Blood Oxygenation Level-dependent fMRI Research Articles

Dynamics of the cerebral blood flow response to brief neural activity in human visual cortex

The blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal depends on an interplay of cerebral blood flow (CBF), oxygen metabolism, and cerebral blood volume. Despite wide usage of BOLD fMRI, it is not clear how these physiological components create the BOLD signal. Here, baseline CBF and its dynamics evoked by a brief stimulus (2 s) in human visual cortex were measured at 3T. We found a stereotypical CBF response: immediate increase, rising to a peak a few second after the stimulus, followed by a significant undershoot. The BOLD hemodynamic response function (HRF) was also measured in the same session. Strong correlations between HRF and CBF peak responses indicate that the flow responses evoked by neural activation in nearby gray matter drive the early HRF. Remarkably, peak CBF and HRF were also strongly modulated by baseline perfusion. The CBF undershoot was reliable and significantly correlated with the HRF undershoot. However, late-time dynamics of the HRF and CBF suggest that oxygen metabolism can also contribute to the HRF undershoot. Combined measurement of the CBF and HRF for brief neural activation is a useful tool to understand the temporal dynamics of neurovascular and neurometabolic coupling.

Language Mapping With fMRI: Current Standards and Reproducibility.

Clinical use of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a relatively new phenomenon, with only about 3 decades of collective experience. Nevertheless, task-based BOLD fMRI has been widely accepted for presurgical planning, over traditional methods, which are invasive and at times perilous. Many studies have demonstrated the ability of BOLD fMRI to make substantial clinical impact with respect to surgical planning and preoperative risk assessment, especially to localize the eloquent motor and visual areas. Reproducibility and repeatability of language fMRI are important in the assessment of its clinical usefulness. There are national efforts currently underway to standardize language fMRI. The American Society of Functional Neuroradiology (ASFNR) has recently provided guidelines on fMRI paradigm algorithms for presurgical language assessment for language lateralization and localization. In this review article, we provide a comprehensive overview of current standards of language fMRI mapping and its reproducibility.

Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults.

There is growing evidence to suggest that the brain is an important target for insulin action, and that states of insulin resistance may extend to the CNS with detrimental effects on cognitive functioning. Although the effect of systemic insulin resistance on peripheral organs is well-studied, the degree to which insulin impacts brain function in vivo remains unclear. This randomized, single-blinded, 2-way-crossover, sham-controlled, pilot study determined the effects of hyperinsulinemia on fMRI brain activation during a 2-back working memory task in 9 healthy older adults (aged 57-79 years). Each participant underwent two clamp procedures (an insulin infusion and a saline placebo infusion, with normoglycemia maintained during both conditions), to examine the effects of hyperinsulinemia on task performance and associated blood-oxygen-level dependent (BOLD) signal using fMRI. Hyperinsulinemia (compared to saline control) was associated with an increase in both the spatial extent and relative strength of task-related BOLD signal during the 2-back task. Further, the degree of increased task-related activation in select brain regions correlated with greater systemic insulin sensitivity, as well as decreased reaction times and performance accuracy between experimental conditions. Together, these findings provide evidence of insulin action in the CNS among older adults during periods of sustained cognitive demand, with the greatest effects noted for individuals with highest systemic insulin sensitivity. This work was funded by the National Institutes of Health (5R21AG051958, 2016).

Role of the inhibitory system in shaping the BOLD fMRI response

The shape of the blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal can vary considerably even across structures of the same sensory pathway. Here, we characterized the temporal behavior of the stimulus-evoked BOLD response in the primary cortical and subcortical regions of the visual and somatosensory whisker systems in awake rabbits. Despite similar BOLD responses in the thalamic nuclei, considerable differences in shape and duration emerged between the sensory cortices. Whereas the BOLD response in the whisker barrel cortex (WBC) was non-adaptive, BOLD in the visual cortex (V1) showed adaptation similar to simultaneously-recorded LFP and single unit activity. Analysis of baseline neuronal activity revealed significantly lower firing rates in V1 vs. WBC. We hypothesized that these changes point to region-dependent differences in the inhibitory systems which shape the hemodynamic response in each structure. To test the effect of neuronal baseline level inhibition on the BOLD signal shape, we locally injected the GABAA agonist muscimol in WBC. Adaptation emerged in the BOLD response after injection, along with an overall decrease in baseline firing rate. These findings point to the importance of region-specific inhibitory shaping in determining the temporal behavior of the BOLD response in different brain areas.

