Echoes from Intrinsic Connectivity Networks in the Subcortex.

Decades of research have greatly improved our understanding of intrinsic human brain organization in terms of functional networks and the transmodal hubs within the cortex at which they converge. However, substrates of multinetwork integration in the human subcortex are relatively uncharted. Here, we leveraged recent advances in subcortical atlasing and ultra-high field (7 T) imaging optimized for the subcortex to investigate the functional architecture of 14 individual structures in healthy adult males and females with a fully data-driven approach. We revealed that spontaneous neural activity in subcortical regions can be decomposed into multiple independent subsignals that correlate with, or "echo," the activity in functional networks across the cortex. Distinct subregions of the thalamus, striatum, claustrum, and hippocampus showed a varied pattern of echoes from attention, control, visual, somatomotor, and default mode networks, demonstrating evidence for a heterogeneous organization supportive of functional integration. Multiple network activity furthermore converged within the globus pallidus externa, substantia nigra, and ventral tegmental area but was specific to one subregion, while the amygdala and pedunculopontine nucleus preferentially affiliated with a single network, showing a more homogeneous topography. Subregional connectivity of the globus pallidus interna, subthalamic nucleus, red nucleus, periaqueductal gray, and locus coeruleus did not resemble patterns of cortical network activity. Together, these finding describe potential mechanisms through which the subcortex participates in integrated and segregated information processing and shapes the spontaneous cognitive dynamics during rest.SIGNIFICANCE STATEMENT Despite the impact of subcortical dysfunction on brain health and cognition, large-scale functional mapping of subcortical structures severely lags behind that of the cortex. Recent developments in subcortical atlasing and imaging at ultra-high field provide new avenues for studying the intricate functional architecture of the human subcortex. With a fully data-driven analysis, we reveal subregional connectivity profiles of a large set of noncortical structures, including those rarely studied in fMRI research. The results have implications for understanding how the functional organization of the subcortex facilitates integrative processing through cross-network information convergence, paving the way for future work aimed at improving our knowledge of subcortical contributions to intrinsic brain dynamics and spontaneous cognition.

Tuned bipolar oscillating gradients for mapping frequency dispersion of diffusion kurtosis in the human brain.

PURPOSE: Oscillating gradient spin-echo (OGSE) sequences have demonstrated an ability to probe time-dependent microstructural features, although they often suffer from low SNR due to increased TEs. In this work we introduce frequency-tuned bipolar (FTB) gradients as a variation of oscillating gradients with reduced TE and demonstrate their utility by mapping the frequency dispersion of kurtosis in human subjects. METHODS: An FTB oscillating gradient waveform is presented that provides encoding of 1.5 net oscillation periods, thereby reducing the TE of the acquisition. Simulations were performed to determine an optimal protocol based on the SNR of kurtosis frequency dispersion-defined as the difference in kurtosis between pulsed and oscillating gradient acquisitions. Healthy human subjects were scanned at 7T using pulsed gradient and an optimized 23 Hz FTB protocol, which featured a maximum b-value of 2500 s/mm2 . In addition, to directly compare existing methods, measurements using traditional cosine OGSE were also acquired. RESULTS: FTB oscillating gradients demonstrated equivalent frequency-dependent diffusion measurements compared with cosine-modulated OGSE while enabling a significant reduction in TE. Optimization and in vivo results suggest that FTB gradients provide increased SNR of kurtosis dispersion maps compared with traditional cosine OGSE. The optimized FTB gradient protocol demonstrated consistent reductions in apparent kurtosis values and increased diffusivity in generated frequency dispersion maps. CONCLUSIONS: This work presents an alternative to traditional cosine OGSE sequences, enabling more time-efficient acquisitions of frequency-dependent diffusion quantities as demonstrated through in vivo kurtosis frequency dispersion maps.

Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users.

