Quantitative 23 Na-MRI of the intervertebral disk at 3 T.

Monitoring the tissue sodium content (TSC) in the intervertebral disk geometry noninvasively by MRI is a sensitive measure to estimate changes in the proteoglycan content of the intervertebral disk, which is a biomarker of degenerative disk disease (DDD) and of lumbar back pain (LBP). However, application of quantitative sodium concentration measurements in 23 Na-MRI is highly challenging due to the lower in vivo concentrations and smaller gyromagnetic ratio, ultimately yielding much smaller signal relative to 1 H-MRI. Moreover, imaging the intervertebral disk geometry imposes higher demands, mainly because the necessary RF volume coils produce highly inhomogeneous transmit field patterns. For an accurate absolute quantification of TSC in the intervertebral disks, the B1 field variations have to be mitigated. In this study, we report for the first time quantitative sodium concentration in the intervertebral disks at clinical field strengths (3 T) by deploying 23 Na-MRI in healthy human subjects. The sodium B1 maps were calculated by using the double-angle method and a double-tuned (1 H/23 Na) transceive chest coil, and the individual effects of the variation in the B1 field patterns in tissue sodium quantification were calculated. Phantom measurements were conducted to evaluate the quality of the Na-weighted images and B1 mapping. Depending on the disk position, the sodium concentration was calculated as 161.6 mmol/L-347 mmol/L, and the mean sodium concentration of the intervertebral disks varies between 254.6 ± 54 mmol/L and 290.1 ± 39 mmol/L. A smoothing effect of the B1 correction on the sodium concentration maps was observed, such that the standard deviation of the mean sodium concentration was significantly reduced with B1 mitigation. The results of this work provide an improved integration of quantitative 23 Na-MRI into clinical studies in intervertebral disks such as degenerative disk disease and establish alternative scoring schemes to existing morphological scoring such as the Pfirrmann score.

VERSE-guided parallel RF excitations using dynamic field correction.

In parallel RF pulse design, peak RF magnitudes and specific absorption rate levels are critical concerns in the hardware and safety limits. The variable rate selective excitation (VERSE) method is an efficient technique to limit the peak RF power by applying a local-only RF and gradient waveform reshaping while retaining the on-resonance profile. The accuracy of the excitation performed by the VERSEd RF and gradient waveforms strictly depends on the performance of the employed hardware. Any deviation from the nominal gradient fields as a result of frequency dependent system imperfections violates the VERSE condition similarly to off-resonance effects, leading to significant excitation errors and the RF pulse not converging to the targeted peak RF power. Moreover, for iterative VERSE-guided RF pulse design (i.e. reVERSE), the k-space trajectory actually changes at every iteration, which is assumed to be constant. In this work, we show both theoretically and experimentally the effect of gradient system imperfections on iteratively VERSEd parallel RF excitations. In order to improve the excitation accuracy besides limiting the RF power below certain thresholds, we propose to integrate gradient field monitoring or gradient impulse response function (GIRF) estimations of the actual gradient fields into the RF pulse design problem. A third-order dynamic field camera comprising a set of NMR field sensors and GIRFs was used to measure or estimate the actual gradient waveforms that are involved in the VERSE algorithm respectively. The deviating and variable k-space is counteracted at each iteration of the VERSE-guided iterative RF pulse design. The proposed approaches are demonstrated for accelerated multiple-channel spatially selective RF pulses, and highly improved experimental performance was achieved at both 3 T and 7 T.

Correction of parallel transmission using concurrent RF and gradient field monitoring.

OBJECTIVES: The accuracy and precision of the parallel RF excitations are highly dependent on the spatial and temporal fidelity of the magnetic fields involved in spin excitation. The consistency between the nominal and effective fields is typically limited by the imperfections of the employed hardware existing both in the gradient system and the RF chain. In this work, we experimentally presented highly improved spatially tailored parallel excitations by turning the native hardware accuracy challenge into a measurement and control problem using an advanced field camera technology to fully correct parallel RF transmission experiment. MATERIALS AND METHODS: An array of NMR field probes is used to measure the multiple channel RF pulses and gradient waveforms recording the high power RF pulses simultaneously with low frequency gradient fields on equal time basis. The recorded waveforms were integrated in RF pulse design for gradient trajectory correction, time imperfection compensation and introduction of iterative RF pre-emphasis. RESULTS: Superior excitation accuracy was achieved. Two major applications were presented at 7 Tesla including multi-dimensional tailored RF pulses for spatially selective excitation and slice-selective spoke pulses for [Formula: see text] mitigation. CONCLUSION: Comprehensive field monitoring is a highly effective means of correcting for the field deviations during parallel transmit pulse design.

