Altered white matter microarchitecture in Parkinson's disease: a voxel-based meta-analysis of diffusion tensor imaging studies / 医学前沿

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson's disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size-signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with 30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses.

Values of Apparent Diffusion Coefficient and Fractional Anisotropy in the Diagnosis of Brucella Spondylitis / 中国医学科学院学报

To compare the differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) between brucella spondylitis (BS) groups at different stages before treatment and the normal control group and to evaluate the change trend of ADC value and FA value at different time points before and after treatment. Totally 53 patients suspected of BS by conventional magnetic resonance imaging (MRI) and later confirmed as BS patients by serological tests were enrolled in this study. These patients underwent conventional MRI and diffusion tensor imaging scans,and the ADC value and FA value were measured. Independent sample test was used to compare the ADC value and FA value between the BS group and the control group,the ADC value and FA value between the BS group at each stage. Repeated measurement ANOV was used to compare the ADC values and FA values at different time points before and after treatment. FA imaging showed that the color code of BS was different from that of the normal control group,and the color code of FA imaging showed increased singal. The ADC values of BS in the acute,subacute,and chronic stages [(1.45±0.02)×10 mm /s,(1.35±0.03)×10 mm /s,(1.26±0.05)×10 mm /s,respectively] were significantly higher than those in the control group [(1.06±0.09) ×10 mm /s](=2.538,=0.009;=1.998,=0.032;=1.575,=0.004),and the FA value (0.55±0.02,0.65±0.03,0.71±0.04,respectively) were significantly lower than those of the control group (0.78±0.02) (=2.440,=0.012; =1.847,=0.041;=2.102,=0.003). Repeated measurement analysis showed that there were statistically significant differences in ADC values and FA values at different time points before and after treatment in the acute,subacute,and chronic stages (ADC:=12.100,<0.001;=8.439,=0.005;=9.704,=0.004,respectively;FA:=7.080,=0.002;=6.607;=0.003;=8.868,=0.001,respectively). The ADC values at different time points after treatment were significantly lower than those before treatment or at a previous time point after treatment (=332.14,<0.001),and the FA values were significantly higher than those before treatment or at a previous time point after treatment (=134.26,<0.001). FA color code can intuitively display differences in BS and normal vertebral bodies and show change of color code before and after treatment. Also,the ADC values and FA values can quantitatively reveal differences between BS and normal vertebral body in different time points and quantify BS vertebral lesion changes before and after treatment. In particular,in BS patients who are recovering from treatment,it can quantify microscopic edema. Therefore,diffusion tensor imaging may be useful objective indicator in evaluating the effectiveness of a specific treatment for BS.

Application of magnetic resonance diffusion tensor imaging in bilirubin-induced neurological dysfunction in neonates / 中国当代儿科杂志

OBJECTIVE@#To study the value of fractional anisotropy (FA) of regions of interest (ROI) on magnetic resonance diffusion tensor imaging (DTI) in bilirubin-induced neurological dysfunction in neonates.@*METHODS@#A total of 91 neonates with hyperbilirubinemia who were hospitalized from January 2017 to January 2018 were enrolled. According to the peak level of total serum bilirubin, they were divided into three groups: mild/moderate increase (n=45), severe increase (n=35), and extremely severe increase (n=11). According to the presence or absence of abnormal neurological manifestations, they were divided into two groups: neurological dysfunction (n=20) and non-neurological dysfunction (n=71). Ten healthy full-term infants were enrolled as the control group. Head DTI was performed for all neonates to measure the FA values of the bilateral globus pallidus, the anterior limb of the internal capsule, the posterior limb of the internal capsule, and the cerebellar dentate nucleus.@*RESULTS@#The extremely severe increase group had significantly lower FA values of the globus pallidus than the control, mild/moderate increase, and severe increase groups (P<0.05). The severe increase group had significantly lower FA values of the globus pallidus than the control group (P<0.05). The extremely severe increase group had significantly lower FA values of the posterior limb of the internal capsule than the control, mild/moderate increase, and severe increase groups (P<0.05). The neurological dysfunction group had significantly lower FA values of the globus pallidus and the posterior limb of the internal capsule than the non-neurological dysfunction group (P<0.05).@*CONCLUSIONS@#Serum bilirubin level combined with the changes in the DTI FA values of the globus pallidus and the posterior limb of the internal capsule can be used to predict the injury of cerebral nuclei and white matter fibers.

