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Quantitative susceptibility mapping (QSM), one of the advanced MRI techniques for evaluating magnetic susceptibility, offers precise quantitative measurements of spatial distributions of magnetic susceptibility. Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and is a substance-specific value. Recently, QSM has been widely used to estimate various levels of substances in the brain, including iron, hemosiderin, and deoxyhemoglobin (paramagnetism), as well as calcification (diamagnetism). By visualizing iron distribution in the brain, it is possible to identify anatomic structures that are not evident on conventional images and to evaluate various neurodegenerative diseases. It has been challenging to apply QSM in areas outside the brain because of motion artifacts from respiration and heartbeats, as well as the presence of fat, which has a different frequency to the proton. In this review, the authors provide a brief overview of the theoretical background and analyze methods of converting MRI phase images to QSM. Moreover, we provide an overview of the current clinical applications of QSM. Online supplemental material is available for this article. © RSNA, 2022.

Introduction: Neurophysiological manifestations selectively associated with amyloid beta and tau depositions in Alzheimer's disease (AD) are useful network biomarkers to identify peptide specific pathological processes. The objective of this study was to validate the associations between reduced neuronal synchrony within alpha oscillations and neurofibrillary tangle (NFT) density in autopsy examination, in patients with AD., Methods: In a well-characterized clinicopathological cohort of AD patients (n = 13), we quantified neuronal synchrony within alpha (8-12 Hz) and delta-theta (2-8 Hz) oscillations, using magnetoencephalography during the disease course, within six selected neocortical and hippocampal regions, including angular gyrus, superior temporal gurus, middle frontal gyrus, primary motor cortex, CA1, and subiculum, and correlated these with regional NFT density quantified at histopathological examination., Results: Abnormal synchrony in alpha, but not in delta-theta, significantly predicted the NFT density at post mortem neuropathological examination., Discussion: Reduced alpha synchrony is a sensitive neurophysiological index associated with pathological tau, and a potential network biomarker for clinical trials, to gauge the extent of network dysfunction and the degree of rescue in treatments targeting tau pathways in AD., (© 2021 the Alzheimer's Association.)

Purpose: Cerebrospinal fluid (CSF) plays an important role in the clearance system of the brain. Recently, low b-value diffusion tensor imaging (low-b DTI) has been reported to be useful in the observation of CSF flow; however, the precise flow property observed by low-b DTI has not been fully investigated. Accordingly, a mathematical framework of low-b DTI is proposed for investigating CSF and clarifying its pseudorandom flow., Theory: The framework will show that the limit of the diffusion tensor as b-value decreases to zero approximately represents the covariance of the velocity distribution of the CSF's pseudorandom flow., Methods: The low b-value diffusion tensor (DT L ) of whole-brain CSF was obtained using diffusion-weighted echo-planar imaging. Seven healthy volunteers were scanned for intersubject analysis; three of the volunteers was consecutively scanned for repeatability analysis. Obtained DT L was visually assessed by ellipsoid-representation map and was statistically evaluated by calculating mean diffusivity (MD) and fractional anisotropy (FA) in regions of interest (ROIs) representing intensive pseudorandom flow., Results: Obtained DT L consistently shows large and anisotropic diffusivity in some segments of CSF, typically the ROIs around the foramen of Monro, the aqueduct, the prepontine cistern, the middle cerebral artery, and the Sylvian fissure throughout the study. The statistical analysis shows high repeatability and consistently high MD and FA in all the ROIs for all the volunteers., Conclusion: From the viewpoint of the proposed framework, the high and anisotropic DT L in the ROIs indicates large covariance of velocity distribution, which represents intensive pseudorandom flows of CSF., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions., Materials and Methods: A total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (K w ) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades: non-lesion, moderate, and severe. In addition, the normal K w level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the K w values (K w-var ) was calculated by squaring the value of the difference between each K w value and the normal K w level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition., Results: Compared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater K w-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of K w-var . In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained., Conclusions: The DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions., Competing Interests: Declaration of competing interest The authors of this manuscript declare relationships with the following companies: “Masami Yoneyama “is currently employed by Philips Electronics Japan. The other authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purposes of this study are to assess the oxygen extraction fraction (OEF) changes on MRI-based quantitative susceptibility mapping (QSM) in systemic lupus erythematosus (SLE) patients and to determine whether QSM-OEF is associated with disease activity in SLE. We enrolled 42 SLE patients and 20 healthy subjects (HS) who had no pathologies on conventional brain MRI. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). For the measurement of QSM-OEF, QSM data were analysed using the Perfusion Mismatch Analyzer software program. Spearman's or Pearson's correlation coefficients were calculated, and independent predictors were identified through a multiple linear regression analysis. QSM-OEF was significantly higher in SLE than that in HS (51.3 ± 10.1 vs. 40.5 ± 3.7, p  < 0.001). QSM-OEF was positively correlated with SLEDAI and the presence of neuropsychiatric symptom (NPS) scores (ρ = 0.663, p  < 0.001 and ρ = 0.340, p  = 0.028). At multiple linear regression analysis, SLEDAI and NPS were independently associated with QSM-OEF (standardized β = 0.426, p  = 0.016 and standardized β = 6.148, p  = 0.029). In the SLE patients, QSM-OEF is associated with disease activity, which might predict an increased risk of stroke in SLE.

