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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 3  |  Page : 386-393

Diagnosis of gray matter lesions in multiple sclerosis using variant sequences of magnetic resonance imaging (T2, fluid-attenuated inversion recovery, and double inversion recovery)


Department of Radiology, Benha University, Benha, Egypt

Date of Submission28-Jul-2018
Date of Acceptance18-Aug-2018
Date of Web Publication07-Jan-2019

Correspondence Address:
Dr. Shimaa A El-Sabbagh
Shirbin Central Hospital, Benha University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bmfj.bmfj_166_18

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  Abstract 


Background and aim Gray matter atrophy is significantly correlated with both physical and cognitive disability in patients with multiple sclerosis (MS).
Patients and methods The study was conducted on 40 patients with definite relapsing-remitting MS according to McDonald criteria. All patients were subjected to conventional MRI [T2 and fluid-attenuated inversion recovery (FLAIR) sequences] and double inversion recovery (DIR) sequence to assess their sensitivity for detecting gray matter lesions in patients with MS.
Results Comparative studies between serial MRI sequences revealed highly significant increase in detected number of white matter lesions in FLAIR and DIR-MRI sequences (P=0.0007). Comparative studies also revealed a nonsignificant difference in detection rate in all 3 MRI sequences (P>0.05). Moreover, there were significant increases in detected number of gray matter lesions in DIR-MRI sequences (P=0.021) and a highly significant increase in detection rate in DIR-MRI sequences compared with T2 and FLAIR-MRI sequences (P<0.001). By using receiver operating characteristic curve analysis, T2-MRI sequences failed to discriminate patients with gray matter lesions from patients without, with failed accuracy, having sensitivity of 17% and specificity of 100% (P=0.051). However, FLAIR-MRI sequences discriminated patients with gray matter lesions from patients without with poor accuracy, having sensitivity of 34% and specificity of 100% (P<0.0001). On the contrary, DIR-MRI sequences discriminated patients with gray matter lesions from patients without, with perfect accuracy, having sensitivity of 100% and specificity of 100% (P<0.0001).
Conclusion DIR is a valuable MRI sequence in imaging of MS because of the following: (a) it showed better delineation between the white matter, the gray matter, and the MS lesions owing to its high image contrast measurements; (b) it detected more MS lesions compared with T2WI and FLAIR sequences in all anatomic locations; (c) it revealed more periventricular and juxta-cortical MS lesions, which are characteristic of MS; and (d) it detected more intracortical lesions as well, which should be considered in all patients with MS.

Keywords: double inversion recovery, fluid-attenuated inversion recovery, gray matter lesions, multiple sclerosis, MRI, T2


How to cite this article:
Youssef AF, Shaalan AE, El-Sabbagh SA. Diagnosis of gray matter lesions in multiple sclerosis using variant sequences of magnetic resonance imaging (T2, fluid-attenuated inversion recovery, and double inversion recovery). Benha Med J 2018;35:386-93

How to cite this URL:
Youssef AF, Shaalan AE, El-Sabbagh SA. Diagnosis of gray matter lesions in multiple sclerosis using variant sequences of magnetic resonance imaging (T2, fluid-attenuated inversion recovery, and double inversion recovery). Benha Med J [serial online] 2018 [cited 2019 Dec 15];35:386-93. Available from: http://www.bmfj.eg.net/text.asp?2018/35/3/386/249419




  Introduction Top


Multiple sclerosis (MS) is a chronic degenerative disease affecting the central nervous system and is a major cause of acquired disability in young adults in the western world. It is characterized by recurrent episodes of immune-mediated demyelination, glial scar formation, and axonal loss, leading to variable clinical outcomes [1]. In a double inversion recovery study of large patient population, cortical lesions were detected in most patients with relapsing-remitting multiple sclerosis (RRMS) (64%) and secondary progressive MS (70%) as well as in 37% of patient with clinically isolated syndrome [2].

Cortical demyelination lesions occur in the early phases of RRMS [3]. Thalamic atrophy predicts conversion of clinical isolated syndrome to MS [4]. Gray matter atrophy is more extensive and occurs at a faster rate in the MS brain [5]. Gray matter atrophy is significantly correlated with both physical and cognitive disability in patients with MS [6].

Recently, double inversion recovery (DIR) sequences have been developed and used to improve further the sensitivity of magnetic resonance imaging in detecting such lesions. DIR imaging depicted more intra-cortical lesions than standard MR imaging techniques [7].

