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Multiple Sclerosis Original article The Neuroradiology Journal 0(00) 1–6 ! The Author(s) 2018 Multiple sclerosis: High prevalence of the Reprints and permissions: sagepub.co.uk/journalsPermissions.nav ‘central vein’ sign in white matter lesions DOI: 10.1177/1971400918763577 on susceptibility-weighted images journals.sagepub.com/home/neu Gianvincenzo Sparacia1 , Francesco Agnello1, Angelo Gambino1, Martina Sciortino2 and Massimo Midiri1 Abstract Purpose: The aim of this study was to determine the occurrence and distribution of the ‘central vein’ sign in white matter lesions on susceptibility-weighted magnetic resonance images in patients with multiple sclerosis (MS) and cerebral small vessel disease (CSVD). Materials and methods: T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of 19 MS patients and 19 patients affected by CSVD were analysed for the presence and localisation of focal hyperintense white matter lesions. Lesions were subdivided into periventricular or non-periventricular (juxtacortical, subcortical, deep white matter and cerebellar) distributed. The number and localisation of lesions presenting with the central vein sign were recorded and compared between MS and CSVD lesions. Results: A total of 313 MS patients and 75 CSVD lesions were identified on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. The central vein sign was found in 128 MS lesions (40.9%), and the majority of them (71/128, 55.5%) had a periventricular distribution. The central vein sign was found in 22 out of 75 (29.3%) CSVD lesions, and periventricular distribution was seen in six out of 22 (27.2%) CSVD lesions. The difference in the proportion of white matter hyperintense lesions that presented with the central vein sign on susceptibility-weighted images in patients with MS and CSVD was statistically different, and a significantly higher number of MS patients presented with lesions with the central vein sign compared to CSVD patients. Conclusion: The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the under- standing of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease. Keywords Central vein sign, susceptibility-weighted imaging, multiple sclerosis, cerebral small vessel disease, magnetic resonance imaging Introduction Efforts have been made to improve the ability of imaging to differentiate MS from its mimic. Multiple sclerosis (MS) is the most common auto- One option may be to detect a small central vein (the immune neurological disorder affecting young adults. ‘central vein’ sign) in MS lesions. Indeed, pathological It is pathologically characterised by multifocal inflam- studies at autopsy have demonstrated that the typical mation, demyelination, axonal injury and neuronal extension and morphology of the MS lesions is due to loss.1 the perivenous localisation in the white matter of the Conventional magnetic resonance imaging (MRI) brain and spine.5,6 As a result of high sensitivity to slow has high sensitivity in demonstrating MS dissemination venous flow, the utility of susceptibility-weighted in time and space.1,2 The current diagnosis of MS is based on a combination of clinical, radiological and 1DIBIMED – Sezione di Scienze Radiologiche, University of Palermo, laboratory findings.2 However, MRI specificity for the Palermo, Italy diagnosis of MS is relatively low because several vascu- 2School of Medicine, University of Palermo, Palermo, Italy lar, infectious, neoplastic, congenital and metabolic dis- Corresponding author: eases can show a similar radiological appearance and 3,4 Gianvincenzo Sparacia, DIBIMEF – Sezione di Scienze Radiologiche, mimic MS at MRI. MS is thus usually a diagnosis of University of Palermo, Via Del Vespro, 127, 90127 Palermo, Italy. exclusion. Email: [email protected] 2 The Neuroradiology Journal 0(00) imaging (SWI) sequence has recently been investigated The MRI protocol included axial and sagittal fast- for the detection of the central vein sign.7,8 spin echo T2-weighted sequences (TR/TE, 5100/110); In a small prospective study, Kau et al.7 have axial FLAIR sequences (TR/TE/TI, 8000/140/2400); reported that although the central vein sign was not axial, sagittal and coronal contrast-enhanced exclusively present in MS lesions it helps differentiate (0.1 mmol/kg of gadobutrol; Gadovist, Bayer, Bonn, MS from non-MS lesions. More recent studies at ultra- Germany) fast-spin echo T1-weighted sequences high-field have demonstrated that the presence of a cen- (TR/TE, 650/12); field-of-view (FOV) 22 cm; matrix tral vein improves the differentiation of MS and 320 Â 320; slice thickness 5 mm; intersection gap vascular lesions.9–11 In addition, Lane et al.8 have 1 mm; number of excitations 2. reported that the detection of the central vein sign The SWI sequences were obtained using a technique helps differentiate MS from dementia. that combines a long-TE high-resolution fully flow-com- There is also an increasing acceptance of the poten- pensated 3DGRE sequence with filtered phase informa- tial role of the