Blood Oxygenation Level-dependent fMRI Research Articles

Dopaminergic modulation of regional cerebral blood flow: An arterial spin labelling study of genetic and pharmacological manipulation of COMT activity

Dopamine has direct and complex vasoactive effects on cerebral circulation. Catechol-O-methyltransferase (COMT) regulates cortical dopamine, and its activity can be influenced both genetically and pharmacologically. COMT activity influences the functional connectivity of the PFC at rest, as well as its activity during task performance, determined using blood oxygen level-dependent (BOLD) fMRI. However, its effects on cerebral perfusion have been relatively unexplored. Here, 76 healthy males, homozygous for the functional COMT Val158Met polymorphism, were administered either the COMT inhibitor tolcapone or placebo in a double-blind, randomised design. We then assessed regional cerebral blood flow at rest using pulsed arterial spin labelling. Perfusion was affected by both genotype and drug. COMT genotype affected frontal regions (Val158 > Met158), whilst tolcapone influenced parietal and temporal regions (placebo > tolcapone). There was no genotype by drug interaction. Our data demonstrate that lower COMT activity is associated with lower cerebral blood flow, although the regions affected differ between those affected by genotype compared with those altered by acute pharmacological inhibition. The results extend the evidence for dopaminergic modulation of cerebral blood flow. Our findings also highlight the importance of considering vascular effects in functional neuroimaging studies, and of exercising caution in ascribing group differences in BOLD signal solely to altered neuronal activity if information about regional perfusion is not available.

The Role of Cerebrovascular-Reactivity Mapping in Functional MRI: Calibrated fMRI and Resting-State fMRI.

Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and associations with fMRI. In particular, CVR estimation is part of a family of techniques called calibrated BOLD fMRI, the purpose of which is to allow the mapping of cerebral oxidative metabolism (CMRO2) using a combination of BOLD and cerebral-blood flow (CBF) measurements. Moreover, CVR has recently been shown to be a major source of vascular bias in computing resting-state functional connectivity, in much the same way that it is used to neutralize the vascular contribution in calibrated fMRI. Furthermore, due to the obvious challenges in estimating CVR using gas challenges, a rapidly growing field of study is the estimation of CVR without any form of challenge, including the use of resting-state fMRI for that purpose. This review addresses all of these aspects in which CVR interacts with fMRI and the role of CVR in calibrated fMRI, provides an overview of the physiological biases and assumptions underlying hypercapnia-based CVR and calibrated fMRI, and provides a view into the future of non-invasive CVR measurement.

Point-spread function of the BOLD response across columns and cortical depth in human extra-striate cortex.

Columns and layers are fundamental organizational units of the brain. Well known examples of cortical columns are the ocular dominance columns (ODCs) in primary visual cortex and the column-like stripe-based arrangement in the second visual area V2. The spatial scale of columns and layers is beyond the reach of conventional neuroimaging, but the advent of high field magnetic resonance imaging (MRI) scanners (UHF, 7 T and above) has opened the possibility to acquire data at this spatial scale, in-vivo and non-invasively in humans. The most prominent non-invasive technique to measure brain function is blood oxygen level dependent (BOLD) fMRI, measuring brain activity indirectly, via changes in hemodynamics. A key determinant of the ability of high-resolution BOLD fMRI to accurately resolve columns and layers is the point-spread function (PSF) of the BOLD response in relation to the spatial extent of neuronal activity. In this study we take advantage of the stripe-based arrangement present in visual area V2, coupled with sub-millimetre anatomical and gradient-echo BOLD (GE BOLD) acquisition at 7 T to obtain PSF estimates and along cortical depth in human participants. Results show that the BOLD PSF is maximal in the superficial part of the cortex (1.78 mm), and it decreases with increasing cortical depth (0.83 mm close to white matter).

Cerebrovascular Reactivity Mapping Using Resting-State BOLD Functional MRI in Healthy Adults and Patients with Moyamoya Disease.

