High-resolution vessel wall magnetic resonance imaging in intracranial vasculopathies: an experience from eastern India

Abstract

Objective:

To evaluate the role of high-resolution intracranial vessel wall imaging (HR-IVWI) in differentiation of various intracranial vasculopathies in addition to luminal and clinical imaging in the largest cohort of Indian stroke patients.

Methods:

A single-center, cross-sectional study was undertaken recruiting consecutive stroke or TIA patients presenting within a month of onset, with luminal irregularity/narrowing upstream from the stroke territory. The patients were initially classified into TOAST and Chinese ischemic stroke sub-classification (CISS) on the basis of clinical and luminal characteristics and reclassified again following incorporation of HR-IVWI findings.

Results:

In our cohort of 150 patients, additional use of HR-IVWI led to a 10.7 and 14% change in initial TOAST and CISS classification respectively (p < 0.001). In TOAST classification, 12 “undetermined aetiology” were reclassified into intracranial atherosclerotic disease (ICAD), 1 “undetermined aetiology” into CNS angiitis and 1 “undetermined aetiology” into arterial dissection. Similarly, in CISS 19 “undetermined aetiology” was reclassified into 16 large artery atherosclerosis (LAA) and 3 “other aetiology” consisting of one CNS angiitis, Moyamoya disease (MMD) and arterial dissection each. Two initial classification of MMD by CISS and TOAST were changed into ICAD. The observed change in diagnosis following incorporation of HR-IVWI was proportionately highest in ICAD (LAA) subgroup (TOAST-9.3%, CISS-12%).

Conclusion:

Adjunctive use of HR-IVWI, to clinical and luminal assessment, can significantly improve diagnostic accuracy during evaluation of intracranial vasculopathies, with its greatest utility in diagnosing in ICAD, CNS angiitis and dissection.

Advances in knowledge:

HR-IVWI allows clearer etiological distinction of intracranial vasculopathies having therapeutic and prognostic implications.

Introduction

Intracranial vasculopathies represent a myriad of disease conditions and are often a major cause of mortality and morbidity worldwide. Common intracranial vasculopathies include intracranial atherosclerotic disease (ICAD), Moyamoya disease (MMD), inflammatory vasculopathies (IVas), reversible cerebral vasoconstriction syndrome (RCVS), and arterial dissection. ^1,2 Early diagnosis is important since treatment strategies vary and inappropriate or delayed therapy can be detrimental. ^1,3–7 Luminal evaluation by digital subtraction angiography (DSA), MR angiography (MRA) or CT angiography(CTA) has been the traditional approach for diagnostic differentiation and characterization. Although luminal imaging remains central to initial evaluation, similarities in patterns of lumenographic findings amongst various intracranial vasculopathies often limits its use in their differentiation. ^1,2,4,6,8,9 High-resolution intracranial vessel wall imaging (HR-IVWI) has emerged in recent years as a useful noninvasive imaging tool allowing in vivo assessment of normal and diseased arterial walls. ^2,4,7 In 2017, the American Society of Neuroradiology recommended the use of HR-IVWI in clinical practice for differentiation of etiology of intracranial arterial narrowing and characterization of symptomatic, non-stenotic intracranial arterial diseases. ³ Although a number of studies have evaluated the use of HR-IVWI in intracranial vasculopathies, ^8–15 the literature pertaining to its use in the Indian sub-continent is sparse. ¹⁶ We herein evaluated the role of HR-IVWI in the differentiation of various intracranial vasculopathies as compared to luminal and clinical imaging in the largest cohort of patients with intracranial vasculopathies from India.