Concurrent recording of RF pulses and gradient fields - comprehensive field monitoring for MRI.

Reconstruction of MRI data is based on exact knowledge of all magnetic field dynamics, since the interplay of RF and gradient pulses generates the signal, defines the contrast and forms the basis of resolution in spatial and spectral dimensions. Deviations caused by various sources, such as system imperfections, delays, eddy currents, drifts or externally induced fields, can therefore critically limit the accuracy of MRI examinations. This is true especially at ultra-high fields, because many error terms scale with the main field strength, and higher available SNR renders even smaller errors relevant. Higher baseline field also often requires higher acquisition bandwidths and faster signal encoding, increasing hardware demands and the severity of many types of hardware imperfection. To address field imperfections comprehensively, in this work we propose to expand the concept of magnetic field monitoring to also encompass the recording of RF fields. In this way, all dynamic magnetic fields relevant for spin evolution are covered, including low- to audio-frequency magnetic fields as produced by main magnets, gradients and shim systems, as well as RF pulses generated with single- and multiple-channel transmission systems. The proposed approach permits field measurements concurrently with actual MRI procedures on a strict common time base. The combined measurement is achieved with an array of miniaturized field probes that measure low- to audio-frequency fields via (19) F NMR and simultaneously pick up RF pulses in the MRI system's (1) H transmit band. Field recordings can form the basis of system calibration, retrospective correction of imaging data or closed-loop feedback correction, all of which hold potential to render MRI more robust and relax hardware requirements. The proposed approach is demonstrated for a range of imaging methods performed on a 7 T human MRI system, including accelerated multiple-channel RF pulses. Copyright © 2015 John Wiley & Sons, Ltd.

Application of portable sleep monitoring devices in pregnancy: a comprehensive review.

Objective.The physiological, hormonal and biomechanical changes during pregnancy may trigger sleep disordered breathing (SDB) in pregnant women. Pregnancy-related sleep disorders may associate with adverse fetal and maternal outcomes including gestational diabetes, preeclampsia, preterm birth and gestational hypertension. Most of the screening and diagnostic studies that explore SDB during pregnancy were based on questionnaires which are inherently limited in providing definitive conclusions. The current gold standard in diagnostics is overnight polysomnography (PSG) involving the comprehensive measurements of physiological changes during sleep. However, applying the overnight laboratory PSG on pregnant women is not practical due to a number of challenges such as patient inconvenience, unnatural sleep dynamics, and expenses due to highly trained personnel and technology. Parallel to the progress in wearable sensors and portable electronics, home sleep monitoring devices became indispensable tools to record the sleep signals of pregnant women at her own sleep environment. This article reviews the application of portable sleep monitoring devices in pregnancy with particular emphasis on estimating the perinatal outcomes.Approach.The advantages and disadvantages of home based sleep monitoring systems compared to subjective sleep questionnaires and overnight PSG for pregnant women were evaluated.Main Results.An overview on the efficiency of the application of home sleep monitoring in terms of accuracy and specificity were presented for particular fetal and maternal outcomes.Significance.Based on our review, more homogenous and comparable research is needed to produce conclusive results with home based sleep monitoring systems to study the epidemiology of SDB in pregnancy and its impact on maternal and neonatal health.

Regional effects of magnetization dispersion on quantitative perfusion imaging for pulsed and continuous arterial spin labeling.

Most experiments assume a global transit delay time with blood flowing from the tagging region to the imaging slice in plug flow without any dispersion of the magnetization. However, because of cardiac pulsation, nonuniform cross-sectional flow profile, and complex vessel networks, the transit delay time is not a single value but follows a distribution. In this study, we explored the regional effects of magnetization dispersion on quantitative perfusion imaging for varying transit times within a very large interval from the direct comparison of pulsed, pseudo-continuous, and dual-coil continuous arterial spin labeling encoding schemes. Longer distances between tagging and imaging region typically used for continuous tagging schemes enhance the regional bias on the quantitative cerebral blood flow measurement causing an underestimation up to 37% when plug flow is assumed as in the standard model.

Arterial spin labeling MRI using spiral acquisitions and concurrent field monitoring.

