Search Results (124)

This study aims to characterize short-wave infrared (SWIR) reflectance spectra at cranial (at the scalp overlying the frontal cortex and the temporal bone window) and extracranial (biceps and triceps) sites in patients with multiple sclerosis (MS) and age-/sex-matched controls. We sought to identify the diagnostic accuracy of wavelength-specific patterns in distinguishing MS from normal controls and spectral markers associated with disability (e.g., Expanded Disability Status Scale scores). To achieve these objectives, we employed a multi-site SWIR spectroscopy acquisition protocol that included measurements from traditional cranial locations as well as extracranial reference sites. Advanced spectral analysis techniques, including wavelength-dependent absorption modeling and machine learning-based classification, were applied to differentiate MS-related hemodynamic changes from normal physiological variability. Classification models achieved perfect performance (accuracy = 1.00), and cortical site regression models showed strong predictive power (EDSS: R²_CV = 0.980; FSS: R²_CV = 0.939). Variable Importance in Projection (VIP) analysis highlighted key wavelengths as potential spectral biomarkers. This approach allowed us to explore novel biomarkers of neural and systemic impairment in MS, paving the way for potential clinical applications of SWIR spectroscopy in disease monitoring and management. In conclusion, spectral analysis revealed distinct wavelength-specific patterns collected from cranial and extracranial sites reflecting biochemical and structural differences between patients with MS and normal subjects. These differences are driven by underlying physiological changes, including myelin integrity, neuronal density, oxidative stress, and water content fluctuations in the brain or muscles. This study shows that portable spectral devices may contribute to bedside individuation and monitoring of neural diseases, offering a cost-effective alternative to repeated imaging. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) remodelling and glial cell activation, has a decisive effect on lesion development and disease progression. Understanding the biological and pathological features of lesions would aid in prognosis and personalised treatment decision making. Positron emission tomography (PET) is an imaging technique that uses radio-labelled tracers to detect specific biological phenomena. Recent PET hardware developments enable high-resolution, quantitative imaging, which may allow biological characterisation of relatively small MS lesions. PET may complement MRI by offering objective, quantitative insights into lesion characteristics, including myelin density, inflammation and axonal integrity. Moreover, PET may provide information on lesion traits supporting decision making on upcoming therapeutic strategies for progressive MS, such as the availability of oligodendrocyte progenitor cells and ECM composition that affect remyelination and/or axon regeneration. This review explores the cellular and molecular ECM signatures and neuropathological processes of white matter MS lesions, discusses current and potential novel PET targets that may help characterise MS lesions in vivo, and addresses the potential of PET as a decision tool for selection and evaluation of therapeutic strategies, with a focus on remyelination. Full article

Glioblastoma (GBM) often exhibits distinct anatomical patterns of relapse after radiotherapy. Tumour cell migration along myelinated white matter tracts is a key driver of disease progression. The failure of conventional imaging to capture subclinical infiltration has driven interest in advanced imaging biomarkers capable of quantifying tumour–brain interactions. Diffusion tensor imaging (DTI), radiomics, and connectomics represent a triad of innovative, non-invasive approaches that map white matter architecture, predict recurrence risk, and inform biologically guided treatment strategies. This review examines the biological rationale and clinical applications of DTI-based metrics, radiomic signatures, and tractography-informed connectomics in GBM. We discuss the integration of these modalities into machine learning frameworks and radiotherapy/surgical planning, supported by landmark studies and multi-institutional data. The implications for personalised neuro-oncology are profound, marking a shift towards risk-adaptive, tract-aware treatment strategies that may improve local control and preserve neurocognitive function. Full article