Methods and materials

A single-center, cross-sectional, prospective cohort study was undertaken from the stroke-unit of the largest tertiary neurological care center in Eastern India (Bangur Institute of Neurosciences, Kolkata, India) from January 2017 to December 2018, following institutional ethics committee approval. Consecutive patients referred to our stroke-unit who met the following inclusion criteria: (1) a clinical diagnosis of ischemic stroke or TIA, (2) evidence of luminal irregularity/narrowing but without occlusion on luminal imaging modalities (MRA, CTA or DSA) upstream from the stroke territory and (3) presenting within a month of the acute stroke event, were recruited for our study after informed written consent. Contraindication to undergoing MRI or receiving intravenous gadolinium contrast or with angiographic evidence of >50% extracranial carotid or aortic stenosis and clinical evidence for cardio-embolic source for ischemic stroke/TIA were exclusion criteria. All recruited patients underwent an initial MRI brain (T1, T2, T2 FLAIR, DWI and T2*-GRE sequence) (Supplementary Table 1 for parameters) for parenchymal evaluation. The baseline demographic, clinical and investigational characteristics were documented and were as follows:

1. demographic- age, gender

2. clinical- risk factors for stroke (hypertension, diabetes mellitus, dyslipidemia, smoking, coronary artery disease [CAD]), baseline NIHSS score and prior history of stroke or TIA.

3. diagnostic- cerebral circulation territory affected in the recent acute event (anterior, posterior or both, right, left), presence and type of chronic infarction on baseline imaging, presence of white matter hyperintensities and Fazekas grading, presence of cerebral microbleeds and CSF analysis (if acquired).

Following evaluation of the above baseline characteristics by two stroke neurologists independently (S.Da, S.Du), the patients were classified according to the Trial of Org 1,0172 in acute stroke treatment (TOAST) classification ¹⁷ [Large artery atherosclerosis (LAA); Stroke of other determined etiology (SoODE) that includes IVas, MMD, RCVS, dissection and others; and Stroke of undetermined etiology (SoUE)] and Chinese ischemic stroke sub-classification (CISS) ¹⁸ [LAA; other etiology (OE) and undetermined etiology (UE)]. In case of disagreement in diagnosis, a third senior stroke neurologist(B.K.R) arbitrated. After the addition of HR-IVWI data (described below), one of the stroke neurology raters(S.Da) re-classified the cases into one of the TOAST stroke subtypes and CISS subtypes.

MRI protocol

[Machine specification- Siemens Magnetom Verio, 3-Tesla field strength, Cube, head coil- 32 channel, gradient strength- VQ engine 45mT/m@200 T/m/s]

All recruited patients then underwent HR-IVWI (parameters listed below):

Pre-contrast 3D T1 HR-IVWI (6 min 5 sec, TE: 15, TR: 700, FOV read: 230 FOV Phase 100, voxel size 0.4 × 0.4 × 1.0 mm), pre-contrast 3D T2 HR-IVWI (6 min 6 sec, TE: 381, TR: 3000, FOV read: 230, FOV Phase 100, voxel size 0.4 × 0.4 X 1.0 mm), Pre-contrast 3D PD HR-IVWI (6 min 2 sec, TE: 24, TR: 1100, FOV read: 230, FOV Phase 100, voxel size 0.4 × 0.4 × 1.0 mm), Post-contrast 3D T1 HR-IVWI (6 min 5 sec, TE: 15, TR: 700, FOV read: 230, FOV Phase 100, voxel size 0.4 × 0.4 × 1.0 mm, performed 6 min after contrast injection).

Image analysis

HR-IVWI was interpreted by a neuroradiologist (M.D) who had undergone training in interpretation of HR-IVWI, which included reviewing a series of articles focused on HR-IVWI interpretation, in-person case reviews, independent test case review with feedback provided and didactic lectures. He was blinded to patient history, clinical and radiology notes. The following HR-IVWI characteristics were reviewed: presence and pattern of vessel wall thickening, presence, pattern and grade of vessel wall enhancement, T2-juxta-luminal hyperintensity, intraplaque hemorrhage and presence of intimal flap with intramural hematoma.

In accordance with the American Society of Neuroradiology expert consensus recommendations, ³ the neuroradiologist reviewing the HR-IVWI classified the individual patients into ICAD, MMD, IVas, RCVS and dissection. Those without any comparable features on HR-IVWI were classified as undetermined aetiology.

