Magnetic Resonance Imaging Assessment Research Articles

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

From convergence insufficiency to functional reorganization: Alongitudinal randomized controlled trial of treatment-induced connectivity plasticity.

Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting-state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office-based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task-related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one-hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting-state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t-tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group-level analysis for correlations with clinical measures. Paired t-test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)-SEF-Right (R)-V1, L-SEF-CV, R-SEF-R-PEF, R-SEF-L-V1, R-SEF-R-V1, R-SEF-CV, R-PEF-CV, L-V1-CV, R-V1-CV, and L-V1-R-V1. Significant correlations were observed between the RSFC strength of the R-SEF-R-PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants.

Elective direct current cardioversion of atrial fibrillation - silent brain infarction and health related quality of life.

Atrial fibrillation (AF) increases the risk for stroke, dementia and impaired health related quality of life (HRQL). Elective direct current cardioversion (ECV) is often used to restore sinus rhythm, but is associated with thromboembolism. While larger strokes usually produce symptoms, subclinical ones may go unrecognized and may cause cognitive and functional decline over time. In the current study, we sought to evaluate the effects of ECV on silent brain infarctions and HRQL in patients with AF. Patients with AF (n=46) underwent brain magnetic resonance imaging (MRI) and HRQL assessment using the EuroQL-5D5L questionnaire before and after ECV. Implantable loop recorders (ILR) were used to observe the rate of early AF recurrences within the first thirty days. All patients were treated with anticoagulants according to guidelines. The primary endpoint was silent brain infarction assessed by brain MRI within the first two weeks after ECV. Secondary endpoints were the change in HRQL and its association with AF recurrence at follow-up and by ILR recordings. New silent brain infarction after ECV was detected in one patient. At follow-up visit after 19.1 days AF recurrence was detected by 12-lead ECG in 13 patients (28.3 %), whereas 27 patients (58.7 %) had AF recurrence recorded by ILR within the first thirty days after ECV. European Heart Rhythm Association (EHRA) symptom score and the EuroQL-5d5L score were improved after ECV. Silent brain infarctions may occur after ECV despite anticoagulation treatment. Early AF recurrence is frequent. ECV positively affects HRQL mainly in those patients with sustained sinus rhythm at follow-up.

Bridge-Enhanced Anterior Cruciate Ligament Restoration: 6-Year Results From the First-in-Human Cohort Study.

Bridge-enhanced anterior cruciate ligament restoration (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with an extracellular matrix implant plus autologous blood to facilitate native ACL healing. The purpose of this study was to compare the 6-year follow-up outcomes of patients who underwent the BEAR procedure with those of a nonrandomized concurrent control group receiving autograft ACL reconstruction (ACLR) in the first-in-human safety study of the BEAR implant (BEAR I trial). Based on the 2-year results, it was hypothesized that isometric hamstring strength after the BEAR procedure would be greater than that after ACLR and that there would be no other differences in outcomes at 6 years. Cohort study, Level of evidence, 2. Ten patients underwent BEAR and 10 received ACLR with a 4-stranded hamstring autograft. Outcomes assessed included the record of subsequent surgeries, the International Knee Documentation Committee (IKDC) Subjective Knee Score, IKDC physical examination grade, the Knee injury and Osteoarthritis Outcome Score, instrumented knee laxity, functional outcomes (ie, muscle strength assessments and hop testing), and qualitative magnetic resonance imaging assessment. Comparisons between treatments were based on computations of the mean differences and the associated 95% CIs. One patient in the BEAR group and 3 patients in the ACLR group were lost to follow-up. In the period between 2 and 6 years, 1 patient in each group underwent revision surgery. There were no differences between groups at the 6-year follow-up in any of the outcome measures except for isometric hamstring strength, which was approximately equal to that of the contralateral knee in the BEAR group and <44% of that in the contralateral knee in the ACLR group (P < .01). This preliminary study suggests that the outcomes of BEAR and ACLR with a hamstring tendon graft may be similar at the 6-year follow-up and warrants investigation of the BEAR procedure in a larger cohort of patients.

