Clinical feasibility of post-contrast accelerated 3D T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) with iterative denoising for intracranial enhancing lesions: a retrospective study.

BACKGROUND: Post-contrast T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) is the preferred 3D T1 spin-echo sequence for evaluating brain metastases, regardless of the prolonged scan time. PURPOSE: To evaluate the application of accelerated post-contrast T1-SPACE with iterative denoising (ID) for intracranial enhancing lesions in oncologic patients. MATERIAL AND METHODS: For evaluation of intracranial lesions, 108 patients underwent standard and accelerated T1-SPACE during the same imaging session. Two neuroradiologists evaluated the overall image quality, artifacts, degree of enhancement, mean contrast-to-noise ratiolesion/parenchyma, and number of enhancing lesions for standard and accelerated T1-SPACE without ID. RESULTS: Although there was a significant difference in the overall image quality and mean contrast-to-noise ratiolesion/parenchyma between standard and accelerated T1-SPACE without ID and accelerated SPACE with and without ID, there was no significant difference between standard and accelerated T1-SPACE with ID. Accelerated T1-SPACE showed more artifacts than standard T1-SPACE; however, accelerated T1-SPACE with ID showed significantly fewer artifacts than accelerated T1-SPACE without ID. Accelerated T1-SPACE without ID showed a significantly lower number of enhancing lesions than standard- and accelerated T1-SPACE with ID; however, there was no significant difference between standard and accelerated T1-SPACE with ID, regardless of lesion size. CONCLUSION: Although accelerated T1-SPACE markedly decreased the scan time, it showed lower overall image quality and lesion detectability than the standard T1-SPACE. Application of ID to accelerated T1-SPACE resulted in comparable overall image quality and detection of enhancing lesions in brain parenchyma as standard T1-SPACE. Accelerated T1-SPACE with ID may be a promising replacement for standard T1-SPACE.

Impact of Dysphonic Schoolteachers' Voices on Children's Reaction Times according to Phonemic Contrasts.

INTRODUCTION: This paper aimed at observing the impact of dysphonic voice on children's reception of a linguistic message by evaluating their reaction times (RTs) to instructions given by functional dysphonic and control female schoolteachers (STs). METHODS: French minimal pairs such as /muʃ/ ("mouche" fly) versus /buʃ/ ("bouche" mouth) embedded in a carrier sentence "click on the drawing of…" were produced by two groups of 10 dysphonic and control female ST, matched in age and year of experience. The phonemical contrasts observed are voicing, nasality, consonantal place of articulation, vowel roundedness, and vowel place of articulation. The experimentation was presented in the form of a computer game to children from 7 to 10 years old. Two images illustrating the target words were presented, accompanied by the oral instructions recorded by ST. With a two-button box created for the experiment, children had to click as quickly as possible on the image corresponding to the instruction. RESULTS: Our results show that the RTs of all children are affected by the ST's dysphonia, regardless of their age and that they have significantly longer RT when discriminating minimal pairs contrasting in voicing when the instruction is given by a dysphonic speaker compared to the same instruction given by a control speaker. CONCLUSION: These observations could be explained by the fact that functional dysphonia is associated with improper use of the vocal folds and thus an alteration of voicing.

Faster Detection of "Darks" than "Brights" by Monkey Superior Colliculus Neurons.

Visual processing is segregated into ON and OFF channels as early as in the retina, and the superficial (output) layers of the primary visual cortex (V1) are dominated by neurons preferring dark stimuli. However, it is not clear how the timing of neural processing differs between "darks" and "brights" in general, especially in light of psychophysical evidence; it is also equally not clear how subcortical visual pathways that are critical for active orienting represent stimuli of positive (luminance increments) and negative (luminance decrements) contrast polarity. Here, we recorded from all visually-responsive neuron types in the superior colliculus (SC) of two male rhesus macaque monkeys. We presented a disk (0.51° radius) within the response fields (RFs) of neurons, and we varied, across trials, stimulus Weber contrast relative to a gray background. We also varied contrast polarity. There was a large diversity of preferences for darks and brights across the population. However, regardless of individual neural sensitivity, most neurons responded significantly earlier to dark than bright stimuli. This resulted in a dissociation between neural preference and visual response onset latency: a neuron could exhibit a weaker response to a dark stimulus than to a bright stimulus of the same contrast, but it would still have an earlier response to the dark stimulus. Our results highlight an additional candidate visual neural pathway for explaining behavioral differences between the processing of darks and brights, and they demonstrate the importance of temporal aspects in the visual neural code for orienting eye movements.SIGNIFICANCE STATEMENT Objects in our environment, such as birds flying across a bright sky, often project shadows (or images darker than the surround) on our retina. We studied how primate superior colliculus (SC) neurons visually process such dark stimuli. We found that the overall population of SC neurons represented both dark and bright stimuli equally well, as evidenced by a relatively equal distribution of neurons that were either more or less sensitive to darks. However, independent of sensitivity, the great majority of neurons detected dark stimuli earlier than bright stimuli, evidenced by a smaller response latency for the dark stimuli. Thus, SC neural response latency can be dissociated from response sensitivity, and it favors the faster detection of dark image contrasts.

