Radial Diffusion Research Articles

Impact of pathogenic variants of the Ras-mitogen-activated protein kinase pathway on major white matter tracts in the human brain.

Noonan syndrome and neurofibromatosis type 1 are genetic conditions linked to pathogenic variants in genes of the Ras-mitogen-activated protein kinase signalling pathway. Both conditions hyper-activate signalling of the Ras-mitogen-activated protein kinase pathway and exhibit a high prevalence of neuropsychiatric disorders. Further, animal models of Noonan syndrome and neurofibromatosis type 1 and human imaging studies show white matter abnormalities in both conditions. While these findings suggest Ras-mitogen-activated protein kinas pathway hyper-activation effects on white matter, it is unknown whether these effects are syndrome-specific or pathway-specific. To characterize the effect of Noonan syndrome and neurofibromatosis type 1 on human white matter's microstructural integrity and discern potential syndrome-specific influences on microstructural integrity of individual tracts, we collected diffusion-weighted imaging data from children with Noonan syndrome (n = 24), neurofibromatosis type 1 (n = 28) and age- and sex-matched controls (n = 31). We contrasted the clinical groups (Noonan syndrome or neurofibromatosis type 1) and controls using voxel-wise, tract-based and along-tract analyses. Outcomes included voxel-wise, tract-based and along-tract fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. Noonan syndrome and neurofibromatosis type 1 showed similar patterns of reduced fractional anisotropy and increased axial diffusivity, radial diffusivity, and mean diffusivity on white matter relative to controls and different spatial patterns. Noonan syndrome presented a more extensive spatial effect than neurofibromatosis type 1 on white matter integrity as measured by fractional anisotropy. Tract-based analysis also demonstrated differences in effect magnitude with overall lower fractional anisotropy in Noonan syndrome compared to neurofibromatosis type 1 (d = 0.4). At the tract level, Noonan syndrome-specific effects on fractional anisotropy were detected in association tracts (superior longitudinal, uncinate and arcuate fasciculi; P < 0.012), and neurofibromatosis type 1-specific effects were detected in the corpus callosum (P < 0.037) compared to controls. Results from along-tract analyses aligned with results from tract-based analyses and indicated that effects are pervasive along the affected tracts. In conclusion, we find that pathogenic variants in the Ras-mitogen-activated protein kinase pathway are associated with white matter abnormalities as measured by diffusion in the developing brain. Overall, Noonan syndrome and neurofibromatosis type 1 show common effects on fractional anisotropy and diffusion scalars, as well as specific unique effects, namely, on temporoparietal-frontal tracts (intra-hemispheric) in Noonan syndrome and on the corpus callosum (inter-hemispheric) in neurofibromatosis type 1. The observed specific effects not only confirm prior observations from independent cohorts of Noonan syndrome and neurofibromatosis type 1 but also inform on syndrome-specific susceptibility of individual tracts. Thus, these findings suggest potential targets for precise, brain-focused outcome measures for existing medications, such as MEK inhibitors, that act on the Ras-mitogen-activated protein kinase pathway.

An integration of neuroimaging and serum proteomics analysis suggests immune and inflammation are associated with white matter microstructure changes in cerebral small vessel disease with depressive symptoms

IntroductionDepressive symptoms are a common concomitant of cerebral small vessel disease (CSVD), of which pathogenesis requires more study. White matter microstructural abnormalities and proteomic alternation have been widely reported regarding depression in the elderly with CSVD. Exploring the relationship between cerebral white matter microstructural alterations and serum proteins may complete the explanation of molecular mechanisms for the findings from neuroimaging research of CSVD combined with depressive symptoms. MethodsAn untargeted proteomics approach based on mass spectrometry was used to obtain serum proteomic profiles, which were clustered into co-expression protein modules. White matter microstructural integrity was measured using the FMRIB Software Library (FSL) and MATLAB to analyze diffusion tensor imaging (DTI) data and calculate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for 50 regions of interest (ROI). Integrating the proteome with the DTI results, weighted gene co-expression analysis (WGCNA) was used to identify protein modules related to white matter microstructural alterations, and the proteins of the corresponding modules were analyzed for functional enrichment through bioinformatics techniques. ResultsDTI measurements were analCerebral small vessel disease (CSVD); Depression; Diffusion tensor imaging (DTI); Proteomics; Inflammationyzed between individuals with CSVD and depressive symptoms (CSVD+D) (n = 24) and those without depressive symptoms (CSVD-D) (n = 35). Results showed an overall increase in MD, AD, and RD within the left hemisphere of the CSVD+D group, suggesting widespread loss of white matter integrity and axonal demyelination, including left superior longitudinal fasciculus (SLF), left posterior corona radiata (PCR) and right external capsule (EC). We identified two protein modules associated with DTI diffusivity, and functional enrichment analyses revealed that complement and coagulation cascades and immune responses participate in the alternation of white matter microstructure in the CSVD+D group. ConclusionThe results suggested immune- and inflammation-related mechanism was associated with white matter microstructure changes in CSVD with depressive symptoms

