The impact of sunlight exposure on brain structural markers in the UK Biobank.

Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose-response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (ß: - 0.051, P < 0.001), white matter (ß: - 0.031, P = 0.023), gray matter (ß: - 0.067, P < 0.001), and white matter hyperintensities (ß: 0.059, P < 0.001). These associations were more pronounced in males and individuals under the age of 60. The results of the restricted cubic spline analysis showed a nonlinear relationship between sunlight exposure and brain structural markers, with the direction changing around 2 h of sunlight exposure. This study demonstrates that prolonged exposure to natural sunlight is associated with brain structural markers change.

A longitudinal, randomized experimental pilot study to investigate the effects of airborne ultrasound on human mental health, cognition, and brain structure.

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants' bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

Retrospective study of late radiation-induced damages after focal radiotherapy for childhood brain tumors.

PURPOSE: To study a robust and reproducible procedure to investigate a relation between focal brain radiotherapy (RT) low doses, neurocognitive impairment and late White Matter and Gray Matter alterations, as shown by Diffusion Tensor Imaging (DTI), in children. METHODS AND MATERIALS: Forty-five patients (23 males and 22 females, median age at RT 6.2 years, median age at evaluations 11.1 years) who had received focal RT for brain tumors were recruited for DTI exams and neurocognitive tests. Patients' brains were parceled in 116 regions of interest (ROIs) using an available segmented atlas. After the development of an ad hoc, home-made, multimodal and highly deformable registration framework, we collected mean RT doses and DTI metrics values for each ROI. The pattern of association between cognitive scores or domains and dose or DTI values was assessed in each ROI through both considering and excluding ROIs with mean doses higher than 75% of the prescription. Subsequently, a preliminary threshold value of dose discriminating patients with and without neurocognitive impairment was selected for the most relevant associations. RESULTS: The workflow allowed us to identify 10 ROIs where RT dose and DTI metrics were significantly associated with cognitive tests results (p<0.05). In 5/10 ROIs, RT dose and cognitive tests were associated with p<0.01 and preliminary RT threshold dose values, implying a possible cognitive or neuropsychological damage, were calculated. The analysis of domains showed that the most involved one was the "school-related activities". CONCLUSION: This analysis, despite being conducted on a retrospective cohort of children, shows that the identification of critical brain structures and respective radiation dose thresholds is achievable by combining, with appropriate methodological tools, the large amount of data arising from different sources. This supported the design of a prospective study to gain stronger evidence.

A flexible workflow for simulating transcranial electric stimulation in healthy and lesioned brains.

Simulating transcranial electric stimulation is actively researched as knowledge about the distribution of the electrical field is decisive for understanding the variability in the elicited stimulation effect. Several software pipelines comprehensively solve this task in an automated manner for standard use-cases. However, simulations for non-standard applications such as uncommon electrode shapes or the creation of head models from non-optimized T1-weighted imaging data and the inclusion of irregular structures are more difficult to accomplish. We address these limitations and suggest a comprehensive workflow to simulate transcranial electric stimulation based on open-source tools. The workflow covers the head model creation from MRI data, the electrode modeling, the modeling of anisotropic conductivity behavior of the white matter, the numerical simulation and visualization. Skin, skull, air cavities, cerebrospinal fluid, white matter, and gray matter are segmented semi-automatically from T1-weighted MR images. Electrodes of arbitrary number and shape can be modeled. The meshing of the head model is implemented in a way to preserve the feature edges of the electrodes and is free of topological restrictions of the considered structures of the head model. White matter anisotropy can be computed from diffusion-tensor imaging data. Our solver application was verified analytically and by contrasting the tDCS simulation results with that of other simulation pipelines (SimNIBS 3.0, ROAST 3.0). An agreement in both cases underlines the validity of our workflow. Our suggested solutions facilitate investigations of irregular structures in patients (e.g. lesions, implants) or new electrode types. For a coupled use of the described workflow, we provide documentation and disclose the full source code of the developed tools.

Decreased dopamine in striatum and difficult locomotor recovery from MPTP insult after exposure to radiofrequency electromagnetic fields.