Magnetic Resonance Imaging Assessment of Pulmonary Vascularity in Preterm Infants with Bronchopulmonary Dysplasia

Introduction: Pulmonary hypertension often complicates bronchopulmonary dysplasia (BPD) and infants with BPD plus pulmonary hypertension experience higher mortality rates. Current methods to evaluate pulmonary hypertension fail to evaluate the primary cause of this disease. We hypothesize that preterm infants with BPD experience altered pulmonary vascular growth and that magnetic resonance imaging (MRI) can be used to assess vascularity in BPD. Methods: In this observational cohort study, preterm infants with BPD (n = 33) and controls (n = 6) received a postnatal chest MRI that included a 2-dimensional time-of-flight acquisition. Semi-automatic segmentation was performed to measure vascularity parameters including vascular volume and density (vascular density = vascular volume/lung volume). Results: Vascular volume on MRI increases with post-menstrual age (877.2 mm3/week); however, the vascular density does not significantly change. Vascular volume is higher in infants with more severe BPD (p < 0.002), but vascular density did not significantly change when comparing mild, moderate, and severe BPD. Vascular density in infants with severe BPD requiring tracheostomy trended lower when compared to infants not requiring tracheostomy (0.18 mm3/mm3 vs. 0.27 mm3/mm3, p = 0.06). Vascular density increases with increasing days of inhaled nitric oxide (iNO) therapy in infants with severe BPD (0.02 mm3/mm3/week of iNO, rho = +0.56, p = 0.03). Conclusion: Neonatal MRI can be used to assess pulmonary vascularity in preterm infants with BPD. Infants with BPD experience altered vascular growth and while higher vascular volume is associated with more severe BPD, lower vascular density trends toward worse clinical outcomes. Vascular density increases with iNO therapy in severe BPD.

MRI assessment of adipose tissue fatty acid composition in the UK Biobank and its association with diet and disease.

This study aimed to assess the fatty acid (FA) composition of abdominal subcutaneous and visceral adipose tissue (ASAT and VAT, respectively) in the UK Biobank imaging cohort (N = 33,823) using magnetic resonance imaging (MRI). We measured the fractions of saturated, monounsaturated, and polyunsaturated FA (fSFA, fMUFA, and fPUFA, respectively) in ASAT and VAT from multiecho MRI scans. We selected a subcohort of participants who followed a vegan and an omnivore diet (N = 36) to validate the effect of diet on adipose tissue. In the wider imaging cohort, we examined the relationships between adipose tissue FA composition and various traits related to disease and body size. We measured adipose tissue FA composition for over 33,000 participants, revealing higher fSFA and fPUFA and lower fMUFA in VAT (p < 0.00016). fMUFA and fPUFA were higher in ASAT and lower in VAT for women (p < 0.00016). Vegan participants exhibited lower fSFA in both ASAT and VAT (p < 0.00016). VAT fSFA and fMUFA showed significant associations with disease, as well as anthropometric variables. This extensive analysis revealed the relationships between adipose tissue FA composition and a range of factors in a diverse population, highlighting the importance of studying body adipose tissue beyond its quantity.

Assessment of 4D flow MRI for quantification of left-to-right shunt in pediatric patients with ventricular septal defect: comparison with right heart catheterization.

