Multiple sclerosis is a common chronic inflammatory disease and a common causes of disability in young adults. Traditionally, MS was considered to be caused by demyelination in white matter; however, the affection of gray matter is becoming increasingly prominent. Grey matter lesions have even been reported to precede white matter demyelination with some recent studies indicate an association of cortical lesion with clinical and cognitive impairment in MS patients [10, 11].
The diagnosis of MS is based mainly on MR imaging with conventional multisequence protocols. Owing to its ability to attenuate the CSF signal, FLAIR imaging is highly sensitive in detection of supratentorial lesions, especially juxtacortical and periventricular white matter lesions. Double inversion recovery (DIR) imaging technique uses a combination of 2 inversion pulses providing a sufficient attenuation of both CSF and the normal appearing white matter [7].
This study aims to investigate whether or not the 3D DIR sequence is superior compared to the 3D FLAIR sequence in detecting brain lesions in MS patients. The correlations between lesion load and disability status and cognitive functions in these patients were also investigated in this study.
DIR showed a significantly higher total number of MS lesions compared to FLAIR (total of 1690 lesions were detected in DIR compared to 1469 lesions in FLAIR), conforming to the study done over 55 patients with MS by Abidi Z. et al [5]. They found a significantly higher total number of lesions were displayed on DIR 2658 lesions while 2513 lesions on FLAIR images (p = 0.000). Also our results agreed with another study performed over 15 MS patients by Elnekeidy AM et al. [12] who found 349 lesions detected by DIR sequence compared to 267 lesions detected by FLAIR.
In our study, more infratentorial lesions were observed on DIR with an average of 2.91 ± 2.66 compared to 2.25 ± 2.18 in FLAIR; also, we found that DIR has higher accuracy to detect intracortical lesions with respect to FLAIR sequence (average of 7.13 ± 7.19 in DIR compared to 1.41 ± 1.76 in FLAIR). Our results were equivalent to previous studies such as Abidi Z. et al [5] who detected an average of 5.1 ± 7.37 infratentorial lesions in DIR compared to 4.23 ± 6.45 in FLAIR with P 0.000 and 1.29 ± 1.04 intracortical lesions in DIR compared to 0.5 ± 0.71 in FLAIR with a P 0.000. Also we agreed with the results of Elnekeidy AM et al. [12] who found an average of 8.21 ± 9.99 infratentorial lesions in DIR compared to 2.07 ± 3.41 in FLAIR (P 0.001) and an average of 6.57 ± 7.44 intracortical lesions in DIR compared to 2.86 ± 3.88 in FLAIR (P 0.003). Our results also conform with Vural G. et al. [13] who studied 34 patients with MS and found that DIR was superior to FLAIR in detection of infratentorial and cortical lesions with an average of 0.8 ± 1.2 infratentorial lesions in DIR compared to 0.7 ± 0.8 in FLAIR and 10.1 ± 7.4 intracortical lesions in DIR compared to 2.7 ± 3.1 in FLAIR.
A higher number of juxtacortical white matter lesions were detected on DIR compared to FLAIR (4.91 ± 5.4 compared to 4.72 ± 5.3), although not statistically significant (P 0.102). Abidi et al. [5] found that DIR detected higher number of lesions than FLAIR which agreed with our results yet with a significant statistical difference (15.20 ± 8.61 compared to 14.07 ± 8.11 with P 0.000). Also Elnekeidy et al. [12] found higher number of lesions in DIR with a significant statistical difference (P 0.002). On the other hand, Geurts et al. [14] reported the highest number of juxtacortical lesions on T2-weighted images. Our results also disagreed with Wattjes et al. [15] who studied seventeen patients presenting with a clinically isolated syndrome (CIS) suggestive of MS and they found higher number of juxtacortical lesions in FLAIR compared to DIR (total of 57 compared to 54 lesions respectively with insignificant statistical difference) (P 0.08). Such disagreement could be related to the lower number of patients in their study.