Concern is growing about possible neuronal effects of human exposure to radiofrequency electromagnetic fields because of the increasing usage of cell phones and the close proximity of these devices to the brain when in use. We found that exposure to a radiofrequency electromagnetic field (RF-EMF) of 835 MHz (4.0 W/kg specific absorption rate [SAR] for 5 h/day for 12 weeks) affects striatal neurons in C57BL/6 mice. The number of synaptic vesicles (SVs) in striatal presynaptic boutons was significantly decreased after RF-EMF exposure. The expression levels of synapsin I and II were also significantly decreased in the striatum of the RF-EMF-exposed group. RF-EMF exposure led to a reduction in dopamine concentration in the striatum and also to a decrease in the expression of tyrosine hydroxylase in striatal neurons. Furthermore, in behavioral tests, exposure to RF-EMF impeded the recovery of locomotor activities after repeated treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These results suggest that the observed decrease in dopamine concentration in the striatum was caused by both a reduction in the number of dopaminergic neurons and a decline in the number of SVs. The decreased dopamine neuron numbers and concentration seen after RF-EMF exposure would have caused the difficult recovery after MPTP treatment. In summary, our results strongly suggest that exposing the brain to RF-EMF can decrease the number of SVs and dopaminergic neurons in the striatum. These primary changes impair the recovery of locomotor activities following MPTP damage to the striatum.

Impact of transcranial direct current stimulation on structural plasticity of the somatosensory system.

While there is a growing body of evidence regarding the behavioral and neurofunctional changes in response to the longitudinal delivery of transcranial direct current stimulation (tDCS), there is limited evidence regarding its structural effects. Therefore, the present study was intended to investigate the effect of repeatedly applied anodal tDCS over the primary somatosensory cortex on the gray matter (GM) and white matter (WM) compartment of the brain. Structural tDCS effects were, moreover, related to effects evidenced by functional imaging and behavioral assessment. tDCS was applied over the course of 5 days in 25 subjects with concomitant assessment of tactile acuity of the right and left index finger as well as imaging at baseline, after the last delivery of tDCS and at follow-up 4 weeks thereafter. Irrespective of the stimulation condition (anodal vs. sham), voxel-based morphometry revealed a behaviorally relevant decrease of GM in the precuneus co-localized with a functional change of its activity. Moreover, there was a decrease in GM of the bilateral lingual gyrus and the right cerebellum. Diffusion tensor imaging analysis showed an increase of fractional anisotropy exclusively in the tDCSanodal condition in the left frontal cortex affecting the final stretch of a somatosensory decision making network comprising the middle and superior frontal gyrus as well as regions adjacent to the genu of the corpus callosum. Thus, this is the first study in humans to identify structural plasticity in the GM compartment and tDCS-specific changes in the WM compartment in response to somatosensory learning.

Longitudinal changes in gray matter regions after cranial radiation and comparative analysis with whole body radiation: a DTI study.

PURPOSE: Radiation-induced white matter changes are well known and vastly studied. However, radiation-induced gray matter alterations are still a research question. In the present study, these changes were assessed in a longitudinal manner using Diffusion Tensor Imaging (DTI) and further compared for cranial and whole body radiation exposure. MATERIALS AND METHODS: Male mice (C57BL/6) were irradiated with cranial or whole body radiation followed by DTI study at 7T animal MRI system during predose, subacute and early delayed phases of radiation sickness. Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained from brain's gray matter regions. RESULTS: Decreased FA with increased MD was observed prominently in animals exposed to cranial radiation showing most changes at 8 months post irradiation. However, whole body radiation induced FA changes were mostly observed at 1 month post irradiation as compared to controls. CONCLUSIONS: The differential response after whole body and cranial irradiation observed in the study depicts that radiation exposure of 5 Gy could induce permanent alterations in gray matter regions prominently as observed in Caudoputamen region at all the time points. Thus, our study has bolstered the role of DTI to probe microstructural changes in gray matter regions of brain after radiation exposure.

Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals.

Transcranial magnetic stimulation (TMS) can stimulate cortical and subcortical brain regions. However, in order to reach subcortical targets, intact monosynaptic connections are required. The goal of this investigation was to evaluate the contribution of white matter integrity and gray matter volume to frontal pole TMS-evoked striatal activity in a large cohort of chronic cocaine users. 49 cocaine users received single pulses of TMS to the frontal pole while BOLD data were acquired - a technique known as interleaved TMS/fMRI. Diffusion tensor imaging and voxel-based morphometry were used to quantify white matter integrity and gray matter volume (GMV), respectively. Stepwise regression was used to evaluate the contribution of clinical and demographic variables to TMS-evoked BOLD. Consistent with previous studies, frontal pole TMS evoked activity in striatum and salience circuitry. The size of the TMS-evoked response was related to fractional anisotropy between the frontal pole and putamen and GMV in the left frontal pole and left ACC. This is the first study to demonstrate that the effect of TMS on subcortical activity is dependent upon the structural integrity of the brain. These data suggest that these structural neuroimaging data types are biomarkers for TMS-induced mobilization of the striatum.

Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion.

BACKGROUND AND PURPOSE: To compare the structural and hemodynamic changes of healthy brain tissue in the cerebral hemisphere contralateral to the tumor following photon and proton radiochemotherapy. MATERIALS AND METHODS: Sixty-seven patients (54.9 ±14.0 years) diagnosed with glioblastoma undergoing adjuvant photon (n = 47) or proton (n = 19) radiochemotherapy with temozolomide after tumor resection underwent T1-weighted and arterial spin labeling MRI. Changes in volume and perfusion before and 3 to 6 months after were compared between therapies. RESULTS: A decrease in gray matter (GM) (-2.2%, P<0.001) and white matter (WM) (-1.2%, P<0.001) volume was observed in photon-therapy patients compared to the pre-radiotherapy baseline. In contrast, for the proton-therapy group, no significant differences in GM (0.3%, P = 0.64) or WM (-0.4%, P = 0.58) volume were observed. GM volume decreased with 0.9% per 10 Gy dose increase (P<0.001) and differed between the radiation modalities (P<0.001). Perfusion decreased in photon-therapy patients (-10.1%, P = 0.002), whereas the decrease in proton-therapy patients, while comparable in magnitude, did not reach statistical significance (-9.1%, P = 0.12). There was no correlation between perfusion decrease and either dose (P = 0.64) or radiation modality (P = 0.94). CONCLUSIONS: Our results show that the tissue volume decrease depends on radiation dose delivered to the healthy hemisphere and differs between treatment modalities. In contrast, the decrease in perfusion was comparable for both irradiation modalities. We conclude that proton therapy may reduce brain-volume loss when compared to photon therapy.

Adverse effects in lumbar spinal cord morphology and tissue biochemistry in Sprague Dawley male rats following exposure to a continuous 1-h a day 900-MHz electromagnetic field throughout adolescence.

Cell phones, an indispensable element of daily life, are today used at almost addictive levels by adolescents. Adolescents are therefore becoming increasingly exposed to the effect of the electromagnetic field (EMF) emitted by cell phones. The purpose of this study was to investigate the effect of exposure to a 900-MHz EMF throughout adolescence on the lumbar spinal cord using histopathological, immunohistochemical and biochemical techniques. Twenty-four Sprague Dawley (28.3-43.9g) aged 21days were included in the study. These were divided equally into three groups - control (CG), sham (SG) and electromagnetic (ELMAG). No procedure was performed on the CG rats until the end of the study. SG and ELMAG rats were kept inside an EMF cage (EMFC) for 1h a day every day at the same time between postnatal days 22 and 60. During this time, ELMAG rats were exposed to the effect of a 900-MHz EMF, while the SG rats were kept in the EMFC without being exposed to EMF. At the end of the study, the lumbar regions of the spinal cords of all rats in all groups were extracted. Half of each extracted tissue was stored at -80°C for biochemical analysis, while the other half was used for histopathological and immunohistochemical analyses. In terms of histopathology, a lumbar spinal cord with normal morphology was observed in the other groups, while morphological irregularity in gray matter, increased vacuolization and infiltration of white matter into gray matter were pronounced in the ELMAG rats. The cytoplasm of some neurons in the gray matter was shrunken and stained dark, and vacuoles were observed in the cytoplasms. The apoptotic index of glia cells and neurons were significantly higher in ELMAG compared to the other groups. Biochemical analysis revealed a significantly increased MDA value in ELMAG compared to CG, while SOD and GSH levels decreased significantly. In conclusion, our study results suggest that continuous exposure to a 900-MHz EMF for 1h a day through all stages of adolescence can result in impairments at both morphological and biochemical levels in the lumbar region spinal cords of Sprague Dawley rats.

Diffusion kurtosis imaging study on temporal lobe after nasopharyngeal carcinoma radiotherapy.

