January-February 2018

Ultra-High-Field MRI Visualization of Cortical Multiple Sclerosis Lesions with T2 and T2*: A Postmortem MRI and Histopathology Study

Jonkman Pic

Laura Jonkman

Although histologic sections of MS brains have shown extensive cortical pathology, visualizing these lesions with MRI has been challenging. A low signal-to-noise ratio due to lower myelin concentrations in cortical gray matter (compared with white matter) has contributed to this difficulty. In turn, initial studies with conventional sequences at standard (1.5T) field strength only yielded very low detection rates of up to 5%.1

Several researchers in the field picked up on this and developed new sequences at standard and high (3T) field strengths, specifically aimed at better visualizing myelination of the gray matter. A double inversion recovery (DIR) sequence visualized up to 18% of cortical lesions,2 and was implemented as a research tool. However, there were questions about whether DIR was the optimal MRI sequence for visualization of cortical lesions at an even higher resolution at higher field strengths.

The current study compared 2 sequences (conventional T2WI and more advanced T2*WI) at ultra-high (7T) field strength in their ability to visualize cortical MS lesions. Results showed that 28% and 16% of cortical lesions were detected with T2 and T2*, respectively. Interestingly enough, the MRI rater was blinded to histopathologic results when scoring the T2 and T2* images, but when she was informed of histologic lesion location and type, up to 82% of lesions were visible. This was much higher than in any previous postmortem study at lower field strength. These numbers indicate that ultra-high-field MRI gives an opportunity for better cortical lesion visualization, but that this opportunity has not yet been fully seized. Perhaps MRI rater training, with histologic feedback on scoring results, could lead to higher detection rates, maybe also at lower field strengths.

After this study, we performed another cortical lesion detection study, comparing 5 sequences (DIR, FLAIR, T1, T2, and T2*) at 2 field strengths (3T and 7T).3 Results showed an overall advantage for 7T, but not for every sequence in comparison with its 3T counterpart. FLAIR and T2* showed better lesion detection in the gray matter of patients with MS at 7T than at 3T. This was not the case for the much-acclaimed (at lower field strength) DIR sequences, indicating that a sequence may be superior at 1 field strength, but not necessarily at ultra-high field strength. Because a fairly high percentage of lesions could retrospectively be visualized, and studies have shown that visible lesions give a good indication of the total cortical lesion

burden (visible + invisible), no further cortical lesion detection studies were undertaken. Instead, we have since focused on validating the pathologic substrate of new MRI sequences, as demonstrated in a recent manuscript on the T1/T2 ratio.4 We will expand on these types of studies, further bridging MRI and histology, to elucidate the pathologic correlate of ever-advancing MRI sequences.

Other endeavors relate to setting up a similar short postmortem delay MRI pathology pipeline in nonneurologic controls. The Normal Aging Brain Collection Amsterdam (NABCA) is a comprehensive collection of postmortem (ultra-)high-field imaging (3T in situ and 7T ex vivo) and fixed and paraffin-embedded tissue with an extensive neuropathologic assessment. Our aim is to make the postmortem MRIs and tissues available for other researchers, providing the scientific community with a means to methodologically translate molecular, cellular, and brain imaging knowledge to the clinical setting. (For more information, please see http://www.nabca.eu.)


  1. Geurts JJG, Bö L, Pouwels PJW, et al. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 2005;26:572–77.
  2. Seewann A, Kooi E-J, Roosendaal SD, et al. Postmortem verification of MS cortical lesion detection with 3D DIR. Neurology 2012;78:302–08, 10.1212/WNL.0b013e31824528a0
  3. Kilsdonk ID, Jonkman LE, Klaver R, et al. Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study. Brain 2016;139:1472–81, 10.1093/brain/aww037
  4. Righart R, Biberacher V, Jonkman LE, et al. Cortical pathology in multiple sclerosis detected by the T1/T2-weighted ratio from routine magnetic resonance imaging. Ann Neurol 2017;82:519–29, 10.1002/ana.25020

Read this article at AJNR.org …