Anterior cingulate cortex-related functional hyperconnectivity underlies sensory hypersensitivity in Grin2b-mutant mice.

Sensory abnormalities are observed in ~90% of individuals with autism spectrum disorders (ASD), but the underlying mechanisms are poorly understood. GluN2B, an NMDA receptor subunit that regulates long-term depression and circuit refinement during brain development, has been strongly implicated in ASD, but whether GRIN2B mutations lead to sensory abnormalities remains unclear. Here, we report that Grin2b-mutant mice show behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). Grin2b-mutant mice with a patient-derived C456Y mutation (Grin2bC456Y/+) show sensory hypersensitivity to mechanical, thermal, and electrical stimuli through supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions. ACC pyramidal neurons show increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity. These results suggest that GluN2B critically regulates ASD-related cortical connectivity and sensory brain functions.

Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing.

To further advance functional MRI (fMRI)-based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume-weighted fMRI was performed with optogenetic stimulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs, and local intracortical circuits to be determined. The ventral posterior thalamic nucleus receives ST inputs, while the posterior medial thalamic nucleus receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the ventral posterolateral nucleus. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half maximum of <150 µm. Long-range synaptic inputs in cortical areas were amplified approximately twofold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based, long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.

Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow.

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to localize brain functions. To further advance understanding of brain functions, it is critical to understand the direction of information flow, such as thalamocortical versus corticothalamic projections. For this work, we performed ultrahigh spatiotemporal resolution fMRI at 15.2 T of the mouse somatosensory network during forepaw somatosensory stimulation and optogenetic stimulation of the primary motor cortex (M1). Somatosensory stimulation induced the earliest BOLD response in the ventral posterolateral nucleus (VPL), followed by the primary somatosensory cortex (S1) and then M1 and posterior thalamic nucleus. Optogenetic stimulation of excitatory neurons in M1 induced the earliest BOLD response in M1, followed by S1 and then VPL. Within S1, the middle cortical layers responded to somatosensory stimulation earlier than the upper or lower layers, whereas the upper cortical layers responded earlier than the other two layers to optogenetic stimulation in M1. The order of early BOLD responses was consistent with the canonical understanding of somatosensory network connections and cannot be explained by regional variabilities in the hemodynamic response functions measured using hypercapnic stimulation. Our data demonstrate that early BOLD responses reflect the information flow in the mouse somatosensory network, suggesting that high-field fMRI can be used for systems-level network analyses.

Contribution of Excitatory and Inhibitory Neuronal Activity to BOLD fMRI.

The BOLD fMRI response in the cortex is often assumed to reflect changes in excitatory neural activity. However, the contribution of inhibitory neurons to BOLD fMRI is unclear. Here, the role of inhibitory and excitatory activity was examined using multimodal approaches: electrophysiological recording, 15.2 T fMRI, optical intrinsic signal imaging, and modeling. Inhibitory and excitatory neuronal activity in the somatosensory cortex were selectively modulated by 20-s optogenetic stimulation of VGAT-ChR2 and CaMKII-ChR2 mice, respectively. Somatosensory stimulation and optogenetic stimulation of excitatory neurons induced positive BOLD responses in the somatosensory network, whereas stimulation of inhibitory neurons produced biphasic responses at the stimulation site, initial positive and later negative BOLD signals, and negative BOLD responses at downstream sites. When the stimulation duration was reduced to 5 s, the hemodynamic response of VGAT-ChR2 mice to optogenetic stimulation was only positive. Lastly, modeling performed from neuronal and hemodynamic data shows that the hemodynamic response function (HRF) of excitatory neurons is similar across different conditions, whereas the HRF of inhibitory neurons is highly sensitive to stimulation frequency and peaks earlier than that of excitatory neurons. Our study provides insights into the neurovascular coupling of excitatory and inhibitory neurons and the interpretation of BOLD fMRI signals.

Characteristics of fMRI responses to visual stimulation in anesthetized vs. awake mice.