Double inversion recovery imaging consists of two adiabatic non-selective inversion pluses applied before a Turbo Spin Echo sequence to suppress the signal from two tissues with different longitudinal relaxation times simultaneously. In the brain, DIR is used to selectively image the gray matter by nulling the signal from white matter and cerebrospinal fluid (CSF) [8].

Although DIR has been shown to improve the sensitivity of the detection of cortical lesions, this sequence has low signal-to-noise ratio, poor delineation of lesion borders, and is prone to image artifacts. Nelson demonstrated that intracortical lesions (ICLs) can be identified and classified with greater confidence, by the combination of DIR with phase-sensitive inversion recovery images [9].

MR imaging quantities are applied as surrogate outcome measures in treatment trials of MS because they are non-invasive, have high sensitivity toward disease activity, and very reliable [10].

Contrast enhancing MS lesions are important markers of active inflammation in diagnostic working of MS and disease monitor with MIR because intra venous contrast agents desire to identify active lesions without using contrast agents [11].


  Patients and methods Top


Patients

The study was conducted on 40 patients with definite RRMS according to McDonald criteria.

The study was done between October 2017 and July 2018. All patients had conventional MRI and clinical findings suggestive of RRMS, and they all were referred to Department of Radiodiagnosis, Faculty of Medicine, Benha University.

The study was done after approval of the ethical board of Benha University, and an informed consent was taken from each participant in the study.

Eligible patients were selected according to the following inclusion and exclusion criteria:

Inclusion criteria included RRMS according to McDonald criteria.

Exclusion criteria included concomitant neurological diseases in conjunction with MS.

Methods

All patients were subjected to the following
  1. Full history taking and thorough clinical examination, including the following:
    1. Name, sex, and age.
    2. Symptoms and signs including the following:
      1. General weakness and fatigue.
      2. Muscle weakness.
      3. Any visual disturbances.
      4. Paresthesias.
  2. Imaging study:
    1. Brain MRI was performed on 1.5 T using a standard quadrate head coil.


All patients were subjected to the following MRI protocols:
  1. Conventional MRI:
    1. T2-weighted images utilizing the following parameters: a repetition time (TR) of 4.4 s, an echo time (TE) of 100 ms, a slice thickness of 5 mm, and FOV of 230 mm.
    2. fluid-attenuated inversion recovery (FLAIR) images utilizing the following parameters: a repetition time (TR) of 11.0 s, an echo time (TE) of 140 ms, TI of 2800 s, a slice thickness of 5 mm, and FOV of 230 mm.
  2. Double inversion recovery MRI sequence: a repetition time (TR) 9.6 s, an echo time (TE) of 25 ms, TI of 3400/325 ms, a slice thickness of 3 mm, and FOV of 230 mm.


Statistical analysis

Data entry, processing, and statistical analysis was carried out using MedCalc ver. 15.8. (MedCalc, Ostend, Belgium). Tests of significance [McNemar’s, repeated measures analysis of variance, Cochran’s Q tests, κ statistics, and receiver operating characteristic (ROC) curve analysis] were used. Data were presented, and suitable analysis was done according to the type of data (parametric and nonparametric) obtained for each variable. P values less than 0.05 (5%) were considered to be statistically significant.


  Results Top


The study was conducted on 40 patients with definite RRMS according to McDonald criteria.

Regarding basic clinical data, we found that the mean age of all patients was 32.65±8.72 years. Regarding sex of the patients, 50% were males and 50% were females. We also found that 55% of the patients had tingling and numbness, 12.5% of the patients had paresthesia, 42.5% of the patients had muscle weakness, 30% of the patients had speech disorder, 45% of the patients had visual disorder, 17.5% of the patients had upper limb tremors, and 12.5% of the patients had hemiparesis.

Regarding T2-MRI sequence results, we found that the detection rate of white matter lesions was 92.5%, whereas for gray matter lesions was 17.2%. The average number of white matter lesions was 3.91±2.25, whereas for gray matter lesions was 1.4±0.54.

Regarding FLAIR-MRI sequence results, we found that the detection rate of white matter lesions was 100%, whereas for gray matter lesions was 34.5%. The average number of white matter lesions was 4.9±3.03, whereas for gray matter lesions was 1.5±0.7.

Regarding DIR-MRI sequence results, we found that the detection rate of white matter lesions was 97.5%, whereas for gray matter lesions was 100%. The average number of white matter lesions was 5.1±3.33, whereas for gray matter lesions was 2.82±1.48.

