Essential clinical dry goods! Magnetic resonance performance of multiple sclerosis, summarized in an article

Combine pictures and texts to master MS imaging signs
.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that pathologically manifests itself with focal inflammation, demyelination, axon loss, and gliosis
.
"Polymultiple" refers to the multiple lesions in space (i.
e.
, multiple lesions in different regions of the brain) and time (i.
e
.
, lesions occurring at different times).

Magnetic resonance imaging (MRI) is one of the most important means to diagnose MS, which can objectively reflect the microscopic pathological changes of MS lesions and normal gray and white matter, and assist in differential diagnosis, evaluation of treatment effect and prognosis
.
The purpose of this article is to comb through the MRI findings of MS to better help clinicians identify the imaging signs of MS
.

MRI scan sequence for MS

The consensus recommendations of MAGNIMS-CMSC-NAIMS on the use of MRI in MS patients, published in Lancet Neurology in 2021, recommend the timing, method and clinical MRI reporting method of MRI detection to improve the diagnosis, prognosis and monitoring of MRI for MS individuals, and the standardized MRI scanning process and sequence of different parts are recommended as follows ^[1]:

1) Brain MRI: The 2015 MS Magnetic Resonance Imaging Alliance (MAGNIMS) and 2016 MS Center Consortium (CMSC) guidelines recommend the use of axial T2-weighted sequences, bi-echo T2-weighted spin-echo sequences, axial and sagittal T2-weighted liquid attenuation inversion recovery (FLAIR), and contrast-enhanced axial T1-weighted sequences, with 3T MRI being superior
.
The 2017 revision of the McDonald Diagnostic Criteria did not substantially modify
the standardization protocol.
However, given the current popularity of 3D techniques (especially FLAIR and T1-weighted sequences) over 2D techniques, sagittal 3D FLAIR sequences are considered to be the core sequence
for MS diagnosis and monitoring based on their high sensitivity.

Figure 1.
Brain MRI is the recommended scanning protocol
.
In selected cases, contrast can be injected prior to 3D T2-weighted FLAIR, and the delay in initiating 2D or 3D-enhanced T1-weighted imaging should be at least 5–10 minutes
.
The spatial resolution parameters of the 3D sequence are ≤1mm×1mm×1mm (i.
e.
, multiplane reconstruction 3mm).

The spatial resolution parameters of the 2D sequence are ≤1mm×1mm≤3mm
.

*Single or double echo, which can be ignored
if there is a high-quality 3D FLAIR sequence in the process.
† for differential diagnosis, axial 2D FLAIR may be considered if 3D FLAIR
is not available or of poor quality.
Macrocyclic gadolinium contrast agent 0.
1 mmol/kg body weight[1].

2) MRI of the spinal cord: The standardized procedure must include at least two of the following three sagittal sequences: a T2WI spin echo sequence with moderate echo times, a proton density-weighted echo sequence, or a short tau inversion recovery (STIR) sequence
.
If repeated intravenous gadolinium contrast agents (GBCA) are used, gadolinium should be added to enhance the T1WI spin echo sequence
.

Figure 2 MRI of the spinal cord is the recommended scanning protocol
.
In selected cases, contrast can be injected prior to the 2D T2-weighted FLAIR scan, and the time required for 2D-enhanced T1-weighted imaging should be at least 5–10 minutes
.

*Select a proton density-weighted sequence or a short tau inversion recovery sequence
.
† only in specific cases, if possible, after an enhanced brain MRI scan (if enhanced MRI is used for both the brain and spinal cord, the spinal cord-enhancing T1-weighted sequence should be delayed by at least 5–10 minutes immediately after the brain-enhanced T1-weighted sequence).

‡Only in specific cases
.
Macrocyclic gadolinium contrast agent 0.
1 mmol/kg body weight[1].

