Neurite density explains cortical T1-weighted/T2-weighted ratio in multiple sclerosis

Preziosa, Paolo; Bouman, Piet M; Kiljan, Svenja; Steenwijk, Martijn D.; Meani, Alessandro; Pouwels, Petra J. W.; Rocca, Maria A.; Filippi, Massimo; Geurts, Jeroen J. G.; Jonkman, Laura E.

doi:10.1136/jnnp-2020-324391

Cited by 26 publications

(34 citation statements)

References 5 publications

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“…We found no significant detection of either in myelinated and demyelinated cerebral cortex. Since neurite density is also found to contribute to T1T2R, 30 staining for axons and dendrites will be considered in future studies. The presence and absence of myelin is the most likely correlate of imaging differences reported.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI

et al. 2021

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Background: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. Objectives: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. Methods: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. Results: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. Conclusions: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.

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Section: Discussionmentioning

confidence: 99%

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI

et al. 2021

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“…It should also be noted that, while T1w/T2w is accepted as a marker of microstructural integrity in the whole brain, 11 , 14 , 32 the exact pathological substrate of T1w/T2w has not yet been determined. Combined MRI-histopathology studies to determine the pathological substrate of T1w/T2w in NAWM, similar to those already conducted in the gray matter, 32 , 36 , 37 are lacking and are required to better understand the underlying damage shown by this method.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation

et al. 2021

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Background: Cross-sectional studies suggest normal appearing white matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting multiple sclerosis (MS). Objective: To investigate the relationship between NAWM integrity and cortical thickness from first clinical presentation longitudinally. Methods: NAWM integrity and cortical thickness were assessed with 3T magnetic resonance imaging (MRI) in 102 patients with clinically isolated syndrome or early MS (33.2 (20.1–60.1) years old, 68% female) from first clinical presentation over 2.8 ± 1.6 years. Fifty healthy controls (HCs) matched for age and sex were included. NAWM integrity was evaluated using the standardized T1w/T2w ratio (sT1w/T2w). The association between sT1w/T2w and cortical thickness was assessed using linear mixed models. The effect of disease activity was investigated using the No Evidence of Disease Activity (NEDA-3) criteria. Results: At baseline, sT1w/T2w ( p = 0.152) and cortical thickness ( p = 0.489) did not differ from HCs. Longitudinally, decreasing sT1w/T2w was associated with cortical thickness and increasing lesion burden (marginal R2 = 0.061). The association was modulated by failing NEDA-3 (marginal R2 = 0.097). Conclusion: sT1w/T2w may be a useful MRI biomarker for early MS, detecting relevant NAWM damage over time using conventional MRI scans, although with less sensitivity compared to quantitative measures.

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“…Thus, the intensity normalization of images aiming for trans-institutional image harmonization was not necessary for preprocessing in calculating the rT1/T2 map. The T2WI was co-registered to the T1WI, further producing rT1/T2 [ 16 ]. An example case presentation for rT1/T2 reconstruction is provided in Figure S1 .…”

Section: Methodsmentioning

confidence: 99%

“…However, we are also aware that T1- and T2-relaxometry is still not a clinically routine imaging sequence for brain tumors. On the other hand, the ratio of T1- and T2-weighted images (T1w/T2w-ratio map: rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain, which helps visualize multiple stenosis lesions [ 13 , 14 , 15 , 16 ]. This research study investigates the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively.…”

Section: Introductionmentioning

confidence: 99%

Prediction and Visualization of Non-Enhancing Tumor in Glioblastoma via T1w/T2w-Ratio Map

et al. 2022

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One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner (p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification.

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Neurite density explains cortical T1-weighted/T2-weighted ratio in multiple sclerosis

Cited by 26 publications

References 5 publications

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI

Sensitivity of T1/T2-weighted ratio in detection of cortical demyelination is similar to magnetization transfer ratio using post-mortem MRI

Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation

Prediction and Visualization of Non-Enhancing Tumor in Glioblastoma via T1w/T2w-Ratio Map

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