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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by a diverse range of debilitating symptoms including autonomic, immunologic, and cognitive dysfunction. Although neurological and cognitive aberrations have been consistently reported, relatively little is known regarding the regional cerebral blood flow (rCBF) in ME/CFS. In this study, we studied a cohort of 31 ME/CSF patients (average age: 42.8 ± 13.5 years) and 48 healthy controls (average age: 42.9 ± 12.0 years) using the pseudo-continuous arterial spin labeling (PCASL) technique on a whole-body clinical 3T MRI scanner. Besides routine clinical MRI, the protocol included a session of over 8 min-long rCBF measurement. The differences in the rCBF between the ME/CSF patients and healthy controls were statistically assessed with voxel-wise and AAL ROI-based two-sample t-tests. Linear regression analysis was also performed on the rCBF data by using the symptom severity score as the main regressor. In comparison with the healthy controls, the patient group showed significant hypoperfusion (uncorrected voxel wise p ≤ 0.001, FWE p ≤ 0.01) in several brain regions of the limbic system, including the anterior cingulate cortex, putamen, pallidum, and anterior ventral insular area. For the ME/CFS patients, the overall symptom severity score at rest was significantly associated with a reduced rCBF in the anterior cingulate cortex. The results of this study show that brain blood flow abnormalities in the limbic system may contribute to ME/CFS pathogenesis.

Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN ar-chitecture for the detection of abnormal cervical cells in cytology images from cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cer-vical image dataset of “Digital Human Body" Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using tra-ditional computer-vision techniques, 6-9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear.

Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals’ current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.

To investigate the impact of adult age on the brain functional connectivity, whole-brain resting-state functional magnetic resonance imaging (R-fMRI) data were acquired on a 3T clinical MRI scanner in a cohort of 227, right-handed, native Swedish-speaking, healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). The dataset is mainly consisted of a younger (18-30 years old n=124, males/females=51/73) and elderly adult (n=76, 60-76 years old, males/females=35/41) subgroups. The dataset was analyzed using a new data-driven analysis (QDA) framework. With QDA two types of threshold-free voxel-wise resting-state functional connectivity (RFC) metrics were derived: the connectivity strength index (CSI) and connectivity density index (CDI), which can be utilized to assess the brain changes in functional connectivity associated with adult age. The dataset can also be useful as a reference to identify abnormal changes in brain functional connectivity resulted from neurodegenerative or neuropsychiatric disorders.

PurposeThe objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC).MethodsWhole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index (CSI) and connectivity density index (CDI) utilizing the convolutions of the cross-correlation (CC) histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately.ResultsWith the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyrus (MFG), posterior cingulate cortex (PCC), right insula and inferior parietal lobule (IPL) of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: 1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; 2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; 3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age.ConclusionThe proposed QDA framework can produce threshold-free, voxel-wise analysis of R-fMRI data the RFC metrics. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging.HighlightsA quantitative data-driven analysis (QDA) framework was proposed to analysis resting-state fMRI data.Threshold-free resting-state functional connectivity (RFC) metrics were derived to assess brain changes with adult age.Separate assessment of the positive and negative correlations improve sensitivity of the RFC metrics.The posterior cingulate and right insula cortices are anti-correlated and tend to manifest declines in both the negative and positive connectivity strength with adult age.Negative connectivity strength enhances with adult age in sensorimotor network.

Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ∼30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

Background Amyotrophic Lateral Sclerosis (ALS) is characterized by a spectrum of phenotypes, but a few study addressed the presence of parkinsonian (PK) symptoms. Aim of our study was to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates. Methods A consecutive series of ALS patients were enrolled and prospectively followed for two years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and 18F-FDG-PET. ALS-PK patients underwent 123I-ioflupane SPECT Results Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factor. 123I-ioflupane SPECT was normal in all but two ALS-PK patients. At 18F-FDG-PET, ALSPK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule. Conclusions In our study about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as complex multisystem disease.

