Segmented spin-echo echo-planar imaging improves whole-brain BOLD functional MRI in awake pigeon brains.

Functional magnetic resonance imaging (fMRI) in awake small animals such as pigeons or songbirds opens a new window into the neural fundaments of cognitive behavior. However, high-field fMRI in the avian brain is challenging due to strong local magnetic field inhomogeneities caused by air cavities in the skull. A spoiled gradient-echo fMRI sequence has already been used to map the auditory network in songbirds, but due to susceptibility artifacts only 50% of the whole brain could be recorded. Since whole-brain fMRI coverage is vital to reveal whole-brain networks, an MRI sequence that is less susceptible to these artifacts was required. This was recently achieved in various bird species by using a rapid acquisition with relaxation enhancement (RARE) sequence. Weak blood oxygen level-dependent (BOLD) sensitivity, low temporal resolution, and heat caused by the long train of RF refocusing pulses are the main limits of RARE fMRI at high magnetic fields. To go beyond some of these limitations, we here describe the implementation of a two-segmented spin-echo echo-planar imaging (SE-EPI). The proposed sequence covers the whole brain of awake pigeons. The sequence was applied to investigate the auditory network in awake pigeons and assessed the relative merits of this method in comparison with the single-shot RARE sequence. At the same imaging resolution but with a volume acquisition of 3 s versus 4 s for RARE, the two-segmented SE-EPI provided twice the strength of BOLD activity compared with the single-shot RARE sequence, while the image signal-to-noise ratio (SNR) and in particular the temporal SNR were very similar for the two sequences. In addition, the activation patterns in two-segmented SE-EPI data are more symmetric and larger than single-shot RARE results. Two-segmented SE-EPI represents a valid alternative to the RARE sequence in avian fMRI research since it yields more than twice the BOLD sensitivity per unit of time with much less energy deposition and better temporal resolution, particularly for event-related experiments.

Lipoprotein receptor loss in forebrain radial glia results in neurological deficits and severe seizures.

The Alzheimer disease-associated multifunctional low-density lipoprotein receptor-related protein-1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knock-out (KO) of the receptor is embryonically lethal. To unravel the receptors' role in the developing brain we generated a mouse mutant by specifically targeting radial glia stem cells of the dorsal telencephalon. The low-density lipoprotein receptor-related protein-1 lineage-restricted KO female and male mice, in contrast to available models, developed a severe neurological phenotype with generalized seizures during early postnatal development. The mechanism leading to a buildup of hyperexcitability and emergence of seizures was traced to a failure in adequate astrocyte development and deteriorated postsynaptic density integrity. The detected impairments in the astrocytic lineage: precocious maturation, reactive gliosis, abolished tissue plasminogen activator uptake, and loss of functionality emphasize the importance of this glial cell type for synaptic signaling in the developing brain. Together, the obtained results highlight the relevance of astrocytic low-density lipoprotein receptor-related protein-1 for glutamatergic signaling in the context of neuron-glia interactions and stage this receptor as a contributing factor for epilepsy.

MRI of Iron Oxide Nanoparticles and Myeloperoxidase Activity Links Inflammation to Brain Edema in Experimental Cerebral Malaria.

Purpose To investigate the association of inflammation and brain edema in a cerebral malaria (CM) mouse model with a combination of bis-5-hydroxy-tryptamide-diethylenetriaminepentaacetate gadolinium, referred to as MPO-Gd, and cross-linked iron oxide nanoparticle (CLIO-NP) imaging. Materials and Methods Female wild-type (n = 23) and myeloperoxidase (MPO) knock-out (n = 5) mice were infected with the Plasmodium berghei ANKA strain from May 2016 to July 2018. Seven healthy mice served as control animals. At a Rapid Murine Coma and Behavioral Scale (RMCBS) score of less than 15, mice underwent MRI at 9.4 T and received gadodiamide, MPO-Gd, or CLIO-NPs. T1-weighted MRI was used to assess MPO activity, and T2*-weighted MRI was used to track CLIO-NPs. Immunofluorescent staining and flow cytometric analyses characterized CLIO-NPs, MPO, endothelial cells, and leukocytes. An unpaired, two-tailed Student t test was used to compare groups; Spearman correlation analysis was used to determine the relationship of imaging parameters to clinical severity. Results MPO-Gd enhancement occurred in inflammatory CM hotspots (olfactory bulb > rostral migratory stream > brainstem > cortex, P < .05 for all regions compared with control mice; mean olfactory bulb signal intensity ratio: 1.40 ± 0.07 vs 0.96 ± 0.01, P < .01). The enhancement was reduced in MPO knockout mice (mean signal intensity ratio at 60 minutes: 1.13 ± 0.04 vs 1.40 ± 0.07 in CM, P < .05). Blood-brain barrier compromise was suggested by parenchymal gadolinium enhancement, leukocyte recruitment, and endothelial activation. CLIO-NPs accumulated mainly intravascularly and at the vascular endothelium. CLIO-NPs were also found in the choroid plexus, indicating inflammation of the ventricular system. Blood-cerebrospinal fluid barrier breakdown showed correlation with brain swelling (r2: 0.55, P < .01) and RMCBS score (r2: 0.75, P < .001). Conclusion Iron oxide nanoparticle imaging showed strong inflammatory involvement of the microvasculature in a murine model of cerebral malaria. Furthermore, bis-5-hydroxy-tryptamide-diethylenetriaminepentaacetate gadolinium imaging depicted parenchymal and intraventricular inflammation. This combined molecular imaging approach links vascular inflammation to breakdown of the blood-brain barrier and blood-cerebrospinal fluid barrier that correlate with global brain edema and disease severity. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