The percentage of shunt fraction significantly impacts the management of patients with congenital shunts, influencing strategic choices such as surgical or interventional procedures. This study compared the estimated shunt fraction (the ratio of pulmonary-to-systemic flow, Qp/Qs) for quantifying the left-to-right shunt in children with ventricular septal defect (VSD) using heart catheterization, four-dimensional (4D) flow, and two-dimensional (2D) flow magnetic resonance imaging (MRI). The goal was to establish a non-invasive and reliable measurement ratio between pulmonary and systemic blood flow in these patients. Between July 2022 and June 2023, patients scheduled to undergo invasive right heart catheterization were included in this study. MRI was performed one hour before the catheterization procedure. The correlation of shunt fraction was assessed between all methods after calculating the Qp/Qs ratio from 2D and 4D flow MRI and catheterization. A total of 24 patients (aged 3-15 years, eight females) were ultimately included in the study. The Qp/Qs ratios obtained from 4D flow had a robust correlation (correlation coefficient r = 0.962) compared to those obtained during catheterization. Cardiac catheterization recorded the mean shunt fraction at 1.499 ± 0.396, while 4D flow measured it at 1.403 ± 0.344, with no significant difference between the two techniques. Moreover, there was a reasonable correlation (r = 0.894) between 2D flow measurements of Qp/Qs and the results obtained from catheterization, with a mean shunt fraction of 1.326 ± 0.283. 4D flow MRI has the potential to be a non-invasive method for accurately measuring the left-to-right shunt in children with VSD.

Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Explainable machine learning on baseline MRI predicts multiple sclerosis trajectory descriptors.

Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: β1, β2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.

Stereo electroencephalography-guided radiofrequency ablation in focal epilepsia partialis continua: illustrative case.

Epilepsia partialis continua (EPC) is a variant of focal motor status epilepticus that can occur as a single or repetitive episode with progressive or nonprogressive characteristics. The authors describe the feasibility of identifying focal EPC in a 33-year-old woman using video electroencephalography (VEEG), electroencephalography source localization, [18F]fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, and psychiatric and neuropsychological assessments and of treating it with stereo electroencephalography-guided radiofrequency (SEEG-RF) ablation. EPC comprised recurrent myoclonus of the right thigh and iliopsoas with a progressive pain syndrome after left anterior-temporo-mesial resection. Switching between VEEG under regular and epidural block helped to define myoclonus as the presenting ictal symptom with a suspected seizure onset zone in the left parietal paramedian lobule. After the epileptic network was identified, SEEG-RF ablation abolished all seizures. No correlation was found between pain and VEEG/SEEG abnormalities. Rehabilitation began 3 days after the SEEG-RF ablation. By 1 year of follow-up, the patient had no EPC and could walk with assistance in rehabilitation; however, due to the abrupt abolishment of EPC and underlying psychological factors, the patient perceived her pain as overriding, which prevented her from walking. The application of SEEG-RF ablation is an efficient therapeutic option for focal EPC with special concerns regarding concurrent nonepileptic pain. https://thejns.org/doi/10.3171/CASE23611.

White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

The Added Value of Diffusion Weighted MR Images in Assessment of Benign Prostatic Lesions and Prostatic Carcinoma

The Added Value of Diffusion Weighted MR Images in Assessment of Benign Prostatic Lesions and Prostatic Carcinoma

