Changes In Neurological Disorders Research Articles

Epigenetics and the neurodegenerative process.

Neurological diseases are multifactorial, geneticand environmental. Environmental factors such as diet, physical activityand emotional state are epigenetic factors. Environmental markers are responsible for epigenetic modifications. The effect of epigenetic changes is increased inflammation of the nervous system and neuronal damage. In recent years, it has been shown that epigenetic changes may cause an increased risk of neurological disordersbut, currently, the relationship between epigenetic modifications and neurodegeneration remains unclear. This review summarizes current knowledge about neurological disorders caused by epigenetic changes in diseases such as Alzheimer's disease, Parkinson's disease, strokeand epilepsy. Advances in epigenetic techniques may bekey to understanding the epigenetics of central changes in neurological diseases.

Evaluation of inpatients neurology consultations in the department of gynecology, obstetrics, and reproductive medicine of a tertiary hospital in Turkey

Background & Objective: It is important to be aware of hormonal changes in neurological disease in neurology training. We aimed to investigate the most common disorders which resulted in the clinicians from the Department of Gynecology, Obstetrics, and Reproductive Medicine (GORM) to ask for neurology consultation from the Department of Neurology. Methods: All the neurology consultations requested from the Department of GORM between 2015 and 2023 at Harran University Hospital, Sanliurfa, Turkey, were retrospectively evaluated with regard to demographic characteristics, the reason for referral, neurologic diagnoses, and treatment, imaging features. SPSS statistical software version 22 (IBM Inc. NC, USA) was used to perform all statistical analyses. Results: There were 333 patients with a mean age of 32.5 years (range 17-68) seeking consultations; 287 had obstetric problems, and 46 had gynecological issues. In the obstetric group, pre-eclampsia and Posterior Reversible Encephalopathy Syndrome (PRES) were the most frequent final neurological diagnoses, while headache and acute cerebrovascular disease were the most common frequent problems in the gynecological group. The number of consultations rose from 23 in 2015 to 66 in 2022. The predicted rate of final diagnosis of GORM residents was 58%. The neurologist’s contribution has substantial influence on the management of 208 (62%) patients. Conclusion: Neurologists have a significant contribution to the management of GORM inpatients. In neurological training, importance should be given to the effect of hormonal changes on neurological diseases in neurology training.

A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging.

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

Application of diffusion tensor imaging in Alzheimer\u2019s disease: quantification of white matter microstructural changes

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia in the aging population, responsible for 60–70% of all demented cases. Diffusion tensor imaging (DTI) is a very recent technique that allows the mapping of white matter (WM) microstructure changes in neurological disorders. The current study was conducted to compare DTI parameters between AD patients and healthy elderly subjects and to determine whether DTI can act as a potential biomarker for AD.ResultsThere were significant differences in Modified Mini-Mental State Examination (MMMSE) and Clinical Dementia Rating (CDR) between the two groups. As regards the DTI parameters, significant differences were found between AD patients versus healthy subjects, in the mean diffusivity (MD) of the splenium [(1.05 ± 0.19) vs. (0.92 ± 0.22) , P=0.03], the MD of the right uncinate fasciculus [(0.92 ± 0.04) vs. (0.87 ± 0.05), P= 0.01], and MD of the right arcuate fasciculus (AF) [(0.83 ± 0.04) vs. (0.79 ± 0.04) P =0.01], as well as the MD of the right and left inferior fronto-occipital fasiculus (IFOF) [(0.89 ± 0.06) vs. (0.83 ± 0.04), P=0.01]. In addition, there were significant differences in the fractional anisotropy (FA) of the right and left cingulum between both groups [(0.45 ± 0.02) vs. (0.47 ± 0.03), P=0.01 and (0.45 ± 0.03) vs. 0.49± 0.04), P=0.01, respectively]. The overall accuracy of the aforementioned parameters ranged between 73 and 81% with the MD of the left cingulum revealing the highest accuracy.ConclusionDTI proofed to be a useful tool in differentiating AD patients from healthy subjects. In our study, we found that the splenium, cingulum, IFOF, and the right UF and right AF are the main tracts involved in AD. The left cingulum provided the highest accuracy in differentiating AD from normal subjects.