Regarding diagnostic accuracy studies, we found the following:
  1. A comparative study between T2-MRI and FLAIR-MRI results revealed a nonsignificant difference in sensitivity and specificity regarding detection of white matter lesions, with fair level of agreement (κ=0.381) (P>0.05). The comparative study also revealed an increase in sensitivity and specificity regarding detection of gray matter lesions in FLAIR-MRI sequence, with substantial level of agreement (κ=0.6), but not reaching statistically significant difference (P>0.05) ([Table 1]).
    Table 1 Agreement between T2-MRI and fluid-attenuated inversion recovery-MRI results regarding diagnostic accuracy parameters

    Click here to view
  2. A comparative study between T2-MRI and DIR-MRI results revealed a nonsignificant difference in sensitivity and specificity regarding detection of white matter lesions, with moderate level of agreement (κ=0.481) (P>0.05). The comparative study also revealed a highly significant increase in sensitivity and specificity regarding detection of gray matter lesions in DIR-MRI sequence, with slight level of agreement (κ=0.1), with highly significant statistical difference (P<0.0001) ([Table 2]).
    Table 2 Agreement between T2-MRI and double inversion recovery-MRI results regarding diagnostic accuracy parameters

    Click here to view
  3. A comparative study between FLAIR-MRI and DIR-MRI results revealed nonsignificant difference in sensitivity and specificity regarding detection of white matter lesions, with moderate level of agreement (κ=0.581) (P>0.05). The comparative study also revealed a highly significant increase in sensitivity and specificity regarding detection of gray matter lesions in DIR-MRI sequence, with fair level of agreement (κ=0.224), with highly significant statistical difference (P<0.0001) ([Table 3]).
    Table 3 Agreement between fluid-attenuated inversion recovery-MRI and double inversion recovery-MRI results regarding diagnostic accuracy parameters

    Click here to view
  4. We analyzed and compared 40 (paired) patients with MS with white matter lesions according to the serial MRI sequences (T2, FLAIR, and DIR).
  5. A comparative study between serial MRI sequences revealed a highly significant increase in detected number of white matter lesions in FLAIR and DIR-MRI sequences (P=0.0007). The comparative study also revealed a nonsignificant difference in detection rate in all 3 MRI sequences (P>0.05) ([Table 4]; [Figure 1]).
    Table 4 Comparison between 40 patients with white matter multiple sclerosis regarding serial MRI sequences

    Click here to view
    Figure 1 Comparison between 29 patients with multiple sclerosis having gray matter lesions regarding serial MRI sequences (detection rate).

    Click here to view


We analyzed and compared 29 (paired) patients with MS with gray matter lesions according to the serial MRI sequences (T2, FLAIR, and DIR):
  1. A comparative study between serial MRI sequences revealed a significant increase in detected number of gray matter lesions in DIR-MRI sequences (P=0.021). The comparative study also revealed a highly significant increase in detection rate in DIR-MRI sequences compared with T2 and FLAIR-MRI sequences (P<0.001) ([Table 5]; [Figure 2]).
    Table 5 Comparison between 29 patients with multiple sclerosis having gray matter lesions regarding serial MRI sequences

    Click here to view
    Figure 2 Comparison between 29 patients with multiple sclerosis having gray matter lesions regarding serial MRI sequences (detection rate).

    Click here to view


We calculated the predictive value of each MRI sequence modality regarding detection of gray matter lesions using ROC curve analysis:
  1. By using ROC curve analysis, T2-MRI sequences failed to discriminate patients with gray matter lesions from patients without, with failed accuracy, having sensitivity of 17% and specificity of 100% (P=0.051).
  2. By using ROC curve analysis, FLAIR-MRI sequences discriminated patients with gray matter lesions from patients without, with poor accuracy, having sensitivity of 34% and specificity of 100% (P<0.0001).
  3. By using ROC curve analysis, DIR-MRI sequences discriminated patients with gray matter lesions from patients without, with perfect accuracy, having sensitivity of 100% and specificity of 100% (P<0.0001) ([Table 6]; [Figure 3]).
    Table 6 Receiver operating characteristic curve analysis to predict patients with gray matter lesions (n=29) from patients with white matter lesions (n=11)

    Click here to view
    Figure 3 Comparison of receiver operating characteristic curves of the three MRI sequences.

    Click here to view



  Discussion Top


MS is the most common chronic inflammatory disease of the central nervous system in young adults and is characterized by the presence of multifocal inflammatory demyelinating lesions disseminated in space and in time. Although MS has been considered a disease primarily affecting the white matter, it has been conclusively shown that MS lesions occur abundantly in the gray matter as well [12].

