The imaging progress of ECTRIMS 2021 MS

On October 13-15, 2021, the 37th European Committee on Treatment and Research of Multiple Sclerosis (ECTRIMS 2021) will be held online
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The application of MRI and the continuous exploration of imaging biomaker are playing an increasingly important role in the diagnosis and treatment of multiple sclerosis (MS).
The exploration of imaging applications is also a topic of concern in this conference
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MRI helps redefine MS subtypes.
In real world and clinical research, the activity of MRI lesions can be more sensitive to assess disease activity than clinical recurrence1
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MS is a progressive disease, and patients can progress from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS)
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SPMS patients can be divided into active (aSPMS) and inactive (naSPMS) according to whether the disease is active
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However, in the real world and clinical research, the significance of the activity and/or recurrence of the lesion in magnetic resonance imaging (MRI) in judging clinical activity remains to be further studied
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Professor Gavin Giovannoni from Queen Mary University of London, UK, conducted research on this issue and released the results of the research at the ECTRIMS conference
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 In the Adelphi Real World MS Disease Special Project (DSP), SPMS patients (3580 cases) were divided into aSPMS cohort (most recent MRI ≥ 1 new lesion and/or recurrence ≥ 1 time in the past 12 months; n=1889) And naSPMS cohort (no new lesions and no recurrence in the past 12 months; n=665)
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In the EXPAND study, a total of 1652 patients were enrolled.
Patients with ≥1 recurrence and/or MRI ≥1 enhancement lesions at baseline at baseline were classified as aSPMS (n=779), and those who were in the screening Patients who did not relapse within the first 2 years and had no enhancement lesions on MRI at baseline were classified as naSPMS (n=866)
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At baseline, 263 patients in the placebo group were aSPMS and 283 were naSPMS; during the study period, evidence of disease activity was assessed by periodic MRI (checked up once a year) or MRI at recurrence (checked when recurrence occurred)
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 Adelphi’s real-world MS DSP study showed that in the past 12 months, naSPMS patients (compared to aSPMS) had higher Extended Disability Status Scale (EDSS) scores and received fewer MRI examinations (the proportion of MRI examinations) Lower, and the number of MRI scans done by each person is less)
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These patients (compared to aSPMS) have a higher proportion of moderate to severe disease (as assessed by clinicians) and have not received any disease modifying treatment (DMT)
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In addition, the study also found that for patients with aSPMS, disease activity is more often found in regular MRI rather than in clinical recurrence checks
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In addition, the EXPAND study found that in the placebo group, more than 50% of patients who were classified as naSPMS at baseline were found to have disease activity during follow-up, and MRI is more sensitive to determine disease activity than clinical relapse Method
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In summary, the above studies suggest that MRI is a more sensitive tool for assessing disease activity than recurrence
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In Adelphi real-world MS DSP, although nsSPMS patients have a higher severity of disease and a large proportion of patients did not receive any DMT treatment, the naSPMS cohort received MRI examination rates much lower than the aSPMS cohort, making the naSPMS cohort detect the disease The chance of mobility decreases and the chance of follow-up treatment decreases, so this issue should be paid attention to
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In addition, the EXPAND study showed that more than 50% of patients who were classified as naSPMS at baseline were found to have disease activity during follow-up
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This shows that it is still difficult to accurately define aSPMS and naSPMS.
Defining patients as naSPMS has potential negative effects, leading to poor management of SPMS patients, which requires attention
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The application of MRI in European countries.
Northern Ireland studies have shown that MRI plays a key role in the management of MS2
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MRI can provide objective and quantitative information on the burden of lesions in MS patients, and can also monitor adverse events, the results of which can affect DMT decision-making
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In order to evaluate the use of MRI by MS physicians in Northern Ireland, S Ramsay et al.
conducted the following research and published the results at the ECTRIMS conference
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 The study analyzed 300 patients, of which 274 had MRI data
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The indications for patients receiving MRI scans were analyzed: 29% were check recurrences, 54% were regular monitoring, 6% were DMT baseline scans, 7% were diagnostic work, and 2% were progressive multifocal leukoencephalopathy (PML).
) Monitoring
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The MRI scans of 268 patients were different.
