiographic stenosis. Earlier studies also support the use of DS for reliably predicting significant stenosis (>50%) with high accuracy^21,22. Invasive treatment is typically reserved for symptomatic patients with greater than 50% stenosis and asymptomatic patients with greater than 60% stenosis²³. These findings suggest that DS could be a reliable diagnostic tool for detecting significant stenosis and guiding treatment decisions, particularly for patients who are unable to undergo MRI or DSA due to contraindications or critical illness.

Scientific research inherently generates new questions and ideas for further investigation. In this vein, the efficacy of velocity criteria for evaluating stenosis severity using portable ultrasound in critically ill patients warrants further study. This could improve patient screening and potentially reduce the need for more invasive procedures like MRI and DSA. Additionally, the heterogeneity of plaques on Doppler ultrasound (DS) and their link to hemorrhage deserve further exploration, as this association could be an indicator of future complications. Research into more quantitative and operator-independent criteria for evaluating plaque morphology, such as video densitometry or radiofrequency-based approaches, would also be valuable.

CONCLUSION:

This study suggests that an abnormal intima-media thickness (IMT) greater than 1 millimeter (mm) is associated with an increased risk of ischemic stroke. The carotid bulb is the most common site for plaque formation. DS demonstrates high sensitivity and specificity for plaque detection compared to magnetic resonance imaging (MRI). Fibrous plaques typically appear isoechoic or heterogeneously isoechoic on DS, while hemorrhagic plaques may appear heterogeneously isoechoic or heterogeneously hypoechoic. While MRI is superior for grading internal carotid artery (ICA) stenosis, DS exhibits high sensitivity and specificity for identifying stenosis exceeding 50% when compared to MRI. However, MRI alone is not reliable for diagnosing partial subclavian steal syndrome.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

The authors would like to thank to staff and patients their kind support during these studies.

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Received on 09.04.2024 Revised on 06.08.2024

Accepted on 03.10.2024 Published on 27.03.2025

Available online from March 27, 2025

Research J. Pharmacy and Technology. 2025;18(3):1021-1027.

DOI: 10.52711/0974-360X.2025.00146

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

High-resolution Doppler Sonography and Magnetic Resonance Imaging in Evaluating Carotid Stenosis and Plaque Morphology