Magnetization Transfer Imaging Research Articles

Unconstrained quantitative magnetization transfer imaging: disentangling T1 of the free and semi-solid spin pools

Abstract Since the inception of magnetization transfer (MT) imaging, it has been widely assumed that Henkelman’s two spin pools have similar longitudinal relaxation times, which motivated many researchers to constrain them to each other. However, several recent publications reported a T1s of the semi-solid spin pool that is much shorter than T1f of the free pool. While these studies tailored experiments for robust proofs-of-concept, we here aim to quantify the disentangled relaxation processes on a voxel-by-voxel basis in a clinical imaging setting, i.e., with an effective resolution of 1.24mm isotropic and full brain coverage in 12min. To this end, we optimized a hybrid-state pulse sequence for mapping the parameters of an unconstrained MT model. We scanned four people with relapsing-remitting multiple sclerosis (MS) and four healthy controls with this pulse sequence and estimated T1f≈1.84s and T1s≈0.34s in healthy white matter. Our results confirm the reports that T1s≪T1f and we argue that this finding identifies MT as an inherent driver of longitudinal relaxation in brain tissue. Moreover, we estimated a fractional size of the semi-solid spin pool of m0 s≈0.212 , which is larger than previously assumed. An analysis of T1f in normal-appearing white matter revealed statistically significant differences between individuals with MS and controls.

So You Want to Image Myelin Using MRI: Magnetic Susceptibility Source Separation for Myelin Imaging.

In MRI, researchers have long endeavored to effectively visualize myelin distribution in the brain, a pursuit with significant implications for both scientific research and clinical applications. Over time, various methods such as myelin water imaging, magnetization transfer imaging, and relaxometric imaging have been developed, each carrying distinct advantages and limitations. Recently, an innovative technique named as magnetic susceptibility source separation has emerged, introducing a novel surrogate biomarker for myelin in the form of a diamagnetic susceptibility map. This paper comprehensively reviews this cutting-edge method, providing the fundamental concepts of magnetic susceptibility, susceptibility imaging, and the validation of the diamagnetic susceptibility map as a myelin biomarker that indirectly measures myelin content. Additionally, the paper explores essential aspects of data acquisition and processing, offering practical insights for readers. A comparison with established myelin imaging methods is also presented, and both current and prospective clinical and scientific applications are discussed to provide a holistic understanding of the technique. This work aims to serve as a foundational resource for newcomers entering this dynamic and rapidly expanding field.

Quantifying Tendon Degeneration Using Magic Angle Insensitive Ultra-Short Echo Time Magnetization Transfer: A Phantom Study in Bovine Tendons.

The aim of this study was to qualitatively and quantitatively assess changes in bovine flexor tendons before and after collagen degradation and at different angles in relation to the static B0 field using 3-dimensional ultra-short echo time (UTE) magnetization transfer (MT) imaging within a clinically feasible acquisition time. Eight bovine flexor tendons were examined at 3 T magnetic resonance imaging including 3-dimensional UTE MT and UTE T2* research application sequences (acquired within 4:04 and 6:38 minutes, respectively) before and after enzyme-induced degradation. The tendons were divided into 2 groups: group 1 (controls) treated with phosphate-buffered saline and group 2 treated with collagenase I to induce collagen degeneration. Magnetic resonance imaging was repeated at 0, 27, 55, and 90 degrees to the B0 field. To calculate quantitative tissue properties, all tendons were semiautomatically segmented, and changes in quantitative UTE T2* and UTE MT ratios (MTRs) were compared at different angles and between groups. In addition to descriptive statistics, the coefficient of variation was calculated to compare UTE MT and UTE T2* imaging. Ultra-short echo time MTR showed a significantly lower coefficient of variation compared with UTE T2* values, indicating a more robust imaging method (UTE MTR 9.64%-11.25%, UTE T2* 18.81%-24.06%, P < 0.001). Both methods showed good performance in detecting degenerated tendons using histopathology as reference standard, with UTE MT imaging having a better area under the curve than UTE T2* mapping (0.918 vs 0.865). Falsely high UTE T2* values were detected at the 55 degrees acquisition angle, whereas UTE MTR values were robust, that is, insensitive to the MAE. Ultra-short echo time MT imaging is a reliable method for quantifying tendon degeneration that is robust to the MAE and can be acquired in a clinically reasonable time.