Molecular Evolution across Mouse Spermatogenesis.

Genes involved in spermatogenesis tend to evolve rapidly, but we lack a clear understanding of how protein sequences and patterns of gene expression evolve across this complex developmental process. We used fluorescence-activated cell sorting (FACS) to generate expression data for early (meiotic) and late (postmeiotic) cell types across 13 inbred strains of mice (Mus) spanning ∼7 My of evolution. We used these comparative developmental data to investigate the evolution of lineage-specific expression, protein-coding sequences, and expression levels. We found increased lineage specificity and more rapid protein-coding and expression divergence during late spermatogenesis, suggesting that signatures of rapid testis molecular evolution are punctuated across sperm development. Despite strong overall developmental parallels in these components of molecular evolution, protein and expression divergences were only weakly correlated across genes. We detected more rapid protein evolution on the X chromosome relative to the autosomes, whereas X-linked gene expression tended to be relatively more conserved likely reflecting chromosome-specific regulatory constraints. Using allele-specific FACS expression data from crosses between four strains, we found that the relative contributions of different regulatory mechanisms also differed between cell types. Genes showing cis-regulatory changes were more common late in spermatogenesis, and tended to be associated with larger differences in expression levels and greater expression divergence between species. In contrast, genes with trans-acting changes were more common early and tended to be more conserved across species. Our findings advance understanding of gene evolution across spermatogenesis and underscore the fundamental importance of developmental context in molecular evolutionary studies.

Temporal collections to study invasion biology.

Biological invasions represent an extraordinary opportunity to study evolution. This is because accidental or deliberate species introductions have taken place for centuries across large geographical scales, frequently prompting rapid evolutionary transitions in invasive populations. Until recently, however, the utility of invasions as evolutionary experiments has been hampered by limited information on the makeup of populations that were part of earlier invasion stages. Now, developments in ancient and historical DNA technologies, as well as the quickening pace of digitization for millions of specimens that are housed in herbaria and museums globally, promise to help overcome this obstacle. In this review, we first introduce the types of temporal data that can be used to study invasions, highlighting the timescale captured by each approach and their respective limitations. We then discuss how ancient and historical specimens as well as data available from prior invasion studies can be used to answer questions on mechanisms of (mal)adaptation, rates of evolution, or community-level changes during invasions. By bridging the gap between contemporary and historical invasive populations, temporal data can help us connect pattern to process in invasion science. These data will become increasingly important if invasions are to achieve their full potential as experiments of evolution in nature.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Sex differences in radioulnar contrasts of the finger ridge counts across 21 human population samples.

Aim: The aim of the present study was to demonstrate the existence of uniform sexual dimorphism in some radioulnar contrasts between different finger ridge counts within the same hand in a large set of populations, thus confirming the universal nature of this dimorphism in humans.Subjects and methods: We analysed individual finger ridge counts (10 values on each hand) of both hands from archival sources (mainly the Brehme-Jantz database). In total, these included 4412 adults from 21 population samples covering all permanently inhabited continents and encompassing very different and geographically distant human populations. We calculated the contrasts (differences) of all pairs of ridge counts (45 per hand) and used diverse methods to assess the direction and degree of dimorphism of them across all population samples.Results: The highest sexual dimorphism was observed for nine contrasts involving the ridge count of the dermatoglyphic pattern on the radial side of the second finger of the right hand (R2r). Among these contrasts, we then found four that had the same direction of dimorphism in all 21 populations. The most dimorphic was the contrast R1rR2r - the difference between the ridge count of the radial side of the thumb and the radial side of the index finger.Discussion: Thus, these dermatoglyphic traits can be further investigated as potential markers of prenatal sex differentiation from ca. 10th week of intrauterine development. However, it will be useful to address the detailed factors and mechanisms for differences in the degree of dimorphism of these traits in different populations.

Stop contrast acquisition in child Kriol: Evidence of stable transmission of phonology post Creole formation.