Statistical analysis

SPSS 25 was used for statistical analysis. Data were summarized by routine descriptive statistics, namely mean and standard deviation for numerical variables that are normally distributed, median and interquartile range (IQR) for skewed numerical variables and counts and percentages for categorical variables. Numerical variables were compared between two groups by Student’s independent samples t-test, if normally distributed, or by Mann-Whitney U-test, if otherwise. For multiple group comparison of skewed variables, Kruskal Wallis ANOVA was used followed by Dunn’s test for post-hoc comparisons between two individual groups. Fischer’s exact test or Pearson’s Chi-square test were employed for intergroup comparisons of categorical variables. Analyses were two-tailed and statistical significance level was set at p < 0.05 for all comparisons. Cohen’s κ was used as a measure of categorical agreement between stroke subclassification system.

Result

The median (range) age of diagnosis of the whole cohort, comprising of 150 ischemic stroke or TIA patients with evidence of luminal irregularity/narrowing, was 40 years (20-54). The baseline demographic, clinical and radiological details are outlined in Table 1.

Table 1.

Baseline demographic, clinical and radiological details of the study population

		Overall (n = 150)	ICAD (n = 67)	Other determined aetiology (ODE)				Undetermined aetiology (n = 28)	p-value (ICAD vs MMA)
				MMA (n = 45)	CNS angiitis (n = 7)	RCVS (n = 2)	Dissection (n = 1)
1.Age (years)		40 (20 – 54)	55 (51 – 59)	17 (10 – 27)	16 (14 – 18)	24 (23 – 25)	25	31 (23.5 – 41.5)	< 0.001
2.Gender (M:F)		90 : 60	51 : 16	16 : 29	4 : 3	0 : 2	1 : 0	18 : 10	< 0.001
3.Risk Factors for Stroke	HTN	51 (34.00)	47 (70.15)	1 (2.22)	⎯	⎯	⎯	3 (10.71)	< 0.001
	Diabetes	43 (28.67)	38 (56.72)	1 (2.22)	⎯	⎯	⎯	4 (14.29)	< 0.001
	Dyslipidemia	35 (25.33)	32 (47.76)	1 (2.22)	⎯	⎯	⎯	2 (7.14)	< 0.001
	Smoking	33 (22.00)	24 (35.82)	⎯	⎯	⎯	⎯	9 (32.14)	< 0.001
	CAD	14 (9.33)	14 (20.90)	⎯	⎯	⎯	⎯	⎯	< 0.001
4.Prior stroke / TIA		44 (29.33)	5 (7.47)	36 (80.00)	⎯	⎯	⎯	3 (10.71)	< 0.001
5.Baseline NIHSS		6 (3 – 9)	7 (5 – 10)	0 (0–6)	13 (9 – 16)	11.5 (10 – 13)	⎯	⎯	< 0.001
6.Acute infarction on brain imaging	Anterior	97 (64.67)	52 (77.61)	21 (46.67)	1 (14.29)	⎯	1 (100.0)	22 (78.57)
	Posterior	12 (8.00)	6 (8.96)	⎯	⎯	1 (50.00)	⎯	5 (17.86)	< 0.001
	Both	13 (8.67)	5 (7.46)	⎯	6 (85.71)	1 (50.00)	⎯	1 (3.57)
7.Presence of chronic infarction on baseline imaging		92 (61.33)	43 (64.18)	38 (84.44)	⎯	⎯	⎯	10 (35.71)	0.030
8.Type of chronic infarction	Lacunar	45 (30.00)	32 (47.76)	5 (11.11)	⎯	⎯	⎯	7 (25.00)	< 0.001
	Non-lacunar	47 (31.33)	11 (16.42)	33 (73.33)	⎯	⎯	⎯	3 (10.71)
9.White matter hyperintensity		89 (59.33)	49 (73.13)	23 (51.11)	4 (57.14)	⎯	⎯	13 (46.43)	0.026
10.Fazekas	Grade 1	59 (39.33)	33 (49.25)	19 (42.22)	2 (28.57)	⎯	⎯	5 (17.86)
	Grade 2	21 (14.00)	11 (16.42)	4 (8.89)	2 (28.57)	⎯	⎯	4 (14.29)	0.065
	Grade 3	5 (3.33)	4 (5.97)	⎯	⎯	⎯	⎯	1 (3.57)
11.Cerebral microbleed		30 (20.00)	16 (23.88)	2 (4.44)	3 (42.86)	1 (50.00)	⎯	8 (28.57)	0.007
12.Intracerebral bleed		8 (5.33)	3 (4.48)	⎯	3 (42.86)	1 (50.00)	⎯	1 (3.57)	0.272
13.CSF analysis	Done	30 (20.00)	2 (2.99)	⎯	7 (100.00)	2 (100.0)	⎯	8 (28.57)	0.515
	Pleocytosis	7 (4.67)	⎯	⎯	7 (100.00)	2 (100.0)	⎯	⎯	0.002
	Increased protein	9 (6.00)	⎯	⎯	7 (100.00)	2 (100.0)	⎯	2 (7.14)	0.002