The Hinrichsen Embryology Collection: Digitization of Historical Histological Human Embryonic Slides and MRI of Whole Fetuses.

The number of human embryology collections is very limited worldwide. Some of these comprise the Carnegie Collection, Kyoto Collection, and the Blechschmidt Collection. One further embryonic collection is the Hinrichsen Collection of the Ruhr University Bochum, Germany, which also contains very well-preserved embryos/fetuses, along with approximately 16,000 histological sections. The digitization of this collection is indispensable to enable conservation of the collection for the future and to provide a large group of embryologists, researchers, and physicians access to these histological slides. A small selection of these scans is available at the website of the Digital Embryology Consortium [https://-human-embryology.org/wiki/Main_Page].

Early Blood-Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules.

BACKGROUND AND PURPOSE: Detection and localization of the early phase of blood-brain barrier disruption (BBBD) in vivo during cerebral ischemia/reperfusion injury remain a major challenge but may be a relevant outcome parameter in stroke. METHODS: We studied early BBBD in mice after transient middle cerebral artery occlusion by multimodal, high-field (9.4T) in vivo magnetic resonance imaging, including the contrast agent gadofluorineM as an albumin-binding tracer. GadofluorineM contrast-enhanced magnetic resonance imaging was performed to determine BBBD at 2, 6, and 24 hours after reperfusion. BBBD was confirmed and localized along the microvascular tree by using fluorescent gadofluorineM and immunofluorescence stainings (cluster of differentiation 31, ephrin type-B receptor 4, alpha smooth muscle actin, ionized calcium binding adaptor molecule 1). RESULTS: GadofluorineM contrast-enhanced magnetic resonance imaging revealed a multifocal spatial distribution of early BBBD and its close association with the microvasculature at a resolution of 40 µm. GadofluorineM leakage was closely associated with ephrin type-B receptor 4-positive but not alpha smooth muscle actin-positive vessels. The multifocal pattern of early BBBD (already at 2 hours after reperfusion) thus occurred in the distal capillary and venular microvascular bed. These multifocal zones showed distinct imaging signs indicative of early vasogenic edema. The total volume of multifocal early BBBD accurately predicted infarct size at 24 hours after reperfusion. CONCLUSIONS: Early BBBD in focal cerebral ischemia initiates multifocally in the distal capillary and venular bed of the cerebral microvasculature. It is closely associated with perimicrovascular vasogenic edema and microglial activation and predicts the extent of final infarction.

Functional MRI in the Nile crocodile: a new avenue for evolutionary neurobiology.

Crocodilians are important for understanding the evolutionary history of amniote neural systems as they are the nearest extant relatives of modern birds and share a stem amniote ancestor with mammals. Although the crocodilian brain has been investigated anatomically, functional studies are rare. Here, we employed functional magnetic resonance imaging (fMRI), never tested in poikilotherms, to investigate crocodilian telencephalic sensory processing. Juvenile Crocodylus niloticus were placed in a 7 T MRI scanner to record blood oxygenation level-dependent (BOLD) signal changes during the presentation of visual and auditory stimuli. Visual stimulation increased BOLD signals in rostral to mid-caudal portions of the dorso-lateral anterior dorsal ventricular ridge (ADVR). Simple auditory stimuli led to signal increase in the rostromedial and caudocentral ADVR. These activation patterns are in line with previously described projection fields of diencephalic sensory fibres. Furthermore, complex auditory stimuli activated additional regions of the caudomedial ADVR. The recruitment of these additional, presumably higher-order, sensory areas reflects observations made in birds and mammals. Our results indicate that structural and functional aspects of sensory processing have been likely conserved during the evolution of sauropsids. In addition, our study shows that fMRI can be used to investigate neural processing in poikilotherms, providing a new avenue for neurobiological research in these critical species.

