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. 2017 Apr 28;30(4):347–351. doi: 10.1177/1971400916678224

Comparison of diffusion-weighted imaging and enhanced T1-weighted sequencing in patients with multiple sclerosis

Amin Abolhasani Foroughi 1, Roohollah Salahi 1,✉, Alireza Nikseresht 2, Hora Heidari 2, Masoume Nazeri 2, Ali Khorsand 1
PMCID: PMC5524272  PMID: 28452571

Abstract

Introduction

The purpose of this study was to assess whether demographic, brain anatomical regions and contrast enhancement show differences in multiple sclerosis (MS) patients with increased diffusion lesions (ID group) compared with diffusion restriction (DR group).

Method

MRI protocol comprised T1- and T2-weighted sequences with and without gadolinium (Gd), and sagittal three-dimensional FLAIR sequence, DWI and ADC maps were prospectively performed in 126 MS patients from January to December 2015. The investigation was conducted to evaluate differences in demographic, cord and brain regional, technical, and positive or negative Gd contrast imaging parameters in two groups of ID and DR. Statistical analysis was performed by using SPSS.

Results

A total of 9.6% of patients showed DR. In the DR group, 66.6% of the patients showed contrast enhancement of plaques, whereas 29.2% of the IR group showed enhancement of plaques. The most prevalent group was non-enhanced plaques in the ID group, followed by Gd-enhanced plaques in the ID group. Patients in the ID group (90.4%) were significantly more than in the DR group (9.6%). Out of the 40 patients with Gd-enhanced plaques, 80.5% was from the ID group and 19.5% from the DR group.

Conclusion

MRI of the brain, unlike of the cord, with Gd demonstrates significant difference in enhancement between the two groups (p < 0.05).

No significant difference was seen in demographic, cord and brain regional, and technical parameters, EDSS, disease duration, and attack rate as well as demographic and regional parameters between the ID and decrease diffusion groups (p > 0.05).

Keywords: Multiple sclerosis, diffusion-weighted imaging, increased diffusion, diffusion restriction

Introduction

Multiple sclerosis (MS), a chronic inflammatory-demyelinating neurodegenerative disease, is a major cause of neurological disability in young adults, which is estimated to affect about 2.5 million patients around the world.1–4 MS has been recognized as a progressive disorder that may develop at any age, but most people are diagnosed at age ranges of 20 to 40 years.5,6 MS is pathologically characterized by lesions with respect to the presence of inflammation, demyelination, axonal loss, and gliosis scattered throughout the brain and spinal cord.7 MS is clinically classified as relapsing–remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and relapsing–progressing (RPMS).8

Although diagnosis of MS is still based on clinical findings, magnetic resonance imaging (MRI) is very sensitive in detecting distribution in space and time of demyelinating lesions in the brain and spinal cord and is now integrated in the diagnostic criteria of the disease.2,9 Serial T1- and T2-weighted imaging with gadolinium (Gd)-enhanced contrast have been recognized as sensitive imaging for diagnosing silent MS lesions, and active enhanced MS plaques in post-Gd MRI is believed to be due to immune cell migration across the blood-brain barrier and active inflammation.10,11 MS plaques are iso- or hypointense on T1 images, and hyperintense on T2 images compared to normal white matter.12 T2-weighted MRI is one of the most sensitive imaging techniques for MS plaque detection. Several MS plaques reveal Gd-enhanced contrast that correlates with inflammation and injury to the blood-brain barrier.13

Diffusion-weighted imaging (DWI) can differentiate various pathologies such as ischemia, infection and tumor by measurement of microscopic motion of water molecules.14,15 Studies have declared that apparent diffusion coefficient (ADC) can detect diffusion abnormalities in MS plaques.16–22 Therefore, we designed this study to compare DWI and enhanced T1-weighted sequencing in patients with MS.

Previous studies have compared DWI with Gd-enhanced sequences; however, the sample volume was small and, despite the prevalence of MS in our center, which is the referral center in the south of Iran, we haven’t sufficient data about this information. This investigation was conducted to answer the question whether there is a correlation between enhancement and the diffusion restriction of MS plaques in MR imaging of MS patients.

Materials and methods

Participants

A total of 126 patients with clinically definite MS9 who were referred by neurologists to our center to undergo brain MRI were included in a single-center study from January to December 2015. Demographic parameters, including sex, duration of disease, family history, type of consumed drug and attack rate were, determined. In this study, 103 individuals were women and the rest were men with mean disease duration of 4.67 ± 4.92 years. Expanded Disability Status Scale (EDSS) score was measured for all patients.

MRI protocol

All patients underwent MRI using a 1.5 Tesla MR system (Siemens, Magnetum Avantto) and phased-array head coil. Conventional MRI protocol comprised a T1-weighted (repetition time (TR)/echo time (TE) = 400/9 ms; slice thickness = 7 mm) sequence with and without Gd, T2-weighted contrasts (TR/TE = 3730/91 ms; slice thickness = 7 mm), and sagittal three-dimensional fluid-attenuated inversion recovery (FLAIR) sequences (TR/TE = 6000/355 ms; flip angle = 120 degrees; slice thickness = 1 mm) of brain images were obtained. The images were obtained on a 384 × 225 matrix after a single excitation.