In the present study, DIR sequence demonstrated a higher number of periventricular WM lesions (11.84 ± 8.07) compared to 11.31 ± 8.07 in FLAIR with a statistically significant difference p < 0.001 which agreed with Elnekeidy et al. [12] who found DIR superior to FLAIR with a significant statistical difference (P 0.038). Our results also agreed to some extent with Abidi et al. [5] who found the average lesions in DIR was 15.34 ± 11.34 compared to 15.18 ± 11.16 in FLAIR yet with insignificant statistical difference (P 0.14) and also with Wattjes et al. [15] who found a total of 85 lesions in DIR compared to 81 lesions in FLAIR with insignificant statistical difference P 0.16.
An equal number of MS lesions were observed in deep white matter in the DIR and FLAIR sequences. However, Vural et al. [13] reported a higher number of detected lesions in deep white matter with T2W and FLAIR imaging compared to DIR (p = 0.022 and p = 0.027, respectively).
MS lesions near the CSF were more countable on DIR compared with FLAIR. This could be explained by the better contrast obtained by suppression of CSF on DIR images. Also the distinction between normal appearing gray matter/normal appearing white matter is markedly improved at DIR images; so, deciding about the location of the lesion in GM or WM was easier compared with FLAIR [5].
Flow artifacts observed in DIR images is seen in the posterior fossa, periventricular white matter, choroid plexus, and periaqueductal region of the brainstem tissue, which may be from CSF pulsation or from sinuses and bigger vessels. Another high signal ribbon-like artifact in the phase direction was often observed in extra-cortical regions. Also, lower SNR in the DIR technique and inhomogeneity of the magnetic field in the cortex of the limbic lobe and diminished inhomogeneity in the cortex of central sulcus should be noticed. Viewing multiple slices and other MRI sequences such as T1-weighted or FLAIR will help to report them as lesions (which are in an irregular shape) or as an artifact resulting from cortical vessels, which is rounded [5]. However, we did not face this artifact to a degree affecting the interpretation of images and it has no impact on our results.
Correlation between clinical and radiological data showed a positive correlation between EDSS and number of periventricular lesions, deep white matter lesions, and infratentorial lesions in both FLAIR and DIR, although not statistically significant (as detailed in Table 3). However, in the previous study done by Calabrese et al. [16], over 380 patients of MS (clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS) found a significant positive correlation between the number of intracortical lesions and EDDS scores which is an indicator for disability (P 0.004).
Ertan et al. 2018 showed that EDSS scores were higher in patients with long disease duration and increased number of intracortical lesions. However, no significant correlation was found between lesion load and the EDSS scores in all regions which is compatible with the results of our study [17].
Studying the correlation between lesion load and cognitive impairment, there was a non-significant negative correlation between the lesion load in FLAIR (p = 0.512 for cortical lesions) and DIR (p = 0.392 for cortical lesions) sequences and the results of SDMT cognitive assessment. The explanation of such weak correlation could be related to the relatively small number of cases and also that subpial cortical lesions, which are associated with physical and cognitive dysfunction in patients with MS, are poorly detected by conventional MRI and even DIR [15].
The study has some limitations including the relatively small sample size, measurement of the number of the lesions only discarding the lesion’s volume, even though several studies reported cortical lesions volume as a more accurate predicting factor of cognitive impairment. However, volumetric measures are usually technically difficult, while cortical lesions count can be easily evaluated. Some studies reported that DIR is a time-consuming sequence and has a high tissue absorption rate. Based on such disadvantages over FLAIR, one might think that its routine use in MS imaging may not be justified [18, 19]; however, in our study, 3D DIR sequence required an additional 4 min 46 s only. The aim of our study was to compare the number of detected lesions on FLAIR and DIR sequences. Thus, it was performed without intravenous contrast administration, so we cannot judge the role of DIR in active MS lesions which needs further larger studies comparing post contrast T1 WIs with DIR and FLAIR images.