White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma.

We aimed to evaluate whether white and gray matter microstructure changes observed with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI) can be used to reflect the progression of chronic brain trauma. The MRI-DTI parameters, neuropathologic changes, and behavioral performance of adult male Wistar rats that underwent moderate (2.1 atm on day "0") or repeated mild (1.5 atm on days "0" and "2") traumatic brain injury (TBI or rmTBI) or sham operation were evaluated at 7 days, 14 days, and 1-9 months after surgery. Neurobehavioral tests showed that TBI causes long-term motor, cognitive and neurological deficits, whereas rmTBI results in more significant deficits in these paradigms. Both histology and MRI show that rmTBI causes more significant changes in brain lesion volumes than TBI. In vivo DTI further reveals that TBI and rmTBI cause persistent microstructural changes in white matter tracts (such as the body of the corpus callosum, splenium of corpus callus, internal capsule and/or angular bundle) of both two hemispheres. Luxol fast blue measurements reveal similar myelin loss (as well as reduction in white matter thickness) in ipsilateral and contralateral hemispheres as observed by DTI analysis in injured rats. These data indicate that the disintegration of microstructural changes in white and gray matter parameters analyzed by MRI-DTI can serve as noninvasive and reliable markers of structural and functional level alterations in chronic TBI.

Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.

Mood disorders are an important public health issue and recent advances in genomic studies have indicated that molecules involved in neurodevelopment are causally related to mood disorders. BLM-s (BCL-2-like molecule, small transcript isoform), a BH3-only proapoptotic BCL-2 family member, mediates apoptosis of postmitotic immature neurons during embryonic cortical development, but its role in the adult brain is unknown. To better understand the physiological role of Blm-s gene in vivo, we generated a Blm-s-knockout (Blm-s-/-) mouse. The Blm-s-/- mice breed normally and exhibit grossly normal development. However, global depletion of Blm-s is highly associated with depression- and anxiety-related behaviors in adult mutant mice with intact learning and memory capacity. Functional magnetic resonance imaging of adult Blm-s-/- mice reveals reduced connectivity mainly in the ventral dentate gyrus (vDG) of the hippocampus with no alteration in the dorsal DG connectivity and in total hippocampal volume. At the cellular level, BLM-s is expressed in DG granule cells (GCs), and Blm-s-/- mice show reduced dendritic complexity and decreased spine density in mature GCs. Electrophysiology study uncovers that mature vGCs in adult Blm-s-/- DG are intrinsically more excitable. Interestingly, certain genetic variants of the human Blm homologue gene (VPS50) are significantly associated with depression traits from publicly resourced UK Biobank data. Taken together, BLM-s is required for the hippocampal mood control function. Loss of BLM-s causes abnormality in the electrophysiology and morphology of GCs and a disrupted vDG neural network, which could underlie Blm-s-null-associated anxiety and depression.

White matter pathology in alzheimer's transgenic mice with chronic exposure to low-level ambient fine particulate matter.

BACKGROUND: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. RESULTS: 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 µg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. CONCLUSIONS: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Three month inhalation exposure to low-level PM2.5 induced brain toxicity in an Alzheimer's disease mouse model.

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD.

Self-pinning of silica suspension droplets on hydrophobic surfaces.

HYPOTHESIS: Self-pinning induced by the aggregation of particles at the edge of a pinned drop is a pre-requisite for the coffee ring formation. The edge (three-phase contact line) of a suspension drop on a hydrophobic surface would depin and shrink in the early stage of evaporation process. It is plausible to conjecture that the self-pinning of silica suspension drops depends on the particle size and surface property. EXPERIMENTS: Two substrate materials, the alkylsilane coated surfaces and the polydimethylsiloxane surfaces, and three different sizes of silica particles are used to explore the criterion of self-pinning of silica suspension drops on these hydrophobic surfaces. The evaporation process of droplets is recorded and further analyzed. FINDINGS: The pinning concentration of silica suspensions of a fixed size linearly depends on the receding contact angle of the surface, irrelevant to the substrate material and initial particle concentration. The pinning concentration decreases along with an increase in particle size. In addition, the pinning concentrations of bi-dispersed silica (e.g. 400 + 1000 nm) suspensions have an excellent agreement with that of larger size (1000 nm) particle system. That implies that the larger particle dominates the system of bi-dispersed silica suspensions to initiate the self-pinning, further verified by SEM images.