Compressed Sensing Magnetic Resonance Imaging (CS-MRI) is an effective technique to reduce MRI data acquisition time. There is currently growing interest in using Alternating Direction Method of Multiplier (ADMM) for CS-MRI reconstruction. In this paper, we propose a flexible plug-and-play framework to incorporate the block matching 3D (BM3D) denoising algorithm as prior into the plug-and-play ADMM reconstruction procedure for CS-MRI reconstruction, termed BM3D Plug-and-play ADMM (BPA) method. We investigated the performance of the proposed BPA method for the construction of highly under-sampled MRI data of two different sampling masks. Compared with other widely used CS-MRI reconstruction methods, such as, PANO, BM3D-IT, BM3D-MRI and BM3D-AMP-MRI, the proposed framework can reconstruct highly under-sampled CS-MRI data with improved gains in Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index Measure (SSIM).

Hierarchical clustering is a useful data-driven approach to classify complex data and has been used to analyze resting-state functional magnetic resonance imaging (fMRI) data and derive functional networks of the human brain at very large scale, such as the entire visual or sensory-motor cortex. In this study, we developed a voxel-wise, whole-brain hierarchical clustering framework to perform multi-stage analysis of group-averaged resting-state fMRI data in different levels of detail. With the framework we analyzed particularly the somatosensory motor and visual systems in fine details and constructed the corresponding sub-dendrograms, which corroborate consistently with the known modular organizations from previous clinical and experimental studies. The framework provides a useful tool for data-driven analysis of resting-state fMRI data to gain insight into the hierarchical organization and degree of functional modulation among the sub-units.

This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. De 2 första författarna delar förstaförfattarskapet.

The internal parking characteristic and parking mode and layout influence factors are analyzed to solve the parking problems in the old residential quarter, and then based on which the principle and layout of the parking mode and layout of parking are researched, and then the forms of parking mode and layout of parking in the old residential quarter are proposed to solve the parking problems in the old residential quarter

The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel-based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS).

Numerous studies over the past decade have shown that magnetic resonance imaging (MRI) has great potential for detecting and quantifying the distribution of iron in the body. With MRI, tissue iron is indirectly identified by the paramagnetic effects of iron on the shortening of water proton MR relaxation times. However, these effects are complex and involve a number of factors, such as tissue hydration, distribution of iron and water within the tissue, and the amount of iron loading within the iron storage molecules. A coherent understanding of how these factors influence the MRI signal is still lacking. The dependence on experimental conditions, such as magnet field strength, pulse sequences, and data acquisition parameters, further complicates iron quantification with MRI. To date, there is no generally accepted MRI approach available for clinical application. In this review, we first explain the basic MR relaxation mechanisms underlying the detection of iron with MRI. We then review the literature on empirical MRI studies of hepatic iron. Finally, we summarize the critical issues that need to be addressed to develop MRI techniques for non‐invasive iron detection in the body.

We report acute and follow-up diffusion- and perfusion-weighted MRI (DWI, PWI) findings in a patient with a prolonged reversible ischaemic neurological deficit. PWI 12 h after the patient was last seen to be without symptoms revealed a large perfusion deficit in the left posterior MCA territory with a relatively inconspicuous and much smaller abnormality on DWI. Follow-up showed resolution of abnormalities on both DWI and PWI, and conventional MRI was normal, apart from a very slight abnormality, visible only on FLAIR images, at the centre of the initially DWI-positive region. These findings demonstrate the utility of PWI when be used in combination with DWI to investigate the pathophysiology of transient ischemic syndromes.