PURPOSE: Diffusion kurtosis imaging (DKI) is a MRI technique which can measure alterations in the diffusion of water molecules to reflect tissue changes in both white and grey matter. This study evaluated the potential of DKI for the early diagnosis of radiation-induced temporal lobe changes in the grey and white matter of the temporal lobe in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Sixty patients with NPC who had normal MRI brain scans were enrolled and underwent DKI at 1 week (n=20), 6 months (n=20) or 1 year (n=20) after radiotherapy; 20 normal control individuals were also evaluated. Nonlinear fitting routines and equations were used to calculate mean diffusion (MD) and mean kurtosis (MK) and fractional anisotropy (FA). Analysis of variance was used to compare the MK/MD/FA values of white and grey matter between groups. RESULTS: Compared to the normal control group, grey and white matter MK values were significantly higher at 1 week after radiotherapy and significantly lower at 6 months and 1 year after radiotherapy in patients with NPC, whereas the grey and white matter MD values were significantly lower at 1 week after radiotherapy and returned to normal by 6 months and 1 year after radiotherapy. CONCLUSION: DKI can be used to detect radiotherapy-induced changes in both the white and grey matter of temporal lobe in patients with NPC. MK and MD values may represent reliable indicators for the early diagnosis of radiation-induced temporal lobe changes in NPC.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation.

OBJECTIVE: While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. APPROACH: A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. MAIN RESULTS: The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10(-3) °C) for a 0.5 s exposure. SIGNIFICANCE: Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

Brain damage following prophylactic cranial irradiation in lung cancer survivors.

Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice.

PURPOSE: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. METHODS AND MATERIALS: Patients were imaged with T1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7-) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. RESULTS: WM volume was significantly decreased following treatment in 7- and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7- group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. CONCLUSIONS: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

Analysis of frequency of deep white matter metastasis on cerebral MRI.

Supratentorial white matter is an important part of the brain and a major site of detrimental effects after whole brain radiotherapy (WBRT). It is not known if prevalence of metastases in white matter justifies standard inclusion of white matter in whole brain treatment. In this retrospective analysis we examined the frequency of metastasis in supratentorial deep cerebral white matter with cerebral magnetic resonance imaging (MRI). Deep white matter (DWM) was defined as white matter in corpus callosum with forceps anterior and posterior and centrum semiovale. Lesions extending from grey matter, gyrus or ventricles into white matter were not classified as DWM metastases. Brain MRI of 198 patients from two centres were analyzed. In total 1330 metastases were counted and only 4.6% were located in DWM. Metastases in DWM were small (median diameter 6 mm). Only 1/41 patients (2%) with a singular metastasis had a DWM metastasis, 2/35 patients (6%) with 2 metastases had a DWM metastasis, 14/79 patients (18%) with 3-9 metastases and 12/43 patients (28%) with >9 metastases had a single or more DWM metastases (p = 0.003). There appeared to be tumor related differences with renal cell carcinoma showing significantly more DWM metastasis (6/17, 35%), than NSCLC (11/85, 13%, p = 0.024), breast cancer (1/20, 5%, p = 0.019) or colorectal cancer (0/10, 0%, p = 0.033). Overall, relevant preservation of DWM from metastases, especially in oligometastatic disease, was shown. This implies that DWM in patients with only few brain metastases is unnecessarily damaged by conventional WBRT.

Neurotoxicity in breast cancer survivors ≥10 years post-treatment is dependent on treatment type.

Adjuvant chemotherapy (CT) for breast cancer (BC) is associated with very late side-effects on brain function and structure. However, little is known about neurotoxicity of specific treatment regimens. To compare neurotoxicity profiles after different treatment strategies, we used neurocognitive testing and multimodality MRI in BC survivors randomized to high-dose (HI), conventional-dose (CON-) CT or radiotherapy (RT) only and a healthy control (HC) group. BC survivors who received CON-CT (n = 20) and HC (n = 20) were assessed using a neurocognitive test battery and multimodality MRI including 3D-T1, Diffusion Tensor Imaging (DTI) and 1H-MR spectroscopy (1H-MRS) to measure various aspects of cerebral white (WM) and gray matter (GM). Data were compared to previously assessed groups of BC survivors who received HI-CT (n = 17) and RT-only (n = 15). Testing took place on average 11.5 years post-CT. 3D-T1 showed focal GM volume reductions both for HI-CT and CON-CT compared to RT-only (p < .004). DTI-derived mean diffusivity and 1H-MRS derived N-acetyl aspartate showed WM injury specific to HI-CT but not CON-CT (p < .05). Residual effects were revealed in the RT-only group compared to HC on MRI and neurocognitive measurements (p < .05). Ten years after adjuvant CT for BC lower cerebral GM volume was found in HI as well as CON-CT BC survivors whereas injury to WM is restricted to HI-CT. This might indicate that WM brain changes after BC treatment may show more pronounced (partial) recovery than GM. Furthermore, our results suggest residual neurotoxicity in the RT-only group, which warrants further investigation.