Using Nanoscale Metal Oxide Films to Investigate the Influence of Anode Interfaces on Lithium Battery Performance

As renewable energy and battery-powered technologies become more widespread, high energy-density and high-performing batteries are required to meet society’s needs. While lithium-ion batteries have been the staple, their energy density development has been slow, and at gravimetric energy densities of around 250 Wh/kg, they are approaching their theoretical limit.1 The lithium-metal battery (LMB) is considered a next-generation battery due to high theoretical energy densities (ex: Lithium-Sulfur, 2600 Wh/kg), and lithium metal’s high gravimetric capacity (3860 mAh/g) and low reduction potential (-3.04 V vs S.H.E.). However, commercialization of LMBs has been limited due to various issues.Two properties that dictate the performance of the LMBs are: 1. The composition of the solid electrolyte interphase (SEI), an electronically conducting, yet passivating, layer at the anode-electrolyte interface, and 2. The morphology of the lithium deposited at the anode. Morphological studies focus on creating dense, low surface area, deposits that limit SEI fracturing and the formation of electronically disconnected lithium. SEI quality is improved by incorporating inorganic or anion-rich SEIs, formed from the electrolyte salt, to promote SEIs that are mechanically robust, ionically conducting, and homogeneous. Our group’s previous work aimed to improve LMB performance via both routes by growing resistive Al2O3 coatings on the copper (Cu) current collector using atomic layer deposition (ALD). Defects in the thin film create areas of low resistance that behave like ultramicroelectrodes which encourage radial diffusion of lithium ions to the nuclei promoting lateral growth and producing low surface area, dense, planar lithium deposits. Simultaneously, the Al2O3 coating’s Lewis acidic properties promote the decomposition and subsequent incorporation of inorganic electrolyte species into the SEI.We present a study of how the different interfaces present at the anode in LMBs impact SEI composition and battery performance. To hold the Li nucleation morphology at the anode constant, we deposit metal oxide films of a fixed resistance onto the Cu current collector, generating planar, low surface area, lithium deposits. This experimental design allows us to decouple the effect of the metal oxide thin film-electrolyte interface on SEI quality and battery performance from that of the lithium morphology. First, as shown in Fig. 1a, different metal oxide films of equal resistance, but different thicknesses, are grown via ALD, confirmed by measuring the first-cycle nucleation overpotential. The resistive metal oxides investigated are Al2O3, HfO2, AlHfxOy, and ZrO2. Scanning electron microscopy results indicate that all cells modified with equal resistance metal oxide films exhibit the same low surface area, dense, planar Li nucleation morphology. However, long-term cycling tests show differences in cell performance and life cycle. Subsequently, the composition of the SEI is investigated using X-ray photoelectron spectroscopy (XPS). Through XPS, an elemental atomic ratio analysis is conducted to investigate the relative number of species derived from the anion of the electrolyte versus the solvent of the electrolyte to reflect the anion-derived nature of the SEI. Additionally, high-resolution peaks are used to determine the relative abundance of high-quality SEI species such as lithium fluoride. This analysis confirms that the metal oxide thin film tunes the SEI composition. Additionally, we identify trends present between the SEI quality of the ALD-modified cell and its performance.To further investigate the thin film-electrolyte interface, a set of cells modified with binary stacked metal oxide thin films with two different stack orders were created, as shown in Fig. 1b. Investigating SEI composition and LMB performance, with the morphology fixed by the nucleation overpotential, allowed for deconvolution of the impact of the Cu-thin film interface and thin film-electrolyte interface. Both interfaces can in principle impact the battery’s function because 1. The Cu-thin film interface controls the electron transport to form Lio from Li+ ion during electrodeposition, and 2. The thin film-electrolyte interface can modulate the SEI. Our results indicated that the SEI and performance were both primarily regulated by the thin film-electrolyte interface. Based on our fixed-resistance and binary stack experimental design, we propose that modulation of the SEI composition by the metal oxide coating controls LMB performance when the Li nucleation morphology is fixed. This result suggests the potential for tuning LMB performance by careful selection of the metal oxide interfacial coating. References (1) Cheng, X.-B., et al. Toward Safe Lithium Metal Anode in Rechargeable Batteries: A Review. Chem. Rev. 2017, 117 (15), 10403–10473. https://doi.org/10.1021/acs.chemrev.7b00115.(2) Oyakhire, S. T., et al. Electrical Resistance of the Current Collector Controls Lithium Morphology. Nature Communications 2022, 13 (1), 3986. https://doi.org/10.1038/s41467-022-31507-w. Figure 1