Cannabis is the most commonly used illicit drug in the world. However, because of a changing legal landscape and rising interest in therapeutic utility, there is an increasing trend in (long-term) use and possibly cannabis impairment. Importantly, a growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding, effects of the drug. However, the neuroadaptations that may underlie cannabis tolerance remain unclear. Therefore, this double-blind, randomized, placebo-controlled, cross-over study assessed the acute influence of cannabis on the brain and behavioral outcomes in two distinct cannabis user groups. Twelve occasional and 12 chronic cannabis users received acute doses of cannabis (300-µg/kg delta-9-tetrahydrocannabinol) and placebo and underwent ultrahigh field functional magnetic resonance imaging and magnetic resonance spectroscopy. In occasional users, cannabis induced significant neurometabolic alterations in reward circuitry, namely, decrements in functional connectivity and increments in striatal glutamate concentrations, which were associated with increases in subjective high and decreases in performance on a sustained attention task. Such changes were absent in chronic users. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users. Taken together, the results suggest a pharmacodynamic mechanism for the development of tolerance to cannabis impairment, of which is important to understand in the context of the long-term therapeutic use of cannabis-based medications, as well as in the context of public health and safety of cannabis use when performing day-to-day operations.

On the reproducibility of hippocampal MEGA-sLASER GABA MRS at 7T using an optimized analysis pipeline.

OBJECTIVES: GABA is the most important inhibitory neurotransmitter. Thus, variation in its concentration is connected to a wide variety of diseases. However, the low concentration and the overlap of more prominent resonances hamper GABA quantification using MR spectroscopy. The hippocampus plays a pivotal role in neurodegeneration. Susceptibility discontinuities in the vicinity of the hippocampus cause strong B0 inhomogeneities, impeding GABA spectroscopy. The aim of this work is to improve the reproducibility of hippocampal GABA+ MRS. METHODS: The GABA+/total creatine ratio in the hippocampus was measured using a MEGA-sLASER sequence at 7 Tesla. 10 young healthy volunteers participated in the study. A dedicated pre-processing approach was established. Spectral quantification was performed with Tarquin. The quantification parameters were carefully adjusted to ensure optimal quantification. RESULTS: An inter-subject coefficient of variation of the GABA+/total creatine of below 15% was achieved. Additional to spectral registration, which is essential to obtain reproducible GABA measures, eddy current compensation and additional difference artifact suppression improved the reproducibility. The mean FWHM was 23.1 Hz (0.078 ppm). CONCLUSION: The increased spectral dispersion of ultra-high-field spectroscopy allows for reproducible spectral quantification, despite a very broad line width. The achieved reproducibility enables the routine use of hippocampal GABA spectroscopy at 7 Tesla.

A new hypertonic saline assay for analgesic screening in mice: effects of animal strain, sex, and diurnal phase.

PURPOSE: There exists a pressing need for the identification of novel analgesics. We recently reported on a new preclinical assay for rapid analgesic screening based on intraplantar (i.pl.) injection of 10% hypertonic saline (HS) in female outbred (CD-1) mice. Herein, we characterized the HS assay's performance in inbred (C57BL/6) mice, sensitivity to sex differences, and effects of diurnal rhythm phase. METHODS: In randomized, controlled, blinded in vivo animal experiments, we studied nociceptive responses induced by i.pl. HS in C57BL/6 (vs CD-1) mice of both sexes (n = 240) and determined diurnal rhythm phase effects in female animals. We established the HS assay's sensitivity to morphine by constructing dose-response curves and calculating half-maximal inhibitory doses (ID50s). RESULTS: The injection of i.pl. HS produced nociceptive (licking and biting) responses in all C57BL/6 mice tested. In both C57BL/6 and CD-1 mice, the mean (95% confidence interval [CI]) response magnitudes were greater in females vs males (C57BL/6: 87 sec [64 to 110] vs 45 sec [29 to 61]; difference in means, 42 sec; 95% CI, 17 to 68; P < 0.001; n = 10/group; CD-1: 110 sec [95 to 126] vs 53 sec [32 to 74]; difference in means, 57 sec; 95% CI, 34 to 79; P < 0.001; n = 10/group). The mean (95% CI) nociceptive responses were greater at 24:00 hr than at 12:00 hr in C57BL/6 mice (64 sec [40 to 88] vs 37 sec [24 to 51]; difference in means, 27 sec; 95% CI, 7 to 47; P = 0.007; n = 10/group), but not in CD-1 mice (P = 0.97). Intravenous morphine dose-dependently attenuated nociceptive responses of both C57BL/6 and CD-1 mice (ID50, 0.6 and 2.5 mg·kg-1, respectively; P = 0.41). CONCLUSION: These findings in inbred and outbred mice solidify the utility of the HS assay as an effective, rapid, robust, and versatile preclinical tool for analgesic screening.