Of these, 29% only scanned the brain, 3% only scanned the spinal cord, and 68% scanned the brain and spinal cord
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Analysis of the activity of 274 cases of MRI scans: 61% had no new lesions, 25% had new lesions, only 1% found enlarged lesions, and 13% lacked previous comparable imaging
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Gadolinium was used in 115 scans
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Among patients who did not receive DMT treatment, 62% had active MRI lesions
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Of the 79 relapsed patients, 42% had new/enlarged lesions
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Of the 148 scans that were regularly monitored, 15% had new/enlarged lesions
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Compared with a single brain scan and a single spinal cord scan, the combined scan of the brain and spinal cord has a higher detection rate of active lesions (18%, 14%, and 30%, respectively)
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However, after analysis, compared with scanning only the brain, combined scanning of the brain and spinal cord in the recurrence check (p=0.
71) or routine monitoring (p=0.
28) did not significantly increase the detection rate of active lesions
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Among the 13 patients treated with natalizumab, 62% of patients needed to be monitored for PML (in line with the MAGNISM definition), and this proportion increased to 75% in high-risk patients
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Of the 274 patients who underwent MRI scans, 14% (37 cases) had received a DMT upgrade, and 12% (33 cases) were waiting for further examination after the scan
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71 scans showed new/enlarged lesions, and 70 patients had changed or may change the treatment plan
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 This study suggests that for MS patients in Northern Ireland, MRI is most commonly used for routine monitoring of the disease, followed by monitoring for clinical recurrence
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Most MRI detection uses a combined scan of the brain and spinal cord, but this method may not increase the detection rate of active lesions
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Therefore, the clinically determined scan is the key
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In general, MRI scans are crucial in the management of MS, and the rational use of this resource in clinical practice is the key
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The unique clinical value of the imaging Biomarker.
Central venous sign can be used as an imaging marker for the diagnosis of MS3
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The accurate diagnosis of MS is the first step in the MS management process, but it is also a challenging step
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For MS patients with abnormal brain MRI and atypical clinical symptoms, it is necessary to strictly abide by the diagnostic criteria for multiple sclerosis, and further clinical, laboratory, and radiological evaluations are necessary to help confirm the diagnosis
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Central venous sign (CVS) can become a new indicator for the diagnosis of multiple sclerosis
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The role of vascular changes in MS has been mentioned as early as the 1860s
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In 2000, Tan et al.
used the T2 sequence to find for the first time that MS lesions were mostly located around veins
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Since then, the vein imaging technology has also been greatly improved
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A study using high-field MRI to image the central vein of brain lesions showed that if the proportion of lesions with central venous signs is greater than 40%, the patient is considered to have MS, and if the proportion of such lesions is less than 40%, the patient is considered to be a patient Not suffering from MS
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The North American MS Imaging Cooperation Organization (NAIMS) has clarified the definition of the central venous sign.
When the following conditions are met in the T2 sequence image, the central vein can be considered to exist: a thin line or small dot with low signal; Seen on the MRI plane and displayed as a thin line on at least one plane (diameter <2mm); part or all of it passes through the lesion; regardless of the shape of the lesion, the vein is located in the center of the lesion (that is, located approximately equidistant from the edge of the lesion) , And cross the edge in no more than two places)
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Exclusion criteria for central venous sign: lesions with a diameter of less than 3mm in any plane, poor visibility of the lesions (due to movement or other artifacts)
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The difference of MRI scanner does not affect the detection of central venous sign
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Studies have evaluated the ability of the central venous sign as an imaging marker for the diagnosis of MS
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The results showed that 54.
2% of CIS patients had central venous lesions, and the median number of lesions was 3; 47.
4% of MS patients had central venous lesions, and the median number of lesions was 4
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In NMOSD, systemic lupus erythematosus (SLE), migraine and cluster headache, diabetes and the elderly control group, the proportions of patients with central venous lesions were 16.
7%, 20.
4%, 17.
4%, and 15.
0%, respectively.
The number of lesions The medians are 0, 1, 1, and 0 respectively
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It suggests that the central venous sign is more common in MS patients
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Taken together, the central venous sign has broad prospects as an imaging marker for the diagnosis of MS
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Iron ring lesions are associated with long-term disability in MS5
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In MS, short-term studies have found that white matter lesions surrounded by iron rings (IR) are associated with more severe clinical manifestations, but long-term studies are still lacking
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A.
