Contribution of new and chronic cortical lesions to disability accrual in multiple sclerosis.

Cortical lesions are common in multiple sclerosis and are associated with disability and progressive disease. We asked whether cortical lesions continue to form in people with stable white matter lesions and whether the association of cortical lesions with worsening disability relates to pre-existing or new cortical lesions. Fifty adults with multiple sclerosis and no new white matter lesions in the year prior to enrolment (33 relapsing-remitting and 17 progressive) and a comparison group of nine adults who had formed at least one new white matter lesion in the year prior to enrolment (active relapsing-remitting) were evaluated annually with 7 tesla (T) brain MRI and 3T brain and spine MRI for 2 years, with clinical assessments for 3 years. Cortical lesions and paramagnetic rim lesions were identified on 7T images. Seven total cortical lesions formed in 3/30 individuals in the stable relapsing-remitting group (median 0, range 0-5), four total cortical lesions formed in 4/17 individuals in the progressive group (median 0, range 0-1), and 16 cortical lesions formed in 5/9 individuals in the active relapsing-remitting group (median 1, range 0-10, stable relapsing-remitting versus progressive versus active relapsing-remitting P = 0.006). New cortical lesions were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Individuals with at least three paramagnetic rim lesions had a greater increase in cortical lesion volume over time (median 16 µl, range -61 to 215 versus median 1 µl, range -24 to 184, P = 0.007), but change in lesion volume was not associated with disability change. Baseline cortical lesion volume was higher in people with worsening disability (median 1010 µl, range 13-9888 versus median 267 µl, range 0-3539, P = 0.001, adjusted for age and sex) and in individuals with relapsing-remitting multiple sclerosis who subsequently transitioned to secondary progressive multiple sclerosis (median 2183 µl, range 270-9888 versus median 321 µl, range 0-6392 in those who remained relapsing-remitting, P = 0.01, adjusted for age and sex). Baseline white matter lesion volume was not associated with worsening disability or transition from relapsing-remitting to secondary progressive multiple sclerosis. Cortical lesion formation is rare in people with stable white matter lesions, even in those with worsening disability. Cortical but not white matter lesion burden predicts disability worsening, suggesting that disability progression is related to long-term effects of cortical lesions that form early in the disease, rather than to ongoing cortical lesion formation.

Cortical lesions uniquely predict motor disability accrual and form rarely in the absence of new white matter lesions in multiple sclerosis.

Background and objectives: Cortical lesions (CL) are common in multiple sclerosis (MS) and associate with disability and progressive disease. We asked whether CL continue to form in people with stable white matter lesions (WML) and whether the association of CL with worsening disability relates to pre-existing or new CL. Methods: A cohort of adults with MS were evaluated annually with 7 tesla (T) brain magnetic resonance imaging (MRI) and 3T brain and spine MRI for 2 years, and clinical assessments for 3 years. CL were identified on 7T images at each timepoint. WML and brain tissue segmentation were performed using 3T images at baseline and year 2. Results: 59 adults with MS had ≥1 7T follow-up visit (mean follow-up time 2±0.5 years). 9 had "active" relapsing-remitting MS (RRMS), defined as new WML in the year prior to enrollment. Of the remaining 50, 33 had "stable" RRMS, 14 secondary progressive MS (SPMS), and 3 primary progressive MS. 16 total new CL formed in the active RRMS group (median 1, range 0-10), 7 in the stable RRMS group (median 0, range 0-5), and 4 in the progressive MS group (median 0, range 0-1) (p=0.006, stable RR vs PMS p=0.88). New CL were not associated with greater change in any individual disability measure or in a composite measure of disability worsening (worsening Expanded Disability Status Scale or 9-hole peg test or 25-foot timed walk). Baseline CL volume was higher in people with worsening disability (median 1010µl, range 13-9888 vs median 267µl, range 0-3539, p=0.001, adjusted for age and sex) and in individuals with RRMS who subsequently transitioned to SPMS (median 2183µl, range 270-9888 vs median 321µl, range 0-6392 in those who remained RRMS, p=0.01, adjusted for age and sex). Baseline WML volume was not associated with worsening disability or transition from RRMS to SPMS. Discussion: CL formation is rare in people with stable WML, even in those with worsening disability. CL but not WML burden predicts future worsening of disability, suggesting that the relationship between CL and disability progression is related to long-term effects of lesions that form in the earlier stages of disease, rather than to ongoing lesion formation.