Triad TMS of Human Motor Cortex

To study cortical excitability changes induced by external stimulation with a certain rhythm, we developed a new method using motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex. In this method, three conditioning TMS with the intensity below the motor threshold are given prior to the supra-threshold test stimulus with the four TMSs were separated by a certain interval (triad-conditioning stimulation: TCS). In healthy volunteers, MEP facilitation was elicited at an interval of 25ms, whereas TCSs with other intervals induced no facilitation. This frequency-dependent facilitation may reflect some intrinsic rhythm of M1 (25ms, i.e. 40Hz). In cortical myoclonus, the facilitation at 25ms was gone whereas facilitation was elicited by triad-conditioning stimulus at 40ms (25Hz), which is consistent with a previously reported abnormal beta rhythm in cortical myoclonus reported previously. Facilitation at 25ms was evoked in neither Parkinson's disease nor in amyotrophic lateral sclerosis. With TCS, we were able to investigate the intrinsic rhythmic activity of M1 and its changes in neurological disorders.

Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations

Quantitative evaluation of brain myelination has drawn considerable attention. Conventional diffusion-based magnetic resonance imaging models, including diffusion tensor imaging and diffusion kurtosis imaging (DKI),11AD: Axial diffusivity; AK: Axial kurtosis; AVF: Axonal volume fraction; AWF: Axonal Water Fraction; DTI: Diffusion Tensor Imaging; DKI: Diffusion Kurtosis Imaging; dMRI: Diffusion magnetic resonance imaging; TE: Echo time; FOV: Field-of-view; FA: Fractional anisotropy; LFB: Luxor fast blue; MD: Mean diffusivity; MK: Mean kurtosis; MRI: Magnetic resonance imaging; MVF: Myelin volume fraction; PLP: Proteolipid protein; RESOLVE: Readout segmentation of long variable echo train; RD: Radial diffusivity; RK: Radial kurtosis; TR: Repetition time; ROI: Region-of-interest; WM: White matter; WMTI: White Matter Tract Integrity. have been used to infer the microstructure and its changes in neurological diseases. White matter tract integrity (WMTI) was proposed as a biophysical model to relate the DKI-derived metrics to the underlying microstructure. Although the model has been validated on ex vivo animal brains, it was not well evaluated with ex vivo human brains. In this study, histological samples (namely corpus callosum) from postmortem human brains have been investigated based on WMTI analyses on a clinical 3T scanner and comparisons with gold standard myelin staining in proteolipid protein and Luxol fast blue. In addition, Monte Carlo simulations were conducted to link changes from ex vivo to in vivo conditions based on the microscale parameters of water diffusivity and permeability. The results show that WMTI metrics, including axonal water fraction AWF, radial extra-axonal diffusivity De⊥, and intra-axonal diffusivity Dawere needed to characterize myelin content alterations. Thus, WMTI model metrics are shown to be promising candidates as sensitive biomarkers of demyelination.

Impaired Topological Properties of Gray Matter Structural Covariance Network in Epilepsy Children With Generalized Tonic-Clonic Seizures: A Graph Theoretical Analysis.

Modern network science has provided exciting new opportunities for understanding the human brain as a complex network of interacting regions. The improved knowledge of human brain network architecture has made it possible for clinicians to detect the network changes in neurological diseases. Generalized tonic–clonic seizure (GTCS) is a subtype of epilepsy characterized by generalized spike-wave discharge involving the bilateral hemispheres during seizure. Network researches in adults with GTCS exhibited that GTCS can be conceptualized as a network disorder. However, the overall organization of the brain structural covariance network in children with GTCS remains largely unclear. Here, we used a graph theory method to assess the gray matter structural covariance network organization of 14 pediatric patients diagnosed with GTCS and 29 healthy control children. The group differences in regional and global topological properties were investigated. Results revealed significant changes in nodal betweenness locating in brain regions known to be abnormal in GTCS (the right thalamus, bilateral temporal pole, and some regions of default mode network). The network hub analysis results were in accordance with the regional betweenness, which presented a disrupted regional topology of structural covariance network in children with GTCS. To our knowledge, the present study is the first work reporting the changes of structural topological properties in children with GTCS. The findings contribute new insights into the understanding of the neural mechanisms underlying GTCS and highlight critical regions for future neuroimaging research in children with GTCS.