Dedicated diffusion phantoms for the investigation of free water elimination and mapping: insights into the influence of T2 relaxation properties.

Conventional diffusion-weighted (DW) MRI suffers from free water contamination due to the finite voxel size. The most common case of free water contamination occurs with cerebrospinal fluid (CSF) in voxels located at the CSF-tissue interface, such as at the ventricles in the human brain. Another case refers to intra-tissue free water as in vasogenic oedema. In order to avoid the bias in diffusion metrics, several multi-compartment methods have been introduced, which explicitly model the presence of a free water compartment. However, fitting multi-compartment models in DW MRI represents a well known ill conditioned problem. Although during the last decade great effort has been devoted to mitigating this estimation problem, the research field remains active. The aim of this work is to introduce the design, characterise the NMR properties and demonstrate the use of two dedicated anisotropic diffusion fibre phantoms, useful for the study of free water elimination (FWE) and mapping models. In particular, we investigate the recently proposed FWE diffusion tensor imaging approach, which takes explicit account of differences in the transverse relaxation times between the free water and tissue compartments.

Development, integration and use of an ultra-high-strength gradient system on a human-size 3 T magnet for small animal MRI.

This study aims to integrate an ultra-high-strength gradient coil system on a clinical 3 T magnet and demonstrate its preclinical imaging capabilities. Dedicated phantoms were used to qualitatively and quantitatively assess the performance of the gradient system. Advanced MR imaging sequences, including diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM), were implemented and executed on an ex vivo specimen as well as in vivo rats. The DTI and QSM results on the phantom agreed well with those in the literature. Furthermore, studies on ex vivo specimens have demonstrated the applicability of DTI and QSM on our system to probe microstructural changes in a mild traumatic brain injury rat model. The feasibility of in vivo rat DTI was also demonstrated. We showed that the inserted ultra-high-strength gradient coil was successfully integrated on a clinically used magnet. After careful tuning and calibration, we verified the accuracy and quantitative preclinical imaging capability of the integrated system in phantom and in vivo rat brain experiments. This study can be essential to establish dedicated animal MRI platform on clinical MRI scanners and facilitate translational studies at clinical settings.

Effects of signal averaging, gradient encoding scheme, and spatial resolution on diffusion kurtosis imaging: An empirical study using 7T MRI.

BACKGROUND: Although diffusion gradient directions and b-values have been optimized for diffusion kurtosis imaging (DKI), little is known about the effect of signal averaging on DKI reliability. PURPOSE: To evaluate how signal averaging influences the reliability of DKI indices using two gradient encoding schemes with three spatial resolutions. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen naïve Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: DKI was performed at 7T using two schemes (30 directions with three b-values [30d-3b] and six directions with 15 b-values [6d-15b]), three resolutions, and eight repetitions. ASSESSMENT: DKI reliability was assessed using voxelwise relative error (σ) and test-retest error of fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) within gray matter (GM) and white matter (WM). The number of excitations (NEX) was optimized by considering DKI reliability. The influence of the partial volume effect (PVE) was also assessed. STATISTICAL TEST: One-way analysis of variance. RESULTS: The 30d-3b scheme, compared with the 6d-15b scheme, exhibited apparently smaller σFA and σMK (eg, at NEX 1, in GM, for three resolutions, σFA : 19.9-38.2% vs. 34.2-61.4%, σMK : 6.9-11.4% vs. 14.1-15.4%) and similar σMD (all differences between two schemes <1.6%). The optimal NEX was determined as 2 for enabling a reliable measurement of DKI-derived indices. The PVE at the lowest resolution apparently increased σFA for both schemes (19.9% for 30d-3b and 34.2% for 6d-15b) and σMK for the 6d-15b scheme (14.7%) in GM, and exerted lower effects on MK values for the 30d-3b scheme (P > 0.05). DATA CONCLUSION: A higher number of diffusion directions would benefit FA and MK estimation. A higher spatial resolution helps to reduce PVE. By using the 30d-3b scheme, MK is considered a robust index to reflect microstructural changes in GM and WM. We propose a systematic approach to determine the optimal DKI protocols for appropriate preclinical settings. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1593-1603.