Effect of motion, cortical orientation and spatial resolution on quantitative imaging of cortical R2* and magnetic susceptibility at 0.3 mm in-plane resolution at 7 T.

MR images of the effective relaxation rate R2* and magnetic susceptibility χ derived from multi-echo T2*-weighted (T2*w) MRI can provide insight into iron and myelin distributions in the brain, with the potential of providing biomarkers for neurological disorders. Quantification of R2* and χ at submillimeter resolution in the cortex in vivo has been difficult because of challenges such as head motion, limited signal to noise ratio, long scan time, and motion related magnetic field fluctuations. This work aimed to improve the robustness for quantifying intracortical R2* and χ and analyze the effects from motion, spatial resolution, and cortical orientation. T2*w data was acquired with a spatial resolution of 0.3 × 0.3 × 0.4 mm3 at 7 T and downsampled to various lower resolutions. A combined correction for motion and B0 changes was deployed using volumetric navigators. Such correction improved the T2*w image quality rated by experienced image readers and test-retest reliability of R2* and χ quantification with reduced median inter-scan differences up to 10 s-1 and 5 ppb, respectively. R2* and χ near the line of Gennari, a cortical layer high in iron and myelin, were as much as 10 s-1 and 10 ppb higher than the region at adjacent cortical depth. In addition, a significant effect due to the cortical orientation relative to the static field (B0) was observed in χ with a peak-to-peak amplitude of about 17 ppb. In retrospectively downsampled data, the capability to distinguish different cortical depth regions based on R2* or χ contrast remained up to isotropic 0.5 mm resolution. This study highlights the unique characteristics of R2* and χ along the cortical depth at submillimeter resolution and the need for motion and B0 corrections for their robust quantification in vivo.

Cerebrovascular activity is a major factor in the cerebrospinal fluid flow dynamics.

Cerebrospinal fluid (CSF) provides physical protection to the central nervous system as well as an essential homeostatic environment for the normal functioning of neurons. Additionally, it has been proposed that the pulsatile movement of CSF may assist in glymphatic clearance of brain metabolic waste products implicated in neurodegeneration. In awake humans, CSF flow dynamics are thought to be driven primarily by cerebral blood volume fluctuations resulting from a number of mechanisms, including a passive vascular response to blood pressure variations associated with cardiac and respiratory cycles. Recent research has shown that mechanisms that rely on the action of vascular smooth muscle cells ("cerebrovascular activity") such as neuronal activity, changes in intravascular CO2, and autonomic activation from the brainstem, may lead to CSF pulsations as well. Nevertheless, the relative contribution of these mechanisms to CSF flow remains unclear. To investigate this further, we developed an MRI approach capable of disentangling and quantifying CSF flow components of different time scales associated with these mechanisms. This approach was evaluated on human control subjects (n = 12) performing intermittent voluntary deep inspirations, by determining peak flow velocities and displaced volumes between these mechanisms in the fourth ventricle. We found that peak flow velocities were similar between the different mechanisms, while displaced volumes per cycle were about a magnitude larger for deep inspirations. CSF flow velocity peaked at around 10.4 s (range 7.1-14.8 s, n = 12) following deep inspiration, consistent with known cerebrovascular activation delays for this autonomic challenge. These findings point to an important role of cerebrovascular activity in the genesis of CSF pulsations. Other regulatory triggers for cerebral blood flow such as autonomic arousal and orthostatic challenges may create major CSF pulsatile movement as well. Future quantitative comparison of these and possibly additional types of CSF pulsations with the proposed approach may help clarify the conditions that affect CSF flow dynamics.

Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI.

