In-vivo Magnetic Resonance Imaging Research Articles

Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy.

White matter hyperintensities (WMHs) are frequently observed on magnetic resonance imaging (MRI) in patients with cerebral amyloid angiopathy (CAA). The neuropathological substrates that underlie WMHs in CAA are unclear, and it remains largely unexplored whether the different WMH distribution patterns associated with CAA (posterior confluent and subcortical multispot) reflect alternative pathophysiological mechanisms. We performed a combined invivo MRI-ex vivo MRI-neuropathological study in patients with definite CAA. Formalin-fixed hemispheres from 19 patients with CAA, most of whom also had invivo MRI available, underwent 3T MRI, followed by standard neuropathological examination of the hemispheres and targeted neuropathological assessment of WMH patterns. Exvivo WMH volume was independently associated with CAA severity (P=0.046) but not with arteriolosclerosis (P=0.743). In targeted neuropathological examination, compared with normal-appearing white matter, posterior confluent WMHs were associated with activated microglia (P=0.043) and clasmatodendrosis (P=0.031), a form of astrocytic injury. Trends were found for an association with white matter rarefaction (P=0.074) and arteriolosclerosis (P=0.094). An exploratory descriptive analysis suggested that the histopathological correlates of WMH multispots were similar to those underlying posterior confluent WMHs. This study confirmed that vascular amyloid β severity in the cortex is significantly associated with WMH volume in patients with definite CAA. The histopathological substrates of both posterior confluent and WMH multispots were comparable, suggesting overlapping pathophysiological mechanisms, although these exploratory observations require confirmation in larger studies.

In-Vivo MRI in Rodents: A Protocol for Optimal Animal Positioning.

Magnetic resonance imaging (MRI) is a potentially powerful novel peripheral nerve diagnosis technique. To determine its validity, in-vivo preclinical studies are necessary. However, when using a rodent model, positioning rats and achieving high-resolution images can be challenging. We present a short report that outlines an optimal protocol for positioning rats for in-vivo MRI acquisition. Female Sprague-Dawley rats with sciatic nerve injury were induced into anesthesia using 4% isoflurane in oxygen and maintained at 1.5%. Rats were placed into a plexiglass cradle in a right lateral recumbent position, and a surface coil was placed over the left leg. Respiration rate and body temperature were monitored throughout the scan. Our protocol was successful as rats were able to undergo MRI scanning safely and efficiently. There were no adverse reactions, and clear images of the left sciatic nerve were obtained. Animal positioning took 30 minutes, and 5 different acquisitions were obtained in 2 hours. The total time from anesthesia induction to recovery was under 3 hours. Given the increasing interest in MRI diagnostic techniques, we hope this report aids other researchers studying peripheral nerve injury imaging in rat models.

The Association between Exposure to Fine Particulate Matter and MRI-Assessed Locus Coeruleus Integrity in the Vietnam Era Twin Study of Aging (VETSA).

Increased exposure to ambient air pollution, especially fine particulate matter () is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. Our aim was to investigate if exposure to was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. We examined the relationship between and invivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio () in 381 men [; standard deviation ] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. Multiple linear regressions revealed a significant association between and rostral-middle (; ), whereby higher exposure to was associated with lower . A co-twin control analysis found that, within monozygotic pairs, individuals with higher exposure showed lower (; ), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between and caudal or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.

Multi-scale Knowledge Transfer Vision Transformer for 3D vessel shape segmentation

In order to facilitate the robust and precise 3D vessel shape extraction and quantification from in-vivo Magnetic Resonance Imaging (MRI), this paper presents a novel multi-scale Knowledge Transfer Vision Transformer (i.e., KT-ViT) for 3D vessel shape segmentation. First, it uniquely integrates convolutional embeddings with transformer in a U-net architecture, which simultaneously responds to local receptive fields with convolution layers and global contexts with transformer encoders in a multi-scale fashion. Therefore, it intrinsically enriches local vessel feature and simultaneously promotes global connectivity and continuity for a more accurate and reliable vessel shape segmentation. Furthermore, to enable using relatively low-resolution (LR) images to segment fine scale vessel shapes, a novel knowledge transfer network is designed to explore the inter-dependencies of data and automatically transfer the knowledge gained from high-resolution (HR) data to the low-resolution handling network at multiple levels, including the multi-scale feature levels and the decision level, through an integration of multi-level loss functions. The modeling capability of fine-scale vessel shape data distribution, possessed by the HR image transformer network, can be transferred to the LR image transformer to enhance its knowledge for fine vessel shape segmentation. Extensive experimental results on public image datasets have demonstrated that our method outperforms all other state-of-the-art deep learning methods.

