Fig 2 - available via license: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Content may be subject to copyright.
Example of lesion evolution. Baseline (A and C) and follow-up (B and D) T1-w/T2-w images from a 33-year-old male patient who presented a spinal cord clinically isolated syndrome, with new brain lesions at 12 months scan. The red arrows show an example of a lesion that reduces in size and increases in signal in the T1-w/T2-w image. The blue arrows show an example of a new lesion (in B) and its corresponding pre-lesional tissue (in A). Overlaid Masks of all lesions: red (in C) represents baseline lesion tissue co-registered to follow-up, where evolution lesion tissue is also colored in red (in D); blue represents new lesion tissue in D and pre-lesional tissue in C. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Source publication
Background
T1w/T2-w ratio has been proposed as a clinically feasible MRI biomarker to assess tissue integrity in multiple sclerosis. However, no data is available in the earliest stages of the disease and longitudinal studies analysing clinical associations are scarce.
Objective
To describe longitudinal changes in T1-w/T2-w in patients with clinic...
Contexts in source publication
Context 1
... Tool (LST) toolbox version 1.2.3. for SPM12, using T2-FLAIR and T1-w images in all cohorts and the corresponding volumes, calculated. In the CIS cohort and the MS cohort, baseline MRI and lesion mask were co-registered to the follow-up MRI scan to create a mask of the evolved lesional tissue, regardless of their appearance on follow-up scans (see Fig. ...
Context 2
... by an expert neuroradiologist. For technical reasons, new lesion masks were only available for 52 out of 59 patients with new lesions. T2-PD images and masks for new lesions were then co-registered to baseline MRI scans using SPM12 (first to follow-up and then to baseline MPRAGE images) to create a mask of baseline pre-lesional tissue (see Fig. ...
Similar publications
Pediatric-onset multiple sclerosis (MS) is a predominantly relapsing-remitting neuroinflammatory disorder characterized by frequent relapses and high magnetic resonance imaging (MRI) lesion burden early in the disease course. Current treatment for pediatric MS relies on early initiation of disease-modifying therapies designed to prevent relapses an...
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Previous studies have shown that aerobic activity is inversely related to MS symptoms and may be restorative and possibly protective. Objectives: This study aimed to compare the effects of high-intensity functional training (HIFT...
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system with presumed autoimmune origin. It is largely accepted that the inflammatory induced loss of axons and neurons is the underlying cause of disability in multiple sclerosis patients. Diffusion tensor imaging (DTI) is a new neuroimaging technique based o...
A review of Russian and foreign medical literature, as well as the Web of Science, PubMed and Scopus databases, revealed 8 cases of multiple sclerosis and Parkinson's disease co-occurrence. Parkinson's disease is a chronic, progressive neurological disease caused by degeneration of dopaminergic neurons in the substantia nigra. Multiple sclerosis is...
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease associated with axonal injury, and neurofilament light chains in serum (sNfL) are considered a biomarker for this damage. We aimed to investigate the relationship between sNfL and the axonal damage in early MS lesions in a special cohort of biopsied patients. sNfL from 106 biop...
Citations
... In the last decade, T1-w/T2-w ratio has been proposed as a broad marker of tissue integrity and has been used in single and multicenter studies comparing MS with healthy controls (HCs), for MS phenotyping, and for establishing associations with clinical measures. [4][5][6][7][8][9][10][11] In addition, there are studies correlating T1-w/T2-w ratio with other MRI-based measures, 12,13 such as magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), and myelin water fraction (MWF), and also with histopathological markers. 4,5,14 The most likely pathological substrates of the ratio in MS are myelin content and axonal/dendrite diameter and density, described together as microstructural integrity. ...
... 4,5,14 Other possible substrates are iron uptake/removal, astrogliosis, and inflammation. 10,11 To exemplify the dynamics of the ratio variations, substrates such as reduced myelin content, and loss of microstructural integrity, may decrease the ratio in the WM and cortical gray matter (GM), while high iron concentration may increase the ratio in the deep GM, with variable contributions to the numerator (T1-w) and/or denominator (T2-w). The association with these substrates may depend on the MS phenotype, the type of tissue studied (normal-appearing gray matter-NAGM-and white matter-NAWM-or focal lesions) and the time course of lesion formation. ...