Chronic pulmonary exposure to traffic-related fine particulate matter causes brain impairment in adult rats.

BACKGROUND: Effects of air pollution on neurotoxicity and behavioral alterations have been reported. The objective of this study was to investigate the pathophysiology caused by particulate matter (PM) in the brain. We examined the effects of traffic-related particulate matter with an aerodynamic diameter of < 1 µm (PM1), high-efficiency particulate air (HEPA)-filtered air, and clean air on the brain structure, behavioral changes, brainwaves, and bioreactivity of the brain (cortex, cerebellum, and hippocampus), olfactory bulb, and serum after 3 and 6 months of whole-body exposure in 6-month-old Sprague Dawley rats. RESULTS: The rats were exposed to 16.3 ± 8.2 (4.7~ 68.8) µg/m3 of PM1 during the study period. An MRI analysis showed that whole-brain and hippocampal volumes increased with 3 and 6 months of PM1 exposure. A short-term memory deficiency occurred with 3 months of exposure to PM1 as determined by a novel object recognition (NOR) task, but there were no significant changes in motor functions. There were no changes in frequency bands or multiscale entropy of brainwaves. Exposure to 3 months of PM1 increased 8-isoporstance in the cortex, cerebellum, and hippocampus as well as hippocampal inflammation (interleukin (IL)-6), but not in the olfactory bulb. Systemic CCL11 (at 3 and 6 months) and IL-4 (at 6 months) increased after PM1 exposure. Light chain 3 (LC3) expression increased in the hippocampus after 6 months of exposure. Spongiosis and neuronal shrinkage were observed in the cortex, cerebellum, and hippocampus (neuronal shrinkage) after exposure to air pollution. Additionally, microabscesses were observed in the cortex after 6 months of PM1 exposure. CONCLUSIONS: Our study first observed cerebral edema and brain impairment in adult rats after chronic exposure to traffic-related air pollution.

Application of amniotic fluid stem cells in repairing sciatic nerve injury in minipigs.

Many studies have demonstrated that combining nerve conduits with neural stem cells or growth factors can repair peripheral nerve injury in rodents. However, nerve damage does occur with longer gaps in human than in rodents, thus findings from rodent studies are difficult to translate to clinical practice. Minipigs have a longer gap that is more closely applicable to the challenge of human nerve grafting in extensive traumatic nerve damage. In this study, human amniotic fluid stem cells (AFSCs) and polylactate nerve conduits were used to repair sciatic nerve injury in minipigs. The AFSCs exhibited the properties of mesenchymal stem cells with a propensity toward neural stem cells. Measurements of compound muscle action potential implied that administration of conduits with AFSCs was beneficial in function recovery in the minipig model compared with conduits alone. The results of diffusion tensor magnetic resonance imaging (DTI) based fiber tractography assay in the minipig model suggest that combining AFSCs with conduits could expedite the repair of sciatic nerve injury. Further, MR-based DTI provides an effective and non-invasive method to visualize the sciatic nerve and to monitor the regeneration progress of injured nerve in a longitudinal study.

Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI.

This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle.

Neonatal Death and Heart Failure in Mouse with Transgenic HSP60 Expression.