Background Cerebrovascular reserve, the potential capacity of brain tissue to receive more blood flow when needed, is a desirable marker in evaluating ischemic risk. However, current measurement methods require acetazolamide injection or hypercapnia challenge, prompting a clinical need for resting-state (RS) blood oxygen level-dependent (BOLD) functional MRI data to measure cerebrovascular reactivity (CVR). Purpose To optimize and evaluate an RS CVR MRI technique and demonstrate its relationship to neurosurgical treatment. Materials and Methods In this HIPAA-compliant study, RS BOLD functional MRI data collected in 170 healthy controls between December 2008 and September 2010 were retrospectively evaluated to identify the optimal frequency range of temporal filtering on the basis of spatial correlation with the reference standard CVR map obtained with CO2 inhalation. Next, the optimized RS method was applied in a new, prospective cohort of 50 participants with Moyamoya disease who underwent imaging between June 2014 and August 2019. Finally, CVR values were compared between brain hemispheres with and brain hemispheres without revascularization surgery by using Mann-Whitney U test. Results A total of 170 healthy controls (mean age ± standard deviation, 51 years ± 20; 105 women) and 100 brain hemispheres of 50 participants with Moyamoya disease (mean age, 41 years ± 12; 43 women) were evaluated. RS CVR maps based on a temporal filtering frequency of [0, 0.1164 Hz] yielded the highest spatial correlation (r = 0.74) with the CO2 inhalation CVR results. In patients with Moyamoya disease, 77 middle cerebral arteries (MCAs) had stenosis. RS CVR in the MCA territory was lower in the group that did not undergo surgery (n = 30) than in the group that underwent surgery (n = 47) (mean, 0.407 relative units [ru] ± 0.208 vs 0.532 ru ± 0.182, respectively; P = .006), which is corroborated with the CO2 inhalation CVR data (mean, 0.242 ru ± 0.273 vs 0.437 ru ± 0.200; P = .003). Conclusion Cerebrovascular reactivity mapping performed by using resting-state blood oxygen level-dependent functional MRI provided a task-free method to measure cerebrovascular reserve and depicted treatment effect of revascularization surgery in patients with Moyamoya disease comparable to that with the reference standard of CO2 inhalation MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wolf and Ware in this issue.

Whole-liver histogram analysis of blood oxygen level-dependent functional magnetic resonance imaging in evaluating hepatic fibrosis.

To explore whole-liver histogram analysis (HA) with blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in evaluating and diagnosing hepatic fibrosis (HF) in a CCl4-induced rabbit model. One hundred rabbits were classified as CCl4-induced HF groups (n=80) and control group (n=20), and were scheduled for BOLD-fMRI examination on a 3.0T scanner. Whole-liver HA metrics, including the mean, median, skewness, kurtosis, inhomogeneity, entropy, and nth percentiles, were extracted from the R2* map. Parameters were compared among the different HF stages using receivers operating characteristic analysis and Mann-Whitney U-test. In all, 17, 18, 19, 17, and 15 rabbits were pathologically diagnosed as F0, F1, F2, F3, and F4, respectively. HA parameters, including the median, inhomogeneity, entropy, and the 75th and 90th percentiles of the BOLD R2* map, demonstrated significant positive correlations with the fibrosis stage (r=0.226-0.718, P≤0.039). The 75th percentiles demonstrated higher diagnostic efficacy than the other HA parameters in fibrosis staging, with an AUC value of 0.86 for ≥ F1, 0.87 for ≥ F2, 0.87 for ≥ F3, and 0.86 for ≥ F4. BOLD-fMRI HA provides increased diagnostic performance in staging HF, especially for the 75th percentiles.

Improving the Breath-Holding CVR Measurement Using the Multiband Multi-Echo EPI Sequence.

