[One Health: a perspective of the informal ministerial network : "What if the One Health approach became the guiding theme of cooperation at the national, European and global level?"] / One Health: Eine Sichtweise des informellen ministeriellen Netzwerkes : "Was wäre, wenn der One-Health-Ansatz zum Leitmotiv von Kooperation auf nationaler, europäischer und globaler Ebene würde?".

In the view of the German government, the One Health approach is a pioneering compass for inter- and transdisciplinary thinking, networking, and action. To protect the health of humans, animals, plants, and ecosystems, it should always receive attention at all its interfaces and activities. The One Health approach has gained political importance in recent years and is being taken into account in several strategies.This article reports on the current strategies using a One Health approach. These include the German Antibiotic Resistance Strategy, the German Strategy for Adaptation to Climate Change, the global initiative Nature for Health, and the international pandemic agreement, which is currently being drafted and in which prevention also plays an important role. The issues of biodiversity loss and climate protection must be placed in a common context that takes into account the interdependencies of the health status of humans, animals, plants, and ecosystems. By involving relevant disciplines at different levels as a matter of course, we can succeed in making a joint contribution to sustainable development, as required by the United Nations' Agenda 2030. This perspective guides Germany's global engagement in global health policy toward greater stability, freedom, diversity, solidarity, and respect for human rights. Thus, a holistic approach such as One Health can contribute to achieving sustainability and strengthening democratic principles.

Uniform combined reconstruction of multichannel 7T knee MRI receive coil data without the use of a reference scan.

BACKGROUND: MR image intensity nonuniformity is often observed at 7T. Reference scans from the body coil used for uniformity correction at lower field strengths are typically not available at 7T. PURPOSE: To evaluate the efficacy of a novel algorithm, Uniform Combined Reconstruction (UNICORN), to correct receive coil-induced nonuniformity in musculoskeletal 7T MRI without the use of a reference scan. STUDY TYPE: Retrospective image analysis study. SUBJECTS: MRI data of 20 subjects was retrospectively processed offline. Field Strength/Sequence: Knees of 20 subjects were imaged at 7T with a single-channel transmit, 28-channel phased-array receive knee coil. A turbo-spin-echo sequence was used to acquire 33 series of images. ASSESSMENT: Three fellowship-trained musculoskeletal radiologists with cumulative experience of 42 years reviewed the images. The uniformity, contrast, signal-to-noise ratio (SNR), and overall image quality were evaluated for images with no postprocessing, images processed with N4 bias field correction algorithm, and the UNICORN algorithm. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was used for measuring the interrater reliability. ICC and 95% confidence intervals (CIs) were calculated using the R statistical package employing a two-way mixed-effects model based on a mean rating (k = 3) for absolute agreement. The Wilcoxon signed-rank test with continuity correction was used for analyzing the overall image quality scores. RESULTS: UNICORN was preferred among the three methods evaluated for uniformity in 97.9% of the pooled ratings, with excellent interrater agreement (ICC of 0.98, CI 0.97-0.99). UNICORN was also rated better than N4 for contrast and equivalent to N4 in SNR with ICCs of 0.80 (CI 0.72-0.86) and 0.67 (CI 0.54-0.77), respectively. The overall image quality scores for UNICORN were significantly higher than N4 (P < 6 × 10-13 ), with good to excellent interrater agreement (ICC 0.90, CI 0.86-0.93). DATA CONCLUSION: Without the use of a reference scan, UNICORN provides better image uniformity, contrast, and overall image quality at 7T compared with the N4 bias field-correction algorithm. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1534-1544.

Comprehensive cellular-resolution atlas of the adult human brain.

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Reducing sensitivity losses due to respiration and motion in accelerated echo planar imaging by reordering the autocalibration data acquisition.

PURPOSE: To reduce the sensitivity of echo-planar imaging (EPI) auto-calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal-to-noise ratio (tSNR) of accelerated EPI time-series data. METHODS: ACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion-match the ACS and time-series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B0 changes. The fast low-angle excitation echo-planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible. RESULTS: Subject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time-series data. Accelerated EPI data reconstructed using FLEET-ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition. CONCLUSION: FLEET-ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional-resolution 3T and high-resolution 7T EPI time-series data.

Automatic voxel positioning for MRS at 7 T.