Manually segmenting multiple sclerosis (MS) cortical lesions (CLs) is extremely time consuming, and past studies have shown only moderate inter-rater reliability. To accelerate this task, we developed a deep-learning-based framework (CLAIMS: Cortical Lesion AI-Based Assessment in Multiple Sclerosis) for the automated detection and classification of MS CLs with 7 T MRI. Two 7 T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5 mm isotropic MP2RAGE acquired four times (MP2RAGE×4), 0.7 mm MP2RAGE, 0.5 mm T2 *-weighted GRE, and 0.5 mm T2 *-weighted EPI. The second dataset consisted of 20 scans including only 0.75 × 0.75 × 0.9 mm3 MP2RAGE. CLAIMS was first evaluated using sixfold cross-validation with single and multi-contrast 0.5 mm MRI input. Second, the performance of the model was tested on 0.7 mm MP2RAGE images after training with either 0.5 mm MP2RAGE×4, 0.7 mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state-of-the-art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGE×4 achieved results comparable to those of the multi-contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain-scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6 µL (lesion-wise detection rate of 71% versus 48%). The proposed framework outperforms previous state-of-the-art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7 T MRI, especially in the field of diagnosis and differential diagnosis of MS patients.

Cortical lesion hotspots and association of subpial lesions with disability in multiple sclerosis.

BACKGROUND: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. OBJECTIVE: Characterize cortical lesions by 7 tesla (T) T2*-/T1-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability. METHODS: Sixty-four adults with MS (45 relapsing-remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing. RESULTS: Cortical lesions were found in 94% (progressive: median 56/range 2-203; relapsing-remitting: 15/0-168; p = 0.004). Lesion distribution across 50 cortical regions was nonuniform (p = 0.006), with highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus. Leukocortical and white matter lesion volumes were strongly correlated (r = 0.58, p < 0.0001), while subpial and white matter lesion volumes were moderately correlated (r = 0.30, p = 0.002). Leukocortical (p = 0.02) but not subpial lesions (p = 0.40) were correlated with paramagnetic rim lesions; both were correlated with spinal cord lesions (p = 0.01). Cortical lesion volumes (total and subtypes) were correlated with expanded disability status scale, 25-foot timed walk, nine-hole peg test, and symbol digit modality test scores. CONCLUSION: Cortical lesions are highly prevalent and are associated with disability and progressive disease. Subpial lesion burden is not strongly correlated with white matter lesions, suggesting differences in inflammation and repair mechanisms.

Autonomic arousals contribute to brain fluid pulsations during sleep.

During sleep, slow waves of neuro-electrical activity engulf the human brain and aid in the consolidation of memories. Recent research suggests that these slow waves may also promote brain health by facilitating the removal of metabolic waste, possibly by orchestrating the pulsatile flow of cerebrospinal fluid (CSF) through local neural control over vascular tone. To investigate the role of slow waves in the generation of CSF pulsations, we analyzed functional MRI data obtained across the full sleep-wake cycle and during a waking respiratory task. This revealed a novel generating mechanism that relies on the autonomic regulation of cerebral vascular tone without requiring slow electrocortical activity or even sleep. Therefore, the role of CSF pulsations in brain waste clearance may, in part, depend on proper autoregulatory control of cerebral blood flow.

Sensitivity limitations of high-resolution perfusion-based human fMRI at 7 Tesla.

The study of the brain's functional organization at laminar and columnar level of the cortex with blood oxygenation-level dependent (BOLD) functional MRI (fMRI) is affected by the contribution of large veins downstream from the microvascular response to brain activity. Blood volume- and especially perfusion-based techniques may reduce this problem because of their reduced sensitivity to venous effects, but may not allow the same spatial resolution because of smaller signal changes associated with brain activity. Here we investigated the practical resolution limits of perfusion-weighted fMRI in human visual stimulation experiments. For this purpose, we used a highly sensitive, single-shot perfusion labeling (SSPL) technique at 7 T and compared sensitivity to detect visual activation at low (2 mm, n = 10) and high (1 mm, n = 8) nominal isotropic spatial, and 3 s temporal, resolution with BOLD in 5½-minute-long experiments. Despite the smaller absolute signal change with activation, 2 mm resolution SSPL yielded comparable sensitivity to BOLD. This was attributed to a superior suppression of physiological noise with SSPL. However, at 1 mm nominal resolution, SSPL sensitivity fell on average at least 42% below that of BOLD, and detection of visual activation was compromised. This is explained by the fact that at high resolution, with both techniques, typically thermal noise rather than physiological noise dominates sensitivity. The observed sensitivity loss implies that to perform 1-mm resolution, perfusion weighted fMRI with a robustness similar to BOLD, scan times that are almost 3 times longer than the comparable BOLD experiment are required. This is in line with or slightly better than previous comparisons between perfusion-weighted fMRI and BOLD. The lower sensitivity has to be weighed against the spatial fidelity advantages of high-resolution perfusion-weighted fMRI.