Blood Oxygen Level–Dependent Response Changes in the Ipsilateral Primary Somatosensory Cortex and Thalamus of Patients With Moyamoya Disease During Median Nerve Electrical Stimulation

The objective of this study was to investigate the changes in the blood oxygen level-dependent (BOLD) response in the ipsilateral primary somatosensory cortex (SI) and thalamus of patients with moyamoya disease (MMD) during sensory stimulation. Sixty-four MMD patients, and 15 healthy volunteers were enrolled. Thirty-three MMD patients exhibited paroxysmal numbness or hypoesthesia in the unilateral limbs. Fifteen patients with acroparesthesia underwent unilateral encephaloduroarteriosynangiosis (EDAS). All volunteers underwent BOLD functional magnetic resonance imaging (BOLD-fMRI) under median nerve electrical stimulation (MNES). Blood oxygen level-dependent fMRI data were processed to obtain time-signal intensity curves in the activation areas of the bilateral SI and thalamus. Processed dynamic susceptibility contrast-enhanced magnetic resonance imaging data were used to measure the time to peak of the BOLD response in the regions of interest, including the bilateral SI, thalamus, and cerebellum. Changes in the time-signal intensity curve-related hemodynamic parameters in the ipsilateral SI and thalamus were examined between healthy controls, nonacroparesthesia patients, and asymptomatic and symptomatic sides of unilateral acroparesthesia patients during MNES. Changes in these parameters in MMD patients before and after EDAS were examined. Compared with healthy volunteers, 3 groups of MMD patients exhibited an increased peak of the positive BOLD response in the ipsilateral thalamus during MNES (0.65 ± 0.24 vs 0.79 ± 0.35, 0.94 ± 0.57, and 0.89 ± 0.50; P = 0.0335). The positive response peak in the ipsilateral SI markedly increased in MMD patients with acroparesthesia during MNES on the asymptomatic side (0.56 ± 0.37 vs 0.38 ± 0.27, P = 0.0243). The time to peak negative response in the ipsilateral SI was prolonged during MNES on the symptomatic side after EDAS (12.14 ± 8.90 seconds vs 18.86 ± 9.20 seconds, P = 0.0201). During sensory stimulation treatment, BOLD response changes occurred in the ipsilateral SI and thalamus of MMD patients. These changes enabled the contralateral hemisphere of the brain to better deal with sensory stimuli.

ACCUMULATION OF DEMENTIA RISK FACTORS ALTERS BRAIN REGIONS OF EPISODIC MEMORY: AN FMRI ANALYSIS

Longitudinal research suggests that genetic, lifestyle, and environmental factors enhance one's risk for developing Alzheimer's disease and related dementias (ADRD). However, it is not known how an accumulation of multiple risk factors alters brain function. One barrier to this research is that increased risk for ADRD affects the cerebrovascular system, thus decoupling neural activity from the fMRI blood oxygen level dependent (BOLD) signal. Previous studies that have found an association between risks for ADRD and brain activity suffer challenges in interpretation because the BOLD signal was not calibrated, likely leading to an overestimation of such associations. We hypothesized that as the number of ADRD risk factors increase, brain regions within the medial temporal lobes and the default mode network (DMN) would exhibit altered brain activity during an episodic memory retrieval task. To reduce the influence of non-neural influences on the BOLD signal, several steps were taken to calibrate fMRI BOLD activity. Participants ranged in age from 50 to 70 years. Participants were recruited with varying levels of risk for dementia and from this initial screening a dementia risk score was calculated. They also underwent a neuropsychological battery to screen out possible dementia. Using fMRI, brain activity was assessed while participants completed a memory task by viewing a pair of pictures, followed by an alternative-forced-choice test, where participants viewed a picture cue and had to determine which of four pictures was paired with the cue. After correcting the fMRI BOLD signal, whole-brain analyses revealed that increased dementia risk was negatively associated with brain activity in the hippocampus—a task positive region—and was positively associated with the lateral parietal cortex—a task negative region. We found evidence that adults with an accumulation of risk factors for dementia exhibit decreased modulation of brain activity in critical regions underlying episodic memory. These findings call into question previous studies that did not calibrate the BOLD signal and found compensatory hyperactivity in these regions. Instead, cumulative risk likely represents early dysfunction of the default mode and brain regions underlying episodic memory.