The functional characteristics of the mouse visual system have not previously been well explored using fMRI. In this research, we examined 9.4 T BOLD fMRI responses to visual stimuli of varying pulse durations (1 - 50 ms) and temporal frequencies (1 - 10 Hz) under ketamine and xylazine anesthesia, and compared fMRI responses of anesthetized and awake mice. Under anesthesia, significant positive BOLD responses were detected bilaterally in the major structures of the visual pathways, including the dorsal lateral geniculate nuclei, superior colliculus, lateral posterior nucleus of thalamus, primary visual area, and higher-order visual area. BOLD responses increased slightly with pulse duration, were maximal at 3 - 5 Hz stimulation, and significantly decreased at 10 Hz, which were all consistent with previous neurophysiological findings. When the mice were awake, the BOLD fMRI response was faster in all active regions and stronger in the subcortical areas compared with the anesthesia condition. In the V1, the BOLD response was biphasic for 5 Hz stimulation and negative for 10 Hz stimulation under wakefulness, whereas prolonged positive BOLD responses were observed at both frequencies under anesthesia. Unexpected activation was detected in the extrastriate postrhinal area and non-visual subiculum complex under anesthesia, but not under wakefulness. Widespread positive BOLD activity under anesthesia likely results from the disinhibition and sensitization of excitatory neurons induced by ketamine. Overall, fMRI can be a viable tool for mapping brain-wide functional networks.

An equal-TE ultrafast 3D gradient-echo imaging method with high tolerance to magnetic susceptibility artifacts: Application to BOLD functional MRI.

PURPOSE: To develop an ultrafast 3D gradient echo-based MRI method with constant TE and high tolerance to B0 inhomogeneity, dubbed ERASE (equal-TE rapid acquisition with sequential excitation), and to introduce its use in BOLD functional MRI (fMRI). THEORY AND METHODS: Essential features of ERASE, including spin behavior, were characterized, and a comparison study was conducted with conventional EPI. To demonstrate high tolerance to B0 inhomogeneity, in vivo imaging of the mouse brain with a fiber-optic implant was performed at 9.4 T, and human brain imaging (including the orbitofrontal cortex) was performed at 3 T and 7 T. To evaluate the performance of ERASE in BOLD-fMRI, the characteristics of SNR and temporal SNR were analyzed for in vivo rat brains at 9.4 T in comparison with multislice gradient-echo EPI. Percent signal changes and t-scores are also presented. RESULTS: For both mouse brain and human brain imaging, ERASE exhibited a high tolerance to magnetic susceptibility artifacts, showing much lower distortion and signal dropout, especially in the regions involving large magnetic susceptibility effects. For BOLD-fMRI, ERASE provided higher temporal SNR and t-scores than EPI, but exhibited similar percent signal changes in in vivo rat brains at 9.4 T. CONCLUSION: When compared with conventional EPI, ERASE is much less sensitive, not only to EPI-related artifacts such as Nyquist ghosting, but also to B0 inhomogeneity including magnetic susceptibility effects. It is promising for use in BOLD-fMRI, providing higher temporal SNR and t-scores with constant TE when compared with EPI, although further optimization is needed for human fMRI.

Non-strangulated adhesive small bowel obstruction: CT findings predicting outcome of conservative treatment.