Microglial activation-sensitive gadolinium complex as a potential MRI contrast agent for Alzheimer’s disease diagnosis

Numerous studies have developed gadolinium (Gd)-based contrast agents (GBCAs) for in-vivo magnetic resonance imaging (MRI) with the aim of diagnosing Alzheimer’s disease (AD). Nevertheless, GBCAs that are capable of identifying microglial activation, a critical early indicator of AD pathology, for in-vivo diagnosis remain scarce. In response to this, we synthesized a novel GBCA, Gd-DO3A-Va, designed specifically to detect microglial activation using MRI. This innovative GBCA, which was conjugated with vanillic acid, demonstrated a high selectivity for microglial activation by targeting Toll-like receptor 4 (TLR4). The use of Gd-DO3A-Va in in-vivo imaging successfully highlighted microglial activation in a transgenic AD mouse model. In particular, the use of Gd-DO3A-Va for contrast-enhanced T1-weighted MRI enabled the detection of microglial activation within the hippocampus and cortex, regions notably affected by AD. The observed enhancements in the MR contrast correlated well with immunohistological evidence of microglial activation. Consequently, Gd-DO3A-Va represents a highly promising GBCA for the identification of microglial activation, providing a novel pathway for the molecular diagnosis of AD.

7 Tesla MRI Liver Fat Quantification in Mice: Data Quality Assessment.

The objective of this study was to evaluate the robustness of proton density fat fraction (PDFF) data determined by magnetic resonance imaging (MRI) and spectroscopy (MRS) via spatially resolved error estimation. Using standard T2* relaxation time measurement protocols, in-vivo and ex-vivo MRI data with water and fat nominally in phase or out of phase relative to each other were acquired on a 7 T small animal scanner. Based on a total of 24 different echo times, PDFF maps were calculated in a magnitude-based approach. After identification of the decisive error-prone variables, pixel-wise error estimation was performed by simple propagation of uncertainty. The method was then used to evaluate PDFF data acquired for an explanted mouse liver and an in vivo mouse liver measurement. The determined error maps helped excluding measurement errors as cause of unexpected local PDFF variations in the explanted liver. For in vivo measurements, severe error maps gave rise to doubts in the acquired PDFF maps and triggered an in-depth analysis of possible causes, yielding abdominal movement or bladder filling as in vivo occurring reasons for the increased errors. The combination of pixel-wise acquisition of PDFF data and the corresponding error maps allows for a more specific, spatially resolved evaluation of the PDFF value reliability.

Neonatal stress disrupts the glymphatic system development and increases the susceptibility to Parkinson's disease in later life.

Neonatal stress disrupts brain development and increases the risk of neurological disorders later in life. However, the impact of neonatal stress on the development of the glymphatic system and susceptibility to Parkinson's disease (PD) remains largely unknown. Neonatal maternal deprivation (NMD) was performed on mice for 14 consecutive days to model chronic neonatal stress. Adeno-associated virus expressing A53T-α-synuclein (α-syn) was injected into the substantia nigra to establish PD model mice. Glymphatic activity was determined using invivo magnetic resonance imaging, exvivo fluorescence imaging and microplate assay. The transcription and expression of aquaporin-4 (AQP4) and other molecules were evaluated by qPCR, western blotting, and immunofluorescence. Animal's responses to NMD and α-syn overexpression were observed using behavioral tests. Glymphatic activity was impaired in adult NMD mice. AQP4 polarization and platelet-derived growth factor B (PDGF-B) signaling were reduced in the frontal cortex and hippocampus of both young and adult NMD mice. Furthermore, exogenous α-syn accumulation was increased and PD-like symptoms were aggravated in adult NMD mice. The results demonstrated that NMD could disrupt the development of the glymphatic system through PDGF-B signaling and increase the risk of PD later in life, indicating that alleviating neonatal stress could be beneficial in protecting the glymphatic system and reducing susceptibility to neurodegeneration.

Femoral condyle configuration and its impact on anterior cruciate ligament reconstruction.

