Diabetic striatopathy: an updated overview of current knowledge and future perspectives.

PURPOSE: Diabetic striatopathy (DS) is a rare complication of poorly controlled diabetes mellitus (DM), characterized by hyperglycemia associated with chorea/ballism and characteristic reversible basal ganglia abnormalities on computed tomography (CT) and/or magnetic resonance imaging (MRI). We propose a narrative review of the literature on this topic, currently unknown to most, and about which physicians should be aware. We intend to summarize, critically review, and take to mean the evidence on this disorder, describing its typical features. METHODS: We searched Pubmed for English-language sources using the following keywords in the title and the abstract: diabetic striatopathy, hyperglycemic non-ketotic hemichorea/hemiballism, chorea/hemichorea associated with non-ketotic hyperglycemia, diabetic hemiballism/hemichorea, chorea, hyperglycemia, and basal ganglia syndrome. We collected scientific articles, including case reports, reviews, systematic reviews, and meta-analyses from the years 1975 to 2023. We eliminated duplicate, non-English language or non-related articles. RESULTS: Older Asian women are more frequently affected. Suddenly or insidiously hemichorea/hemiballism, mainly in the limbs, and high blood glucose with elevated HbA1c in the absence of ketone bodies have been observed. Furthermore, CT striatal hyperdensity and T1-weighted MRI hyperintensity have been observed. DS is often a treatable disease following proper hydration and insulin administration. Histopathological findings are variable, and no comprehensive hypothesis explains the atypical cases reported. CONCLUSION: DS is a rare neurological manifestation of DM. If adequately treated, although treatment guidelines are lacking, the prognosis is good and life-threatening complications may occur occasionally. During chorea/hemiballism, we recommend blood glucose and HbA1c evaluation. Further studies are needed to understand the pathogenesis.

Caspase-3-Triggered Intracellular Gadolinium Nanoparticle Formation for T1-Weighted Magnetic Resonance Imaging of Apoptosis In Vivo.

Apoptosis, with a hallmark of upregulated protease Caspase-3, has been frequently imaged with various probes to reveal the therapeutic efficiencies of different drugs. However, activatable molecular probes with programmable self-assembling behaviors that enable enhanced T1-weighted magnetic resonance imaging (MRI) of apoptosis remain scarce. Herein, taking advantage of a CBT-Cys click reaction, we rationally designed a Caspase-3-activatable self-assembling probe Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys(DOTA(Gd))-CBT (DEVDCS-Gd-CBT) for apoptosis imaging in vivo. After Caspase-3 cleavage in apoptotic cells, DEVDCS-Gd-CBT underwent CBT-Cys click reaction to form a cyclic dimer, which self-assembled into Gd nanoparticles. With this probe, enhanced T1-weighted MR images of apoptosis were achieved at low magnetic fields in vitro, in cis-dichlorodiamineplatinum-induced apoptotic cells and in tail-amputation-simulated apoptotic zebrafish. We anticipate that the smart probe DEVDCS-Gd-CBT could be applied for T1-weighted MRI of apoptosis-related diseases in the clinic in the future.

Reliability of spinal cord measures based on synthetic T1-weighted MRI derived from multiparametric mapping (MPM).

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T1-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T1-w MRI (synT1-w) estimated from the MPM, in order to measure CSA. SynT1-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R1) and effective transverse (R2*) relaxation rates. The reliability of CSA measurements from synT1-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT1-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT1-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm2 compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT1-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT1-w images, thereby reducing scan time significantly.

Multi-atlas thalamic nuclei segmentation on standard T1-weighed MRI with application to normal aging.

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.

Structural brain characteristics and gene co-expression analysis: A study with outcome label from normal cognition to mild cognitive impairment.

BACKGROUND: Longitudinal studies reported that some elderly people with normal cognition (NC) converted to mild cognitive impairment (MCI), and some remained normal state (NC_S). The underlying factor for this difference conversion of NC is worthy of exploration METHODS: Eighty-three NC participants were tracked for eight years. Thirty participants transitioned from NC to MCI (NC_MCI). The remaining 53 participants retained an NC_S. The structural brain features and genetic expression of the 83 NC participants were obtained. We applied weighted gene co-expression network analysis (WGCNA) to inquire into the co-expression network of those. Mediator effect analysis of regulatory roles was conducted to inquire into the associations between brain measures, expression values, and clinical scores. RESULTS: The main results are: 1) 20 brain features and 740 gene expression had significant differences between the two groups, 2) one module including 187 genes had the most correlation with cortical thickness of left superior temporal sulcus (L.STS), 3) NFKBIA and RARA genes were the top two genes that made the greatest contribution to L.STS thickness, and 4) mediating effect was found between the L.STS thickness, the NFKBIA and RARA expression levels, and clinical scores. CONCLUSION: Our results provide a theoretical foundation based on gene expression and brain imaging for the factors of NC with different outcomes.