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to measure cerebrovascular reactivity (CVR), which can convey insightful information about neurovascular health. Breath-holding (BH) has been shown to be a practical vasodilatory stimulus for measuring CVR in clinical settings. The conventional BOLD fMRI approach has some limitations, however, such as susceptibility-induced signal dropout at air tissue interfaces and low BOLD sensitivity especially in areas of low . These drawbacks can potentially be mitigated with multi-echo sequences, which acquire several images at different echo times in one shot. When combined with multiband techniques, high temporal resolution images can be acquired. This study compared an advanced multiband multi-echo (MBME) echo planar imaging (EPI) sequence with an existing multiband single-echo (MB) sequence to evaluate the repeatability and sensitivity of BH activation and CVR mapping. Images were acquired from 28 healthy volunteers, of which 18 returned for repeat imaging. Both MBME and MB data were pre-processed using both standard and advanced denoising techniques. The MBME data was further processed by combining echoes using a -weighted approach and denoising using multi-echo independent component analysis. BH activation was calculated using a general linear model and the respiration response function. CVR was computed as the percent change related to the activation. To account for differences in CVR related to TE, relative CVR (rCVR) was computed and normalized to the mean gray matter CVR. Test–retest metrics were assessed with the Dice coefficient, rCVR difference, within subject coefficient of variation, and the intraclass correlation coefficient. Our findings demonstrate that rCVR for MBME scans were significantly higher than for MB scans across most of the gray matter. In areas of high susceptibility-induced signal dropout, however, MBME rCVR was significantly less than MB rCVR due to artifactually high rCVR for MB scans in these regions. MBME rCVR showed improved test–retest metrics compared with MB. Overall, the MBME sequence displayed superior BOLD sensitivity, improved specificity in areas of signal dropout on MBME scans, enhanced reliability, and reduced variability across subjects compared with MB acquisitions. Our results suggest that the MBME EPI sequence is a promising tool for imaging CVR.

Blood oxygen level dependent fMRI and perfusion MRI in the sheep brain

The ovine model could be an effective translational model but remains underexplored. Here, Blood Oxygen Level dependent functional MRI during visual stimulation and resting-state perfusion MRI were explored. We aimed at investigating the impact of isoflurane anesthesia during visual stimulation and evaluate resting cerebral blood flow and cerebral blood volume parameters in the lamb and adult sheep brain.BOLD fMRI and perfusion MRI after a bolus of DOTAREM were conducted in 4 lambs and 6 adult ewes at 3 T. A visual stimulation paradigm was delivered during fMRI at increasing isoflurane doses (1–3%).Robust but weak BOLD responses (0.21 ± 0.08%) were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. No significant differences were found beween BOLD responses in the range 1 to 3% ISO (p > 0.05). However, LGN cluster size decreased and functional localization became less reliable at high ISO doses (2.5–3% ISO). BOLD responses were weaker in adult sheep than in lambs (4.6 ± 1.5 versus 13.6 ± 8.5; p = 0.08). Relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher (p < 0.0001) in lambs than in adult sheep for both gray and white matter.The impact of volatile anesthesia was explored for the first time on BOLD responses demonstrating increased reliability of functional localization of brain activity at low doses. Perfusion MRI was conducted for the first time in both lambs and adult ewes. Assessment of baseline cerebrovascular values are of interest for future studies of brain diseases allowing an improved interpretation of BOLD responses.

Improving the sensitivity of spin-echo fMRI at 3T by highly accelerated acquisitions.

Spin-echo (SE) functional MRI (fMRI) can be highly advantageous compared to gradient-echo (GE) fMRI with respect to magnetic field-inhomogeneity artifacts. However, at 3T, the majority of blood oxygenation level-dependent (BOLD) fMRI experiments are performed using -weighted GE sequences because of their superior sensitivity compared to SE-fMRI. The presented SE implementation of a highly accelerated GE pulse sequence therefore aims to improve the sensitivity of SE-fMRI while profiting from a reduction of susceptibility-induced signal dropout. Spin-echo MR encephalography (SE-MREG) is compared with the more conventionally used spin-echo echo-planar imaging (SE-EPI) and spin-echo simultaneous multislice (SE-SMS) at 3T in terms of capability to detect neuronal activations and resting-state functional connectivity. For activation analysis, healthy subjects underwent consecutive SE-MREG (pulse repetition time [TR] = 0.25 seconds), SE-SMS (TR = 1.3 seconds), and SE-EPI (TR = 4.4 seconds) scans in pseudorandomized order applied to a visual block design paradigm for generation of t-statistics maps. For the investigation of functional connectivity, additional resting-state data were acquired for 5 minutes and a seed-based correlation analysis using Stanford's FIND (Functional Imaging in Neuropsychiatric Disorders) atlas was performed. The increased sampling rate of SE-MREG relative to SE-SMS and SE-EPI improves the sensitivity to detect BOLD activation by 33% and 54%, respectively, and increases the capability to extract resting-state networks. Compared with a brain region that is not affected by magnetic field inhomogeneities, SE-MREG shows 2.5 times higher relative signal strength than GE-MREG in mesial temporal structures. SE-MREG offers a viable possibility for whole-brain fMRI with consideration of brain regions that are affected by strong susceptibility-induced magnetic field gradients.

