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Purpose: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T., Methods: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated., Results: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups., Conclusion: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling (pCASL) technique at 7T that offers the capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 ms shorter than in middle/deep layers revealing the time course of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla., Methods: Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated., Results: Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest B 1 + amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate., Conclusion: Optimized wideband uniform rate smooth truncation pulse with the highest B 1 + amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling., (© 2021 International Society for Magnetic Resonance in Medicine.)

Increased cerebroarterial pulsations are thought to be contributing factors in microvascular damage and cognitive impairment. In this study, we assessed the utility of two-dimensional (2D) phase-contrast MRI (PC-MRI) in quantifying cerebroarterial pulsations and evaluated the associations of pulsatile and non-pulsatile hemodynamic measures with cognitive performance and white matter hyperintensities (WMH). Neurocognitive assessments on 50 elderly subjects were performed using clinical dementia rating (CDR) and Montreal cognitive assessment (MoCA). An electrocardiogram-gated 2D PC-MRI sequence was used to calculate mean flow rate, pulsatility index (PI), and resistivity index (RI) of the internal carotid artery. For each subject, whole brain global cerebral blood flow (gCBF) and relative WMH volume were also quantified. Elevated RI was significantly associated with reduced cognitive performance quantified using MoCA ( p  =   0.04) and global CDR ( p  =   0.02). PI and RI were both significantly associated with relative WMH volume ( p  =   0.01, p  <   0.01, respectively). However, non-pulsatile hemodynamic measures were not associated with cognitive impairment or relative WMH volume. This study showed that the cerebroarterial pulsatile measures obtained using PC-MRI have stronger association with the measures of cognitive impairment compared to global blood flow measurement and as such, might be useful as potential biomarkers of cerebrovascular dysfunction in preclinical populations.

Ultrahigh field offers increased resolution and contrast for neurovascular imaging. Arterial spin labeling methods benefit from an increased intrinsic signal-to-noise ratio of MR imaging signal and a prolonged tracer half-life at ultrahigh field, allowing the visualization of layer-dependent microvascular perfusion. Arterial spin labeling-based time-resolved 4-dimensional MR angiography at 7T provides a detailed depiction of the vascular architecture and dynamic blood flow pattern with high spatial and temporal resolutions. High-resolution black blood MR imaging at 7T allows detailed characterization of small perforating arteries such as lenticulostriate arteries. All techniques benefit from advances in parallel radiofrequency transmission technologies at ultrahigh field., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The lenticulostriate arteries (LSAs) with small diameters of a few hundred microns take origin directly from the high flow middle cerebral artery (MCA), making them especially susceptible to damage (e.g. by hypertension). This study aims to present high resolution (isotropic ∼0.5 mm), black blood MRI for the visualization and characterization of LSAs at both 3 T and 7 T., Materials and Methods: T1-weighted 3D turbo spin-echo with variable flip angles (T1w TSE-VFA) sequences were optimized for the visualization of LSAs by performing extended phase graph (EPG) simulations. Twenty healthy volunteers (15 under 35 years old, 5 over 60 years old) were imaged with the T1w TSE-VFA sequences at both 3 T and 7 T. Contrast-to-noise ratio (CNR) was quantified, and LSAs were manually segmented using ITK-SNAP. Automated Reeb graph shape analysis was performed to extract features including vessel length and tortuosity. All quantitative metrics were compared between the two field strengths and two age groups using ANOVA., Results: LSAs can be clearly delineated using optimized 3D T1w TSE-VFA at 3 T and 7 T, and a greater number of LSA branches can be detected compared to those by time-of-flight MR angiography (TOF MRA) at 7 T. The CNR of LSAs was comparable between 7 T and 3 T. T1w TSE-VFA showed significantly higher CNR than TOF MRA at the stem portion of the LSAs branching off the medial middle cerebral artery. The mean vessel length and tortuosity were greater on TOF MRA compared to TSE-VFA. The number of detected LSAs by both TSE-VFA and TOF MRA was significantly reduced in aged subjects, while the mean vessel length measured on 7 T TSE-VFA showed significant difference between the two age groups., Conclusion: The high-resolution black-blood 3D T1w TSE-VFA sequence offers a new method for the visualization and quantification of LSAs at both 3 T and 7 T, which may be applied for a number of pathological conditions related to the damage of LSAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the feasibility and sensitivity of cellular magnetic resonance imaging (MRI) with ferumoxytol nanocomplex-labeled macrophages at ultrahigh magnetic field of 7 T., Materials and Methods: THP-1-induced macrophages were labeled using self-assembling heparin + protamine + ferumoxytol nanocomplexes which were injected into a gelatin phantom visible on both microscope and MRI. Susceptibility-weighted imaging (SWI) and balanced steady-state free precession (bSSFP) pulse sequences were applied at 3 and 7 T. The average, maximum intensity projection, and root mean square combined images were generated for phase-cycled bSSFP images. The signal-to-noise ratio and contrast-to-noise ratio (CNR) efficiencies were calculated. Ex vivo experiments were then performed using a formalin-fixed pig brain injected witĥ100 and ~1,000 labeled cells, respectively, at both 3 and 7 T., Results: A high cell labeling efficiency (.90%) was achieved with heparin + protamine + ferumoxytol nanocomplexes. Less than 100 cells were detectable in the gelatin phantom at both 3 and 7 T. The 7 T data showed more than double CNR efficiency compared to the corresponding sequences at 3 T. The CNR efficiencies of phase-cycled bSSFP images were higher compared to those of SWI, and the root mean square combined bSSFP showed the highest CNR efficiency with minimal banding. Following co-registration of microscope and MR images, more cells (51/63) were detected by bSSFP at 7 T than at 3 T (36/63). On pig brain, botĥ100 and ~1,000 cells were detected at 3 and 7 T. While the cell size appeared larger due to blooming effects on SWI, bSSFP allowed better contrast to precisely identify the location of the cells with higher signal-to-noise ratio efficiency., Conclusion: The proposed cellular MRI with ferumoxytol nanocomplex-labeled macrophages at 7 T has a high sensitivity to detect, 100 cells. The proposed method has great translational potential and may have broad clinical applications that involve cell types with a primary phagocytic phenotype., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