In vivo measurement of T1 and T2 relaxation times in awake pigeon and rat brains at 7T.

PURPOSE: Establishment of regional longitudinal (T1 ) and transverse (T2 ) relaxation times in awake pigeons and rats at 7T field strength. Regional differences in relaxation times between species and between two different pigeon breeds (homing pigeons and Figurita pigeons) were investigated. METHODS: T1 and T2 relaxation times were determined for nine functionally equivalent brain regions in awake pigeons and rats using a multiple spin-echo saturation recovery method with variable repetition time and a multi-slice/multi-echo sequence, respectively. Optimized head fixation and habituation protocols were applied to accustom animals to the scanning conditions and to minimize movement. RESULTS: The habituation protocol successfully limited movement of the awake animals to a negligible minimum, allowing reliable measurement of T1 and T2 values within all regions of interest. Significant differences in relaxation times were found between rats and pigeons but not between different pigeon breeds. CONCLUSION: The obtained T1 and T2 values for awake pigeons and rats and the optimized habituation protocol will augment future MRI studies with awake animals. The differences in relaxation times observed between species underline the importance of the acquisition of T1 /T2 values as reference points for specific experiments. Magn Reson Med 79:1090-1100, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream.

It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal pattern of microglial activation in ECM involving primarily the OB+RMS axis, a distinct pathway utilized by neuroblasts and immune cells. Our data suggest significant crosstalk between these two cell populations to be operative in deeper brain infiltration and further imply that the manifestation and progression of cerebral malaria may depend on brain areas otherwise serving neurogenesis.

Functional Connectivity Pattern of the Internal Hippocampal Network in Awake Pigeons: A Resting-State fMRI Study.

In the last two decades, the avian hippocampus has been repeatedly studied with respect to its architecture, neurochemistry, and connectivity pattern. We review these insights and conclude that we unfortunately still lack proper knowledge on the interaction between the different hippocampal subregions. To fill this gap, we need information on the functional connectivity pattern of the hippocampal network. These data could complement our structural connectivity knowledge. To this end, we conducted a resting-state fMRI experiment in awake pigeons in a 7-T MR scanner. A voxel-wise regression analysis of blood oxygenation level-dependent (BOLD) fluctuations was performed in 6 distinct areas, dorsomedial (DM), dorsolateral (DL), triangular shaped (Tr), dorsolateral corticoid (CDL), temporo-parieto-occipital (TPO), and lateral septum regions (SL), to establish a functional connectivity map of the avian hippocampal network. Our study reveals that the system of connectivities between CDL, DL, DM, and Tr is the functional backbone of the pigeon hippocampal system. Within this network, DM is the central hub and is strongly associated with DL and CDL BOLD signal fluctuations. DM is also the only hippocampal region to which large Tr areas are functionally connected. In contrast to published tracing data, TPO and SL are only weakly integrated in this network. In summary, our findings uncovered a structurally otherwise invisible architecture of the avian hippocampal formation by revealing the dynamic blueprints of this network.

Self-navigation under non-steady-state conditions: Cardiac and respiratory self-gating of inversion recovery snapshot FLASH acquisitions in mice.

PURPOSE: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs. METHODS: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference. RESULTS: Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference. CONCLUSION: The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Quantification of perfusion in murine myocardium: A retrospectively triggered T1 -based ASL method using model-based reconstruction.

PURPOSE: A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice. METHODS: A flow-sensitive alternating inversion recovery arterial spin labeling method using an untriggered FLASH-read out with random sampling is used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism to reduce deviation from Look-Locker conditions are needed. Electrocardiogram and respiratory data are recorded for retrospective gating and triggering. A model-based technique is used to reconstruct missing k-space data to cope with the undersampling inherent in retrospectively gated methods. Acquisition and reconstruction were validated numerically and in phantom measurements before in vivo experimentation. RESULTS: Quantitative perfusion maps were acquired within a single slice measurement time of 11 min. Perfusion values are in good accordance to literature values. Myocardial infarction could be clearly visualized and results were confirmed with histological results. CONCLUSION: The proposed method is capable of producing quantitative perfusion maps on arbitrary positions in the heart cycle within a short measurement time. The method is robust against irregular breathing patterns and heart rate changes and can be implemented on all scanners.

Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

Monitoring of monocyte recruitment in reperfused myocardial infarction with intramyocardial hemorrhage and microvascular obstruction by combined fluorine 19 and proton cardiac magnetic resonance imaging.