Thyroid-Associated Orbitopathy: Evaluating Microstructural Changes of Extraocular Muscles and Optic Nerves Using Readout-Segmented Echo-Planar Imaging-Based Diffusion Tensor Imaging

OBJECTIVE: We aimed to investigate the ability of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in assessing the microstructural change of extraocular muscles (EOMs) and optic nerves in patients with thyroid-associated orbitopathy (TAO) as well as in evaluating disease activity.MATERIALS AND METHODS: We enrolled 35 TAO patients and 22 healthy controls (HCs) who underwent pre-treatment rs-EPI-based DTI. Mean, axial, and radial diffusivity (MD, AD, and RD) and fractional anisotropy (FA) of the medial and lateral EOMs and optic nerve for each orbit were calculated and compared between TAO and HC groups and between active and inactive TAO groups. Factors such as age, sex, disease duration, mediation, and smoking history between groups were also compared. Logistic regression analysis was used to evaluate the predictive value of significant variables for disease activity.RESULTS: Disease duration was significantly shorter in active TAOs than in inactive ones (p < 0.001). TAO patients showed significantly lower FA and higher MD, AD, and RD than HCs for both medial and lateral EOMs (p < 0.001), but not the AD value of lateral EOMs (p = 0.619). Active patients had significantly higher FA, MD, and AD than inactive patients for medial EOMs (p < 0.005), whereas only FA differed significantly in the lateral EOMs (p = 0.018). The MD, AD, and RD of optic nerves were significantly lower in TAO patients than HCs (p < 0.05), except for FA (p = 0.129). Multivariate analysis showed that the MD of medial EOMs and disease duration were significant predictors for disease activity. The combination of these two parameters showed optimal diagnostic efficiency for disease activity (area under the curve, 0.855; sensitivity, 68.4%; specificity, 96.9%).CONCLUSION: rs-EPI-based DTI is promising in assessing microstructural changes of EOMs and optic nerves and can help to indicate the disease activity of TAO, especially through the MD of medial EOMs.

Volumetría de fascículos cerebrales en población sana / Brain fascicles volumetry in healthy population

Objetivo Desde la aparición de la tractografía, al tratarse de una técnica no invasiva y que usa la ampliamente conocida resonancia magnética (RM), el estudio de la sustancia blanca se ha facilitado. A partir de eso, se han logrado grandes descubrimientos en cuanto a fascículos cerebrales involucrados en funciones cognitivas. Sin embargo, su evaluación sigue siendo subjetiva y depende de la experiencia y entrenamiento del evaluador, razón por la cual se ha limitado su aplicabilidad en la práctica clínica. En ese sentido, es conveniente parametrizar volúmenes cerebrales de sustancia blanca en población sana a través de una herramienta electrónica que se pueda reproducir y así poderlo aplicar en enfermos. Materiales y métodos Se reportan 10 sujetos sanos desde el punto de vista neurológico. Para cada sujeto, se adquirieron imágenes ponderadas por difusión y los resultados se visualizaron mediante FiberNavigator (http://scilus.github.io/fibernavigator). Finalmente, esa misma herramienta fue utilizada para purificar los fascículos objeto de estudio y realizar el conteo de las fibras. Resultados Se obtuvieron valores de volumetría del fascículo longitudinal superior (FLS), fascículo longitudinal inferior (FLI), fascículo frontoccipital inferior (FFI), fascículo uncinado (FU) y fascículo del cíngulo (FC), identificando que no existen diferencias estadísticamente significativas entre el número de fibras que componen los fascículos cerebrales. Discusión Los resultados alcanzados de la anatomía y la direccionalidad de fibras de los fascículos cerebrales de este estudio coinciden con el resto de la evidencia publicada hasta el momento, sin encontrar diferencias en cuanto a su organización y recorrido. Conclusión Aunque esos resultados no sirven como valores de referencia para ser aplicados en pacientes con patología neurológica, brindamos información inexistente hasta el momento, con ese equipo en específico y la reproducción entre los distintos usuarios y el software.