The effect of changes in baseline regional cerebral blood flow (rCBF) values on the cerebral blood flow response during neuronal activation was studied with functional magnetic resonance imaging (fMRI). Using a breath-holding challenge as a hypercapnic stimulus, rCBF alterations during photic stimulation under normo- and hypercapnia were determined in nine volunteers. With breath-holding, baseline rCBF in areas corresponding to the visual cortex significantly increased from 54 ± 5 ml/100 g/min to 85 ± 9 ml/100 g/min (P < 0.001). Despite this significant change in baseline flow values, the rCBF increase during visual stimulation was very similar under normo- and hypercapnic conditions (28 ± 8 ml/100 g/min versus 26 ± 8 ml/100 g/min, respectively). This study supports the notion that within wide physiologic variations, task-induced cerebral blood flow changes are independent of baseline rCBF values. J. Magn. Reson. Imaging 2000;12:757–762. © 2000 Wiley-Liss, Inc.

The aim of the study was to assess the relative number of bone trabeculae in different orientations by using magnetic inhomogeneity measurements by MR imaging. Twelve defatted human vertebrae (L2-L4) were studied by MR imaging and CT. In the MR measurements the reversible transaxial decay rate, R2', was determined using the GESFIDE sequence. The relative contribution to R2' of bone trabeculae oriented along the x (R2'x), y (R2'y) and z (R2'y) axes was assessed, by rotation of the specimen in the magnetic field. The results were validated by CT measurements of trabecular structure at a resolution of 0.2 x 0.2 x 1 mm. using custom-made software. R2' ranged from 4.9 to 32 s-1. After separation, theoretical R2'x ranged from 2.3 to 10.7 s-1, R2'y ranged from 2.6 to 14.0 s-1 and R2'z ranged from 4.7 to 17.9 s-1. The number of bone trabeculae per millimeter identified in axial CT images ranged from 0.15 to 0.38 and from 0.039 to 0.22 per millimeter in sagittal images. The difference between axial and sagittal CT images was statistically significant and due to anisotropic voxels. The correlation between R2' and the number of bone trabeculae per millimeter was statistically significant (r = 0.83, p < 0.001 for x orientation: r = 0.63 for y orientation, and r = 0.59 for z orientation, p < 0.05 for both). The relative amount of bone trabeculae in different orientations can be assessed in vitro using R2' measurements.

BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating inversion recovery) imaging techniques were used to investigate the oxygenation and hemodynamic responses of human brain during repeated challenges of breath holding and prolonged single breath holding. The effects of different breathing techniques on BOLD and FAIR image contrasts were carefully examined. With a periodic breath-holding paradigm of 30 s, global changes in gray matter were observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1-4% relative signal intensity increases, while FAIR images demonstrated relative cerebral blood flow (CBF) increase up to 30-70%. The activated pixels depicted in FAIR images were about three times less than those seen in T*2-weighted images. With prolonged breath holding, it was observed that signal intensities in T*2-weighted and FAIR images were dependent on the breathing techniques used. Breath holding after expiration gave rise to immediate signal intensity increases in T*2-weighted and FAIR images, whereas breath holding performed after deep inspiration signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and FAIR signals showed a transient decrease before rising above the baseline level.

Diffusion-weighted MRI based on single-shot echo planar imaging (EPI) has been established as a useful tool to study acute cerebral ischemia. However, EPI is prone to spatial distortion and ghosting artifacts. In this study, a pulse sequence for diffusion-weighted imaging (DWI) based on a single-shot spiral readout is presented. Using this technique, multislice apparent diffusion coefficient (ADC) mapping can be performed in an interleaved fashion with the same temporal resolution as EPI. Other advantages associated with ADC mapping by the single-shot spiral method include minimal ghosting artifacts, reduced spatial distortion, and capability to scan in arbitrary planes. This technique has been successfully tested in five normal volunteers and three stroke patients. It has been demonstrated that the single-shot spiral technique is capable of producing high quality DWI and ADC trace maps (128 x 128) in the axial, sagittal, and coronal planes, which facilitate clinical diagnosis.