Poster 336: Reliability of Preoperative MRI in the Prediction of ACL Tear Type

Objectives: Anterior cruciate ligament (ACL) tears are among the most frequent ligament injuries in the United States. Most of these injuries are treated surgically, depending on patient-specific factors. Management of these injuries includes nonoperative management with stepwise rehabilitation or surgical treatment with ACL repair or reconstruction. Patient goals, a clinical evaluation, and preoperative MRI imaging are generally assessed to inform the choice of treatment. Classification of ACL tear-type based on stump morphology is critical to preoperative planning, as it can determine a patient’s eligibility for ACL preservation techniques. We aim to determine the efficacy of preoperative magnetic resonance imaging (MRI) in predicting ruptured ACL stump morphology and thus assist in preoperative planning and decision-making. Methods: This retrospective observational study utilized chart review from the case log of a single surgeon at an urban tertiary institution. The review identified patients who underwent the Bridge Enhanced ACL Repair (BEAR) procedure between January 1, 2022 and August 31, 2023. The inclusion criteria included patients who underwent a primary ACL repair with the BEAR technique and had adequate intraoperative and MRI images available for review. Patients excluded were those with inadequate intraoperative imaging or MRI imaging that was unavailable for review. For each patient included, the two senior authors assessed the morphology of the ACL stump on MRI (sagittal T2, coronal T2) and intraoperative arthroscopy images in a blinded manner and assigned a classification grade to each. The MRI-based morphology and the intraoperative image morphology of the tears were classified based on a system validated by DeFelice et al, which includes types 1 to 5 based on the location of the tear from most proximal to most distal. The correlation between the preoperative MRI assessment and the intraoperative arthroscopic assessment was interrogated using simple linear regression quantified with the Pearson correlation coefficient. Results: A total of 35 patients that underwent the BEAR procedure were identified. One patient was excluded due to inadequate intraoperative images. Of the remaining patients, 13 (38.2%) were male and 21 (61.8%) were female. The average patient age was 31, with a median age of 28. Most patients were injured while skiing (32.4%), while the second and third most prevalent mechanisms of injury were nonsports-related (23.4%) and soccer injuries (17.6%), respectively. Of the MRI tears that were analyzed, 9 (26.5%) were classified as type 1, 19 (55.9%) were type 2, and 5 (14.7%) were type 3. There were no tears identified as types 4 or 5 tears. Of the arthroscopic images that were analyzed, 21 (61.8%) were classified as type 1, 10 (29.4%) were type 2, 3 (8.8%) were type 3. Similarly, there were no tears identified as types 4 or 5. MRI accurately predicted the ACL tear type seen arthroscopically 55.9% (19/34) of the time. Of the (15) cases in which MRI did not correlate with the arthroscopic tear type, the MRI classification grade was within 1 grade of the arthroscopic grade 93.3% of the time (14/15). In the cases in which MRI was not correct in its grading, 93.3% of them (14/15) were classified as too high of a grade (MRI perceiving the tear to be more distal than it was in actuality). The Pearson correlation coefficient assessing the correlation between MRI identified tear type and arthroscopy identified tear type was 0.56. Conclusions: MRI accurately predicted the ACL tear type seen arthroscopically in only 55.9% of patients. In &gt;90% of incorrect predictions, arthroscopy determined the ACL tear to be one classification more proximal than predicted by MRI. Our results demonstrate that while preoperative MRI can be useful in identifying approximate ACL tear location, it is essential to examine the ACL at time of arthroscopy for final determination of ACL stump size and viability for ACL restoration procedures. Moreover, a greater percentage of patients may be eligible for an ACL restoration procedure than predicted by preoperative MRI, highlighting the importance of discussing both ACL repair and ACL reconstruction with patients preoperatively. [Figure: see text]

Identifying significant structural factors associated with knee pain severity in patients with osteoarthritis using machine learning

Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients. Additionally, we assessed the potential of various classes of imaging data using machine learning techniques to gauge knee pain severity. The data of semi-quantitative assessments of knee radiographs, semi-quantitative assessments of knee magnetic resonance imaging (MRI), and MRI images from 567 individuals in the Osteoarthritis Initiative (OAI) were utilized to train a series of machine learning models. Models were constructed using five machine learning methods: random forests (RF), support vector machines (SVM), logistic regression (LR), decision tree (DT), and Bayesian (Bayes). Employing tenfold cross-validation, we selected the best-performing models based on the area under the curve (AUC). The study results indicate no significant difference in performance among models using different imaging data. Subsequently, we employed a convolutional neural network (CNN) to extract features from magnetic resonance imaging (MRI), and class activation mapping (CAM) was utilized to generate saliency maps, highlighting regions associated with knee pain severity. A radiologist reviewed the images, identifying specific lesions colocalized with the CAM. The review of 421 knees revealed that effusion/synovitis (30.9%) and cartilage loss (30.6%) were the most frequent abnormalities associated with pain severity. Our study suggests cartilage loss and synovitis/effusion lesions as significant structural factors affecting pain severity in patients with knee osteoarthritis. Furthermore, our study highlights the potential of machine learning for assessing knee pain severity using radiographs.

Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson’s disease

BackgroundPeople with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD.MethodsIn a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression.DiscussionMIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future.Trial registrationClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.

Characterizing the association between complement-mediated TMA and cognitive dysfunction using MRI and neurocognitive assessment

AbstractComplement-mediated thrombotic microangiopathy (CM-TMA) is a rare, life-threatening thrombotic microangiopathy caused by a defect in the alternative complement pathway. It is associated with renal failure and acute encephalopathy, but long-term neurocognitive effects are uncertain. Using magnetic resonance imaging (MRI) and neurocognitive tests, we can further evaluate the long-term neurocognitive complications in CM-TMA and compare them with controls. In this study, we analyzed microstructural changes in the cerebral white matter and neurocognitive testing results of patients with CM-TMA. Seven adult patients with CM-TMA in remission and 6 healthy controls were included. All patients were treated with C5 complement blockade. They were followed-up for 12 months after study entry. All patients had consecutive MRI scans (standard-of-care and quantitative sequences) to assess for white matter changes and concurrent neurocognitive testing. Patients with CM-TMA had increased white matter signal intensity in most regions of the brain compared with controls. This was accompanied by increased depression and neurocognitive dysfunction (impaired concentration, short-term memory, and verbal memory). These findings were also present up to 12 months after the initial study visit. In summary, patients with previous CM-TMA were found to have significant, albeit nonspecific, cerebral white matter abnormalities, with impaired memory and concentration. Larger studies with longitudinal follow-up to assess neurocognitive complications in CM-TMA are required. This trial was registered at Clinical Trials Ontario (ctontario.ca; project ID: 1318).

Brain and cervical spinal cord MRI correlates of sensorimotor impairment in patients with multiple sclerosis.

Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879-0.900), VDT (R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.

Synergistic effect of folate and MTHFR C677T on hippocampal subfields and perfusion in Alzheimer's disease

BackgroundLow folate intake and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been suggested to increase the risk of Alzheimer's disease (AD). However, the synergistic effects and their impact on brain structure and perfusion remain unclear. MethodsThis study explored the effects of dietary and genetic deficiencies in folate metabolism on the volume of the hippocampal subregions, cerebral perfusion, and cognitive decline in 71 cognitively unimpaired (CU) individuals and 102 patients with mild cognitive impairment (MCI) due to AD or AD. All participants underwent magnetic resonance imaging, laboratory examinations, and neuropsychological assessments. The hippocampal subfields were segmented using Freesurfer, and arterial spin labeling was used to measure the cerebral blood flow. ResultsWe found a significant group-by-MTHFR interaction effect on folate. Patients with AD and the 677 T allele showed hypoperfusion in the left precuneus compared to patients without this mutation, which mediated the relationship between low folate level and cognitive decline in patients carrying the 677 T allele. Moreover, a synergistic effect was observed for the combination of decreased folate concentrations and the presence of the MTHFR 677 T allele on the atrophy of specific hippocampal subregions in patients with AD. ConclusionsIn addition to offering insights into the neuronal mechanism underlying gene-dependent folate-induced cognitive impairment in AD, these findings may have clinical significance for the allocation of auxiliary folate supplementation therapy in patients with AD with low folate levels and carrying the MTHFR 677 T allele and may eventually promote the selection of early individualized AD drug therapy.

Anterior–temporal hippocampal network mechanisms of left angular gyrus-navigated rTMS for memory improvement in aMCI: A sham-controlled study

IntroductionNeuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior–temporal (AT) and posterior–medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI. MethodsSixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response. ResultsCompared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group. ConclusionsNeuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI.