Improvement of the thalamocortical white matter network in people with stable treated relapsing-remitting multiple sclerosis over time.

Advanced imaging techniques (tractography) enable the mapping of white matter (WM) pathways and the understanding of brain connectivity patterns. We combined tractography with a network-based approach to examine WM microstructure on a network level in people with relapsing-remitting multiple sclerosis (pw-RRMS) and healthy controls (HCs) over 2 years. Seventy-six pw-RRMS matched with 43 HCs underwent clinical assessments and 3T MRI scans at baseline (BL) and 2-year follow-up (2-YFU). Probabilistic tractography was performed, accounting for the effect of lesions, producing connectomes of 25 million streamlines. Network differences in fibre density across pw-RRMS and HCs at BL and 2-YFU were quantified using network-based statistics (NBS). Longitudinal network differences in fibre density were quantified using NBS in pw-RRMS, and were tested for correlations with disability, cognition and fatigue scores. Widespread network reductions in fibre density were found in pw-RRMS compared with HCs at BL in cortical regions, with more reductions detected at 2-YFU. Pw-RRMS had reduced fibre density at BL in the thalamocortical network compared to 2-YFU. This effect appeared after correction for age, was robust across different thresholds, and did not correlate with lesion volume or disease duration. Pw-RRMS demonstrated a robust and long-distance improvement in the thalamocortical WM network, regardless of age, disease burden, duration or therapy, suggesting a potential locus of neuroplasticity in MS. This network's role over the disease's lifespan and its potential implications in prognosis and treatment warrants further investigation.

Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS.

PURPOSE: To investigate how the microstructural neural integrity of cortico-thalamic-striatal (CTS) tracts correlate with fatigue and disability over time. The primary outcome was diffusion tensor imaging (DTI) metrics change over time, and the secondary outcome was correlations with fatigue and disability in people with RRMS (pw-RRMS). METHODS: 76 clinically stable pw-RRMS and 43 matched healthy controls (HCs). The pw-RRMS cohort consisted of three different treatment subgroups. All participants underwent disability, cognitive, fatigue and mental health assessments. Structural and diffusion scans were performed at baseline (BL) and 2-year follow-up (2-YFU) for all participants. Fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD, AD) of normal-appearing white matter (NAWM) and white matter lesion (WML) in nine tracts-of-interests (TOIs) were estimated using our MRtrix3 in-house pipeline. RESULTS: We found significant BL and 2-YFU differences in most diffusion metrics in TOIs in pw-RRMS compared to HCs (pFDR ≤ 0.001; false-detection-rate (FDR)-corrected). There was a significant decrease in WML diffusivities and an increase in FA over the follow-up period in most TOIs (pFDR ≤ 0.001). Additionally, there were no differences in DTI parameters across treatment groups. AD and MD were positively correlated with fatigue scores (r ≤ 0.33, p ≤ 0.01) in NAWM-TOIs, while disability (EDSS) was negatively correlated with FA in most NAWM-TOIs (|r|≤0.31, p ≤ 0.01) at both time points. Disability scores correlated with all diffusivity parameters (r ≤ 0.29, p ≤ 0.01) in most WML-TOIs at both time points. CONCLUSION: Statistically significant changes in diffusion metrics in WML might be indicative of integrity improvement over two years in CTS tracts in clinically stable pw-RRMS. This finding represents structural changes within lesioned tracts. Measuring diffusivity in pw-RRMS affected tracts might be a relevant measure for future remyelination clinical trials.

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

BACKGROUND: Cognitive 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. METHODS: A 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. RESULTS: The 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). CONCLUSION: Multi-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.

MR myelin imaging in multiple sclerosis: A scoping review.