We evaluated 3D pseudo-continuous arterial spin labeling (pCASL) using turbo spin echo with a pseudo-steady-state (PSS) readout in comparison with the other major readout methods of 3D spiral and 2D echo-planar imaging (EPI). 3D-PSS produced cerebral blood flow (CBF) values well correlated to those of the 3D spiral readout. By visual evaluation, the image quality of 3D-PSS pCASL was superior to that of 2D-EPI. The 3D-PSS technique was suggested useful as pCASL readout.

Purpose: The feasibility of steady-state sequences for 17 O imaging was evaluated based on a kinetic analysis of the brain parenchyma and cerebrospinal fluid (CSF)., Materials and Methods: The institutional review board approved this prospective study with written informed consent. Dynamic 2D or 3D steady-state sequences were performed in five and nine participants, respectively, with different parameters using a 3T scanner. During two consecutive dynamic scans, saline was intravenously administered for control purposes in the first scan, and 20% 17 O-labeled water (1 mL/Kg) was administered in the second scan. Signal changes relative to the baseline were calculated, and kinetic analyses of the curves were conducted for all voxels. Region of interest analysis was performed in the brain parenchyma, choroid plexus, and CSF spaces., Results: Average signal drops were significantly larger in the 17 O group than in the controls for most of the imaging parameters. Different kinetic parameters were observed between the brain parenchyma and CSF spaces. Average and maximum signal drops were significantly larger in the CSF spaces and choroid plexus than in the brain parenchyma. Bolus arrival, time to peak, and the first moment of dynamic curves of 17 O in the CSF space were delayed compared to that in the brain parenchyma. Significant differences between the ventricle and subarachnoid space were also noted., Conclusion: Steady-state sequences are feasible for indirect 17 O imaging with reasonable temporal resolution; this result is potentially important for the analysis of water kinetics and aquaporin function for several disorders.

Background: Respiration-induced phase shift affects B 0 /B 1 mapping repeatability in parallel transmission (pTx) calibration for 7T brain MRI, but is improved by breath-holding (BH). However, BH cannot be applied during long scans.+ mapping repeatability in parallel transmission (pTx) calibration for 7T brain MRI, but is improved by breath-holding (BH). However, BH cannot be applied during long scans., Purpose: To examine whether interleaved acquisition during calibration scanning could improve pTx repeatability and image homogeneity., Study Type: Prospective., Subjects: Nine healthy subjects., Field Strength/sequence: 7T MRI with a two-channel RF transmission system was used., Assessment: Calibration scanning for B 0 /B 1 + mapping was performed under sequential acquisition/free-breathing (Seq-FB), Seq-BH, and interleaved acquisition/FB (Int-FB) conditions. The B 0 map was calculated with two echo times, and the B 1 + map was obtained using the Bloch-Siegert method. Actual flip-angle imaging (AFI) and gradient echo (GRE) imaging were performed using pTx and quadrature-Tx (qTx). All scans were acquired in five sessions. Repeatability was evaluated using intersession standard deviation (SD) or coefficient of variance (CV), and in-plane homogeneity was evaluated using in-plane CV., Statistical Tests: A paired t-test with Bonferroni correction for multiple comparisons was used., Results: The intersession CV/SDs for the B 0 /B 1 + maps were significantly smaller in Int-FB than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The intersession CVs for the AFI and GRE images were also significantly smaller in Int-FB, Seq-BH, and qTx than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The in-plane CVs for the AFI and GRE images in Seq-FB, Int-FB, and Seq-BH were significantly smaller than in qTx (Bonferroni-corrected P < 0.01 for all)., Data Conclusion: Using interleaved acquisition during calibration scans of pTx for 7T brain MRI improved the repeatability of B 0 /B 1 + mapping, AFI, and GRE images, without BH., Level of Evidence: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background and Purpose: Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy., Materials and Methods: Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images., Results: Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively., Conclusions: Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy., (© 2017 by American Journal of Neuroradiology.)