OBJECTIVES: To clarify CT findings that predict outcome of conservative treatment in patients with non-strangulated adhesive small bowel obstruction (SBO). METHODS: Unenhanced and contrast-enhanced abdominopelvic CT studies in 189 patients with adhesive SBO who had initial conservative treatment were reviewed. The CT findings included transition zone, beak signs, maximum bowel diameter, bowel diameter ratio, decreased bowel wall enhancement, increased unenhanced bowel wall attenuation, anterior parietal adhesion, bowel wall thickening, closed-loop obstruction, small bowel feces sign, whirl sign, mesenteric haziness, mesenteric, peritoneal fluid, and submucosal edema. These findings were statistically compared according to the success or failure of treatment. RESULTS: Conservative treatment succeeded in 144 patients (76.2%) and failed in 45 patients (23.8%). At multivariate analysis, the lack of small bowel feces sign, focal, diffuse mesenteric haziness, and moderate amount of mesenteric fluid were independent findings predicting failure of conservative treatment, with odds ratios of 5.23, 5.5, 13.55, and 4.89, respectively. The presence of all significant findings showed a high specificity of 97.2% with positive likelihood ratio of 8.8. If CT scans showed none of the three significant findings, the negative predictive value was 97.6% and negative likelihood ratio was 0.08. CONCLUSIONS: The lack of small bowel feces sign, focal, diffuse mesenteric haziness, and moderate amount of mesenteric fluid are independent CT findings predicting the failure of conservative treatment in patients with non-strangulated adhesive SBO. The combination of all CT findings suggests the need for surgery; absence of two or all CT findings should suggest an attempt for conservative treatment. KEY POINTS: • To minimize delayed operation, it is important to identify non-strangulated adhesive small bowel obstruction patients in whom initial conservative treatment is likely to fail. • The lack of small bowel feces sign, the presence of mesenteric haziness, and a moderate amount of mesenteric fluid are independent factors predicting the failure of conservative treatment in patients with non-strangulated adhesive small bowel obstruction. • The combination of all three CT findings suggests the need for surgery; absence of two or all three CT findings should suggest an attempt for conservative treatment.

Mouse BOLD fMRI at ultrahigh field detects somatosensory networks including thalamic nuclei.

Forepaw somatosensory stimulation induces neural activities in relay thalamic nuclei, the primary somatosensory cortex of forelimb (S1FL), and the secondary somatosensory cortex (S2). However, rodent fMRI studies of somatosensory stimulation have commonly reported BOLD changes only in S1FL, which may be due to side effects of anesthetics and/or the low sensitivity in the thalamus. Thus, we have obtained mouse BOLD fMRI under newly-adopted ketamine-xylazine anesthesia. High-resolution BOLD fMRI obtained with same imaging parameters at 9.4T versus 15.2T shows the improvement of functional detectability by ≥ 2 times at 15.2T due to higher signal intensity and larger BOLD response. The fMRI responses at 15.2T were robustly observed at well-known somatosensory networks including thalamus. Second, echo-time-dependent BOLD signals are dominant based on multi-echo fMRI data. A ratio of BOLD responses in S1FL to thalamus is ∼2, which is not related to different baseline T2∗ or different cerebral blood volume. Third, group-averaged 15.2T BOLD maps show activities in S1FL, S2, motor cortices, and thalamic nuclei, which agree well with neural tracing network data from the Allen Institute, demonstrating that fMRI detects entire somatosensory networks. Our data suggest that ultrahigh field fMRI provides a unique window into understanding functional networks in normal and transgenic mouse models noninvasively.

Physical exercise enhances adult cortical plasticity in a neonatal rat model of hypoxic-ischemic injury: Evidence from BOLD-fMRI and electrophysiological recordings.

Neuroplasticity is considered essential for recovery from brain injury in developing brains. Recent studies indicate that it is especially effective during early postnatal development and during the critical period. The current study used functional magnetic resonance imaging (fMRI) and local field potential (LFP) electrophysiological recordings in rats that experienced neonatal hypoxic-ischemic (HI) injury during the critical period to demonstrate that physical exercise (PE) can improve cortical plasticity even when performed during adulthood, after the critical period. We investigated to what extent the blood oxygen level-dependent (BOLD)-fMRI responses were increased in the contralesional spared cortex, and how these increases were related to the LFP electrophysiological measurements and the functional outcome. The balance of excitation and inhibition was assessed by measuring excitatory and inhibitory postsynaptic currents in stellate cells in the primary somatosensory (S1) cortex, which was compared with the BOLD-fMRI responses in the contralesional S1 cortex. The ratio of inhibitory postsynaptic current (IPSC) to excitatory postsynaptic current (EPSC) at the thalamocortical (TC) input to the spared S1 cortex was significantly increased by PE, which is consistent with the increased BOLD-fMRI responses and improved functional outcome. Our data clearly demonstrate in an experimental rat model of HI injury during the critical period that PE in adulthood enhances neuroplasticity and suggest that enhanced feed-forward inhibition at the TC input to the S1 cortex might underlie the PE-induced amelioration of the somatosensory deficits caused by the HI injury. In summary, the results of the current study indicate that PE, even if performed beyond the critical period or during adulthood, can be an effective therapy to treat neonatal brain injuries, providing a potential mechanism for the development of a potent rehabilitation strategy to alleviate HI-induced neurological impairments.