Introduction: Hyperbilirubinemia in newborns can lead to kernicterus, a severe form of neonatal encephalopathy caused by bilirubin toxicity. Despite timely interventions such as exchange transfusion, kernicterus can still develop, especially in high-risk infants. MRI is crucial for detecting early and evolving signs of bilirubin-induced brain damage. Case Report: We report a term newborn who developed severe hyperbilirubinemia and kernicterus despite receiving exchange transfusion. The infant presented on day 3 of life with jaundice, hypotonia, and feeding difficulties and had a bilirubin level of 51 mg/dL. After exchange transfusion, bilirubin levels normalized, but neurotoxicity persisted. Initial MRI at one month showed mild T1 hyperintensity in the hippocampi with no changes in the basal ganglia. At two months, T1 hyperintensities in the hippocampi partially resolved. By six months, MRI revealed T2 hyperintensities in the globus pallidus and hippocampal atrophy, consistent with kernicterus. Magnetic resonance spectroscopy (MRS) showed reduced N-acetylaspartate (NAA) levels, indicating neuronal loss. Discussion: MRI is essential in monitoring bilirubin-induced brain injury. In this case, early MRI findings showed mild hippocampal T1 hyperintensity, which resolved partially. At six months, T2 hyperintensities in the globus pallidus confirmed chronic bilirubin encephalopathy. MRS demonstrated a reduction in N-acetylaspartate, indicative of neuronal loss. Susceptibility-Weighted Imaging (SWI) showed no abnormalities, likely due to the myelination process in neonates. Conclusions: This case highlights the importance of repeated MRI in detecting bilirubin-induced brain damage. Early neuroimaging enables timely interventions and improves long-term neurodevelopmental outcomes in infants with severe hyperbilirubinemia. Full article

Background/Objectives: Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath of the central nervous system, which includes the brain and spinal cord. Although MS lesions in the brain are more frequently investigated, MS lesions in the cervical spinal cord (CSC) can be much more specific for the diagnosis of the disease. Furthermore, as lesion burden in the CSC is directly related to disease progression, the presence of lesions in the CSC may help to differentiate MS from other neurological diseases. Methods: In this study, two novel deep learning models based on fractal architectures are proposed for the automatic detection and segmentation of MS lesions in the CSC by improving the convolutional and connection structures used in the layers of the U-Net architecture. In our previous study, we introduced the FractalSpiNet architecture by incorporating fractal convolutional block structures into the U-Net framework to develop a deeper network for segmenting MS lesions in the CPC. In this study, to improve the detection of smaller structures and finer details in the images, an attention mechanism is integrated into the FractalSpiNet architecture, resulting in the Att-FractalSpiNet model. In addition, in the second hybrid model, a fractal convolutional block is incorporated into the skip connection structure of the U-Net architecture, resulting in the development of the Con-FractalU-Net model. Results: Experimental studies were conducted using U-Net, FractalSpiNet, Con-FractalU-Net, and Att-FractalSpiNet architectures to detect the CSC region and the MS lesions within its boundaries. In segmenting the CSC region, the proposed Con-FractalU-Net architecture achieved the highest Dice Similarity Coefficient (DSC) score of 98.89%. Similarly, in detecting MS lesions within the CSC region, the Con-FractalU-Net model again achieved the best performance with a DSC score of 91.48%. Conclusions: For segmentation of the CSC region and detection of MS lesions, the proposed fractal-based Con-FractalU-Net and Att-FractalSpiNet architectures achieved higher scores than the baseline U-Net architecture, particularly in segmenting small and complex structures. Full article

With the increased availability of hybrid PET/MRI in recent years, this method is increasingly used for neuroimaging in clinical practice. It combines the advantages of MRI (including high-resolution imaging of intracerebral lesions and data provided from specialised MRI sequences) with the benefits of PET, which visualises functional alterations in the brain, as well as assesses the myelin quantity changes and the severity of inflammation. The use of PET/MRI may help to eliminate the limitations of MRI indicated in imaging demyelinating inflammatory diseases (such as low specificity in imaging demyelination and a weak correlation of findings with clinical symptoms), as well as insufficient sensitivity in detecting lesions present in encephalitis. In addition to supporting the diagnosis of encephalitis, PET/MRI facilitates monitoring of the disease course and assessing the treatment efficacy of inflammatory demyelinating diseases and encephalitis, as well as evaluating the risk of multiple sclerosis relapse. Further multi-centre longitudinal studies are necessary to assess the real clinical potential of PET/MRI among patients with inflammatory demyelination or encephalitis. In addition to MS and AIE, these studies should also include other inflammatory demyelinating diseases (ADEM, NMO, NMOSD, and MOGAD) as well as encephalitis of viral and parasitic aetiology. Full article