Purpose: To establish an optimized sequence design for fast acceleration of arterial spin labeling (ASL)-based time-resolved magnetic resonance angiography (MRA) by acquisition of control and labeled images in the same shot (fast ACTRESS) and a scan time of <1min, for the evaluation of intracranial vessels., Materials and Methods: Ten healthy volunteers with no unilateral symptomatic arterial stenosis, who underwent 3-tesla MRI, were investigated. Imaging parameters for the fast ACTRESS sequence were set with an acquisition time of 45s. During post-processing, the first phase in the multi-phase readout, which was defined as the control image, was subtracted from each of the other phases. Thus, four-dimensional (4D)-MRA images of each phase were obtained. The maximum intensity projection was used for the reconstruction of 4D-MRA images and time-to-signal intensity curves (TIC) obtained for each vessel. The area under the curve (AUC), peak time, and maximum signal intensity were obtained from TIC. The different labeling types were broadly divided into six groups: L1, L2, L3, L4, L5, and L6 according to the actual number of labeling pulse., Results: A total of 5040 regions of interest were evaluated. The peak SI of L3, except for those in the A2 segment of the anterior cerebral artery, was significantly higher than that of L5. However, there were no significant differences between L4 and L5. Although the AUCs of L3 and L4 for anterior circulation were relatively higher than that of the other subgroups, the AUC of L3 was significantly higher than that of L4., Conclusion: The fast ACTRESS was optimized and indicated that the labeling type of L3 was the most appropriate for the well visualization of intracranial arteries. The fast ACTRESS sequence was useful to acquire well-delineated images of intracranial vessels in ˂1min., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Great variations in the size, shape, color, feather structure and behavior are observed among fowl breeds. Because many types of domestic fowls have been bred for various purposes, they are ideal to assess the relationship between brain morphology and avian biology. However, little is known about changes in brain shape that may have occurred during fowl domestication. We analyzed the brains of red jungle fowl and domestic fowl to clarify differences in the brain shape between these breeds, as well as the shape changes associated with size enlargement using three-dimensional geometric morphometrics. Principal component and multivariate regression analyses showed that ventrodorsal bending, anteroposterior elongation and width reduction were significantly correlated with brain size. According to the size-dependent analysis, the red jungle fowl brain has an intermediate shape between the brain of young broilers and that of large domestic fowl and adult broilers. After the size effect is removed, geometric morphometric analyses show that the brain of red jungle fowl is different from that of domestic fowl, with large round cerebral hemispheres. Significant correlations exist between the skull length and brain volume among fowl, while the brain volume relative to the skull length is distinctly larger in red jungle fowl compared with domestic fowl. The distinct brain shape and increased relative brain size of red jungle fowl may be driven by the presence of large, rounded cerebral hemispheres., (© 2017 Anatomical Society.)

Purpose: The B0 and B1+ maps required for calculation of the radiofrequency (RF) pulse of parallel transmission (pTx) are obtained in calibration scans; however, they may be affected by respiratory motion. We aimed to compare the reproducibility of B0 and B1+ maps and gradient echo (GRE) images of the brain scanned with pTx at 7T between free-breathing (FB) and breath-holding (BH) conditions during the calibration scan., Methods: Nine healthy volunteers were scanned by 7T MRI using a two-channel quadrature head coil. In the pTx calibration scans performed with FB and BH, the B0 map was obtained from two different TE images and the B1+ map was calculated by the Bloch-Siegert method. A GRE image (gradient-recalled-acquisition in steady state) was also obtained with RF shimming and RF design of pTx with spoke method, as well as quadrature transmission (qTx). All the scans were repeated over five sessions. The reproducibility of the B0 and B1+ maps and GRE image was evaluated with region-of-interest measurements using inter-session standard deviation (SD) and coefficient of variation (CV) values. Intensity homogeneity of GRE images was also assessed with in-plane CV., Results: Inter-session SDs of B0 and B1+ maps were significantly smaller in BH (P < 0.01). Inter-session CVs of GRE images were significantly smaller in qTx than BH and FB (P < 0.01, both); however, the CVs of BH were significantly smaller (P < 0.01). In-plane CVs of FB and BH with RF shimming were not significantly different with qTx; however, CVs of FB and BH with RF design were significantly smaller than those of qTx (P < 0.05 and P < 0.01, respectively)., Conclusion: BH could improve the reproducibility of B0 and B1+ maps in pTx calibration scans and GRE images. These results might facilitate the development of pTx in human brain at 7T.

The purposes of this study are to establish oxygen extraction fraction (OEF) measurements using quantitative susceptibility mapping (QSM) of magnetic resonance imaging (MRI), and to compare QSM-OEF data with the gold standard (15)O positron emission tomography (PET). Twenty-six patients with chronic unilateral internal carotid artery or middle cerebral artery stenosis or occlusion, and 15 normal subjects were included. MRI scans were conducted using a 3.0 Tesla scanner with a three-dimensional spoiled gradient recalled sequence. QSM images were created using the morphology-enabled dipole inversion method, and OEF maps were generated from QSM images using extraction of venous susceptibility induced by deoxygenated hemoglobin. Significant correlation of relative OEF ratio to contra-lateral hemisphere between QSM-OEF and PET-OEF was observed (r = 0.62, p < 0.001). The local (intra-section) correlation was also significant (r = 0.52, p < 0.001) in patients with increased PET-OEF. The sensitivity and specificity of OEF increase in QSM was 0.63 (5/8) and 0.89 (16/18), respectively, in comparison with PET. In conclusion, good correlation was achieved between QSM-OEF and PET-OEF in the identification of elevated OEF in affected hemispheres of patients with unilateral chronic steno-occlusive disease., (© The Author(s) 2015.)