Pathological significance of tRNA-derived small RNAs in neurological disorders.

Non-coding RNAs (ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs (tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs (tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points: (1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes. (2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. (3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma. (4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis.

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease‐related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders.

SEMIQUANTITATIVE EVALUATION OF 99MTCTRODAT1 BINDING POTENTIAL BY TWO METHODS OF SPECT IMAGE RECONSTRUCTION.

TRODAT-1 is a radiopharmaceutical derived from tropane and linked to tecnecium-99m ([99mTc] TRODAT-1) has been used in studies of dopamine transporter (DAT) in central nervous system. Associated with the SPECT technique of acquisition, is able to detect changes in neurological disorders like Parkinson´s disease, evaluating the binding potential (BP) of DAT. The aim of this study was to evaluate the influence of the image reconstruction methods, Filtered Back Projection (FBP) and iterative reconstruction (OSEM), in BP values at the striatal region in 30 healthy volunteers. Images were analyzed by visual inspection and semi-quantitative analysis. Regions of interest (ROI) were made over striatal areas on both sides. Nonparametric Wilcoxon statistical analysis was performed between the BP values from the FBP and OSEM methods. Our results showed that the reconstruction methods have a statistical significant BP values difference in the total striatum (Z = -2,2787 p = 0.005), right striatum (Z = -2,602 p = 0.009) and left striatum (Z= 2,746 p = 0.006). The effect size was calculated to see if there influence in this test: the "large effect size" for all measurements was observed (total striatum r= -0.51; right striatum r= -0.48; left striatum r= -0.50). FBP is the usual method of reconstruction for brain SPECT images, and our results showed influence of the OSEM method in BP. It is concluded that the method of image reconstruction adopted should be standardized to avoid incorrect evaluations of BP values using [99mTc]TRODAT-1.

Evaluation of Hyponatremia in Ischemic Stroke Patients in a Tertiary Care Hospital of Karachi, Pakistan.

IntroductionElectrolyte disturbances are commonly found in acute stroke settings. Hypernatremia, hyponatremia and hypokalemia are the commonest types of electrolyte disturbances. Data on electrolyte changes in neurological disorders like stroke is insufficient in Asia. This study aims to quantify the decrease in sodium levels in patients of ischemic stroke and to see whether the presence of co-morbidities like hypertension and diabetes result in decrement in the sodium level of the patients admitted.MethodologyThis is a cross-sectional study conducted in Ruth M Pfau Civil hospital Karachi on 132 consenting patients diagnosed with ischemic stroke on a clinical and radiological basis using a preformed questionnaire with all the necessary information to evaluate the objective like gender, level of sodium and co-morbidities. The data was analyzed using Chi‑squared test using SPSS (Statistical Package for Social Science) software version 22 (IBM, NY, USA).ResultThe study showed that the majority of the patients (25%) had mild hyponatremia (130-134 mMol/L), only a few (9.8%) had moderate (125-129 mMol/L) or profound (<125) hyponatremia (3.8%) and 17 out of 44 patients who were hypertensive had their sodium levels changed while only 10 out of 17 diabetics had fluctuating sodium levels (p-value = 0.00). We also found out that most of the patients with altered sodium levels were male in the age range of above 55.ConclusionPatients with ischemic stroke do develop hyponatremia, but only with a slight alteration in the sodium levels.

CSF Sample Preparation for Data-Independent Acquisition.

To study changes in neurological diseases and to identify disease-related mechanisms or biomarkers for diagnosis, cerebrospinal fluid (CSF) is frequently used for proteomic-based discovery. In the last years, development and application of mass spectrometry (MS) techniques have made essential contributions to proteomic studies including protein identification as well as quantification. Until recently, biomarker discovery studies were performed through bottom-up proteomics utilizing data-dependent acquisition. However, drawbacks like stochastic selection of precursor ions cause the exclusion of low-abundant ions from fragmentation as well as from data analysis leading to technical variances among different samples and result in inconsistent data sets. In contrast, data-independent acquisition (DIA) enables almost complete and reproducible quantitative analysis gaining more and more interest as a method for reliable MS-based protein quantification. Besides the utilization of a proper analysis platform, a prerequisite for biomarker studies is the selection of suitable samples and sample processing strategies. Especially for CSF, blood contamination has tremendous impact on the quantitative analysis. In addition, complex processing methods such as protein or peptide fractionation prior to MS analysis can lead to variabilities that affect the reliability of the quantitative results. Here we present methods to evaluate in a first step the CSF quality in regard to blood contamination for the subsequent MS-based sample preparation and finally a DIA method for the analysis of CSF.