The inability of disease-modifying therapies to stop the progression of multiple sclerosis (MS), has led to the development of a new therapeutic strategy focussing on myelin repair. While conventional MRI lacks sensitivity for quantifying myelin damage, advanced MRI techniques are proving effective. The development of targeted therapeutics requires histological validation of myelin imaging results, alongside the crucial task of establishing correlations between myelin imaging results and clinical assessments, so that the effectiveness of therapeutic interventions can be evaluated. The aims of this scoping review were to identify myelin imaging methods - some of which have been histologically validated, and to determine how these approaches correlate with clinical assessments of people with MS (pwMS), thus allowing for effective therapeutic evaluation. A search of two databases was undertaken for publications relating to studies on adults MS using either MRI/MR-histology of the MS brain in the range 1990-to-2022. The myelin imaging methods specified were relaxometry, magnetization transfer, and quantitative susceptibility. Relaxometry was used most frequently, with myelin water fraction (MWF) being the primary metric. Studies conducted on tissue from various regions of the brain showed that MWF was significantly lower in pwMS than in healthy controls. Magnetization transfer ratio indicated that the macromolecular content of lesions was lower than that of normal-appearing tissue. Higher magnetic susceptibility of lesions were indicative of myelin breakdown and iron accumulation. Several myelin imaging metrics were correlated with disability, disease severity and duration. Many studies showed a good correlation between myelin measured histologically and by MR myelin imaging techniques.

Non-contrast based approach for liver function quantification using Bayesian-based intravoxel incoherent motion diffusion weighted imaging: A pilot study.

PURPOSE: Liver cirrhosis disrupts liver function and tissue perfusion, detectable by magnetic resonance imaging (MRI). Assessing liver function at the voxel level with 13-b value intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) could aid in radiation therapy liver-sparing treatment for patients with early impairment. This study aimed to evaluate the feasibility of IVIM-DWI for liver function assessment and correlate it with other multiparametric (mp) MRI methods at the voxel level. METHOD: This study investigates the variability of apparent diffusion coefficient (ADC) derived from 13-b value IVIM-DWI and B1-corrected dual flip angle (DFA) T1 mapping. Experiments were conducted in-vitro with QIBA and NIST phantoms and in 10 healthy volunteers for IVIM-DWI. Additionally, 12 patients underwent an mp-MRI examination. The imaging protocol included a 13-b value IVIM-DWI sequence for generating IVIM parametric maps. B1-corrected DFA T1 pulse sequence was used for generating T1 maps, and Gadoxatate low temporal resolution dynamic contrast-enhanced (LTR-DCE) MRI was used for generating the Hepatic extraction fraction (HEF) map. The Mann-Whitney U test was employed to compare IVIM-DWI parameters (Pure Diffusion, Dslow ; Pseudo diffusion, Dfast ; and Perfusion Fraction, Fp ) between the healthy volunteer and patient groups. Furthermore, in the patient group, statistical correlations were assessed at a voxel level between LTR-DCE MRI-derived HEF, T1 post-Gadoxetate administration, ΔT1%, and various IVIM parameters using Pearson correlation. RESULTS: For-vitro measurements, the maximum coefficient of variation of the ADC and T1 parameters was 12.4% and 16.1%, respectively. The results also showed that Fp and Dfast were able to distinguish between healthy liver function and mild liver function impairment at the global level, with p = 0.002 for Fp and p < 0.001 for Dfast . Within the patient group, these parameters also exhibited a moderate correlation with HEF at the voxel level. CONCLUSION: Overall, the study highlighted the potential of Dfast and Fp for detecting liver function impairment at both global and pixel levels.

Fast WASABI post-processing: Access to rapid B0 and B1 correction in clinical routine for CEST MRI.

CEST MRI methods, such as APT and NOE imaging reveal biomarkers with significant diagnostic potential due to their ability to access molecular tissue information. Regardless of the technique used, CEST MRI data are affected by static magnetic B0 and radiofrequency B1 field inhomogeneities that degrade their contrast. For this reason, the correction of B0 field-induced artefacts is essential, whereas accounting for B1 field inhomogeneities have shown significant improvements in image readability. In a previous work, an MRI protocol called WASABI was presented, which can map simultaneously B0 and B1 field inhomogeneities, while maintaining the same sequence and readout types as used for CEST MRI. Despite the highly satisfactory quality of B0 and B1 maps computed from the WASABI data, the post-processing method is based on an exhaustive search of a four-parameter space and an additional four-parameter non-linear model fitting step. This leads to long post-processing times that are prohibitive in clinical practice. This work provides a new method for fast post-processing of WASABI data with outstanding acceleration of the parameter estimation procedure and without compromising its stability. The resulting computational acceleration makes the WASABI technique suitable for clinical use. The stability of the method is demonstrated on phantom data and clinical 3 Tesla in vivo data.