Sensing and seeing associated with overlapping occipitoparietal activation in simultaneous EEG-fMRI.

The presence of a change in a visual scene can influence brain activity and behavior, even in the absence of full conscious report. It may be possible for us to sense that such a change has occurred, even if we cannot specify exactly where or what it was. Despite existing evidence from electroencephalogram (EEG) and eye-tracking data, it is still unclear how this partial level of awareness relates to functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) activation. Using EEG, fMRI, and a change blindness paradigm, we found multi-modal evidence to suggest that sensing a change is distinguishable from being blind to it. Specifically, trials during which participants could detect the presence of a colour change but not identify the location of the change (sense trials), were compared to those where participants could both detect and localise the change (localise or see trials), as well as change blind trials. In EEG, late parietal positivity and N2 amplitudes were larger for localised changes only, when compared to change blindness. However, ERP-informed fMRI analysis found no voxels with activation that significantly co-varied with fluctuations in single-trial late positivity amplitudes. In fMRI, a range of visual (BA17,18), parietal (BA7,40), and mid-brain (anterior cingulate, BA24) areas showed increased fMRI BOLD activation when a change was sensed, compared to change blindness. These visual and parietal areas are commonly implicated as the storage sites of visual working memory, and we therefore argue that sensing may not be explained by a lack of stored representation of the visual display. Both seeing and sensing a change were associated with an overlapping occipitoparietal network of activation when compared to blind trials, suggesting that the quality of the visual representation, rather than the lack of one, may result in partial awareness during the change blindness paradigm.

Rearrangement of the Activity of Neural Networks in the Human Brain on Reaching the Recognition Threshold for Fragmented Images

Common patterns of rearrangements of neural networks in the whole human brain on reaching the threshold of recognition of images in conditions of uncertainly were identifi ed. This result was obtained using a combination of digital synthesis of dynamic images and a brain activity mapping method using fMRI BOLD (blood oxygen level-dependent) signals. Reaching the threshold of recognition of images of objects was found to be associated with increases in the BOLD signal in some parts of the brain and decreases in the activity of neural networks in other areas. Brain areas whose activity was maximal at the time corresponding to the recognition threshold and task solution were described, and this activity was shown to be lesser in subthreshold and even suprathreshold conditions for observation of dynamic images. Areas in which this activity was minimal were identified. The data were interpreted in the framework of multichannel and multilevel model of systems taking decisions relating to visual signals.

1116 Microstructural & functional changes in the placenta during the COVID-19 pandemic

To study the impact of the COVID-19 pandemic on in vivo microstructural and functional placental development using intra-voxel incoherent motion (IVIM) and blood oxygen level dependent (BOLD) MRI, respectively. This is prospective, observational study of pregnant women with singleton gestations during the COVID-19 pandemic (May 2020-present), compared to pre-pandemic historical controls (July 2014-February 2020). Placental imaging was identical for pandemic and pre-pandemic cohorts: including T2W anatomic images, PGSE sequences for IVIM [TE/TR=53.8/8000ms with 9 b-values (0-900s/mm2)], gradient-echo planar imaging sequences for BOLD imaging (TE/TR=60/2000ms) using a 6 minute maternal hyperoxia design, followed by 6 minutes of normoxia as return to baseline. 28 pregnant women during COVID-19 were included and compared to 100 pre-pandemic healthy controls (IVIM) and 57 pre-pandemic healthy controls (BOLD). The average gestational age (GA) was 28.6±6.0, 29.2±5.8 and 30.1±3.9, respectively. IVIM metrics trended higher for placental diffusion and lower for placental perfusion compared to pre-pandemic controls (Table 1). BOLD functional MRI revealed significantly lower placental oxygenation during minutes 2-6 of maternal hyperoxia and during minutes 1-3 of return to resting state (post hyperoxia) compared to pre-pandemic controls (Figure 1). Respiratory pandemics have been associated with altered intrauterine programing that can result in fetal onset of adult diseases. While the mechanisms are unclear, the placenta is a critical organ that mediates maternal well-being with fetal development. We report altered microstructural and functional placental development during the COVID-19 pandemic in COVID-19 negative women. Neurodevelopmental assessments of these infants are ongoing to determine the short- and long-term effects of these changes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