With the use of clinical data and luminal imaging only, the categorization of stroke etiologies according to the TOAST classification resulted in 53 ICAD patients, 42 of “SoUE” and 55 patients with “SoODE”. Among the 55 “SoODE”, MMD constituted 47, CNS angiitis constituted 6 (3 each of primary and secondary CNS angiitis) and 2 RCVS. Similarly, during categorization according to CISS, 49, 47 and 54 patients were diagnosed as “LAA”, “UE”, and “OE”, respectively. Inclusion of HR-IVWI interpretation to the existing clinical and luminal imaging investigation characteristics additionally led to TOAST re-classification in 10.7% cases; 12 “SoUE” were reclassified into ICAD, 1 “SoUE” into CNS angiitis and 1 “SoUE” into arterial dissection. Two patients with previous classification as MMD were re-classified into ICAD. Similarly, 14% of cases were reclassified following additional HR-IVWI in CISS; 19 “UE” was reclassified into 16 LAA and 3 “OE” consisting of one CNS angiitis, MMD and arterial dissection each. Two patients previously classified as MMD by CISS were re-classified into ICAD. With the inclusion of HR-IVWI, there was significant change in revised classification (p < 0.001 for both TOAST and CISS). The revised diagnosis included 67 ICAD patients, 28 of “undetermined etiologies” and 55 patients with “other determined etiologies” (MMD-45, CNS angiitis-7, RCVS-2 and arterial dissection-1). The observed change in diagnosis following incorporation of HR-IVWI was proportionately highest in ICAD (LAA) subgroup (9.3% in TOAST, 12% in CISS).(Table 2)

Table 2.

Comparison of stroke categorization according to toast and ciss classification based on clinical and luminal imaging and additional vessel wall imaging

Stroke categorization		Clinical + Luminal Imaging (N = 150)		Additional vessel wall (N = 150)
		Toast	CISS
1. LAA (ICAD)		53 (35.3%)	49 (32.7%)	67 (44.7%)
2. Undetermined aetiology		42 (28%)	47 (31.3%)	28 (18.7%)
3. Other determined aetiology
(A) Moyamoya		47 (31.3%)	46 (30.7%)	45 (30%)
(B) CNS Angiitis	Primary	3 (2%)	3 (2%)	3 (2%)
	Secondary	3 (2%)	3 (2%)	4 (2.7%)
(C) RCVS		2 (1.3%)	2 (1.3%)	2 (1.3%)
(D) Dissection		0	0	1 (0.7%)

p < 0.001 for both TOAST and CISS recategorization of stroke subgroups following HR-IVWI

ICAD demonstrated eccentric wall thickening pattern in 94%, significantly different from MMD (p < 0.001) and CNS angiitis (p < 0.001). Grade two vessel wall enhancement was seen in all CNS angiitis patients.The pattern of vessel wall enhancement was predominantly heterogeneous (52.2%) or focal (31.3%) in ICAD, and was significantly different from MMD (p < 0.001) or CNS angiitis (p < 0.001). The T2 juxta-luminal hyperintensity and intraplaque hemorrhage was exclusively seen in patients with ICAD, accounting for 86.6 and 11.9% of ICAD patients. The only patient with diagnosis of arterial dissection showed intramural hematoma.(Table 3)

Table 3.