3) MRI of the optic nerve: MRI of the optic nerve does not require routine examination
according to the 2017 McDonald criteria diagnosis.
However, under certain conditions, optic nerve imaging has important value
.
Standardized optic nerve imaging protocols include axial and coronal fat inhibitory T2WI sequences or STIR and fat inhibitory gadolinium-enhanced T1WI sequences
.

MRI typical imaging findings of MS

Imaging plays an important role
in the diagnosis of MS.
The latest diagnostic criteria for MS McDonald released in 2017 specifically emphasize that patients with suspected MS should have a brain MRI scan ^[2].

Therefore, clinicians should be proficient in MS imaging
.

Table 1.
2017 Revision of the McDonald Diagnostic Criteria for Multiple Sclerosis [2].

MS lesions appear as high-signal regions
on either T2-weighted sequences or proton density-weighted sequences.
Typical lesions range in shape from round to oval, ranging from
a few millimeters in diameter to more than one or two centimeters.
Although lesions can occur in any central nervous system region, several specific areas are commonly affected, such as periventricular and paracortical leukus, corpus callosum, subentheturesal regions (especially the pons and cerebellum), and spinal cord ^[3].

1) Paraventricular lesions: T2 high-intensity white matter lesions
that directly contact the lateral ventricles.
Lesions that come into contact with the ventricles and are located in the corpus callosum are also included in
this definition.

Figure 3 Features
of typical ("green flag"), atypical ("red flag"), and periventricular MS lesions that should not be counted in lesion counts.
Left (A, B): Green flag: A.
Periventricular lesions suggestive of MS; B.
Periventricular lesion perpendicular to the corpus callosum (Dawson indication).

Middle (C-G): Red flag: C.
Multiple leukolesions involve paraventricular and deep gray matter areas, suggesting ischaemic small vessel disease; D.
Extensive involvement of corpus callosum pressure and bilateral diencephalic hyperintensity lesions in neuromyelitis optica spectrum disease; E.
Autosomal dominant cerebral artery disease with subcortical infarction (CADASIL) involving deep white matter, external capsule and temporal lobe; F.
"snowballing" foci in the body of the callosum in Susac syndrome; G.
Diffuse and widespread lesions of systemic lupus erythematosus involve both bilateral white matter and deep gray matter
.
Right (H-K): should not be considered a periventricular lesion: H.
foci that do not touch the lateral ventricles; I.
Symmetrical "caped sign" of anterior and posterior ventricular angles; J.
The longest axis of the lesion is less than 3 mm; K.
Symmetrical linear hyperintensity adjacent to the lateral ventricle[3].

2) Proximal cortical or cortical lesions: T2 high-signal white matter lesions
that directly contact the cortex without affecting normal white matter.

Figure 4 Typical ("green flag"), atypical ("red flag"), and cortical/proximal cortical MS lesions
that should not be counted in lesion counts.
Upper left (A, B): Green flag: suggests proximal cortical (A) and cortical (B) lesions
in MS.
Top right: C.
No contact with the cortex or white matter lesions
located within the cortex.
Bottom: Red flag: D.
Multiple leukolesions involving subcortical and deep white matter, suggesting small vessel disease; E.
Progressive multifocal leukoencephalopathy lesions involve different lobe-gray-white matter boundaries with unclear boundaries; F.
Enlarged perivascular space, displayed as a punctate or streaked multiple well-defined cerebrospinal fluid-like signal; G.
Low signal on T2-weighted sequences suggests hemosiderin deposition due to microbleeds; H.
In central nervous system vasculitis, multiple pia mater and cortical hyperintensities are presented on T-weighted imaging with gradient echo sequence hypointensities [3].

3) Subcurtorial lesions: T2 hyperintense lesions
of the brainstem, cerebellar feet or cerebellum.
These lesions are usually close to the surface or are usually round or oval
when close to the center.