Purpose: To develop and evaluate an improved stack-of-stars radial sampling strategy for reducing streaking artifacts., Methods: The conventional stack-of-stars sampling strategy collects the same radial angle for every partition (slice) encoding. In an undersampled acquisition, such an aligned acquisition generates coherent aliasing patterns and introduces strong streaking artifacts. We show that by rotating the radial spokes in a golden-angle manner along the partition-encoding direction, the aliasing pattern is modified, resulting in improved image quality for gridding and more advanced reconstruction methods. Computer simulations were performed and phantom as well as in vivo images for three different applications were acquired., Results: Simulation, phantom, and in vivo experiments confirmed that the proposed method was able to generate images with less streaking artifact and sharper structures based on undersampled acquisitions in comparison with the conventional aligned approach at the same acceleration factors. By combining parallel imaging and compressed sensing in the reconstruction, streaking artifacts were mostly removed with improved delineation of fine structures using the proposed strategy., Conclusions: We present a simple method to reduce streaking artifacts and improve image quality in 3D stack-of-stars acquisitions by re-arranging the radial spoke angles in the 3D partition direction, which can be used for rapid volumetric imaging. Magn Reson Med 78:2290-2298, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in the central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (ΔCBV) and change in arterial pressure (ΔBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, and gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To identify potential biomarkers of the renal impairment in lupus nephritis using a multi-parametric renal quantitative MRI (qMRI) protocol including diffusion weighted imaging (DWI), blood oxygen level dependent (BOLD), arterial spin labeling (ASL) and T1rho MRI between a cohort of healthy volunteers and lupus nephritis (LN) patients., Materials and Methods: The renal qMRI protocol was performed twice with repositioning in between on 10 LN patients and 10 matched controls at 1.5 T. Navigator-gated and breath-hold acquisitions followed by non-rigid image registration were used to control respiratory motion. The repeatability of the 4 MRI modalities was evaluated with the intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Unpaired t-test and stepwise logistic regression were carried out to evaluate qMRI parameters between the LN and control groups., Results: The reproducibility of the 4 qMRI modalities ranged from moderate to good (ICC=0.4-0.91, wsCV≤12%) with a few exceptions. T1rho MRI and ASL renal blood flow (RBF) demonstrated significant differences between the LN and control groups. Stepwise logistic regression yielded only one significant parameter (medullar T1rho) in differentiating LN from control groups with 95% accuracy., Conclusion: A reasonable degree of test-retest repeatability and accuracy of a multi-parametric renal qMRI protocol has been demonstrated in healthy volunteers and LN subjects. T1rho and ASL RBF are promising imaging biomarkers of LN., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There has been tremendous interest in applying functional magnetic resonance imaging-based resting-state functional connectivity (rs-fcMRI) measurements to the study of brain function. However, a lack of understanding of the physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI findings. In this work, the authors examine the regional associations between rs-fcMRI estimates and dynamic coupling between the blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual-echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas macrovascular volume fraction was estimated using time-of-flight MR angiography. Functional connectivity within well-known functional networks—including the default mode, frontoparietal, and primary sensory-motor networks—was calculated using a conventional seed-based correlation approach. They found the functional connectivity strength to be significantly correlated with the regional increase in CBF-BOLD coupling strength and inversely proportional to macrovascular volume fraction. These relationships were consistently observed within all functional networks considered. Their findings suggest that highly connected networks observed using rs-fcMRI are not likely to be mediated by common vascular drainage linking distal cortical areas. Instead, high BOLD functional connectivity is more likely to reflect tighter neurovascular connections, attributable to neuronal pathways.

Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

The present study explored multi-scale entropy (MSE) analysis to investigate the entropy of resting state fMRI signals across multiple time scales. MSE analysis was developed to distinguish random noise from complex signals since the entropy of the former decreases with longer time scales while the latter signal maintains its entropy due to a "self-resemblance" across time scales. A long resting state BOLD fMRI (rs-fMRI) scan with 1000 data points was performed on five healthy young volunteers to investigate the spatial and temporal characteristics of entropy across multiple time scales. A shorter rs-fMRI scan with 240 data points was performed on a cohort of subjects consisting of healthy young (age 23 ± 2 years, n = 8) and aged volunteers (age 66 ± 3 years, n = 8) to investigate the effect of healthy aging on the entropy of rs-fMRI. The results showed that MSE of gray matter, rather than white matter, resembles closely that of f (-1) noise over multiple time scales. By filtering out high frequency random fluctuations, MSE analysis is able to reveal enhanced contrast in entropy between gray and white matter, as well as between age groups at longer time scales. Our data support the use of MSE analysis as a validation metric for quantifying the complexity of rs-fMRI signals.

Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies., (© 2013.)

Purpose: To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in normal aging and cognitive decline associated with familial Alzheimer's disease (fAD)., Materials and Methods: Resting state BOLD fMRI data were acquired at 3T from two independent cohorts of subjects consisting of healthy young (age 23 ± 2 years, n = 8) and aged volunteers (age 66 ± 3 years, n = 8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2 ± 15.8 years; and eight nonmutation carrying family members, age 28.8 ± 5.9 years). Mean ApEn values were compared between the two age groups and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain., Results: Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis., Conclusion: ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases., (Copyright © 2012 Wiley Periodicals, Inc.)

