Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: The NeuroSTREAM MSBase study

Barnett, Michael; Bergsland, Niels; Weinstock‐Guttman, Bianca; Butzkueven, Helmut; Kalinčík, Tomáš; Desmond, Patricia; Gaillard, Frank; Pesch, Vincent Van; Özakbaş, Serkan; Rojas, Juan Ignacio; Boz, Cavit; Altıntaş, Ayşe; Wang, Chenyu; Dwyer, Michael G.; Yang, Suzie; Jakimovski, Dejan; Kyle, Kain; Ramasamy, Deepa P.; Zivadinov, Robert

doi:10.1016/j.nicl.2021.102802

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…No other MRI measures examined in this study on T2-FLAIR or 2D-T1-WI and 3D-T1-WI were associated with DP, including change in T2-LV, accumulation of new/enlarging T2 lesions, LVV enlargement and development of whole brain atrophy. This is in line with some other recent multicentre real-world studies of similar follow-up time,39 but different from those with longer follow-up17 that showed that changes in brain atrophy and lesion burden are associated with development of DP over mid-term follow-up, similar to what has been observed in other research studies 40…”

Section: Discussionsupporting

confidence: 90%

“…Previous approaches have focused on research-quality MRI, leaving a potential gap for reliable measurement on clinical-quality scans. T2-FLAIR MRI is a common denominator in clinical routine MS imaging, but current methods for thalamic volumetry are not applicable to it 17 18. Assessing GM, and in particular thalamic atrophy on conventional T2-FLAIR images would be particularly beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…Based on these premises, there is an increasing need to translate TV measurement into the clinical routine follow-up of MS patients, in order to allow more informed clinical and treatment decisions. Nevertheless, measurement of thalamic atrophy typically requires high-resolution three-dimensional (3D) T1-weighted images (WI), which frequently require prestandardisation of MRI protocols that are not common practice for many clinical centres, and are not easily applied to legacy clinical routine datasets outside of specific research studies or clinical trials, to better understand real-world observations 17 18. Although thalamic atrophy measurement is performed in some academic centres using reliable research tools like FMRIB’s Integrated Registration and Segmentation Tool (FIRST)19 and FreeSurfer,20 or Food and Drug Administration and CE (European Conformity) approved ones like NeuroQuant and Icometrix,21 22 these are primarily applicable to high-resolution 3D-T1-WI and generally require preplanned MRI protocols.…”

Section: Introductionmentioning

confidence: 99%

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Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-world study is associated with disability progression

Zivadinov

Bergsland

Jakimovski

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundThe thalamus is a key grey matter structure, and sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports indicated that thalamic volumetry using artificial intelligence (AI) on clinical-quality T2-fluid-attenuated inversion recovery (FLAIR) images alone is fast and reliable.ObjectiveTo investigate whether thalamic volume (TV) loss, measured longitudinally by AI, is associated with disability progression (DP) in patients with MS, participating in a large multicentre study.MethodsThe DeepGRAI (Deep Grey Rating via Artificial Intelligence) Registry is a multicentre (30 USA sites), longitudinal, observational, retrospective, real-word study of relapsing-remitting (RR) MS patients. Each centre enrolled between 30 and 35 patients. Brain MRI exams acquired at baseline and follow-up on 1.5T or 3T scanners with no prior standardisation were collected. TV measurement was performed on T2-FLAIR using DeepGRAI, and on two dimensional (D)-weighted and 3D T1-weighted images (WI) by using FMRIB’s Integrated Registration and Segmentation Tool software where possible.Results1002 RRMS patients were followed for an average of 2.6 years. Longitudinal TV analysis was more readily available on T2-FLAIR (96.1%), compared with 2D-T1-WI (61.8%) or 3D-T1-WI (33.2%). Over the follow-up, DeepGRAI TV loss was significantly higher in patients with DP, compared with those with disability improvement (DI) or disease stability (−1.35% in DP, −0.87% in DI and −0.57% in Stable, p=0.045, Bonferroni-adjusted, age-adjusted and follow-up time-adjusted analysis of covariance). In a regression model including MRI scanner change, age, sex, disease duration and follow-up time, DP was associated with DeepGRAI TV loss (p=0.022).ConclusionsThalamic atrophy measured by AI in a multicentre clinical routine real-word setting is associated with DP over mid-term follow-up.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-world study is associated with disability progression