Perfusion MRI based on arterial spin labeling (ASL) has intrinsically very low signal-to-noise ratio (SNR). Signal acquisition at shorter echo times (TE) is necessary to boost the SNR of the ASL images. Spiral trajectories provide substantially shorter TE yielding increased SNR and are among the fastest k-space sampling schemes to encode a given field of view and resolution. Moreover, they provide approximately isotropic point-spread functions and inherent refocusing of motion- and flow-induced phase errors. However, the efficiency of the spiral acquisitions in ASL-MRI has been limited because these advantages are counterbalanced by practical technical challenges. This is because spiral acquisitions are highly sensitive to encoding deficiencies such as static off-resonance in the main magnetic field manifested as blurring artifacts in the image. Moreover, deviation of the gradient fields from the nominal waveforms due to the imperfection of the employed hardware critically limits the practical utilization of spiral trajectories. In this work, I provide single- and multiple-shot spiral ASL images that are robust against typical spiral encoding drawbacks enabled by deploying a comprehensive signal model involving static off-resonance and coil sensitivity maps and actual B0 and gradient field dynamics up to third order in space. The spiral ASL signal acquisition was concurrently monitored using a 3rd order dynamic field camera based on NMR field probes. The reconstructed ASL images at 3 mm and 2 mm in-plane resolution associating with the monitored field dynamics and the static off-resonances exhibited strongly reduced blurring- and aliasing artifacts and distortion. Concurrent field monitoring also enables to account for quasi-static B0 drifts by encompassing the parametric input data with consistent encoding geometry and physiological field fluctuations. In conclusion, concurrent field monitoring in spiral ASL acquisition largely overcomes traditional vulnerability of spiral trajectories in practice providing high quality ASL images with increased SNR, speed and motion robustness.

Retinotopic maps and hemodynamic delays in the human visual cortex measured using arterial spin labeling.

Cortical representations of the visual field are organized retinotopically, such that nearby neurons have receptive fields at nearby locations in the image. Many studies have used blood oxygenation level-dependent (BOLD) fMRI to non-invasively construct retinotopic maps in humans. The accuracy of the maps depends on the spatial extent of the metabolic and hemodynamic changes induced by the neural activity. Several studies using gradient-echo MRI at 1.5 T and 3T showed that most of the BOLD signal originates from veins, which might lead to a spatial displacement from the actual site of neuronal activation, thus reducing the specificity of the functional localization. In contrast to BOLD signal, cerebral blood flow (CBF) as measured using arterial spin labeling (ASL) is less or not at all affected by remote draining veins, and therefore spatially and temporally more closely linked to the underlying neural activity. In the present study, we determined retinotopic maps in the human brain using CBF as well as using BOLD signal in order to compare their spatial relationship and the temporal delays of each imaging modality for visual areas V1, V2, V3, hV4 and V3AB. We tested the robustness and reproducibility of the maps across different sessions, calculated the overlap as well as signal delay times across visual areas. While area boundaries were relatively well preserved, we found systematic differences of response latencies between CBF and the BOLD signal between areas. In summary, CBF data obtained using ASL allows reliable retinotopic maps to be constructed; this approach is, therefore, suitable for studying visual areas especially in close proximity to large veins where the BOLD signal is spatially inaccurate.

Differential effects of intranasal insulin and caffeine on cerebral blood flow.

Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task-induced CBF as well as blood oxygenation level-dependent (BOLD) response in the visual cortex using pulsed arterial spin-labeling MRI. An intranasal insulin application was used to avoid peripheral hyperinsulinaemia, which would lead to a cascade of hormonal changes. In a control experiment, caffeine was applied due to its well-known impact on the vasculature of the brain leading to a reliable reduction of CBF. Eight lean subjects were included in the study. On 2 separate days, intranasal human insulin or caffeine tablets were given to the subjects after fasting over night. On each day, basal CBF and task-induced CBF were measured before and 30 min after application of insulin or caffeine in each subject. During the task condition, a flickering checkerboard was presented. Insulin had no effect on basal CBF and task-induced CBF in comparison with drug-free baseline measurement in the visual cortex and control regions. After caffeine application, however, there was a significant decrease of CBF during stimulation in the visual cortex. The BOLD response was not altered by insulin or caffeine between pre- and postdose measurements. In conclusion, we found no evidence for a direct vasodilatory effect of intranasal insulin on the cerebral vascular system in this study.

Functional localization in the human brain: Gradient-Echo, Spin-Echo, and arterial spin-labeling fMRI compared with neuronavigated TMS.