Modeling fMRI BOLD signals and temporal mismatches in the cerebellar cortex

To understand brain activity relating neurons to circuits to learning and behavior, we explored a bottom-up computational reconstruction of population signals arising from cerebellum granular layer. As a first implementation, using bio-realistic computational models of cerebellum granule cell, in vivo spike train patterns were computed and then translated into functional Magnetic Resonance Imaging, Blood Oxygen-Level Dependent (BOLD) signals. The BOLD response was generated from averaged activity arising from center-surround organization modeled by using excitatory-inhibitory ratios related to experimental data. The averaged responses were converted to BOLD signals using the balloon and modified Windkessel models. Although both models generated BOLD responses corresponding to neural activity, the temporal mismatch was attributed to the response by the delayed compliance parameter in the Windkessel model. The modeling suggests that experimental variability observed in the cerebellar micro-zones could be related to compliance chances, activation patterns and number of neurons. Although detailed neuro-vasculature information was not modeled, the advantage in this methodology is that cerebellar cortex may allow seemingly linear transformations of underlying spiking that could be then used to validate network reconstructions.

Differential effects of anesthetics on resting state functional connectivity in the mouse

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is a standard approach to examine resting state functional connectivity (RSFC), but fMRI in animal models is challenging. Recently, functional optical intrinsic signal imaging—which relies on the same hemodynamic signal underlying BOLD fMRI—has been developed as a complementary approach to assess RSFC in mice. Since it is difficult to ensure that an animal is in a truly resting state while awake, RSFC measurements under anesthesia remain an important approach. Therefore, we systematically examined measures of RSFC using non-invasive, widefield optical intrinsic signal imaging under five different anesthetics in male C57BL/6J mice. We find excellent seed-based, global, and interhemispheric connectivity using tribromoethanol (Avertin) and ketamine–xylazine, comparable to results in the literature including awake animals. Urethane anesthesia yielded intermediate results, while chloral hydrate and isoflurane were both associated with poor RSFC. Furthermore, we found a correspondence between the strength of RSFC and the power of low-frequency hemodynamic fluctuations. In conclusion, Avertin and ketamine–xylazine provide robust and reproducible measures of RSFC in mice, whereas chloral hydrate and isoflurane do not.

Normalization of aberrant pretherapeutic dynamic functional connectivity of extrastriate visual system in patients who underwent thalamotomy with stereotactic radiosurgery for essential tremor: a resting-state functional MRI study.

The tremor circuitry has commonly been hypothesized to be driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus, and primary motor cortex. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by changes within the right extrastriate cortex, at both the structural and functional level. The purpose of this work was to evaluate the role of the extrastriate cortex in tremor generation and further arrest after left unilateral stereotactic radiosurgery thalamotomy (SRS-T). The authors considered 12 healthy controls (HCs, group 1); 15 patients with essential tremor (ET, right-sided, drug-resistant; group 2) before left unilateral SRS-T; and the same 15 patients (group 3) 1 year after the intervention, to account for delayed effects. Blood oxygenation level-dependent functional MRI during resting state was used to characterize the dynamic interactions of the right extrastriate cortex, comparing HC subjects against patients with ET before and 1 year after SRS-T. In particular, the authors applied coactivation pattern analysis to extract recurring whole-brain spatial patterns of brain activity over time. The authors found 3 different sets of coactivating regions within the right extrastriate cortex in HCs and patients with pretherapeutic ET, reminiscent of the "cerebello-visuo-motor," "thalamo-visuo-motor" (including the targeted thalamus), and "basal ganglia and extrastriate" networks. The occurrence of the first pattern was decreased in pretherapeutic ET compared to HCs, whereas the other two patterns showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. Clinical improvement after SRS-T was related to changes in occurrences of the basal ganglia and extrastriate cortex circuitry, which returned to HC values after the intervention, suggesting that the dynamics of the extrastriate cortex had a role in tremor generation and further arrest after the intervention. The data in this study point to a broader implication of the visual system in tremor generation, and not only through visual feedback, given its connections to the dorsal visual stream pathway and the cerebello-thalamo-cortical circuitry, with which its dynamic balance seems to be a crucial feature for reduced tremor. Furthermore, SRS-T seems to bring abnormal pretherapeutic connectivity of the extrastriate cortex to levels comparable to those of HC subjects.