Investigating the potential of NH2-Functionalized MIL-53(Fe) nanoparticle as a carrier for 5-fluorouracil through molecular dynamics simulation

This study investigates the role of the NH2-functionalized MIL-53(Fe) nanoparticle as a carrier for the anti-cancer drug 5-fluorouracil (5-Fu) through molecular dynamics (MD) simulation. The Atom in Molecules (AIM) method was used to determine the interaction type between 5-Fu and NH2-MIL-53(Fe). The Steered Molecular Dynamics (SMD) approach was employed to calculate the free energy of drug encapsulation. The simulation included the NH2-MIL-53(Fe) nanoparticle containing 5-FU molecules and water molecules at different temperatures and 1 atm pressure. The properties analyzed included density, radial distribution functions, displacement, diffusion, and binding energy of the drug with NH2-MIL-55(Fe). It is shown that the drug was encapsulated in the framework channels and the variation of density of the system with temperature in the presence of nanoparticles decreased. The drug's mean square displacement, total self-diffusion coefficient, and diffusion coefficient in channel direction increased with time as temperature rose. The drug was aligned to have its oxygen atoms towards the metal nodes of the framework. However, The nitrogen atom of the amine functional group in NH2-MIL-53(Fe) interacts more with the F atom of 5-Fu which shows the effect of this functional group on the adsorption of the 5-Fu. The drug's adsorption percentage increased from 298 K to 328 K. The calculated binding energy increased with temperatures and was desirable as it countered the drug's repulsive forces with atoms of NH2-MIL-53(Fe). The results of the molecular docking simulation confirmed MD simulation.

Non-invasive Assessment of Microstructural Changes After CyberKnife Radiosurgery for Trigeminal Neuralgia Using Diffusion Tensor Imaging

Background and Aims: Given the absence of a universally accepted non-invasive and objective clinical tool to predict a patient’s response to stereotactic radiosurgery for Trigeminal Neuralgia (TN), this research endeavoured to appraise the potential of Diffusion Tensor Imaging as a predictive tool in managing TN. Objective: This study aimed to assess microstructural changes in the trigeminal nerve following CyberKnife radiosurgery (CKRS) for TN using diffusion tensor imaging (DTI) and to correlate these changes with clinical outcomes. Methods: Twenty-eight TN patients treated with CKRS underwent pre and 4-month post-treatment Three-Tesla magnetic resonance imaging scans with DTI metrics, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were collected. Clinical outcomes were assessed using the Barrow Neurological Institute Pain Intensity Score (BNI-PIS) at fourth, sixth and ninth months post-CKRS. Results: Twenty-four patients reported good pain relief (responders), while four patients did not experience adequate relief (non-responders). Responders exhibited significantly lower FA (mean drop of 13.8%, P &lt; .001) and lower RA (mean drop of 16.1%, P &lt; .001) compared to non-responders. RD, AD and MD remained constant across the study cohort. Conclusion: DTI metrics, particularly FA and RA, at 4 months post-CKRS, emerged as predictors of long-term treatment effectiveness for TN. These findings suggest the potential utility of DTI in evaluating microstructural changes in the trigeminal nerve post-CKRS and predicting clinical outcomes.

Amyloid, Tau, and APOE in Alzheimer's Disease: Impact on White Matter Tracts.