Background and Purpose —Recently, noninvasive MRI methods have been developed that are now capable of detecting and mapping regional hemodynamic responses to various stress tests, which involve the use of vasoactive substances such as acetazolamide or inhalation of carbon dioxide. The aim of this study was to assess regional cerebral blood oxygenation changes during breath holding at 1.5 T. Methods —In 6 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 10 minutes during alternating periods of breath holding and normal breathing at 40-second intervals after inspiration, at 30-second intervals after expiration, and at 18 seconds after expiration. To quantify the relative signal changes, 2.5-minute baseline image sampling with normal breathing was carried out. Results —Repeated challenges of breath holding of various durations induced an overall rise in blood oxygen level–dependent (BOLD) signal intensities. In general, BOLD signal intensity increases were greatest in gray matter and nonsignificant in white matter. Depending on the breath-holding duration and techniques, BOLD signal intensity increases of all activated pixels varied from 0.8% to 3.5%. Conclusions —The present study demonstrates that cerebral blood oxygenation changes during breath holding can be detected by means of fMRI at 1.5 T. The breath-holding test, a short and noninvasive method to study cerebral hemodynamics with fMRI, could become a useful alternative to the acetazolamide or CO 2 test.

Diffusion-weighted MR imaging has been used in studies on experimental animal models and on patients with acute cerebral ischemia. Compared with CT and conventional MR techniques, diffusion-weighted imaging can provide earlier and more precise detection of the location and the extent of an ischemic lesion during the critical first few hours after the onset of stroke Quantitative apparent diffusion coefficient (ADC) mapping of the brain water can also be carried out by recording a series of diffusion-weighted images with different amplitudes of the displacement encoding gradients. ADC maps can provide important information about the extra- and intracellular water homeostasis. ADC reduction of the tissue water is one of the early signals of the pathophysiological cascade resulting from ischemic tissue injury. Diffusion MR imaging has become a valuable tool in stroke research. It may also prove a valuable tool in monitoring the efficiency of therapeutic effects in stroke patients It is our intention to provide an overview of the recent development in this area with emphasis on the diffusion-weighted MR techniques, and to discuss the possible underlying biophysical mechanisms responsible for the contrast of diffusion-weighted imaging

Background Biochemical changes in the cerebrospinal fluid (CSF) could reflect pathophysiological processes in Alzheimer's disease (AD). However, it is still not clear how these processes correlate with grey matter (GM) volume and microstructural changes in the brain. Objective To assess the relationship between CSF biomarkers and structural brain changes in AD. Design and setting Cross-sectional study in a memory clinic-based sample. Subjects A total of 78 subjects were included in the study: 22 with subjective cognitive impairment (SCI), 35 with mild cognitive impairment (MCI) and 21 with AD. Main outcome measures Voxel-wise correlations between CSF biomarkers, including β-amyloid42 (Aβ42), tau phosphorylated at position threonine 181 and total tau protein, and GM volume, self-diffusion fractional anisotropy (FA) and mean diffusivity (MD) maps using voxel-based morphometry and tract-based spatial statistical analyses. FA and MD maps were obtained using diffusion tensor imaging. Results In the whole sample (patients with SCI, MCI and AD), there was positive correlation between GM volume and Aβ42 concentration, and negative correlation with total tau protein. Higher FA was only related to higher concentration of Aβ42. MD showed significant negative correlation with Aβ42 and positive correlation with T-tau levels. The majority of brain regions with significant correlation with CSF biomarkers overlapped with the default mode network and extended to the adjacent white matter. Conclusions Early AD pathological changes can be detected with voxel-based morphometric analysis and diffusion tensor imaging measurements. Furthermore, there was an association between CSF AD biomarkers and structural brain changes in areas related to the default mode network.