Many Aboriginal Australian communities are undergoing language shift from traditional Indigenous languages to contact varieties such as Kriol, an English-lexified Creole. Kriol is reportedly characterised by lexical items with highly variable phonological specifications, and variable implementation of voicing and manner contrasts in obstruents (Sandefur, 1986). A language, such as Kriol, characterised by this unusual degree of variability presents Kriol-acquiring children with a potentially difficult language-learning task, and one which challenges the prevalent theories of acquisition. To examine stop consonant acquisition in this unusual language environment, we present a study of Kriol stop and affricate production, followed by a mispronunciation detection study, with Kriol-speaking children (ages 4-7) from a Northern Territory community where Kriol is the lingua franca. In contrast to previous claims, the results suggest that Kriol-speaking children acquire a stable phonology and lexemes with canonical phonemic specifications, and that English experience would not appear to induce this stability.

Questions of value, questions of magnitude: An exploration and application of methods for comparing indirect effects in multiple mediator models.

Mediation analysis is widely used to test and inform theory and debate about the mechanism(s) by which causal effects operate, quantitatively operationalized as an indirect effect in a mediation model. Most effects operate through multiple mechanisms simultaneously, and a mediation model is likely to be more realistic when it is specified to capture multiple mechanisms at the same time with the inclusion of more than one mediator in the model. This also allows an investigator to compare indirect effects to each other. After an overview of the mechanics of mediation analysis, we advocate formally comparing indirect effects in models that include more than one mediator, focusing on the important distinction between questions and claims about value (i.e., are two indirect effects the same number?) versus magnitude (i.e., are two indirect effects equidistant from zero or the same in strength?). After discussing the shortcomings of the conventional method for comparing two indirect effects in a multiple mediator model-which only answers a question about magnitude in some circumstances-we introduce several methods that, unlike the conventional approach, always answer questions about difference in magnitude. We illustrate the use of these methods and provide code that implements them in popular software. We end by summarizing simulation findings and recommending which method(s) to prefer when comparing like- and opposite-signed indirect effects.

Predicting individual task contrasts from resting-state functional connectivity using a surface-based convolutional network.

Task-based and resting-state represent the two most common experimental paradigms of functional neuroimaging. While resting-state offers a flexible and scalable approach for characterizing brain function, task-based techniques provide superior localization. In this paper, we build on recent deep learning methods to create a model that predicts task-based contrast maps from resting-state fMRI scans. Specifically, we propose BrainSurfCNN, a surface-based fully-convolutional neural network model that works with a representation of the brain's cortical sheet. BrainSurfCNN achieves exceptional predictive accuracy on independent test data from the Human Connectome Project, which is on par with the repeat reliability of the measured subject-level contrast maps. Conversely, our analyses reveal that a previously published benchmark is no better than group-average contrast maps. Finally, we demonstrate that BrainSurfCNN can generalize remarkably well to novel domains with limited training data.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Simultaneous confidence intervals for contrasts of quantiles.

Skewed distributions and inferences concerning quantiles are common in the health and social science researches. And most standard simultaneous inference procedures require the normality assumption. For example, few methods exist for comparing the medians of independent samples or quantiles of several distributions in general. To our knowledge, there is no easy-to-use method for constructing simultaneous confidence intervals for multiple contrasts of quantiles in a one-way layout. In this paper, we develop an asymptotic method for constructing such intervals both for differences and ratios of quantiles and extend the idea to that of right-censored time-to-event data in survival analysis. Small-sample performance of the proposed method and a bootstrap method were assessed in terms of coverage probabilities and average widths of the simultaneous confidence intervals. Good coverage probabilities were observed for most of the distributions considered in our simulations. The proposed methods have been implemented in an R package and are used to analyze two motivating datasets.

Individual differences in processing non-speech acoustic signals influence cue weighting strategies for L2 speech contrasts.

How could individual differences in processing non-speech acoustic signals influence their cue weighting strategies for L2 speech contrasts? The present study investigated this question by testing forty L1 Chinese-L2 English listeners with two tasks: one for testing the listeners' sensitivity to pitch and temporal information of non-speech acoustic signals; the other for testing their cue weighting (VOT, F0) strategies for distinguishing voicing contrasts in English stop consonants. The results showed that the more sensitive the listeners were to temporal differences of non-speech acoustic signals, the more they relied on VOT to differentiate between the voicing contrasts in English stop consonants. No such association was found between listeners' differences in sensitivity to pitch changes of non-speech acoustic signals and their reliance on F0 to cue the voicing contrasts. The results could shed light on the different processing mechanisms for pitch and temporal information of acoustic signals.