The pancreas-to-muscle signal intensity ratio on T1-weighted MRI as a predictive biomarker for postoperative pancreatic fistula after distal pancreatectomy: a single-center retrospective study.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the serious complications of pancreatic surgery. When POPF occurs and becomes severe, it causes secondary complications and a longer treatment period. We previously reported a correlation between pancreatic fibrosis and magnetic resonance imaging (MRI) findings, and MRI may have the potential to predict POPF. This study aimed to assess the predictive ability of the pancreas-to-muscle signal intensity ratio on T1-weighted MRI (SIR on T1-w MRI) for POPF after distal pancreatectomy (DP). METHODS: This single-institution retrospective study comprised 117 patients who underwent DP. It was conducted between 2010 and 2021 at the Gifu University Hospital. We statistically analyzed pre-, intra-, and postoperative factors to assess the correlation with POPF. RESULTS: According to the definition and grading of the International Study Group of Pancreatic Fistula (ISGPF), 29 (24.8%) of the 117 patients had POPF grades B and C. In the univariate analysis, POPF was significantly associated with the pancreas-to-muscle SIR on T1-w MRI, the drainage fluid amylase concentration (D-Amy) levels on postoperative day (POD) 1 and 3, white blood cell count on POD 1 and 3, C-reactive protein level on POD 3, and heart rate on POD 3. In multivariate analysis, only the pancreas-to-muscle SIR on T1-w MRI (>1.37; odds ratio [OR] 23.25; 95% confidence interval [CI] 3.93-454.03; p < 0.01) and D-Amy level on POD 3 (>737 U/l; OR 3.91; 95% CI 1.02-16.36; p = 0.046) were identified as independent predictive factors. CONCLUSIONS: The pancreas-to-muscle SIR on T1-w MRI and postoperative D-Amy levels were able to predict the development of POPF after DP. The pancreas-to-muscle SIR on T1-w MRI may be a potential objective biomarker reflecting pancreatic status.

Functional connectivity and structural changes of thalamic subregions in episodic migraine.

BACKGROUND: The thalamus plays a crucial role in transmitting nociceptive information to various cortical regions involving migraine-related allodynia and photophobia. Abnormal structural and functional alterations related to the thalamus have been well established. However, it is unknown whether the brain structure and function of the thalamic subregions are differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing the structure and function of 16 thalamic subregions between patients with episodic migraine (EM) and healthy controls (HCs). METHODS: Twenty-seven patients with EM and 30 sex-, age- and education-matched HCs underwent resting-state functional and structural magnetic resonance imaging scans. Functional connectivity (rsFC), grey matter volume (GMV), and diffusion tensor imaging (DTI) parameters of each subregion of the thalamus were calculated and compared between the two groups. Furthermore, correlation analyses between neuroimaging changes and clinical features were performed in this study. RESULTS: First, compared with HCs, patients with EM exhibited decreased rsFC between the anterior-medial-posterior subregions of the thalamus and brain regions mainly involved in the medial system of the pain processing pathway and default mode network (DMN). Second, for the whole thalamus and each of its subregions, there were no significant differences in GMV between patients with EM and HCs (P > 0.05, Bonferroni corrected). Third, there was no significant difference in DTI parameters between the two groups (P > 0.05). Finally, decreased rsFC was closely related to scores on the Hamilton Rating Scale for Anxiety (HAMA) and Big Five Inventory (BFI) scales. CONCLUSION: Selective functional hypoconnectivity in the thalamic subregions provides neuroimaging evidence supporting the important role of thalamocortical pathway dysfunction in episodic migraine, specifically, that it may modulate emotion and different personality traits in migraine patients.

DeepAtrophy: Teaching a neural network to detect progressive changes in longitudinal MRI of the hippocampal region in Alzheimer's disease.