During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Arterial spin labeling (ASL) methods have been widely used for evaluation of cerebral blood flow (CBF) by magnetic resonance imaging. However, ASL methods require setting of the post labeling delay (PLD) time for obtaining images. As the hemodynamic status cannot be estimated in each patient, the resultant quantitative values of blood flow may not be accurate. The multi-phase pseudo continuous arterial spin labeling (pCASL) method can be used to obtain images at various time-points. The purpose of this study was to create the transit-time maps for correcting the delayed blood flow and evaluate CBF using the transit-time maps obtained by the multi-phase pCASL method., Materials and Methods: Twelve patients who underwent both 3.0-tesla magnetic resonance imaging (MRI) and single photon emission computed tomography with iodine-123-N-isopropyl-p-iodoamphetamine (123I-IMP) were investigated. This study was approved by the institutional review board of our institution. MRI acquisitions included PLD time-fixed (1525ms) and multi-phase pCASL sequences. The transit-time maps were calculated from multi-phase pCASL images by software. The transit-time maps were applied to PLD-fixed pCASL images pixel by pixel, for calculating the CBF value corrected for peak blood transit time. Regions of interest were drawn on the brain. IMP-CBF, ASL-CBF (default and corrected) and transit time were measured for each segment., Results: Twelve patients and 264 segments were investigated. The mean IMP-CBF, ASL-CBF (default, corrected) and transit time were 28.4, 23.0, 29.6, [ml/min/100g] and 1977.5 [ms], respectively. There were no significant differences between IMP-CBF and ASL-CBF (corrected)., Conclusion: CBF values can be corrected by using the transit-time maps obtained using the multi-phase pCASL method., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background & Purpose: In this work, we demonstrate oxygen extraction fraction (OEF) measurement using 7T MRI with susceptibility-weighted imaging (SWI), in sedated and nonsedated adults., Methods: Ten healthy subjects (30.3 ± 4.5 years, 9 men, 1 woman) formed control (n = 5) and sedation groups (n = 5). Midazolam and propofol injection was administered to the same sedation group subjects during 2 different scanning sessions. Two-dimensional SPGR imaging was performed before, during, and twice after (propofol, +10, +30 minutes; midazolam, +10, +40 minutes) conscious sedation. The equivalent procedure was performed with the control group without sedation. After SWI analysis, change in OEF between scans was quantified, and parcelated ΔOEF maps were generated with 77 gray matter (GM)-containing volumes-of-interest (VOIs)., Results: Significant decreases in OEF were shown in 14 GM VOIs during sedation relative to the control group, most notably during midazolam sedation (P < .05). In contrast, no significant decrease was observed after 10 minutes and in only 4 VOIs after 40 minutes recovery., Conclusion: Significant change in ΔOEF during conscious sedation using midazolam and propofol could be measured using SWI at 7T in vivo. This may be a potentially useful approach for the noninvasive assessment of OEF in the brain on a clinical basis., (Copyright © 2014 by the American Society of Neuroimaging.)

Hyperhomocystemia has been reported to be associated with cardiovascular disease, especially stroke. The resistive index (RI) estimated by carotid ultrasound is an established variable for estimating the risk of cerebral infarction. The aim of this study was to evaluate the relationship between homocysteine concentration and carotid RI, a marker of cerebral vascular resistance in essential hypertensive patients. We measured serum total homocysteine and carotid RI in 261 patients. Multiple linear regression analysis was used to determine the association of homocysteine with carotid RI and intima media thickness (IMT). Age, sex, BMI, systolic blood pressure (SBP), homocysteine, total cholesterol, high density lipoprotein-cholesterol (HDL-C), uric acid, CRP, HbA1c, estimated glomerular filtration rate, and use of antihypertensive agents were included as independent variables. Age, sex, use of antihypertensive agents, HDL-C and homocysteine levels were shown to be significant predictors of carotid RI, but not IMT. Multiple regression analysis in men older than 65 years showed homocysteine and SBP were associated significantly with carotid RI. In elderly male patients, homocysteine was the strongest predictor of carotid RI (B = 0.0068, CI = 0.0017-0.0120, P = 0.011) in the multivariate model. In conclusion, hyperhomocysteinemia is associated with carotid RI, a surrogate marker of cerebral vascular resistance, especially in elderly men.

Purpose: To evaluate the performance and efficacy for intensity inhomogeneity correction of various sequences of the human brain in 7T MRI using the extended version of the unified segmentation algorithm., Materials: Ten healthy volunteers were scanned with four different sequences (2D spin echo [SE], 3D fast SE, 2D fast spoiled gradient echo, and 3D time-of-flight) by using a 7T MRI system. Intensity inhomogeneity correction was performed using the "New Segment" module in SPM8 with four different values (120, 90, 60, and 30 mm) of full width at half maximum (FWHM) in Gaussian smoothness. The uniformity in signals in the entire white matter was evaluated using the coefficient of variation (CV); mean signal intensities between the subcortical and deep white matter were compared, and contrast between subcortical white matter and gray matter was measured. The length of the lenticulostriate (LSA) was measured on maximum intensity projection (MIP) images in the original and corrected images., Results: In all sequences, the CV decreased as the FWHM value decreased. The differences of mean signal intensities between subcortical and deep white matter also decreased with smaller FWHM values. The contrast between white and gray matter was maintained at all FWHM values. LSA length was significantly greater in corrected MIP than in the original MIP images., Conclusions: Intensity inhomogeneity in 7T MRI can be successfully corrected using SPM8 for various scan sequences.