Rupture of the anterior cruciate ligament (ACL) is one of the most common knee injuries and has substantial impact on knee function. Beside primary ruptures, an increasing number of re-(re-)ruptures occur, representing a therapeutical challenge for the treating surgeon. Several risk factors for re-ruptures have been previously identified, including an increased tibial slope. In this study, we investigated the effect of femoral condyle configuration on ACL-ruptures and re-ruptures. In-vivo magnetic resonance imaging scans of three different groups of patients were compared. Group 1 included patients with an intact ACL on both sides, group 2 included patients with primary, unilateral ACL-rupture, while group 3 included patients with an ACL-re-rupture or re-(re-)rupture. Fourteen different variables were obtained and analyzed regarding their impact on ACL-re-(re-)rupture. Overall, 334 knees were investigated. Our data allowed us to define parameters to identify anatomical configurations of bones associated with an increased risk of ACL-re-rupture. Our results show, that patients with ACL-re-rupture show increased radii of the extension facet of the lateral femoral condyle (p< 0.001) as well as of the extension facet of the medial femoral condyle (p< 0.001). We conclude that a spherical femoral condyle form does influence the clinical outcome after ACL-reconstruction.

Inverse material parameter estimation of patient-specific finite element models at the carotid bifurcation: The impact of excluding the zero-pressure configuration and residual stress.

The carotid bifurcation experiences a complex loading environment due to its anatomical structure. Previous in-vivo material parameter estimation methods often use simplified model geometries, isotropic hyperelastic constitutive equations or neglect key aspects of the vessel, such as the zero-pressure configuration or residual stress, all of which have independently been shown to alter the stress environment of the vessel wall. Characterizing the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. However, excluding the afore-mentioned zero-pressure configuration, residual stress and patient-specific material parameters can lead to an incorrect estimation of the true stress values observed, meaning that stress alone as a risk indicator of rupture is insufficient. In this study, we investigate how the estimated material parameters and overall stress distributions in geometries of carotid bifurcations, extracted from in-vivo MR images, alter with the inclusion of the zero-pressure configuration and residual stress. This approach consists of the following steps: (1) geometry segmentation and hexahedral meshing from in-vivo magnetic resonance images (MRI) at two known phases; (2) computation of the zero-pressure configuration and the associated residual stresses; (3) minimization of an objective function built on the difference between the stress states of an "almost true" stress field at two known phases and a "deformed" stress field by altering the input material parameters to determine patient-specific material properties; and (4) comparison of the stress distributions throughout these carotid bifurcations for all cases with estimated material parameters. This numerical approach provides insights into the need for estimation of both the zero-pressure configuration and residual stress for accurate material property estimation and stress analysis for the carotid bifurcation, establishing the reliability of stress as a rupture risk metric.

Diffusion tensor imaging of superficial prefrontal white matter in healthy aging

The prefrontal cortex (PFC) is a heterogenous structure that is highly susceptible to the effects of aging. Few studies have investigated age effects on the superficial white matter (WM) contained within the PFC using in-vivo magnetic resonance imaging (MRI). This study used diffusion tensor imaging (DTI) tractography to examine the effects of age, sex, and intracranial volume (ICV) on superficial WM within specific PFC subregions, and to model the relationships with age using higher order polynomial regression modelling. PFC WM of 140 healthy individuals, aged 18–85, was segmented into medial and lateral orbitofrontal, medial prefrontal, and dorsolateral prefrontal subregions. Differences due to age in microstructural parameters such as fractional anisotropy (FA), axial and radial diffusivities, and macrostructural measures of tract volumes, fiber counts, average fiber lengths, and average number of fibers per voxel were examined. We found that most prefrontal subregions demonstrated age effects, with decreases in FA, tract volume, and fiber counts, and increases in all diffusivity measures. Age relationships were mostly non-linear, with higher order regressions chosen in most cases. Declines in PFC FA began at the onset of adulthood while the greatest changes in diffusivity and volume did not occur until middle age. The effects of age were most prominent in medial tracts while the lateral orbitofrontal tracts were less affected. Significant effects of sex and ICV were also observed in certain parameters. The patterns mostly followed myelination order, with late-myelinating prefrontal subregions experiencing earlier and more pronounced age effects, further supporting the frontal theory of aging.

Gadolinium-Coated Mesoporous Silica Nanoparticle for Magnetic Resonance Imaging.

Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd2O3) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity (r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd2O3 to produce Gd2O3@MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity (r 1 ) as high as 51.85 ± 1.38 mM−1s−1. Gd2O3@MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI.