Mitochondrial heat shock proteins, such as HSP60, are chaperones responsible for the folding, transport, and quality control of mitochondrial matrix proteins and are essential for maintaining life. Both prosurvival and proapoptotic roles have been proposed for HSP60, and HSP60 is reportedly involved in the initiation of autoimmune, metabolic, and cardiovascular diseases. The role of HSP60 in pathogenesis of these diseases remains unclear, partly because of the lack of mouse models expressing HSP60. In this study we generated HSP60 conditional transgenic mice suitable for investigating in vivo outcomes by expressing HSP60 at the targeted organ in disease models. Ubiquitous HSP60 induction in the embryonic stage caused neonatal death in mice at postnatal day 1. A high incidence of atrial septal defects was observed in HSP60-expressing mice, with increased apoptosis and myocyte degeneration that possibly contributed to massive hemorrhage and sponge-like cardiac muscles. Our results showed that neonatal heart failure through HSP60 induction likely involves developmental defects and excessive apoptosis. The conditional HSP60 mouse model is useful for studying crucial biological questions concerning HSP60.

Observation of the rose petal effect over single- and dual-scale roughness surfaces.

Rose petals exhibit superhydrophobicity with strong adhesion to pin water drops, known as the 'petal effect.' It is generally believed that the petal effect is attributed to dual-scale roughness, that is, the surface possesses both a nanostructure and a microstructure (Feng et al 2008 Langmuir 24 4114). In this study, we demonstrate that the dual-scale roughness is not a necessary condition for a surface of the petal effect. A surface of single-scale roughness, either at the nanoscale or the microscale alone, within a certain roughness region may also exhibit the petal effect. The surface roughness plays the essential role on the wetting behavior and governs the contact angle in the Wenzel or Cassie state, as well as the contact angle hysteresis. A water drop on the surface of the petal effect under the condition of the advancing and receding contact angle would fall into, respectively, the Cassie and Wenzel state, which leads to a contact angle hysteresis large enough to pin the water drop. On both single and dual textured hydrophobic surfaces, a sequence of wetting transitions: Wenzel state → petal state (sticky superhydrophobic state) → lotus state (slippery superhydrophobic state) is consistently observed by simply increasing the surface roughness.

Estimation of fiber orientation by filtered q-ball imaging*.

We proposed a filtered q-ball imaging (fQBI) method for the reconstruction of fiber orientation distribution function (ODF) together with the quantitative comparison to unfiltered QBI. The filter kernel increases the high angular frequency content that is beneficial for the angular resolution in resolving crossing fibers. Through a series of simulations using Monte-Carlo model, the angular resolution of fQBI was demonstrated better than traditional QBI but the deviation of fiber orientation estimate also becomes larger. The improvement of the angular resolution can also reduce the underestimation of separation angles as well as the bias of fiber orientation estimations. In conclusion, fQBI was demonstrated to improve the angular resolution of QBI in resolving crossing fibers. This improvement will be helpful to precisely reconstruct fiber tract and brain network in applications by QBI.

Investigating the effects of streamline-based fiber tractography on matrix scaling in brain connective network.

Investigating the brain connective network using the modern graph theory has been widely applied in cognitive and clinical neuroscience research. In this study, we aimed to investigate the effects of streamline-based fiber tractography on the change of network properties and established a systematic framework to understand how an adequate network matrix scaling can be determined. The network properties, including degree, efficiency and betweenness centrality, show similar tendency in both left and right hemispheres. By employing the curve-fitting process with exponential law and measuring the residuals, the association between changes of network properties and threshold of track numbers is found and an adequate range of investigating the lateralization of brain network is suggested. The proposed approach can be further applied in clinical applications to improve the diagnostic sensitivity using network analysis with graph theory.

Early detection of Lewis lung carcinoma tumor control by irradiation using diffusion-weighted and dynamic contrast-enhanced MRI.