RéSUMé: OBJECTIF: Il existe un besoin impérieux d'identification de nouveaux analgésiques. Nous avons récemment publié les conclusions d'un nouveau test préclinique portant sur le dépistage analgésique rapide basé sur l'injection intraplantaire (i.pl.) d'une solution saline hypertonique à 10 % (HS) chez des souris femelles croisées (CD-1). Dans notre présente étude, nous avons caractérisé la performance du test de HS chez des souris consanguines (C57BL/6), la sensibilité aux différences de sexe, et les effets des phases de rythme diurne. MéTHODE: Dans le cadre d'expériences animales in vivo en aveugle randomisées contrôlées, nous avons étudié les réponses nociceptives induites par une i.pl. de HS chez des souris C57BL/6 (vs CD-1) des deux sexes (n = 240) et déterminé les effets des phases du rythme diurne chez les animaux femelles. Nous avons établi la sensibilité du test HS à la morphine en construisant des courbes de dose-réponse et en calculant des doses inhibitrices semi-maximales (DI50). RéSULTATS: L'injection i.pl. de HS a produit des réponses nociceptives (léchage et morsure) chez toutes les souris C57BL/6 testées. Chez les souris C57BL/6 et CD-1, les magnitudes de réponse moyenne [intervalle de confiance (IC) 95 %] étaient plus élevées chez les femelles que chez les mâles (C57BL/6 : 87 [64 à 110] vs 45 [29 à 61] sec; différence de moyennes, 42 sec; IC 95 %, 17 à 68; P < 0,001; n = 10/groupe; CD-1: 110 [95 à 126] vs 53 [32 à 74] sec; différence de moyennes, 57 sec; IC 95 %, 34 à 79; P < 0,001; n = 10/groupe). Les réponses nociceptives moyennes [IC 95 %] étaient plus importantes à minuit (24 h) qu'à midi (12 h) chez les souris C57BL/6 (64 [40 à 88] sec vs 37 [24 à 51] sec; différence de moyennes, 27 sec; IC 95 %, 7 à 47; P = 0,007; n = 10/groupe), mais pas chez les souris CD-1 (P = 0,97). La morphine intraveineuse a atténué de façon dose-dépendante les réponses nociceptives chez les souris C57BL/6 et CD-1 (DI50, 0,6 et 2,5 mg·kg−1, respectivement; P = 0,41). CONCLUSION: Ces résultats chez les souris croisées et consanguines appuient l'utilité du test de HS comme un outil préclinique efficace, rapide, robuste et polyvalent pour le dépistage analgésique.

Can We Accurately Identify Peritoneal Metastases Based on Their Appearance? An Assessment of the Current Practice of Intraoperative Gastrointestinal Cancer Staging.

BACKGROUND: Peritoneal lesions are common findings during operative abdominal cancer staging. The decision to perform biopsy is made subjectively by the surgeon, a practice the authors hypothesized to be imprecise. This study aimed to describe optical characteristics differentiating benign peritoneal lesions from peritoneal metastases. METHODS: The study evaluated laparoscopic images of 87 consecutive peritoneal lesions biopsied during staging laparoscopies for gastrointestinal malignancies from 2014 to 2017. A blinded survey assessing these lesions was completed by 10 oncologic surgeons. Three senior investigators categorized optical features of the lesions. Computer-aided digital image processing and machine learning was used to classify the lesions. RESULTS: Of the 87 lesions, 28 (32%) were metastases. On expert survey, surgeons on the average misidentified 36 ± 19% of metastases. Multivariate analysis identified degree of nodularity, border transition, and degree of transparency as independent predictors of metastases (each p < 0.03), with an area under the receiver operating characteristics curve (AUC) of 0.82 (95% confidence interval [CI], 0.72-0.91). Image processing demonstrated no difference using image color segmentation, but showed a difference in gradient magnitude between benign and metastatic lesions (AUC, 0.66; 95% CI 0.54-0.78; p = 0.02). Machine learning using a neural network with a tenfold cross-validation obtained an AUC of only 0.47. CONCLUSIONS: To date, neither experienced oncologic surgeons nor computerized image analysis can differentiate peritoneal metastases from benign peritoneal lesions with an accuracy that is clinically acceptable. Although certain features correlate with the presence of metastases, a substantial overlap in optical appearance exists between benign and metastatic peritoneal lesions. Therefore, this study suggested the need to perform biopsy for all peritoneal lesions during operative staging, or at least to lower the threshold significantly.