central vein sign as a biomarker of tion in each voxel both to enhance the contrast in inflammatory demyelination in the most recent guide- magnitude images and add the susceptibility differences lines for MS diagnosis.12–15 However, further research between tissues as a new source of information.15–18 is required to consider the central vein sign a reliable The SWI images were obtained without the injection diagnostic criterion of MS. As the most common differ- of contrast material (TR/TE, 34/24; flip angle 10; FOV ential diagnosis for MS is focal white matter hyperin- 22 cm; matrix 256 Â 512; slice thickness 1.2 mm; no tensity due to cerebral small vessel disease (CSVD), the intersection gap; number of images 140; number of purpose of our study was to compare the occurrence excitations 1; and acquisition time 5.40 minutes). and distribution of the central vein sign in white matter The SWI images were also post-processed with the min- lesions among patients with MS and CSVD. imum intensity projection (MinIP) algorithm in the axial plane with a slice thickness of 3–10 mm to visual- Materials and methods ize better the ‘signal void’ of the vessel structures. This retrospective study was approved by the institu- Image evaluation tional review board of our institution, and informed consent was waived; however, informed written consent The T2-weighted and FLAIR images, presented in for the MRI was obtained in all patients. random order on a picture archiving and communica- This study included 19 patients (nine men, 10 tion system (Agfa HealthCare GmbH, Bonn, women; aged 19–53 years, mean age 36.9 years) with Germany), were analysed in consensus by two neuror- MS and 19 patients (nine men, 10 women; aged 59–72 adiologists, each with at least 10 years of experience years, mean age 61.2 years) with CSVD. All MS who were unaware of the patients’ clinical information, patients underwent brain MRI examination as part of for the presence and localisation of focal hyperintense the routine follow-up. MRI examinations were per- white matter lesions. formed between December 2016 and April 2017. Lesions were subdivided into periventricular or non- Inclusion criteria for MS patients were age over 18 periventricular distributed. Non-periventricular lesions years, clinical diagnosis of MS and fulfillment of 2010 were subdivided into juxtacortical, subcortical, deep revised McDonald criteria for MS.2 The mean disease white matter and cerebellar. Only white matter lesions duration for MS was 8.1 Æ 6.5 years. Eleven patients greater than 5 mm in largest diameter were considered, (57.9%) had the relapsing–remitting clinical subtype, limiting the overall number of lesions greater than six (31.5%) had the secondary progressive clinical sub- 3 mm in largest diameter to a maximum of eight. type, and two (10.5%) had the primary progressive clin- Confluent lesions were excluded. We chose these inclu- ical subtype. The Expanded Disability Status Scale sion criteria that have been reported better to reflect (EDSS) of the patients with MS ranged between 1 equivocal cases in clinical routine and better reflect and 4.5, with a mean of 1.9 Æ 0.8. the critical lesion load regarding the Barkhof criteria.7 Diagnosis of CSVD required lack of symptoms sug- The SWI images were evaluated for the presence or gestive of another white matter disease, identification of absence of a venous structure within the MS lesions. To vascular risk factors, and the presence of cerebral white better differentiate the signal void of a vessel, the MinIP matter hyperintensities on T2-weighted and fluid-atte- post-processed SWI images were also used. The pres- nuated inversion recovery (FLAIR) MRI, as commonly ence of a vein within the MS lesion was defined accord- seen in CSVD. ing to the standard radiological definition established in the North American Imaging in Multiple Sclerosis 15 MRI protocol (NAIMS) guidelines, which recommend that the vein appears as a thin hypointense line or small hypoin- All MRI examinations were performed on a 1.5 T MR tense dot; when technically possible, the vein can be scanner (Achieva, Philips Medical Systems, Best, visualised in at least two perpendicular planes; the The Netherlands) using an 8-channel phased-array vein runs partially or entirely through the lesion, but head coil. must be located centrally regardless of the lesion’s Sparacia et al. 3 shape; the vein has a small (<2 mm) apparent diameter. hyperintense lesions were identified in CSVD patients. As exclusion criteria, the standard radiological defin- All lesions were clearly visible both on the T2-weighted ition was also used: the lesion is less than 3 mm in diam- and FLAIR images. eter in any plane; the lesion merges with another lesion In MS patients, periventricular distribution was (confluent lesion); the lesion has multiple distinct veins; found in 139 (44.4%) lesions while non-periventricular the lesion is poorly visible (as a result of motion or distribution was found in 174 (55.6%) lesions.
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