Rationale and Objectives: The effects of low thyroid hormone level during embryogenesis on MRI of the brain and social behaviors of hatchlings were examined using "fertilized hen's egg-embryo-chick" system., Methods and Results: Control and hatchlings treated with methimazole (20 μmol/egg), which hatched 3 days later than controls were examined. The results are as follows: 1. The MRI examination of the midsagittal section of the brain on hatch day showed that the sizes, by T1- and ADC values by diffusion-weighted images, of the optic lobe and cerebellum of the MMI-hatchlings were significantly bigger than those of the controls. 2. The social behaviors on post-hatch day 3 were based on the following tests: (a) Aggregation test: The speed of four chicks, individually isolated by cardboard barriers in a box, to make a group upon the removal of barriers. (b) Belongingness tests: The speed of a chick isolated at a corner to join the group of three chicks placed at the opposite corner. (c) Vocalization test: The number of decibel produced by a chick isolated at a corner using a sound meter. These tests demonstrated that MMI-hatchlings took longer times and had weaker vocalization than the controls, significantly. 3. Upregulation of THRβ mRNA after MMI treatment suggested that THR was necessary for cerebellum development., Conclusions: The MMI exposure during the last week of embryogenesis possibly delayed the myelination of certain brain regions and impaired the social behaviors of hatchlings. The chick embryos can be easily induced with hypothyroidism without maternal influences, and the hatchling's behaviors were analyzed using a video camera. The present method will be useful for assessing the effects of unfavorable influences during embryogenesis on social behaviors in later life.

Background: Carotid endarterectomy (CEA) might improve cognitive function. Fractional anisotropy (FA) values in the cerebral white matter derived from diffusion tensor magnetic resonance imaging (DTI) correlate with cognitive function in patients with various central nervous system diseases., Objective: To use tract-based spatial statistics to determine whether postoperative changes of FA values in the cerebral white matter derived from DTI are associated with cognitive improvement after uncomplicated CEA., Methods: In 80 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), FA values in the cerebral white matter were derived from DTI before and 1 month after surgery and were analyzed by using tract-based spatial statistics. Neuropsychological testing, consisting of the Wechsler Adult Intelligence Scale Revised, the Wechsler Memory Scale and the Rey-Osterreith Complex Figure test, was also performed preoperatively and after the first postoperative month., Results: Based on the neuropsychological assessments, 11 (14%) patients were defined as having postoperatively improved cognition. The difference between the 2 mean FA values (postoperative values minus preoperative values) in the cerebral hemisphere ipsilateral to surgery was significantly associated with postoperative cognitive improvement (95% confidence intervals, 2.632-9.877; P = .008). White matter FA values in patients with postoperative cognitive improvement were significantly increased after surgery in the whole ipsilateral cerebral hemisphere, in the contralateral anterior cerebral artery territory, and in the watershed zone between the contralateral anterior and middle cerebral arteries., Conclusion: Postoperative increase in cerebral white matter FA on DTI is associated with cognitive improvement after uncomplicated CEA.

Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to maternal swimming. In conclusion, maternal swimming exercise induced neurometabolic programing in the offspring that could be of benefit to the rats against future cerebral insults., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: To develop a map to detect changes in oxygen extraction fraction (OEF) utilizing susceptibility-weighted (SW) phase images and to correlate such changes in OEF with those in cerebral blood flow (CBF)., Materials and Methods: The study protocol was approved by the institutional review board, and written informed consent was obtained from all subjects. Eight healthy volunteers (mean age ± standard deviation, 29.8 years ± 4.6) were included in the study. Subjects were evaluated by using SW imaging, and the change in OEF was calculated by subtracting the image at baseline from one of the images obtained during six different conditions, including two at resting state, three different types of respiratory challenges, and one drug challenge with acetazolamide. Arterial spin labeling was carried out to measure CBF, while SW imaging was used to generate maps of change in OEF in response to a given condition. Statistical tests included one-way analysis of variance and Dunnett multiple comparisons to compare among the six conditions the magnitude of change from baseline for both OEF and CBF, by using the OEF change at resting state (resting 1) as the control., Results: Hyperventilation caused a statistically significant decrease in CBF (-29.3%, P < .001) and an increase in OEF (+5.2%, P < .001) compared with the control, resting 1 (+2.2%, -0.7%, respectively). Acetazolamide caused a significant increase in CBF (+39.7%, P < .001) and a decrease in OEF (-3.4%, P = .040). Carbogen also induced a CBF increase (+16.2%); however, the change was not significant (P = .090), even though OEF decreased significantly (-4.2%, P = .003). Oxygen administration resulted in a significant CBF decrease (-27.2%, P < .001), whereas OEF showed no significant difference (-0.6%, P > .99)., Conclusion: Maps of changes in OEF generated from SW phase images revealed changes in OEF corresponding to anticipated changes in CBF induced by various conditions; SW phase imaging might, in the future, be applied to evaluate cerebrovascular and other cerebral disorders in which changes in oxygen metabolism are important for planning therapeutic strategies., (© RSNA, 2011.)