Cumulative Dosage of Intrathecal Chemotherapy Agents Predicts White Matter Integrity in Long-Term Survivors of Acute Lymphoblastic Leukemia: A PETALE Study.

Acute lymphoblastic leukemia (ALL) stands as the most prevalent form of pediatric cancer in North America, with a current five-year survival rate of 85%. While more children achieved ALL remission and transition into adulthood, the prevalence of long-term treatment-related effects, especially neurocognitive sequelae, remains significant. This study pursues two objectives. Firstly, it investigates if Magnetization Transfer Ratio (MTR), a method assessing myelin integrity, is sensitive to white matter (WM) microstructural changes in long-term ALL survivors and whether these relate to cognitive impairments. Secondly, it examines the dose-related effects of chemotherapy agents on the MTR and its relationship to other risk factors such as female sex, early age diagnosis, and cranial radiotherapy. Magnetization transfer imaging was utilized to assess WM integrity in 35 survivors at a mean of 18.9 years after the onset of ALL (range since diagnosis: 6.9-26.8). Additionally, 21 controls matched for age, sex, and education level, with no history of cancer, were included. MTR was extracted from both the entire brain's WM and the corpus callosum through semi-automated procedures. The results indicated lower MTR means in survivors, which is linked to cognitive function. Negative associations between MTR means and intrathecal agents' (MTX, cytarabine, and hydrocortisone) cumulative doses received were highlighted. This study offers valuable insights into the connections between myelin deterioration, cognitive impairment, and the implications of IT chemotherapy, enhancing our understanding of ALL survivorship dynamics. It underscores MTR's relevance in monitoring neurotoxicity during oncological drug follow-up examinations.

Feasibility study to assess lesion repair in relapsing-remitting multiple sclerosis: A randomized controlled pilot clinical trial of domperidone add-on treatment

BackgroundIdentification of therapies to promote repair in multiple sclerosis is challenged by the lack of an accepted trial model and associated outcome measures. The goal of this study was to determine the feasibility of a new trial model that enrolls disease modifying therapy (DMT)-treated relapsing-remitting multiple sclerosis (RRMS) participants who have enhancing lesions on clinically indicated brain MRI, and to explore estimates of lesion repair using MRI. MethodsThis was a single site randomized controlled clinical trial. Recruitment took place between November 2015 and January 2019, with final follow-up in February 2019. DMT-treated RRMS participants aged 18–60 years with at least one gadolinium-enhancing lesion on clinically indicated brain MRI were included. Participants were randomized 2:1 to oral domperidone add-on 10-mg three times daily for 16 weeks or no add-on treatment (control). The primary outcomes were feasibility of the model pre-defined as recruitment of 24 participants within 36 months with a 79 % completion rate, and MRI outcomes of lesion repair measured at 16 and 32 weeks using texture analysis, magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI). The impact of domperidone on serum prolactin at 6 and 16 weeks was also evaluated. ResultsOf 237 RRMS participants screened, 17 (14 women) were randomized: 12 to domperidone add-on and 5 to control. All completed the study. Median (range) age was 38.9 (26.7–55.9) years; EDSS was 1.5 (1.0–3.5); and disease duration was 12.9 (2.9–23.3) years. Both groups showed improvement in MRI texture and diffusion fractional anisotropy (FA) at 32 weeks, and the domperidone group demonstrated additional recovery at 16 weeks in both texture and FA. There was no significant group difference in any MRI outcome. Of the 12 domperidone participants, 7 had ≥4x higher serum prolactin than normal. There were no serious adverse events. ConclusionThe recruitment target was not met and therefore the trial model was not feasible despite a full completion rate. The imaging techniques performed well, especially MRI texture analysis, suggesting the sample size being sufficient for estimating lesion repair. The main challenge of this trial model may be recruiting gadolinium-enhancing lesions in DMT-treated RRMS participants. Prolactin is safe and may hold promise as a remyelination therapy. Trial registrationClinicalTrials.gov Identifier: NCT02493049.