Background: Inherited white matter (WM) disorders of the central nervous systems (CNS), or leukodystrophies, are devastating diseases that primarily affect children, many of whom die early in life or suffer from long-term disability. Methods: q-Space diffusion MR imaging (QSI) and diffusion tensor MR imaging (DTI) with the same resolution and timing parameters were used to study the spinal cords (SCs) of two myelin mutants that are experimental models of WM diseases of different severity, namely the 28-day-old taiep and Long–Evans Shaker (les) rats. The aim was to verify if and which of the diffusion methodologies used is more suitable for early detection of the milder taiep pathology and to characterize its early phase. We also aimed to compare the diffusion MRI results with quantitative electron microscopy (EM) findings. Results: We found that at this early age (28 days), both QSI and DTI were able to detect the severe les WM pathology, while the milder WM pathology in the SC of the taiep rats was detected only by QSI. An increase in the mean radial displacement (RaDis), representing the MRI axon diameter (AD), and a decrease in the probability for zero displacement (PZD) were observed in the dorsal column (ROI 1) of the taiep SCs. In other WM areas, the same trends were observed but the differences were not of statistical significance. In DTI, we found some lower fractional anisotropy (FA) values in the taiep SCs compared to the controls; however, these differences were not statistically significant. For the more severe les pathology, we observed a dramatic increase in the RaDis values and a large decrease in PZD values in all ROIs examined. There, even the FA values were lower than that of the control SCs in all ROIs, albeit with much smaller statistical significance. These MRI results, which show a higher detectability of WM pathology with heavier diffusion weighting, followed histological findings that showed significant myelin deficiency in the dorsal column in the taiep SCs and a practically complete myelin loss in all WM areas in the les SCs. This study also revealed that, under the experimental conditions used here, the apparent increase in RaDis agrees better with myelin thickness and not with average AD extracted form EM, probably reflecting the effect of water exchange. Conclusions: These results, corroborated by diffusion time-dependent QSI, also imply that while diffusion MRI in general and QSI in particular provide acceptable apparent axon diameter estimations in heathy and mature WM, this appears not to be the case in severely damaged WM where exchange appears to play a more important role. Full article

The long-term impact of stroke on Alzheimer’s disease (AD) progression, particularly regarding sex-specific differences, remains unknown. Using a longitudinal study design, we investigated transient middle cerebral artery occlusion in 3.5-month-old APP_swe/PS1_dE9 (APP/PS1) and wild-type mice. In vivo, we assessed behavior, cerebral blood flow (CBF), and structural integrity by neuroimaging, as well as post-mortem myelin integrity (polarized light imaging, PLI), neuroinflammation, and amyloid beta (Aβ) deposition. APP/PS1 mice exhibited cognitive decline, white matter degeneration (reduced fractional anisotropy (FA) via diffusion tensor imaging (DTI)), and decreased myelin density via PLI. Despite early hypertension, APP/PS1 mice showed only sporadic hypoperfusion. Cortical thickening and hippocampal hypertrophy likely resulted from Aβ accumulation and neuroinflammation. Stroke-operated mice retained cognition despite cortical thinning and hippocampal atrophy due to cerebrovascular adaptation, including increased CBF in the hippocampus and thalamus. Stroke did not worsen AD pathology, nor did AD exacerbate stroke outcomes. Sex differences were found: female APP/PS1 mice had more severe Aβ deposition, hyperactivity, lower body weight, and reduced CBF but less neuroinflammation, suggesting potential neuroprotection. These findings highlight white matter degeneration and Aβ pathology as key drivers of cognitive decline in AD, with stroke-related deficits mitigated by (cerebro)vascular adaptation. Sex-specific therapies are crucial for AD and stroke. Full article