OBJECT: The purpose of this study was to test, for the first time, whether spectroscopy voxels could be positioned automatically with high accuracy and reproducibility in ultrahigh-field longitudinal magnetic resonance spectroscopy (MRS) studies. MATERIALS AND METHODS: MRS voxels were automatically positioned in two cingulate subregions of 12 healthy subjects using a vendor-provided automatic voxel positioning (AutoAlign) technique, and were manually placed in the same regions of 10 healthy subjects by an experienced technician in three 7 T MRS scan sessions. Different coils were used for manual (24-channel coil) and automatic (32-channel coil) voxel placement, and the effects of signal-to-noise-ratio differences on the spectra were considered. RESULTS: Over three scan sessions and two regions scanned for each subject, a mean voxel geometric overlap ratio of 0.91 for automatic positioning reflected accurate voxel alignment, while the geometric overlap ratio was only 0.70 for voxels placed manually. Comparable voxel positions among the three scan sessions (p > 0.05) indicated high reproducibility of automatic voxel alignment. In comparison, significant voxel displacement among scan sessions (p < 0.05) was found using manual voxel positioning. CONCLUSIONS: In view of the highly accurate and reproducible voxel alignment with automatic voxel positioning, we propose the application of automatic rather than manual voxel positioning in future ultrahigh-field longitudinal MRS studies.

Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis.

Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of ~10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV)=2.1%, interobserver COV=5.2%, and scan-rescan COV=5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P=0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS.

Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network.

BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.

H.M.'s contributions to neuroscience: a review and autopsy studies.

H.M., Henry Molaison, was one of the world's most famous amnesic patients. His amnesia was caused by an experimental brain operation, bilateral medial temporal lobe resection, carried out in 1953 to relieve intractable epilepsy. He died on December 2, 2008, and that night we conducted a wide variety of in situ MRI scans in a 3 T scanner at the Massachusetts General Hospital (Mass General) Athinoula A. Martinos Center for Biomedical Imaging. For the in situ experiments, we acquired a full set of standard clinical scans, 1 mm isotropic anatomical scans, and multiple averages of 440 µm isotropic anatomical scans. The next morning, H.M.'s body was transported to the Mass General Morgue for autopsy. The photographs taken at that time provided the first documentation of H.M.'s lesions in his physical brain. After tissue fixation, we obtained ex vivo structural data at ultra-high resolution using 3 T and 7 T magnets. For the ex vivo acquisitions, the highest resolution images were 210 µm isotropic. Based on the MRI data, the anatomical areas removed during H.M.'s experimental operation were the medial temporopolar cortex, piriform cortex, virtually all of the entorhinal cortex, most of the perirhinal cortex and subiculum, the amygdala (except parts of the dorsal-most nuclei-central and medial), anterior half of the hippocampus, and the dentate gyrus (posterior head and body). The posterior parahippocampal gyrus and medial temporal stem were partially damaged. Spared medial temporal lobe tissue included the dorsal-most amygdala, the hippocampal-amygdalo-transition-area, ∼2 cm of the tail of the hippocampus, a small part of perirhinal cortex, a small portion of medial hippocampal tissue, and ∼2 cm of posterior parahippocampal gyrus. H.M.'s impact on the field of memory has been remarkable, and his contributions to neuroscience continue with a unique dataset that includes in vivo, in situ, and ex vivo high-resolution MRI.

Quantitative comparison of cortical surface reconstructions from MP2RAGE and multi-echo MPRAGE data at 3 and 7 T.

The Magnetization-Prepared 2 Rapid Acquisition Gradient Echo (MP2RAGE) method achieves spatially uniform contrast across the entire brain between gray matter and surrounding white matter tissue and cerebrospinal fluid by rapidly acquiring data at two points during an inversion recovery, and then combining the two volumes so as to cancel out sources of intensity and contrast bias, making it useful for neuroimaging studies at ultrahigh field strengths (≥7T). To quantify the effectiveness of the MP2RAGE method for quantitative morphometric neuroimaging, we performed tissue segmentation and cerebral cortical surface reconstruction of the MP2RAGE data and compared the results with those generated from conventional multi-echo MPRAGE (MEMPRAGE) data across a group of healthy subjects. To do so, we developed a preprocessing scheme for the MP2RAGE image data to allow for automatic cortical segmentation and surface reconstruction using FreeSurfer and analysis methods to compare the positioning of the surface meshes. Using image volumes with 1mm isotropic voxels we found a scan-rescan reproducibility of cortical thickness estimates to be 0.15 mm (or 6%) for the MEMPRAGE data and a slightly lower reproducibility of 0.19 mm (or 8%) for the MP2RAGE data. We also found that the thickness estimates were systematically smaller in the MP2RAGE data, and that both the interior and exterior cortical boundaries estimated from the MP2RAGE data were consistently positioned within the corresponding boundaries estimated from the MEMPRAGE data. Therefore several measureable differences exist in the appearance of cortical gray matter and its effect on automatic segmentation methods that must be considered when choosing an acquisition or segmentation method for studies requiring cortical surface reconstructions. We propose potential extensions to the MP2RAGE method that may help to reduce or eliminate these discrepancies.

Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive performance in MS.

OBJECTIVES: Evaluate cross-sectionally the contribution of focal cortical lesion (CL) subtypes at ultra-high-field MRI and traditional MRI metrics of brain damage to neurologic disability and cognitive performance in a heterogeneous multiple sclerosis (MS) cohort. METHODS: Thirty-four patients with early or established disease including clinically isolated syndrome, relapsing-remitting MS, and secondary progressive MS were scanned on a human 7-tesla (7T) (Siemens) scanner to acquire fast low-angle shot (FLASH) T2*-weighted images for characterization of white matter and deep gray matter lesion volume, and CL types. Patients also underwent anatomical 3T MRI for cortical thickness estimation, and neuropsychological testing within 1 week of the 7T scan. Twenty-seven patient scans were acceptable for further analysis. Neurologic disability was measured using the Expanded Disability Status Scale. RESULTS: Type III-IV CLs had the strongest relationship to physical disability (ρ = 0.670, p < 0.0001). White matter lesion volume and type I CLs are each significantly associated with 6 of 11 neuropsychological test variables. Type III-IV CLs significantly correlate with 4 of 11 neuropsychological test variables whereas type II CLs, deep gray matter lesion volume, and cortical thickness metrics are less frequently associated with cognitive performance. CONCLUSIONS: Leukocortical (type I) and subpial (III-IV) CLs identified on 7T FLASH-T2* sequences are potential cortical biomarkers of cognitive and neurologic status in MS.

Disconnection of the ascending arousal system in traumatic coma.

Traumatic coma is associated with disruption of axonal pathways throughout the brain, but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness-arousal and awareness-in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. High angular resolution diffusion imaging tractography guided tissue sampling in the neuropathologic analysis. High angular resolution diffusion imaging tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical "awareness pathways." Neuropathologic examination, which used ß-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of high angular resolution diffusion imaging tract disruption. Axonal injury was also present within the gray matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain.

Radial and tangential neuronal migration pathways in the human fetal brain: anatomically distinct patterns of diffusion MRI coherence.

Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventricular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique insight into three-dimensional trajectories beyond those visualized using traditional histological techniques. Our results suggest that ex-vivo fetal MRI is a potentially useful modality in understanding normal human development and various disease processes whose etiology may originate in aberrant fetal neuronal migration.

Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders.

The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initial evidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state.

Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based predictive models.

BACKGROUND: Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO), an investigational stroke treatment, using data from a pilot study of NBO in acute stroke. METHODS: The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy) was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control. RESULTS: Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007) than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth. CONCLUSIONS: This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.

Focal cortical lesion detection in multiple sclerosis: 3 Tesla DIR versus 7 Tesla FLASH-T2.

PURPOSE: To evaluate the inter-rater agreement of cortical lesion detection using 7 Tesla (T) FLASH-T2 and 3T DIR sequences. MATERIALS AND METHODS: Twenty-six patients with multiple sclerosis were scanned on a human 7T (Siemens) and 3T MRI (TIM Trio, Siemens) to acquire 3T DIR/MEMPR and 7T FLASH-T2 sequences. Four independent reviewers scored and categorized cortical lesions in the bilateral precentral gyri (motor strips) as leukocortical, intracortical, or subpial. Inter-rater agreement was assessed according to lesion category using the kappa statistic. The sensitivity of recent MAGNIMS consensus guidelines for cortical lesion detection using 3T DIR was assessed with 7T FLASH-T2 as the reference gold standard. RESULTS: Inter-rater agreement at 7T was excellent compared with 3T (k = 0.97 versus 0.12). FLASH-T2 at 7T detected subpial lesions while 3T DIR did not. The predicted sensitivity of 3T DIR sequence for cortical lesions in vivo is modest (range of 13.6 to 18.3%). CONCLUSION: The 7T FLASH-T2 detects more cortical-particularly subpial-lesions compared with 3T DIR. In the absence of DIR/postmortem data, 7T FLASH-T2 is a suitable gold-standard instrument and should be incorporated into future consensus guidelines.