Objective: The authors examined whether (1)H-magnetic resonance spectroscopy (MRS) can identify damage to the centrum semiovale in the subacute phase after CO exposure., Methods: Subjects comprised 29 adult patients who were treated with hyperbaric oxygenation within a range of 4-95 h (mean 18.7 h) after CO exposure. Subjects were classified into three groups according to clinical behaviours: Group A, patients with transit acute symptoms only; Group P, patients with persistent neurological symptoms; and Group D, patients with 'delayed neuropsychiatric sequelae' occurring after a lucid interval. MRS of bilateral centrum semiovale was performed 2 weeks after CO inhalation for all patients and 13 healthy volunteers. The mean ratios of choline-containing compounds/creatine ((mean)Cho/Cr) and N-acetylaspartate/Cr ((mean)NAA/Cr) for bilateral centrum semiovale were calculated and compared between the three CO groups and controls. Myelin basic protein (MBP) concentration in cerebrospinal fluid was examined at 2 weeks to evaluate the degree of demyelination in patients., Results: MBP concentration was abnormal for almost all patients in Groups P and D, but was not abnormal for any Group A patients. The (mean)Cho/Cr ratios were significantly higher in Groups P and D than in Group A. No significant difference in (mean)NAA/Cr ratio was seen between the three pathological groups and controls. A significant correlation was identified between MBP and (mean)Cho/Cr ratio., Conclusions: These results suggest that the Cho/Cr ratio in the subacute phase after CO intoxication represents early demyelination in the centrum semiovale, and can predict chronic neurological symptoms.

The time-to-maximum of the tissue residue function (T(max)) perfusion index has proven very predictive of infarct growth in large clinical trials, yet its dependency on simple tracer delays remains unknown. Here, we determine the dependency of computed tomography (CT) perfusion (CTP) T(max) estimates on tracer delay using a range of deconvolution techniques and digital phantoms. Digital phantom data sets simulating the tracer delay were created from CTP data of six healthy individuals, in which time frames of the left cerebral hemisphere were shifted forward and backward by up to ±5 seconds. These phantoms were postprocessed with three common singular value decomposition (SVD) deconvolution algorithms-standard SVD (sSVD), block-circulant SVD (bSVD), and delay-corrected SVD (dSVD)-with an arterial input function (AIF) obtained from the right middle cerebral artery (MCA). The T(max) values of the left hemisphere were compared among different tracer delays and algorithms by a region of interest-based analysis. The T(max) values by sSVD were positively correlated with 'positive shifts' but unchanged with 'negative shifts,' those by bSVD had an excellent positive linear correlation with both positive and negative shifts, and those by dSVD were relatively constant, although slightly increased with the positive shifts. The T(max) is a parameter highly dependent on tracer delays and deconvolution algorithm.

Introduction: We attempted to detect alterations in the cerebrospinal fluid (CSF) space in patients with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based morphometry (VBM)., Methods: We obtained sagittal volume images of the entire head by three-dimensional T1-weighted magnetic resonance imaging and compared the regional distribution of CSF in 12 patients with iNPH, 14 patients with Alzheimer's disease (AD), and 17 healthy individuals using VBM with automatically extracted CSF objects., Results: VBM demonstrated significant widening at the lateral ventricles and Sylvian fissures and narrowing of the CSF space at the high convexity/midline areas in iNPH patients, compared to the AD patients and healthy controls (p < 0.05, after correction with a false-discovery rate). In addition, the ratio of the CSF volume in the lateral ventricle/Sylvian fissure area to that in the high convexity/midline area in iNPH patients (3.9 +/- 1.2) was remarkably greater than that in AD patients (1.2 +/- 0.3) and controls (0.9 +/- 0.3; one-way ANOVA, p < 0.001; post hoc Tukey's test, p < 0.001); we could discriminate iNPH patients from those in the other two groups without any overlap, when using a cutoff level of 1.9., Conclusion: VBM using CSF objects can be used to delineate the characteristic alteration of the CSF space in iNPH patients, which has been evaluated by visual interpretation.

We review research on athletes' brains based on data obtained using non-invasive neurophysiological and neuroimaging methods; these data pertain to cognitive processing of visual, auditory, and somatosensory (tactile) stimulation as well as to motor processing, including preparation, execution, and imagery. It has been generally accepted that athletes are faster, stronger, able to jump higher, more accurate, more efficient, more consistent, and more automatic in their sports performances than non-athletes. These claims have been substantiated by neuroscientific evidence of the mechanisms underlying the plastic adaptive changes in the neuronal circuits of the brains of athletes. Reinforced neural networks and plastic changes are induced by the acquisition and execution of compound motor skills during extensive daily physical training that requires quick stimulus discrimination, decision making, and specific attention. In addition, it is likely that the manner of neuronal modulation differs among sports. We also discuss several problems that should be addressed in future studies.