CEST 2022 - Differences in APT-weighted signal in T1 weighted isointense lesions, black holes and normal-appearing white matter in people with relapsing-remitting multiple sclerosis.

PURPOSE: To evaluate amide proton transfer weighted (APTw) signal differences between multiple sclerosis (MS) lesions and contralateral normal-appearing white matter (cNAWM). Cellular changes during the demyelination process were also assessed by comparing APTw signal intensity in T1weighted isointense (ISO) and hypointense (black hole -BH) MS lesions in relation to cNAWM. METHODS: Twenty-four people with relapsing-remitting MS (pw-RRMS) on stable therapy were recruited. MRI/APTw acquisitions were undertaken on a 3 T MRI scanner. The pre and post-processing, analysis, co-registration with structural MRI maps, and identification of regions of interest (ROIs) were all performed with Olea Sphere 3.0 software. Generalized linear model (GLM) univariate ANOVA was undertaken to test the hypotheses that differences in mean APTw were entered as dependent variables. ROIs were entered as random effect variables, which allowed all data to be included. Regions (lesions and cNAWM) and/or structure (ISO and BH) were the main factor variables. The models also included age, sex, disease duration, EDSS, and ROI volumes as covariates. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of these comparisons. RESULTS: A total of 502 MS lesions manually identified on T2-FLAIR from twenty-four pw-RRMS were subcategorized as 359 ISO and 143 BH with reference to the T1-MPRAGE cerebral cortex signal. Also, 490 ROIs of cNAWM were manually delineated to match the MS lesion positions. A two-tailed t-test showed that mean APTw values were higher in females than in males (t = 3.52, p < 0.001). Additionally, the mean APTw values of MS lesions were higher than those of cNAWM after accounting for covariates (mean lesion = 0.44, mean cNAWM = 0.13, F = 44.12, p < 0.001).The mean APTw values of ISO lesions were higher than those of cNAWM after accounting for covariates (mean ISO lesions = 0.42, mean cNAWM = 0.21, F = 12.12, p < 0.001). The mean APTw values of BH were also higher than those of cNAWM (mean BH lesions = 0.47, mean cNAWM = 0.033, F = 40.3, p < 0.001). The effect size (i.e., difference between lesion and cNAWM) for BH was found to be higher than for ISO (14 vs. 2). Diagnostic performance showed that APT was able to discriminate between all lesions and cNAWM with an accuracy of >75% (AUC = 0.79, SE = 0.014). Discrimination between ISO lesions and cNAWM was accomplished with an accuracy of >69% (AUC = 0.74, SE = 0.018), while discrimination between BH lesions and cNAWM was achieved at an accuracy of >80% (AUC = 0.87, SE = 0.021). CONCLUSIONS: Our results highlight the potential of APTw imaging for use as a non-invasive technique that is able to provide essential molecular information to clinicians and researchers so that the stages of inflammation and degeneration in MS lesions can be better characterized.

Stability of longitudinal DTI metrics in MS with treatment of injectables, fingolimod and dimethyl fumarate.