Measures of change in hippocampal volume derived from longitudinal MRI are a well-studied biomarker of disease progression in Alzheimer's disease (AD) and are used in clinical trials to track therapeutic efficacy of disease-modifying treatments. However, longitudinal MRI change measures based on deformable registration can be confounded by MRI artifacts, resulting in over-estimation or underestimation of hippocampal atrophy. For example, the deformation-based-morphometry method ALOHA (Das et al., 2012) finds an increase in hippocampal volume in a substantial proportion of longitudinal scan pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, unexpected, given that the hippocampal gray matter is lost with age and disease progression. We propose an alternative approach to quantify disease progression in the hippocampal region: to train a deep learning network (called DeepAtrophy) to infer temporal information from longitudinal scan pairs. The underlying assumption is that by learning to derive time-related information from scan pairs, the network implicitly learns to detect progressive changes that are related to aging and disease progression. Our network is trained using two categorical loss functions: one that measures the network's ability to correctly order two scans from the same subject, input in arbitrary order; and another that measures the ability to correctly infer the ratio of inter-scan intervals between two pairs of same-subject input scans. When applied to longitudinal MRI scan pairs from subjects unseen during training, DeepAtrophy achieves greater accuracy in scan temporal ordering and interscan interval inference tasks than ALOHA (88.5% vs. 75.5% and 81.1% vs. 75.0%, respectively). A scalar measure of time-related change in a subject level derived from DeepAtrophy is then examined as a biomarker of disease progression in the context of AD clinical trials. We find that this measure performs on par with ALOHA in discriminating groups of individuals at different stages of the AD continuum. Overall, our results suggest that using deep learning to infer temporal information from longitudinal MRI of the hippocampal region has good potential as a biomarker of disease progression, and hints that combining this approach with conventional deformation-based morphometry algorithms may lead to improved biomarkers in the future.

Temporal and extratemporal atrophic manifestation of temporal lobe epilepsy using voxel-based morphometry and corticometry: clinical application in lateralization of epileptogenic zone.

BACKGROUND: Advances in MRI acquisition and data processing have become important for revealing brain structural changes. Previous studies have reported widespread structural brain abnormalities and cortical thinning in patients with temporal lobe epilepsy (TLE), as the most common form of focal epilepsy. METHODS: In this research, healthy control cases (n = 20) and patients with left TLE (n = 19) and right TLE (n = 14) were recruited, all underwent 3.0 T MRI with magnetization-prepared rapid gradient echo sequence to acquire T1-weighted images. Morphometric alterations in gray matter were identified using voxel-based morphometry (VBM). Volumetric alterations in subcortical structures and cortical thinning were also determined. RESULTS: Patients with left TLE demonstrated more prevailing and widespread changes in subcortical volumes and cortical thickness than right TLE, mainly in the left hemisphere, compared to the healthy group. Both VBM analysis and subcortical volumetry detected significant hippocampal atrophy in ipsilateral compared to contralateral side in TLE group. In addition to hippocampus, subcortical volumetry found the thalamus and pallidum bilaterally vulnerable to the TLE. Furthermore, the TLE patients underwent cortical thinning beyond the temporal lobe, affecting gray matter cortices in frontal, parietal, and occipital lobes in the majority of patients, more prevalently for left TLE cases. Exploiting volume changes in individual patients in the hippocampus alone led to 63.6% sensitivity and 100% specificity for lateralization of TLE. CONCLUSION: Alteration of gray matter volumes in subcortical regions and neocortical temporal structures and also cortical gray matter thickness were evidenced as common effects of epileptogenicity, as manifested by the majority of cases in this study.

Ellagic acid-Fe nanoscale coordination polymer with higher longitudinal relaxivity for dual-modality T1-weighted magnetic resonance and photoacoustic tumor imaging.

