3T Magnetic Resonance Research Articles

Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) impact iron metabolism in patients with heart failure but mechanisms are incompletely understood. This post hoc analysis explored interrelations between iron homeostasis, cardiac structure/function, exercise capacity, haematopoiesis, and sympathetic activity at baseline, and the effects of 6-month treatment with empagliflozin vs. placebo by anaemia status in EMPATROPISM-FE study participants. Myocardial iron content (MIC, estimated by cardiac magnetic resonance T2* imaging), left ventricular (LV) volumes and LV ejection fraction (LVEF), exercise capacity, laboratory iron markers (LIM), haemoglobin/haematocrit, erythropoietin, and plasma norepinephrine were determined at baseline and 6 months. At baseline, 24/80 participants (30%) had anaemia (haemoglobin < 13/<12 mg/dL in men/women). Patients with vs. without anaemia had higher T2* (indicating lower MIC, P < .001), lower peak oxygen consumption (VO2max, P = .024) and hepcidin (P = .017), and higher erythropoietin (P = .040) and norepinephrine (P = .016). Across subgroups, lower MIC correlated with higher LV volumes (P < .01) and norepinephrine (P < .001), and lower LVEF (P < .01), VO2max (P < .001) and haemoglobin/haematocrit (P < .001). Associations with LIM were poor (all P > .10). Empagliflozin increased MIC (P < .012), improved exercise capacity, and activated haematopoiesis. Changes in LIM and norepinephrine suggested progressive systemic iron depletion and sympatholysis. LV reverse remodelling was greater in individuals with anaemia. Dysregulated cellular iron uptake/availability may be a shared mechanism in myocardial structural/functional impairment, reduced exercise capacity, and restricted haematopoiesis in heart failure, which are worse in patients with anaemia, and improve with empagliflozin. Empagliflozin increases MIC and decreases norepinephrine. Given this inverse association, sympatholysis may help explain the diverse cardiac and systemic benefits from SGLT2i therapy. NCT03485222 (www.clinicaltrials.gov).

Capillary water migration characteristics of sandstone with different porosities and calculation methods for pore surface relaxation strength

The relaxation strength of pore surfaces (ρ2) plays a pivotal role in transforming the nuclear magnetic resonance (NMR) T2 spectrum into the pore size distribution, rendering it an indispensable parameter for characterizing the microstructure via NMR techniques. In this study, spontaneous imbibition (SI) experiments, real-time NMR measurements, and mercury intrusion porosimetry (MIP) tests were conducted on three sandstones with different porositirs. We propose a novel approach for calculating ρ2 using the capillary water absorption coefficient while analyzing the characteristics of capillary water migration during SI through entropy theory. The results demonstrate a positive correlation between porosity and the capillary water absorption coefficient, indicating that micropores and mesoporous channels play dominant roles in this process. Moreover, the migration rate of capillary water is influenced primarily by porosity, followed by pore size. Additionally, the equilibrium time of entropy during SI is negatively correlated with both the porosity and the capillary water absorption coefficient. Furthermore, the capillary water absorption coefficient can be utilized to calculate ρ2. Notably, when comparing the difference ratios of ρ2 obtained through the capillary water absorption coefficient method and MIP for samples A1, B1, and C1 (5.075%, 2.746%, and 7.583%, respectively) were compared, except for tight sandstone A1, the difference is less than 10%. This suggests that this method is not only feasible but also reliable for not particularly dense rocks. Moreover, this method is simple, widely applicable, enables nondestructive testing of samples, and incurs a low experimental cost; thus, this method has promising application prospects.

Glymphatic system clearance and Alzheimer’s disease risk: a CSF proteome-wide study

BackgroundThe emerging evidence of the role of the glymphatic system (GS) in Alzheimer’s disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers. MethodsWe performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs).ResultsA total of seven different proteins were significantly associated with GS health (p-value < 6.4 × 10–4). The stronger correlations were identified for NSUN6, GRAAK, OLFML3, ACTN2, RUXF, SHPS1 and TIM-4. A pathway enrichment analysis revealed that the proteins associated with GS health were mainly implicated in neurodegenerative processes, immunity and inflammation. In Stage 2, we validated these proteomic results in a new cohort of aMCI participants (with and without evidence of AD pathology in CSF (aMCI(-) and aMCI/AD( +); n = 22 and 7, respectively) and healthy controls (n = 10). Proteomic prediction models were generated in each ROI. These were compared with demographic-only models for identifying participants with aMCI(-) and aMCI/AD( +) vs controls. This analysis was repeated to determine if the models could identify those with aMCI/AD( +) from both aMCI(-) and controls. The proteomic models were found to outperform the demographic-only models.ConclusionsOur study identifies proteins linked with GS health and involved the immune system in aMCI participants.