... The hallmark of MS pathology is the focal demyelinated lesion, most typically detected in WM. 20 Crosssectional studies and baseline results from longitudinal cohorts have consistently demonstrated that the lowest T1-w/T2-w values are found in WM lesions, compared to NAGM and NAWM. 7,10,11 This evidence has been demonstrated either by comparing the lesional tissue with the contralateral non-lesioned WM areas 7 or with the overall mean T1-w/T2-w ratio of the NAWM and NAGM. 10,11 Histopathological evidence explains this difference, 20 since the ratio is mainly reduced by severe tissue destruction, represented by major demyelination (much more intense in lesions than in NAWM and NAGM), neuroaxonal damage, inflammation, astrogliosis, and loss of iron (colocalized with myelin). ...
T1/T2-weighted ratio is a novel magnetic resonance imaging (MRI) biomarker based on conventional sequences, related to microstructural integrity and with increasing use in multiple sclerosis (MS) research. Different from other advanced MRI techniques, this method has the advantage of being based on routinely acquired MRI sequences, a feature that enables analysis of retrospective cohorts with considerable clinical value. This article provides an overview of this method, describing the previous cross-sectional and longitudinal findings in the main MS clinical phenotypes and in different brain tissues: focal white matter (WM) lesions, normal-appearing white matter (NAWM), cortical gray matter (GM), and deep normal-appearing gray matter (NAGM). We also discuss the clinical associations, possible reasons for conflicting results, correlations with other MRI-based measures, and histopathological associations. We highlight the limitations of the biomarker itself and the methodology of each study. Finally, we update the reader on its potential use as an imaging biomarker in research.
... T1w/T2w ratios are lower in lesioned white matter regions compared to non-lesioned white matter regions, consistent with known disease-related reduced myelin content, while no differences have been observed in the T1w/T2w ratio in normal-appearing white matter regions of multiple sclerosis subjects and the white matter of controls. Nonetheless, another study found that patients with clinically isolated syndrome, some of whom later developed multiple sclerosis, a decrease in T1w/T2w was demonstrated prior to the onset of lesion formation [47]. ...
Background: Patients with Alzheimer’s disease (AD) demonstrate progressive white matter atrophy and myelin loss. Restoring myelin content or preventing demyelination has been suggested as a therapeutic approach for AD. Objective: Herein, we investigate the effects of non-invasive, combined visual and auditory gamma-sensory stimulation on white matter atrophy and myelin content loss in patients with AD. Methods: In this study, we used the magnetic resonance imaging (MRI) data from the OVERTURE study (NCT03556280), a randomized, controlled, clinical trial in which active treatment participants received daily, non-invasive, combined visual and auditory, 40 Hz stimulation for six months. A subset of OVERTURE participants who meet the inclusion criteria for detailed white matter (N = 38) and myelin content (N = 36) assessments are included in the analysis. White matter volume assessments were performed using T1-weighted MRI, and myelin content assessments were performed using T1-weighted/T2-weighted MRI. Treatment effects on white matter atrophy and myelin content loss were assessed. Results: Combined visual and auditory gamma-sensory stimulation treatment is associated with reduced total and regional white matter atrophy and myelin content loss in active treatment participants compared to sham treatment participants. Across white matter structures evaluated, the most significant changes were observed in the entorhinal region. Conclusions: The study results suggest that combined visual and auditory gamma-sensory stimulation may modulate neuronal network function in AD in part by reducing white matter atrophy and myelin content loss. Furthermore, the entorhinal region MRI outcomes may have significant implications for early disease intervention, considering the crucial afferent connections to the hippocampus and entorhinal cortex.
... It is worth noting that the ratio of T1w to T2w anatomical images is Frontiers in Physiology frontiersin.org 11 known, rightly or wrongly, in other contexts as the "myelin map" (Glasser and Van Essen, 2011;Boaventura et al., 2022) due to its strong association with myelin content in the non-lesioned brain. The ratio of T1 to T2 in myelin maps or T2 to T1 in TIGR maps is a representation of microstructure differences across brain regions-which, in a healthy brain can grossly be attributed to regional differences in myelination. ...
Introduction: Response to post-stroke aphasia language rehabilitation is difficult to anticipate, mainly because few predictors can help identify optimal, individualized treatment options. Imaging techniques, such as Voxel-based Lesion Symptom Mapping have been useful in linking specific brain areas to language behavior; however, further development is required to optimize the use of structural and physiological information in guiding individualized treatment for persons with aphasia (PWA). In this study, we will determine if cerebral blood flow (CBF) mapped in patients with chronic strokes can be further used to understand stroke-related factors and behavior.