MRI is a valuable diagnostic tool that is able to noninvasively show demyelinating lesions in the brain and spinal cord. Pulse sequences like FLAIR and double inversion recovery (DIR) suppress the signal of CSF, whereas DIR also attenuates the signal of white matter (WM), and have proved to be more sensitive for brain lesions in WM and gray matter (GM) than proton density (PD) or T2-weighted (T2w) and T1-weighted (T1w) MR sequences at 1.5 and 3.0 T [13].

The main interest of our study is to detect gray matter lesions in patients known to have multiple sclerosis using the conventional magnetic resonance imaging especially (T2 and FLAIR) sequences and double inversion recovery, which is better in detecting the cortical and juxta-cortical MS lesions more than the conventional MRI alone.

In fact, DIR improves the specificity of MRI in detection of the gray matter lesions and helps better in the diagnosis of the MS.

The present study included 40 patients. All were diagnosed as having RRMS and on follow-up. They included 20 (50%) female and 20 (50%) male patients, and their ages ranged between 17 and 52 years. The most commonly affected age was between 30 and 40 years (36.67%).

The patients in the age group between 40 and 52 years in our study were cases known to have MS since the age of 30 years and on follow-up.

In the present study, the DIR sequence achieved an improvement in the image contrast ratio between the MS lesions and the surroundings compared with the corresponding T2WI and FLAIR imaging, as the DIR imaging provided higher image contrast ratios between lesions and the normal-appearing gray matter in all anatomic locations compared with FLAIR and T2WI imaging. Moreover, DIR imaging provided better delineation of the white matter lesions with higher contrast between the lesion and the normal-appearing white matter.

By using the DIR sequence, 29 cases of 40 cases in our study were found to have gray matter lesions besides having white matter lesions, and by this sequence, we can differentiate whether the lesion was pure cortical in the gray matter or mixed gray/white matter or juxta-cortical (which just abuts the cortex).

In our study DIR sequence detect more numbers of total lesions than T2 or FLAIR as DIR detect 29 cases approved to have gray matter lesions.

The only artifact found by using DIR sequence was the presence of hyper-intense areas, especially in posterior fossa, and this is in agreement with the study by Wattjes et al. [14], which reported that the DIR images showed slightly more artifacts in the posterior fossa in terms of vascular and flow artifacts than the corresponding FLAIR and T2 TSE images. However, those artifacts did not impair the diagnostic quality compared with the FLAIR and T2 TSE images. The attenuation of the CSF was sufficient and similar on the FLAIR and DIR images [14].

The findings of our present study were in agreement with the findings reported in the study by Simon et al. [12], which reported that the DIR showed greater benefit in the detection of pure intracortical lesions compared with FLAIR or conventional T2WI sequences at both 1.5 and 3 T, and they also reported that these findings were mainly based on two different observations: on a better contrast between lesions and the surrounding normal-appearing gray matter owing to a slight attenuation of the cortex itself on DIR and also because of a better distinction between pure cortical and juxta-cortical lesions on DIR images.

Madelin et al. [15] demonstrated the feasibility of DIR with CSF and fat suppression at high-field MRI, and they recommended that future studies will focus on the improvement of image homogeneity at 7 T and on the assessment of the cortex in neurological disorders.

Our study findings were consistent with the findings reported by Geurts [7] regarding the total number of MS lesions, where the DIR showed higher number of MS lesions compared with T2WI.

The study by de Graaf [13] reported that the DIR showed more intracortical lesions (nine lesions) compared with FLAIR sequence (six lesions) and T2WI (three lesions).

Regarding the total number of supratentorial MS lesions in our study, the DIR showed higher number of lesions compared with T2WI and FLAIR sequences. The supratentorial lesions were categorized according to their anatomic location into white matter lesions (noted in the periventricular, deep white matter and juxtacortical) and intracortical lesions.

These findings were in agreement with those reported by Geurts et al. [7] and Simon et al. [14] where the DIR showed higher number of supra-tentorial lesions compared with T2WI and FLAIR sequences and the lesions were also categorized in the same manner, but they added a category including mixed white matter- gray matter lesions.

Geurts [7] found that MR imaging with 3D DIR enabled increasing ICL detection in the MS brain, as well as improved distinction between juxta cortical and white matter-gray matter lesions and also DIR imaging enabled a better definition of mixed white matter–gray matter lesions because of greater contrast between the lesion and its surroundings. Moreover, they found regarding the number of lesions that there was no difference between DIR and FLAIR sequences but the DIR sequence detected more number of lesions than T2 sequence [7].