Using BayesModelS to provide Bayesian- and phylogenetically-informed primate body mass predictions.

An accurate prediction of the body mass of an extinct species can greatly inform the reconstruction of that species' ecology. Therefore, paleontologists frequently predict the body mass of extinct taxa from fossilized materials, particularly dental dimensions. Body mass prediction has traditionally been performed in a frequentist statistical framework, and accounting for phylogenetic relationships while calibrating prediction models has only recently become more commonplace. In this article, we apply BayesModelS-a phylogenetically informed Bayesian prediction method-to predict body mass in a sample of 49 euarchontan species (24 strepsirrhines, 20 platyrrhines, 3 tarsiids, 1 dermopteran, and 1 scandentian) and compare this approach's body mass prediction accuracy with other commonly used techniques, namely ordinary least squares, phylogenetic generalized least squares, and phylogenetic independent contrasts (PICs). When predicting the body masses of extant euarchontans from dental and postcranial variables, BayesModelS and PICs have substantially higher predictive accuracy than ordinary least squares and phylogenetic generalized least squares. The improved performances of BayesModelS and PIC are most evident for dentally derived body mass proxies or when body mass proxies have high degrees of phylogenetic covariance. Predicted values generated by BayesModelS and PIC methods also show less variance across body mass proxies when applied to the Eocene adapiform Notharctus tenebrosus. These more explicitly phylogenetically based methods should prove useful for predicting body mass in a paleontological context, and we provide executive scripts for both BayesModelS and PIC to increase ease of application.

Pith width, leaf size, and twig thickness.

PREMISE: To support large leaves, many woody plant species evolved a cost-effective way to thicken twigs. As an extension of E. J. H. Corner's rule that twig diameter increases with leaf size, we hypothesized that pith width also increases with leaf size. The benefit to the plant from the proposed relationship is that pith is a low-cost tissue that reduces the metabolic cost of large diameter twig production. METHODS: Leaf sizes and cross-sectional areas of bark, xylem, and pith of 81 species of trees and shrubs growing in Gainesville, Florida were measured and compared with standardized major axis regressions of pairwise species trait values and phylogenetically independent contrasts. RESULTS: Pith area increases with leaf size with or without accounting for phylogenetic relationships. In agreement with Corner's rule, overall twig diameter as well as bark and wood thickness also increase with leaf size. Thicker twigs showed more variation in relative pith, wood, and bark cross-sectional areas compared to thinner twigs. CONCLUSIONS: Investments in pith, a tissue of low density found in the centers of twigs, provides a low-cost way to increase twig circumference and thereby space for attachment of large leaves while increasing the overall second moment of area of twigs, which increases their ability to biomechanically support large leaves.

Adventurous tourism: acclimatization problems and decisions in trans-boundary travels.

As the twenty-first-Century Maritime Silk Road tourism program aims on development of new tourist routes with special interest on the polar regions of the Arctic and the Antarctic, as well as the Tibetan Plateau, management of climate risks in travels and their reduction is an important issue for achievement of its goals at national and local levels. Acclimatization is crucial for adventurous tourists, and especially for those traveling to extremely cold and highly elevated environments, when climate and weather in tourist destination differ significantly from those at home. The Acclimatization Thermal Strain Index for Tourism (ATSIT) is designed and used to measure numerically the physiological expenses a traveler pays during the acclimatization process. The purpose of the present study is to examine acclimatization consequences for travels from Beijing, capital of China, to destinations at the Arctic, the Antarctic, and the Tibetan Plateau, collectively referred to as the 3Polar regions, during the main seasons of winter and summer, and back. The results show that acclimatizing to cold involves greater physiological strain than adjustment to heat. Acclimatization load in winter is low for all travels from Beijing and back home. ATSIT projections detect the most harmful degree of discomfort for summer travels from Beijing. The greatest acclimatization impact comes when changing locales from hot and humid to cold and dry climatic conditions, which might cause high and very high physiological strain. Moreover, as many destinations in the 3Polar regions, mostly in the Tibetan Plateau, are located in mountains, a special acclimatization plan is required to weaken the threat of mountain sickness. The results will be helpful for warning stakeholders and the decision makers in the tourism sector of economies, and are expected to be translated into action for the development of proper intervention procedures in health control, to minimize population loss.

Deep learning-based MR-to-CT synthesis: The influence of varying gradient echo-based MR images as input channels.