Objective Since the appearance of tractography, as it is a non-invasive technique and uses the widely known magnetic resonance (MR), the study of white matter has been facilitated. After this, great discoveries have been made regarding the brain fascicles involved in cognitive functions. However, its evaluation continues to be subjective and depends on the evaluator's experience and training. That the reason why its applicability has been limited in clinical practice. Because of this, it is convenient to parametrize cerebral volumes of white matter in healthy population through an electronic, reproducible tool that could be applied in patients. Materials and Methods Ten neurologically healthy subjects are reported, for each subject we acquired images weighted by diffusion and the results were visualized by means of FiberNavigator (http://scilus.github.io/fibernavigator). Finally, this same tool was used to purify the fascicles under study and perform the fiber count. Results Volumetric values of the upper longitudinal fasciculus, inferior longitudinal fasciculus, inferior frontoccipital fasciculus, uncinated fasciculus and cingulate fasciculus were obtained, identifying that there are not statistically significant differences in the number of fibers that make up the cerebral fascicles. Discussion The results achieved of the anatomical and fiber directionality of the cerebral fascicles of this study, coincide with the rest of the evidence published up to now, without finding differences regarding its organization and route. Conclusion Although these results do not serve as reference values to be applied in patients with neurological pathology, do we provide nonexistent information so far, with this specific equipment and the reproducibility between the different users and the software.

Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.

Diffusion Metrics as a Potential Prognostic Biomarker in Cervical Myelopathy

Diffusion tensor imaging (DTI) has a diagnostic value in cervical myelopathy. The usefulness of diffusion metrics as a potential prognostic biomarker was assessed in this review. Various diffusion metrics, such as fractional anisotropy, mean diffusivity, apparent diffusion coefficient, and radial diffusivity, were significant in correlation with functional recovery after surgery. Changes in diffusion metrics not only at the compression level, but also above and below the compression level were confirmed. However, it was difficult to confirm the results owing to the diversity of studies. Further efforts to make a consensus on spinal cord DTI are needed.

White matter integrity in patients with mild cognitive impairment complicated with lacunar infarctions by diffusion tensor imaging / 中南大学学报(医学版)

To evaluate the white-matter integrity and its correlation with cognitive function in patients with mild cognitive impairment (MCI) complicated with lacunar infarctions (LI) by diffusion tensor imaging (DTI) of magnetic resonance (MR).
 Methods: Twenty-six patients with MCI were selected including 14 patients with combined LI and 12 patients without combined LI, and 16 healthy volunteers were recruited as normal control. All subjects completed cognitive function assessment and DTI sequence of MR. Factional anisotropy (FA) and mean diffusivity (MD) values among the MCI with LI group (MCI-LI), the MCI without LI group (MCI-non LI), and the normal control group (NC) were compared, and the correlation between DTI parameters and cognition was determined by multiple linear stepwise regression.
 Results: Compared with the MCI-non LI group, the FA values were significantly decreased (P<0.05) and MD values were significantly increased (P<0.05) in the white matter fiber bundles (such as the left hippocampus of the cingulate tract, the frontal fascicle of the corpus callosum, the right inferior frontal occipital fascicle, and the right superior longitudinal fascicle) in the MCI-LI group. In the MCI-LI group, the FA value of right cingulate gyrus was significantly correlated with Activity of Daily Living Scale (ADL) score (B=-50.2, 95% CI -77.7 to -22.7, P=0.003); the FA value of left anterior thalamic radiation (B=443.8, 95% CI 222.9 to 664.8, P=0.001) and MD value of left inferior longitudinal tract (B=-318.5, 95% CI -534.7 to -102.3, P=0.009) were significantly correlated with Wechsler digit symbol substitution (WDSS) score; the FA value of left superior temporal lobe longitudinal tract was significantly correlated with Backward Digit Span (BDSP) score (B=12.5, 95% CI 1.5 to 23.4, P=0.030).
 Conclusion: The integrity of white matter is significantly destroyed in MCI patients with LI than that in MCI patients without LI, and there is a correlation between cognitive function and DTI parameters in some white matter tracts in MCI patients with LI.

Imaging changes in brain microstructural in long-term abstinent from methamphetamine-dependence / 中南大学学报(医学版)

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.