A spatial mismatch of up to 14 mm between optimal transcranial magnetic stimulation (TMS) site and functional magnetic resonance imaging (fMRI) signal has consistently been reported for the primary motor cortex. The underlying cause might be the effect of magnetic susceptibility around large draining veins in Gradient-Echo blood oxygenation level-dependent (GRE-BOLD) fMRI. We tested whether alternative fMRI sequences such as Spin-Echo (SE-BOLD) or Arterial Spin-Labeling (ASL) assessing cerebral blood flow (ASL-CBF) may localize neural activity closer to optimal TMS positions and primary motor cortex than GRE-BOLD. GRE-BOLD, SE-BOLD, and ASL-CBF signal changes during right thumb abductions were obtained from 15 healthy subjects at 3 Tesla. In 12 subjects, tissue at fMRI maxima was stimulated with neuronavigated TMS to compare motor-evoked potentials (MEPs). Euclidean distances between the fMRI center-of-gravity (CoG) and the TMS motor mapping CoG were calculated. Highest SE-BOLD and ASL-CBF signal changes were located in the anterior wall of the central sulcus [Brodmann Area 4 (BA4)], whereas highest GRE-BOLD signal changes were significantly closer to the gyral surface. TMS at GRE-BOLD maxima resulted in higher MEPs which might be attributed to significantly higher electric field strengths. TMS-CoGs were significantly anterior to fMRI-CoGs but distances were not statistically different across sequences. Our findings imply that spatial differences between fMRI and TMS are unlikely to be caused by spatial unspecificity of GRE-BOLD fMRI but might be attributed to other factors, e.g., interactions between TMS-induced electric field and neural tissue. Differences between techniques should be kept in mind when using fMRI coordinates as TMS (intervention) targets.

Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes.

In glioblastoma, the benefit from temozolomide chemotherapy is largely limited to a subgroup of patients (30-35%) with tumors exhibiting methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. In order to allow more patients to benefit from this treatment, we explored magnetic resonance image-guided microbubble-enhanced low-intensity pulsed focused ultrasound (LIFU) to transiently open the blood-brain barrier and deliver a first-in-class liposome-loaded small molecule MGMT inactivator in mice bearing temozolomide-resistant gliomas. We demonstrate that a liposomal O6-(4-bromothenyl)guanine (O6BTG) derivative can efficiently target MGMT, thereby sensitizing murine and human glioma cells to temozolomide in vitro. Furthermore, we report that image-guided LIFU mediates the delivery of the stable liposomal MGMT inactivator in the tumor region resulting in potent MGMT depletion in vivo. Treatment with this new liposomal MGMT inactivator facilitated by LIFU-mediated blood-brain barrier opening reduced tumor growth and significantly prolonged survival of glioma-bearing mice, when combined with temozolomide chemotherapy. Exploring this novel combined approach in the clinic to treat glioblastoma patients with MGMT promoter-unmethylated tumors is warranted.

Closed-loop cavitation control for focused ultrasound-mediated blood-brain barrier opening by long-circulating microbubbles.

Focused ultrasound (FUS) exposure in the presence of microbubbles (MBs) has been successfully used in the delivery of various sizes of therapeutic molecules across the blood-brain barrier (BBB). While acoustic pressure is correlated with the BBB opening size, real-time control of BBB opening to avoid vascular and neural damage is still a challenge. This arises mainly from the variability of FUS-MB interactions due to the variations of animal-specific metabolic environment and specific experimental setup. In this study, we demonstrate a closed-loop cavitation control framework to induce BBB opening for delivering large therapeutic molecules without causing macro tissue damages. To this end, we performed in mice long-term (5 min) cavitation monitoring facilitated by using long-circulating MBs. Monitoring the long-term temporal kinetics of the MBs under varying level of FUS pressure allowed to identify in situ, animal specific activity regimes forming pressure-dependent activity bands. This enables to determine the boundaries of each activity band (i.e. steady oscillation, transition, inertial cavitation) independent from the physical and physiological dynamics of the experiment. However, such a calibration approach is time consuming and to speed up characterization of the in situ, animal specific FUS-MB dynamics, we tested a novel method called 'pre-calibration' that closely reproduces the results of long-term monitoring but with a much shorter duration. Once the activity bands are determined from the pre-calibration method, an operation band can be selected around the desired cavitation dose. To drive cavitation in the selected operation band, we developed an adaptive, closed-loop controller that updates the acoustic pressure between each sonication based on measured cavitation dose. Finally, we quantitatively assessed the safety of different activity bands and validated the proposed methods and controller framework. The proposed framework serves to optimize the FUS pressure instantly to maintain the targeted cavitation level while improving safety control.

Fat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans.