BACKGROUND: Monocytes and macrophages are indispensable in the healing process after myocardial infarction (MI); however, the spatiotemporal distribution of monocyte infiltration and its correlation to prognostic indicators of reperfused MI have not been well described. METHODS AND RESULTS: With combined fluorine 19/proton ((1)H) magnetic resonance imaging, we noninvasively visualized the spatiotemporal recruitment of monocytes in vivo in a rat model of reperfused MI. Blood monocytes were labeled by intravenous injection of (19)F-perfluorocarbon emulsion 1 day after MI. The distribution patterns of monocyte infiltration were correlated to the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage. In vivo, (19)F/(1)H magnetic resonance imaging performed in series revealed that monocyte infiltration was spatially inhomogeneous in reperfused MI areas. In the absence of MVO, monocyte infiltration was more intense in MI regions with serious ischemia-reperfusion injuries, indicated by severe intramyocardial hemorrhage; however, monocyte recruitment was significantly impaired in MVO areas accompanied by severe intramyocardial hemorrhage. Compared with MI with isolated intramyocardial hemorrhage, MI with MVO resulted in significantly worse pump function of the left ventricle 28 days after MI. CONCLUSIONS: Monocyte recruitment was inhomogeneous in reperfused MI tissue. It was highly reduced in MVO areas defined by magnetic resonance imaging. The impaired monocyte infiltration in MVO regions could be related to delayed healing and worse functional outcomes in the long term. Therefore, monocyte recruitment in MI with MVO could be a potential diagnostic and therapeutic target that could be monitored noninvasively and longitudinally by (19)F/(1)H magnetic resonance imaging in vivo.

Myocardial perfusion quantification using the T1 -based FAIR-ASL method: the influence of heart anatomy, cardiopulmonary blood flow and look-locker readout.

PURPOSE: The quantification of myocardial perfusion using a Look-Locker flow-sensitive alternating inversion recovery- arterial spin labeling experiment is considered. Due to the anatomy of the heart, a substantial but unintended partial inversion of the inflowing blood occurs during the slice-selective inversion. Both, the partial inversion as well as the Look-Locker pulse train, influence the myocardial perfusion quantification and are addressed in this work. METHODS: The mean relaxation time approximation is used to calculate the monoexponential relaxation time of the signal in perfused tissue under Look-Locker readout. The left ventricular blood serves as an approximation of the inflowing blood in the description of FAIR-ASL measurements with global and slice-selective inversion to correctly quantify the myocardial perfusion. RESULTS: The analysis shows that the myocardial perfusion can be overestimated if the T1 -based quantification method is not adapted respecting the Look-Locker pulse train explicitly. Additionally, it turns out that without correction for the partial inversion of the blood pool during the slice-selective inversion the myocardial perfusion is underestimated. CONCLUSION: It is shown that the Look-Locker readout as well as the nonideal slice-selective inversion experiment have a considerable influence and have to be included properly to correctly quantify myocardial perfusion.

Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation.

Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng(-/-) mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng(-/-) mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases.

Spatial phase encoding exploiting the Bloch-Siegert shift effect.

OBJECTIVE: The present work introduces an alternative to the conventional B0-gradient spatial phase encoding technique. By applying far off-resonant radiofrequency (RF) pulses, a spatially dependent phase shift is introduced to the on-resonant transverse magnetization. This so-called Bloch-Siegert (BS) phase shift has been recently used for B1(+)-mapping. The current work presents the theoretical background for the BS spatial encoding technique (BS-SET) using RF-gradients. MATERIALS AND METHODS: Since the BS-gradient leads to nonlinear encoding, an adapted reconstruction method was developed to obtain undistorted images. To replace conventional phase encoding gradients, BS-SET was implemented in a two-dimensional (2D) spin echo sequence on a 0.5 T portable MR scanner. RESULTS: A 2D spin echo (SE) measurement imaged along a single dimension using the BS-SET was compared to a conventional SE 2D measurement. The proposed reconstruction method yielded undistorted images. CONCLUSIONS: BS-gradients were demonstrated as a feasible option for spatial phase encoding. Furthermore, undistorted BS-SET images could be obtained using the proposed reconstruction method.

Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach.