Introduction Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for pharmaceutical magnetic resonance imaging (phMRI) studies to investigate how drugs change the cerebral perfusion status and further, neuronal activity. Materials and method Twelve healthy normal male volunteers participated in the study which was based on a double blinded design. Six subjects were randomly selected to receive a single oral dose of 20 mg d -amphetamine and six were given placebo. Perfusion measurements by pseudo-continuous ASL (pCASL) technique were repeatedly performed at 10 different time points with a 3T clinical MRI scanner during a 10 hour period after dose together with physiologic data and blood sample collections. The dynamic changes in cerebral perfusion in response to the plasma concentration variations of d -amphetamine were analyzed at voxel-level and for regions of interest. Results Compared to the placebo group a 20% reduction in cerebral blood flow (CBF) was observed in gray matter for the subjects that received d -amphetamine. The most significant reduction of regional CBF (rCBF) was detected in the basal ganglia, frontal region and insular cortex using voxel based analysis. A relation between d -amphetamine exposure and CBF response was found using PK/PD modeling, which predicted on average a 15% decrease of the CBF in gray matter at a plasma concentration of 30 ng/ml. Conclusion In this study we have demonstrated that repeated perfusion measurements by pCASL technique was sufficiently robust to differentiate the neurological response between the groups that received d -amphetamine and placebo. Quantitative and repetitive CBF measurements can be used for PK/PD modeling of CNS drug responses in humans.

Background Reduced white matter integrity, as indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD), has been related to poorer perceptual speed (PS) performance. As the e4 allele has been associated with lower white matter integrity in old age, this represents a potential mechanism through which APOE may affect PS. Objective To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia. Method Participants were selected from the population-based SNAC-K study. After excluding persons with dementia, preclinical dementia, and other neurological disorders, 652 persons (age range 78–90) were included in the study, of which 89 had data on diffusion tensor imaging (DTI). We used structural equation modeling to form seven latent white matter factors (FA and MD) and one latent PS factor. Separate analyses were performed for FA and MD and mediational analyses were carried out for tracts where significant associations were observed to both APOE and PS. Results APOE was associated with white matter microstructure in 2 out of 14 tracts; e4 carriers had significantly lower FA in forceps major and higher MD in the cortico-spinal tract. Allowing the white matter microstructure indicators in these tracts to mediate the association between APOE and PS resulted in a markedly attenuated association between these variables. Bootstrapping statistics in the subsample with DTI data (n = 89) indicated that FA in forceps major significantly mediated the association between APOE and PS (indirect effect: -0.070, 95% bias corrected CIs -0.197 to -0.004). Conclusion Lower white matter integrity may represent one of several mechanisms through which APOE affects PS performance in elderly persons free of dementia and preclinical dementia.

MRI at high magnetic field strength potentially allows for an increase in resolution and image contrast. The gains are particularly dramatic for T 2 * -weighted imaging, which is sensitive to susceptibility effects caused by a variety of sources, including deoxyhemoglobin, iron concentration, and tissue microstructure. On the other hand, the acquisition of high quality whole brain MRI at high field is hampered by the increased inhomogeneity in B o and B 1 fields. In this report, high-resolution gradient echo MRI was performed using an 8-channel detector to obtain T 2 * -weighted images over large brain areas. The high SNR achieved with the multi-channel array enabled T 2 * -weighted images of the brain with an unprecedented spatial resolution of up to 0.2 × 0.2 × 0.5 mm 3 . This high resolution greatly facilitated the detection of microscopic susceptibility effects. In addition to the expected contrast between gray, white matter, cerebral spinal fluid, and veins, a large degree of heterogeneity in contrast was observed throughout the white matter of normal brain. The measured T 2 * values in white matter varied as much as 30% with some of the variation apparently correlating with the presence of large fiber bundles.