BACKGROUND: The hypothalamus is the central homeostatic control region of the brain and, therefore, highly influenced by nutrients such as glucose and fat. Immediate and prolonged homeostatic effects of glucose ingestion have been well characterized. However, studies that used stimulation with fat have mainly investigated immediate perceptional processes. Besides homeostatic processes, the gustatory cortex, including parts of the insular cortex, is crucial for the processing of food items. OBJECTIVE: The aim of this study was to investigate the effect of high- compared with low-fat meals on the hypothalamus and the insular cortex. DESIGN: Eleven healthy men participated in a single-blinded, functional MRI study of high- and low-fat meals on 2 measurement days. Cerebral blood flow (CBF) was measured before and 30 and 120 min after intake of high- and low-fat yogurts. Hunger was rated and blood samples were taken before each CBF measurement. RESULTS: High-fat yogurt induced a pronounced decrease in CBF in the hypothalamus, and the corresponding CBF change correlated positively with the insulin change. Furthermore, insular activity increased after 120 min in the low-fat condition only. The CBF change in both regions correlated positively in the high-fat condition. CONCLUSIONS: The decrease in hypothalamic activity and the interaction with the insular cortex elicited by fat may contribute to an efficient energy homeostasis. Therefore, fat might be a modulator of homeostatic and gustatory brain regions and their interaction. This trial was registered at clinicaltrials.gov as NCT01516021.

Quantifying the link between anatomical connectivity, gray matter volume and regional cerebral blood flow: an integrative MRI study.

BACKGROUND: In the graph theoretical analysis of anatomical brain connectivity, the white matter connections between regions of the brain are identified and serve as basis for the assessment of regional connectivity profiles, for example, to locate the hubs of the brain. But regions of the brain can be characterised further with respect to their gray matter volume or resting state perfusion. Local anatomical connectivity, gray matter volume and perfusion are traits of each brain region that are likely to be interdependent, however, particular patterns of systematic covariation have not yet been identified. METHODOLOGY/PRINCIPAL FINDINGS: We quantified the covariation of these traits by conducting an integrative MRI study on 23 subjects, utilising a combination of Diffusion Tensor Imaging, Arterial Spin Labeling and anatomical imaging. Based on our hypothesis that local connectivity, gray matter volume and perfusion are linked, we correlated these measures and particularly isolated the covariation of connectivity and perfusion by statistically controlling for gray matter volume. We found significant levels of covariation on the group- and regionwise level, particularly in regions of the Default Brain Mode Network. CONCLUSIONS/SIGNIFICANCE: Connectivity and perfusion are systematically linked throughout a number of brain regions, thus we discuss these results as a starting point for further research on the role of homology in the formation of functional connectivity networks and on how structure/function relationships can manifest in the form of such trait interdependency.

May Toxoplasma gondii increase suicide attempt-preliminary results in Turkish subjects?

Suicide attempts are one of the risk factors of suicide. Possible mechanisms by which Toxoplasma gondii may affect human behavior and it may also cause humans to attempt suicide. The aim of this study is to find out whether or not T. gondii is one of the reasons in suicide attempts. We investigated the sero-positivity level for anti-Toxoplasma IgG and IgM antibodies by enzyme-linked immunosorbent assay in subjects who have attempted to suicide to find out whether there is a probable relationship between T. gondii and suicide attempts. In our study, we selected 200 cases of suicide attempts and 200 healthy volunteers. The sero-positivity level for anti-Toxoplasma IgG antibodies among suicide attempts (41%) was significantly higher than the control group (28%). This signifies that there might be a causal relationship between toxoplasmosis and the etiology of suicide attempt.

Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification.

Arterial spin labeling (ASL) using magnetic resonance imaging (MRI) is a powerful noninvasive technique to investigate the physiological status of brain tissue by measuring cerebral blood flow (CBF). ASL assesses the inflow of magnetically labeled arterial blood into an imaging voxel. In the last 2 decades, various ASL sequences have been proposed which differ in their ease of implementation and their sensitivity to artifacts. In addition, several quantification methods have been developed to determine the absolute value of CBF from ASL magnetization difference images. In this study, we evaluated three pulsed ASL sequences and three absolute quantification schemes. It was found that FAIR-QUIPSSII implementation of ASL yields 10-20% higher signal-to-noise ratio (SNR) and 18% higher CBF as compared with PICORE-Q2TIPS (with FOCI pulses) and PICORE-QUIPSSII (with BASSI pulses). In addition, quantification schemes employed can give rise to up to a 35% difference in CBF values. We conclude that, although all quantitative ASL sequences and CBF calibration methods should in principle result in the similar CBF values and image quality, substantial differences in CBF values and SNR were found. Thus, comparing studies using different ASL sequences and analysis algorithms is likely to result in erroneous intra- and intergroup differences. Therefore, (i) the same quantification schemes should consistently be used, and (ii) quantification using local tissue proton density should yield the most accurate CBF values because, although still requiring definitive demonstration in future studies, the proton density of blood is assumed to be very similar to the value of gray matter.