AIMS: The purpose of this clinical trial was to investigate whether cardiovascular magnetic resonance imaging (CMR) using ferumoxytol (Feraheme™, FH), an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO), allows more detailed characterization of infarct pathology compared with conventional gadolinium-based necrosis/fibrosis imaging in patients with acute myocardial infarction. METHODS AND RESULTS: Fourteen patients who had experienced an acute ST-elevation myocardial infarction were included in this study. Following coronary angiography, a first baseline study (pre-FH) was performed followed by subsequent CMR studies (post-FH) 48 h after intravenous ferumoxytol administration. The CMR studies comprised cine-CMR, T(2)-weighted short tau inversion recovery spin echo imaging, T(2)-mapping, and T(1)-weighted late gadolinium enhancement (LGE) imaging. The median extent of short-axis in-plane LGE was 30% [inter-quartile range (IQR) 26-40%]. The median in-plane extent of T(2)-weighted 'hypoenhancement' in the region of myocardial infarction, which was not present prior to ferumoxytol administration in any patient, was 19% (IQR 14-22%; P < 0.001 compared with the extent of LGE). The median in-plane extent of areas showing signal void in T(2)-mapping images post-FH in the region of myocardial infarction was 16% (IQR 12-18%; P < 0.001 compared with the extent of LGE; P = 0.34 compared with the extent of T(2)-weighted hypoenhancement). A substantial drop in absolute T(2)-values was observed not only in the infarct core and peri-infarct zone, but also in the remote 'healthy' myocardium, although there was only a minor change in the skeletal muscle. Substantial ferumoxytol uptake was detected only in cultured macrophages, but not in peripheral blood monocytes from study patients. CONCLUSION: We could demonstrate in humans that USPIO-based contrast agents enable a more detailed characterization of myocardial infarct pathology mainly by detecting infiltrating macrophages. Considering the multi-functionality of USPIO-based particles and their superior safety profile compared with gadolinium-based compounds, these observations open up new vistas for the clinical application of USPIO.

Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory.

BACKGROUND: The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed. METHODS: The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence. RESULTS: In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method. CONCLUSION: With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.

MRI assessment of experimental gliomas using 17.6 T.

INTRODUCTION: Using ultra-high-field contrast-enhanced magnetic resonance imaging (MRI), an increase of field strength is associated with a decrease of T 1 relaxivity. Yet, the impact of this effect on signal characteristics and contrast-enhanced pathology remains unclear. Hence, we evaluated the potential of a 17.6-T MRI to assess contrast-enhancing parts of experimentally induced rat gliomas compared to 3 T. METHODS: A total of eight tumor-bearing rats were used for MRI assessments either at 17.6 T (four rats) or at 3 T (four rats) at 11 days after stereotactic implantation of F98 glioma cells into the right frontal lobe. T 1-weighted sequences were used to investigate signal-to-noise-ratios, contrast-to-noise-ratios, and relative contrast enhancement up to 16 min after double-dose contrast application. In addition, tumor volumes were calculated and compared to histology. RESULTS: The 17.6-T-derived contrast-enhancing volumes were 31.5 ± 15.4 mm(3) at 4 min, 38.8 ± 12.7 mm(3) at 8 min, 51.1 ± 12.6 mm(3) at 12 min, and 61.5 ± 10.8 mm(3) at 16 min after gadobutrol injection. Corresponding histology-derived volumes were clearly higher (138.8 ± 8.4 mm(3); P < 0.01). At 3 T, contrast-enhancing volumes were 85.2 ± 11.7 mm(3) at 4 min, 107.3 ± 11.0 mm(3) at 8 min, 117.0 ± 10.5 mm(3) at 12 min, and 129.1 ± 10.0 mm(3) at 16 min after contrast agent application. Averaged histology-derived volumes (139.1 ± 13.4 mm(3)) in this group were comparable to the 16-min volume (P ↔16 min = 0.38). Compared to ultra-high-field MRI, all 3-T-derived volumes were significantly higher (P < 0.02). CONCLUSION: Compared to 3-T-derived images and histology, tumor volumes were underestimated by approximately 50 % at 17.6 T. Hence, contrast-enhanced 17.6-T MRI provided no further benefits in tumor measurement compared to 3 T.

Wide-spread brain activation and reduced CSF flow during avian REM sleep.

Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins, which the glymphatic system is thought to clear by flushing cerebral spinal fluid (CSF) through the brain. In mice, this process occurs during non-rapid eye movement (NREM) sleep. In humans, ventricular CSF flow has also been shown to increase during NREM sleep, as visualized using functional magnetic resonance imaging (fMRI). The link between sleep and CSF flow has not been studied in birds before. Using fMRI of naturally sleeping pigeons, we show that REM sleep, a paradoxical state with wake-like brain activity, is accompanied by the activation of brain regions involved in processing visual information, including optic flow during flight. We further demonstrate that ventricular CSF flow increases during NREM sleep, relative to wakefulness, but drops sharply during REM sleep. Consequently, functions linked to brain activation during REM sleep might come at the expense of waste clearance during NREM sleep.