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aβ) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populations in vivo. In this work, we applied BUAN (Bundle Analytics) tractometry to 3D diffusion MRI data from 730 participants in ADNI3 (phase 3 of the Alzheimer's Disease Neuroimaging Initiative; age range: 55-95 years, 349M/381F, 214 with mild cognitive impairment, 69 with AD, and 447 cognitively healthy controls). Using along-tract statistical analysis, we assessed the localized impact of amyloid, tau, and APOE genetic variants on the brain's neural pathways. BUAN quantifies microstructural properties of white matter tracts, supporting along-tract statistical analyses that identify factors associated with brain microstructure. We visualize the 3D profile of white matter tract associations with tau and amyloid burden in Alzheimer's disease; strong associations near the cortex may support models of disease propagation along neural pathways. Relative to the neutral genotype, APOE ϵ3/ϵ3, carriers of the AD-risk conferring APOE ϵ4 genotype show microstructural abnormalities, while carriers of the protective ϵ2 genotype also show subtle differences. Of all the microstructural metrics, mean diffusivity (MD) generally shows the strongest associations with AD pathology, followed by axial diffusivity (AxD) and radial diffusivity (RD), while fractional anisotropy (FA) is typically the least sensitive metric. Along-tract microstructural metrics are sensitive to tau and amyloid accumulation, showing the potential of diffusion MRI to track AD pathology and map its impact on neural pathways.

Synergistic effects of GFAP and Aβ42: Implications for white matter integrity and verbal memory across the cognitive spectrum

BackgroundPlasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. MethodsIn a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. ResultsIn individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. DiscussionHigher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.

Monoexponential and advanced diffusion-weighted imaging for hepatic fibrosis staging based on high inter-examiner reliability.

To determine the diagnostic efficiencies of multiple diffusion-weighted imaging (DWI) techniques for hepatic fibrosis (HF) staging under the premise of high inter-examiner reliability. Participants with biopsy-confirmed HF were recruited and divided into the early HF (EHF) and advanced HF (AHF) groups; healthy volunteers (HVs) served as controls. Two examiners analyzed intravoxel incoherent motion (IVIM) using the IVIM-DWI and diffusion kurtosis imaging (DKI) models. Intravoxel incoherent motion-DWI, DKI, and diffusion tensor imaging parameters with intraclass correlation coefficients (ICCs) of ≥0.6 were used to create regression models: HVs vs. EHF and EHF vs. AHF. We enrolled 48 HVs, 59 EHF patients, and 38 AHF patients. Mean, radial, and axial kurtosis; fractional anisotropy; mean, radial, and axial diffusivity; and α exhibited excellent reliability (ICCs: 0.80-0.98). Fractional anisotropy of kurtosis, f, and apparent diffusion coefficient showed good reliability (ICCs: 0.69-0.92). The real (0.58-0.67), pseudo- (0.27-0.76), and distributed diffusion coefficients (0.58-0.67) showed low reliability. In the HVs versus (vs.) EHF model, α (p=0.008) and ADC (p=0.011) presented statistical differences (area under curve [AUC]: 0.710). In the EHF vs. AHF model, α (p=0.04) and distributed diffusion coefficient (p=0.02) presented significant differences (AUC: 0.758). Under the premise of high inter-examiner reliability, DWI and IVIM-derived stretched-exponential model parameters may help stage HF.

Variability of energetic proton flux and pitch angle distributions in the Earth's radiation belt modulated by geomagnetic storms

Energetic protons trapped in the radiation belt, as a vital component of the ring current system, are observationally and theoretically modulated by geomagnetic disturbances. Utilizing Van Allen Probe observations, we statistically analyzed their temporal variations at 55–489 keV as well as their pitch angle distributions (PADs) index n (fitted by sinn∂, where ∂ is the pitch angle) in response to geomagnetic storms. It shows that protons at low energies are more easily accelerated during storms. The threshold of accelerations becomes greater for high-energy protons, while a large value of n can persist for a few days to months. Further investigations suggest that one-quarter of the storms increase the proton flux at all energy channels (55–489 keV) both inside and outside the plasmapause location (Lpp). Specifically, more than half of the storms enhance the flux for protons at Ek &amp;gt; 400 keV inside and close to the Lpp as well as protons at Ek &amp;lt; 100 keV deep inside the Lpp. Comparably, protons at larger pitch angles (near 90°) are more easily lost outside the Lpp, which results in more pronounced pancake PADs with larger n. The index n preferentially decreases at L &amp;gt; 5 during 75% of the storms on the dayside, while it decreases at L = ∼4 during 50% of the storms on the nightside, showing significant day–night asymmetry. Further detailed investigations revealed that source and loss processes, including radial diffusion, magnetopause shadowing, and wave–particle interactions, account for the statistical results. The present study provides quantitative information on the overall characteristics of energetic proton fluxes, which can enhance the comprehension of the radiation belts.

Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

The integrity of the corticospinal tract and corpus callosum, and the risk of ALS: univariable and multivariable Mendelian randomization

Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (PFDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178–1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.

Experimental study on granule trajectory tracking for the EPB shield tunneling in sandy cobble stratum

An investigation into the movement characteristics of granules during Earth Pressure Balance (EPB) shield tunneling contributes significantly to understanding the interaction between the shield machine and the soil. This understanding also enables researchers to gain deeper insights into the cutting and guiding effects of the shield cutterhead on the soil, thus providing a scientific basis for optimizing shield tunneling parameters and cutterhead designs. To achieve this, indoor model shield tunneling experiments were conducted using independently developed shield tunneling equipment and spatial positioning devices developed by our research group. The research investigated the spatial movement trajectories, radial diffusion, and axial movement characteristics of granules at the face subjected to the action of a spoke-type cutterhead. Furthermore, the study proposes the use of average diffusion degree and movement rates of granules as metrics for evaluating the cutting and steering performance of the cutterhead. The influence of cutterhead rotational speed and advance rate on the movement characteristics of granules was further explored based on these two indicators. The study’s findings reveal the following: (1) Granules at the face predominantly exhibit a spiral movement trajectory when the EPB shield tunneling machine operates in a dynamic equilibrium state. (2) The cutting and steering performance of the cutterhead’s various areas is enhanced progressively from the center to the outer edge, as evidenced by a gradual decrease in the average diffusion degree of granules and an increase in the average axial movement rate (AMR). (3) The AMR and average diffusion degree of granules are influenced by both the rotational speed of the cutterhead and the advance rate of the shield machine. Optimal matching of the rotational speed and advance rate maximizes the average AMR of granules, minimizes the average diffusion degree, reduces the torque on the cutterhead to its lowest point, and consequently, optimizes the efficiency of shield tunneling. This research presents a novel perspective and methodology for understanding the movement characteristics of granules during shield tunneling operations. The outcomes of this study provide valuable insights for the structural design of shield machine cutterheads and the optimization of tunneling parameters.

Diffusion decrease in normal-appearing white matter structures following photon or proton irradiation indicates differences in regional radiosensitivity

PurposeRadio(chemo)therapy (RCT) as part of the standard treatment of glioma patients, inevitably leads to radiation exposure of the tumor-surrounding normal-appearing (NA) tissues. The effect of radiotherapy on the brain microstructure can be assessed by magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI). The aim of this study was to analyze regional DTI changes of white matter (WM) structures and to determine their dose- and time-dependency. MethodsAs part of a longitudinal prospective clinical study (NCT02824731), MRI data of 23 glioma patients treated with proton or photon beam therapy were acquired at three-monthly intervals until 36 months following irradiation. Mean, radial and axial diffusivity (MD, RD, AD) as well as fractional anisotropy (FA) were investigated in the NA tissue of 15 WM structures and their dependence on radiation dose, follow-up time and distance to the clinical target volume (CTV) was analyzed in a multivariate linear regression model. Due to the small and non-comparable patient numbers for proton and photon beam irradiation, a separate assessment of the findings per treatment modality was not performed. ResultsFour WM structures (i.e., internal capsule, corona radiata, posterior thalamic radiation, and superior longitudinal fasciculus) showed statistically significantly decreased RD and MD after RT, whereas AD decrease and FA increase occurred less frequently. The posterior thalamic radiation showed the most pronounced changes after RCT [i.e., ΔRD = −8.51 % (p = 0.012), ΔMD = −6.14 % (p = 0.012)]. The DTI changes depended significantly on mean dose and time. ConclusionSignificant changes in DTI for WM substructures were found even at low radiation doses. These findings may prompt new radiation dose constraints sparing the vulnerable structures from damage and subsequent side-effects.