Digital subtraction angiography (DSA) remains the gold standard to diagnose intracranial arteriovenous malformations (AVMs) but is invasive. Existing magnetic resonance angiography (MRA) is suboptimal for assessing the hemodynamics of AVMs. The objective of this study was to evaluate the clinical utility of a novel noncontrast four-dimensional (4D) dynamic MRA (dMRA) in the evaluation of intracranial AVMs through comparison with DSA and time-of-flight (TOF) MRA. Nineteen patients (12 women, mean age 26.2±10.7 years) with intracranial AVMs were examined with 4D dMRA, TOF and DSA. Spetzler-Martin grading scale was evaluated using each of the above three methods independently by two raters. Diagnostic confidence scores for three components of AVMs (feeding artery, nidus and draining vein) were also rated. Kendall's coefficient of concordance was calculated to evaluate the reliability between two raters within each modality (dMRA, TOF, TOF plus dMRA). The Wilcoxon signed-rank test was applied to compare the diagnostic confidence scores between each pair of the three modalities. dMRA was able to detect 16 out of 19 AVMs, and the ratings of AVM size and location matched those of DSA. The diagnostic confidence scores by dMRA were adequate for nidus (3.5/5), moderate for feeding arteries (2.5/5) and poor for draining veins (1.5/5). The hemodynamic information provided by dMRA improved diagnostic confidence scores by TOF MRA. As a completely noninvasive method, 4D dMRA offers hemodynamic information with a temporal resolution of 50-100 ms for the evaluation of AVMs and can complement existing methods such as DSA and TOF MRA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We investigated the biophysical mechanism of low-frequency drift in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) (0.00-0.01 Hz), by exploring its spatial distribution, dependence on imaging parameters, and relationship with task-induced brain activation. Cardiac and respiratory signals were concurrently recorded during MRI scanning and subsequently removed from MRI data. It was found that the spatial distribution of low-frequency drifts in human brain followed a tissue-specific pattern, with greater drift magnitude in the gray matter than in white matter. In gray matter, the dependence of drift magnitudes on TE was similar to that of task-induced BOLD signal changes, i.e., the absolute drift magnitude reached the maximum when TE approached T(2)* whereas relative drift magnitude increased linearly with TE. By systematically varying the flip angle, it was found that drift magnitudes possessed a positive dependence on image intensity. In phantom experiments, the observed drift was not only much smaller than that of human brain, but also showed different dependence on TE and flip angle. In fMRI studies with visual stimulation, a strong positive correlation between drift effects at baseline and task-induced BOLD signal changes was observed both across subjects and across activated pixels within individual participants. We further demonstrated that intrinsic, physiological drift effects are a major component of the spontaneous fluctuations of BOLD fMRI signal within the frequency range of 0.0-0.1 Hz. Our study supports brain physiology, as opposed to scanner instabilities or cardiac/respiratory pulsations, as the main source of low-frequency drifts in BOLD fMRI.

Voxel-based morphometry (VBM) is an objective whole-brain technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. In the current study, we used VBM to examine possible cerebral gray matter abnormalities in patients with posttraumatic stress disorder (PTSD) due to fire. The subjects included 12 victims of a fire disaster with PTSD and 12 matched victims of the same fire without PTSD. Magnetic resonance images were obtained on a 1.5-Tesla General Electric scanner at Central South University, and an entire brain volume of 248 contiguous slices was obtained for each subject. Then, gray matter density in patients with PTSD and control groups was compared by using a VBM approach in SPM2. Group analysis was thresholded at P<0.001, uncorrected, at the voxel level. The following three regions of reduced gray matter volume were found in patients with PTSD compared with controls: left hippocampus, left anterior cingulate cortex (ACC), and bilateral insular cortex. It was concluded that there are structural abnormalities of the hippocampus, the ACC and the insular cortex in patients with PTSD due to fire.

A widely used tool for functional magnetic resonance imaging (fMRI) data analysis, statistical parametric mapping (SPM), is based on the general linear model (GLM). SPM therefore requires a priori knowledge or specific assumptions about the time courses contributing to signal changes. In contradistinction, independent component analysis (ICA) is a data-driven method based on the assumption that the causes of responses are statistically independent. Here we describe a unified method, which combines ICA, temporal ICA (tICA), and SPM for analyzing fMRI data. tICA was applied to fMRI datasets to disclose independent components, whose number was determined by the Bayesian information criterion (BIC). The resulting components were used to construct the design matrix of a GLM. Parameters were estimated and regionally-specific statistical inferences were made about activations in the usual way. The sensitivity and specificity were evaluated using Monte Carlo simulations. The receiver operating characteristic (ROC) curves indicated that the unified SPM-ICA method had a better performance. Moreover, SPM-ICA was applied to fMRI datasets from twelve normal subjects performing left and right hand movements. The areas identified corresponded to motor (premotor, sensorimotor areas and SMA) areas and were consistently task related. Part of the frontal lobe, parietal cortex, and cingulate gyrus also showed transiently task-related responses. The unified method requires less supervision than the conventional SPM and enables classical inference about the expression of independent components. Our results also suggest that the method has a higher sensitivity than SPM analyses.