BACKGROUND AND PURPOSE: Diffusion MRI (dMRI) is sensitive to microstructural changes in white matter of people with relapse-remitting multiple sclerosis (pw-RRMS) that lead to progressive disability. The role of diffusion in assessing the efficacy of different therapies requires more investigation. This study aimed to evaluate selected dMRI metrics in normal-appearing white matter and white matter-lesion in pw-RRMS and healthy controls longitudinally and compare the effect of therapies given. MATERIAL AND METHODS: Structural and dMRI scans were acquired from 78 pw-RRMS (29 injectables, 36 fingolimod, 13 dimethyl fumarate) and 43 HCs at baseline and 2-years follow-up. Changes in dMRI metrics and correlation with clinical parameters were evaluated. RESULTS: Differences were observed in most clinical parameters between pw-RRMS and HCs at both timepoints (p ≤ 0.01). No significant differences in average changes over time were observed for any dMRI metric between treatment groups in either tissue type. Diffusion metrics in NAWM and WML correlated negatively with most cognitive domains, while FA correlated positively at baseline but only for NAWM at follow-up (p ≤ 0.05). FA correlated negatively with disability in NAWM and WML over time, while MD and RD correlated positively only in NAWM. CONCLUSIONS: This is the first DTI study comparing the effect of different treatments on dMRI parameters over time in a stable cohort of pw-RRMS. The results suggest that brain microstructural changes in a stable MS cohort are similar to HCs independent of the therapies used.

Determination of hepatic extraction fraction with gadoxetate low-temporal resolution DCE-MRI-based deconvolution analysis: validation with ALBI score and Child-Pugh class.

INTRODUCTION: In this study, we aimed to investigate the feasibility of gadoxetate low-temporal resolution (LTR) DCE-MRI for voxel-based hepatic extraction fraction (HEF) quantification for liver sparing radiotherapy using a deconvolution analysis (DA) method. METHODS: The accuracy and consistency of the deconvolution implementation in estimating liver function was first assessed using simulation data. Then, the method was applied to DCE-MRI data collected retrospectively from 64 patients (25 normal liver function and 39 cirrhotic patients) to generate HEF maps. The normal liver function patient data were used to measure the variability of liver function quantification. Next, a correlation between HEF and ALBI score (a new model for assessing the severity of liver dysfunction) was assessed using Pearson's correlation. Differences in HEF between Child-Pugh score classifications were assessed for significance using the Kruskal-Wallis test for all patient groups and Mann-Whitney U-test for inter-groups. A statistical significance was considered at a P-value <0.05 in all tests. RESULTS: The results showed that the implemented method accurately reproduced simulated liver function; root-mean-square error between estimated and simulated liver response functions was 0.003, and the coefficient-of-variance of HEF was <20%. HEF correlation with ALBI score was r = -0.517, P < 0.0001, and HEF was significantly decreased in the cirrhotic patients compared to normal patients (P < 0.0001). Also, HEF in Child-Pugh B/C was significantly lower than in Child-Pugh A (P = 0.024). CONCLUSION: The study demonstrated the feasibility of gadoxetate LTR-DCE MRI for voxel-based liver function quantification using DA. HEF could distinguish between different grades of liver function impairment and could potentially be used for functional guidance in radiotherapy.

Neurometabolic changes in multiple sclerosis: Fingolimod versus beta interferon or glatiramer acetate therapy.

BACKGROUND AND PURPOSE: Fingolimod has been shown to be more effective in reducing relapse rate and disability than injectable therapies in clinical trials. An increase in N-acetylaspartate (NAA) as measured by MR spectroscopy is correlated with maintaining axonal metabolic functions. This study compared the neurometabolic and volumetric changes in relapsing-remitting multiple sclerosis (RRMS) patients on fingolimod or injectable therapies with healthy controls (HCs). METHODS: Ninety-eight RRMS (52 on fingolimod, 46 on injectable therapies (27 on glatiramer acetate and 19 on interferon) were age and sex-matched to 51 HCs. RRMS patients underwent cognitive, fatigue, and mental health assessments, as well as an Expanded disability status scale (EDSS). MRI/S was acquired from the hippocampus, posterior cingulate gyrus (PCG), and prefrontal cortex (PFC). Volumetric and neurometabolic measures were compared across cohorts using a univariate general linear model and correlated with clinical severity and neuropsychological scores. RESULTS: Clinical parameters, MR-volumetric, and neurometabolic profiles showed no differences between treatment groups (p > .05). Compared to HCs, both RRMS cohorts showed volume changes in white matter (-13%), gray matter (-16%), and cerebral spinal fluid (CSF) (+17-23%), as well as reduced NAA (-17%, p = .001, hippocampus), (-7%, p = .001, PCG), and (-9%, p = .001, PFC). MRI/S metrics in three regions were moderately correlated with cognition and fatigue functions. CONCLUSION: While both treatment arms showed overall similar volumetric and neurometabolic profiles, longitudinal studies are warranted to clarify neurometabolic changes and associations with treatment efficacy.