Assessment of cardiac iron deposition and genotypic classification in pediatric beta-thalassemia major: the role of cardiac MRI

BackgroundBeta thalassemia major (β-TM) is a severe genetic anemia with considerable phenotypic heterogeneity. This study investigated whether genotype correlates with distinct myocardial iron overload patterns, assessed by cardiovascular magnetic resonance (CMR) T2* values.MethodsCMR data for cardiac iron deposition evaluation, which recruited pediatric participants between January 2021 and December 2024, were analyzed with CVI42. The patients were classified into three genetic subgroups of β0/β0, β0/β+, and β+/β+ based on their genetic outcomes. The CMR results classified patients into normal myocardial T2* value and myocardial iron overload groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics.ResultsThe study included 145 pediatric β-TM patients, with 24 (17%) exhibiting cardiac iron deposition based on CMR T2* values. There were significant differences in iron chelation treatment strategies across genotypes, with the β0/β0 genotype accounting for 54% (13/24) of patients in the cardiac iron deposition group. Regardless of genotype, the mid-inferolateral segment consistently showed the lowest CMR T2* values and the highest prevalence of iron deposition.ConclusionThe risk of cardiac iron deposition increases as age progresses, and the mid-inferolateral segment is more susceptible to iron accumulation. The β0/β0 genotype is more likely to suffer from cardiac iron overload, emphasizing the need for closer clinical monitoring and regular cardiac MRI evaluations.

Defect-Engineered Biomimetic Piezoelectric Nanocomposites With Enhanced ROS Production, Macrophage Re-polarization, and Ca2+ Channel Activation for Therapy of MRSA-Infected Wounds and Osteomyelitis.

Antibiotic-resistant bacteria often cause lethal infections in both the surficial and deep organs of humans. Failure of antibiotics in resistant infections leads to more effective alternative therapies, like spatiotemporally controllable piezodynamic therapy (PZDT) with deep penetration. Currently, PZDT demands further investigation for improved treatment outcomes and the corresponding therapeutic mechanisms. Herein, a nanocomposite cloaked is reported with a biomimetic coating of TLR-upregulated macrophage membrane for targeted PZDT against MRSA-induced skin wound infection and osteomyelitis, representing surficial and deep infection models, respectively. To boost the therapeutic efficacy, crystal defect engineering is applied by impregnating Fe2+ into bismuth oxy-iodide nanosheets to increase the crystal defects. This results in a significantly higher piezoelectric coefficient than in previous reports, contributing to an amplified reactive oxygen species generation for bacterial killing. More importantly, the notable piezoelectric effect not only re-programs the macrophages into ananti-inflammatory M2 phenotype for accelerating bacterial wound healing but also stimulates the opening of the piezo-stimulated Ca2+ channels and boosts the differentiation of mesenchymal stem cells into osteoblasts for expediting bone tissue repair in osteomyelitis model. Moreover, the Fe-doping supplements T2-magnetic resonance imaging for real-time visualization of nanocomposite distribution. This theranostic system opens a new avenue for future treatment of drug-resistant bacteria-caused diseases.

Distinguishing benign and malignant myxoid soft tissue tumors: Performance of radiomics vs. radiologists.

Benign and malignant myxoid soft tissue tumors have shared clinical, imaging, and histologic features that can make diagnosis challenging. The purpose of this study is comparison of the diagnostic performance of a radiomic based machine learning (ML) model to musculoskeletal radiologists. Manual segmentation of 90 myxoid soft tissue tumors (45 myxomas and 45 myxofibrosarcomas) was performed on axial T1, and T2FS or STIR magnetic resonance imaging sequences. Eighty-seven radiomic features from each modality were extracted. Five ML models were trained to classify tumors as benign or malignant in 40 tumors and then tested with an additional 50 tumors using cross validation. The accuracy of the best ML model based on area under the receiver operating characteristic curve (AUC) was compared to the consensus diagnosis of three musculoskeletal radiologists. Correlation between radiologist confidence (equivocal, probably, consistent with) and accuracy was tested. The best ML classifier was a logistic regression model (AUC 0.792). Using T1 + T2/STIR images, the ML model classified 78% (39/50) of tumors correctly at a similar rate compared to 74% (37/50) by radiologists. When radiologists disagreed, the consensus diagnosis classified 50% of tumors (7/14) correctly compared to 86% (12/14) by the ML model, though this did not reach statistical significance. Radiologists had a cumulative accuracy of 91% (30/33) when they rated their confidence 'consistent with' compared to 61% (31/51) when they rated their confidence 'equivocal/probably' (P = 0.006). For cases when radiologists rated their confidence 'equivocal/probably', the ML model had 76% accuracy (39/51). A radiomic based ML model predicted benign or malignant diagnosis in myxoid soft tissue tumors similarly to the consensus diagnosis by three musculoskeletal radiologists. Radiologist confidence in the diagnosis strongly correlated with their diagnostic accuracy. Though radiomics and radiologists perform similarly overall, radiomics may provide novel diagnostic utility when radiologist confidence is low, or when radiologists disagree.

