Forty-two patients (16 males and 26 females, mean age 29 ± 6 years) with established diagnosis of MS were included in this retrospective study. These patients were referred from the neurology department in our institution to undergo MRI examination from Oct 2017 till Sep 2019. All the included patients are chronic MS patients who were previously diagnosed based on clinical, laboratory, electrophysiological, and previous MR studies. Patients in a state of clinical relapse or under corticosteroid therapy within 1 month of the study were excluded, in addition to exclusion of patients with contraindication to MRI examination (e.g. cerebral aneurysm clips and cardiac pacemakers) and claustrophobia. Patients who found to have any MRI-detectable lesions in the thalami (including lacunar infarcts and very small lesions) were also excluded from the study. The study was approved by the institutional ethics committee. All participants gave informed written consent.
Image acquisition
MR study was conducted using 1.5 Tesla machine (Achieva, Philips Medical systems, Best, The Netherlands) using 16channel SENSE head coil.
Imaging protocol includes T1-weighted images: repetition time (TR) 488 ms, echo time (TE) 15 ms, field of view (FOV) 230 mm, 18 sections with slice thickness 6 mm, and matrix 208 × 134. T2-weighted images: repetition time (TR) 1000 ms, echo time (TE) 100 ms, field of view (FOV) 230 mm, 18 sections with slice thickness 6 mm, and matrix 192 × 156. Post contrast T1-weighted imaging was done 4–5 min after IV administration of gadopentetate dimeglumine 0.1 mmol/kg. 3D FLAIR sequence: repetition time (TR) 4800 ms, echo time (TE) 307 ms, inversion time (TI) 1660 ms, field of view (FOV) 250 mm, 128 sections with slice thickness 1.2 mm, matrix 228 × 227, and scan time 5 min. Diffusionweighted imaging using singleshot pulsed gradientecho echoplanar sequence with diffusion encoding gradients in 15 noncollinear directions with b = 0 and b = 800 s/mm2: TR 8000 ms, TE 67 ms, 60 contiguous 2-mmthick axial sections, FOV 224 mm, matrix 112 × 128, and number of signal averages 2.
Image analysis
The images were analysed using Philips extended work station (EWS) View Forum 2.6.
First, 3D FLAIR images were reviewed to confirm absence of abnormal MR signal within the thalami.
Every section of the FLAIR sequence was inspected to detect any high MR signal lesions within the white matter. Purely cortical lesions were not included in this study as special MR techniques, such as double inversion recovery images, are needed to visualize these lesions [12]. The margins of every lesion were manually traced using a computer mouse to completely surround the lesion without including adjacent normal white matter, grey matter, or CSF. Magnification of images was done to magnify small lesions in order to be able to trace their margins easily and accurately. After tracing, the area of the lesion can then be automatically calculated (Fig. 1). This was repeated in all the sections covering the entire brain. The sum of the measured areas was calculated to obtain the total area of lesions in all brain sections of the patient (as indicator of whole brain WML burden).
Automatic reconstruction of bo images, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps from the echoplanar diffusion images was done. bo images show better anatomical details than ADC and FA maps, so allowing accurate placement of the region of interest (ROI). In the bo images, ROI was placed within the right and left thalami in three consecutive sections (ROI = 20 voxels). ROIs were placed within the widest parts of the thalami to ensure pure sampling of thalamic tissues (Fig. 2). Once a ROI placed within a bo image, an identical ROI will appear in the corresponding location in the ADC and FA maps. For each patient, average ADC and FA from the values of the three contiguous sections was calculated.
The radiological evaluation and post processing were done by an experienced radiologist, M.H. (more than 10 years’ experience). Intra-observer agreement κ = 0.56
Statistical analysis
Continuous variables were presented as mean ± SD. Categorical data were expressed as absolute frequencies and percentages. MannWhitney U test was used to test statistical significance. Spearman’s correlation coefficient (r) was used to correlate between continuous variables where r ranges from − 1 to 1, positive values indicate linear positive correlation, and negative values indicate linear negative correlation. When r is closer to 1 or − 1, the linear correlation is stronger.
The strength of the correlation is either very weak ( r = 0.00–0.19), weak (r = 0.2–0.39), moderate (r = 0.4–0.59), strong (r = 0.6–0.79), or very strong (r = 0.8–1.0). p value < 0.05 was considered statistically significant. Statistical Package for the Social Sciences software (SPSS for Windows, version 15.0, SPSSInc. Chicago, IL) was used for statistical analysis.