Prediction of Conversion from CIS to Clinically Definite Multiple Sclerosis Using Convolutional Neural Networks.

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system (CNS). Early diagnosis of MS is highly desirable as treatments are more effective in preventing MS-related disability when given in the early stages of the disease. The main aim of this research is to predict the occurrence of a second MS-related clinical event, which indicates the conversion of clinically isolated syndrome (CIS) to clinically definite MS (CDMS). In this study, we apply a branch of artificial intelligence known as deep learning and develop a fully automated algorithm primed with convolutional neural network (CNN) that has the ability to learn from MRI scan features. The basic architecture of our algorithm is that of the VGG16 CNN model, but amended such that it can handle MRI DICOM images. A dataset comprised of scans acquired using two different scanners was used for the purposes of verification of the algorithm. A group of 49 patients had volumetric MRI scans taken at onset of the disease and then again one year later using one of the two scanners. In total, this yielded 7360 images which were then used for training, validation, and testing of the algorithm. Initially, these raw images were taken through 4 steps of preprocessing. In order to boost the efficiency of the process, we pretrained our algorithm using the publicly available ADNI dataset used to classify Alzheimer's disease. Finally, we used our preprocessed dataset to train and test the algorithm. Clinical evaluation conducted a year after the first time point revealed that 26 of the 49 patients had converted to CDMS, while the remaining 23 had not. Results of testing showed that our algorithm was able to predict the clinical results with an accuracy of 88.8% and with an area under the curve (AUC) of 91%. A highly accurate algorithm was developed using CNN approach to reliably predict conversion of patients with CIS to CDMS using MRI data from two different scanners.

Effect of high-intensity interval training on hippocampal metabolism in older adolescents.

Although well-evidenced in older adults, the effects of exercise on the hippocampus in youth are relatively unknown. This study examined the impact of a 6-month school-based physical activity intervention on hippocampal metabolism in adolescents using magnetic resonance spectroscopy. A subset of lower fit older adolescents [N = 56, 61% female, 16.1 ± 0.4 years] was included from four secondary schools (10 classes) in New South Wales, Australia, who were participating in a larger cluster randomized controlled trial. Participants were randomized to the Burn 2 Learn (B2L) intervention (five classes, 30 participants) or a control group (five classes, 26 participants). Changes in hippocampal metabolism were assessed using linear mixed models adjusted for clustering at the class level. We observed group-by-time effects for the B2L intervention on N-acetylaspartate (NAA) (+2.66 mmol/L, 95% CI 0.20 to 5.11, d = 0.66) and glutamate+glutamine (Glx) (+3.38 mmol/L, 95% CI 0.34 to 6.42, d = 0.67) in the left hippocampus. Increases in left hippocampal NAA and Glx concentrations were associated with improvements in cardiorespiratory fitness (NAA: rs  = 0.52, p = .016; Glx: rs  = 0.57, p = .007), lower body muscular fitness (NAA: rs  = 0.49, p = .018; Glx: rs  = 0.59, p = .003), and working memory (NAA: rs  = 0.42, p = .032; Glx: rs  = 0.43, p = .028) in the intervention group. Our findings suggest physical activity may improve hippocampal metabolism in lower fit older adolescents with implications for working memory. Further studies involving larger samples are needed to replicate our findings.