Increased white matter diffusivity associated with phantom limb pain

BACKGROUND: We utilized diffusion tensor imaging (DTI) to evaluate the cerebral white matter changes that are associated with phantom limb pain in patients with unilateral arm amputation. It was anticipated that this would complement previous research in which we had shown that changes in cerebral blood volume were associated with the cerebral pain network. METHODS: Ten patients with phantom limb pain due to unilateral arm amputation and sixteen healthy age-matched controls were enrolled. The intensity of phantom limb pain was measured by the visual analogue scale (VAS) and depressive mood was assessed by the Hamilton depression rating scale. Diffusion tensor-derived parameters, including fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD), were computed from the DTI. RESULTS: Compared with controls, the cases had alterations in the cerebral white matter as a consequence of phantom limb pain, manifesting a higher AD of white matter in both hemispheres symmetrically after adjusting for individual depressive moods. In addition, there were associations between the RD of white matter and VAS scores primarily in the hemispheres related to the missing hand and in the corpus callosum. CONCLUSIONS: The phantom limb pain after unilateral arm amputation induced plasticity in the white matter. We conclude that loss of white matter integrity, particularly in the hemisphere connected with the missing hand, is significantly correlated with phantom limb pain.

Comparison of Fornix and Stria Terminalis Connectivity among First-Episode Schizophrenia, Chronic Schizophrenia and Healthy Controls

OBJECTIVES: Disrupted integrities of the fornix and stria terminalis have been suggested in schizophrenia. However, very few studies have focused on the fornix and stria terminalis comparing first-episode schizophrenia (FESZ), chronic schizophrenia (CS), and healthy controls (HCs) with the application of diffusion-tensor imaging (DTI) technique. The objective of this study is to compare the connectivity of the fornix and stria terminalis among FESZ, CS, and HCs. METHODS: We included the 44 FESZ patients, 39 CS patients and 20 HCs in this study. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics to analyze the connectivity of fornix and stria terminalis. In addition, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate clinical symptom severities. RESULTS: There were no significant differences between the FESZ, CS, and HCs in age, sex, education years. The SAPS and SANS scores of the schizophrenia groups showed no significant differences. FA values of the right fornix cres/stria terminalis in the CS group were significantly lower than those in FESZ and HCs. There were no significant differences of FA values of the right fornix cres/stria terminalis between the FESZ and the HCs. Pearson correlation analyses revealed that significant correlation between FA values of the right fornix cres/stria terminalies of the the FESZ group and positive, negative symptom scales, and FA values of the right fornix cres/stria terminalis of the CS group and negative symptom scales. CONCLUSIONS: This study shows that FA values of the fornix and stria terminalis in the CS were lower than in the FESZ and the HCs. These results suggest that the fornix and stria terminalis can play a role in pathophysiology of schizophrenia. Thus current study can broaden our understanding of the pathophysiology of schizophrenia.

Gray Matter Microstructural Abnormalities and Working Memory Deficits in Individuals with Schizophrenia

OBJECTIVE: Working memory impairments serve as prognostic factors for patients with schizophrenia. Working memory deficits are mainly associated with gray matter (GM) thickness and volume. We investigated the association between GM diffusivity and working memory in controls and individuals with schizophrenia. METHODS: T1 and diffusion tensor images of the brain, working memory task (letter number sequencing) scores, and the demographic data of 90 individuals with schizophrenia and 97 controls were collected from the SchizConnect database. T1 images were parcellated into the 68 GM Regions of Interest (ROI). Axial Diffusivity (AD), Fractional Anisotropy (FA), Radial Diffusivity (RD), and Trace (TR) were calculated for each of the ROIs. RESULTS: Compared to the controls, schizophrenia group showed significantly increased AD, RD, and TR in specific regions on the frontal, temporal, and anterior cingulate area. Moreover, working memory was negatively correlated with AD, RD, and TR in the lateral orbitofrontal, superior temporal, inferior temporal, and rostral anterior cingulate area on left hemisphere in the individuals with schizophrenia. CONCLUSION: These results demonstrated GM microstructural abnormalities in the frontal, temporal, and anterior cingulate regions of individuals with schizophrenia. Furthermore, these regional GM microstructural abnormalities suggest a neuropathological basis for the working memory deficits observed clinically in individuals with schizophrenia.