Altokhis et al.
conducted a 10-year observational study to investigate whether the presence and frequency of IR lesions (IRL) in CIS and MS patients is related to more severe disability
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The results showed that a total of 132 IRL was found in 41 patients at baseline (median 2, IQR1-5)
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At follow-up, among 57 patients with RRMS and CIS, 18 had progressed to SPMS (50% IR+) and 39 had not developed progressive disease (33% IR+)
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At baseline and follow-up, patients with IR lesions had higher median EDSS scores and age-related multiple sclerosis severity (ARMSS) scores
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Even after adjusting for the course of the disease, the number of IRLs at baseline is a predictor of the EDSS score after 10 years (p=0.
005)
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This study shows that IRL assessed using 7T is associated with clinical disability at baseline and 10 years later
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Patients with IRL had an average of 1 higher ARMSS/EDSS than patients without IRL
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Whether DMT can affect the development of IR lesions remains to be further studied
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 The fusion of 11C-PBR28 PET and MRI revealed that there is a correlation between activated microglia in the white matter of MS and myelin content 6
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Activated microglia have both destructive and protective effects on myelination
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Valeria Barletta and others combined 11C-PBR28 PET and MRI technology to study the relationship between the changes in myelin content, microglia activation and myelination in active and inactive WM lesions in MS patients at different stages.
And the relationship between microglia activation and demyelination and clinical outcomes
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The results showed that white matter (WM) surrounding active lesions had lower myelin content than inactive lesions (p=0.
003), but there was no significant difference compared with white matter lesions (WML) and normal-appearing white matter (NAWM)
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Voxel analysis showed that the pseudo-reference zone (SUVR) of several WM regions was negatively correlated with myelin content (p<0.
05)
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Neurological disability is related to the increase of SUVR in all WM areas and the low myelin content of WM and NAWM (but not WML) around the lesion; the lower information processing speed is related to the low myelin content of NAWM
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This study suggests that 11C-PBR28 PET is a practical tool to detect inflammatory activity in MS WM.
Inflammatory activity in WM (especially WM around the lesion) shows an adverse effect on myelination
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This finding highlights the importance of surrounding tissues in the progression of MS
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Since both myelin content and 11C-PBR28 intake are related to clinical disability, preventing the occurrence of WML is still the main goal of disease management
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MRI standardization and the definition of MS curative effect MRI can be used for MS disease diagnosis and curative effect monitoring4
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What are the standardized MRI acquisition procedures for diagnosis and treatment efficacy monitoring? For diagnosis, brain MRI and spinal cord MRI are mainly performed: ➤Brain MRI: Contrast agent should be injected first, followed by scanning with PD-TSE, T2-FLAIR and T1-Gd sequences
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The injection of contrast agent and the T1-Gd sequence scan should be separated by at least 5 minutes
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The recommended magnetic field strength is 3T, the spatial resolution is 3D, or a high-quality 2D sequence
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➤MRI of the spinal cord: a contrast agent (double dose) should also be injected first
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It is recommended to use sagittal T2 weighting, proton density (PD) weighting, and sagittal T1 weighting sequence (at least 5 minutes apart from the injection of contrast agent)
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If conditions permit, the axis T2 weighted sequence can also be used
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The recommended magnetic field strength is 1.
5T, and the spatial resolution is 2D
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It is very important to double the dose of contrast agent in spinal cord MRI.
The sensitivity of PD and STIR sequences is much higher than that of T2-weighted sequences
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For the monitoring of MS, consensus recommends that initial MRI should be performed before diagnosis and treatment, the baseline should be reset after 3-6 months of treatment, and the first follow-up should be performed 12 months after the baseline reset, and 24 months later Follow-up for the second time and then every year thereafter
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It is only recommended to use MRI-gadolinium-enhanced scan at the beginning, after which enhanced scan is not necessary
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It is also recommended that even patients with stable conditions should be followed up annually if conditions permit
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Is MRI the best way to rule out other diagnoses? How can MS be differentiated from other diseases, such as cerebrovascular disease, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease? MRI is a very promising diagnosis and treatment technique
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In terms of imaging diagnosis, perhaps the most challenging is to distinguish MS from small vessel disease, because the imaging findings of the two are similar
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In addition, some patients (especially migraine) have the same demographic characteristics as MS, which makes the differential diagnosis more difficult
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One of the main points of identification is the distribution of lesions
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Small vessel disease involves deeper white matter, and the periventricular lesions are mostly/more cup-shaped and curved.