Comparative analysis of Voxel-based morphometry using T1 and T2-weighted magnetic resonance imaging to explore the relationship between brain structure and cognitive abilities.

Voxel-based morphometry (VBM) of T1-weighted (T1-w) magnetic resonance imaging (MRI) is primarily used to study the association of brain structure with cognitive functions. However, in theory, T2-weighted (T2-w) MRI could also be used in VBM studies because of its sensitivity to pathology and tissue changes. We aimed to compare the T1-w and T2-w images to study brain structures in association with cognitive abilities. VBM analysis was applied to T1-w and T2-w MRI data of 120 healthy participants aged 20 to 40. The MRI data was collected using a 3T machine, and it was analyzed with CAT12 to extract maps of Gray matter(GM). We used six cognitive tasks to assess cognitive abilities, including the balloon analog risk task (BART), block design, forward and backward digit span (FDST and BDST), and trail-making tasks A and B. Compared to T2-w, T1-w data showed more brain voxels in the BART, block design, FDST, TMT-A, and TMT-B tasks. However, T2-w imaging identified a greater number of voxels in the BDST. T1-w images identified more correlated brain regions with cognitive scores in the FDST, TMT-A, and B tasks than T2-w. In BART and Block design tasks, both methods revealed the same number of correlated regions, and T2-w just showed more regions than T1-w in the BDST. Findings revealed distinct patterns of sensitivity between T1-w and T2-w imaging in detecting brain regions associated with cognition. The two approaches demonstrated different strengths in identifying areas correlated with cognitive abilities. This study provides valuable guidance for selecting appropriate methods for identifying the optimal approach for detecting brain regions that exhibit the strongest correlations with cognitive abilities.

Assessment of hypoxia status in a rat chronic liver disease model using IVIM and T1 mapping.

This study was aimed to assess the diagnostic performance of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and T1 mapping in detecting hypoxia status of chronic liver disease using a carbon tetrachloride (CCl4)-induced rat model. The hypoxia group of chronic liver disease consisted of eight rats induced by injection of CCl4 and the control group consisted of nine rats injected with pure olive oil. All 17 rats underwent MRI examination at week 13 after injection, using T1 mapping and IVIM. Liver specimens were subjected to immunohistochemical staining for the exogenous hypoxia marker pimonidazole and the endogenous hypoxia marker HIF-1α and scored semi-quantitatively. Differences in MRI multiparameters, pimonidazole H-scores, and HIF-1α were analyzed between the control and hypoxia groups. Correlations between MRI multiparameters and H-score, and MRI multiparameters and HIF-1α, were analyzed, and the diagnostic performance of multiparameter MRI was evaluated by receiver operating characteristic (ROC) curve analysis. There were significant differences between the control group and the hypoxia group in D* values (p = 0.01) and f values (p = 0.025) of IVIM parameters, T1 mapping (p = 0.003), HIF-1α (p < 0.001) and pimonidazole scores (p = 0.004). D* (r = 0.508, p = 0.037) and T1 mapping (r = 0.489, p = 0.046) values positively correlated with pimonidazole scores. D* (r = 0.556, p = 0.020) and T1 mapping (r = 0.505, p = 0.039) showed a positive correlation with HIF-1α. The optimal cut-off value of T1 mapping was 941.527, and the sensitivity, specificity, and AUC were 87.5, 77.8, and 0.889 (95% confidence interval [CI]: 0.734-1), respectively. IVIM and T1 Mapping are promising methods for non-invasive detection of hypoxia status in chronic liver diseases.

Cross-Sectional Association Between Left Ventricular Geometric Patterns, Cortical Cerebral Microinfarcts, and Cognition.