Zivadinov

Bergsland

Jakimovski

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Other studies found that including ventricular cerebrospinal fluid (CSF) volume as an MRI-extracted metric in advanced statistical models increased the prediction of confirmed disability progression (Zivadinov et al, 2016). Also, higher change in lateral ventricular volume over time is associated with disease activity (Millward et al, 2020;Barnett et al, 2021). Recently, the choroid plexus (CP) within the lateral ventricles showed enlarged volumes in MS patients (Gauthier, 2023) and were found to occur in conjunction with chronic lesions and brain atrophy (Klistorner et al, 2022).…”

Section: Brain Regions Of Interestmentioning

confidence: 99%

A review on multiple sclerosis prognostic findings from imaging, inflammation, and mental health studies

Brasanac

Chien

2023

Front. Hum. Neurosci.

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Magnetic resonance imaging (MRI) of the brain is commonly used to detect where chronic and active lesions are in multiple sclerosis (MS). MRI is also extensively used as a tool to calculate and extrapolate brain health by way of volumetric analysis or advanced imaging techniques. In MS patients, psychiatric symptoms are common comorbidities, with depression being the main one. Even though these symptoms are a major determinant of quality of life in MS, they are often overlooked and undertreated. There has been evidence of bidirectional interactions between the course of MS and comorbid psychiatric symptoms. In order to mitigate disability progression in MS, treating psychiatric comorbidities should be investigated and optimized. New research for the prediction of disease states or phenotypes of disability have advanced, primarily due to new technologies and a better understanding of the aging brain.

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“…Conversely, Otero-Romero S et al showed that menopause did not modify disability trajectories in a longitudinal cohort of women with MS who were followed from disease onset, after controlling for age and disease duration ( 16 ), thereby leaving controversial aspects to be investigated. Additionally, even less explored are the effects of menopause on neuroradiological activity and brain volume measurements in women with MS, which are significantly related to long-term disability ( 17 ). With regard to the latter point, a longitudinal study has recently shown that ovarian aging, as defined by anti-Müllerian hormone (AMH) levels, is associated with greater clinical disability and grey matter loss in women with MS ( 18 ) and is independent of the chronological age and disease duration, highlighting the crucial role of sex hormones in MS disease outcomes ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Menopausal transition in multiple sclerosis: relationship with disease activity and brain volume measurements

Lorefice

Fenu²,

Fronza

et al. 2023

Front. Neurol.

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BackgroundRecent evidence has shown a significant association between menopause and multiple sclerosis (MS) progression. This study investigated the possible role of menopause in influencing MS from clinical and neuroradiological perspectives. Notably, the possible association between menopause and brain atrophy has been evaluated.Materials and methodsThis study included women with MS whose ages ranged from 45 to 55 years. Demographic and clinical characteristics were collected, and the reproductive phase was defined as non-menopausal or menopausal based on the final menstrual period. Thus, MS activity over the past year was reported as the annualised relapse rate (ARR), and MRI activity (defined as new T2 lesions and/or the presence of gadolinium-enhancing lesions at the last MRI assessment in comparison with the MRI performed within the previous 12 months) were compared between non-menopausal women (non-MW) and menopausal women (MW). Volume measurements of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated using the SIENAX software, and the possible relationship with menopausal status was assessed by regression analysis.ResultsThe study included 147 women with MS. Eighty-four (57.1%) were MW, with a mean age of 48.5 ± 4.3 years at menopause onset and a mean duration of menopause of 4.1 ± 1.1 years. When compared for ARR, MW reported a lower rate than the non-MW (ARR of 0.29 ± 0.4 vs. 0.52 ± 0.5; p < 0.01). MRI activity was observed in 13.1% of MW and 20.6% of non-MW (p = 0.03). Lower cortical GM volumes (578.1 ± 40.4 mL in MW vs. 596.9 ± 35.8 mL in non-MW; p < 0.01) have also been reported. Finally, multivariate analysis showed a significant association of lower ARR (p = 0.001) and cortical GM volume (p = 0.002) with menopausal status after correction for chronological age and other variables.DiscussionMenopause may be an adverse prognostic factor of MS. Our preliminary results suggest that menopause may facilitate cortical GM atrophy, probably due to a decline in the neuroprotective effects of estrogen, with negative effects on MS evolution.

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Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: The NeuroSTREAM MSBase study

Cited by 10 publications

References 40 publications

Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-world study is associated with disability progression

Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-world study is associated with disability progression

A review on multiple sclerosis prognostic findings from imaging, inflammation, and mental health studies

Menopausal transition in multiple sclerosis: relationship with disease activity and brain volume measurements

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