Purpose: Recently, the cerebellum's role in Parkinson's disease (PD) has been highlighted. Therefore, this study sought to test the hypothesis that functional connectivity (FC) between cerebellar and cortical nodes of the resting-state networks differentiates PD patients from controls by scanning participants at rest using functional magnetic resonance imaging (fMRI) and investigating connectivity of the cerebellar nodes of the resting-state networks.Materials and Methods: Sixty-two PD participants off medication for at least 12 h and 33 normal controls (NCs) were scanned at rest using blood oxygenation level-dependent fMRI scans. Motor and cognitive functions were assessed with the Movement Disorder Society's Revision of the Unified Parkinson's Disease Rating Scale III and Montreal Cognitive Assessment, respectively. Connectivity was investigated with cerebellar seeds defined by Buckner's 7-network atlas.Results: PD participants had significant differences in FC when compared to NC participants. Most notably, PD patients had higher FC between cerebellar nodes of the somatomotor network (SMN) and the corresponding cortical nodes. Cognitive functioning was differentially associated with connectivity of the cerebellar SMN and dorsal attention network. Further, cerebellar connectivity of frontoparietal and default mode networks correlated with the severity of motor function.Conclusion: Our study demonstrates altered cerebello-cortical FC in PD, as well as an association of this FC with PD-related motor and cognitive disruptions, thus providing additional evidence for the cerebellum's role in PD.

Systematic Review: Anesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)-Part B: Effects of Anesthetic Agents, Doses and Timing.

Simple SummaryTo understand brain function in rats and mice functional magnetic resonance imaging of the brain is used. With this type of “brain scan” regional changes in blood flow and oxygen consumption are measured as an indirect surrogate for activity of brain regions. Animals are often anesthetized for the experiments to prevent stress and blurred images due to movement. However, anesthesia may alter the measurements, as blood flow within the brain is differently affected by different anesthetics, and anesthetics also directly affect brain function. Consequently, results obtained under one anesthetic protocol may not be comparable with those obtained under another, and/or not representative for awake animals and humans. We have systematically searched the existing literature for studies analyzing the effects of different anesthesia methods or studies that compared anesthetized and awake animals. Most studies reported that anesthetic agents, doses and timing had an effect on functional magnetic resonance imaging results. To obtain results which promote our understanding of brain function, it is therefore essential that a standard for anesthetic protocols for functional magnetic resonance is defined and their impact is well characterized.In rodent models the use of functional magnetic resonance imaging (fMRI) under anesthesia is common. The anesthetic protocol might influence fMRI readouts either directly or via changes in physiological parameters. As long as those factors cannot be objectively quantified, the scientific validity of fMRI in rodents is impaired. In the present systematic review, literature analyzing in rats and mice the influence of anesthesia regimes and concurrent physiological functions on blood oxygen level dependent (BOLD) fMRI results was investigated. Studies from four databases that were searched were selected following pre-defined criteria. Two separate articles publish the results; the herewith presented article includes the analyses of 83 studies. Most studies found differences in BOLD fMRI readouts with different anesthesia drugs and dose rates, time points of imaging or when awake status was compared to anesthetized animals. To obtain scientifically valid, reproducible results from rodent fMRI studies, stable levels of anesthesia with agents suitable for the model under investigation as well as known and objectively quantifiable effects on readouts are, thus, mandatory. Further studies should establish dose ranges for standardized anesthetic protocols and determine time windows for imaging during which influence of anesthesia on readout is objectively quantifiable.

Detecting Task Functional MRI Activation Using the Multiband Multiecho (MBME) Echo-Planar Imaging (EPI) Sequence.