Left ventricular (LV) geometric patterns are associated with cognitive impairment and cerebral small vessel disease. As a novel magnetic resonance imaging marker of cerebral small vessel disease and a risk factor for cognitive dysfunction, cortical cerebral microinfarcts (CMIs) have been associated with heart disease through mechanisms including cardioembolism and cerebral hypoperfusion. Further investigation is required to determine whether cortical CMIs could arise from hemodynamic changes related to LV geometry, thus elucidating the connection between LV geometry and cognitive function. This study aims to investigate the cross-sectional relationship between LV geometric patterns, cortical CMIs, and cognition. A total of 261 patients, aged 75.3±6.8 years, were enrolled from a memory clinic study. LV dimensions were obtained using 2-dimensional echocardiography. LV mass index and relative wall thickness were determined to categorize LV geometric patterns. Cortical CMIs were graded on 3T magnetic resonance imaging. Cognition was assessed using neuropsychological tests and clinical diagnosis. Linear, zero-inflated Poisson, and logistic regression were employed for continuous, count, and binary outcomes, respectively. Mediation analysis was conducted to examine the mediation effect of cortical CMIs. A significant association was observed between concentric LV hypertrophy and cortical CMI counts (rate ratio, 3.85 [95% CI, 1.85-8.01]), as well as the odds of having dementia (odds ratio, 2.86 [95% CI, 1.07-7.89]), in the fully adjusted model. Cortical CMIs may partly explain the relationship between concentric LV hypertrophy and cognitive function. Concentric LV hypertrophy was associated with cortical CMIs and dementia. Further verification is warranted to determine the role of cortical CMIs in the association between LV geometry and cognition.

Identification of Sulcal Hyperintense Vessel (Vessel Wall MR Ivy Sign) in Adult Moyamoya Disease with High-resolution Vessel Wall Imaging : A Pilot Study.

The leptomeningeal ivy sign is a distinctive finding of moyamoya disease (MMD), characterized by a linear high signal intensity along the cortical sulci on contrast-enhanced T1 magnetic resonance imaging (MRI) and fluid-attenuated inversion-recovery MRI. We recently identified a similar linear enhancement along the cortical sulci using gadolinium-enhanced vessel wall MRI (VWMR) in patients with MMD. The aim of this study was to introduce the concept of the "VWMR ivy sign (VIS)". Eighteen MMD patients underwent gadolinium-enhanced VWMR. We identified the VIS in gadolinium-enhanced VWMR, represented by a linear high intensity along the cortical sulci. The VIS was assessed by comparing pre and postcontrast T1 black blood sequences on VWMR and was investigated in the precentral, central, and postcentral sulci. "VIS scores" were calculated by the sum of VIS in the three sulci, ranged from 0 to 3. We compared the VIS scores according to different stroke presentations (non-stroke, ischemic stroke, and hemorrhagic stroke). The inter-modality agreement for identifying VIS and fluid-attenuated inversion-recovery (FLAIR)/cortical sulci on contrast-enhanced T1 MRI (CEMR) ivy sign was determined using Cohen's kappa statistics. The VIS scores were significantly different among the three groups (P = 0.004). The VIS scores in both the ischemic and hemorrhagic groups were significantly higher than those in the non-stroke group (ischemic vs. non-stroke, P = 0.009; hemorrhagic vs. non-stroke, P = 0.004). After adjusting for age and sex using the non-stroke group as a reference group, the VIS scores were significantly higher in the ischemic and hemorrhagic groups (P=0.046, OR 8.27, 95% CI 1.03-66.19 and P=0.039, OR 7.78, 95% CI 1.11-54.48, respectively). Inter-modality agreement between VIS and FLAIR ivy sign was substantial, perfect, and substantial in the precentral, central, and postcentral sulci, respectively (precentral sulcus, κ=0.609, 95% CI=0.213-1; central sulcus, κ=1; and postcentral sulcus, κ=0.769, 95% CI=0.475-1). Inter-modality agreement between the VIS and CEMR ivy sign was substantial in the precentral, central, and postcentral sulci, respectively (precentral sulcus, κ=0.727, 95% CI=0.384-1; central sulcus, κ=0.609, 95% CI=0.384-1; and postcentral sulcus, κ=0.649, 95% CI=0.310-0.998). This preliminary series introduces the concept of VIS, possibly indicating slow and retrograde flow of sulcal vessels via leptomeningeal collaterals. Future studies are needed to develop an optimal scoring system for VIS and establish its clinical correlation with stroke presentations in MMD patients.

Basolateral amygdala volume in affective disorders using 7T MRI in vivo.