Purpose To develop a multishot magnetic resonance imaging (MRI) pulse sequence and reconstruction algorithm for diffusion-weighted imaging (DWI) in the brain with submillimeter in-plane resolution. Materials and Methods A self-navigated multishot acquisition technique based on variable-density spiral k-space trajectory design was implemented on clinical MRI scanners. The image reconstruction algorithm takes advantage of the oversampling of the center k-space and uses the densely sampled central portion of the k-space data for both imaging reconstruction and motion correction. The developed DWI technique was tested in an agar gel phantom and three healthy volunteers. Results Motions result in phase and k-space shifts in the DWI data acquired using multishot spiral acquisitions. With the two-dimensional self-navigator correction, diffusion-weighted images with a resolution of 0.9 × 0.9 × 3 mm3 were successfully obtained using different interleaves ranging from 8–32. The measured apparent diffusion coefficient (ADC) in the homogenous gel phantom was (1.66 ± 0.09) × 10−3 mm2/second, which was the same as measured with single-shot methods. The intersubject average ADC from the brain parenchyma of normal adults was (0.91 ± 0.01) × 10−3 mm2/second, which was in a good agreement with the reported literature values. Conclusion The self-navigated multishot variable-density spiral acquisition provides a time-efficient approach to acquire high-resolution diffusion-weighted images on a clinical scanner. The reconstruction algorithm based on motion correction in the k-space data is robust, and measured ADC values are accurate and reproducible. J. Magn. Reson. Imaging 2005;21:468–475. Published 2005 Wiley-Liss, Inc.

In order to keep subscribers up-to-date with the latest developments in their field, John WileySons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books, Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5 Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver, Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

In this study the noise sensitivity of various anisotropy indices has been investigated by Monte-Carlo computer simulations and magnetic resonance imaging (MRI) measurements in a phantom and 5 healthy volunteers. Particularly, we compared the noise performance of indices defined solely in terms of eigenvalues and those based on both the eigenvalues and eigenvectors. It is found that anisotropy indices based on both eigenvalues and eigenvectors are less sensitive to noise, and spatial averaging with neighboring pixels can further reduce the standard deviation. To reduce the partial volume effect caused by the spatial averaging with neighboring voxels, an averaging method in the time domain based on the orientation coherence of eigenvectors in repeated experiments has been proposed.

Background and Purpose —Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) have been used increasingly in recent years to evaluate acute stroke in the emergency setting. In the present study, we compared DWI and PWI findings in acute stroke patients with and without severe extracranial internal carotid artery (ICA) disease. Methods —Twenty-seven patients with nonlacunar ischemic stroke were selected for this analysis. DWI, PWI, and conventional MRI were performed in all patients within 24 hours of symptom onset and after 1 week. To exclude patients with partial or complete reperfusion, we included only patients with a PWI deficit larger than the DWI lesion. Severe ICA disease (>70% stenosis) was present unilaterally in 9 and bilaterally in 2 patients. Acute DWI lesion volume, the size of the acute PWI/DWI mismatch, and final infarct size (on T2-weighted images) were determined. Results —The PWI/DWI mismatch was significantly larger in patients with severe ICA disease than in patients without extracranial carotid stenosis, both when time-to-peak and mean transit time maps ( P P =0.14), despite the larger PWI/DWI mismatch, and final infarct size was smaller in the stenosis group ( P Conclusions —In most acute stroke patients with severe ICA stenosis, a considerably smaller fraction of the total PWI/DWI mismatch is at risk than in patients without carotid disease.

Using functional magnetic resonance imaging techniques CBF and oxygenation changes were measured during sustained checkerboard stimulation in 38 right-handed healthy volunteers (18 men and 20 women). The average blood oxygenation level dependent (BOLD) contrast technique signal intensity change was 1.67 ± 0.6% in the group of male volunteers and 2.15 ± 0.6% in the group of female volunteers ( P < .05). Baseline regional CBF (rCBF) values in activated gray matter areas within the visual cortex were 57 ± 1 mL · 100 g−1 · min−1 in women and 50 ± 12 mL · 100 g−1 · min−1 in men, respectively ( P = .09). Despite a broad overlap between both groups the rCBF increase was significantly higher in women compared to men (33 ± 5 mL · 100 g−1 · min−1 versus 28 ± 4 mL · 100 g−1 · min−1, P < .01). The increase of rCBF was not correlated with the baseline rCBF (mL · 100 g−1 · min−1) (rs = 0.01, P = .9). Moreover, changes of rCBF were not correlated with changes in BOLD signal intensities (rs = 0.1, P = .7). Enhanced rCBF response in women during visual stimulation could be related to gender differences in visual physiology or may reflect gender differences in the vascular response to focal neuronal activation. Gender differences must be considered when interpreting the results of functional magnetic resonance imaging studies.

