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Arterial recanalization to restore the blood supply and limit the brain damage is the primary goal in the management of acute ischemic stroke (AIS). Since the publication of pivotal randomized clinical trials in 2015, endovascular thrombectomy has become part of the standard of care in selected cases of AIS from large-vessel occlusions up to 6 hours after the onset of symptoms. However, the association between endovascular reperfusion and improved functional outcome is not strictly time dependent. Rather than on rigid time windows, candidates should be selected based on vascular and physiologic information. This approach places imaging data at the center of treatment decisions. Advances in imaging-based management of AIS provide crucial information about vessel occlusion, infarct core, ischemic penumbra, and degree of collaterals. This information is invaluable in identifying patients who are likely to benefit from reperfusion therapies and excluding those who are unlikely to benefit or are at risk of adverse effects. The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work-up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from "Time is Brain" to "Imaging is Brain." This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is used to track the first pass of an exogenous, paramagnetic, nondiffusible contrast agent through brain tissue, and has emerged as a powerful tool in the characterization of brain tumor hemodynamics. DSC-MRI parameters can be helpful in many aspects, including tumor grading, prediction of treatment response, likelihood of malignant transformation, discrimination between tumor recurrence and radiation necrosis, and differentiation between true early progression and pseudoprogression. This review aims to provide a conceptual overview of the underlying principles of DSC-MRI of the brain for clinical neuroradiologists, scientists, or students wishing to improve their understanding of the technical aspects, pitfalls, and controversies of DSC perfusion MRI of the brain. Future consensus on image acquisition parameters and postprocessing of DSC-MRI will most likely allow this technique to be evaluated and used in high-quality multicenter studies and ultimately help guide clinical care. J. Magn. Reson. Imaging 2015;41:296–313.© 2013 Wiley Periodicals, Inc.

Objectives: To determine whether a specific, standardized training regimen can improve muscle strength and physical functioning in people with dementia. Design: Double-blinded, randomized, controlled trial with 3-month intervention and 3-month follow-up period in 2006 to 2009. Setting: Outpatient geriatric rehabilitation. Participants: Individuals with confirmed mild to moderate dementia, no severe somatic or psychological disease, and ability to walk 10 m. Most participants were still living independently with or without supportive care. Intervention: Supervised, progressive resistance and functional group training for 3 months specifically developed for people with dementia (intervention, n = 62) compared with a low-intensity motor placebo activity (control, n = 60). Measurements: Primary outcome measures were one-repetition maximum in a leg press device for maximal strength and duration of the five-chair-stand test for functional performance. Secondary outcome measures were assessed for a number of established parameters for maximal strength, physical function, and physical activity. Results: Training significantly improved both primary outcomes (percentage change from baseline: maximal strength, intervention group (IG): +51.5 ± 41.5 kg vs control group (CG): �1.0 ± 28.9 kg, P < .001; functional performance, IG: �25.9 ± 15.1 seconds vs CG: +11.3 ± 60.4 seconds, P < .001). Secondary analysis confirmed effects for all strength and functional parameters. Training gains were partly sustained during follow-up. Low baseline performance on motor tasks but not cognitive impairment predicted positive training response. Physical activity increased significantly during the intervention (P < .001). Conclusion: The intensive, dementia-adjusted training was feasible and substantially improved motor performance in frail, older people with dementia and may represent a model for structured rehabilitation or outpatient training.

BACKGROUND AND PURPOSE Imaging studies of patients with schizophrenia have described a variety of cerebral alterations. However, long-term medication and the chronicity of the disorder may have contributed substantially to these alterations. Studies examining patients in the early stages of the disorder reduce the possibility of such confounding factors but are rare. In light of this, the aim of the present study was to examine adolescents in the early stages of the disorder to observe primary structural brain abnormalities. METHODS Gray and white matter were measured in 13 adolescents with schizophrenia and 13 healthy controls matched for age, gender, handedness, and school type using voxel-based morphometry. RESULTS Subjects with schizophrenia displayed decreased gray matter in the cerebellar vermis, and alterations in the left putamen and in several parts of the visual system. CONCLUSIONS These findings support cerebellar involvement in the pathogenesis of schizophrenia, and the alterations observed in several parts of the visual system may provide insights into the nature of hallucinations and delusional interpretations.

Summary Gadofosveset Trisodium (Vasovist) is a safe and well tolerated intravascular contrast agent, currently approved in Europe and Canada. It has proved to be effective in the asessment of vascular diseases at all vascular territories. The possibility to image at steady state opens new horizons by increasing the spatial resolution and the robustness of diagnostic MRA. Initial studies proved the possibility to image beyond the vascular territory and to assess enhancing lesions as known from studies with standard contrast agents.