The basolateral complex of the amygdala is a crucial neurobiological site for Pavlovian conditioning. Investigations into volumetric alterations of the basolateral amygdala in individuals with major depressive disorder (MDD) have yielded conflicting results. These may be reconciled in an inverted U-shape allostatic growth trajectory. This hypothesized trajectory unfolds with an initial phase of volumetric expansion, driven by enhanced dendritic arborization and synaptic plasticity. The increase in volume is followed by a reduction phase, as glucocorticoid exposure cumulatively results in excitotoxic damage, reflecting allostatic load. 7T magnetic resonance brain imaging was conducted on a total of 84 participants (mean age 38 ± 12 years), comprising 20 unmedicated and 20 medicated individuals with MDD, 21 individuals suffering from bipolar disorder and 23 healthy controls. We employed FreeSurfer 7.3.2 for automatic high-resolution segmentation of nine amygdala subnuclei. We conducted analyses of covariance, with volumes of the basolateral complex, the lateral nucleus and, exploratively, the whole amygdala, as dependent variables, while controlling for the total intracranial volume and sex. Quadratic regressions were computed within the MDD group and in relevant subgroups to investigate the presence of a U-shaped relationship between the number of preceding major depressive episodes or the duration of the disease since the first episode and the dependent variables. Diagnostic groups did not exhibit statistically significant differences in the volumes of the basolateral amygdala (left F (3,75) = 0.66, p >.05; right F (3,76) = 1.80, p >.05), the lateral nucleus (left F (3,75) = 1.22, p >.05; right F (3,76) = 2.30, p >.05)), or the whole amygdala (left F (3,75) = 0.48, p >.05; right F (3,76) = 1.58, p >.05). No quadratic associations were observed between surrogate parameters of disease progression and any of the examined amygdala volumes. There were no significant correlations between subregion volumes and clinical characteristics. We found no evidence for the hypothesis of an inverted U-shaped volumetric trajectory of the basolateral amygdala in MDD. Future research with larger sample sizes, including the measurement of genetic and epigenetic markers, will hopefully further elucidate this compelling paradigm.

Longitudinal investigation of neuroimaging changes related to memory decline in multiple sclerosis: Testing a mechanistic model

Background: Memory decline is common in multiple sclerosis (MS), although pathophysiological mechanisms are not fully understood. Objective: The objective was to investigate the relationship of changes in structural and functional neuroimaging markers to memory decline over 3-year follow-up. Methods: Participants with MS underwent cognitive evaluation and structural, diffusion, and functional 3T magnetic resonance imaging (MRI) scans at baseline and 3-year follow-up. Changes in neuroimaging metrics from baseline to follow-up were compared between memory stable and memory decline groups. Our hypothesis that structural and functional connectivity changes mediate the association of atrophy to memory decline was tested. Results: A total of 249 MS patients completed baseline visit; 169 (67.8%) returned at 3-year follow-up. Based on ⩾10% decline, memory decline was observed in 44.4% ( n = 75). Those with memory decline showed marginally greater whole-brain volume loss over time compared with those with stable memory performance ( p = 0.08). In those with memory decline, changes in white matter tract integrity were related to regional cortical thinning ( p &lt; 0.01). Exploratory mediation analysis revealed structural and functional connectivity to mediate the relationship of atrophy to verbal and visual memory decline. Conclusion: Further work is needed to characterize complex interrelationships of atrophy and structural/functional connectivity changes to memory decline in MS.

Abdominal synthetic CT generation for MR-only radiotherapy using structure-conserving loss and transformer-based cycle-GAN.

Recent deep-learning based synthetic computed tomography (sCT) generation using magnetic resonance (MR) images have shown promising results. However, generating sCT for the abdominal region poses challenges due to the patient motion, including respiration and peristalsis. To address these challenges, this study investigated an unsupervised learning approach using a transformer-based cycle-GAN with structure-preserving loss for abdominal cancer patients. A total of 120 T2 MR images scanned by 1.5 T Unity MR-Linac and their corresponding CT images for abdominal cancer patient were collected. Patient data were aligned using rigid registration. The study employed a cycle-GAN architecture, incorporating the modified Swin-UNETR as a generator. Modality-independent neighborhood descriptor (MIND) loss was used for geometric consistency. Image quality was compared between sCT and planning CT, using metrics including mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structure similarity index measure (SSIM) and Kullback-Leibler (KL) divergence. Dosimetric evaluation was evaluated between sCT and planning CT, using gamma analysis and relative dose volume histogram differences for each organ-at-risks, utilizing treatment plan. A comparison study was conducted between original, Swin-UNETR-only, MIND-only, and proposed cycle-GAN. The MAE, PSNR, SSIM and KL divergence of original cycle-GAN and proposed method were 86.1 HU, 26.48 dB, 0.828, 0.448 and 79.52 HU, 27.05 dB, 0.845, 0.230, respectively. The MAE and PSNR were statistically significant. The global gamma passing rates of the proposed method at 1%/1 mm, 2%/2 mm, and 3%/3 mm were 86.1 ± 5.9%, 97.1 ± 2.7%, and 98.9 ± 1.0%, respectively. The proposed method significantly improves image metric of sCT for the abdomen patients than original cycle-GAN. Local gamma analysis was slightly higher for proposed method. This study showed the improvement of sCT using transformer and structure preserving loss even with the complex anatomy of the abdomen.