Also, sagittal and axial T1-weighted with and without Gd, two-dimensional T2-weighted and proton density (PD) MRI of the spinal cord were performed. DWI images were obtained (TR/TE = 3500/136 ms; flip angle = 90 degrees; field of view (FOV) = 150 × 230; slice thickness = 7 mm).

Each set of images was reviewed by two expert radiologists. MS plaques were described according to the site of more commonly involved brain regions in MS patients (cerebral white matter, posterior fossa, and corpus callosum), its signal and enhancement. MS lesions with iso- or hypointense signals in ADC sequences were considered as diffusion restricted (DR), while MS lesions with hyperintense signals were determined as increased diffusion (ID).

Relationship between diffusion measures and demographic, regional, and technical parameters

Demographic data, regional parameters and technical factors were recorded in a questionnaire form to evaluate the possible relation between these factors and diffusion restriction. Enhancement of plaques as well as the following data were also evaluated and recorded.

  • – Demographic parameters include sex, family history, type of consumed drugs, and type of MS;

  • – Regional parameters include involvement of cord and brain regions of cerebral white matter, posterior fossa, and corpus callosum);

  • – Technical parameters include positive or negative enhancement with Gd; and

  • – Disease duration, attack rate and EDSS differences were assessed in MS patients.

Patients were divided into two groups according to types of restriction, i.e. patients with DR plaques and individuals with ID of plaques. The mentioned data (including demographic, regional, technical, disease duration, attack rate and EDSS) were compared between the two groups to know the possible effect of these data on diffusion restriction. Also, by comparing the rate of enhancement of plaques in the two groups, we aimed to detect a probable relation between the enhancement of plaques and diffusion restriction.

Statistical analysis

Data were expressed as mean ± SD. Statistical analysis was performed using SPSS software version 22 (Chicago, IL, USA). Differences between the studied groups were analyzed by chi-square Pearson and Fisher’s exact test, as well as Mann-Whitney test using two-tailed p values.

The ethics committee approved our study design and written informed consents were obtained from all patients.

Results

The relationship between demographic parameters and DWI of MS patients are presented in Table 1. Mann-Whitney statistical test revealed that there was no significant differences in EDSS, disease duration and attack rate between MS patients in the ID and DR groups (p > 0.05). According to the results of this study, we found that there was not a significant association between the treatment (including interferon, immunosuppressant drug, interferon plus immunosuppressants, and fingolimod) and restriction of disease in whole types of different MS types (Table 1, p > 0.05).

Table 1.

Demographic and clinical characteristics of patients with multiple sclerosis.

Variables Diffusion
 p value
Increase Restriction
Demographic parameters Sex Female 94 (91.3%) 9 (8.7%) 0.525
Male 20 (87%) 3 (13%)
Family history Positive 16 (100%) 0 (0%) 0.583
Type of consumed drug None 17 (77.3%) 5 (22.7%) –
Interferons 82 (93.2%) 6 (6.8%)
Immunosuppressants 2 (66.7%) 1 (33.3%)
Interferons plus immunosuppressants 9 (100%) 0 (0%)
Fingolimod 3 (100%) 0 (0%)
Type of MS First attack 10 (76.9%) 3 (23.1%) –
RRMS 98 (93.3%) 7 (6.7%)
SPMS 6 (85.7%) 1 (14.3%)
PRMS 0 (0%) 1 (100%)
Disease duration 4.82 (4.954) 3.5 (4.079) 0.347 0.347
Attack rate 2.15 (2.082) 1.6 (0.548) 0.985 0.985
EDSS 1.047 (0.9625) 0.8 (0.4472) 0.65 0.65
Technical parameters Brain MRI with gadolinium Enhanced 33 (80.5%) 8 (19.5%) 0.009
Regional parameters Cerebral white matter Involved 110 (90.2%) 12 (9.8%) 1.000
Posterior fossa Involved 62 (86.1%) 10 (13.9%) 0.058
Corpus callosum Involved 95 (89.6%) 11 (10.4%) 0.691
Cord Involved 82 (92.1%) 7 (7.9%) 0.371
Cord MRI with gadolinium Enhanced 9 (90%) 1 (10%) 0.931
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RRMS: relapsing–remitting multiple sclerosis; SPMS: secondary progressive multiple sclerosis; RPMS: relapsing–progressing multiple sclerosis; EDSS: Expanded Disability Status Scale; MRI: magnetic resonance imaging.

Evaluating regional differences between ID and DR groups, we demonstrated that involvement of the posterior fossa, as well as cerebral white matter and corpus callosum and spinal cord in the ID group, was not significantly different from the DR group (p > 0.05). Although, enhancement of plaques was significantly different between the two groups (p < 0.05), a valuable difference in cord imaging was not shown between the two studied groups (p > 0.05).