Background: The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months., Methods and Design: 1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up., Discussions: The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task., Trial Registration: clinicaltrials.gov NCT00715533.

The fluid-attenuated inversion recovery imaging sequence is a widely used MRI sequence of the brain. It is an inversion recovery pulse sequence, designed to suppress signals from the cerebrospinal fluid. It is highly sensitive for detection of lesions adjacent to or within the cerebrospinal fluid, associated with T(2) prolongation or T(1) shortening. The term "hyperintense cerebrospinal fluid" is used to describe failed suppression or hyperintensity of cerebrospinal fluid on fluid-attenuated inversion recovery imaging of the brain. It is often encountered in many important pathological conditions, including subarachnoid haemorrhage, meningitis and leptomeningeal metastasis. However, certain non-pathological states in which there is no definite cerebrospinal fluid abnormality can also present with hyperintense cerebrospinal fluid. Correct interpretation of abnormalities is important to arrive at an appropriate diagnosis. This pictorial review provides fluid-attenuated inversion recovery images of hyperintense cerebrospinal fluid of the brain and describes distinguishing features, focusing on non-pathological conditions.

The fluid-attenuated inversion recovery imaging sequence is a widely used MRI sequence of the brain. It is an inversion recovery pulse sequence, designed to suppress signals from the cerebrospinal fluid. It is highly sensitive in detection of lesions adjacent to or within the cerebrospinal fluid associated with T(2) prolongation or T(1) shortening. The term "hyperintense cerebrospinal fluid" is used to describe failed suppression, or hyperintensity, of cerebrospinal fluid on fluid-attenuated inversion recovery imaging of the brain. It is often encountered in many important pathological conditions, including subarachnoid haemorrhage, meningitis and leptomeningeal metastasis. However, certain non-pathological states in which there is no definite cerebrospinal fluid abnormality can also present with hyperintense cerebrospinal fluid. Correct interpretation of abnormalities is important to arrive at an appropriate diagnosis. This pictorial review provides fluid-attenuated inversion recovery images of hyperintense cerebrospinal fluid of the brain and describes distinguishing features. Part I features pathological conditions whereas Part II focuses on non-pathological conditions.

Institutional review board approval and informed consent were obtained. The purpose was to evaluate the differences in tracer delay-induced effects of various deconvolution algorithms for computed tomographic (CT) perfusion imaging by using digital phantoms created from actual source data. Three methods of singular value decomposition (SVD) were evaluated. For standard SVD (sSVD), the delays induced significant errors in cerebral blood flow and mean transit time. In contrast, for block-circulant SVD (bSVD), these values remained virtually unchanged, whereas for delay-corrected SVD (dSVD), mild changes were observed. bSVD was superior to sSVD and dSVD for avoiding the tracer delay-induced effects in CT perfusion imaging.

Purpose: To evaluate the efficacy of susceptibility weighted imaging (SWI) in comparison to standard T1 weighted postgadolinium contrast (T1-Gd) MRI in patients with Sturge-Weber Syndrome (SWS)., Materials and Methods: Twelve children (mean age, 5.6 years) with the diagnosis of SWS and unilateral hemispheric involvement were recruited prospectively and examined with high resolution three dimensional SWI and conventional T1-Gd. Both SWI and T1-Gd images were evaluated using a four-grade scoring system according to six types of imaging findings (enlargement of transmedullary veins, periventricular veins, and choroid plexus, as well as leptomeningeal abnormality, cortical gyriform abnormality, and gray matter/white matter junctional abnormality). The scores of SWI versus T1-Gd images were then compared for each type of abnormality., Results: SWI was superior to T1-Gd in identifying the enlarged transmedullary veins (P = 0.0020), abnormal periventricular veins (P = 0.0078), cortical gyriform abnormalities (P = 0.0020), and gray matter/white matter junction abnormalities (P = 0.0078). Conversely, T1-Gd was better than SWI in identifying enlarged choroid plexus (P = 0.0050) and leptomeningeal abnormalities (P = 0.0050)., Conclusion: SWI can provide useful and unique information complementary to conventional contrast enhanced T1 weighted MRI for characterizing SWS. Therefore, SWI should be integrated into routine clinical MRI protocols for suspected SWS., ((c) 2008 Wiley-Liss, Inc.)

We investigated the difference between brain activities in speeded and precisely timed responses to identical visual stimulus using fMRI. Stimulus used was a row of seven light-emitting diodes (LEDs) lightened up one after another with constant speed within a trial but with various speeds between trials. Subjects were asked to execute finger-thumb tapping with the right hand in response to the onset of the first LED light in the reaction time (RT) task and in anticipation of the onset of the last (i.e., seventh) LED light in the timing task. In control condition, they were asked to passively view the stimulus without motor response. Results showed that various movement-related areas including contralateral cingulate motor cortex were commonly activated for both tasks relative to the control condition, suggesting these structures are involved in general perception and response execution rather than specific function for speeded or precisely timed responses. In the RT task, the presupplementary motor area extending to the cingulate sulcus was activated more strongly than in the timing task probably to focus attention to the onset of the first LED light unpredictably presented after random foreperiods. The lateral occipital area extending to the temporo-parieto-occipital junction was activated more strongly in the timing task than in the RT task; the same area was deactivated in the RT task relative to the control condition. Auditory-related areas were also deactivated in the both tasks. This inter- and intramodal task-specific modification including deactivation underscores significance of the context for perception and action and can have an important role in dexterous or skilled performance., (Copyright 2004 Elsevier Inc.)