Longitudinal Changes in Medial Meniscal Extrusion After ACL Injury and Reconstruction and Its Relationship With Cartilage Degeneration Assessed Using MRI-Based T1ρ and T2 Analysis

Background: Anterior cruciate ligament (ACL) injury often leads to posttraumatic osteoarthritis (PTOA), despite ACL reconstruction (ACLR). Medial meniscal extrusion (MME) is implicated in PTOA progression but remains understudied after ACL injury and ACLR. Hypothesis/Purpose: It was hypothesized that MME would increase longitudinally after ACL injury and ACLR, with greater changes in the ipsilateral knee compared with the contralateral knee, leading to cartilage degeneration. The study aimed to assess MME 3 years after ACLR and its relationship with magnetic resonance imaging (MRI) T1ρ and T2 as cartilage degeneration markers. Study Design: Cohort study; Level of evidence, 2. Methods: MME and relative percentage of extrusion (RPE) were measured on 3 coronal slices of 3-dimensional fast spin-echo images and the mean values were used. T1ρ and T2 sequences were obtained and cartilage compositional measurements were performed using in-house developed software with MATLAB. Mixed models were used to assess the longitudinal changes and linear regression was used to assess the relationships between RPE and T1ρ and T2 values. Results: A total of 54 participants with unilateral ACL injuries underwent preoperative bilateral knee MRI. A total of 36 participants completed MR scans at 6 months and 3 years after ACLR. MME and RPE measurements demonstrated high reliability (ICC > 0.88 and > 0.91, respectively). The predicted values of MME and RPE from the mixed models showed that the ipsilateral side had significantly greater MME and RPE than the contralateral side at all 3 time points (P = .023 for MME; P = .013 for RPE at baseline; and P < .001 at 6 months and P < .001 at 3 years for both MME and RPE). The rate of change of MME and RPE on the ipsilateral side was significantly greater than that on the contralateral side (P < .001). Postoperative RPE was associated with T1ρ and T2 values in the posterior medial femoral condyle. Conclusion: MME and RPE obtained pre- and postoperatively after ACLR on the ipsilateral side were significantly greater than those on the contralateral side, and the longitudinal increases on the ipsilateral side were greater than those on the contralateral side. Postoperative RPE was significantly associated with cartilage degeneration in the posterior medial femoral condyle.

Choroid plexus morphology in schizophrenia and early-stage psychosis: A cross-sectional study.

The choroid plexus is an important structure within the ventricular system. Schizophrenia has been associated with morphological changes to the choroid plexus but the presence and extent of alterations at different illness stages is unclear. We examined choroid plexus volumes in participants at clinical high-risk for psychosis (N=110), participants with first-episode psychosis (N=37), participants with schizophrenia (N=28), clinical (N=38) and non-clinical controls (N=75). Automated segmentation (Gaussian mixture model) was used to estimate choroid plexus volumes from T1 magnetic resonance (MR) images. We then conducted a linear model and Bayes factor analysis to investigate group differences. In addition, the relationship between choroid plexus volumes and clinical characteristics was assessed. Schizophrenia patients were characterized by increased choroid plexus and ventricular volume while first-episode psychosis and clinical high-risk for psychosis participants showed no differences in choroid plexus volumes. However, choroid plexus volumes in schizophrenia patients did not significantly differ from controls when controlling for ventricular volume. Finally, choroid plexus volumes were not associated with clinical characteristics in the clinical high-risk group. Our findings suggest that morphological alterations are not specific to the choroid plexus in schizophrenia and early-stage psychosis. Previously reported choroid plexus abnormalities in schizophrenia patients could be explained by changes in ventricular volume.