Background Previous studies using hierarchical clustering approach to analyze resting-state fMRI data were limited to a few slices or regions-of-interest (ROIs) after substantial data reduction. Purpose To develop a framework that can perform voxel-wise hierarchical clustering of whole-brain resting-state fMRI data from a group of subjects. Materials and Methods Resting-state fMRI measurements were conducted for 86 adult subjects using a single-shot echo-planar imaging (EPI) technique. After pre-processing and co-registration to a standard template, pair-wise cross-correlation coefficients (CC) were calculated for all voxels inside the brain and translated into absolute Pearson's distances after imposing a threshold CC≥0.3. The group averages of the Pearson's distances were then used to perform hierarchical clustering with the developed framework, which entails gray matter masking and an iterative scheme to analyze the dendrogram. Results With the hierarchical clustering framework, we identified most of the functional connectivity networks reported previously in the literature, such as the motor, sensory, visual, memory, and the default-mode functional networks (DMN). Furthermore, the DMN and visual system were split into their corresponding hierarchical sub-networks. Conclusion It is feasible to use the proposed hierarchical clustering scheme for voxel-wise analysis of whole-brain resting-state fMRI data. The hierarchical clustering result not only confirmed generally the finding in functional connectivity networks identified previously using other data processing techniques, such as ICA, but also revealed directly the hierarchical structure within the functional connectivity networks.

A time-averaged method to obtain quantitative measurements in turbulent flow by phase flow encoding NMR imaging is introduced. With this method time-averaged velocity profiles and turbulence intensities can be determined. Time-averaged velocity profiles for pipe flow of water driven by a constant pressure gradient at Reynolds numbers from 1200 to 9400 were visualized. A precise correlation between the pixel intensity of the time-averaged NMR flow image and the local turbulence intensity of the flow is derived. The measured turbulence intensities are in agreement with published data obtained using other experimental methods.

Objective: To determine if coronary artery bypass graft (CABG) surgery without cardiopulmonary bypass (CPB) avoids the brain swelling known to occur after CPB, to quantify these brain water compartment changes, and to identify the water shifts as due to intracellular or extracellular water. Design: Prospective, controlled, and blinded. Setting: Cardiac surgical unit in a university teaching hospital. Subjects: Patients scheduled for CABG who were assigned to conventional (n = 10) or off-pump (n = 7) surgery according to their coronary anatomy. Interventions: Magnetic resonance imaging (MRI) examinations were performed 1 day before surgery and 1 hour and 1 week after CABG surgery. Main Outcome Measures: Extracellular and intracellular water homeostasis was described quantitatively by calculating the averaged apparent diffusion coefficient of brain water using diffusion-weighted MRI. Blinded visual ordering of the images from the three examinations was performed according to brain size using conventional MRI. Results: The average diffusion coefficient of brain water increased 4.7% ± 1.5% immediately after CABG with CPB and normalized after 1 week but did not change after CABG without CPB. No focal ischemic changes were seen in either group, and no gross neurologic deficits were observed. Visual analysis showed consistent brain swelling after CPB and variable changes in those operated without CPB. Conclusion: Changes consistent with increased extracellular brain water seen after CABG with CPB were not observed in patients undergoing CABG without CPB. The clinical significance of brain water changes and increased brain water content after surgery with CPB remains undefined.

Purpose: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Material and Methods: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Results: Both global and tissue averages of the diffusion coefficient are significantly correlated with age ( p Conclusion: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest.