Methods: We collected perfusion MRI data using pseudo-Continuous Arterial Spin Labeling (pCASL) using a single post-labeling delay of 2,200 ms in 14 chronic PWA, along with high-resolution structural MRI to compute maps of tissue damage using Tissue Integrity Gradation via T2w T1w Ratio (TIGR). To quantify the CBF in chronic stroke lesions, we tested at what point spatial smoothing should be applied in the ASL analysis pipeline. We then related CBF to tissue damage, time since stroke, age, sex, and their respective cross-terms to further understand the variability in lesion CBF. Finally, we assessed the feasibility of computing multivariate brain-behavior maps using CBF and compared them to brain-behavior maps extracted with TIGR MRI.
Results: We found that the CBF in chronic stroke lesions is significantly reduced compared to its homologue grey and white matter regions. However, a reliable CBF signal (although smaller than expected) was detected to reveal a negative relationship between CBF and increasing tissue damage. Further, the relationship between the lesion CBF and age, sex, time since stroke, and tissue damage and cross-terms suggested an aging-by-disease interaction. This relationship was strongest when smoothing was applied in the template space. Finally, we show that whole-brain CBF relates to domain-general visuospatial functioning in PWA. The CBF-based brain-behavior maps provide unique and complementary information to structural (lesion-based) brain-behavior maps.
Discussion: Therefore, CBF can be detected in chronic stroke lesions using a standard pCASL MRI acquisition and is informative at the whole-brain level in identifying stroke rehabilitation targets in PWAs due to its relationship with demographic factors, stroke-related factors, and behavior.
... 12 16 In patients with a CIS, T1-weighted (T1w)/T2-weighted (T2w) alterations precede lesion formation and are associated with disease activity. 19 Recently, lower lesional and cortical T1w/T2w ratio values have been shown to be associated with longer disease duration, higher Expanded Disability Status Scale (EDSS), higher brain lesional volume and lower normalised brain volume at all MS disease stages. 9 19 Recent work using independent component analysis (ICA) of volumetric brain MRI scans has shown spatial patterns of cortical GM atrophy. ...
... years. From the replication cohort, 19.5% (31 out of 159) of participants with RRMS had 24-week CDP by the end of the study, after a mean time to progression of 2.76 (SD=2.40) years. ...
... Being this structure highly involved in motor functions, this might explain the association of this network with EDSS in MS. Previous studies showed an association between higher EDSS and a decrease in T1/T2 ratio values in GM. 19 The predictive ability of the GM network for CDP might be explained by the presence in this component of the parietal cortex. Parietal brain regions have extensive connections with visual, auditory and somatosensory systems, and sends outputs to several cortical and subcortical areas, particularly to the frontal motor cortex. ...
Background:
Network-based measures are emerging MRI markers in multiple sclerosis (MS). We aimed to identify networks of white (WM) and grey matter (GM) damage that predict disability progression and cognitive worsening using data-driven methods.
Methods:
We analysed data from 1836 participants with different MS phenotypes (843 in a discovery cohort and 842 in a replication cohort). We calculated standardised T1-weighted/T2-weighted (sT1w/T2w) ratio maps in brain GM and WM, and applied spatial independent component analysis to identify networks of covarying microstructural damage. Clinical outcomes were Expanded Disability Status Scale worsening confirmed at 24 weeks (24-week confirmed disability progression (CDP)) and time to cognitive worsening assessed by the Symbol Digit Modalities Test (SDMT). We used Cox proportional hazard models to calculate predictive value of network measures.
Results:
We identified 8 WM and 7 GM sT1w/T2w networks (of regional covariation in sT1w/T2w measures) in both cohorts. Network loading represents the degree of covariation in regional T1/T2 ratio within a given network. The loading factor in the anterior corona radiata and temporo-parieto-frontal components were associated with higher risks of developing CDP both in the discovery (HR=0.85, p<0.05 and HR=0.83, p<0.05, respectively) and replication cohorts (HR=0.84, p<0.05 and HR=0.80, p<0.005, respectively). The decreasing or increasing loading factor in the arcuate fasciculus, corpus callosum, deep GM, cortico-cerebellar patterns and lesion load were associated with a higher risk of developing SDMT worsening both in the discovery (HR=0.82, p<0.01; HR=0.87, p<0.05; HR=0.75, p<0.001; HR=0.86, p<0.05 and HR=1.27, p<0.0001) and replication cohorts (HR=0.82, p<0.005; HR=0.73, p<0.0001; HR=0.80, p<0.005; HR=0.85, p<0.01 and HR=1.26, p<0.0001).