Forest disturbance and vector transmitted diseases in the lowland tropical rainforest of central Panama.

OBJECTIVE: To explore possible changes in the community attributes of haematophagous insects as a function of forest disturbance. We compare the patterns of diversity and abundance, plus the behavioural responses of three epidemiologically distinct vector assemblages across sites depicting various levels of forest cover. METHODS: Over a 3-year period, we sampled mosquitoes, sandflies and biting-midges in forested habitats of central Panama. We placed CDC light traps in the forest canopy and in the understorey to gather blood-seeking females. RESULTS: We collected 168 405 adult haematophagous dipterans in total, including 26 genera and 86 species. Pristine forest settings were always more taxonomically diverse than the disturbed forest sites, confirming that disturbance has a negative impact on species richness. Species of Phlebotominae and Culicoides were mainly classified as climax (i.e. forest specialist) or disturbance-generalist, which tend to decrease in abundance along with rising levels of disturbance. In contrast, a significant portion of mosquito species, including primary and secondary disease vectors, was classified as colonists (i.e. disturbed-areas specialists), which tend to increase in numbers towards more disturbed forest habitats. At pristine forest, the most prevalent species of Phlebotominae and Culicoides partitioned the vertical niche by being active at the forest canopy or in the understorey; yet this pattern was less clear in disturbed habitats. Most mosquito species were not vertically stratified in their habitat preference. CONCLUSION: We posit that entomological risk and related pathogen exposure to humans is higher in pristine forest scenarios for Culicoides and Phlebotominae transmitted diseases, whereas forest disturbance poses a higher entomological risk for mosquito-borne infections. This suggests that the Dilution Effect Hypothesis (DEH) does not apply in tropical rainforests where highly abundant, yet unrecognised insect vectors and neglected zoonotic diseases occur. Comprehensive, community level entomological surveillance is, therefore, the key for predicting potential disease spill over in scenarios of pristine forest intermixed with anthropogenic habitats. We suggest that changes in forest quality should also be considered when assessing arthropod-borne disease transmission risk.

OBJECTIF: Explorer les changements possibles dans les attributs communautaires des insectes hématophages en fonction de la perturbation des forêts. Nous comparons les modèles de diversité et d'abondance, ainsi que les réponses comportementales de trois assemblages de vecteurs épidémiologiquement distincts sur des sites illustrant divers niveaux de couverture forestière. MÉTHODES: Au cours d'une période de trois ans, nous avons échantillonné des moustiques, des phlébotomes et des moucherons piqueurs dans les habitats forestiers du centre de Panama. Nous avons placé des pièges à lumière CDC dans la canopée de la forêt et dans le sous-étage pour recueillir les femelles en quête de sang. RÉSULTATS: Nous avons collecté un total de 168.405 diptères hématophages adultes, dont 26 genres et 86 espèces. Les environnements de forêt intacts étaient toujours plus diversifiés du point de vue taxonomique que les sites forestiers perturbés, confirmant que les perturbations avaient un impact négatif sur la richesse en espèces. Les espèces de phlébotome et Culicoïdes étaient principalement classés comme climax (spécialiste de la forêt) ou généralistes de perturbation, qui ont tendance à diminuer en abondance parallèlement aux niveaux croissants de perturbation. En revanche, une partie importante des espèces de moustiques, y compris les vecteurs primaires et secondaires de maladies, a été classée dans la catégorie des colons (c'est-à-dire spécialistes des zones perturbées), qui ont tendance à se multiplier vers des habitats forestiers plus perturbés. Dans la forêt vierge, les espèces de phlébotomes et Culicoïdes les plus répandues cloisonnaient la niche verticale en étant actives dans la canopée de la forêt ou dans le sous-étage; pourtant, cette tendance était moins nette dans les habitats perturbés. La plupart des espèces de moustiques n'étaient pas stratifiées verticalement dans leur préférence d'habitat. CONCLUSION: Nous estimons que le risque entomologique et l'exposition associée des agents pathogènes à l'homme est plus élevé dans les scénarios de forêt vierge pour les maladies transmises par les phlébotomes et Culicoïdes, alors que la perturbation des forêts pose un risque entomologique plus élevé pour les infections transmises par les moustiques. Cela suggère que l'hypothèse de l'effet de dilution ne s'applique pas dans les forêts tropicales humides où se reproduisent très abondamment les insectes vecteurs, mais non reconnus, et où des maladies zoonotiques négligées surviennent. Une surveillance entomologique approfondie au niveau de la communauté est donc la clé pour prédire le potentiel de propagation des maladies dans des scénarios de forêt vierge mélangée à des habitats anthropiques. Nous suggérons que les changements dans la qualité des forêts soient également pris en compte lors de l'évaluation du risque de propagation de maladies transmises par les arthropodes.