Intracranial vessel wall characteristics in various stroke etiologies by toast classification

VESSEL WALL CHARACTERISTICS		Overall (n = 150)	ICAD (n = 67)	MMA (n = 45)	CNS ANGITIS (n = 7)	p-value (ICAD vs MMA)	p-value (ICAD vs CNS ANGIITIS)	p-value (MMA vs CNS ANGIITIS)
1.Thickening		117 (78.00)	65 (97.01)	10 (22.22)	7 (100.00)	< 0.001	1.000	< 0.001
2.Thickening pattern	Eccentric	66 (44.00)	63 (94.03)	⎯	⎯	< 0.001	< 0.001	< 0.001
	Concentric	52 (34.67)	2 (2.99)	10 (22.22)	7 (100.00)
3.Enhancement		114 (76.00)	58 (86.57)	11 (24.44)	7 (100.00)	< 0.001	0.669	< 0.001
4.Grade Of enhancement	Grade 1	88 (58.67)	48 (71.64)	10 (22.22)	⎯	< 0.001	< 0.001	< 0.001
	Grade 2	26 (17.33)	10 (14.93)	1 (2.22)	7 (100.00)
5.Enhancement pattern	Focal	23 (15.33)	21 (31.34)	⎯	⎯	< 0.001	< 0.001	< 0.001
	Diffuse	52 (34.67)	2 (2.99)	11 (24.44)	7 (100.00)
	Heterogeneous	39 (26.00)	35 (52.24)	⎯	⎯
6 .T2 juxta-luminal hyperintensity		58 (38.67)	58 (86.57)	⎯	⎯	< 0.001	< 0.001	⎯
7.Intraplaque hemorrhage		8 (5.33)	8 (11.94)	⎯	⎯	0.021	1.000	⎯

Inter-reader agreement was for TOAST and CISS classification without and with HR-IVWI was strong, 0.846 with 95% confidence interval between 0.776 and 0.917 for without HR-IVWI and 0.800 with 95% confidence interval between 0.723 and 0.878 with inclusion of HR-IVWI, respectively.

Discussion

The current study shows the value of HR-IVWI in reclassifying stroke etiologic classifications, even when complete patient work-up and clinical diagnosis was taken into consideration. The misclassified cases would have remained so until or beyond future secondary stroke events. Our study showed that the largest categorization change with inclusion of HR-IVWI was re-classification of 14 cases to ICAD, including 12 cases switched from undetermined etiology to ICAD.

Mossa–Basha et al had revealed that 79% of symptomatic ICAD lesions showed at least one component of T2 vessel wall hyperintensity‚ as compared to none from the IVas and RCVS groups; while eccentric vessel wall thickening was noted in 91% of the ICAD group compared to 7% in the angiitis group and 18% in the RCVS group. ⁸ Echoing with previous observations, the strongest HR-IVWI parameters which enabled ICAD to be differentiated from IVas in our study included focal eccentric vessel wall thickening, focal eccentric vessel wall enhancement and presence of T2 juxtaluminal hyperintensity with surrounding hypointensity (Figure 1). ^2,3,8,16 T2 juxta-luminal hyperintensity seen in HR-IVWI is considered 100% specific in differentiating ICAD from IVas and RCVS. ^2,8 Heterogeneous vessel wall enhancement was the commonest pattern in our study similar to the observation made by Mossa–Basha et al, ⁸ differing from the only previous Indian study by Kesav et al, ¹⁶ which reported 15.8% of lesions showing heterogeneous vessel wall enhancement pattern. A possible explanation for this disparity could be related to the differences in the patient profile wherein a heterogeneous eccentric pattern of contrast enhancement might suggest a more advanced and prominent lesion. ^3,8 Besides, technical factors like imaging resolution, sequence parameters or post-contrast timing differences and a smaller cohort leading to selection bias could have also accounted for this divergent observation in the study by Kesav et al. ¹⁶ Vessel wall enhancement is an indicator of ongoing inflammation, neovascularity, and plaque instability. ^{1,3,6,8,19,20} The fact that vessel wall enhancement was observed in 86.6% of our patients with ICAD is probably indicative that ongoing inflammatory processes might have contributed to the precipitation of acute cerebrovascular event, or may represent sequelae of plaque rupture, or both. ³ Intraplaque hemorrhage was observed in 11.6% of our patients with ICAD. It has been proven to be an important risk factor for plaque vulnerability, with increased rates of plaque complications and stroke. ^2,4,21

Figure 1.