Optogenetic fMRI interrogation of brain-wide central vestibular pathways

Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject's ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.

Study on resting-state cerebral functional magnetic resonance imaging and ambulatory urodynamics monitoring in children with primary monosympt-omatic nocturnal enuresis

Objective To investigate the significance of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and ambulatory urodynamics monitoring (AUM) to find the cause of primary monosymptomatic nocturnal enuresis (PMNE) in children. Methods Thirty-seven children with PMNE (20 males and 17 females) were selected, with a mean age of (11.3±4.1) years old.A clinical management tool, 3-day urination record, daytime BOLD-fMRI scan, conventional urodynamics (CUD) and AUM were performed respectively.Thirty-seven gender-age matched children(19 males, 18 females) who would receive surgery treatment because of upper urinary tract disease and were confirmed to have no lower urinary tract dysfunction by CUD were enrolled as controls, with a mean age of (11.1±2.9) years old, and 13 cases underwent BOLD-fMRI scanning. Results It was found that the ALFF value of the left middle frontal gyrus of PMNE was decreased and the ReHo value of the left superior occipital gyrus was increased compared with the control group by the resting BOLD-fMRI.The maximum voiding volume of PNME children was (303.11±87.48) mL, the total urine volume at night was (568.65±208.48) mL, and the nighttime bladder volume was (217.43±81.53) mL.The incidence of maximum voiding volume reduction, nocturnal polyuria and decreased nocturnal bladder volume were 24.32% and 56.76%, and 64.86%, respectively.However, AUM results showed that maximum detrusor pressure in the PMNE group was (39.22±7.78) cmH2O(1 cmH2O=0.098 kPa), which was statistically significantly higher than that in CUD (32.22±9.00) cmH2O, and the difference was statistically significant (P 0.05). Conclusions The abnormal functions of the left middle frontal gyrus and left superior occipital gyrus, nighttime DO and the decrease of bladder capacity at night are considered to be key causes of enuresis in children with PMNE.AUM and resting state BOLD-fMRI evaluations are helpful in differentiating the pathogenesis of PMNE. Key words: Enuresis; Ambulatory urodynamics monitoring; Functional magnetic resonance imaging; Resting state

Acute ketamine administration attenuates lipopolysaccharide-induced depressive-like behavior by reversing abnormal regional homogeneity in the nucleus accumbens.

Ketamine has rapid antidepressant effects, but no study to date has investigated changes in resting-state brain activity following ketamine administration in inflammation-induced depression. The purpose of this study was to use blood oxygen level-dependent functional MRI to explore changes in the resting-state brain activity in a rat model of depression induced by lipopolysaccharide (LPS, 1 mg/kg) challenge and to examine whether acute ketamine administration can reverse LPS-induced depressive-like behavior. Here, we showed LPS-induced depressive-like behavior as evidenced by significantly reduced motility in the forced swim test. In addition, LPS-induced increases in plasma levels of proinflammatory cytokines were not completely reversed by acute ketamine administration, suggesting that ketamine exerts its antidepressant effects independently of a possible interference with LPS-induced inflammatory signaling. However, increased regional homogeneity (ReHo) was observed in some brain regions of LPS-exposed animals, including bilateral caudate putamen and nucleus accumbens, which were parts of the mood-regulating circuit. Moreover, ReHo values of bilateral caudate putamen and nucleus accumbens showed significant positive correlations with immobility time. Notably, the LPS-induced depressive-like behavior and increase of ReHo value in the right nucleus accumbens was reversed by acute ketamine administration. In summary, this study suggests that acute ketamine administration is capable of attenuating LPS-induced depressive-like behavior, at least partially by reversing abnormal ReHo in the right nucleus accumbens.

Amygdala and prefrontal cortex activity varies with individual differences in the emotional response to psychosocial stress.

Stress elicits a variety of psychophysiological responses that show large interindividual variability. Determining the neural mechanisms that mediate individual differences in the emotional response to stress would provide new insight that would have important implications for understanding stress-related disorders. Therefore, the present study examined individual differences in the relationship between brain activity and the emotional response to stress. In the largest stress study to date, 239 participants completed the Montreal Imaging Stress Task (MIST) while heart rate, skin conductance response (SCR), cortisol, self-reported stress, and blood oxygen level dependent (BOLD) functional MRI (fMRI) signal responses were measured. The relationship between differential responses (heart rate, SCR, cortisol, and self-reported stress) and differential BOLD fMRI data was analyzed. Dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and amygdala activity varied with the behavioral response (i.e., SCR and self-reported stress). These results suggest the PFC and amygdala support processes that are important for the expression and regulation of the emotional response to stress, and that stress-related PFC and amygdala activity underlie interindividual variability in peripheral physiologic measures of the stress response. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Central nervous system signatures of affect in asthma: associations with emotion-induced bronchoconstriction, airway inflammation, and asthma control.