Phase-based regional oxygen metabolism (PROM) using MRI.

Venous oxygen saturation (Y(v) ) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO(2)) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Y(v) and CMRO(2) using noninvasive imaging. This article proposes a technique to quantify CMRO(2) from independent MRI estimates of Y(v) and cerebral blood flow. The approach uses standard gradient-echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient-echo phase images, Y(v) was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Fick's principle of arteriovenous difference was then used to quantify CMRO(2) locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% ± 2.3% for Y(v), 51.7 ± 6.4 mL/100 g/min for cerebral blood flow, and 158 ± 18 µmol/100 g/min for CMRO(2) (mean ± SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI.

Six is enough? Comparison of diffusion parameters measured using six or more diffusion-encoding gradient directions with deterministic tractography.

Diffusion tensor imaging tractography is commonly used to quantify white matter tracts in the human brain via parameters such as fractional anisotropy and mean diffusivity. Simulation studies recommend the use of more than six directions for robust parameter estimates; however, no study has examined the impact of the number of gradient directions on deterministic tractography-derived diffusion parameters in human brain. Here, for 10 major white matter tracts in 11 healthy volunteers at 1.5 T, six-direction diffusion tensor imaging data were compared to 30- or 60-direction data, keeping scan time and number of b = 0 images constant within each test. Mean diffusivity was systematically lower for six-direction protocols (20/40 comparisons); six-direction data had higher fractional anisotropy in the superior longitudinal fasciculus and smaller tract volume for the genu of the corpus callosum. In general, parameter differences due to the number of directions were smaller than those from intersubject variation or signal-to-noise ratio. Despite some absolute differences, standard deviations were significantly different for only one of 160 comparisons. Thus, six-direction data provide diffusion measures with comparable robustness to 30- or 60-direction data and yield appropriate parameter values for most white matter tracts, although there are clear advantages in acquiring higher angular resolution data.

Diffusion imaging with prospective motion correction and reacquisition.

A major source of artifacts in diffusion-weighted imaging is subject motion. Slow bulk subject motion causes misalignment of data when more than one average or diffusion gradient direction is acquired. Fast bulk subject motion can cause signal dropout artifacts in diffusion-weighted images and results in erroneous derived maps, e.g., fractional anisotropy maps. To address both types of artifacts, a fully automatic method is presented that combines prospective motion correction with a reacquisition scheme. Motion correction is based on the prospective acquisition correction method modified to work with diffusion-weighted data. The images to reacquire are determined automatically during the acquisition from the imaging data, i.e., no extra reference scan, navigators, or external devices are necessary. The number of reacquired images, i.e., the additional scan duration can be adjusted freely. Diffusion-weighted prospective acquisition correction corrects slow bulk motion well and reduces misalignment artifacts like image blurring. Mean absolute residual values for translation and rotation were <0.6 mm and 0.5°. Reacquisition of images affected by signal dropout artifacts results in diffusion maps and fiber tracking free of artifacts. The presented method allows the reduction of two types of common motion related artifacts at the cost of slightly increased acquisition time.

Simulation and optimization of pulsed radio frequency irradiation scheme for chemical exchange saturation transfer (CEST) MRI-demonstration of pH-weighted pulsed-amide proton CEST MRI in an animal model of acute cerebral ischemia.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is capable of measuring dilute labile protons and microenvironmental properties. However, the CEST contrast is dependent upon experimental conditions-particularly, the radiofrequency (RF) irradiation scheme. Although continuous-wave RF irradiation has been used conventionally, the limited RF pulse duration or duty cycle of most clinical systems requires the use of pulsed RF irradiation. Here, the conventional numerical simulation is extended to describe pulsed-CEST MRI contrast as a function of RF pulse parameters (i.e., RF pulse duration and flip angle) and labile proton properties (i.e., exchange rate and chemical shift). For diamagnetic CEST agents undergoing slow or intermediate chemical exchange, simulation shows a linear regression relationship between the optimal mean RF power of pulsed-CEST MRI and continuous-wave-CEST MRI. The optimized pulsed-CEST contrast is approximately equal to that of continuous-wave-CEST MRI for exchange rates less than 50 s(-1), as confirmed experimentally using a multicompartment pH phantom. In the acute stroke animals, we showed that pulsed- and continuous-wave-amide proton CEST MRI demonstrated similar contrast. In summary, our study elucidated the RF irradiation dependence of pulsed-CEST MRI contrast, providing useful insights to guide its experimental optimization and quantification.