T1 and T2 cardiac magnetic resonance fingerprinting for discrimination of cardiac amyloidosis and hypertrophic cardiomyopathy

T1 and T2 cardiac magnetic resonance fingerprinting for discrimination of cardiac amyloidosis and hypertrophic cardiomyopathy

Compromised cerebrovascular reactivity related to presence of white matter hyperintensities in cryptogenic stroke with right-to-left shunts.

This study investigates cerebrovascular reactivity (CVR) changes in cryptogenic stroke (CS) patients with right-to-left shunts (RLS) and evaluates the relationship between CVR and white matter hyperintensities (WMHs). The breath-holding index (BHI), representing CVR, was measured from the middle cerebral artery (MCA) using the breath-holding method. WMHs were defined as clearly hyperintense areas on 3T magnetic resonance imaging (MRI), assessed separately as periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH). RLS was diagnosed based on a contrast-enhanced transcranial Doppler (c-TCD) examination. Among 260 CS patients and 128 controls, BHI was significantly lower in CS groups (0.68±0.27 vs. 0.83±0.31, P<0.001), particularly in those with RLS (0.64±0.28 vs. 0.71±0.25,P = 0.030). CS patients with WMHs exhibited lower BHI than those without WMHs (0.50±0.22 vs.0.60±0.35, P = 0.012), and PVH showed lower BHI compared to DWMH (0.45±0.24 vs.0.58±0.16, P = 0.003). A negative correlation was found between WMH severity and BHI (0.60±0.35 vs.0.51±0.21 vs.0.48±0.20 vs.0.38±0.28, P = 0.025). Reduced BHI was an independent risk factor for WMHs (OR = 0.283; 95 % CI = 0.081-0.995, P = 0.049). CS patients, especially those with RLS, show reduced CVR, which correlates with the location and severity of WMHs. These findings suggest that RLS may significantly contribute to WMH development in CS patients.

Multivariable prognostic prediction of efficacy and safety outcomes and response to fingolimod in people with relapsing-remitting multiple sclerosis.

The individual treatment response in people with relapsing-remitting multiple sclerosis (RRMS) remain unpredictable. In order to support medical decisions, we aimed to predict response to fingolimod compared to placebo, by developing and validating prognostic multivariable models. We included two-year follow-up from intention-to-treat populations of two multi-country placebo-controlled randomized controlled trials (RCT) of daily fingolimod 0.5 mg. The data was accessed via ClinicalStudyDataRequest.com (Proposal Number: 11223) The RCTs were in adult RRMS patients with active disease. We used four Cox proportional hazards based penalized (elastic net and grouped lasso) and tree methods (transformation tree and forest) to predict time-to relapse and other relevant efficacy and safety endpoints in data from the RCT FREEDOMS. Treatment arm, 80 baseline variables and their interaction with treatment were considered as candidate predictors in the models. A nested cross-validation scheme ensured independent tuning parameter optimization and internal model performance evaluation. The generalizability of the models with the highest cross-validated time-dependent area under the receiver operating curve (AUC) was further evaluated in terms of discrimination (AUC), calibration (plots, intercept, slope), clinical utility (decision curve analysis), and treatment response plots by external validation in data from the RCT FREEDOMS II. The best performing model predicting relapse risk (331 events) in the development sample (n=843) was an elastic net regression with main terms for four predictors alongside treatment: EDSS score, volume of Gadolinium enhanced T1 lesions, number of relapses in the last 2 years, and number of prior MS treatments. In external validation (n=713), it had an AUC of 0.68 (95% CI 0.63-0.72), but the predictions were overestimating the actual risk (358 events) with a calibration-in-the-large of -0.17 (-0.3 - -0.04) and a slope of 1.06 (0.78-1.35). Almost no heterogeneity (variability 0.001) was detected in the predicted relapse risk change in response to fingolimod. FREEDOMS II participants were predicted to have 0.21 to 0.31 absolute relapse risk reduction with fingolimod compared to placebo. The selected model predicting new or enlarging T2 magnetic resonance imaging (MRI) lesions had an AUC of 0.74 (0.70-0.78), moderate calibration, but no treatment response variability. The final model predicting confirmed disability progression had an AUC of 0.59 (0.54-0.64) and the predicted treatment response heterogeneity was not significant. The overall safety outcome could not be predicted with sufficient discrimination. However, the final model predicting infections or neoplasms had an AUC of 0.69 (0.63-0.74) and non-significant treatment response heterogeneity. For the efficacy outcomes, important predictors were related to (para)clinical disease activity or disability. Unexpected influential predictors included concomitant disorders. Relapse and new or enlarging T2 MRI lesions were moderately predictable in an independent sample with the developed prognostic models. Fingolimod was expected to decrease the risk of these events for all patients, with no predictable heterogeneity. Disability and safety outcomes could not be well-predicted and it is yet unresolved whether the change in their risk as response to fingolimod is heterogeneous or not.