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

Simple SummaryThis study aims at using a multi-technique approach to detect and analyze the effects of high dose rate spatially fractionated radiation therapies and to compare them to seamless broad beam irradiation targeting healthy and glioblastoma-bearing rat brains and delivering three different doses per each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray phase contrast imaging–computed tomography, histology, immunohistochemistry, X-ray fluorescence, and small- and wide-angle X-ray scattering to achieve detailed visualization, characterization and classification in 3D of the radio-induced effects on brain tissues. The original results bring new insights to the understanding of the response of cerebral tissue and tumors treated with high dose rate spatially fractioned radiotherapies and put the basis for channeling studies of in-vivo applications for monitoring RT effects.The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques.

GPU based parallel framework for receiver coil sensitivity estimation in SENSE reconstruction

Magnetic Resonance Imaging (MRI) uses non-ionizing radiations and is safer as compared to CT and X-ray imaging. MRI is broadly used around the globe for medical diagnostics. One main limitation of MRI is its long data acquisition time. Parallel MRI (pMRI) was introduced in late 1990's to reduce the MRI data acquisition time. In pMRI, data is acquired by under-sampling the Phase Encoding (PE) steps which introduces aliasing artefacts in the MR images. SENSitivity Encoding (SENSE) is a pMRI based method that reconstructs fully sampled MR image from the acquired under-sampled data using the sensitivity information of receiver coils. In SENSE, precise estimation of the receiver coil sensitivity maps is vital to obtain good quality images. Eigen-value method (a recently proposed method in literature for the estimation of receiver coil sensitivity information) does not require a pre-scan image unlike other conventional methods of sensitivity estimation. However, Eigen-value method is computationally intensive and takes a significant amount of time to estimate the receiver coil sensitivity maps. This work proposes a parallel framework for Eigen-value method of receiver coil sensitivity estimation that exploits its inherent parallelism using Graphics Processing Units (GPUs). We evaluated the performance of the proposed algorithm on in-vivo and simulated MRI datasets (i.e. human head and simulated phantom datasets) with Peak Signal-to-Noise Ratio (PSNR) and Artefact Power (AP) as evaluation metrics. The results show that the proposed GPU implementation reduces the execution time of Eigen-value method of receiver coil sensitivity estimation (providing up to 30 times speed up in our experiments) without degrading the quality of the reconstructed image.

Registration of histopathology to magnetic resonance imaging of prostate cancer.

Background and purposeThe diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration.Materials and methodsFor twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen’s fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack.ResultsEighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration.ConclusionsOur registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.

Toward a more reliable characterization of fractal properties of the cerebral cortex of healthy subjects during the lifespan

The cerebral cortex manifests an inherent structural complexity of folding. The fractal geometry describes the complexity of structures which show self-similarity in a proper interval of spatial scales. In this study, we aimed at evaluating in-vivo the effect of different criteria for selecting the interval of spatial scales in the estimation of the fractal dimension (FD) of the cerebral cortex in T1-weighted magnetic resonance imaging (MRI). We compared four different strategies, including two a priori selections of the interval of spatial scales, an automated selection of the spatial scales within which the cerebral cortex manifests the highest statistical self-similarity, and an improved approach, based on the search of the interval of spatial scales which presents the highest rounded R2adj coefficient and, in case of equal rounded R2adj coefficient, preferring the widest interval in the log–log plot. We employed two public and international datasets of in-vivo MRI scans for a total of 159 healthy subjects (age range 6–85 years). The improved approach showed strong associations of FD with age and yielded the most accurate machine learning models for individual age prediction in both datasets. Our results indicate that the selection of the interval of spatial scales of the cerebral cortex is thus critical in the estimation of FD.

Muscle phenotype of a rat model of Duchenne muscular dystrophy.

Our aim was to assess key muscle imaging and contractility parameters in the Duchenne muscular dystrophy (DMD) rat model (Dmd-KO rat), which have not yet been characterized sufficiently. We performed in-vivo magnetic resonance imaging (MRI) for thigh and leg muscles, and performed hematoxylin and eosin (H&E) staining and in-vivo muscle contractility testing in specific hindlimb muscles. MRI prior to testing muscle contractility revealed multiple, unevenly distributed focal hyperintensities in the Dmd-KO rat quadriceps and tibialis anterior muscles. H&E staining showed corresponding areas of inflammation and ongoing regeneration. In-vivo contractile testing showed maximal force generated by Dmd-KO muscles was significantly lower, and susceptibility to injury was ~ two-fold greater in the Dmd-KO rats compared to wild-type (WT) rats. Together, the MRI findings, histological findings, and the low strength and high susceptibility to injury in muscles support use of the Dmd-KO rat as an animal model of DMD.