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) has been widely applied to detect brain activations. Recent advances in multiband (MB) and multiecho (ME) techniques have greatly improved fMRI methods. MB imaging improves temporal and/or spatial resolution, while ME imaging has been shown to improve BOLD sensitivity. This study aimed to evaluate the novel MBME echo planar imaging (EPI) sequence utilizing MB and ME simultaneously to determine if the MBME outperform the MB single echo (MBSE) sequence for task fMRI. To compare the performance of MBME with MBSE in a task fMRI study. Prospective. A total of 29 healthy volunteers aged 20-46 years (9 male, 20 female). MBSE and MBME gradient-echo EPI sequences were applied at 3T. Additional T1 -weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) was collected. A checkerboard visual task was presented during the functional MBSE and MBME scans. The MBME or MBSE signal was evaluated using the temporal signal-to-noise ratio (tSNR). Task activation was evaluated using the z-score, volume, sensitivity, and specificity. Test-retest metrics of task activation were examined with the Dice coefficient (DC) and intraclass correlation coefficient (ICC) on subjects with repeated scans. A linear mixed-effects model was used to compared MBME and MBSE activation at the voxel base. The paired t-test was used to compare tSNR, activation z-score, and volume, along with sensitivity, specificity, and DC between MBSE and MBME. While similar task activation was detected in the visual cortex, MBME showed higher activation volume and higher sensitivity compared with MBSE (P < 0.05). ICC was higher for MBME than MBSE, while there was a trend of differences in DC (P = 0.08). MBME resulted in higher task fMRI activation volume and sensitivity without losing specificity. Reliability was also higher for MBME scans compared with MBSE. 1 TECHNICAL EFFICACY STAGE: 1.

Validating Linear Systems Analysis for Laminar fMRI: Temporal Additivity for Stimulus Duration Manipulations

Advancements in ultra-high field (7 T and higher) magnetic resonance imaging (MRI) scanners have made it possible to investigate both the structure and function of the human brain at a sub-millimeter scale. As neuronal feedforward and feedback information arrives in different layers, sub-millimeter functional MRI has the potential to uncover information processing between cortical micro-circuits across cortical depth, i.e. laminar fMRI. For nearly all conventional fMRI analyses, the main assumption is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal adheres to the principles of linear systems theory. For laminar fMRI, however, directional blood pooling across cortical depth stemming from the anatomy of the cortical vasculature, potentially violates these linear system assumptions, thereby complicating analysis and interpretation. Here we assess whether the temporal additivity requirement of linear systems theory holds for laminar fMRI. We measured responses elicited by viewing stimuli presented for different durations and evaluated how well the responses to shorter durations predicted those elicited by longer durations. We find that BOLD response predictions are consistently good predictors for observed responses, across all cortical depths, and in all measured visual field maps (V1, V2, and V3). Our results suggest that the temporal additivity assumption for linear systems theory holds for laminar fMRI. We thus show that the temporal additivity assumption holds across cortical depth for sub-millimeter gradient-echo BOLD fMRI in early visual cortex.

Separating vascular and neuronal effects of age on fMRI BOLD signals.

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

Multi-shot acquisitions for stimulus-evoked spinal cord BOLD fMRI.

To demonstrate the feasibility of 3D multi-shot magnetic resonance imaging acquisitions for stimulus-evoked blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in the human spinal cord in vivo. Two fMRI studies were performed at 3T. The first study was a hypercapnic gas challenge where data were acquired from healthy volunteers using a multi-shot 3D fast field echo (FFE) sequence as well as single-shot multi-slice echo-planar imaging (EPI). In the second study, another cohort of healthy volunteers performed an upper extremity motor task while fMRI data were acquired using a 3D multi-shot acquisition. Both 2D-EPI and 3D-FFE were shown to be sensitive to BOLD signal changes in the cervical spinal cord, and had comparable contrast-to-noise ratios in gray matter. FFE exhibited much less signal drop-out and weaker geometric distortions compared to EPI. In the motor paradigm study, the mean number of active voxels was highest in the ventral gray matter horns ipsilateral to the side of the task and at the spinal level associated with innervation of finger extensors. Highly multi-shot acquisition sequences such as 3D-FFE are well suited for stimulus-evoked spinal cord BOLD fMRI.

Age-related alterations in the cerebrovasculature affect neurovascular coupling and BOLD fMRI responses: Insights from animal models of aging.