In a patient of ICAD, MRI Brain Diffusion weighted imaging sequence showing acute restrictions in the Left centrum semiovale suggestive of acute cerebral infarction (a); Time of flight MRA showing Focal narrowing seen at right cavernous and supraclinoid ICA (b); HR-IVWI, axial and coronal section showing asymmetric vessel wall thickening and eccentric vessel wall enhancement (arrow) at right supraclinoid ICA (c and d).

Moyamoya syndrome secondary to atherosclerosis(aMMS) can mimic MMD because of significant overlap of luminal imaging (compensatory collateralization may be seen in aMMS or collaterals may be absent in MMD depending on the stage; besides both can present with either bilateral or unilateral disease) and clinical features, more so in adult presentations of moyamoya angiopathy (MMA). This is especially pertinent in Asian populations, in whom both the disease states are prevalent. ^22–26 However, distinction is of utmost importance due to differences in their treatment strategies. ^24,27 Our study showed that incorporation of HR-IVWI led to correct attribution of two cases of aMMS, which were previously labeled as MMD from clinical and luminal imaging alone. Vessel wall thickening pattern, enhancement pattern and presence of T2 juxta-hyperintensity in HR-IVWI was significantly different between MMD and ICAD groups in our study. Vessel wall thickening was observed in 22.2% of MMD patients in our cohort, all having concentric thickening pattern. This is similar to previous observations from North America by Mossa–Basha et al. ⁹ (13.3%) and the previous study by Kathuveetil et al evaluating an Indian cohort ²⁸ (6.6%), but lower frequency in comparison to the previous Chinese study by Yaun et al. (83.3%). ²⁹ In our study, vessel wall enhancement was observed in 24.4% of MMD patients, all having diffuse and most having Grade one enhancement. While it was similar to observations made in North America by Mossa–Basha et al. ⁹ (13.3%) and South-India by Kathuveetil et al. ²⁸ (6.02%), it was markedly lower in comparison to studies from South Korea by Ryoo et al. ¹⁴ (93.3%), and in China by Wang et al. ³⁰ (63.2%).These differences could be related to variability in timing of HR-IVWI in the disease course of MMD patients. Furthermore,differences in MMD phenotype between East Asian countries and Western hemisphere is well-known and is attributed to the regional differences in effect size of p.R4810K mutation. Recent epidemiological studies have shown intercountry differences in genetic makeup between Asian countries. ²⁷ Additionally, differences in environmental and socio-economic factors might also contribute to phenotypic differences. The regional differences in vessel wall characteristics amongst MMD patients further upholds the influences of complex interplay of genetic and environmental influences on the poorly understood MMA pathophysiology. ^23,24,27,31 Other considerations include technical and pathophysiological factors. “Pseudoenhancement” attributable to slow, in-plane, or turbulent flow, can be exacerbated in the setting of stenosis or occlusion, as is seen in MMD. This issue can be exacerbated depending on parameters used with 3D techniques, but also mitigated with use of blood suppression techniques. ³² Either the degree of stenosis or occlusion or the technique used can contribute to false enhancement or exaggeration of enhancement.