Recent clinical trials of transcranial direct current stimulation (tDCS) in depression have shown contrasting results. Consequently, we used in-vivo neuroimaging to confirm targeting and modulation of depression-relevant neural circuitry by tDCS. Depressed participants (N = 66, Baseline Hamilton Depression Rating Scale (HDRS) 17-item scores ≥14 and

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants. Isoproterenol infusions induced dose-dependent increases in heart rate and cardiorespiratory interoception, with all participants endorsing increased sensations at the highest dose. These reports were accompanied by increased BOLD and ASL activation of the right insular cortex at the highest dose. Different responses across insula subregions were also observed. During anticipation, insula activation increased in more anterior regions. During stimulation, activation increased in the mid-dorsal and posterior insula on the right, but decreased in the same regions on the left. This study demonstrates the feasibility of phMRI for assessing brain activation during adrenergic interoceptive stimulation, and provides further evidence supporting a dynamic role for the insula in representing changes in cardiorespiratory states.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

The neurobiological interpretation of developmental BOLD fMRI findings remains difficult due to the confounding issues of potentially varied baseline of brain function and varied strength of neurovascular coupling across age groups. The central theme of the present research is to study the development of brain function and neuronal activity through in vivo assessments of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) both at baseline and during the performance of a working memory task in a cohort of typically developing children aged 7 to 18years. Using a suite of 4 emerging MRI technologies including MR blood oximetry, phase-contrast MRI, pseudo-continuous arterial spin labeling (pCASL) perfusion MRI and concurrent CBF/BOLD fMRI, we found: 1) At baseline, both global CBF and CMRO2 showed an age related decline while global OEF was stable across the age group; 2) During the working memory task, neither BOLD nor CBF responses showed significant variations with age in the activated fronto-parietal brain regions. Nevertheless, detailed voxel-wise analyses revealed sub-regions within the activated fronto-parietal regions that show significant decline of fractional CMRO2 responses with age. These findings suggest that the brain may become more "energy efficient" with age during development.

PurposeTo investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient-echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively.Materials and methodsEach sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment (MCI), and one participant with Alzheimer's disease (AD). Eight of these subjects also underwent H2 (15) O positron emission tomography (PET) scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV).ResultsThe ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant.ConclusionThe 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects.

Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.

Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies.

Highlights • Brain lesions are common in Chinese NMOSD patients. • Thirty patients (25%) showed typical-NMOSD abnormalities. • BBB permeability was significantly higher in the abnormal brain MRI group. • BBB permeability was not correlated to distribution or enhancement brain lesions. • Qalb was associated with Expanded Disability Status Scale score. Abstract Objective The aims of this study were to report brain characteristic abnormalities and to evaluate the relationship of blood-brain barrier (BBB) disruption and brain lesions in Chinese patients with NMOSD. Methods Brain magnetic resonance imaging characteristics and cerebrospinal fluid (CSF) laboratory tests of 121 patients with NMOSD at acute attack were reviewed retrospectively. Qalb (CSF albumin/serum albumin) was used for assessment of disruption of BBB. Results Brain MRI abnormalities were observed in 36.4% (44/121) of the NMOSD patients. Thirty patients (25%) showed typical-NMOSD abnormalities, including dorsal medulla lesions (n = 16, 13.2%), brainstem/cerebellum (n = 11, 9.1%), thalamus/hypothalamus (n = 3, 2.5%), periventricular white matter lesions (n = 4, 3.3%) hemispheric white matter (n = 4, 3.3%). Twenty-five patients (20.7%) had nonspecific lesions. Compared to the NMOSD patients without brain lesion, the proportion of patients who had abnormal BBB permeability was significantly higher in the abnormal brain MRI group (47.7% vs. 27.3%, P < 0.05). BBB permeability was not correlated to distribution of brain lesions or enhancement lesions. Qalb was associated with higher Expanded Disability Status Scale scores (r = 0.689, P < 0.05). Conclusions Brain lesions are common in NMOSD patients. Marker of BBB permeability is associated with brain lesion and EDSS scores of NMOSD. [ABSTRACT FROM AUTHOR]