Evaluation of Age- and Radical-Prostatectomy Related Changes in Male Pelvic Floor Anatomy Based on Magnetic Resonance Imaging and 3-Dimensional Reconstruction.

PurposePuborectalis muscles (PRM) and ischiocavernosus muscles (ICM) play important roles in urinary continence and male erectile functions. Understanding of anatomy and surgical-injury related changes to these muscles is critical to monitor changes in continence or erectile function. Anatomical description of these muscles has undergone revisions because these conclusions were derived from cadavers. Our objectives were to: (i) elucidate male pelvic muscles by in-vivo magnetic resonance imaging (MRI) and 3-dimensional (3-D) reconstruction of these images and (ii) compare PRM and ICM thickness in healthy volunteers and symptomatic patients.Materials and MethodsHealthy young male (mean age, 25 years; n=5), older male (age, 65–70 years; n=5), and post-prostatectomy patients with erectile dysfunction and urinary incontinence (age, 65–70 years; n=5) were scanned on a 3T-magnetic resonance scanner. Images were acquired from slices above urinary bladder base to urethra entry into penis. Pelvic bone, bladder/urethra, corpus cavernosum, ICM, PRM, and prostate were segmented. 3-D models of each structure were generated and assembled into composite images, and ICM and PRM thicknesses were calculated.ResultsWe successfully reconstructed 3-D male pelvic floor anatomy including ICM, PRM, bladder, urethra, bulbospongiosus, corpus cavernosa, prostate and bones from the two groups. We documented significant reduction in PRM and ICM thickness in older men.ConclusionsThis is perhaps the first 3-D reconstruction of male pelvic floor structures based on in-vivo MRI in healthy and symptomatic patients. Observed reduction in PRM and ICM thickness is possibly due to age-related atrophy.

Sonographic and 3T-MRI-based evaluation of the tongue in ALS

A few systematic imaging studies employing ultrasound (HRUS) and magnetic resonance imaging (MRI) have suggested tongue measures to aid in diagnosis of amyotrophic lateral sclerosis (ALS). The relationship between structural tongue alterations and the ALS patients' bulbar and overall motor function has not yet been elucidated. We here thus aimed to understand how in-vivo tongue alterations relate to motor function and motor function evolution over time in ALS. Our study included 206 ALS patients and 104 age- and sex-matched controls that underwent HRUS and 3T MRI of the tongue at baseline. Sonographic measures comprised coronal tongue echointensity, area, height, width and height/width ratio, while MRI measures comprised sagittal T1 intensity, tongue area, position and shape. Imaging-derived markers were related to baseline and longitudinal bulbar and overall motor function. Baseline T1 intensity was lower in ALS patients with more severe bulbar involvement at baseline. Smaller baseline coronal (HRUS) and sagittal (MRI) tongue area, smaller coronal height (HRUS) and width (HRUS) as well as more rounded sagittal tongue shape predicated more rapid functional impairment - not only of bulbar, but also of overall motor function - in ALS. Our results suggest that in-vivo sonography und MRI tongue measures could aid as biomarkers to reflect bulbar and motor function impairment.

Quantitative age-dependent differences in human brainstem myelination assessed using high-resolution magnetic resonance mapping

Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21–94 years) and found a decrease in myelination with age in most brainstem regions studied, with several regions exhibiting a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.

Gd2O3 Nanoparticles Coated with a Fluorescent Carbon Layer for Potential T1-Weighted Magnetic Resonance and Cells Imaging

Herein, we report the bifunctional core-shell nanoprobes that can be used as a T1-weighted magnetic resonance imaging (MRI) contrast agent and fluorescent marker for cells imaging. Gd2O3 nanoprobes coated with fluorescent carbon layer were prepared and their physicochemical properties were characterized by FETEM and XRD. A Small-animal MRI scanner (1.5 T) was utilized to measure the T1-weighted relaxivity rate (r1 = 5.57 ± 0.33 mM-1 s-1) of prepared nanoprobes. We showed that prepared nanoprobes exhibited powerful green fluorescence when they penetrated into the living cells. A pilot cytotoxicity study on L-929 fibroblastic cells showed that prepared nanoprobes are relatively safe at concentrations ≤ 8 μg/ml. Thus, prepared samples can be utilized as a promising bifunctional nanoprobe for in-vivo small animal MRI imaging and in-vitro tissues/cells study.