Dual-modality contrast agents for T1-weighted magnetic resonance imaging (MRI) and photoacoustic imaging have attracted substantial attention as they combine the advantages of unlimited penetration depth and high sensitivity. However, most of the reported agents are Gd-based materials that exhibit nephrotoxicity, and few studies have focused on Fe-based materials owing to their lower relaxivity. This work describes the development of an ellagic acid (EA)-Fe nanoscale coordination polymer with high longitudinal relaxivity and strong near-infrared absorption for dual-modality T1-weighted MRI and photoacoustic imaging. The longitudinal relaxivity (r1) of the prepared EA-Fe@BSA nanoparticles was 2.54 mM-1 s-1, an increase of 185% compared with previously reported gallic acid-Fe nanoparticles. Furthermore, in vitro and in vivo experiments demonstrate that the EA-Fe@BSA NPs are an excellent T1-weighted MRI and photoacoustic dual-modality contrast agent with the advantages of convenient synthesis and low toxicity, exhibiting great potential for clinical use in tumor imaging.

Brainstem enlargement in preschool children with autism: Results from an intermethod agreement study of segmentation algorithms.

The intermethod agreement between automated algorithms for brainstem segmentation is investigated, focusing on the potential involvement of this structure in Autism Spectrum Disorders (ASD). Inconsistencies highlighted in previous studies on brainstem in the population with ASD may in part be a result of poor agreement in the extraction of structural features between different methods. A sample of 76 children with ASD and 76 age-, gender-, and intelligence-matched controls was considered. Volumetric analyses were performed using common tools for brain structures segmentation, namely FSL-FIRST, FreeSurfer (FS), and Advanced Normalization Tools (ANTs). For shape analysis SPHARM-MAT was employed. Intermethod agreement was quantified in terms of Pearson correlations between pairs of volumes obtained by the different methods. The degree of overlap between segmented masks was quantified in terms of the Dice index. Both Pearson correlations and Dice indices, showed poor agreement between FSL-FIRST and the other methods (ANTs and FS), which by contrast, yielded Pearson correlations greater than 0.93 and average Dice indices greater than 0.76 when compared with each other. As with volume, shape analyses exhibited discrepancies between segmentation methods, with particular differences noted between FSL-FIRST and the others (ANT and FS), with under- and over-segmentation in specific brainstem regions. These data suggest that research on brain structure alterations should cross-validate findings across multiple methods. We consistently detected an enlargement of brainstem volume in the whole sample and in the male cohort across multiple segmentation methods, a feature particularly driven by the subgroup of children with idiopathic intellectual disability associated with ASD.

An efficient MRI agent targeting extracellular markers in prostate adenocarcinoma.

PURPOSE: Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)-AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin-fibronectin (FB-FN) complex. METHODS: The peptide CREKA (Cys-Arg-Glu-Lys-Ala), targeting the FB-FN complex in the reactive stroma of the tumor, was synthesized by solid phase peptide synthesis (SPPS) and conjugated to the tetramer dL-(Gd-AAZTA)4 . The resulting probe was characterized by 1 H relaxometry, tested in vitro on FB clots and in vivo on an orthotopic mouse model of PCa. RESULTS: CREKA-dL-(Gd-AAZTA)4 showed a remarkable relaxivity of 18.2 m MGd-1s-1 (0.47 T, 25°C) because of the presence of 2 water molecules (q = 2) in the inner coordination sphere of each Gd3+ ion, whose rotational motion (τR ) is lengthened as the result of the relatively high molecular weight. The probe displayed a detectable affinity for plasma-derived FB clots. On intravenous injection of the probe in an orthotopic mouse model of PCa, a significant increase in the prostate T1 contrast (~40%) was observed. The MRI signal appears statistically higher either with respect to the one observed for the control probes and to the one detected when CREKA-dL-(Gd-AAZTA)4 was administered to healthy animals. CONCLUSIONS: This study demonstrated the ability of the CREKA-dL-(Gd-AAZTA)4 probe to specifically localize in prostate tumor after injection. The high relaxivity of the probe allows the reduction of the injected dose to 20 µmolGd /kg, yielding a good in vivo contrast enhancement in the region of prostate tumor.

Clinical Evaluation of Silent T1-Weighted MRI and Silent MR Angiography of the Brain.

