MS has classically been described as a WM disorder [9]; however, over the few past years, an increased attention has been pointed toward the involvement of GM in the pathophysiology of MS [10]. The acknowledgment of GM involvement in MS has led to the incorporation of cortical/juxtacortical lesions in the recent 2017 revised McDonald’s diagnostic criteria for MS [3]. Since abnormalities in cortical gray matter have been correlated with both physical and neuropsychological deficits in MS patients, it is essential to create a better assessment and a more accurate estimation of gray matter lesion load in vivo [10].
The majority of our patients (91.1%) were categorized according to their clinical course as RRMS, while only 5.6% were categorized as SPMS and 3.3% were categorized as PPMS. This is in consensus with the fact that RRMS is the most common disease course.
DIR detected significantly more cortical lesions in our patients when compared to T2 (P value 0.003, relative gain about 98%) and FLAIR (P value 0.004 relative gain about 80). This was equivalent to studies done by Geurts et al. [10] and Elnekeidy et al. [11].
Besides the increased sensitivity to cortical lesions, we found the second major advantage of DIR imaging is its apparent potential for better differenation between mixed white matter–gray matter lesions and juxtacortical lesions. In our study, some of the lesions which were scored as juxtacortical on T2 and FLAIR images often turned out to be mixed white matter–gray matter lesions on DIR images. This is supported by the observation of a reduced number of juxtacortical lesions scored on DIR images compared with T2 (P = 0.696 relative loss about 2%) and FLAIR (P = 0.622, relative loss about 5%).
On the other hand, there was a statistically significant increase in mixed white matter–gray matter lesions detection on DIR imaging at the expense of T2 (P < 0.001 relative gain about 47%) and FLAIR (P = 0.009, relative gain about 24% (.The acceptable explanation for these different detection rates in the juxtacortical lesions and mixed white matter–gray matter lesions is the sharp delineation between gray and white matter on DIR, which allowed strict differentiation between purely juxtacortical lesions and lesions already touching the cortical area (Fig. 2).
As regard juxtacortical lesions, our results were consistent with the findings of the study done by Wattjes et al. [5]. However, our results were in contrary with the results done by Geurts et al. [10] which detected the highest number of lesions with T2. Regarding mixed white matter–gray matter lesions, our study was consistent with the reported results of Vural et al. [1].
Another benefit of DIR in our study was its ability to detect periventricular white matter (PVWM) lesions. DIR detected significantly more lesions in comparison with T2 (P = 0.033, relative gain about 31). Not surprisingly, DIR detected lesions with a slightly higher difference in comparison to FLAIR; this difference was below the statistical importance (P = 0.927, relative gain about 4%).The converged results between DIR and FLAIR return to CSF signal nulling in both sequences. However, we must point that DIR added a better morphological characterization and delineation of lesions which become more countable compared with confluent configuration in FLAIR and T2. Our results were equivalent to the reported results from Abidi et al. [2] and Wattjes et al. [5] but inconsistent with the reported results from Elnekeidy et al. [11] who found that no significant difference in lesion load between DIR and T2.
In the present study, we concluded almost similar detection rates as regard deep white matter (DWM) lesions by all sequences, with no statistically significant difference between them. Our results correlated to the results reported by Abidi et al. [2]; however, our results were in contrary with the results done by Elnekeidy et al. [11] which detected a higher number of lesions by DIR in comparison to T2 and FLAIR.
Another important advantage of DIR in our study was its ability to detect infra-tentorial lesions. DIR identified significantly more lesions in comparison to FLAIR (P = 0.002, relative gain about 63%). But, it was worthy of attention that DIR detected higher lesions even when compared with the T2, which is considered the “gold standard” in the infra-tentorial region (P = 0.023, relative gain about 39%).This was consistent with the results done by Abidi et al. [2] and by Elnekeidy et al. [11] but in contrary with results done by Moraal et al. [12] who found a similar number of lesions in the infra-tentorial region with DIR, FLAIR, and T2 images.
On the light of previously discussed results of diagnostic accuracy of DIR in different anatomical locations in comparison with T2 and FLAIR, we concluded that the increased rate of cortical lesion detection by DIR does not affect its accuracy in white matter lesions count. Moreover, DIR provided a better morphological characterization and delineation of white matter lesion with good differentiation between juxtacortical and mixed white matter–gray matter lesions. This means that DIR can be useful for clinical purposes as a supplement to or even as a replacement for standard T2 and FLAIR.