Central nervous system(CNS) angiitis can result in severe morbidity and mortality and thus warrants an early diagnosis and institution of prompt immunosuppressive treatment. ² It can further be stressed that the classic appearance of CNS angiitis on DSA has sensitivity of 27–90% and specificity as low as 30%. ^4,33,34 The limitation in sensitivity is primarily related to the difficulty of DSA in the detection of subtle changes or very distal small vessel involvement. Non-targeted biopsy in the diagnosis of CNS angiitis also has a low sensitivity of <50%, besides the inherent risks of its invasive nature. ^2,4,35 Previous reports have shown high prevalence of intense, concentric vessel wall enhancement and wall thickening in CNS angiitis, reported in 85.2 and 92.6% of patients in one series. ³⁶ Vasculitic enhancement on post-contrast MRI can extend beyond the vessel wall into the periadventitia, increasing the conspicuity of the affected segments and potentially enabling detection of microvascular involvement that is otherwise angiographically occult. ^4,34 Our study demonstrated concentric vessel wall thickening with intense Grade two contrast enhancement in all our patients (100%) with CNS angiitis (Figure 2). This agrees with findings from a previous Indian study by Kesav et al., ¹⁶ which showed diffuse, concentric vessel wall thickening in 100% of patients and homogeneous contrast enhancement of vessel wall in 92.3% patients. Given that HR-IVWI is particularly sensitive to vessel wall enhancement and that other diagnostic tests such as DSA or CSF analysis are often inconclusive and lead to invasive brain biopsy, it serves as a suitable tool to ascertain the diagnosis. With advances in HR-IVWI, findings diagnostic for angiitis may limit the need for biopsy, and in cases where biopsy is required, localization of active disease on IVWI can guide surgeons to increase diagnostic yield. In addition, the degree of enhancement indicates the activity of angiitis. ^{2–5,10,36–41}

Figure 2.

In a patient of CNS angiitis, MRI IVWI Axial T2 sequence showing hyperintensities at bilateral frontal and right parietal lobes subacute cerebral infarction (a); Diffusion weighted imaging sequence showing restrictions near right dentate nucleus suggestive of acute infarction (b); MR angiogram of intracranial vessel shows attenuated PCA bilaterally (c); HR-IVWI, sagittal section showing focal concentric wall thickening(arrow) at basilar top region (d); concentric wall thickening and enhancement(arrow) at vertebral and basilar arteries respectively in post-contrast 3D T1 SPC (e,f)

RCVS must be differentiated from CNS angiitis which often has similar radiological characteristics, since treatment strategies vary widely. ^2,3 The most specific criterion for RCVS is reversibility within 3 months of the onset of symptoms. ⁴² HR-IVWI in RCVS typically shows non-enhancing (or mildly enhancing) vessel wall compared with the typical intense wall enhancement in CNS angiitis. ^2–4,43 Both of our RCVS patients did not show any vessel wall contrast enhancement, conforming to the previous literature. ^3,8,16

Our study provides evidence on the value of HR-IVWI in the diagnostic evaluation of intracranial vasculopathic disorders in a South Asian population, with its greatest impact on ICAD, IVas and arterial dissection subgroups. The utilization of HR-IVWI with baseline luminal imaging findings enabled 14 and 19 subjects in the stroke of “undetermined aetiology” of TOAST and CISS sub-classification respectively to be re-classified into one of the definite subtypes, when compared to the full patient workup without HR-IVWI. This understates the utility of HR-IVWI as an additional tool in the diagnostic armamentarium of intracranial vasculopathic disorders, the majority of which lack a true gold standard. ^2–4,15 HR-IVWI findings when incorporated along with baseline clinical and luminal imaging findings enabled 81.3% of the study population to be classified into definite etiological subgroup based on current classification criteria. Thus, patients without a definite etiological diagnosis were reduced to 18.7% from 31.3–28% following the addition of HR-IVWI. If compared to cryptogenic stroke which accounts for 30–40% of ischemic stroke, a work-up of ischemic stroke incorporating HR-IVWI seems useful. ⁴⁴

The limitations of the study include single-centered study, with possibility of referral bias, corroborated by an increased number of MMD patients. Only the predominant lesion was characterized on vessel wall imaging, leaving a small chance of missing out on additional co-existent vessel wall pathology in the same patient. Histopathological confirmation was not done in most cases. The biggest strength of our study included our large sample size and use of uniform luminal imaging modality for all the patients.

Conclusion

The additional use of HR-IVWI can serve as a valuable adjunctive investigation tool that can significantly improve diagnostic accuracy in the evaluation of ischemic stroke and its classification, especially with appropriate clinical and luminal imaging characteristic corroboration. The improved differentiation of the various stroke subtypes is of paramount interest as this can help in timely institution of etiology-specific therapies. Its greatest utility is subserved in identifying ICAD, IVas and dissection subgroups; and differentiating MMD from ICAD.