White Matter Tract-Cognitive Relationships in Children with High-Functioning Autism Spectrum Disorder

OBJECTIVE: The purpose of the present study was to clarify the relationship between white matter tracts and cognitive symptoms in children with high-functioning autism spectrum disorder (ASD). METHODS: We examined the cognitive functions of 17 children with high-functioning ASD and 18 typically developing (TD) controls and performed diffusion tensor imaging (DTI) tractography. We compared the results between the groups and investigated the correlations between the cognitive scores and DTI parameters within each group. RESULTS: The Comprehension scores in the ASD group exhibited a positive correlation with mean diffusivity (MD) in the forceps minor (F minor). In the TD group, the Comprehension scores were positively correlated with fractional anisotropy (FA) in the right inferior fronto-occipital fasciculus (IFO) and left anterior thalamic radiation (ATR), and negatively correlated with MD in the left ATR, radial diffusivity (RD) in the right IFO, and RD in the left ATR. Additionally, a positive correlation was observed between the Matching Numbers scores and MD in the left uncinate fasciculus and F minor, and RD in the F minor. Furthermore, the Sentence Questions scores exhibited a positive correlation with RD in the right inferior longitudinal fasciculus. Relative to TD controls, the specific tract showing a strong correlation with the cognitive scores was reduced in the ASD group. CONCLUSION: Our findings indicate that white matter tracts connecting specific brain areas may exhibit a weaker relationship with cognitive functions in children with ASD, resulting in less efficient cognitive pathways than those observed in TD children.

Language-Related White-Matter-Tract Deficits in Children with Benign Epilepsy with Centrotemporal Spikes: A Retrospective Study

BACKGROUND AND PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS) is one of the most common pediatric epilepsies, and it generally has a good prognosis. However, recent research has indicated that the epileptic activity of BECTS can cause cognitive defects such as language, visuospatial, and auditory verbal memory deficits. This study assessed language-delivery deficits in BECTS patients using diffusion-tensor magnetic resonance imaging (DTI). METHODS: T1-weighted MRI, DTI, and language tests were conducted in 16 BECTS patients and 16 age-matched controls. DTI data were analyzed using the TRActs Constrained by Underlying Anatomy tool in FreeSurfer 5.3, and 18 major white-matter tracts were extracted, which included 4 language-related tracts: the inferior longitudinal fasciculus, superior longitudinal fasciculus-parietal terminations, superior longitudinal fasciculus-temporal terminations, and uncinate fasciculus (UNC). Language tests included the Korean version of the Receptive and Expressive Vocabulary Test, Test of Problem-Solving Abilities (TOPS), and the mean length of utterance in words. RESULTS: The BECTS group exhibited decreased mean fractional anisotropy and increased mean radial diffusivity, with significant differences in both the superior longitudinal fasciculus and the left UNC (p<0.05), which are the language-related white-matter tracts in the dual-loop model. The TOPS language test scores were significantly lower in the BECTS group than in the control group (p<0.05). CONCLUSIONS: It appears that BECTS patients can exhibit language deficits. Seizure activities of BECTS could alter DTI scalar values in the language-related white-matter tracts.

Alteration of White Matter Integrity in Dyslexic Children: Case-Control Study / 신경정신의학

OBJECTIVES: To compare the white matter microstructure of dyslexic children with normal children using diffusion tensor imaging. METHODS: Twenty one dyslexic children and 24 normal control children were recruited in the second and third grade of elementary school students. The fractional anisotropy (FA) values of 20 representative white matter tracts were estimated from the diffusion tensor imaging data of each subject using the Johns Hopkins University-white matter tractography atlas to determine the difference in white matter integrity between the dyslexic children and normal children. RESULTS: Compared to the normal control group, the FA values of the left inferior longitudinal fasciculus [F(1,39)=5.908, p<0.05] and temporal part of the right superior longitudinal fasciculus [F(1,39)=7.328, p=0.010] were significantly higher in the dyslexic group and there was no significant difference in the other tracts. CONCLUSION: In dyslexic children, compensatory pathways develop in the left inferior longitudinal fasciculus and in the temporal part of the right superior longitudinal fasciculus.

Quantitative Predictive Imaging Biomarkers of Lumbar Intervertebral Disc Degeneration

STUDY DESIGN: Observational comparative study. PURPOSE: To compare fractional anisotropy (FA) maps with T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) of intervertebral discs in healthy volunteers and patients to develop a predictive disc health scale. OVERVIEW OF LITERATURE: T2-weighted magnetic resonance imaging (MRI) is not sensitive to early morphological changes and provides no quantitative biomarker profile for early degeneration. METHODS: We examined 59 healthy controls and 59 patients with back pain by MRI using T2 relaxometry and diffusion tensor imaging (DTI). Each group was divided into three age subgroups: A (50 years, n=21). We obtained FA values for AF and NP and T2 values for NP for each intervertebral disc. Furthermore, we calculated the FA (AF/NP) ratios. RESULTS: We categorized 590 intervertebral discs from 118 participants, 566 of which were analyzed with T2 relaxometry and DTI. The T2 values were as follows: subgroup A, 55.8±4.4 ms; B, 48.5±6.9 ms; C, 45.8±8.7 ms (p120 ms, 90–100 ms, and 70 ms, respectively (p<0.001). Control subgroup A had higher T2 values and AF/NP ratios than subgroups B and C; the AF values were not significantly different. Control subgroup B had higher T2 values and AF/NP ratios than subgroup C but lower FA (NP). CONCLUSIONS: FA maps of the AF/NP ratio and T2 values of NP are potential microstructure biomarkers of normal and degenerating discs and can help detect early degeneration using a predictive disc health score on a continuous scale.