The effects of asthma on affect have been noted for some time, but little is known about associated brain processes. We therefore examined whether emotion-induced bronchoconstriction, airway inflammation, and asthma control are related to specific patterns of brain activity during processing negative affective stimuli. Fifteen adults with asthma viewed alternating blocks of distressing film clips (negative condition), affectively neutral film clips (neutral condition), and a crosshair image (baseline condition) while undergoing blood oxygenation level-dependent (BOLD) functional MRI (fMRI). Block-design fMRI analysis evaluated the BOLD response to "negative-baseline" and "neutral-baseline" contrasts. Airway response to these film clips was also assessed with impulse oscillometry in a separate session. Measures of airway inflammation [fractional exhaled nitric oxide (FENO)] and asthma control [Asthma Control Questionnaire (ACQ)] were additionally obtained. A whole brain voxel-based regression analysis of contrast maps was performed against respiratory resistance increase during negative and neutral films, FENO, and ACQ. Peak airway obstruction to negative affective stimulation was associated with stronger activation of the anterior and middle cingulate gyrus, including the dorsal anterior cingulate cortex (dACC). Stronger airway inflammation and lower asthma control were associated with reduced activation to negative stimuli in the superior frontal gyrus, middle cingulate gyrus, and supplementary motor area. Activation of the dACC in negative-affect-induced airway obstruction could be part of an integrated defensive response to critical environmental change. In addition, reduced frontal and limbic activation during processing of negative affect may reflect consequences of pathophysiological processes for CNS functioning. NEW & NOTEWORTHY This functional magnetic resonance imaging study shows, for the first time, that the degree of airway constriction due to negative affective stimuli in asthma is associated with stronger response to these stimuli in the dorsal anterior and middle cingulate cortex. Asthma patients with stronger airway inflammation and reduced asthma control also show reduced activation in a number of cortical and subcortical areas relevant for affective processing and breathing control.

Investigation of Resting-State BOLD Networks in the Human Brainstem and Spinal Cord

Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to investigate networks within the cortex and has also provided some insight into the networks present in the brainstem (BS) and spinal cord (SC). The purpose of this study was to investigate resting-state blood oxygenation-level dependent (BOLD) fluctuations in the BS/SC and to identify resting-state networks (RSNs) across these regions. Resting-state BOLD fMRI data were obtained from the entire BS and cervical SC in 16 healthy participants, at 3 T, with T2-weighted single-shot fast spin-echo imaging. Data were spatially normalized and processed to remove physiological noise. Cluster-cluster functional connectivity was investigated across the entire 3D region by means of temporal correlations, and structural equation modeling (SEM) was used to investigate RSNs. Extensive connectivity was observed within and across BS and SC regions, with connections spanning up to 120 mm, although shorter connections were more prevalent. SEM results revealed extensive brainstem-cord connectivity that included specific anatomical regions within the brainstem. The results indicate the presence of a complex resting-state network which is highly interconnected in the spinal cord. Known anatomical connections between cortical and BS regions support the conclusion that the observed resting-state BOLD fluctuations in the BS/SC may be related to autonomic regulation. Future studies are required to further investigate these resting-state BOLD networks.

Sensorimotor network hypersynchrony as an endophenotype in families with genetic generalized epilepsy: A resting-state functional magnetic resonance imaging study.