ATEP: an advanced transport model for energetic particles

In this paper we report on the implementation and verification of a phase-space resolved energetic particle (EP) transport model. It is based on a first-principle theoretical framework, i.e. the system of non-linear gyrokinetic equations and the related transport equations. Its focus is primarily directed toward understanding the meso-scale character of EPs and its consequences. Compared to the conventional description of thermal radial transport via a one-dimensional radial diffusion equation, the newly developed model is three-dimensional using canonical constants-of-motion (CoM) variables. The model does not assume diffusive processes to be dominant a priori, instead the EP fluxes are self-consistently calculated and directly evolved in CoM space. We use the EP-Stability workflow and the HAGIS code to determine the phase space fluxes explicitly either in the limit of constant mode amplitudes or an energy-conserving quasi-linear model. As an application of the model the transport of neutral-beam-generated EPs due to a toroidal Alfvén eigenmode in an ITER plasma is investigated. As there are no sources and collisions taken into account so far (for an extension of the model see the companion paper (Meng et al 2024 Nucl. Fusion accepted)), the results cannot be considered as an exhaustive study, but rather as a practical demonstration of the conceptual framework on the way to a comprehensive reduced description of burning plasmas.

Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach.

Existing diffusion tensor imaging (DTI) studies of neurological injury following high-level blast exposure (hlBE) in military personnel have produced widely variable results. This is potentially due to prior studies often not considering the quantity and/or recency of hlBE, as well as co-morbidity with non-blast head trauma (nbHT). Herein, we compare commonly used DTI metrics: fractional anisotropy and mean, axial, and radial diffusivity, in Veterans with and without history of hlBE and/or nbHT. We use both the traditional method of dividing participants into 2 equally weighted groups and an alternative method wherein each participant is weighted by quantity and recency of hlBE and/or nbHT. While no differences were detected using the traditional method, the alternative method revealed diffuse and extensive changes in all DTI metrics. These effects were quantified within 43 anatomically defined white matter tracts, which identified the forceps minor, middle corpus callosum, acoustic and optic radiations, fornix, uncinate, inferior fronto-occipital and inferior longitudinal fasciculi, and cingulum, as the pathways most affected by hlBE and nbHT. Moreover, additive effects of aging were present in many of the same tracts suggesting that these neuroanatomical effects may compound with age.

Diffusion tensor imaging biomarkers and clinical assessments in amyotrophic lateral sclerosis (ALS) patients: an exploratory study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Biomarkers are needed to improve diagnosis, gauge progression, and evaluate treatment. Diffusion tensor imaging (DTI) is a promising biomarker for detecting microstructural alterations in the white matter tracts. This study aimed to assess DTI metrics as biomarkers and to examine their relationship with clinical assessments in patients with ALS. Eleven patients with ALS and 21 healthy controls (HCs) underwent 3T MRI with DTI. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were compared between key motor and extra-motor tract groups. Group comparisons and correlations between DTI metrics also correlated with clinical scores of disability (ALSFRS-R), muscle strength (dynamometry), and motor unit loss (MUNIX). Widespread differences were found between patients with ALS and HCs in DTI metrics, including decreased FA and increased diffusivity metrics. However, MD and RD are more sensitive metrics for detecting white matter changes in patients with ALS. Significant interhemispheric correlations between the tract DTI metrics were also observed. DTI metrics showed symmetry between the hemispheres and correlated with the clinical assessments. MD, RD, and AD increases significantly correlated with lower ALSFRS-R and MUNIX scores and weaker dynamometry results. DTI reveals microstructural damage along the motor and extra-motor regions in ALS patients. DTI metrics can serve as quantitative neuroimaging biomarkers for diagnosis, prognosis, monitoring of progression, and treatment. Combined analysis of imaging, electrodiagnostic, and functional biomarkers shows potential for characterizing disease pathophysiology and progression.

Prediction of Motor Recovery Using Diffusion Tensor Imaging and Regional Cerebral Blood Flow in Postoperative Brain Tumors.