Ultra-high resolution blood volume fMRI and BOLD fMRI in humans at 9.4 T: Capabilities and challenges.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

Association between Cortical GABA and Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Humans.

Loudness dependence of auditory evoked potentials (LDAEP) is a widely used EEG-based biomarker for central serotonergic activity. Serotonin has been shown to be associated with different psychiatric disorders such as depression and schizophrenia. Despite its clinical significance, the underlying neurochemical mechanism of this promising marker is not fully understood, and further research is needed to improve its validity. Other neurotransmitters might have a significant impact on this measure. Thus, we assessed the inhibitory action through individual GABA/H20 concentrations and GABA/glutamate ratios by means of magnetic resonance spectroscopy at 3T in healthy subjects. The measurements were assessed in the primary auditory cortex to investigate the association with the LDAEP, whose generators are mainly in the primary auditory cortex. For the first time, this study examines the link between GABAergic neurotransmission and LDAEP, and the data preliminary show that GABA may not contribute to the generation of EEG-based LDAEP.

GABA metabolism and its role in gamma-band oscillatory activity during auditory processing: An MRS and EEG study.

Gamma-aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency-specific synchronization of neuronal excitability within the gamma band (30-80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30-200 Hz) and time (-200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975-3987, 2017. © 2017 Wiley Periodicals, Inc.

Microstructural and functional correlates of glutamate concentration in the posterior cingulate cortex.

Glutamate is the major excitatory neurotransmitter in the human brain and has a central role in both intrinsic and stimulus-induced activity. We conducted a study in a cohort of healthy, male volunteers in which glutamate levels were measured in the posterior cingulate cortex (PCC) using 1H magnetic resonance spectroscopy at 3T. The advantages of simultaneous electroencephalography and magnetic resonance imaging (EEG-MRI) were exploited and the subjects were measured in the same session and under the same physiological conditions. Diffusion tensor imaging (DTI), functional MRI (fMRI) and EEG were measured in order to investigate the functional and microstructural correlates of glutamate. The concentration of glutamate (institute units) was calculated and those values were tested for correlation with the metrics of resting state fMRI, DTI, and EEG electrical sources. Our results showed that the concentration of glutamate in the PCC had a significant negative correlation with the tissue mean diffusivity in the same area. The analysis of resting state networks did not show any relationship between the concentration of glutamate and the intrinsic activity of the resting state networks. The concentration of glutamate showed a positive correlation with the electrical generators of α-1 frequency and a negative correlation with the generators of α-2 and ß-1 electrical generators. © 2017 Wiley Periodicals, Inc.

Estimating and eliminating the excitation errors in bipolar gradient composite excitations caused by radiofrequency-gradient delay: Example of bipolar spokes pulses in parallel transmission.

PURPOSE: To eliminate a slice-position-dependent excitation error commonly observed in bipolar-gradient composite excitations such as spokes pulses in parallel transmission. THEORY AND METHODS: An undesired timing delay between subpulses in the composite pulse and their bipolar slice-selective gradient is hypothesized to cause the error. A mathematical model is presented here to relate this mismatch to an induced slice-position-dependent phase difference between the subpulses. A new navigator method is proposed to measure the timing mismatch and eliminate the error. This is demonstrated at 7 Tesla with flip-angle maps measured by a presaturation turbo-flash sequence and in vivo images acquired by a simultaneous multislice/echo-planar imaging (SMS-EPI) sequence. RESULTS: Error-free flip-angle maps were obtained in two ways: 1) by correcting the time delay directly and 2) by applying the corresponding slice-position-dependent phase differences to the subpulses. This confirms the validity of the mathematical description. The radiofrequency (RF)-gradient delay measured by the navigator method was of 6.3 µs, which agreed well with the estimate from flip-angle maps at different delay times. By applying the timing correction, accurately excited EPI images were acquired with bipolar dual-spokes SMS-2 excitations. CONCLUSION: An effective correction is proposed to mitigate slice-position-dependent errors in bipolar composite excitations caused by undesired RF-gradient timing delays. Magn Reson Med 78:1883-1890, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High-resolution gradient-recalled echo imaging at 9.4T using 16-channel parallel transmit simultaneous multislice spokes excitations with slice-by-slice flip angle homogenization.