A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203

Clinical features and corneal optical anisotropies in a rabbit model of limbal stem cell deficiency / Fenótipos clínicos e anisotropias ópticas da córnea em coelhos com deficiência de células tronco limbais

ABSTRACT Purposes: To investigate the intra-laboratory reproducibility of clinical features and to evaluate corneal optical anisotropies in a rabbit model of limbal stem cell deficiency. Methods: Limbal injury was induced in the right eye of 23 adult New Zealand White rabbits using a highly aggressive protocol that combined 360 degrees limbal peritomy, keratolimbectomy, alkaline chemical burn, and mechanical removal of the epithelium. Clinical evaluation of the injured eyes was performed for 28 days and included corneal impression cytology. Corneas with a severe clinical outcome set typical of limbal stem cell deficiency were then collected, subjected to a histopathological examination, and examined for optical anisotropies. Corneas from healthy rabbit eyes were used as controls. Differences in optical path due to stromal collagen birefringence, as well as linear dichroism related to the expression and spatial orientation of glycosaminoglycan chains from proteoglycans, were measured from cross-sections under a quantitative polarized light microscope. Results: One eye showed signs of hypopyon and was excluded. Signs of ocular inflammation were observed in all eyes studied (n=22). Corneal impression cytology did not detect goblet cells. Twelve of the 22 corneas presented a clinical outcome set typical of limbal stem cell deficiency, which is characterized by the presence of epithelial defects, inflammatory cells, moderate-to-severe opacity, and neovascularization. Microscopic studies under polarized light revealed that relative to controls, limbal stem cell deficiency caused a 24.4% increase in corneal optical path differences. Further, corneas with limbal stem cell deficiency were less dichroic than controls. Conclusions: These results suggest that rabbit models of limbal stem cell deficiency must be rigorously screened for use in preclinical studies to ensure experimental homogeneity because protocols used to create limbal stem cell deficiency could be not associated with good intra-laboratory reproducibility of clinical features. Limbal stem cell deficiency, as induced herein, altered the optical anisotropic properties of the corneal stroma. Such alterations are indicative of changes in collagen packing and the spatial orientation of glycosaminoglycan chains from proteoglycans. Knowledge of these changes is important to potentiate strategies aimed at restoring the morphofunctional integrity of the corneal stroma affected by limbal stem cell deficiency.

RESUMO Objetivos: Investigar a reprodutibilidade intra-la­boratorial dos fenótipos clínicos e avaliar anisotropias ópticas em córneas de coelhos com deficiência de células tronco limbais. Métodos: Lesões ao limbo foram feitas no olho direito de 23 coelhos adultos da Nova Zelândia Branco, usando um protocolo altamente agressivo, que envolveu peritomia limbal em 360 graus, ceratolimbectomia, cauterização por álcali, e remoção mecânica de epitélio remanescente. Os olhos foram clinicamente avaliados por 28 dias, inclusive por citologia de impressão corneal. As córneas que manifestaram um conjunto de alterações típicas de deficiência de células tronco limbais foram coletadas e submetidas à estudos em histopatologia e em anisotropias ópticas. Córneas saudáveis foram usadas como controles. Diferenças de caminho óptico de birrefringência relacionada à organização do colágeno estromal, e dicroísmo linear relacionado à expressão e à orientação das cadeias de glicosaminoglicanos dos proteoglicanos estromais, foram quantificados por microscopia de luz polarizada. Resultados: Um olho apresentou hipópio e foi excluído do estudo. Todos os olhos estudados (n=22) apresentaram sinais de inflamação ocular. A citologia de impressão não detectou células caliciformes na superfície corneal. Doze de 22 córneas manifestaram alterações clínicas típicas de deficiência de células tronco limbais, caracterizado por defeitos epiteliais, infiltrados inflamatórios, opacidade de moderada à severa, e neovascularização. Estudos por microscopia de luz polarizada mostraram que a deficiência de células tronco limbais aumentou a diferenças de caminho óptico corneal em 24,4% (versus controles). As cór­neas com deficiência de células tronco limbais foram menos dicroicas do que as córneas controle. Conclusões: Coelhos com deficiência de células tronco limbais, para aplicações em estudos pré-clínicos, devem ser rigorosamente selecionados para assegurar homogeneidade experimental, pois há evidências de que protocolos utilizados para indução de deficiência de células tronco limbais não estão associados com boa reprodutibilidade intra-laboratorial de fenótipos clínicos. A deficiência de células tronco limbais, como induzida aqui, alterou as propriedades ópticas anisotrópicas do estroma corneal. Tais alterações são indicativas de mudanças no empacotamento de colágeno e na orientação das cadeias de glicosaminoglicanos dos proteoglicanos. Conhecimentos nessas alterações são importantes para potencializar estratégias que visam a restabelecer a integridade morfofuncional do estromal corneal acometido pela deficiência de células tronco limbais.