PURPOSE: To investigate the correlation between diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) derived parameters and radioresponsiveness of Lewis lung carcinoma (LLC) tumor. MATERIALS AND METHODS: LLC tumor growth in C57BL/6 mouse limb was used for the experiment. The tumors were irradiated with 10 Gy×5, or 30 Gy×2 vs. sham irradiation. Fourteen tumors were subjected to DW-MRI and DCE-MRI pre-radiotherapy and weekly imaging after radiotherapy. The temporal changes in apparent diffusion coefficient (ADC) and DCE-MRI derived parameters (K(trans), k(ep), v(e), and v(p)) were correlated with tumor size, and were histologically compared with CD31 staining of resected tumors. RESULTS: The 10 Gy×5 dose inhibited tumor growth for a week, while 30 Gy×2 controlled tumor growth for a 3-week observation period. One week after radiotherapy (week 2), irradiated tumors showed significantly higher values of ADC than untreated ones (10 Gy×5, p = 0.004; 30 Gy×2, p = 0.01). Significantly higher values of v(e) were shown earlier by 30 Gy×2 vs. sham (p = 0.01) and 10 Gy×5 vs. sham irradiation (p = 0.05). Sustained higher v(e) from 10 Gy×5 compared to sham irradiated tumors was evident at week 3 (p = 0.016) and week 4 (p = 0.046). A 13.8% early increase in ADC for 30 Gy×2 tumor group (p = 0.002) and a 16.5% increase for 10 Gy×5 group were noted (p = 0.01) vs. sham irradiation (which showed a 2.2% decrease). No differences were found for K(trans), k(ep), or v(p). Both radiotherapy groups demonstrated significant reduction in microvessel counts. CONCLUSION: Early increase in ADC and v(e) correlated with tumor control by irradiation.

Improving DTI tractography by including diagonal tract propagation.

Tractography algorithms have been developed to reconstruct likely WM pathways in the brain from diffusion tensor imaging (DTI) data. In this study, an elegant and simple means for improving existing tractography algorithms is proposed by allowing tracts to propagate through diagonal trajectories between voxels, instead of only rectilinearly to their facewise neighbors. A series of tests (using both real and simulated data sets) are utilized to show several benefits of this new approach. First, the inclusion of diagonal tract propagation decreases the dependence of an algorithm on the arbitrary orientation of coordinate axes and therefore reduces numerical errors associated with that bias (which are also demonstrated here). Moreover, both quantitatively and qualitatively, including diagonals decreases overall noise sensitivity of results and leads to significantly greater efficiency in scanning protocols; that is, the obtained tracts converge much more quickly (i.e., in a smaller amount of scanning time) to those of data sets with high SNR and spatial resolution. Importantly, the inclusion of diagonal propagation adds essentially no appreciable time of calculation or computational costs to standard methods. This study focuses on the widely-used streamline tracking method, FACT (fiber assessment by continuous tracking), and the modified method is termed "FACTID" (FACT including diagonals).

Variations in connectivity in the sensorimotor and default-mode networks during the first nocturnal sleep cycle.

The function of sleep in humans has been investigated using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging recordings to provide accurate sleep scores with spatial precision. Recent studies have demonstrated that spontaneous brain oscillations and functional connectivity dissociate during nonrapid eye movement (NREM) sleep; this leads to spontaneous cognitive processes, such as memory consolidation and emotional modulation. However, variations in network connectivity across the sleep stages or between sleep/wake transitions require further elucidation. We observed changes in the connectivity of the sensorimotor and default-mode networks (DMN) mediated by midnight sleep among 18 healthy participants. The results indicated that (1) functional connectivity in both networks showed increasing dissociation as NREM sleep deepened, whereas hyperconnectivity occurred during rapid eye movement (REM) sleep; and (2) compared with connectivity before sleep, the DMN presented a comparable connectivity pattern immediately after awakening, whereas the connectivity of the sensorimotor network remained disrupted. These findings showed that connectivity patterns dissociate and reconnect coherently in both cortical networks during NREM and REM sleep, respectively. After the person awakened, the DMN connectivity was re-established before the sensorimotor reconnection. These dynamic sleep-related dissociations and reconnections between sleep/wake conditions might provide the key to understanding cognitive modulations in sleep. If so, connectivity changes might serve as an alternative indicator beyond the EEG signature to unveil the spontaneous processes that occur during sleep.

Impaired small-world network efficiency and dynamic functional distribution in patients with cirrhosis.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a 'small-world' network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI). Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions disturbed the functional network to further alter the global topology and efficiency of the whole brain network. These findings provide insights into the functional changes in the human brain in HE.