Deep structure and geothermal resource effects of the Gonghe basin revealed by 3D magnetotelluric

In order to better understand the crustal shortening and orogenic uplift in the northeastern margin of the Tibetan Plateau, as well as the geothermal resource effects formed during this process, we used ModEM software to perform 3D MT imaging on broadband magnetotelluric survey points deployed at 710 points in the Gonghe Basin and its surrounding areas. The resistivity model suggests that the Gonghe Basin exhibits a low–high–low overall electrical structure, with high conductivity widely distributed in the middle and lower crust. The resistivity model also reveals a significant discontinuity between high and low resistivity blocks at various depths in the upper and middle crust. These discontinuities are align with the faults observed on the surface related to strong crustal fluctuations, which are connected to high conductors in the middle and upper crust. Using empirical formulas for high-temperature and high-pressure testing of granite, it is estimated that the melting volume of these high conductors ranges from 3 to 43%, demonstrating good "plasticity". These high conductors can act as detachment layers for crustal shortening and deformation during the expansion of the Tibetan Plateau towards the northeast edge and can continuously conduct heat energy upwards, creating a high thermal background in the Gonghe Basin.

MRI AND BLOOD-BASED BIOMARKERS ASSOCIATED WITH SURGICAL MANAGEMENT IN CHILDREN AND ADULTS WITH SMALL BOWEL CROHN'S DISEASE

Abstract BACKGROUND Despite advances in medical therapy, many children and adults with ileal Crohn’s Disease (CD) progress to fibrostenosis requiring surgery. Prior studies have identified circulating and imaging biomarkers associated with strictures, although their associations with need for surgery are not well-established. PURPOSE We aimed to identify MRI and circulating biomarkers associated with the need for surgical management in chidlren and adults with ileal CD. METHODS This prospective, multi-center study included pediatric and adult CD cases undergoing ileal resection (n=50), and CD controls receiving medical therapy (n=83). Noncontrast research MRI examinations measured bowel wall three-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA) (Figure 1). Circulating biomarkers included CD64, ECM1, and GM-CSF autoantibodies (Ab). Clinical variables, including demographics, anthropometrics, and routine clinical laboratory data (e.g., CRP, fecal calprotectin), also were obtained at the research visit. Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS Mean participant age was 23.9±13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR]=2.87; p=0.0009), normalized 3D MTR (OR=1.05; p=0.002), log MOLLI T1 (OR=0.01; p=0.02), log IVIM perfusion fraction (f) (OR=0.38; p=0.04), and IVIM apparent diffusion coefficient (ADC) (OR=0.3; p=0.001). MRI and circulating biomarker Tukey box plots are presented in Figure 2. The multivariable model for surgery based upon AICc criteria included age (OR=1.03; p=0.29), BMI (OR=0.91; p=0.09), log GM-CSF Ab (OR=3.37; p=0.01), normalized 3D MTR (OR=1.07; p=0.007), sMaRIA (OR=1.14; p=0.61), luminal narrowing (OR=10.19; p=0.003), log CRP (normalized) (OR=2.75; p=0.10), and hematocrit (OR=0.90; p=0.13). CONCLUSION After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with need for surgery in ileal CD. GM-CSF autoantibodies and MRI biomarker sequences may be useful for guiding management decisions in CD patients. Figure 1 Research MRI images from a surgical Crohn’s disease patient with stricturing behavior involving the terminal ileum. A and B. Coronal and axial fat-saturated T2-weighted single-shot fast spin-echo (SSFSE) images show wall thickening and luminal narrowing of the terminal ileum (arrows) with more proximal bowel dilation measuring greater than 3 cm. C. Axial 3D magnetization transfer images – MT pulse on (bottom image, arrow), MT pulse off (top image, arrow). D. Axial modified Look-Locker inversion recovery (MOLLI) T1 relaxation image (arrow). E. Representative axial intravoxel incoherent motion diffusion-weighted images with increasing b-values (left to right, arrows). Figure 2 Variation in circulating and imaging biomarkers in Crohn’s disease patients with medical and surgical management. Ctrl: non-IBD healthy controls; Med: CD patients with nonsurgical medical management; Surg: CD patients with surgical management.

Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis.

Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed up for 5 years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex. We investigated 140 people with MS (37 clinically isolated syndrome, 71 relapsing-MS, 32 progressive-MS), who were clinically assessed at baseline and after 5 years and, along with 84 healthy controls, underwent a 3 T-MRI protocol including MTI at baseline and after 1 year. Changes in cortical volume over the radiological follow-up were computed with a Jacobian integration method. Magnetization transfer ratio was employed to calculate for each patient an index of cortical demyelination at baseline and of dynamic cortical demyelination and remyelination over the follow-up period. The three indices of cortical myelin content change were heterogeneous across patients but did not significantly differ across clinical phenotypes or treatment groups. Cortical remyelination, which tended to fail in the regions closer to CSF (-11%, P < 0.001), was extensive in half of the cohort and occurred independently of age, disease duration and clinical phenotype. Higher indices of cortical dynamic demyelination (β = 0.23, P = 0.024) and lower indices of cortical remyelination (β = -0.18, P = 0.03) were significantly associated with greater cortical atrophy after 1 year, independently of age and MS phenotype. While the extent of cortical demyelination predicted a higher probability of clinical progression after 5 years in the entire cohort [odds ratio (OR) = 1.2; P = 0.043], the impact of cortical remyelination in reducing the risk of accumulating clinical disability after 5 years was significant only in the subgroup of patients with shorter disease duration and limited extent of demyelination in cortical regions (OR = 0.86, P = 0.015, area under the curve = 0.93). In this subgroup, a 30% increase in cortical remyelination nearly halved the risk of clinical progression at 5 years, independently of clinical relapses. Overall, our results highlight the critical role of cortical myelin dynamics in the cascade of events leading to neurodegeneration and to the subsequent accumulation of irreversible disability in MS. Our findings suggest that early-stage myelin repair compensating for cortical myelin loss has the potential to prevent neuro-axonal loss and its long-term irreversible clinical consequences in people with MS.

Multimodal imaging with magnetization transfer and diffusion tensor imaging reveals evidence of myelin damage in children and youth treated for a brain tumor.

The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI. Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial-spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI- fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls. MTR was decreased across multiple white matter tracts in patients when compared to healthy children, P < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, P < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, Ps < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, Ps < .01, but not healthy control children. Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption.

Folate receptor α deficiency - Myelin-sensitive MRI as a reliable biomarker to monitor the efficacy and long-term outcome of a new therapeutic approach.

Cerebral folate transport deficiency, caused by a genetic defect in folate receptor α, is a devastating neurometabolic disorder that, if untreated, leads to epileptic encephalopathy, psychomotor decline and hypomyelination. Currently, there are limited data on effective dosage and duration of treatment, though early diagnosis and therapy with folinic acid appears critical. The aim of this long-term study was to identify new therapeutic approaches and novel biomarkers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, biochemical, structural and quantitative MRI parameters of seven patients with genetically confirmed folate receptor α deficiency were acquired over 13 years. Multimodal MRI approaches comprised MR-spectroscopy (MRS), magnetization transfer (MTI) and diffusion tensor imaging (DTI) sequences. Patients started oral treatment immediately following diagnosis or in an interval of up to 2.5 years. Escalation to intravenous and intrathecal administration was performed in the absence of effects. Five patients improved, one with a presymptomatic start of therapy remained symptom-free, and one with inconsistent treatment deteriorated. While CSF 5-methyltetrahydrofolate and MRS parameters normalized immediately after therapy initiation, myelin-sensitive MTI and DTI measures correlated with gradual clinical improvement and ongoing myelination under therapy. Early initiation of treatment at sufficient doses, considering early intrathecal applications, is critical for favorable outcome. The majority of patients showed clinical improvements that correlated best with MTI parameters, allowing individualized monitoring of myelination recovery. Presymptomatic therapy seems to ensure normal development and warrants newborn screening. Furthermore, the quantitative parameters of myelin-sensitive MRI for therapy assessments can now be used for hypomyelination disorders in general.

Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes

BackgroundPrevious studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).Methods3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data.ResultsThe sciatic nerve’s MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r =  − 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve’s MTR peroneal NCV (r =  − 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016).ConclusionsLower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D.Trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03022721. 16 January 2017.Relevance statementMagnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes.Key points• Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients.• Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes.• Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.Graphical

Comparison of 3D Magnetization-transfer- and Spectral-presaturation-with-inversion-recovery-based Neuromelanin Imaging.

Neuromelanin is visualized by optimizing the conditions of longitudinal relaxation (T1)-weighted imaging (T1WI). Although it was originally developed in 2D imaging, 3D imaging has been also reported, and T1WI sequences with magnetization transfer (MT) pulses are now widely used in 3D gradient echo (GRE) sequences. In this study, we assert that the use of spectral presaturation with inversion recovery (SPIR) may also be useful as an alternative to MT pulses, and we optimize SPIR and compare it with MT. Neuromelanin images with MT pulse and SPIR (flip angles [FAs] = 19º, 22º, and 25º) were acquired from 30 healthy volunteers. To achieve the same acquisition time of 5 min, the slab thickness of the MT images was less than 1/3 of those of the SPIR images; the acquisition areas for MT and SPIR were the brainstem and the whole brain, respectively. Visual and quantitative evaluation was performed and compared on the four sequences acquired for the substantia nigra pars compacta (SNc) and the locus coeruleus (LC). For visual assessment, we used the mean score from a 3-point scale by two evaluators. For quantitative evaluation, the contrast ratios of SNc and LC were calculated in comparison with the background tissue signal. In visual assessments, the mean scores of the SPIR FA19º and FA22º images were better than others in the SNc. Regarding LC, the SPIR FA22º image yielded the best mean score. In quantitative evaluations, the MT image was significantly lower than the other three images in SNc. Regarding LC, there were no significant differences among the four acquired images (MT and SPIR FA19º, FA22º, and FA25º). Detection of neuromelanin in SNc and LC was improved by the use of SPIR compared to MT pulse in 3D neuromelanin imaging.

Quantitative magnetic resonance neurography in chronic inflammatory demyelinating polyradiculoneuropathy: A longitudinal study over 6 years.

To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2-weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI). Nerve cross-sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross-sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05). This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response.

Multi-modal neuroimaging signatures predict cognitive decline in multiple sclerosis: A 5-year longitudinal study