(23)Na MRI has the potential to noninvasively detect sodium (Na) content changes in vivo. The goal of this study was to implement (23)Na MRI in a clinical setting for neurooncological and muscular imaging. Due to the biexponential T(2) decay of the tissue Na signal with a short component, which ranges between 0.5-8 ms, the measurement of total Na content requires imaging techniques with echo times (TEs) below 0.5 ms. A 3D radial pulse sequence with a TE of 0.2 ms at a spatial resolution of 4 x 4 x 4 mm(3) was developed that allows the acquisition and presentation of Na images on the scanner. This sequence was evaluated in patients with low- and high-grade gliomas, and higher (23)Na MR signals corresponding to an increased Na content were found in the tumor regions. The contrast-to-noise ratio (CNR) between tumor and white matter increased from 0.8 +/- 0.2 to 1.3 +/- 0.3 with tumor grade. In patients with an identified muscular (23)Na channelopathy (Paramyotonia congenita (PC)), induced muscle weakness led to a signal increase of approximately 18% in the (23)Na MR images, which was attributed to intracellular Na(+) accumulation in this region.

In past decades, much effort has been invested in developing therapies for spinal injuries. Lack of standardization of clinical read-out measures, however, makes direct comparison of experimental therapies difficult. Damage and therapeutic effects in vivo are routinely evaluated using rather subjective behavioral tests. Here we show that manganese-enhanced magnetic resonance imaging (MEMRI) can be used to examine the extent of damage following spinal cord injury (SCI) in mice in vivo. Injection of MnCl2 solution into the cerebrospinal fluid leads to manganese uptake into the spinal cord. Furthermore, after injury MEMRI-derived quantitative measures correlate closely with clinical locomotor scores. Improved locomotion due to treating the detrimental effects of SCI with an established therapy (neutralization of CD95Ligand) is reflected in an increase of manganese uptake into the injured spinal cord. Therefore, we demonstrate that MEMRI is a sensitive and objective tool for in vivo visualization and quantification of damage and functional improvement after SCI. Thus, MEMRI can serve as a reproducible surrogate measure of the clinical status of the spinal cord in mice, potentially becoming a standard approach for evaluating experimental therapies.

Arteriovenous malformations (AVM) can be treated with stereotactic radiosurgery. An infrequent, but important complication of this treatment is radionecrosis, which can be detected by MRI. However, the imaging characteristics of necrosis are unspecific in conventional MRI. Here, we report a case of necrosis after radiotherapy of an AVM to illustrate the potential of 7 Tesla MRI including amide proton transfer (APT) for necrosis imaging.

With the advent of new and more effective drugs for the treatment of Alzheimer's disease (AD), establishment of objective surrogate markers of disease progression has become an issue of high clinical relevance. In order to investigate the potential of volumetric magnetic resonance imaging (MRI) for monitoring disease progression, we investigated the progression rates of hippocampal and generalized brain atrophy in a group of AD patients with respect to rates of clinical deterioration. While AD, in comparison to healthy aging, was characterized by a rapid decline of hippocampal volumes, only a moderate decrease of whole brain volumes occurred, indicating that hippocampal atrophy was not merely a function of generalized brain atrophy. Progression of hippocampal atrophy, but not of whole brain atrophy, was significantly correlated with clinical deterioration. These findings indicate that progressive hippocampal volume reduction underlies clinical deterioration in AD and that the rate of hippocampal atrophy might be used as a morphometric index of disease progression in clinical drug trials. Drug Dev. Res. 56:51-56, 2002. � c 2002 Wiley-Liss, Inc.

To detect a renal artery stenosis and assess its hemodynamic and functional significance in five breath holds. In a single MR exam, T1 weighted FLASH and T2 weighted fast spin echo techniques are used to assess renal morphology, multiphase 3D gadolinium (Gd) MRA to evaluate the renal arteries, and a segmented EPI cine phase-contrast technique to measure renal artery blood flow. A standardized image analysis is performed to assess kidney size, corticomedullar differentiation (CMD), parenchymal enhancement, the degree of renal artery stenosis, abnormalities in blood flow pattern, and any associated abdominal vascular disease. Multiphase 3D-Gd-MRA accurately assesses atherosclerotic renal artery disease particularly in the presence of an associated aortic aneurysm. Delayed parenchymal enhancement, loss of CMD, and decrease in kidney size can be detected. In combination with decreased systolic velocity components, the diagnosis of a hemodynamically and functionally significant stenosis can be made. High-resolution single-phase 3D-Gd-MRA is preferable for evaluation of fibromuscular dysplasia or hypoplastic vessels. The combination of different breath hold techniques in a single, standardized MR exam allows to detect the hemodynamic and functional significance of a renal artery stenosis. J. Magn. Reson. Imaging 1999;10:347–356. © 1999 Wiley-Liss, Inc.