Enhancing quality in Diffusion Tensor Imaging with anisotropic anomalous diffusion filter

Abstract Introduction: Diffusion tensor imaging (DTI) is an important medical imaging modality that has been useful to the study of microstructural changes in neurological diseases. However, the image noise level is a major practical limitation, in which one simple solution could be the average signal from a sequential acquisition. Nevertheless, this approach is time-consuming and is not often applied in the clinical routine. In this study, we aim to evaluate the anisotropic anomalous diffusion (AAD) filter in order to improve the general image quality of DTI. Methods A group of 20 healthy subjects with DTI data acquired (3T MR scanner) with different numbers of averages (N=1,2,4,6,8, and 16), where they were submitted to 2-D AAD and conventional anisotropic diffusion filters. The Relative Mean Error (RME), Structural Similarity Index (SSIM), Coefficient of Variation (CV) and tractography reconstruction were evaluated on Fractional Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) maps. Results The results point to an improvement of up to 30% of CV, RME, and SSIM for the AAD filter, while up to 14% was found for the conventional AD filter (p<0.05). The tractography revealed a better estimative in fiber counting, where the AAD filter resulted in less FA variability. Furthermore, the AAD filter showed a quality improvement similar to a higher average approach, i.e. achieving an image quality equivalent to what was seen in two additional acquisitions. Conclusions In general, the AAD filter showed robustness in noise attenuation and global image quality improvement even in DTI images with high noise level.

Increased Modularity of Resting State Networks Supports Improved Narrative Production in Aphasia Recovery.

The networks that emerge in the analysis of resting state functional magnetic resonance imaging (rsfMRI) data are believed to reflect the intrinsic organization of the brain. One key property of such complex biological networks is modularity, a measure of community structure. This topological characteristic changes in neurological disease and recovery. Nineteen subjects with language disorders after stroke (aphasia) underwent neuroimaging and behavioral assessment at multiple time points before (baseline) and after an imitation-based therapy. Language was assessed with a narrative production task. Group independent component analysis was performed on the rsfMRI data to identify resting state networks (RSNs). For each participant and each rsfMRI acquisition, we constructed a graph comprising all RSNs. We assigned nodal community based on a region's RSN membership, calculated the modularity score, and then correlated changes in modularity and therapeutic gains on the narrative task. We repeated this comparison controlling for pretherapy performance and using a community structure not based on RSN membership. Increased RSN modularity was positively correlated with improvement on the narrative task immediately post-therapy. This finding remained significant when controlling for pretherapy performance. There were no significant findings for network modularity and behavior when nodal community was assigned without consideration of RSN membership. We interpret these findings as support for the adaptive role of network segregation in behavioral improvement in aphasia therapy. This has important clinical implications for the targeting of noninvasive brain stimulation in poststroke remediation and suggests potential for further insight into the processes underlying such changes through computational modeling.

Age, Gender and Normalization Covariates for Spinal Cord Gray Matter and Total Cross-Sectional Areas at Cervical and Thoracic Levels: A 2D Phase Sensitive Inversion Recovery Imaging Study

The source of inter-subject variability and the influence of age and gender on morphometric characteristics of the spinal cord, such as the total cross-sectional area (TCA), the gray matter (GM) and white matter (WM) areas, currently remain under investigation. Understanding the effect of covariates such as age, gender, brain volumes, and skull- and vertebra-derived metrics on cervical and thoracic spinal cord TCA and GM areas in healthy subjects would be fundamental for exploring compartment specific changes in neurological diseases affecting the spinal cord. Using Magnetic Resonance Imaging at 3T we investigated 32 healthy subjects using a 2D phase sensitive inversion recovery sequence and we measured TCA, GM and WM areas at 4 cervical and thoracic levels of the spinal cord. We assessed age and gender relationships of cord measures and explored associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics. Age and gender had a significant effect on TCA, WM and GM areas (with women and elderly having smaller values than men and younger people respectively), but not on the GM area/TCA ratio. The total intracranial volume and C3 vertebra dimensions showed the highest correlations with cord measures. When used in multi-regression models, they reduced cord areas group variability by approximately a third. Age and gender influences on cord measures and normalization strategies here presented might be of use in the study of compartment specific changes in various neurological diseases affecting the spinal cord.