Mouse fMRI under ketamine and xylazine anesthesia: Robust contralateral somatosensory cortex activation in response to forepaw stimulation.

Mouse fMRI is critically useful to investigate functions of mouse models. Until now, the somatosensory-evoked responses in anesthetized mice are often widespread and inconsistent across reports. Here, we adopted a ketamine and xylazine mixture for mouse fMRI, which is relatively new anesthetics in fMRI experiments. Forepaw stimulation frequency was optimized using cerebral blood volume (CBV)-weighted optical imaging (n = 11) and blood-oxygenation-level dependent (BOLD) fMRI with a gradient-echo time of 16 ms at 9.4 T, and 4 Hz stimulation with 0.5 ms and 0.5 mA pulses induced the highest hemodynamic response. For 20-s 4-Hz unilateral forepaw stimulation, localized BOLD activity was consistently found in the contralateral primary forelimb somatosensory cortex (S1FL), while no significant change was observed in the ipsilateral S1FL. The mean magnitude was 1.44 ±â€¯0.20% SEM (n = 9) in the contralateral S1FL and 0.69 ±â€¯0.10% in the contralateral thalamus. The variability of evoked fMRI responses across sessions was investigated by comparing with resting state fMRI (rsfMRI) functional connectivity (FC). Evoked responses in S1FL were correlated positively with rsfMRI FC between bilateral S1FL (r = 0.63 to 0.69) and negatively with FC between S1FL and the anterior cingulate cortex (r = -0.50 to -0.57), suggesting that rsfMRI FC is a good index of the evoked fMRI response and anesthetized animal condition. Finally, three weekly fMRI scans were performed in 5 mice, and localized activity was reproducibly observed in S1FL, with a success rate of 70-95%. In summary, our developed fMRI protocol can be used for mapping functions of mouse models.

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats.

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel-based analysis are highly dependent on the user-hypothesis and parameter settings for implementation. In contrast, tract-based spatial statistics (TBSS) allows for reliable voxel-wise analysis via the projection of diffusion-derived parameters onto an alignment-invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI-derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2-4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post-stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post-stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo-normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.

Anastomotic Recurrence After Curative Resection for Colorectal Cancer.

BACKGROUND: A precise understanding of anastomotic recurrence (AR) permits efficient surveillance and treatment strategies. This study aimed to evaluate the clinicopathologic characteristics of patients with AR undergoing curative resection for colorectal cancer (CRC), compare colonic with rectal tumors and investigate the risk factors related to AR. METHODS: A single-institution, retrospective cohort of 9024 patients who underwent curative surgery for CRC between 2000 and 2010 was enrolled. Patients were classified into AR group (n = 53) or non-AR group (n = 8971) and were also characterized by tumor location. RESULTS: The AR group was independently associated with old age (p = 0.046), advanced N stage (p = 0.003), the rectum (p = 0.001), a large tumor (p = 0.001) and mucinous differentiation (MU) (p = 0.026). In colon cancers, the AR group (n = 20) was independently associated with MU (p = 0.022) and lymphovascular invasion (LVI) (p = 0.001). In rectal cancers, the AR group (n = 33) was independently associated with N2 stage (p = 0.007) and a large tumor (p < 0.001). AR is a burden to patients and physicians because these tumors have a poor prognosis and more advanced pathologic stages than the primary tumors. However, N0 stage and curative resection of an AR tumor (p = 0.001 and p < 0.001, respectively) were found to be independently associated with improved survival in a Cox regression model. CONCLUSION: AR is independently associated with the rectum. In colon cancers, MU and LVI are independent risk factors for AR. In rectal cancers, a large tumor and N2 stage are independent risk factors for AR. Although AR shows a poor prognosis, early detection and curative resection may lead to an improved survival.

Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes.

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake.

Neuroplasticity for spontaneous functional recovery after neonatal hypoxic ischemic brain injury in rats observed by functional MRI and diffusion tensor imaging.

For infants and children, an incredible resilience from injury is often observed. There is growing evidence that functional recovery after brain injury might well be a consequence of the reorganization of the neural network as a process of neuroplasticity. We demonstrate the presence of neuroplasticity at work in spontaneous recovery after neonatal hypoxic ischemic (HI) injury, by elucidating a precise picture in which such reorganization takes place using functional MRI techniques. For all 12 siblings, 6 rats were subjected to severe HI brain injury and 6 rats underwent sham operation only. Severe HI brain injury was induced to postnatal day 7 (p7) Sprague-Dawley rats according to the Rice-Vannucci model (right carotid artery occlusion followed by 150min of hypoxia with 8% O2 and 92% of N2). Brain activation maps along with anatomical and functional connectivity maps related to the sensory motor function were obtained at adult (p63) using blood oxygen level dependent (BOLD)-functional MRI (fMRI), resting state-functional MRI (rs-fMRI) and diffusion tensor imaging (DTI); each of these MRI data was related to sensory motor functional outcome. In-depth investigation of the functional MRI data revealed: 1) intra-hemispheric expansion of BOLD signal activation in the contralesional undamaged hemisphere for ipsilesional forepaw stimuli to include the M2 and Cg1 in addition to the S1 and M1 wide spreading in the anterior and posterior directions, 2) inter-hemispheric transfer of BOLD signal activation for contralesional forepaw stimuli, normally routed to the injured hemisphere, to analogous sites in the contralesional undamaged hemisphere, localized newly to the M1 and M2 with a reduced portion of the S1, 3) inter-hemispheric axonal disconnection and axonal rewiring within the undamaged hemisphere as shown through DTI, and 4) increased functional interactions within the cingulate gyrus in the HI injured rats as shown through rs-fMRI. The BOLD signal amplitudes as well as DTI and rs-fMRI data well correlate with behavioral tests (tape to remove). We found that function normally utilizing what would be the injured hemisphere is transferred to the uninjured hemisphere, and functionality of the uninjured hemisphere remains not untouched but is also rewired in an expansion corresponding to the newly formed sensorimotor function from both the contralesional and the ipsilesional sides. The conclusion drawn from the data in our current study is that enhanced motor function in the contralesional hemisphere governs both the normal and damaged sides, indicating that active plasticity with brain laterality was spontaneously generated to overcome functional loss and established autonomously through normal experience via modification of neural circuitry for neonatal HI injured brain.

Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type.

AIMS: An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH). METHODS: Eleven patients with SVaD-BT and 11 age-, sex-, education- and grade of WMH-matched ncWMH underwent magnetic resonance imaging, including 3-D volumetric images for cortical atrophy and diffusion tensor imaging for integrity of white matter. RESULTS: Compared to ncWMH, SVaD-BT patients showed cortical atrophies in frontal (i.e. frontal pole, precentral gyrus and frontal medial cortex) and occipital areas (i.e. lingual gyrus) followed by atrophies in temporal (i.e. fusiform cortex and middle temporal gyrus) areas. Along with cortical atrophies, reduced integrity with low fractional anisotropy and high mean diffusivity values in genu and splenium of the corpus callosum were detected in SVaD-BT patients. CONCLUSIONS: Our findings suggest that cognitive decline from ncWMH to SVaD-BT may be associated with cortical atrophy and reduced integrity of white matter.