The present and future research efforts in cognitive neuroscience and psychophysiology rely on the measurement, understanding, and interpretation of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to effectively investigate brain function. Aging and age-associated pathophysiological processes change the structural and functional integrity of the cerebrovasculature which can significantly alter how the BOLD signal is recorded and interpreted. In order to gain an improved understanding of the benefits, drawbacks, and methodological implications for BOLD fMRI in the context of cognitive neuroscience, it is crucial to understand the cellular and molecular mechanism of age-related vascular pathologies. This review discusses the multifaceted effects of aging and the contributions of age-related pathologies on structural and functional integrity of the cerebral microcirculation as they has been investigated in animal models of aging, including age-related alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage, vascular rarefaction, blood-brain barrier disruption, senescence, humoral deficiencies as they relate to, and potentially introduce confounding factors in the interpretation of BOLD fMRI.

Changed ACC-DMN functional connectivity after acupuncture with deqi for functional dyspepsia treatment: 针刺得气对功能性消化不良患者前扣带回-默认网络功能连接度的影响

ObjectiveTo clarify altered whole brain functional connectivity of the anterior cingulate cortex (ACC) in functional dyspepsia (FD) patients, and then to explore cerebral influence of acupuncture with deqi treating for FD. MethodsThirty-two FD patients and 35 healthy subjects (HS) were firstly scanned by the resting-state blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) to compare differences of ACC-based functional connectivity (FC). Then 32 FD patients were randomized to receive 20 sessions' acupuncture treatment with (n=16) and without deqi (n=16), as well as underwent functional magnetic resonance imaging (fMRI) scans after treatment. After group re-division according to deqi response, changes of ACC subregions-based resting-state FC (rsFC) were compared between the actual with and without deqi group. Two seeds with bilateral of each were selected as regions of interest (ROIs) of the ACC, including two from the dorsal ACC: S2 (BA24) (x=±5,y=2, z=46, r=3.5 mm) and two from the pregenual ACC: I7 (BA24) (x=±5,y=38, z=6, r=3.5 mm). The clinical changes of the Nepean Dyspepsia Index (NDI) that measuring symptoms and quality of life (QOL) were also used to further assess the correlation with ACC subregions rsFC in FD patients. ResultsCompared to HS, FD patients showed significantly increased ACC subregions rsFC with left fusiform gyrus, temporal cortex, hippocampus(HIPP)/amygdala, temporal pole, and right INS, superior occipital gyrus, and bilateral precuneus, superior parietal lobule (SPL), and decreased rsFC with left postcentral/precentral gyrus (PoG/PrG), supplementary motor area (SMA) and right cerebellum. 32 FD patients which were then re-divided into the actual deqi group (n=16) and actual without deqi group (n=16). The decrease of the NDI symptom score(pre-pos) in the actual deqi group was significantly greater than that in the actual without deqi group (P<0.05). Among the two groups, the actual deqi group showed increased ACC subregions rsFC with right SMA and bilateral PrG/PoG, and decreased rsFC with right precuneus, middle occipital gyrus, bilateral posterior cingulate cortex (PCC), HIPP/paraHIPP, angular gyrus and SPL after treatment. In addition, the changed NDI QOL scores(pre-post) of the actual deqi group was significantly positively correlated with their Fisher's transformed Z value of the altered ACC subregion (left I7) rsFC with right SPL(r=-0.597, P=0.04<0.05, FDR corrected P>0.05). ConclusionThe results tested the hypothesis that the advantage of deqi on efficacy is related to affecting the ACC subregions rsFC. It suggested that deqi might participate in the adaptive modulation of disrupted relationship between the ACC subregions and the default mode network (DMN).

Cap-Based Transcranial Optical Tomography in an Awake Infant.

Although Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI) is widely used to examine brain function in adults, the need for general anesthesia limits its practical utility in infants and small children. Functional Near-Infrared Spectroscopy - Diffuse Optical Tomography (fNIRS-DOT) imaging promises to be an alternative brain network imaging technique. Yet current versions of continuous-wave fNIRS-DOT systems are restricted to the cortical surface measurements and do not probe deep structures that are frequently injured especially in premature infants. Herein we report a transcranial near infrared optical imaging system, called Cap-based Transcranial Optical Tomography (CTOT) able to image whole brain hemodynamic activity with 3 seconds of data acquisition time. We show the system is capable of whole brain oxygenation mapping in an awake child, and that tomographically reconstructed static CTOT-derived oxy- and deoxygenated blood volumes are spatially correlated with the time-averaged BOLD fMRI volumes. By removing time bottlenecks in the current system, dynamic CTOT mapping should be possible, which would then enable evaluation of functional connectivity in awake infants.