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, and neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery and the prevention of further damage. A key area of focus is the remyelination process, where researchers are studying the effects of pharmacotherapy on myelin repair mechanisms. Multiple compounds are being tested for their potential to foster remyelination in different clinical settings through the application of less or more complex techniques to assess their efficacy. Objective: To review current methods and biomarkers to track myelin regeneration and recovery over time in people with MS (PwMS), with potential implications for promyelinating drug testing. Methods: Narrative review, based on a selection of PubMed articles discussing techniques to measure in vivo myelin repair and functional recovery in PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are being implemented to track myelin repair, while other techniques like evoked potentials, functional MRI, and digital markers allow the assessment of functional recovery. These methods, alone or in combination, have been employed to obtain precise biomarkers of remyelination and recovery in various clinical trials on MS. Conclusions: Combining different techniques to identify myelin restoration in MS could yield novel biomarkers, enhancing the accuracy of clinical trial outcomes for remyelinating therapies in PwMS. Full article

Objectives: This study evaluated the efficacy of teriparatide (TPTD) and alendronate (ALN) in mitigating bone loss, enhancing bone structure, and facilitating motor function recovery following spinal cord injury (SCI). Methods: All the rats were allocated into four groups: a sham surgery group (SHAM group), a normal saline group (SCI + NS group), a TPTD treatment group after SCI (SCI + TPTD group), and an ALN treatment group after SCI (SCI + ALN group). The Basso, Beattie, and Bresnahan (BBB) scores and gait analyses were used to assess the motor abilities of rats following SCI and the effects of treatment. HE staining, Masson’s trichrome staining, and LFB staining were performed to evaluate the extent of spinal cord tissue damage. Micro-CT was used to measure 12 bone-related parameters of the proximal tibia and create 3D images, and structural changes in the proximal tibial bone tissue were observed under a light microscope after HE staining. Results: After 12 weeks of treatment, the micro-CT data indicated that TPTD significantly increased key bone indicators, such as bone mineral density, after SCI (p < 0.01), whereas ALN did not significantly improve these indicators (p > 0.05). Compared with the SCI + NS group, the SCI + TPTD group presented significantly greater BBB scores and near-normal gait parameters (p < 0.05). Analyses of pathological sections revealed that TPTD significantly reduced the cavity area in the spinal cord after SCI, decreased the proportion of scar tissue, and increased the retention of neural myelin (p < 0.05). However, ALN had no significant effect on these indicators (p > 0.05). Conclusions: TPTD was more effective than ALN at mitigating bone loss and promoting motor function recovery after SCI, and it demonstrated significant advantages in reducing spinal cord damage and improving tissue structure. Full article

Background/Objectives: Although multiple magnetic resonance imaging (MRI) indices are known to be sensitive to the noninvasive assessment of myelin integrity, their relative sensitivities have not been directly compared. This study aimed to identify the most sensitive MRI index for characterizing myelin composition in the spinal cord’s gray matter (GM) and white matter (WM). Methods: MRI was performed on a deer’s ex vivo cervical spinal cord. Quantitative indices known to be sensitive to myelin, including the myelin water fraction (MWF), magnetization transfer ratio (MTR), the signal ratio between T1- and T2-weighted images (T1W/T2W), fractional anisotropy (FA), mean diffusivity (MD), electrical conductivity (σ), and T1, T2, and T1ρ relaxation times were calculated. Their mean values were compared using repeated measures analysis of variance (ANOVA) and post hoc Bonferroni tests or Friedman and post hoc Wilcoxon tests to identify differences across GM and WM columns possessing distinct myelin distributions, as revealed by histological analysis. Relationships among the indices were examined using Spearman’s rank-order correlation analysis. Corrected p < 0.05 was considered statistically significant. Results: All indices except σ differed significantly between GM and all WM columns. Two of the three WM columns had significantly different MWF, FA, MD, and T2, whereas one WM column had significantly different MTR, σ, T1, and T1ρ from the others. A significant moderate to very strong correlation was observed among most indices. Conclusions: The sensitivity of MRI indices in distinguishing spinal cord regions varied. A strategic combination of two or more indices may allow the accurate differentiation of spinal cord regions. Full article