The aim of this study was to investigate whether MR imaging of trabecular bone structure using magnetic inhomogeneity measurements is related to the amount of bone mineral in human vertebrae. Weight, bone mineral content (BMCDXA), bone mineral per area (BMADXA) and bone mineral density (BMDCT) were determined in 12 defatted human lumbar vertebrae (L2-L4) by weighing, dual X-ray absorptiometry (DXA) and CT. Inhomogeneity caused by susceptibility differences between trabecular bone and surrounding water was studied with MR imaging at 1.5 T using the GESFIDE sequence. The pulse sequence determines the transverse relaxation rate R2(*) and its two components, the non-reversible transverse relaxation rate (R2) and the reversible transverse relaxation rate (R2'; i. e. relaxation rate due to magnetic susceptibility) in a single scan. Voxel size was 0.9 x 1.9 x 5.0 mm. Positive significant correlations between R2' and weight, BMCDXA, BMADXA and BMDCT were observed (r0.61 and p0.05 for all). Unexpectedly, R2 was also positively correlated with weight, BMCDXA and BMDCT (r0.66 and p0.05 for all), but not with BMADXA. Thus, R2' measurements are related to the amount of bone mineral, but they also provide information which is not obtainable from bone mineral measurements.

Respiration effects and cardiac pulsatility can induce signal modulations in functional MR image time series that increase noise and degrade the statistical significance of activation signals. A simple image-based correction method is described that does not have the limitations of k-space methods that preclude high spatial frequency correction. Low-order Fourier series are fit to the image data based on time of each image acquisition relative to the phase of the cardiac and respiratory cycles, monitored using a photoplethysmograph and pneumatic belt, respectively. The RETROICOR method is demonstrated using resting-state experiments on three subjects and compared with the k-space method. The method is found to perform well for both respiration- and cardiac-induced noise without imposing spatial filtering on the correction. Magn Reson Med 44:162‐167, 2000. © 2000 Wiley-Liss, Inc.

Functional magnetic resonance imaging (fMRI) based on multiple-echo T(2)* mapping has attracted much attention recently. The contrasts in the parametric T(2)* maps are usually too low to allow direct image registration. In this study, an image registration strategy has been proposed for single-shot multi-echo data sets acquired for dynamic T(2)* mapping. We performed image registration of the T(2)*-weighted images before the calculation of the T(2)* parameter maps using two different strategies. One is to perform separate image registration on each echo and the other is to use the same motion correction parameters extracted from the second echo for all the data. Both strategies increase the number of activated voxels and reduce the effective noise level. The results also indicate that, for a single-shot dual-echo image data set, it is slightly preferable to use the second echo for direct image registration and then apply the same motion correction parameters to the first echo images. J. Magn. Reson Imaging 1999;10:154-158.

In this study, the hemodynamic response and changes in oxidative metabolism during functional activation were measured using three functional magnetic resonance imaging (fMRI) techniques: the blood oxygenation level-dependent (BOLD) technique, flow-sensitive alternating inversion recovery (FAIR), and bolus tracking (BT) of an MR contrast agent. With these three techniques we independently determined changes in BOLD signal, relative cerebral blood flow (rCBF), and cerebral blood volume (rCBV) associated with brain activation in eight healthy volunteers. In the motor cortex, the BOLD signal increased by 1.8 +/- 0.5%, rCBF by 36.3 +/- 8.2% (FAIR), and 35.1 +/- 8.6% (BT), and rCBV by 19.4 +/- 4.1% (BT) in response to simultaneous bilateral finger tapping. In the visual cortex, BOLD signal increased by 2.6 +/- 0.5%, rCBF by 38.5% +/- 7.6 (FAIR), and 36.9 +/- 8.8% (BT), and rCBV by 18.8 +/- 2.8% (BT) during flickering checkerboard stimulation. Comparing the experimentally measured rCBV with the calculated rCBV using Grubb's power-law relation, we conclude that the use of power-law relationship results in systematic underestimate of rCBV.