To determine whether diffusion tensor image (DTI) parameters and regional cerebral blood flow (rCBF) serve to preoperatively predict postoperative motor outcomes in patients with brain tumors. We included 81 patients with brain tumors who underwent surgical treatment. Motor function was assessed using the manual muscle test in the upper and lower limbs at admission and discharge. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and their ratios (rFA, rMD, rAD, and rRD) were measured at the corona radiata, internal capsule, and cerebral peduncle of the corticospinal tract (CST). In addition, DTI and single photon emission computed tomography (SPECT) were synthesized to measure rCBF at the CST. Both DTI parameters and rCBF at the CST in the preoperative motor weakness group significantly differed from those of the preoperative normal function group. rFA at the cerebral peduncle and the internal capsule was considerably higher in those showing postoperative motor recovery than in those postoperative unchanged or with deteriorated motor function (P < 0.05). Moreover, there was significantly lower rMD and rRD at the internal capsule in the motor recovery group (P < 0.05, P < 0.01).Furthermore, rCBF was higher at all the cerebral peduncle, internal capsule, and corona radiate in the motor recovery group than in the unchanged and deteriorated motor function group (P < 0.05, P < 0.01, P < 0.01). The analysis of DTI parameters and rCBF is useful in predicting postoperative motor outcomes in patients with brain tumors.

Association between sleep stages and brain microstructure in preterm infants: Insights from DTI analysis

Study objectivesThe aim of this study was to investigate the relationship between sleep stages and neural microstructure – measured using diffusion tensor imaging – of the posterior limb of the internal capsule and corticospinal tract in preterm infants. MethodsA retrospective cohort of 50 preterm infants born between 24 + 4 and 29 + 3 weeks gestational age was included in the study. Sleep stages were continuously measured for 5–7 consecutive days between 29 + 0 and 31 + 6 weeks postmenstrual age using an in-house-developed, and recently published, automated sleep staging algorithm based on routinely measured heart rate and respiratory rate. Additionally, a diffusion tensor imaging scan was conducted at term equivalent age as part of standard care. Region of interest analysis of the posterior limb of the internal capsule was performed, and tractography was used to analyze the corticospinal tract. The association between sleep and white matter microstructure of the posterior limb of the internal capsule and corticospinal tract was examined using a multiple linear regression model, adjusted for potential confounders. ResultsThe results of the analyses revealed an interaction effect between sleep stage and days of invasive ventilation on the fractional anisotropy of the left and right posterior limb of the internal capsule (β = 0.04, FDR-adjusted p = 0.001 and β = 0.04, FDR-adjusted p = 0.02, respectively). Furthermore, an interaction effect between sleep stage and days of invasive ventilation was observed for the radial diffusivity of the mean of the left and right PLIC (β = −4.1e-05, FDR-adjusted p = 0.04). ConclusionsPrevious research has shown that, in very preterm infants, invasive ventilation has a negative effect on white matter tract maturation throughout the brain. A positive association between active sleep and white matter microstructure of the posterior limb of the internal capsule, may indicate a protective role of sleep in this vulnerable population.

Glymphatic system dysfunction in mood disorders: Evaluation by diffusion magnetic resonance imaging

The glymphatic system, an expansive cerebral waste-disposal network, harbors myriad enigmatic facets necessitating elucidation of their nexus with diverse pathologies. Murine investigations have revealed a relationship between the glymphatic system and affective disorders. This study aimed to illuminate the interplay between bipolar disorder and the glymphatic system. Fifty-eight individuals afflicted with bipolar disorder were identified through meticulous psychiatric assessment. These individuals were juxtaposed with a cohort of 66 comparably aged and sex-matched, mentally stable subjects. Subsequent analysis entailed the application of covariance analysis to evaluate along with the perivascular space (ALPS) index, a novel magnetic resonance imaging method for assessing brain interstitial fluid dynamics via diffusion tensor imaging within the bipolar and control cohorts. We also evaluated the correlation between the ALPS index and clinical parameters, which included the Hamilton Depression scale scores, disease duration, and other clinical assessments. Moreover, partial correlation analyses, incorporating age and sex as covariates, were performed to investigate the relationships between the ALPS index and clinical measures within the two cohorts. A noteworthy adverse correlation was observed between the ALPS index and illness duration. A free-water imaging analysis revealed a substantial elevation in the free-water index within the white-matter tracts, prominently centered on the corpus callosum, within the bipolar cohort relative to that in the control group. In analogous cerebral regions, a conspicuous affirmative correlation was observed between the free-water–corrected radial diffusivity and depression rating scales. Our results showed that the protracted course of bipolar disorder concomitantly exacerbated glymphatic system dysregulation.

Diffusion indices alteration in major white matter tracts of children with tic disorder using TRACULA

BackgroundTic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis.MethodsWe analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts.ResultsOur findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation.ConclusionThese results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.