Background and Purpose: Blood vessels are usually conspicuous on dynamic CT perfusion images. The presence of large vessels may lead to overestimation of the quantitative value of cerebral blood flow (CBF). We evaluated the efficacy of the vascular-pixel elimination (VPE) method in quantitative CT perfusion imaging, in comparison with positron emission tomography (PET)., Methods: Five healthy volunteers underwent CT perfusion and PET studies. A four-channel multi-detector row CT scanner was used. Dynamic cine scanning was performed after bolus injection of an intravenous contrast agent. CT-CBF was calculated by the central volume principle and deconvolution method. PET was performed after infusion of (15)O-labeled water. PET-CBF was calculated by using a nonlinear least squares method. Average CBF values of the whole section, gray matter, and white matter with both CT and PET were compared after image registration. The comparison was performed with and without VPE. In the VPE method, the vascular pixels were defined by the cerebral blood volume value of the pixel. The threshold of VPE was changed from 5 to 20 mL/100 g. Pixel-by-pixel correlation between CT-CBF and PET-CBF and linear regression analysis were also performed., Results: Without VPE, CT-CBF was overestimated in all subjects. As the VPE threshold decreased, CT-CBF decreased and the correlation coefficient increased. The best correlation was observed at a VPE threshold of 8 mL/100 g in four of the five subjects. Average CT-CBF values, without VPE, of the whole section, gray matter, and white matter were 59.01, 66.73, and 42.53 mL/100 g/min, respectively. With VPE (threshold, 8 mL/100 g), average CT-CBF values of the whole section, gray matter, and white matter were 45.56, 52.75, and 30.38, respectively. The corresponding PET-CBF values were 46.86, 50.89, and 38.20 mL/100 g/min, respectively., Conclusion: Vascular pixels should be excluded from the calculation of CT-CBF to avoid overestimation of the CBF values. If vascular pixels are excluded, CBF calculation with CT perfusion imaging is considerably accurate.

The concentrations of ethanol in peripheral blood, subdural hematomas and various regions of the brain were determined 1, 2, 4, and 6 h after the induction of a hemorrhage into a subdural space in the right temple of rabbits. The concentrations were compared to cases of intravenous administration of ethanol-free i.v. fluid. Concentrations of ethanol in the subdural hematomas gradually decreased to correspond to those in the peripheral blood. The influence of an intravenous infusion of ethanol-free i.v. fluid was not observed. Concentrations in the brain of the right temporal, parietal and frontal lobes were high and those in the right temporal lobe were maintained during the 6 h of our experiment. Therefore, to determine if a human victim was under the influence of ethanol at the time of injury, we recommend that brain concentrations of ethanol be determined. This is apparently the first study to confirm that the estimation of ethanol in the brain provides a more accurate determination of how much ethanol had been ingested.

Previously, we have identified 200 cDNA fragments as antidepressant related genes/ESTs. In this study, using these cDNAs, we developed our original cDNA microarray for rapid secondary screening of candidate genes as the novel therapeutic targets. With this microarray, we found that the expression of a novel gene, ADRG34, was significantly increased in rat hippocampus which had been chronically treated with a selective serotonin reuptake inhibitor antidepressant, sertraline. RT-PCR analysis also demonstrated the induction of ADRG34 at mRNA levels in rat hippocampus and the frontal cortex. This cDNA encoded 685 amino acid residues containing a RING-H2 finger motif at the carboxy-terminal. Sequence analysis of ADRG34 with the EMBL/GenBank database showed significant homology to mouse and human kf-1 gene. Our data suggest that ADRG34, a possible rat homologue of kf-1, may be one of the common functional molecules induced after chronic antidepressant treatment., (Copyright 2000 Academic Press.)

Brain death was diagnosed by analyzing drug distribution in human tissues. Concentrations of diazepam and phenobarbital in human tissues, administered therapeutically to 3 patients in a critical condition, were determined by gas chromatography with a nitrogen phosphorus detector and gas chromatography-mass spectrometry. In 2 patients administered drugs while the brain was functioning, drug concentrations in the brain were high compared with those in the other tissues. In the other patient given the drugs after vital signs of the brain ceased, the level of drugs in the brain was much lower than seen in other tissues. We propose that a forensic diagnosis of patients who are brain dead can be made by comparing the concentrations of drugs in the brain given at the time of critical condition with concentration of these agents in other tissues. When cerebral function ceased can be roughly estimated by the variable distribution patterns of drugs and time of administration of these drugs.