In our study, lesion-to-background signal ratio was calculated objectively in order to avoid creating subjective data by visual evaluation of signal ratio, which may be affected by windows and levels, magnification, and monitor brightness. We demonstrated a significantly higher signal ratio of lesions to NAWM on the DIR in comparison with T2W and FLAIR in all anatomical regions (infra-tentorial, periventricular, juxtacortical, and DWM) with (P < 0.001) which allowed better delineation of lesions by DIR. The higher contrast ratio detected by DIR can be explained by its complete suppression of white matter signal. Furthermore, the contrast ratio of lesions to CSF was significantly higher in DIR compared to T2 (P < 0.001). However, there was no statistically significant difference between the DIR and FLAIR regarding the contrast of lesion compared to CSF (P = 0.071) which was explained by CSF nulling by both sequences. It is important to mention that CSF suppression on DIR was less homogenous in some of our cases, but it was suitable for lesion detection even in the worst conditions.
On the other hand, there was no statistically significant difference between DIR and both FLAIR and T2 as regards the signal ratio of lesion to NAGM which explained that the three sequences have the same gray matter signal intensity. But, it was worthy of attention that the DIR allowed better delineation of gray matter.
The diagnosis of MS is based on the 2017 revised McDonald’s criteria which depend on the demonstration of lesion dissemination in both space and time. On MRI, the detection of at least one lesion on the spinal cord in addition to at least one cerebral lesion can fulfill the dissemination in space criteria [3]. Therefore, it was important to assess if there is an added value of DIR in spinal cord lesion detection.
In our work, Spinal lesions were observed in 31 out of 90 MS patients (34.4%). The importance of DIR in the spinal cord lesion detection is highlighted by three cases, in which a definite diagnosis of MS was highly suspected clinically, but not confirmed by radiology yet. One of them had a prominent lesion in the cervical cord by both T2 and DIR; however, a detection of a second lesion that is only visible in DIR largely excluded a neoplastic process and favored the diagnosis of an inflammatory disease.
In the other two cases, spinal cord lesion was only revealed by DIR that helped us to complete the criteria of dissemination in space, changing the diagnosis from “possible” to “definite” MS. In the rest of the cases, there was no difference between DIR and T2 as regard the number of detected lesions. However, the lesion-to-background contrast was higher in DIR that provided better lesion visualization.
Our previously discussed results were quite promising as we found that DIR provided a more exact delineation of spinal cord lesions and slightly improved lesion-detection rates.
Since cortical lesions are associated with more diffuse and severe pathologic process resulting in poor clinical prognosis, it was an important aspect to evaluate associated factors for developing cortical lesions. Cortical lesions were detected in 45.6% of patients, 26 were males and 15 of them were females. Therefore, males were significantly more at risk to have cortical lesions (P < 0.001). The predominance of cortical lesions in males deserved attention as despite higher prevalence of MS in females, the poor prognosis was associated with male gender. Our results correlated with the study done by Bergamaschi [13] which reported that male sex is a negative prognostic factor for MS, as well as the study done by Calabrese et al. [14] which confirmed the same results. However, our results were in contrary to the study done by Tremlett et al. [15] which reported that the male sex was not associated with worse disease outcome.
In our study, we found that cortical lesions were significantly more frequent and numerous at later MS stages (disease duration > 10 years) with (P = 0.003). This was in agreement with the results done by Elnekeidy et al. [11] and Calabrese et al. [14]. But, we cannot ignore that cortical lesions were also observed in few cases in earlier stages of the disease (disease duration < 5 years). The observation of cortical lesions early proved that the GM affection in MS does not always occur as a secondary change to WM affection, but may occur as a result of independent pathology of the GM.
From the clinical aspect, we observed that patients with cortical lesions presented clinical disability, cognitive changes, and higher EDSS score. There was a significant correlation between cortical lesions and EDSS (P < 0.001). This was consistent with the finding of the study done by Calabrese et al. [14] and Vural et al. [1]. The positive association of clinical outcome and cortical lesion load which was detected by DIR is considered a great advantage of the DIR sequence. It helps us to overcome the “clinico-radiological paradox” in MS which refers to the weak correlation of conventional MRI lesion load with clinical disability due inability of conventional MRI techniques to demonstrate all of the histopathological changes present in MS.
The main limitation in our study was DIR-related artifacts which were observed at posterior fossa, choroid plexus, and periventricular WM that may be from CSF pulsation or from sinuses and bigger vessels, and in addition to that, there were some bilateral high-signal ribbon-like artifacts which were observed in extra-cortical regions and their appearance changed in continual sections. To overcome that, we observed multiple slices and other MRI sequences such as T2 and FLAIR to help us to differentiate lesions from artifacts.
Another limitation in our study is that we were limited to perform 2D-DIR in spite of the advantages of 3D-DIR because of the high scan time of 3D-DIR. Therefore, we compared 2D-DIR in optimal parameters with 2D-FLAIR and 2D-T2W-TSE.