Conclusions:
GM and WM networks of microstructural changes predict disability and cognitive worsening in MS. Our approach may be used to identify patients at greater risk of disability worsening and stratify cohorts in treatment trials.
... In the study done by Boaventure, et al. on 2022 they suggested that the pathological abnormalities affecting lesions consist of major demyelination and severe tissue destruction; in contrast, abnormalities affecting normal appearing tissue mainly consist of axonaldamage and loss and microglial activation, but do not include major demyelination [47]. ...
... Contrastingly, our work aimed to provide the microstructural features of the brain that can be used in neuroscience and clinical studies to identify markers of specific psychiatric or neurological conditions. For example, the microstructure-sensitive proxy can be used to investigate alterations in brain network organization of Alzheimer's disease, schizophrenia, epilepsy, and multiple sclerosis (Bernhardt et al., 2018;Boaventura et al., 2022;Ganzetti et al., 2015;Pelkmans et al., 2019;Yasuno et al., 2017), and we can assess behavioral and cognitive traits during typical and atypical development [53]- [55]. Moreover, microstructural features can be used to investigate multiscale neural organization. ...
A bstract
Multimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community, and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT .
... In addition, magnetization transfer ratio values and R1 mapping, two commonly MRI approaches used to indirectly measure myelin density, have shown to be highly correlated with T1w/T2w ratio maps [68][69][70]. However, mounting evidence suggests that variations in the T1w/T2w ratio could be influenced by factors other than demyelination [51,[70][71][72][73][74][75][76][77][78], thus challenging the specificity of the T1w/T2w ratio to myelin content. Therefore, cortical T1w/T2w ratio maps are currently considered as a measure of the microstructural integrity of the normal-appearing cortical GM [79] that is sensible to intracortical myelin content [65]. ...
Background
Non-modifiable risk factors of Alzheimer’s disease (AD) have lifelong effects on cortical integrity that could be mitigated if identified at early stages. However, it remains unknown whether cortical microstructure is affected in older individuals with non-modifiable AD risk factors and whether altered cortical tissue integrity produces abnormalities in brain functional networks in this AD-risk population.
Methods
Using relative T1w/T2w (rT1w/T2w) ratio maps, we have compared tissue integrity of normal-appearing cortical GM between controls and cognitively normal older adults with either APOE4 ( N = 50), with a first-degree family history (FH) of AD ( N = 52), or with the co-occurrence of both AD risk factors (APOE4+FH) ( N = 35). Additionally, individuals with only one risk factor (APOE4 or FH) were combined into one group ( N = 102) and compared with controls. The same number of controls matched in age, sex, and years of education was employed for each of these comparisons. Group differences in resting state functional connectivity (rs-FC) patterns were also investigated, using as FC seeds those cortical regions showing significant changes in rT1w/T2w ratios.
Results
Overall, individuals with non-modifiable AD risk factors exhibited significant variations in rT1w/T2w ratios compared to controls, being APOE4 and APOE4+FH at opposite ends of a continuum. The co-occurrence of APOE4 and FH was further accompanied by altered patterns of rs-FC.
Conclusions
These findings may have practical implications for early detection of cortical abnormalities in older populations with APOE4 and/or FH of AD and open new avenues to monitor changes in cortical tissue integrity associated with non-modifiable AD risk factors.
... The present study aimed to explore the possibility of retrieving quantitative data from qualitative conventional structural MRI by utilizing rT1/T2, a method initially proposed as an imaging surrogate of myelin content within the brain 17 . Although the exact pathological mechanism is unknown 19,32 , the relatively high sensitivity of rT1/ T2 for detecting multiple sclerosis suggests that it might be suitable for characterizing tissue microstructure within the brain 33 . As shown in Fig. 3, a good correlation was demonstrated between rT1/T2 and the T1-and T2-relaxation times of tissues. ...