According to enhancement and diffusion pattern, we classified the patients into four groups including: non-enhanced plaques with increased diffusion group (n: 80), Gd-enhanced plaques with increased diffusion group (n: 33), Gd-enhanced plaques with decreased diffusion group (n: 8), non-enhanced plaques with decreased diffusion group (n: 5).

In patients in the IR group, 70.8% (80 out of 113 patients) did not show enhancement of plaques; however, 29.2% of the patients in this group (33 out of 113) had enhancement of plaques. In the DR group, 66.6% of the patients showed contrast enhancement of the plaques. Out of the 40 patients with Gd-enhanced plaques, 33 patients (80.5%) were from the IR group and eight patients (19.5%) were from the DR group.

Discussion

In this study, ID and DR patients with a history of RRMS, SPMS, PPMS and PRMS were studied for cerebral lesions, demonstrating no significant differences between the ID and DR groups in demographic, regional parameters, and technical parameters; however, enhancement of cerebral plaques was significantly different between the two groups (p < 0.05).

A total of 114 patients (90.4%) had restricted plaques, in contrast to 12 patients (9.6%) in whom plaques showed restricted diffusion. In the DR group, 66.6% of the patients showed contrast enhancement of the plaques, whereas 29.2% of the IR group showed enhancement of plaques. According to enhancement and diffusion pattern, the most prevalent group was non-enhanced plaques in the ID group, followed by Gd-enhanced plaques in the ID group. Patients in the IR group (90.4%) were significantly more than in the DR group (9.6%). Out of the 40 patients with Gd-enhanced plaques, 80.5% were from the IR group and 19.5% from the DR group.

According to the evidence, Yurtsever et al. demonstrated active MS plaques as hyperintense on DWI in RRMS and SPMS patients.23 These findings were consistent with data concluded by Roychowdhury et al.24 They showed that acute increase of apparent diffusion coefficients (ADC) may be associated with inflammation, astrocytic hyperplasia and edema, whereas demyelination and axonal damage underlie the chronic increase of ADC. In our study, like others, diffusion restriction was noted both in some enhanced and non-enhanced plaques and it is thought that this can be caused by restricted diffusion of protons within the plaques due to energetic failure or cytotoxic edema.13

Although there is a little literature on an association between EDSS and DWI findings, there is evidence indicating a non-significant correlation between diffusivity and EDSS, in accordance with our results.23,25,26 Yurtsever et al. revealed higher ADC values of normal white matter of the centrum semiovale and occipital horn in patients with MS compared to a control group, while no statistical significance between ADC values and EDSS at these regions was found.23,27 Otherwise, our study showed no statistically significant difference between type of MS and diffusion restriction that was the same as the results of Yurtsever et al.23

Regarding previous studies, Eisele et al. screened 72 consecutive patients with MS and evaluated the patients according to age, sex, disease duration/diagnosis, and maximum ADC. Their results emphasize the presence of a transient reduction of diffusion in acute MS lesions.28 In another study, Sbardella et al. acquired diffusion tensor imaging (DTI) sequences of the corpus callosum, internal capsule, posterior thalamic, cerebral peduncles and cerebellum, and found no correlation between global MRI measures and EDSS.29

Balashov et al. retrospectively compared MRI characteristics of RRMS patients with typical active symptomatic contrast-enhancing lesions with increased or normal diffusion in the patients. They assessed the patients with acute demyelinating lesions with restricted diffusion (ADLRD) and categorized them based on age/sex, type of MS, and MRI of the spinal cord. DWI could introduce ADLRD as a new variant of lesion in MS and suggests etiological heterogeneity in the development of acute MS lesions.30

The discrimination of diffusivity in patients with MS and healthy individuals creates a potential role for DWI to diagnosis and evaluate the treatment process. However, there was no investigation for declaration of the hypothesis whether a correlation exists between ID and diffusion restriction in MS patients. Therefore, this investigation tried to study the possible differences between MS patients in the ID and DR groups regarding demographic, technical and regional factors.

There were some limitations in our study, as our center was the only academic center in which DW images were available. Also, some patients did not agree to have their history taken by our neurologists.

For the first time, our study demonstrated that there were no significant differences in the most specific demographic, technical, and cord and brain regional parameters in MS patients in the ID and DR groups, and enhancement with and without Gd was relatively different in the two studied groups. Interestingly, our results may alter the prior assumption that diffusivity is increased in MS lesions. Further prospective studies can declare essential predisposing factors underlying DR in MS patients undergoing DWI.

Considering the low percentage of DR plaques in our study, this hypothesis came to us that diffusion restriction evolves rapidly to normal diffusion after a short time, but to our knowledge a definite duration has not been determined yet. Also, interestingly, we noticed that 95.2% of the patients with enhanced plaques were from the ID group, meaning that change of DR to ID is not at the same time that enhancement changes to loss of enhancement, i.e. enhancement of plaques persists for a longer duration than in decreased diffusion. Therefore, there should be some time relation between enhancement and diffusion of MS plaques in the course of the disease. To realize this time-relationship, we are preparing a prospective study to determine this time-dependent relation between change in enhancement and change in diffusion restriction in the course of the disease.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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