Interaction Between a High-Fat Diet and Tau Pathology in Mice: Implications for Alzheimer's Disease.

BACKGROUND: Obesity is a modifiable risk factor for Alzheimer's disease (AD). However, its relation with tau pathology (i.e., aberrant tau protein behavior in tauopathies such as AD) has been inconclusive. OBJECTIVE: This study investigated the interaction between a high-fat diet (HFD) and tau pathology in adult male mice. METHODS: Transgenic mice overexpressing human P301S Tau (those with the pathology) and wild-type (WT) littermates were subjected to behavioral tests, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and western blotting analysis to investigate the effects of prolonged HFD versus regular diet during adulthood. RESULTS: HFD increased body weight in both WT and P301S mice but had minimal effect on blood glucose levels. The brain response to HFD was tau genotype-specific. WT mice exhibited decreased recognition memory and enhanced network connectivity in fMRI, while P301S mice exhibited white matter tract disorganization in DTI as the sole significant finding. The reduction of insulin receptor ß, insulin downstream signaling, neuronal nuclear protein, CD68-positive phagocytic activity, and myelin basic protein level were confined to the cortex of WT mice. In contrast to P301S mice, WT mice showed significant changes in the tau protein and its phosphorylation levels along with increased soluble neurofilament light levels in the hippocampus. CONCLUSIONS: HFD-induced brain dysfunction and pathological changes were blunted in mice with the pathology and more profound in healthy mice. Our findings highlight the need to consider this interaction between obesity and tau pathology when tailoring treatment strategies for AD and other tauopathies.

A preliminary study of super-resolution deep learning reconstruction with cardiac option for evaluation of endovascular-treated intracranial aneurysms.

OBJECTIVES: To investigate the usefulness of super-resolution deep learning reconstruction (SR-DLR) with cardiac option in the assessment of image quality in patients with stent-assisted coil embolization, coil embolization, and flow-diverting stent placement compared with other image reconstructions. METHODS: This single-center retrospective study included fifty patients (mean age, 59 years; range, 44-81 years; 13 men) who were treated with stent-assisted coil embolization, coil embolization, and flow-diverting stent placement between January and July 2023. The images were reconstructed using filtered back projection (FBP), hybrid iterative reconstruction (IR), and SR-DLR. The objective image analysis included image noise in the Hounsfield unit (HU), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and full width at half maximum (FWHM). Subjectively, two radiologists evaluated the overall image quality for the visualization of the flow-diverting stent, coil, and stent. RESULTS: The image noise in HU in SR-DLR was 6.99 ± 1.49, which was significantly lower than that in images reconstructed with FBP (12.32 ± 3.01) and hybrid IR (8.63 ± 2.12) (p < 0.001). Both the mean SNR and CNR were significantly higher in SR-DLR than in FBP and hybrid IR (p < 0.001 and p < 0.001). The FWHMs for the stent (p < 0.004), flow-diverting stent (p < 0.001), and coil (p < 0.001) were significantly lower in SR-DLR than in FBP and hybrid IR. The subjective visual scores were significantly higher in SR-DLR than in other image reconstructions (p < 0.001). CONCLUSIONS: SR-DLR with cardiac option is useful for follow-up imaging in stent-assisted coil embolization and flow-diverting stent placement in terms of lower image noise, higher SNR and CNR, superior subjective image analysis, and less blooming artifact than other image reconstructions. ADVANCES IN KNOWLEDGE: SR-DLR with cardiac option allow better visualization of the peripheral and smaller cerebral arteries. SR-DLR with cardiac option can be beneficial for CT imaging of stent-assisted coil embolization and flow-diverting stent.

Protocol for mouse optogenetic fMRI at ultrahigh magnetic fields.