Subtentorial lesions are usually symmetrical and develop in a concentric manner (the lesions develop in an eccentric manner in MS)
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In addition, it can also be identified by combining 3D FLAIR and SWI (called FLAIR*)
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FLAIR* can present central venous signs well and can distinguish MS from other types of diseases in the clinic
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How to define the success or failure of treatment? In rheumatology immunology, no evidence of disease activity (NEDA) has been identified as the goal of clinical research and patient care
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NEDA may also be applied to MS to assess the success or failure of treatment
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Expert comment on expert profile Professor Liu Yaou, Doctor of Medicine, Chief Physician, Head of Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Young Beijing Scholar, Double Ph.
D.
(Capital Medical University of China 2013, Vrije Universiteit Amsterdam 2017) Main social position Editor of "Neuroradiology", a member of the Central Committee of the Asia-Pacific Society of Multiple Sclerosis, presided over 5 projects from the National Natural Science Foundation and Beijing Natural Science Foundation.
, Beijing’s “High Innovation Program” young top-notch talents published more than 130 articles, with a cumulative impact factor of more than 500.
Imaging provides clinicians with a new perspective from understanding multiple sclerosis (MS), an inflammatory demyelinating and neurodegenerative disease
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This European Multiple Sclerosis Treatment and Research Council Conference (ECTRIMS 2021) also brought many new developments in imaging
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 Research by Professor Gavin Giovannoni from Queen Mary University of London, UK suggests that MRI active lesions are a more sensitive tool for assessing disease activity than clinical assessment of recurrence.
In the future, the definition of MS subtypes may rely more on MRI assessment
.

As a relatively high-cost examination technology, what is the utilization and value output of MRI in clinical practice? Northern Ireland studies have shown that MRI plays a key role in the management of MS disease, but combined brain and spinal cord scanning may not improve the detection rate of active lesions
.

Therefore, the rational application of this technology in clinical practice is the key
.

In addition, with the development of imaging technology, studies have found that the central venous sign has a unique value for the diagnosis of MS.
This sign can be used as a relatively specific MS imaging marker and has broad prospects in the future
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The conference also focused on the steps of MRI standardized acquisition in the 2021 latest MAGNIMS imaging guide
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Under the premise of standardized acquisition, the results of MRI will directly affect the clinical judgment of the success or failure of the treatment
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Based on the pathological nature of the coexistence of MS demyelination and inflammatory activities, the advanced imaging technology combined with 11C-PBR28 PET and MRI can simultaneously show the activation of microglia and changes in myelin content
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 The continuous exploration of imaging allows us to see more insights, to look at MS from a pathological perspective, and to provide indispensable and important information for clinical diagnosis, disease monitoring, subtype classification, and treatment success or failure
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References: 1.
Giovannoni G, et al.
MRI Activity versus Relapses as Markers of DiseaseActivity in SPMS: Data from Real World and Pivotal Clinical Studies.
ECTRIMS2021.
2.
Ramsay S.
Evaluating the use and impact of Magnetic ResonanceImaging in the management of Multiple Sclerosis in Northern Ireland.
ECTRIMS2021.
3.
Evangelou N.
The central vein sign and its diagnostic contribution to MS.
ECTRIMS 2021.
4.
Meet Expert 2: MRI in clinical practice: lesions, atrophy and beyond.
ECTRIMS 2021.
5.
Altokhis A, et al.
Clinical longitudinal study of iron rims in whitematter MS lesions.
ECTRIMS 2021.
6.
Barletta V, et al.
Multimodal imaging with 11C-PBR28 MR-PET and synthetic MRI reveals a direct association between activated microglia and myelin content in the MS brain white matter.
ECTRIMS 2021.