Use of UMFNPs/Ce6@MBs in multimodal imaging-guided sono-photodynamic combination therapy for hepatocellular carcinoma.

Early diagnosis of liver cancer and appropriate treatment options are critical for obtaining a good prognosis. However, due to technical limitations, it is difficult to make an early and accurate diagnosis of liver cancer, and the traditional imaging model is relatively simple. Therefore, we synthesized multifunctional diagnostic/therapeutic nanoparticles, UMFNPs/Ce6@MBs, loaded with ultra-small manganese ferrite nanoparticles (UMFNPs) and chlorin e6 (Ce6). This nanoplatform can take full advantage of hypoxia, acidic pH (acidosis) and increased levels of reactive oxygen species (e.g. H2O2) in the tumor microenvironment (TME). Specific imaging and drug release can also enhance tumor therapy by modulating the hypoxic state of the TME to achieve the combined effect of sonodynamic therapy and photodynamic therapy (SPDT). In addition, the prepared UMFNPs/Ce6@MBs have H2O2 and pH-sensitive biodegradability and can release UMFNPs and photosensitizer Ce6 in the TME while producing O2 and Mn2+. The obtained Mn2+ ion nanoparticles can be used for T1 magnetic resonance imaging of tumor-bearing mice, and the released Ce6 can provide fluorescence imaging function at the same time. Because UMFNPs/Ce6@MB ultrasonic microbubbles show good ultrasonic imaging results, UMFNPs/Ce6@MBs can simultaneously provide multi-modal imaging functions for magnetic resonance imaging (MRI), ultrasound and fluorescence imaging. In conclusion, UMFNPs/Ce6@MBs realize the synergistic treatment of SDT and PDT under multi-mode near-infrared fluorescence imaging and CEUS monitoring, demonstrating its great potential in tumor precision medicine.

Shared and distinctive changes of the white matter integrity in generalized anxiety disorder with or without depressive disorder.

Generalized anxiety disorder (GAD) is a prevalent anxiety disorder often comorbid with major depressive disorder (MDD). Previous neuroimaging studies have shown that white matter (WM) microstructural alterations are critical for efficient communication between brain regions, and play an important role in the pathology of GAD. However, the exact profile of WM abnormalities in GAD with and without comorbid MDD remain unclear. This study aimed to uncover them using a novel global probabilistic tractography technology named Tracts Constrained by Underlying Anatomy (TRACULA), and to assess the correlations between fascicle integrity and symptom severity. We recruited 20 pure GAD (p-GAD) patients, 14 GAD comorbid with MDD (GAD+MDD) patients, and 41 age- and sex-matched healthy controls (HCs). All participants underwent T1 magnetic resonance imaging and diffusion tensor imaging. For each subject, 42 WM fiber bundles of the whole brain were successfully tracked and calculated with five metrics including volume, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Group comparison were firstly performed between the whole GAD patients and HCs. Then, we compared the differences among the three groups (the p-GAD, GAD+MDD patients and HCs) using the one-way ANCOVA and post hoc analysis with the Bonferroni correction. Furthermore, correlations between abnormal WM metrics and clinical symptom severity were examined using partial correlations analyses among patients. Compare to HCs, both p-GAD and GAD+MDD patients exhibited decreased FA values in left superior longitudinal fasciculus (SLF) II, and right dorsal of cingulum bundle (CBD); Moreover, GAD+MDD patients showed decreased FA, increased MD and RD values in the central and temporal section of the body of the corpus callosum (CC-BODY), right SLF I and II compared to HCs. Within the GAD+MDD group, GAD-7 scores were negatively correlated with FA values (r=-0.75, p=0.008) and positively correlated with RD values (r=0.7, p=0.017) in the right CBD. This study identified both shared and distinctive changes in GAD patients with and without MDD. The shared WM disruption in the p-GAD and GAD+MDD groups located in the left SLF and right CBD, while only GAD+MDD patients showed distinctive changes in the central and temporal sections of the CC-BODY and right SLF. Current study gave a comprehensive characterization of WM abnormalities among these patients, and highlighted TRACULA's value in identifying critical WM changes.