Monitoring White and Grey Matter Pathology
- Conventional magnetic resonance imaging (MRI) detects the majority of White Matter (WM) damages but is insensitive to cortical Grey Matter (GM) lesions1
- More advanced MRI techniques have significantly improved detection of cortical lesions2-5
- In the absence of more advanced MRI techniques, GM pathology can be monitored manually by measuring the cerebral third ventricle enlargement6-8
Neuroimaging techniques make it possible to assess the development and progression of WM and GM pathology in Multiple Sclerosis (MS). Conventional T2-weighted MRI is very sensitive and has been successful for the detection of most WM lesions.1 However, limitations in this technique make it much less sensitive for detecting GM lesions.1 Part of this challenge is attributed to the low density of myelin in the GM, which generates little contrast on MRI in a demyelinating lesion.9
There are different classifications of cortical demyelinating lesions, depending on the location.1,10 Type I lesions, also known as leukocortical or juxtacortical lesions, involve both WM and GM. Type II lesions are contained within the cortex in their entirety. Type III lesions extend from the subpial surface into layers 3 and 4 of the cortex. Type IV lesions span the entire cortex without extending into WM.1,10 Types II to IV lesions are collectively referred to as intracortical lesions.11
MRI techniques for detecting Grey Matter lesions
Advances in MRI techniques led to the introduction of fluid-attenuated inversion recovery (FLAIR). FLAIR suppresses signals from the cerebrospinal fluid (CSF), increasing lesion contrast.2 FLAIR magnetic resonance sequence has been shown to improve the detection of cortical and juxtacortical GM lesions by 60% compared with T2-weighted images; however, many lesions still go undetected.1,2,9
Increases in the Ability of Advancing MRI Techniques to Detect GM Lesions
|MRI technique||Detected lesion type||Percent increase in lesion detection|
|FLAIR||Mostly juxtacortical||60% increase compared with T2 MRI2|
|DIR||Juxtacortical + intracortical||Up to 538% compared with T2 MRI3|
|DIR + PSIR||Juxtacortical + intracortical||337% increase compared with FLAIR alone4|
In 2005, Geurts and colleagues acquired images with a 1.5 Tesla (T) magnetic resonance imager using DIR sequence in 10 patients with chronic, clinically definite MS.3 DIR was shown to have outperformed both T2-weighted and FLAIR images and improved intracortical lesion detection by up to 538% and 152%, respectively.3 DIR also improved detection of juxtacortical lesions because of an increase in White and Grey Matter contrast and increased contrast between lesions and their surroundings.3
However, with significant imaging improvement comes limitations for DIR. Postmortem histopathologic analysis of 56 tissue samples from 14 patients with chronic MS confirmed that a significant number of purely cortical lesions (types II to IV) were unidentified.12 Furthermore, they show a high DIR sensitivity to leukocortical lesions (type I).12 In another study, Seewann et al noted that discrepancies in lesion detection are primarily due to size, with certain lesions evading detection because of their small size rather than differences in pathology.13 In addition, DIR is prone to image artifacts and has a low signal-to-noise ratio.4 Despite the drawback and limited sensitivity to some lesions, DIR provided a solid foundation for complementary techniques to improve upon sensitivity to different lesion types.
DIR has been used in conjunction with T1-weighted 3-D imaging and PSIR techniques.1 In a cohort of 16 patients with MS, images acquired using a 3T imager showed that PSIR improves upon White and Grey Matter contrast and increases delineation of shape, size, and boundary between lesions and surrounding GM.4 Combining it with DIR resulted in a 337% increase in the total number of lesions detected when compared with FLAIR.4
Is there an alternative method to monitor Grey Matter pathology?
As indicated above, imaging using higher magnetic field strength and updated sequences improves detection of cortical lesions; a 3T MRI detected 192% more intracortical lesions and 30% more leukocortical lesions than a 1.5T MRI.14 As expected, an ultrahigh magnetic field strength, such as 7T or higher provides even greater improvements in signal-to-noise ratio, spatial resolution, and image contrast, which increases detection of GM lesions.15-17
Although the 1.5T and 3T MRIs are available in many clinical care centers, a small amount of patients have access to the more advanced ≥7T.18 To monitor GM pathology in the absence of more advanced imaging, measurement of the cerebral third ventricle width has been applied. The cerebral ventricles are a series of CSF-filled spaces; the third ventricle is spanned on both sides by the right and left thalamus.19 A study by Müller et al that involved 54 patients with MS showed that the third ventricle width was greater in patients than in controls.6 This enlargement of the third ventricle was indicative of brain atrophy in patients with MS, and the width of the third ventricle was significantly related to EDSS and MS duration.6 Another study conducted in 37 patients with MS demonstrated that the third ventricular width accounted for variance in learning, delayed recall, Paced Auditory Serial Addition Test score, and Symbol Digit Modality Test performance.20 This supports the idea that the third ventricular enlargement is a result of atrophy of nearby GM structures, including the thalamus,7 especially because these 2 cerebral structures are anatomically connected.21
Before computer-based methodology for linear measurements, measuring the third ventricular enlargement was performed using a transparent ruler.8 Tekok-Kilic et al described the steps to accomplish this manual measurement: A line is drawn through the long axis of the third ventricle to measure its length. Then, a second line is drawn perpendicular to the midpoint of the first line. The second line is measured in millimeters.7,22 An advantage of this method is the ability to retrospectively measure and determine how the third ventricle width has changed in patients over time, which can help gain further insights on patients based on previous MRIs.
Reducing the complexity in tracking Grey Matter changes
In the absence of sophisticated MRI techniques, changes in GM structures can be monitored by manually tracking enlargement in the third ventricle over time. This method provides a simple and effective way to measure GM atrophy while delivering a cost-efficient option for a more comprehensive routine checkup.