OBJECTIVE: New MRI sequences based on rapid radial acquisition have reduced gradient noise. The purpose of this study was to compare Silent T1-weighted and unenhanced MR angiography (MRA) against conventional sequences in a clinical population. MATERIALS AND METHODS: The study cohort consisted of 40 patients with suspected brain metastases (median age, 60 years; range, 23-91 years) who underwent T1-weighted contrast-enhanced MRI and 51 patients with suspected vascular lesions or cerebral ischemia (median age, 60 years; range, 16-94 years) who underwent unenhanced intracranial MRA. Three neuroradiologists reviewed the images blindly and rated several measures of image quality on a 5-point Likert scale. Reviewers recorded the number of enhancing lesions and whether Silent images were better than, worse than, or equivalent to conventional images. RESULTS: For T1-weighted MR images, ratings were slightly lower for Silent versus conventional images, except for diagnostic confidence. Although more lesions were detected on conventional images, this difference was not statistically significant; agreement was seen in 88% of cases. In 48% of cases, T1-weighted scans were deemed equivalent, but when a preference existed, it was usually for conventional images (38% vs 14%). Conventional MRA images were rated higher on all image quality metrics and were strongly preferred (reviewers preferred conventional images in 69% of cases, rated the images as equivalent in 27% of cases, and preferred Silent images in 4% of cases). In some cases, artifacts on Silent images caused reduced vessel caliber, vessel irregularities, and even absent vessels. CONCLUSION: Although conventional T1-weighted images were preferred overall, most Silent T1-weighted images were rated as equivalent to or better than conventional images and represent a potential alternative for imaging of noise-averse patients. Silent MRA scored significantly worse and could not be recommended at this time, suggesting that it requires additional refinement before routine clinical use.

Integrated multimodal network approach to PET and MRI based on multidimensional persistent homology.

Finding underlying relationships among multiple imaging modalities in a coherent fashion is one of the challenging problems in multimodal analysis. In this study, we propose a novel approach based on multidimensional persistence. In the extension of the previous threshold-free method of persistent homology, we visualize and discriminate the topological change of integrated brain networks by varying not only threshold but also mixing ratio between two different imaging modalities. The multidimensional persistence is implemented by a new bimodal integration method called 1D projection. When the mixing ratio is predefined, it constructs an integrated edge weight matrix by projecting two different connectivity information onto the one dimensional shared space. We applied the proposed methods to PET and MRI data from 23 attention deficit hyperactivity disorder (ADHD) children, 21 autism spectrum disorder (ASD), and 10 pediatric control subjects. From the results, we found that the brain networks of ASD, ADHD children and controls differ, with ASD and ADHD showing asymmetrical changes of connected structures between metabolic and morphological connectivities. The difference of connected structure between ASD and the controls was mainly observed in the metabolic connectivity. However, ADHD showed the maximum difference when two connectivity information were integrated with the ratio 0.6. These results provide a multidimensional homological understanding of disease-related PET and MRI networks that disclose the network association with ASD and ADHD. Hum Brain Mapp 38:1387-1402, 2017. © 2016 Wiley Periodicals, Inc.

Prominent Inferior Intercavernous Sinus on Sagittal T1-Weighted Images: A Sign of Intracranial Hypotension.

OBJECTIVE: The purpose of this study is to describe the diagnostic accuracy of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension and to raise awareness of this anatomic structure, which can be mistaken for a focal pituitary lesion. MATERIALS AND METHODS: Sagittal T1-weighted images of 26 patients with intracranial hypotension and 28 control subjects were evaluated to determine the presence of a distended inferior intercavernous sinus. Information about the shape, size, and signal of the inferior intercavernous sinus was also collected. The chi-square test was used to compare both groups. Sensitivity and specificity of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension were calculated. RESULTS: A visible inferior intercavernous sinus was found in 13 of 26 patients with intracranial hypotension (50%) and in four of 28 control subjects (14.3%). These percentages were significantly different (p = 0.005). There was no significant difference in size of the inferior intercavernous sinus in the intracranial hypotension group (median, 5.86 mm(2); interquartile range, 6.28 mm(2)) compared with the control group (median, 8.25 mm(2); interquartile range, 16.69 mm(2)). Changes in the size of the inferior intercavernous sinus were detected in congruence with the appearance or resolution of intracranial hypotension. CONCLUSION: Dilatation of the inferior intercavernous sinus is frequently associated with intracranial hypotension, although it can also be found in the healthy adult as a normal anatomic variant. Recognition of this anatomic structure is important to avoid mistaking it for a focal pituitary lesion.

Reliability of quantifying the spatial distribution of fatty infiltration in lumbar paravertebral muscles using a new segmentation method for T1-weighted MRI.