BackgroundCognitive impairment is a hallmark of multiple sclerosis (MS) but is usually an under-recorded symptom of disease progression. Identifying the predictive signatures of cognitive decline in people with MS (pwMS) over time is important to ensure effective preventative treatment strategies. Structural and functional brain characteristics as measured by various magnetic resonance (MR) methods have been correlated with variation in cognitive function in MS, but typically these studies are limited to a single MR modality and/or are cross-sectional designs. Here we assess the predictive value of multiple different MR modalities in relation to cognitive decline in pwMS over 5 years. MethodsA cohort of 43 pwMS was assessed at baseline and 5 years follow-up. Baseline (input) data consisted of 70 multi-modal MRI measures for different brain regions including magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and standard volumetrics. Age, sex, disease duration and treatment were included as clinical inputs. Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS) and the Symbol Digit Modalities Test (SDMT). Prediction modelling was performed using the machine learning package - GLMnet, where a penalised regression was applied to identify multi-modal signatures with the most predictive value (and the least error) for each outcome. ResultsThe multi-modal approach to neuroimaging was able to accurately predict cognitive decline in pwMS. The best performing model for change in total ARCS (tARCS) included 16 features from across the various MR modalities and explained 54 % of the variation in change over time (R2=0.54, 95 % CI=0.48–0.51). The features included nine MRS, four volumetric and two DTI parameters. The model also selected disease duration, but not treatment, as a predictive feature. By comparison, the best model for SDMT included several of the same above features and explained 39 % of the change over time (R2=0.39, 95 % CI=0.48–0.51). Conventional volumetric measures were about half as good at predicting change in tARCS score compared to the best multi-modal model (R2=0.26 95 % CI:0.22–0.29). The clinical interpretation of the best predictive model for change in tARCS showed that cognitive decline could be predicted with >90 % accuracy in this cohort (AUC=0.92, SE=0.86 - 0.94). ConclusionMulti-modal MRI signatures can predict cognitive decline in a cohort of pwMS over 5 years with high accuracy. Future studies will benefit from the inclusion of even more MR modalities e.g., functional MRI, quantitative susceptibility mapping, magnetisation transfer imaging, as well as other potential predictors e.g., genetic and environmental factors. With further validation, this signature could be used in future trials with high-risk patients to personalise the management of cognitive decline in pwMS, even in the absence of relapses.

Rapid quantitative magnetization transfer imaging: Utilizing the hybrid state and the generalized Bloch model.

To explore efficient encoding schemes for quantitative magnetization transfer (qMT) imaging with few constraints on model parameters. We combine two recently proposed models in a Bloch-McConnell equation: the dynamics of the free spin pool are confined to the hybrid state, and the dynamics of the semi-solid spin pool are described by the generalized Bloch model. We numerically optimize the flip angles and durations of a train of radio frequency pulses to enhance the encoding of three qMT parameters while accounting for all eight parameters of the two-pool model. We sparsely sample each time frame along this spin dynamics with a three-dimensional radial koosh-ball trajectory, reconstruct the data with subspace modeling, and fit the qMT model with a neural network for computational efficiency. We extracted qMT parameter maps of the whole brain with an effective resolution of 1.24 mm from a 12.6-min scan. In lesions of multiple sclerosis subjects, we observe a decreased size of the semi-solid spin pool and longer relaxation times, consistent with previous reports. The encoding power of the hybrid state, combined with regularized image reconstruction, and the accuracy of the generalized Bloch model provide an excellent basis for efficient quantitative magnetization transfer imaging with few constraints on model parameters.

Grey-matter structure in cortical and limbic regions correlates with general cognitive ability in old age

According to the maintenance hypothesis (Nyberg et al., 2012), structural integrity of the brain’s grey matter helps to preserve cognitive functioning into old age. A corollary of this hypothesis that can be tested in cross-sectional data is that grey-matter structural integrity and general cognitive ability are positively associated in old age. Building on Köhncke et al. (2021), who found that region-specific latent factors of grey-matter integrity are positively associated with episodic memory ability among older adults, we examine associations between general factors of grey-matter integrity and a general factor of cognitive ability in a cross-sectional sample of 1466 participants aged 60–88 years, 319 of whom contributed imaging data. Indicator variables based on T1-weighted images (voxel-based morphometry, VBM), magnetization-transfer imaging (MT), and diffusion tensor imaging-derived mean diffusivity (MD) had sufficient portions of variance in common to establish latent factors of grey-matter structure for a comprehensive set of regions of interest (ROI). Individual differences in grey-matter factors were positively correlated across neocortical and limbic areas, allowing for the definition of second-order, general factors for neocortical and limbic ROI, respectively. Both general grey-matter factors were positively correlated with general cognitive ability. For the basal ganglia, the three modality-specific indicators showed heterogenous loading patterns, and no reliable associations of the general grey-matter factor to general cognitive ability were found. To provide more direct tests of the maintenance hypothesis, we recommend applying the present structural modeling approach to longitudinal data, thereby enhancing the physiological validity of latent constructs of brain structure.

