MS is classified as an inflammatory disease of CNS targeting myelin sheath and the formation of white matter and disrupts the blood-brain barrier . Till date, the precise diagnosis of MS is still challenging in spite of numerous imaging modalities [15, 25, 26]. Advances in MRI has transformed MS diagnosis and makes it possible for early and definite diagnosis. Routinely, contrast-enhanced T1-Weighted MRI is used to diagnose and follow-up on MS patients [12, 27]. Standard sequence post-contrast T1 weighted imaging can detect active plaque. The major disadvantage of the gadolinium-enhanced T1-weighted MRI (Gd-T1w MRI) technique is the need for injection of contrast media, which makes MRI less minimally invasive, more time consuming, more expensive and contraindicated in patients with sensitivity to contrast agents and renal impairment. The development of quantitative MRI techniques launched a new era in better appreciating the histopathology of MS [28, 29]. DWI is a non-invasive method based on local water motion in the tissue which was introduced by Larsson et al. (1993) for detecting acute MS lesions .
The present study investigated the effectiveness of DWI as an acceptable alternative technique for T1-Weighted MRI for diagnosing MS patients with acute attack. Comparing the accuracy of CE-MRI and DW-MRI, we found that the contrast-enhanced T1 plaques were more commonly detected than diffusion-restricted plaques in the study population. Our statistical analysis demonstrated higher accuracy of contrast-enhanced MRI in the detection of MS plaques, whereas that of DWI was relatively low (63.5% vs 27.1%). However, Meftahi et al. reported an AUC of 84% for 12 directional DWI and concluded the diagnostic significance of DWI 12 when CE-MRI is worried . The data obtained showed that contrast T1-Weighted MRI is effective for monitoring MS activity, but DW-MRI is not a suitable alternative in patients suffering from an acute attack of MS and can be used only as an additive sequence. In this study three patients presented with a positive DW-MRI without any evidence of contrast-enhanced plaques in CE-MRI. Similarly, Davoudi et al. expressed concerned about DWI positive cases that showed CE-MRI negative results . The diagnostic capability of DWI in MS is still under debate. Consistent with findings in the present study, several studies concluded that DWI findings are nonspecific and cannot differentiate lesions of acute MS attacks from other lesions [7, 28, 32]. Therefore, DWI could not substitute for contrast MRI; however, concomitant use of these two modalities could increase the probability of correct detection of active MS plaques . Nevertheless, the diagnosis of another differential diagnosis of acute demyelinating lesions such as acute ischemia was shown to improve with DW-MRI .
In the 1970s vitamin D was identified as a key factor in MS development and various types of studies have been conducted to quantify and clarify how vitamin D influences MS . The present study also investigated the association between different MRI sequences and serum level of vitamin D3 in patients suffering from acute attack of MS. MRI is an accepted modality for the diagnosis and monitoring of MS and it is more reliable in the prediction of the disease course . Hence, if the MRI evidence of disease activity correlates with vitamin D, careful monitoring of serum vitamin D may help in providing a better treatment strategy for the prevention of MS attacks. Vitamin D3 deficiency, serum 25-hydroxyvitamin D (25(OH)D), has been known as a widespread health problem, affecting approximately one billion people worldwide . Vitamin D3 deficiency is associated with higher risk of MS disease [22, 23].
In the present study, patients with Contrast+ plaques showed significant differences from patients without contrast-enhanced lesions in terms of serum vitamin D3 levels (P = 0.001). Conversely, the patients of DW+-MRI and DW−-MRI were not significantly different from one another in terms of vitamin D3 deficiency (P = 0.51). Martínez-Lapiscina EH et al.  in a systematic review and meta-analysis reviewed 13 studies and 3498 patients. They showed that higher serum levels of vitamin D3 are associated with a marginal decrease in rate of relapse and radiological inflammatory activities in patients with MS. Furthermore, Weinstock-Guttman B et al.  demonstrated that vitamin D3 metabolites protect MS patients against brain atrophy and disability.
Despite the established significance of vitamin D3 in MS, the clinical definition of vitamin D deficiency and what constitutes optimal levels has been the subject of debate. The blood levels of 25(OH)D as suggested by the Endocrine Society for categories of deficient, insufficient, and sufficient are ≤ 20 ng/ml, 21–29 ng/ml, and ≥ 30 ng/ml, respectively . However, a sharp cutoff point of vitamin D3 for MS has not been addressed yet in the literature. In this study, we have determined a vitamin D3 cutoff in relation to CE-MRI and DW-MRI. Based on the Youden index, an optimal cutoff of 23.33 ng/ml was obtained where we perform contrast-based imaging on the patients. Hence, patients with vitamin D3 levels < 23.33 ng/ml are most likely to show Contrast+ lesions with a sensitivity of 83.33% and specificity of 61.29% in their CE-MRI study. Through DW-MRI, we measured a vitamin D3 threshold of 13.8 ng/ml with low specificity (34.78%), but relatively high specificity (82.26%). However, our statistical analyses proved that there is no significant correlation between vitamin D3 deficiency and positive DW-MRI (P = 0.51) and the AUC of the cutoff obtained (AUC = 0.546) fails to discriminate between the DWI groups. Therefore, the cutoff obtained for DWI in terms of vitamin D3 deficiency is of little importance and further investigation is required in this regard.
Furthermore, we performed a gender-based analysis to study the vitamin D3 threshold level in male and female patients. Through CE-MRI study, the discrimination of female patients with positive and negative results of CE-MRI was acceptable (AUC = 0.71) based on calculated vitamin D3 cutoff; however, the effect of vitamin D3 in the detection of MS plaques across a male group of CE-MRI, and male and female groups of DW-MRI suggested no discrimination (AUC < 0.7). An optimal cutoff of 23.33 in the female group of CE-MRI had 90.7% sensitivity and 52.38% specificity which was the same cutoff measured in CE-MRI regardless of the gender. This may be due to the fact that the majority of our patients were female and the cutoff obtained is more realistic. (Supplementary data)
In this study, we showed that what threshold of vitamin D3 deficiency is associated with the imaging activity of MS disease. This finding may favor the protective effect of vitamin D3 in inflammatory activities of the disease. Also, if MS patient reports serum vitamin D levels less than 23.33 ng/ml, the CE-MRI detection of MS lesion is possible with the highest sensitivity and specificity. The difference in age and sex distribution, lacking a control group, and absence of patients’ follow-up were the major limitations of the current study. Hence, we recommend the scientists conduct unbiased studies with a larger sample size in this regard.