PURPOSE: To study the influence of gradient echo-based contrasts as input channels to a 3D patch-based neural network trained for synthetic CT (sCT) generation in canine and human populations. METHODS: Magnetic resonance images and CT scans of human and canine pelvic regions were acquired and paired using nonrigid registration. Magnitude MR images and Dixon reconstructed water, fat, in-phase and opposed-phase images were obtained from a single T1 -weighted multi-echo gradient-echo acquisition. From this set, 6 input configurations were defined, each containing 1 to 4 MR images regarded as input channels. For each configuration, a UNet-derived deep learning model was trained for synthetic CT generation. Reconstructed Hounsfield unit maps were evaluated with peak SNR, mean absolute error, and mean error. Dice similarity coefficient and surface distance maps assessed the geometric fidelity of bones. Repeatability was estimated by replicating the training up to 10 times. RESULTS: Seventeen canines and 23 human subjects were included in the study. Performance and repeatability of single-channel models were dependent on the TE-related water-fat interference with variations of up to 17% in mean absolute error, and variations of up to 28% specifically in bones. Repeatability, Dice similarity coefficient, and mean absolute error were statistically significantly better in multichannel models with mean absolute error ranging from 33 to 40 Hounsfield units in humans and from 35 to 47 Hounsfield units in canines. CONCLUSION: Significant differences in performance and robustness of deep learning models for synthetic CT generation were observed depending on the input. In-phase images outperformed opposed-phase images, and Dixon reconstructed multichannel inputs outperformed single-channel inputs.

Composite MRA: statistical approach to generate an MR angiogram from multiple contrasts.

PURPOSE: To develop a method to use information from multiple MRI contrasts to produce a composite angiogram with reduced sequence-specific artifacts and improved vessel depiction. METHODS: Bayesian posterior vessel probability was determined as a function of black blood (BB), contrast enhanced angiography (CE-MRA), and phase-contrast MRA (PC-MRA) intensities from training subjects (N = 4). To generate composite angiogram in evaluation subjects (N = 12), the voxel-wise vessel probabilities were weighted with a confidence measure and combined as a weighted product to yield angiogram intensity. For 23 internal carotid artery (ICA) segments (N = 23) from evaluation subjects, segmentation accuracy of composite MRA was evaluated and compared against CE-MRA using dice similarity coefficient (DSC). RESULTS: The composite MRA suppressed venous contaminations in CE-MRA, reduced flow artifacts, and velocity aliasing seen in PC-MRA and removed signal ambiguities in BB images. For ICA segmentations, the composite MRA improved segmentation over CE-MRA per DSC (0.908 ± 0.037 vs. 0.765 ± 0.079). Compared with CE-MRA, the composite MRA showed conservative changes in vessel appearance to small threshold changes. However, small vessels that are sensitive to registration errors or visible only weakly in CE-MRA were susceptible to poor depiction in composite MRA. CONCLUSION: By dynamically weighting vessel information from multiple contrasts and extracting their complementary information, the composite MRA produces reduced sequence-specific artifacts and improved vessel contrast. It is a promising technique for semi-automatic segmentation of vessels that are hard to segment because of artifacts.

Whole-brain chemical exchange saturation transfer imaging with optimized turbo spin echo readout.

PURPOSE: To achieve fast whole-brain chemical exchange saturation transfer (CEST) imaging with negligible susceptibility artifact. METHODS: An optimized turbo spin echo readout module, also known as sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE), was deployed in the CEST sequence. The SPACE-CEST sequence was tested in a phantom, 6 healthy volunteers, and 3 brain tumor patients on a 3T human scanner. A dual-echo gradient echo sequence was used for B0 inhomogeneity mapping. In addition, the proposed SPACE-CEST sequence was compared with the widely used turbo spin echo-CEST sequence for amide proton transfer-weighted (APTw) images. RESULTS: The SPACE-CEST sequence generated highly consistent APTw maps to those of the turbo spin echo-CEST sequence in the phantom. In healthy volunteers, the SPACE-CEST sequence yielded whole-brain 2.8-mm isotropic APTw source images within 5 minutes, with no discernible susceptibility artifact. As for the B0 maps in the whole brain, its mean, median, and standard deviation B0 offset values were 5.0 Hz, 5.6 Hz, and 16 Hz, respectively. Regarding the APTw map throughout the whole brain, its mean, median, and standard deviation values were 0.78%, 0.56%, and 1.74%, respectively. The SPACE-CEST sequence was also successfully applied to a postsurgery brain tumor patient, suggesting no disease progression. In addition, on the newly diagnosed brain tumor patients, the SPACE-CEST and turbo spin echo-CEST sequences yielded essentially identical APTw values. CONCLUSION: The proposed SPACE-CEST technique can rapidly generate whole-brain CEST source images with negligible susceptibility artifact.