Shared and distinct abnormalities of brain magnetization transfer ratio in schizophrenia and major depressive disorder: a comparative voxel-based meta-analysis.

Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.

SIMPLEX: Multiple phase-cycled bSSFP quantitative magnetization transfer imaging with physic-guided simulation learning of neural network

Most quantitative magnetization transfer (qMT) imaging methods require acquiring additional quantitative maps (such as T1) for data fitting. A method based on multiple phase-cycled bSSFP was recently proposed to enable high-resolution 3D qMT imaging based on least square fitting without any extra acquisition, and thus has high potential for simplifying the qMT procedure. However, the quantification of qMT parameters with this method was suboptimal, limiting its potential for clinical application despite its simpler protocol and higher spatial resolution. To improve the fitting of qMT data obtained with multiple phase-cycled bSSFP, we propose SIMulation-based Physics-guided Learning of neural network for qMT parameters EXtraction, or SIMPLEX. In contrast to previous deep learning supervised approaches for quantitative MR that require the acquisition of input data and corresponding ground truth for training, we leveraged the MR signal model to generate training samples without expensive data curation. The network was trained exclusively with simulation data by predicting the simulation parameters. The same network was applied directly to in-vivo data without additional training. The approach was verified with both simulation and in-vivo data. SIMPLEX showed a decrease in fitting mean squared error for all simulation data compared to the existing least-square fitting method. The in-vivo experiment revealed that the network performed well with the real in vivo data unseen during training. For all experiments, we observed that SIMPLEX consistently improved the quantification quality of the qMT parameters whilst being more robust to noise compared to the prior technique. The proposed SIMPLEX will expedite the routine clinical application of qMT by providing qMT parameters (exchange rate, pool fraction) as well as T1, T2, and ΔB0 maps simultaneously with high spatial resolution, better reliability, and reduced processing time.

Microstructural changes of peripheral nerves in early multiple sclerosis: A prospective magnetic resonance neurography study.

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS). However, there is increasing evidence of peripheral nerve involvement. This study aims to characterize the pattern of peripheral nerve changes in patients with newly diagnosed MS using quantitative magnetic resonance (MR) neurography. In this prospective study, 25 patients first diagnosed with MS according to the revised McDonald criteria (16 female, mean age = 32.8 ± 10.6 years) and 14 healthy controls were examined with high-resolution 3-T MR neurography of the sciatic nerve using diffusion kurtosis imaging (DKI; 20 diffusional directions, b = 0, 700, 1200 s/mm2 ) and magnetization transfer imaging (MTI). In total, 15 quantitative MR biomarkers were analyzed and correlated with clinical symptoms, intrathecal immunoglobulin synthesis, electrophysiology, and lesion load on brain and spine MR imaging. Patients showed decreased fractional anisotropy (mean = 0.51 ± 0.04 vs. 0.56 ± 0.03, p < 0.001), extra-axonal tortuosity (mean = 2.32 ± 0.17 vs. 2.49 ± 0.17, p = 0.008), and radial kurtosis (mean = 1.40 ± 0.23 vs. 1.62 ± 0.23, p = 0.014) and higher radial diffusivity (mean = 1.09 ∙ 10-3  mm2 /s ± 0.16 vs. 0.98 ± 0.11 ∙ 10-3  mm2 /s, p = 0.036) than controls. Groups did not differ in MTI. No significant association was found between MR neurography markers and clinical/laboratory parameters or CNS lesion load. This study provides further evidence of peripheral nerve involvement in MS already at initial diagnosis. The characteristic pattern of DKI parameters indicates predominant demyelination and suggests a primary coaffection of the peripheral nervous system in MS. This first human study using DKI for peripheral nerves shows its potential and clinical feasibility in providing novel biomarkers.

Effects of in utero thyroid hormone exposure on adolescent myelination: Quantitative magnetization transfer imaging in the controlled antenatal thyroid screening study

Effects of in utero thyroid hormone exposure on adolescent myelination: Quantitative magnetization transfer imaging in the controlled antenatal thyroid screening study