Current contribution of diffusion tensor imaging in the evaluation of diffuse axonal injury / Contribuição atual da imagem por tensor de difusão na avaliação da lesão axonal difusa

ABSTRACT Traumatic brain injury (TBI) is the number one cause of death and morbidity among young adults. Moreover, survivors are frequently left with functional disabilities during the most productive years of their lives. One main aspect of TBI pathology is diffuse axonal injury, which is increasingly recognized due to its presence in 40% to 50% of all cases that require hospital admission. Diffuse axonal injury is defined as widespread axonal damage and is characterized by complete axotomy and secondary reactions due to overall axonopathy. These changes can be seen in neuroimaging studies as hemorrhagic focal areas and diffuse edema. However, the diffuse axonal injury findings are frequently under-recognized in conventional neuroimaging studies. In such scenarios, diffuse tensor imaging (DTI) plays an important role because it provides further information on white matter integrity that is not obtained with standard magnetic resonance imaging sequences. Extensive reviews concerning the physics of DTI and its use in the context of TBI patients have been published, but these issues are still hazy for many allied-health professionals. Herein, we aim to review the current contribution of diverse state-of-the-art DTI analytical methods to the understanding of diffuse axonal injury pathophysiology and prognosis, to serve as a quick reference for those interested in planning new studies and who are involved in the care of TBI victims. For this purpose, a comprehensive search in Pubmed was performed using the following keywords: "traumatic brain injury", "diffuse axonal injury", and "diffusion tensor imaging".

RESUMO O traumatismo cranioencefálico (TCE) é a principal causa de morbimortalidade entre adultos jovens. Aqueles que sobrevivem são frequentemente deixados com sequelas funcionais nos anos mais produtivos de suas vidas. O principal aspecto fisiopatológico do TCE é a lesão axonial difusa (LAD), cada vez mais destacada pois está presente em 40 a 50% dos casos que necessitam de internação hospitalar. LAD é definida como a injúria axonial extensa caracterizada pela axoniotomia completa assim como pelas reações secundárias a axoniopatia, que são demonstradas por métodos de neuroimagem como áreas de edema e micro-hemorragia. Entretanto, os achados da LAD são frequentemente subestimados em estudos de neuroimagem convencional. É neste contexto que imagens por tensor de difusão (DTI) ganharam ênfase, já que permitem obter informações sobre a integridade da substância branca que não eram obtidas por sequências convencionais de ressonância magnética (RM). Existem artigos extensos sobre os fundamentos físicos e as aplicações de DTI em pacientes vítimas de TCE, no entanto, estes assuntos permanecem ainda nebulosos a alguns profissionais da área de saúde. Deste modo, propomos uma revisão didática sobre a contribuição do estado da arte de diferentes métodos analíticos de DTI no entendimento do processo da fisiopatologia e prognóstico da LAD, servindo assim como uma ferramenta acessível para aqueles interessados em planejamento de novos estudos e aqueles envolvidos no tratamento de vítimas de TCE. Uma pesquisa abrangente foi realizada no Pubmed com as seguintes palavras-chave: "traumatismo cranioencefálico", "lesão axonial difusa", "imagem por tensor de difusão".