Mouse optogenetic functional magnetic resonance imaging (opto-fMRI) is critical for linking genes and functions and for mapping cell-type-specific neural circuits in the whole brain. Herein, we describe how opto-fMRI images can be reliably obtained in anesthetized mice with minimal distortions at ultrahigh magnetic fields. The protocol includes surgical and anesthesia procedures, animal cradle modification, animal preparation and setup, animal physiology maintenance, and pilot fMRI scanning. This protocol will enable reproducible mouse opto-fMRI experiments. For complete details on the use and execution of this protocol, please refer to Jung et al. (2021),1 Jung et al. (2022),2 and Moon et al. (2021).3.

Distribution Pattern of Atherosclerosis in the Abdomen and Lower Extremities and Its Association with Clinical and Hematological Factors.

PURPOSE: Abdominal arteries differ from the arteries located at the extremities in histological composition and clinical features. This study investigated the distributional pattern of atherosclerosis in arteries of the abdomen and lower extremities and its association with clinical and hematologic factors. PATIENTS AND METHODS: This retrospective study included 227 patients with atherosclerosis who underwent computed tomography angiography (CTA) of the abdomen and lower extremities. The distributional pattern of atherosclerosis was categorized into type 1 (suprainguinal elastic), type 2 (infrainguinal muscular), and type 3 (both arterial involvement). Chi-square tests, Mann-Whitney U-tests, and logistic regression analysis were used to investigate the data. RESULTS: Of the 227 patients, 132 (58%) had type 1 and 95 (42%) had type 3 atherosclerosis. None had type 2. Older age, heavier smoking, and higher levels of HbA1c and homocysteine were the significant risk factors for type 3 atherosclerosis (odds ratio: 1.076, 1.023, 1.426, and 1.130, respectively). Patients with type 3 showed significantly lower right and left ankle and toe brachial indices compared to type 1 (P: 0.029, 0.023, 0.003, and <0.001, respectively). CONCLUSION: In arteries of the abdomen and lower extremities, atherosclerosis may occur initially at suprainguinal elastic arteries. In addition, the significant risk factors for type 3 atherosclerosis may contribute to the development of atherosclerosis at infrainguinal muscular arteries and deteriorate the peripheral arterial circulation. Therefore, if atherosclerotic lesions are found at the suprainguinal elastic arteries on CTA, to prevent atherosclerosis at infrainguinal muscular arteries and subsequent peripheral arterial ischemic disease, cessation of smoking and control of blood glucose and homocysteine may be recommended, especially in elderly patients.

Predictors of reoperation for perianal fistula in Crohn's disease.

OBJECTIVE: Treating perianal fistula in cases of Crohn's disease (CD) remains challenging and the postoperative recurrence rate of perianal fistula is 22%-28%. This study aimed to identify the predictive risk factors for reoperation in Korean CD patients with perianal fistula. METHODS: Medical records of the patients with clinically and pathologically confirmed CD who underwent surgical treatment for perianal fistulas at four referral centers in Korea between March 2010 and February 2020 were retrospectively reviewed. The rate of reoperation due to perianal fistula recurrence, which was defined as any subsequent surgery for perianal fistula or abscess, and the potential risk factors for reoperation were analyzed. RESULTS: Fifty-one patients at a mean age of 22 years were included in the study. During a median follow-up period of 26 months (range 2-89 mo), 21 (41.2%) patients underwent reoperation because of recurrent perianal fistula or abscess. The median interval from the first surgery to reoperation was 13 months. A multivariate Cox regression analysis revealed that drug escalation (from 5-aminosalicylic acid [5-ASA] to thiopurine or from 5-ASA or thiopurine to anti-tumor necrosis factor agents) after the first surgery was associated with a reduced likelihood of reoperation (hazard ratio 0.316, 95% confidence interval 0.117-0.858, P = 0.024). CONCLUSIONS: The postoperative recurrence rate was relatively high (41.2%) after the first surgery for perianal fistula in Korean patients with CD. Drug escalation therapy after the first surgery may help reduce the need for reoperation for perianal fistula.