Figure 5.
Typical ("green flag") and atypical ("red flag") subcurtain MS lesions
.
Left: Green flag: A.
Subcurtain lesions
suggestive of MS.
Right: Red Flag: B.
symmetrical central pons lesions in small-vessel disease; C.
Periaqueduct lesions in neuromyelitis optica spectrum disorders; D.
Posterior zone lesions in neuromyelitis optica spectrum disorders; E.
Midbrain-diencephalopathy with anti-MOG syndrome; F.
Large oval lesions near the base of the fourth ventricle in neurobehcet's disease ^[3].

4) Myelopathy: usually multiple and short
head-tail diameter.
Hyperintense on T2-weighted sequences can occur throughout the spinal cord (cervix, thoracic, or lumbar), with cervical portions more commonly affected
.

Figure 6.
Typical ("green flag"), atypical ("red flag"), and spinal cord MS lesions
that should not be counted in lesion counts.
Top left: Green flag: A.
Sagittal short-term reversal recovery sequence of upper cervical and thoracic pulp lesions; B.
Cervical myelopathy shown as low-signal (green arrow) on 3T-T1WI; C.
Cervical myeloid lesions with lateral column and central gray matter involvement (green arrow)
are shown in T2WI and phase-sensitive inversion recovery sequences.
Top right: D.
Ill-defined "diffuse" spinal cord lesions do not meet the definition of
spinal cord involvement.
Bottom: Red flag: E.
long-segmented transverse myelitis of neuromyelitis optica spectrum disease, affecting more than three vertebral segments; F.
Long-segmented spinal cord lesions in neurosarcoidosis, involving more than three vertebral segments, with leptomeningeal and peripheral spinal cord-enhancing foci; G.
Extensive selective lateral and posterior column involvement in subacute combined neurodegeneration; H.
syringomyelia in syringomyelia; I.
Extensive T2 hyperintensity lesion of arteriovenous fistula, extending from the conus of the spinal cord to the cephalic side, with enhanced spots and tortuous areas visible; J.
Hyperintense lesions of the anterior part of the thoracic spinal cord in subacute ischemic myelopathy, extending beyond two vertebral segments; K.
T2-cervical cord hyperintensity in myelopathy, with "pancake-like" gadolinium enhancement [3].

5) Gadolinium-enhanced lesions: Enhanced lesions are defined as areas of at least 3 mm on T1-weighted images obtained at least 5 minutes after contrast administration with clear high-signal regions
.
In most cases, the enhancement of new inflammatory demyelinating lesions is brief (usually 2 to 8 weeks, usually less than 4 weeks), so enhancement can be used to distinguish recent lesions from previous lesions
.
Enhancement of lesions older than 3 months should take into account the possibility of
other diseases.

Figure 7 Typical ("green flag"), atypical ("red flag"), and gadolinium-enhanced MS lesions
that should not be counted in lesion counts.
Top left: Green flag: Enhancement lesion suggestive of MS: A.
Tuber; B.
Open ring; C.
Closed loop; D.
Nodular strengthening
of the spinal cord.
Top right: E.
Telangiectasia (not included in diagnostic criteria).

Bottom: Red flag: F.
Large tumors (> 2 cm) are unevenly strengthened, suggesting atypical idiopathic inflammatory demyelinating lesions; G.
balò disease banding enhancement; H.
Diencephalon, corpus callosum ("cloud-shaped") and long-segmented spinal cord involvement in patients with neuromyelitis optica spectrum disorders; I.
irregular leptomeninge, cortical and subcortical enhancement foci in central nervous system vasculitis; J.
Enhancement of the pia mater and pia mater in neurosarcoidosis and axial "trident sign"; K.
Homogeneous diencephalic reinforcement against Ma2 encephalitis; L.
Irregular and uneven intensification of glioblastoma[3].

6) Optic neuropathy: in the currently used diagnostic criteria for MS, spatial multiplexing does not require optic nerve imaging, but can help confirm optic nerve involvement in MS and exclude atypical optic neuropathy
.
Optic nerve imaging for lesion identification should include a coronary fat suppression T2-weighted sequence
.