PURPOSE: In order to fully benefit from the improved signal-to-noise and contrast-to-noise ratios at 9.4T, the challenges of B1+ inhomogeneity and the long acquisition time of high-resolution 2D gradient-recalled echo (GRE) imaging were addressed. THEORY AND METHODS: Flip angle homogenized excitations were achieved by parallel transmission (pTx) of 3-spoke pulses, designed by magnitude least-squares optimization in a slice-by-slice fashion; the acquisition time reduction was achieved by simultaneous multislice (SMS) pulses. The slice-specific spokes complex radiofrequency scaling factors were applied to sinc waveforms on a per-channel basis and combined with the other pulses in an SMS slice group to form the final SMS-pTX pulse. Optimal spokes locations were derived from simulations. RESULTS: Flip angle maps from presaturation TurboFLASH showed improvement of flip angle homogenization with 3-spoke pulses over CP-mode excitation (normalized root-mean-square error [NRMSE] 0.357) as well as comparable excitation homogeneity across the single-band (NRMSE 0.119), SMS-2 (NRMSE 0.137), and SMS-3 (NRMSE 0.132) 3-spoke pulses. The application of the 3-spoke SMS-3 pulses in a 48-slice GRE protocol, which has an in-plane resolution of 0.28 × 0.28 mm, resulted in a 50% reduction of scan duration (total acquisition time 6:52 min including reference scans). CONCLUSION: Time-efficient flip angle homogenized high-resolution GRE imaging at 9.4T was accomplished by using slice-specific SMS-pTx spokes excitations. Magn Reson Med 78:1050-1058, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

B1+ inhomogeneity mitigation in CEST using parallel transmission.

PURPOSE: In order to benefit from the increased spectral bandwidth at ultrahigh field (UHF), the use of parallel transmission (pTx) to mitigate flip-angle inhomogeneity in chemical exchange saturation transfer (CEST) imaging is investigated. THEORY AND METHODS: A pTx basis pulse is homogenised by magnitude least-squares (MLS) optimization and expanded to form a frequency-selective saturation pulse for CEST. The pTx saturation pulse was simulated with a three-pool Bloch-McConnell equation to evaluate the impact of pTx on CEST contrast. In vivo CEST imaging performance (7 T) of the pTx saturation pulse and the standard Gaussian saturation in circularly polarized mode were compared. Two-spokes pTx homogeneous excitation was used in all in vivo experiments to ensure fair comparison of the two saturation pulses. Magnetization transfer ratio and inverse Z-spectrum analyses were used as metrics in evaluating the data from 3 healthy volunteers. RESULTS: Bloch-McConnell simulations showed that side bands of the pTx saturation pulse at ±20 ppm did not affect any CEST contrast. Improved homogeneity in contrasts and relaxation-compensated CEST metrics were observed in our in vivo data when the pTx saturation pulse was used. CONCLUSION: A pTx-based pulsed CEST presaturation scheme is proposed and validated by simulations and 7T in vivo imaging. Magn Reson Med 78:2216-2225, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Application of the limited-memory quasi-Newton algorithm for multi-dimensional, large flip-angle RF pulses at 7T.