SummaryRecent evidence suggests that three specific brain networks show state‐dependent levels of synchronization before, during, and after episodes of generalized spike‐wave discharges (GSW) in patients with genetic generalized epilepsy (GGE). Here, we investigate whether synchronization in these networks differs between patients with GGE (n = 13), their unaffected first‐degree relatives (n = 17), and healthy controls (n = 18). All subjects underwent two 10‐minute simultaneous electroencephalographic–functional magnetic resonance imaging (fMRI) recordings without GSW. Whole‐brain data were divided into 90 regions, and blood oxygen level–dependent (BOLD) phase synchrony in a 0.04–0.07‐Hz band was estimated between all pairs of regions. Three networks were defined: (1) the network with highest synchrony during GSW events, (2) a sensorimotor network, and (3) an occipital network. Average synchrony (mean node degree) was inferred across each network over time. Notably, synchrony was significantly higher in the sensorimotor network in patients and in unaffected relatives, compared to controls. There was a trend toward higher synchrony in the GSW network in patients and in unaffected relatives. There was no difference between groups for the occipital network. Our findings provide evidence that elevated fMRI BOLD synchrony in a sensorimotor network is a state‐independent endophenotype of GGE, present in patients in the absence of GSW, and present in unaffected relatives.

Blood oxygen level–dependent functional magnetic resonance imaging can evaluate the efficiency of transcatheter arterial chemoembolization in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is among the most common malignant tumors worldwide, and transcatheter arterial chemoembolization (TACE) technology has become the first-line treatment for advanced HCC. Another important, recently developed technique is blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI), which utilizes hemoglobin as an endogenous contrast agent and measures deoxygenated hemoglobin content by sampling the oxygen content of tissues, thus reflecting the hemodynamics and pathophysiologic changes in body organs. Currently this technology is being used in patients with liver tumors; that is, it serves as an important tool in follow-up after TACE. The present paper summarizes these developments.

Absence of dentate nucleus resting-state functional connectivity changes in nonneurological patients with gadolinium-related hyperintensity on T1 -weighted images.

The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. To assess whether gadolinium-dependent high signal intensity of the cerebellum on T1 -weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting-state functional connectivity (RSFC) of the cerebellum and dentate nucleus. Observational, cross-sectional. Fifteen patients affected by Crohn's disease were compared with 16 healthy age- and gender-matched control subjects. All participants underwent neurological, neurocognitive-psychological assessment, and blood sampling. 1.5-T magnet blood oxygenation level-dependent (BOLD) functional MRI. High signal intensity on T1 -weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. An unpaired two-sample t-test (age and sex were nuisance variables) was used to investigate between-group differences in cerebellar and dentate nucleus functional connectivity. Z-statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)-corrected cluster significance threshold of P = 0.05. Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium-dependent high signal intensity on T1 -weighted images and controls. Pre- and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE-corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). Crohn's disease patients with gadolinium-dependent hyperintense dentate nuclei on unenhanced T1 -weighted images do not show dentate nucleus RSFC changes. 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445-455.

Simultaneous task-based BOLD-fMRI and [18-F] FDG functional PET for measurement of neuronal metabolism in the human visual cortex

Studies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2.5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were jointly coupled in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.

Fractional amplitude of low-frequency fluctuations and functional connectivity in comatose patients subjected to resting-state functional magnetic resonance imaging

Objective:The objective of the study is to investigate the changes of fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity (FC) in the brain function of comatose patients with resting-state blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI) and to discuss the underlying neurophysiological mechanism of disease.Materials and Methods:Resting-state BOLD-fMRI scans were conducted on 20 comatose patients and 20 age-matched and gender-matched controls. The differences of fALFF between two groups were analyzed with two-sample t-test; significant differences of connectivity between groups were acquired to calculate the FC of the precuneus with other brain regions.Results:Compared to the control group, the comatose patients exhibited a significant reduction in fALFF in various areas, including the right cingulate gyrus, left precuneus, right inferior parietal lobule, right superior parietal lobule, bilateral anterior/posterior central gyrus, middle frontal gyrus, right superior frontal gyrus, right superior temporal gyrus, and the bilateral cerebellar hemispheres (P < 0.05, Alphasim correction). Compared with controls, the brain region FC correlated with the precuneus reduced mainly located in the bilateral inferior parietal lobule, posterior central gyrus, lenticular nucleus, left anterior central gyrus, left medial frontal gyrus, left anterior lobe of the cerebellum, right insula, right transverse temporal gyri, and right thalamus. Regions whose FC increased include the left superior frontal gyrus, left side of the callosum, left superior parietal lobule, and both sides of the cingulate (P < 0.05, Alphasim correction).Conclusion:Measurements of fALFF and FC obtained by resting-state BOLD-fMRI could provide considerable information for the analysis and evaluation of the brain function of comatose patients from the perspective of local function and global functional network and provide the theoretical basis for the study of coma nerve physiological mechanism.