Neural diffusion tensor imaging metrics correlate with clinical measures in people with relapsing-remitting MS.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) can detect microstructural changes of white matter in multiple sclerosis (MS) and might clarify mechanisms responsible for disability. Thus, we aimed to compare DTI metrics in relapsing-remitting MS patients (RRMS) with healthy controls (HCs), and explore the correlations between DTI metrics, total brain white matter (TBWM) and white matter lesion (WML) with clinical parameters compared to volumetric measures. MATERIAL AND METHODS: 37 RRMS patients and 19 age/sex-matched HCs were included. All participants had clinical assessments, structural and diffusion scans on a 3T MRI. Volumetric and white matter DTI metrics; fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD and AD) were estimated and correlated with clinical parameters. The mean group differences were calculated using t-tests, and univariate correlations with Pearson correlation coefficients. RESULTS: Compared to HCs, statistically significant increases in MD (+3.6%), RD (+4.8%), AD (+2.7%) and a decrease in FA (-4.3%) for TBWM in RRMS was observed (p < .01). MD and RD in TBWM and AD in WML correlated moderately with disability status. Volumetric segmentation indicated a decrease in the total brain volume, GM and WM(-5%) with a reciprocal increase in CSF(+26%) in RRMS(p < .01). Importantly, DTI parameters showed a medium correlation with cognitive domains in contrast to white matter-related volumetric measurements in RRMS(Pearson correlation, p < .05). CONCLUSIONS: Our study shows a correlation of DTI metrics with clinical symptoms of MS, in particular cognition. More generally, these findings indicated that DTI is a useful and unique technique for evaluating the clinical features of white matter disease and warrants further investigation into its clinical role.

Quantified hemodynamic parameters of the venous system in multiple sclerosis: A systematic review.

BACKGROUND: Multiple Sclerosis (MS) is a complex neurodegenerative condition that is influenced by a combination of genetic and environmental factors. Included in these factors is the venous system, however, the extent to which it influences the etiology of MS has yet to be fully characterised. The aim of this review is to critically summarize the literature available concerning the venous system in MS, primarily concerning specific data on the venous pressure and blood flow in this system. METHODS: A systematic review was conducted with the application of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The advanced search functions of both the Scopus and PubMed databases were used to conduct the literature search, resulting in 136 unique articles initially identified. Applying relevant exclusion criteria, 22 of the studies were chosen for this review. RESULTS: The selected studies were analysed for venous pressure and blood flow related findings, with 14 studies contributing data on the internal jugular vein (IJV) flow rate, 5 on blood flows of the intracranial venous sinuses, 2 on blood flow pulsatility and 6 supplying information relevant to the venous pressure (3 studies contributed to multiple areas). The general findings of the review included that the IJV flow was not significantly different between MS patients and controls, however, there were variances between stenotic (S) and non-stenotic (NS) MS patients. Due to the limited data in the other two areas defined in this review, further research is required to establish if any variances in MS are present. CONCLUSION: It remains unclear if there are significant differences in many flow variables between MS patients and controls considered in this review. It would be advantageous if future work in this area focused on understanding the hemodynamics of this system, primarily concerning how the flow rate, venous pressure and vascular resistance are related, and any impact that these factors have on the etiology of MS.

The emerging role of artificial intelligence in multiple sclerosis imaging.

BACKGROUND: Computer-aided diagnosis can facilitate the early detection and diagnosis of multiple sclerosis (MS) thus enabling earlier interventions and a reduction in long-term MS-related disability. Recent advancements in the field of artificial intelligence (AI) have led to the improvements in the classification, quantification and identification of diagnostic patterns in medical images for a range of diseases, in particular, for MS. Importantly, data generated using AI techniques are analyzed automatically, which compares favourably with labour-intensive and time-consuming manual methods. OBJECTIVE: The aim of this review is to assist MS researchers to understand current and future developments in the AI-based diagnosis and prognosis of MS. METHODS: We will investigate a variety of AI approaches and various classifiers and compare the current state-of-the-art techniques in relation to lesion segmentation/detection and prognosis of disease. After briefly describing the magnetic resonance imaging (MRI) techniques commonly used, we will describe AI techniques used for the detection of lesions and MS prognosis. RESULTS: We then evaluate the clinical maturity of these AI techniques in relation to MS. CONCLUSION: Finally, future research challenges are identified in a bid to encourage further improvements of the methods.

Indexing cerebrovascular health using near-infrared spectroscopy.