The study by Simon [12] reported that the DIR showed greater benefit in the detection of pure intracortical lesions compared with FLAIR or conventional T2WI sequences at both 1.5 and 3 T, as at 1.5 T, the DIR revealed 26 intracortical lesions compared with seven lesions detected by T2WI and 10 lesions detected by FLAIR, and on 3 T. the DIR revealed 76 intracortical lesions compared with 13 lesions detected by FLAIR and five lesions detected by T2WI. He reported that this finding was mainly based on two different observations: on a better contrast between lesions and the surrounding normal-appearing gray matter owing to a slight attenuation of the cortex itself on DIR, and also because of a better distinction between pure cortical and juxta-cortical lesions on DIR images [12].

The study by Filippi reported that DIR imaging depicted more ICLs than standard MR imaging techniques such as conventional T2-weighted and FLAIR sequences. The increased contrast between lesions and their surroundings resulted in an improved distinction between juxtacortical and mixed WM-GM lesions. With DIR sequences, ICLs have been detected in all the major MS clinical phenotypes [8].

Calabrese [16] found that types of cortical lesions on a double inversion recovery sequence can be artifact ribbon-like hyperintense areas located in extracortical regions, sometimes bilateral and symmetric; round or ovoid ICLs; worm-shaped ICLs; wedge-shaped ICLs with a subpial base and the apex toward the white matter; and cluster of microgranular spot-like lesions that involve several gyri.These findings were in agreement with our study cases to some extent, as in our cases, we found on DIR images some hyperintense areas of artifacts, wedge shaped, microgranular spot like, round and ovoid ICLs.

Regarding the infratentorial region in our present study, we find better detection, delineation, and increase in number of lesions detected in cerebellum and brain stem. These findings were in agreement with the study by Wattjes which reported that DIR brain imaging at 3 T provides the highest sensitivity in the detection of MS lesions especially in the infratentorial region.

Wattjes [14] differed in their findings from our study as they reported a higher number of juxta-cortical lesions detected by the 3 T FLAIR imaging and a higher number of mixed gray white matter lesions on DIR imaging. Then they referred that the cause of decreased number of juxtacortical lesions with DIR imaging is the sharp delineation between gray and white matter on the DIR, which allows a very stringent differentiation between purely juxtacortical lesions and lesions already touching the cortical area. Therefore, some of the lesions initially identified as juxtacortical lesions on the FLAIR and T2 TSE have to be categorized as mixed white matter-gray matter lesions on the DIR, leading to lower numbers of juxtacortical and higher numbers of mixed white matter-gray matter lesions [14].

The overall findings in our study were in agreement with the findings reported by the other studies regarding the value of DIR sequence in detecting more MS lesions than the T2WI and the FLAIR sequences. However, there were some differences concerning the relative ratio measurements, and these differences may be attributing to the fact that the present study was done on 1.5 T MR system, but the study by Wattjes was done on 3 T MR system, the study by Simon was done on both 1.5 and 3 T MR system, the study by de Graaf and colleagues was done on 7 T, and the study by Madelin and colleagues was done using DIR with fat suppression.


  Conclusion Top


The DIR is a valuable MRI sequence in imaging of MS because of the following: (a) It showed better delineation between the white matter, the gray matter, and the MS lesions owing to its high image contrast measurements; (b) it detected more MS lesions compared with T2WI and FLAIR sequences in all anatomic locations; (c) it revealed more periventricular and juxta-cortical MS lesions, which are characteristic for MS; and (d) it detected more intra-cortical lesions as well, which should be considered in all patients with MS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Frohman EM, Racke MK, Raine CS. Multiple sclerosis − the plaque and its pathogenesis. N Engl J Med 2006; 354:942–955.  Back to cited text no. 1
    
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Lucchinetti CF. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 2011; 365:2188–2197.  Back to cited text no. 3
    
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Rocca MA. Thalamic damage and long-term progression of disability in multiple sclerosis. Radiology 2010; 257:463–469.  Back to cited text no. 4
    
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Simon B. Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla. Eur Radiol 2010; 20:1675–1683.  Back to cited text no. 12
    
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De Graaf WL. Lesion detection at seven Tesla in multiple sclerosis using magnetisation prepared 3D-FLAIR and 3D-DIR. Eur Radiol 2012; 22:221–231.  Back to cited text no. 13
    
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Wattjes M, Double inversion recovery brain imaging at 3T: diagnostic value in the detection of multiple sclerosis lesions. Am J Neuroradiol 2007; 28:54–59.  Back to cited text no. 14
    
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Madelin G, Inglese M, Oesingmann N. Double inversion recovery MRI with fat suppression at 3T and 7T. Proc Intl Soc Mag Reson Med 2008; 20:87–92.  Back to cited text no. 15
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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