BACKGROUND: To our knowledge, there are no methods allowing for quantification of the spatial distribution of lumbar paravertebral muscle fatty infiltration (FI) in the transverse plane. There is an increasing emphasis on muscle tissues as modifiable factors in lumbar spine health. Population datasets based on conventional T1-weighted (T1-W) magnetic resonance imaging (MRI) represent a valuable resource for examining all spinal tissues, and methods with reliability are needed. The aim of our study was to determine the reliability of a novel method quantifying lumbar paravertebral muscle fat content based on conventional T1-W MRI. METHODS: Axial 3-Tesla T1W MRIs from ten adult subjects (3W, 7M; mean age 52.8 ± SD 7.2 years) were randomly selected from the large prospective cross-sectional Hong Kong Population-based Disc Degeneration Cohort study examining lumbar spine degeneration. The selected sample included subjects with mixed imaging-determined disc degeneration and low back pain history. Two raters with MRI lumbar paravertebral muscle analysis experience (R1 > 250 h and R2 > 1000 h) repeat-measured the image-set a week apart. Multifidus and erector spinae (spinalis, longissimus and iliocostalis) were manually outlined together on a single-slice from the inferior vertebral end-plates of L1 to L5 using a semi-automated, quartile-defining (Q1-4 (medial to lateral) and Qmean) MatLab-based programme. Bland-Altman plots and intra-class correlation coefficients (ICC) with 95 % confidence intervals (CI) describe intra- and inter-rater reliability according to lumbar level, quartile, and side, and combined level and quartile. RESULTS: There was good intra- (ICC = 0.88; CI: 0.87-0.90) and inter-rater agreement (ICC = 0.82; CI: 0.80-0.84). Intra-rater values for Qmean (ICC; CI) were higher at L5 (0.89; 0.79-0.94) than L1 (0.61; 0.37-0.78). Higher intra-rater values for L1-5 were shown at Q1 (0.93; 0.91-0.95) than Q3 (0.83; 0.78-0.87) or Q4 (0.81; 0.76-0.85), and on the right (0.91; 0.90-0.93) than left (0.85; 0.83-0.88). Similar observations were made for inter-rater values in terms of lumbar level and quartile, with no differences between sides shown. CONCLUSIONS: In our study of ten cases we demonstrate a reliable method to quantify the spatial distribution of fat content in lumbar paravertebral muscles based on T1W MRI. Understanding the geography of fat content in these muscles may offer additional insight in determining and improving spinal health. The clinical relevance and application of this method require testing across various populations to build on the early feasibility established in this study.

T1-weighted MRI of targeting atherosclerotic plaque based on CD40 expression on engulfed USPIO's cell surface.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of cholesterol within the arterial wall. Its progression can be monitored via magnetic resonance imaging (MRI). Ultrasmall Superparamagnetic Particles of Iron Oxide (USPIO) (<5 nm) have been employed as T1 contrast agents for MRI applications. In this study, we synthesized USPIO with an average surface carboxylation of approximately 5.28 nm and a zeta potential of -47.8 mV. These particles were phagocytosed by mouse aortic endothelial cells (USPIO-MAECs) and endothelial progenitor cells (USPIO-EPCs), suggesting that they can be utilized as potential contrast agent and delivery vehicle for the early detection of atherosclerosis. However, the mechanism by which this contrast agent is delivered to the plaque remains undetermined. Our results demonstrated that with increasing USPIO concentration during 10-100 µg ml-1, consistent change appeared in signal enhancement on T1-weighted MRI. Similarly, T1-weighted MRI of MAECs and EPCs treated with these concentrations exhibited a regular change in signal enhancement. Prussian blue staining of USPIO revealed substantial absorption into MAECs and EPCs after treatment with 50 µg ml-1USPIO for 24 h. The iron content in USPIO-EPCs was much higher (5 pg Fe/cell) than in USPIO-MAECs (0.8 pg Fe/cell). In order to substantiate our hypothesis that CD40 protein on the cell surface facilitates migration towards inflammatory cells, we utilized AuNPs-PEI (gold nanoparticles-polyethylenimine) carrying siRNACD40to knockout CD40 expression in MAECs. It has been documented that gold nanoparticle-oligonucleotide complexes could be employed as intracellular gene regulation agents for the control of protein level in cells. Our results confirmed that macrophages are more likely to bind to MAECs treated with AuNPs-PEI-siRNANC(control) for 72 h than to MAECs treated with AuNPs-PEI-siRNACD40(reduced CD40 expression), thus confirming CD40 targeting at the cellular level. When USPIO-MAECs and MAECs (control) were delivered to mice (high-fat-fed) via tail vein injection respectively, we observed a higher iron accumulation in plaques on blood vessels in high-fat-fed mice treated with USPIO-MAECs. We also demonstrated that USPIO-EPCs, when delivered to high-fat-fed mice via tail vein injection, could indeed label plaques by generating higher T1-weighted MRI signals 72 h post injection compared to controls (PBS, USPIO and EPCs alone). In conclusion, we synthesized a USPIO suitable for T1-weighted MRI. Our results have confirmed separately at the cellular and tissue andin vivolevel, that USPIO-MAECs or USPIO-EPCs are more accessible to atherosclerotic plaques in a mouse model. Furthermore, the high expression of CD40 on the cell surface is a key factor for targeting and USPIO-EPCs may have potential therapeutic effects.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