The current study aimed to test whether the ratio of T1-weighted to T2-weighted signal intensity (T1W/T2W ratio: rT1/T2) derived from conventional MRI could act as a surrogate relaxation time predictive of IDH mutation status in histologically lower-grade gliomas. Strong exponential correlations were found between rT1/T2 and each of T1- and T2-relaxation times in eight subjects (rT1/T2 = 1.63exp−0.0005T1-relax + 0.30 and rT1/T2 = 1.27exp−0.0081T2-relax + 0.48; R² = 0.64 and 0.59, respectively). In a test cohort of 25 patients, mean rT1/T2 (mrT1/T2) was significantly higher in IDHwt tumors than in IDHmt tumors (p < 0.05) and the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666–0.677, (AUC = 0.75, p < 0.05), which was validated in an external domestic cohort of 29 patients (AUC = 0.75, p = 0.02). However, this result was not validated in an external international cohort derived from TCIA/TCGA (AUC = 0.63, p = 0.08). The t-Distributed Stochastic Neighbor Embedding analysis revealed a greater diversity in image characteristics within the TCIA/TCGA cohort than in the two domestic cohorts. The failure of external validation in the TCIA/TCGA cohort could be attributed to its wider variety of original imaging characteristics.
... Multiple Sclerosis is one of the most predominant neurological diseases, where MRI scans, are usually used for its diagnosis. However, better detection and monitoring of multiple sclerosis is an urgent need [1]. Especially, segmentation of new lesions at an early stage is of utmost importance. ...
The objective of the research work is to accurately segment multiple sclerosis (MS) lesions in brain Magnetic Resonance Imaging (MRI) of varying sizes and also to classify its types. Designing effective automatic segmentation and classification tool aid the doctors in better understanding MS lesion progressions. In meeting research challenges, this paper presents Noise Invariant Convolution Neural Network (NICNN). The NICNN model is efficient in the detection and segmentation of MS lesions of varying sizes in comparison with standard CNN-based segmentation methods. Further, this paper introduced a new cross-validation scheme to address the class imbalance issue by selecting effective features for classifying the type of MS lesion. The experiment outcome shows the proposed method provides improved Dice Similarity Coefficient (DSC), Positive Predicted Value (PPV), and True Positive Rate (TPR) value compared to the state-of-art CNN-based MS lesion segmentation method. Further, achieves better accuracy in classifying MS lesion types compared to standard MS lesion type classification models.
... Data from previous studies employing T1/T2 methology and incorporating historipathological correlation have supported its sensitivity for cortical pathological processes in MS 14,20 . There remains some debate concerning whether T1/T2 may be a better indicator of tissue integrity, rather than a specific marker of cortical myelin status [12][13]19 . ...
Background
Cortical demyelinated lesions are prevalent in multiple sclerosis (MS) and associated with disability; their presence on MRI has recently been incorporated into MS diagnostic criteria. Presently, advanced and ultra-high-field MRI — not routinely available in clinical practice — are the most sensitive methods for detection of cortical lesions, and approaches utilizing MRI sequences obtainable in routine clinical practice remain an unmet need.
Objective
To assess the sensitivity of the ratio of T 1 -weighted and T 2 -weighted (T 1 /T 2 ) signal intensity for focal cortical lesions in comparison to other established, sensitive, advanced and high-field imaging methods.
Methods
3-tesla (3T) and 7-tesla (7T) MRI collected from 10 adults with MS participating in a natural history study at the National Institutes of Health were included in the study. T 1 /T 2 images were calculated by dividing 3T T 1 w images by 3T T 2 w fluid-attenuated inversion recovery (FLAIR) images for each participant. Cortical lesions were identified using 7T T 2 *w and T 1 w images and corresponding voxels were assessed on registered 3T images. For each participant, ratios derived from the median signal intensity of nonlesional tissue in the cortical region of the lesion and the median lesional voxel intensity were computed. These values were compared across 3T imaging sequences, including the calculated T 1 /T 2 image, as well as T 1 w, T 2 w, and Inversion Recovery Susceptibility Weighted Imaging with Enhanced T 2 weighting (IR-SWIET) images.
Results
614 cortical lesions were identified on 7T images. 3T T 1 /T 2 images demonstrated a larger contrast between median nonlesional cortical signal intensity and median cortical lesion signal intensity (median ratio = 1.29, range 1.19 – 1.38) when compared to T 1 w (1.01, 0.97 – 1.10, p<0.002), T 2 w (1.17, 1.07 – 1.26, p<0.002), and IR-SWIET (1.21, 1.01 – 1.29, p<0.03).
Conclusion
T 1 /T 2 images are sensitive to cortical lesions. Approaches incorporating T 1 /T 2 could improve the accessibility of cortical lesion detection in research settings and clinical practice.