Radiation-induced endothelial cell loss and reduction of the relative magnitude of the blood flow in the rat spinal cord.

The main purpose of the present study was to examine the time-dependent alterations in the endothelial cell density that occur in the first 180 days after irradiation of the spinal cord and the functional role of these alterations in the spinal cord blood flow. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a (60)Co irradiator to deliver 30 Gy. A significant loss of forelimb motor function was observed 180 days post-irradiation. The number of neurons in the anterior horn of the spinal cord began to decrease significantly 3 days post-irradiation compared with normal controls, reaching the lowest number at 90 days post-irradiation. A significant reduction in the endothelial cell density was observed from 14 days post-irradiation in the white matter and from 3 days post-irradiation in the gray matter. The lowest endothelial cell density was reached at 30 days post-irradiation in the white matter and at 60 days post-irradiation in the gray matter. A significant reduction in the microvessel density was observed from 3 days post-irradiation in both the white matter and the gray matter. The lowest microvessel density was reached at 90 days post-irradiation in both the white matter and the gray matter. A significant reduction in the relative magnitude of spinal cord blood flow was observed from 21 days post-irradiation. The lowest relative magnitude of spinal cord blood flow was reached at 90 days post-irradiation. We did not find any evidence of demyelination. The results revealed that a single 30-Gy irradiation dose resulted in impaired forelimb motor function, a decreased number of neurons, and reduced endothelial cell density, microvessel density and relative magnitude of spinal cord blood flow. However, a 30-Gy single-dose irradiation was not sufficient to induce demyelination in the rat spinal cord.

Radiation-induced changes in normal-appearing gray matter in patients with nasopharyngeal carcinoma: a magnetic resonance imaging voxel-based morphometry study.

INTRODUCTION: Evidence is accumulating that temporal lobe radiation necrosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT) could involve gray matter (GM). The purpose of the study was to assess the radiation-induced GM volume differences between NPC patients who had and had not received RT and the effect of time after RT on GM volume differences in those patients who had received RT. METHODS: We used magnetic resonance imaging voxel-based morphometry (VBM) to assess differences in GM volume between 30 NPC patients with normal-appearing whole-brain GM after RT and 15 control patients with newly diagnosed but not yet medically treated NPC. Correlation analyses were used to investigate the relationship between GM volume changes and time after RT. RESULTS: Patients who had received RT had GM volume decreases in the bilateral superior temporal gyrus, left middle temporal gyrus, right fusiform gyrus, right precentral gyrus, and right inferior parietal lobule (p < 0.001, uncorrected, cluster size >100 voxels). Moreover, the correlation analysis indicated that regional GM volume loss in the left superior temporal gyrus, left middle temporal gyrus, and right fusiform gyrus were negatively related to the mean dose to the ipsilateral temporal lobe, respectively. CONCLUSION: These results indicate that GM volume deficits in bilateral temporal lobes in patients who had received RT might be radiation-induced. Our findings might provide new insight into the pathogenesis of radiation-induced structural damage in normal-appearing brain tissue. Yet this is an exploratory study, whose findings should therefore be taken with caution.

Assessment of electric field distribution in anisotropic cortical and subcortical regions under the influence of tDCS.

The focus of this study is to estimate the contribution of regional anisotropic conductivity on the spatial distribution of an induced electric field across gray matter (GM), white matter (WM), and subcortical regions under transcranial direct current stimulation (tDCS). The assessment was conducted using a passive high-resolution finite element head model with inhomogeneous and variable anisotropic conductivities derived from the diffusion tensor data. Electric field distribution was evaluated across different cortical as well as subcortical regions under four bicephalic electrode configurations. Results indicate that regional tissue heterogeneity and anisotropy cause the pattern of induced fields to vary in orientation and strength when compared to the isotropic scenario. Different electrode montages resulted in distinct distribution patterns with noticeable variations in field strengths. The effect of anisotropy is highly montage dependent and directional conductivity has a more profound effect in defining the strength of the induced field. The inclusion of anisotropy in the GM and subcortical regions has a significant effect on the strength and spatial distribution of the induced electric field. Under the (C3-Fp2) montage, the inclusion of GM and subcortical anisotropy increased the average percentage difference in the electric field strength of brain from 5% to 34% (WM anisotropy only). In terms of patterns distribution, the topographic errors increased from 9.9% to 40% (WM anisotropy only) across the brain.