A Characteristic Magnetic Resonance Imaging Finding to Identify Morton Neuroma: The Slug Sign.

Background: Morton neuroma is a common cause of forefoot pain and sensory disturbances, but it is difficult to identify on magnetic resonance imaging (MRI). The aim of this study was to verify the usefulness of a characteristic MRI finding (slug sign) for identifying Morton neuroma and to clarify the relationship between excised neuroma characteristics and preoperative MRI findings. Methods: Twenty-two web spaces were retrospectively assessed from the second and third intermetatarsal spaces of 11 feet of 10 patients (7 women and 3 men, aged average 59.5 years) who underwent surgical excision of Morton neuroma between 2017 and 2022. Asymptomatic web spaces were used as control. Neuromas with 2 branches of the plantar digital nerves on axial T1-weighted MRI (MRI-T1WI) were considered the slug sign. We investigated the preoperative presence of the slug sign in Morton neuroma and asymptomatic control web spaces. We also investigated the relationship between the maximum transverse diameter of the excised specimen and that estimated on coronal MRI-T1WI. Results: A total of 15 Morton neuromas were excised and assessed. The slug signs were present in 10 intermetatarsal spaces in 15 web spaces with Morton neuroma whereas the sign was found in 1 intermetatarsal space in 7 asymptomatic web spaces. The sensitivity and specificity for the slug sign to diagnose Morton neuroma was 66.7% and 85.7%, respectively. The positive and negative predictive values were 90.9% and 54.5%, respectively. The mean maximum transverse diameter of excised neuromas was 4.7 mm. The mean maximum transverse diameter of neuromas on coronal MRI-T1WI was 3.4 mm. A significant positive correlation was found between the maximum transverse diameters of excised specimens and diameters estimated on coronal MRI-T1WI (r = 0.799, P < .001). Conclusion: The slug sign may be a useful indicator of Morton neuroma on MRI to confirm nerve involvement after bifurcation. Level of Evidence: Level IV, retrospective series.

Nanodiamond-Enhanced Magnetic Resonance Imaging.

Nanodiamonds (ND) hold great potential for diverse applications due to their biocompatibility, non-toxicity, and versatile functionalization. Direct visualization of ND by means of non-invasive imaging techniques will open new venues for labeling and tracking, offering unprecedented and unambiguous detection of labeled cells or nanodiamond-based drug carrier systems. The structural defects in diamonds, such as vacancies, can have paramagnetic properties and potentially act as contrast agents in magnetic resonance imaging (MRI). The smallest nanoscale diamond particles, detonation ND, are reported to effectively reduce longitudinal relaxation time T1 and provide signal enhancement in MRI. Using in vivo, chicken embryos, direct visualization of ND is demonstrated as a bright signal with high contrast to noise ratio. At 24 h following intravascular application marked signal enhancement is noticed in the liver and the kidneys, suggesting uptake by the phagocytic cells of the reticuloendothelial system (RES), and in vivo labeling of these cells. This is confirmed by visualization of nanodiamond-labeled macrophages as positive (bright) signal, in vitro. Macrophage cell labeling is not associated with significant increase in pro-inflammatory cytokines or marked cytotoxicity. These results indicate nanodiamond as a novel gadolinium-free contrast-enhancing agent with potential for cell labeling and tracking and over periods of time.