Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

Abstract

ObjectiveIn multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown.MethodsUsing a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors.ResultsPatients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin.InterpretationThe T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529

Gray matter T1‐w/T2‐w ratios are higher in Alzheimer's disease

“…Previous studies have suggested that myelin is the predominant source of MR contrast in T1‐weighted and T2‐weighted images (Bock, Kocharyan, Liu, & Silva, ; Eickhoff et al, ; Laule et al, ; Wallace et al, ), and by using the ratio of these images the contrast sensitivity to detect myelin content is increased further due to attenuation of the shared intensity biases (Glasser & Van Essen, ). Although, other studies have questioned the sensitivity of the T1‐w/T2‐w ratio for myelin content, and argued that it is likely not the only factor contributing to the T1‐w/T2‐w image (Arshad et al, ; Righart et al, ; Uddin et al, ). Still, it has been shown that T1‐w/T2‐w ratio differentiates between high and low myelinated cortex as determined by myelin proteolipid protein staining (Nakamura et al, ).…”

“…However, it remains unclear what biological substrate higher T1‐w/T2‐w values reflect. Disorders with a strong demyelinating component such as MS, have consistently showed lower T1‐w/T2‐w values in pathologically vulnerable regions (Beer et al, ; Nakamura et al, ; Righart et al, ). Additionally, lowered T1‐w/T2‐w ratios in several brain regions in schizophrenia (Ganzetti et al, ; Iwatani et al, ) and bipolar disorder patients (Ishida et al, ) have been identified.…”

“…In disorders with a strong demyelinating component such as multiple sclerosis (MS), the T1‐w/T2‐w ratio is lowered in pathologically vulnerable regions (Beer et al, ; Nakamura, Chen, Ontaneda, Fox, & Trapp, ). However, recent studies have raised controversy on the interpretation of the T1‐w/T2‐w ratio, showing that this measure may also reflect tissue microstructure other than myelin, such as axon and dendrite density or iron content (Arshad, Stanley, & Raz, ; Righart et al, ; Uddin, Figley, Marrie, & Figley, ; van Rooden et al, ). Because disrupted brain connectivity is an important feature of AD (Dicks et al, ; Fornito et al, ; Pievani et al, ), an intracortical reduction of myelin content in AD could be hypothesized.…”

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease

“…5, 9, 37 A recent MRI-pathology study has linked the T1w/T2w ratio to dendrite density but not myelin content. 22 Thus, the T1w/T2w ratio in the midbrain may reflect a sum of multiple PD-related changes involving neurons, dendrites, microglia, and iron content. This information might generate a more potent contrast that may be superior to other MRI sequences in capturing PD-related pathology and can be used as a biomarker for PD early detection.…”

“…Originally proposed by Glasser et al, 19 a simple division of these images can yield a new quantitative contrast (T1w/T2w ratio) with high spatial resolution, test-retest reliability, and sensitivity to neurodegenerative changes demonstrated by recent studies. 20–22 Its simplicity and broad availability make it a promising candidate for studying PD-related changes. To our knowledge, there is neither a study that has used the T1w/T2w ratio to study structures other than cortical regions, nor has it been applied yet to a PD population.…”