Application of 7T magnetic resonance in MS diagnosis

In recent years, with the continuous advancement of imaging technology, the application of 7T magnetic resonance imaging (7T MRI) in clinical practice has gradually increased
.
7T MRI can provide better neuroimaging than conventional MRI, especially in small and early lesions, opening up a broad path for early diagnosis and clinical research of central nervous system diseases ^[4].

Among them, in the diagnosis of MS, 7T MRI can provide a higher signal-to-noise ratio, which can clearly display MS lesions in the cortex, expand our understanding of the MS disease process, and help to deepen the research on MS-related epilepsy and cognitive dysfunction ^[5].

The characteristic radiographic findings of MS on 7T MRI are as follows ^[6]:

1) Lesion stage: when the demyelinating lesion begins to move in the early stage, the enhancer gadolinium leaks from the central vein to the peripheral area; A few weeks after lesion formation, the enhancement pattern shifts and the enhancer flows toward the center, which may reflect the inflammation-healing response
of the brain parenchyma.
Persistent low signal is often seen at the edge of the white matter lesion in the 7T MRI gradient echo sequence, suggesting ferrous deposition, which is usually caused by the engulfment of iron by microglia activated at the lesion edge, commonly known as the "iron rim", which some researchers believe is an imaging sign of chronic active lesions, suggesting more severe clinical disability and disease progression
.

2) Central vein sign: according to the McDonald criteria, the central vein sign is more
predictive of MS than the location of the lesion within the anatomical area of MS features.
Compared with 3T MRI, 7T MRI can better visualize the central venous sign.

Figure 8.
Figure A shows T2*WI, showing the central vein sign; Figure B shows SWI, showing the iron ring sign
.
The solid red box is an enlarged view
of the lesion.
(Photo courtesy of Beijing Tiantan Hospital affiliated to Capital Medical University)

3) Cortical lesions: 7T MRI can more accurately detect cortical gray matter lesions
due to improved spatial resolution and tissue contrast.

Figure 9.
MS U-shaped fiber involvement (Courtesy of Beijing Tiantan Hospital, Capital Medical University)

Figure 10.
MS cortical lesions (Courtesy of Beijing Tiantan Hospital affiliated to Capital Medical University)

4) Enhancement of the pia mater: MS-related meningeal inflammation has been gradually recognized
in recent years.
The positive rate of meningeal inflammation in MS on 3T MRI scans ranged from 1% to 50%, but 7T MRI enhanced scans found positive rates of pia mater enhancement (LME) in MS up to 90%.

There are two main modes of the LME:

• Nodules: round nodules located on the surface of the pia mater or in the subarachnoid space

• Diffusion: leakage
  of contrast agent through the subarachnoid space.
  It may represent a disruption
  of the meningeal barrier near the site of meningeal inflammation.
  

Figure 11.
"Nodule" enhancement lesions in MS [6].

Figure 12.
"Diffusion" of the enhanced lesion in MS [6].

In recent years, smoldering lesions have been mentioned
more and more in MS.
According to the progress of MR imaging and histopathology, MS lesions are currently classified as acute active lesions, chronic active lesions (slowly dilating/smoldering lesions) and chronic inactive lesions, of which smoldering lesions seem to be the driving factor of persistent neurodegeneration ^[7].

Loss of brain volume due to chronic smoldering lesions has been shown to be more associated with disability and cognitive impairment in patients with MS ^[8,9].

The pathological essence of smoldering lesions is a chronic, active inflammatory lesion surrounded by macrophages and activated microglia
.
Paramagnetic rings (iron rings) appear around lesions on 3.
0T or 7.
0T magnetic resonance magnetically sensitive sequences (eg, SWI) ^[10-14].

Figure 13.
Typical evolution of paramagnetic ring lesions (PRLs) on 7T MRI [10].

Expert reviews

Thanks to Professor Tian Decai and Professor Su Lei of Beijing Tiantan Hospital affiliated to Capital Medical University for providing pictures, and reviewing and commenting on this article