Hyperconnectivity is a fundamental response to neurological disruption.

In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity.

Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of these iPSCs into differentiated cells. In particular, much interest has focused on the ability to differentiate human iPSCs into neuronal progenitors and functional neurons for relevance to a large number of pathologies including mental retardation and behavioral or degenerative syndromes. Current differentiation protocols are time-consuming and generate limited amounts of cells, hindering use on a large scale. We describe a feeder-free method relying on the use of a chemically defined medium that overcomes the need for embryoid body formation and neuronal rosette isolation for neuronal precursors and terminally differentiated neuron production. Four days after induction, expression of markers of the neurectoderm lineage is detectable. Between 4 and 7 days, neuronal precursors can be expanded, frozen, and thawed without loss of proliferation and differentiation capacities or further differentiated. Terminal differentiation into the different subtypes of mature neurons found in the human brain were observed. At 6-35 days after induction, cells express typical voltage-gated and ionotrophic receptors for GABA, glycine, and acetylcholine. This specific and efficient single-step strategy in a chemically defined medium allows the production of mature neurons in 20-40 days with multiple applications, especially for modeling human pathologies.

A Learning Based Fiducial-driven Registration Scheme for Evaluating Laser Ablation Changes in Neurological Disorders.

In this work, we present a novel learning based fiducial driven registration (LeFiR) scheme which utilizes a point matching technique to identify the optimal configuration of landmarks to better recover deformation between a target and a moving image. Moreover, we employ the LeFiR scheme to model the localized nature of deformation introduced by a new treatment modality - laser induced interstitial thermal therapy (LITT) for treating neurological disorders. Magnetic resonance (MR) guided LITT has recently emerged as a minimally invasive alternative to craniotomy for local treatment of brain diseases (such as glioblastoma multiforme (GBM), epilepsy). However, LITT is currently only practised as an investigational procedure world-wide due to lack of data on longer term patient outcome following LITT. There is thus a need to quantitatively evaluate treatment related changes between post- and pre-LITT in terms of MR imaging markers. In order to validate LeFiR, we tested the scheme on a synthetic brain dataset (SBD) and in two real clinical scenarios for treating GBM and epilepsy with LITT. Four experiments under different deformation profiles simulating localized ablation effects of LITT on MRI were conducted on 286 pairs of SBD images. The training landmark configurations were obtained through 2000 iterations of registration where the points with consistently best registration performance were selected. The estimated landmarks greatly improved the quality metrics compared to a uniform grid (UniG) placement scheme, a speeded-up robust features (SURF) based method, and a scale-invariant feature transform (SIFT) based method as well as a generic free-form deformation (FFD) approach. The LeFiR method achieved average 90% improvement in recovering the local deformation compared to 82% for the uniform grid placement, 62% for the SURF based approach, and 16% for the generic FFD approach. On the real GBM and epilepsy data, the quantitative results showed that LeFiR outperformed UniG by 28% improvement in average.

Electroanalytical Sensors and Methods for Assays and Studies of Neurological Biomarkers

AbstractDiverse methods have been developed to reveal biochemical changes in neurological disorders and to detect biomarkers present in clinical samples. Electrochemical biosensors are attractive because of their low costs, high sensitivity, and easiness for miniaturization. They have the potential for both point‐of‐care and in vivo monitoring. With clever surface modification and effective immobilization of capture ligands, selective detection of neurological biomarkers can be achieved. This review covers select applications of electroanalytical methods/sensors for proteins, peptides, small molecules, metal ions, and neurotransmitters. Designs of various sensors and devices are reviewed and issues to be addressed for clinically viable sensors are discussed.

Visualization of intra-thalamic nuclei with optimized white-matter-nulled MPRAGE at 7 T

Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.