OBJECTIVE: Ultrahigh field MRI provides great opportunities for medical diagnostics and research. However, ultrahigh field MRI also brings challenges, such as larger magnetic susceptibility induced field changes. Parallel-transmit radio-frequency pulses can ameliorate these complications while performing advanced tasks in routine applications. To address one class of such pulses, we propose an optimal-control algorithm as a tool for designing advanced multi-dimensional, large flip-angle, radio-frequency pulses. We contrast initial conditions, constraints, and field correction abilities against increasing pulse trajectory acceleration factors. MATERIALS AND METHODS: On an 8-channel 7T system, we demonstrate the quasi-Newton algorithm with pulse designs for reduced field-of-view imaging with an oil phantom and in vivo with scans of the human brain stem. We used echo-planar imaging with 2D spatial-selective pulses. Pulses are computed sufficiently rapid for routine applications. RESULTS: Our dataset was quantitatively analyzed with the conventional mean-square-error metric and the structural-similarity index from image processing. Analysis of both full and reduced field-of-view scans benefit from utilizing both complementary measures. CONCLUSION: We obtained excellent outer-volume suppression with our proposed method, thus enabling reduced field-of-view imaging using pulse trajectory acceleration factors up to 4.

Laparoscopic narrow band imaging for detection of occult cancer metastases: a randomized feasibility trial.

BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the underlying malignancy. The aim of this study was to evaluate the feasibility and effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and detection of occult peritoneal cancer metastases. METHODS: A randomized, controlled feasibility trial with crossover design evaluating adult patients with gastrointestinal or gynecologic malignancies who have a clinical indication for diagnostic laparoscopy was conducted. Twenty-three patients were randomized to white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity was sufficiently illuminated. An enhanced contrast of microvasculature and organ surface pattern was appreciated. Eight of the 20 patients (40%) were found to have metastases of the peritoneal surface. While NBI did not show any additional peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light imaging were not visible on NBI (p = 0.50). The median diameter of all the nodules identified was 2 mm (range 1-50 mm) and was identical with each method. CONCLUSIONS: The information from this feasibility study demonstrated that NBI provides adequate illumination of the abdominal cavity and a unique contrast that enhances microvasculature and architectural surface pattern. The results suggest that NBI laparoscopy is not superior in detecting peritoneal metastases compared to standard white-light laparoscopy, but might provide a technology that could be applied for other abdominal pathologies.

Volumetric imaging with homogenised excitation and static field at 9.4 T.

OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner. MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively. RESULTS: Over six in vivo acquisitions, the B0-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 ± 0.9 to 9.2 ± 0.7 % with all B 1 (+)  voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image. CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.

RF peak power reduction in CAIPIRINHA excitation by interslice phase optimization.

The purpose of this work was to show that the overall peak power of RF pulses for CAIPIRINHA excitation can be substantially reduced by applying interslice phase relaxation. The optimal phases are scan dependent and can be quickly calculated by the proposed method. The multi-band RF pulse design is implemented as the minimization of a linear objective function with quadratic constraints. The interslice phase is considered to be a variable for optimization. In the case of a phase cycling scheme (CAIPIRINHA), the peak power is considered over all pulses. The computation time (about 1 s) is compatible with online RF pulse design. It is shown that the optimal interslice phases depend on the CAIPIRINHA scheme used and that RF peak power is reduced when the CAIPIRINHA phase cycling is taken into account in the optimization. The proposed method is extremely fast and results in RF pulses with low peak power for CAIPIRINHA excitation. The MATLAB implementation is given in the appendix; it allows for online determination of scan-dependent phase parameters. Furthermore, the method can be easily extended to pTx shimming systems in the context of multi-slice excitations, and this possibility is included in the software.

From shadow to light: visualization of extrahepatic bile ducts using image-enhanced laparoscopy.

BACKGROUND: Correct recognition of the extrahepatic bile ducts is thought to be crucial to reduce the risk of bile duct injuries during various laparoscopic procedures. Image-enhanced laparoscopy techniques, utilizing various optical modalities other than white light, may help in detecting structures "hidden" underneath connective tissue. METHODS: A systematic literature search was conducted of studies describing image-enhanced laparoscopy techniques for visualization of the extrahepatic bile ducts. RESULTS: In all, 29 articles met inclusion criteria. They describe various techniques in the animal or human setting, including autofluorescence imaging, drug-enhanced fluorescence imaging, infrared thermography, and spectral imaging. This review describes these various techniques and their results. CONCLUSION: Image-enhanced laparoscopy techniques for real-time visualization of extrahepatic bile ducts are still in its infancy. Out of the techniques currently described, indocyanine green-enhanced near-infrared fluorescence laparoscopy has the most mature results, but other techniques also appear promising. It can be expected that in the future, image-enhanced laparoscopy might become a routine adjunct to any white-light laparoscopic operation near the hepatic hilum.