This article reviews the experience available to date on microcirculation assessment in cancer of the cervix including correlation studies of magnetic resonance (MR) microcirculatory parameters with histo-morphometric predictors and direct correlation with patient outcome. The data suggest that MR microcirculation parameters do not always correlate with histo-morphometric parameters, while there is evidence that MR parameters predict patients' treatment outcome. These observations raise the issue that perhaps the histo-morphometric parameters, accepted gold standards for tumor angiogenesis and prognostic factors, reflect anatomical information at a “static” single time point and may not always provide sufficient information on the “dynamic” microcirculation function of the tumor. MR microcirculation assessment reflects both anatomical and functional information and may provide this additional information on the “dynamic” angiogenic and metabolic status of a tumor. Therefore, assessment of tumor microcirculation may augment the individual risk profile in cervical cancer patients and has the potential to impact on therapy selection and treatment outcome. J. Magn. Reson. Imaging 1999;10:267–276. © 1999 Wiley-Liss, Inc.

ECG-gated phase contrast (CINE-PC) flow measurements in the renal artery help to differentiate between low- and high-grade stenoses. Because conventional CINE-PC acquisitions with high temporal resolution require acquisition times of several minutes, respiratory motion results in a systematic overestimation of renal artery flow. With the use of an interleaved gradient echo-planar technique (IGEPI), total measurement times can be shortened to about 30 seconds, while a high spatial and temporal resolution is maintained. In this study, an IGEPI CINE-PC flow measurement pulse sequence with 16 gradient echoes was compared with a non-breathheld conventional CINE-PC technique. Flow-time curves were measured in volunteers and in patients with suspected renal artery stenosis. With IGEPI CINE-PC, mean flow velocity, vessel cross-sectional area, and mean blood flow were substantially lower by 90% to 25%. Contrast-enhanced 3D MR angiography was used to compare stenosis grading based on flow-time curve patterns with morphologic grading. With IGEPI CINE-PC, all high-grade stenoses (n = 5) were detected, whereas only 66% (n = 3) were found with conventional CINE-PC.

With the advances in MR techniques, information related to tumor microcirculation now can be obtained in the clinical setting. This information can be valuable in the assessment of tumor blood supply/oxygenation status and tumor response to therapy. In this article, we review the tracer-kinetic modeling for tumor microcirculatory parameters derived from dynamic contrast MR imaging and report several preliminary results from both an animal model and early experience with human tumors. Despite the application of different MR protocols and tracer-kinetic models, the initial results of these pioneer studies consistently support the role of MR-derived microcirculatory tumor parameters, in providing prognostic information to assess and predict the response of cancers to cytotoxic therapy.

Alzheimer’s disease is a hyperphosphorylated form of the microtubulebinding protein tau. Hyperphosphorylation of tau, which occurs significantly within the proline-rich domain, is associated with structural and functional changes that are poorly understood. Understanding the relationship between hyperphosphorylation of tau and structural changes in tau is a central question in the mechanism of neurofibrillary tangle formation. Methods: Peptides and larger protein constructs derived from the proline-rich region of tau as well as other tau domains were synthesized with defined phosphrylation states. The non-phosphorylated and phosphorylated peptides and proteins were analyzed by NMR and circular dichroism in order to identify the specific local changes in the structure of tau that are induced by hyperphosphorylation. Results: Phosphorylation of serine and threonine residues throughout the proline-rich domain of tau induced structural changes from a disordered conformation to a type II polyproline helix. The largest phosphorylation-induced structural changes were observed in tau peptides derived from residues 174-183 or residues 229-238. Phosphorylation-induced changes to polyproline helix were also observed in tau peptides incorporating residues 211-219. Phosphorylation of tau peptides derived from tau residues 196-209 resulted in the disruption of a nascent -helix. In these peptides, phosphoserine and phosphothreonine residues exhibited ordered values of phi ( ) (3J N 3.1-6.2 Hz; mean 4.7 Hz) compared to non-phosphorylated serine and threonine, indicating specific conformational restriction upon phosphorylation. Phosphorylation within the proline-rich domain did not affect the cis-trans isomerization equilibrium of the peptides examined, suggesting that phosphorylation-associated cis-trans isomerism is due to long-range interactions. As the proline-rich domains are linker regions between hydrophobic and aggregation-prone domains of tau, these results suggest that global reorganization of tau may occur upon hyperphosphorylation of proline-rich domain in tau. These results provide insight into possible mechanisms of phosphorylation-dependent structural changes of tau in Alzheimer’s disease. Conclusions: Hyperphosphorylation within the proline-rich domain of tau can induce specific local structural changes from a disordered conformation to an ordered polyproline II helix conformation.