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, [Formula: see text], of cerebrovascular health. [Formula: see text] is a novel use of the NiRS technology. [Formula: see text] is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both [Formula: see text] and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, [Formula: see text], and magnetic resonance imaging (MRI) blood flow pulsatility index, [Formula: see text]. The [Formula: see text] correlations with Age, CRF, [Formula: see text] and [Formula: see text] all are significant, i.e., [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.

Diagnosis of transition zone prostate cancer by multiparametric MRI: added value of MR spectroscopic imaging with sLASER volume selection.

BACKGROUND: Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refocusing (sLASER) sequence with gradient offset independent adiabaticity (GOIA) pulses in addition to the routine mp-MRI, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and quantitative dynamic contrast enhancement (DCE) for transition zone prostate cancer detection, localization and grading. METHODS: Forty-one transition zone prostate cancer patients underwent mp-MRI with an external phased-array coil. Normal and cancer regions were delineated by two radiologists and divided into low-risk, intermediate-risk, and high-risk categories based on TRUS guided biopsy results. Support vector machine models were built using different clinically applicable combinations of T2WI, DWI, DCE, and MRSI. The diagnostic performance of each model in cancer detection was evaluated using the area under curve (AUC) of the receiver operating characteristic diagram. Then accuracy, sensitivity and specificity of each model were calculated. Furthermore, the correlation of mp-MRI parameters with low-risk, intermediate-risk and high-risk cancers were calculated using the Spearman correlation coefficient. RESULTS: The addition of MRSI to T2WI + DWI and T2WI + DWI + DCE improved the accuracy, sensitivity and specificity for cancer detection. The best performance was achieved with T2WI + DWI + MRSI where the addition of MRSI improved the AUC, accuracy, sensitivity and specificity from 0.86 to 0.99, 0.83 to 0.96, 0.80 to 0.95, and 0.85 to 0.97 respectively. The (choline + spermine + creatine)/citrate ratio of MRSI showed the highest correlation with cancer risk groups (r = 0.64, p < 0.01). CONCLUSION: The inclusion of GOIA-sLASER MRSI into conventional mp-MRI significantly improves the diagnostic accuracy of the detection and aggressiveness assessment of transition zone prostate cancer.

Altered in vivo brain GABA and glutamate levels are associated with multiple sclerosis central fatigue.

PURPOSE: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as  γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. METHODS: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). RESULTS: RRMS patients had higher fatigue scores relative to HC (p ≤  0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p =  0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p =  0.008) and Glx (r = 0.511, p =  0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤  0.04) and positively with PFC Glx (r = 0.480, p =  0.028). CONCLUSION: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS.

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy.

BACKGROUND AND PURPOSE: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY). METHODS: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤ .05). Only GPC showed positive correlation with all fatigue domains (r = .537, P ≤ .05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = -.345 to -.580, P ≤ .05). While tyrosine showed positive correlation with MFIS (r = .499, P ≤ .05), cognitive fatigue was negatively correlated with total GSH (r = -.530, P ≤ .05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.

Indexing Cerebrovascular Health Using Transcranial Doppler Ultrasound.

Transcranial Doppler (TCD) blood flow velocity has been extensively used in biomedical research as it provides a cost-effective and relatively simple approach to assess changes in cerebral blood flow dynamics and track cerebrovascular health status. In this article we introduce a new TCD-based timing index, TITCD, as an indicator of vascular stiffening and vascular health. We investigate the correlations of the new index and the existing indices, namely the pulsatility index and the augmentation index, with age, cardiorespiratory fitness (CRF) and magnetic resonance imaging (MRI) blood flow pulsatility index (PIMRI). Notably, the new index showed stronger correlations with CRF (r = -0.79) and PIMRI (r = 0.53) compared with the augmentation index (r = -0.65 with CRF and no significant correlation with PIMRI) and the pulsatility index (no significant correlations with CRF or PIMRI), and a similar correlation with age as the augmentation index. The clearer relationship of the proposed timing index with vascular aging factors underlines its utility as an early indicator of vascular stiffening.