Cobalt is a trace element, crucial for red blood cell formation and neurological function. Cobalt toxicity is often only diagnosed after severe manifestations, including visual impairment. We aimed to investigate whether optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can effectively detect cobalt-induced ocular toxicity in a murine model. Five wild-type mice (WT, C57Bl6) received daily intraperitoneal cobalt chloride injections for 28 days with a dosage of 12.5 mg/kg. Another 5 WT mice served as controls. After 28 days, all mice underwent manganese contrast-enhanced MRI and OCT examinations. Macroscopic and histological analysis of the enucleated eyes were performed. MRI revealed an increased signal in the optic nerves of injected mice. Anterion OCT provided in vivo visualization of the entire eye, demonstrating incipient cataract formation in the cobalt-injected mice. Both Spectralis domain OCT and Anterion, followed by histological analyses, confirmed preserved retinal structure with decreased thickness in the cobalt-injected group, with only minor neuronal damage and cell loss. Optic nerve analysis demonstrated myelin loss and increased inflammation with high levels of reactive gliosis. This study demonstrates optic neuropathy induced by cobalt toxicity, as shown by increased optic nerve signal on MRI without significant retinopathy. Anterion OCT showed incipient cataracts in the anterior segment. Full article

Using a pediatric-focused lens, this review article briefly summarizes the presentation of several demyelinating and neuroinflammatory diseases using conventional magnetic resonance imaging (MRI) sequences, such as T1-weighted with and without an exogenous gadolinium-based contrast agent, T2-weighted, and fluid-attenuated inversion recovery (FLAIR). These conventional sequences exploit the intrinsic properties of tissue to provide a distinct signal contrast that is useful for evaluating disease features and monitoring treatment responses in patients by characterizing lesion involvement in the central nervous system and tracking temporal features with blood–brain barrier disruption. Illustrative examples are presented for pediatric-onset multiple sclerosis and neuroinflammatory diseases. This work also highlights findings from advanced MRI techniques, often infrequently employed due to the challenges involved in acquisition, post-processing, and interpretation, and identifies the need for future studies to extract the unique information, such as alterations in neurochemistry, disruptions of structural organization, or atypical functional connectivity, that may be relevant for the diagnosis and management of disease. Full article

Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPKα1 activation is crucial. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Myeloid-specific AMPKα1 KO mice were generated by crossing AMPKα1^Flox/Flox and LysM^cre to carry out the study. We induced TON in mice by using a controlled impact system. Mice (mixed sex) were randomized in six experimental groups for Sham (mock); Sham (RIC); AMPKα1^F/F (TON); AMPKα1^F/F (TON+RIC); AMPKα1^F/F LysM^Cre (TON); AMPKα1^F/F LysM^Cre (TON+RIC). RIC therapy was given every day (5–7 days following TON). Data were generated by using Western blotting (pAMPKα1, ICAM1, Brn3 and GAP43), immunofluorescence (pAMPKα1, cd11b, TMEM119 and ICAM1), flow cytometry (CD11b, F4/80, CD68, CD206, IL-10 and LY6G), ELISA (TNF-α and IL-10) and transmission electron microscopy (TEM, for demyelination and axonal degeneration), and retinal oxygenation was measured by a Unisense sensor system. First, we observed retinal morphology with funduscopic images and found TON has vascular inflammation. H&E staining data suggested that TON increased retinal inflammation and RIC attenuates retinal ganglion cell death. Immunofluorescence and Western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in the TON [AMPKα1^F/F] vs. Sham group, but TON+RIC [AMPKα1^F/F] attenuated the expression level of these markers. Interestingly, higher microglia activation was observed in the myeloid AMPKα1^F/F KO group following TON, and RIC therapy did not attenuate microglial expression. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers, increased anti-inflammatory macrophage polarization and improved oxygen level in the TON+RIC [AMPKα1^F/F] group; however, RIC therapy did not reduce inflammatory signaling activation in the myeloid AMPKα1 KO mice. The transmission electron microscopy (TEM) data of the optic nerve showed increased demyelination and axonal degeneration in the TON [AMPKα1^F/F] group, and RIC improved the myelination process in TON [AMPKα1^F/F], but RIC had no significant effect in the AMPKα1 KO mice. The myeloid AMPKα1c deletion attenuated RIC induced anti-inflammatory macrophage polarization, and that suggests a molecular link between RIC and immune activation. Overall, these data suggest that RIC therapy provided protection against inflammation and neurodegeneration via myeloid AMPKα1 activation, but the deletion of myeloid AMPKα1 is not protective in TON. Further investigation of RIC and AMPKα1 signaling is warranted in TON. Full article