Navigator-Guided Motion and B0 Correction of T2*-Weighted Magnetic Resonance Imaging Improves Multiple Sclerosis Cortical Lesion Detection.

BACKGROUND: Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations. PURPOSE: The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T2*w magnetic resonance imaging. MATERIALS AND METHODS: In this prospective study, a gradient-recalled echo sequence incorporating a navigator allowing for motion and B0 field correction was applied to collect T2*w images at 7 T from adults with MS between August 2019 and March 2020. T2*-weighted images were acquired in 1 to 3 partially overlapping scans per individual and were reconstructed using global average B0 correction ("uncorrected") or motion correction and spatially linear B0 correction ("corrected"). Image quality rating and manual segmentation of cortical lesions were performed on uncorrected and corrected images. Lesions seen on a single scan were retrospectively evaluated on the complementary scan. The association of cortical lesions with clinical disability was assessed. Mixed models were used to determine the effect of correction on lesion detection as well as on the relationship between disability and lesion count. RESULTS: A total of 22 T2*w scans were performed on 11 adults with MS (mean [SD] age, 49 [11] years; 8 women). Quality improved for 20 of 22 scans (91%) after correction. A total of 69 cortical lesions were identified on uncorrected images (median per scan, 2; range, 0-11) versus 148 on corrected images (median per scan, 4.5; range, 0-25; rate ratio [RR], 2.1; P < 0.0001). For low-quality uncorrected scans with moderate to severe motion artifact (18/22, 82%), there was an improvement in cortical lesion detection with correction (RR, 2.5; P < 0.0001), whereas there was no significant change in cortical lesion detection for high-quality scans (RR, 1.3; P = 0.43). CONCLUSIONS: Navigator-guided motion and B0 correction substantially improves the overall image quality of T2*w magnetic resonance imaging at 7 T and increases its sensitivity for cortical lesions.

FMRI based on transition-band balanced SSFP in comparison with EPI on a high-performance 0.55 T scanner.

PURPOSE: Low-field (<1 tesla) MRI scanners allow more widespread diagnostic use for a range of cardiac, musculoskeletal, and neurological applications. However, the feasibility of performing robust fMRI at low field has yet to be fully demonstrated. To address this gap, we investigated task-based fMRI using a highly sensitive transition-band balanced steady-state free precession approach and standard EPI on a 0.55 tesla scanner equipped with modern high-performance gradient coils and a receive array. METHODS: TR and flip-angle of transition-band steady-state free precession were optimized for 0.55 tesla by simulations. Static shimming was employed to compensate for concomitant field effects. Visual task-based fMRI data were acquired from 8 healthy volunteers. For comparison, standard EPI data were also acquired with TE = T2∗ . Retrospective image-based correction for physiological effects (RETROICOR) was used to quantify physiological noise effects. RESULTS: Activation was robustly detected using both methods in a 4-min scan time. Transition-band steady-state free precession was found to be sensitive to interference from subtle spatial and temporal (field drift, respiration) variations in the magnetic field, counteracting potential advantages of the reduced magnetic susceptibility effects compared to its utilization at high field. These adverse effects could be partially remedied with static shimming and postprocessing approaches. Standard EPI proved more robust against the sources of interference. CONCLUSION: BOLD contrast is sufficiently large at 0.55 tesla for robust detection of brain activation and may be employed to broaden the spectrum of applications of low-field MRI. Standard EPI outperforms transition-band steady-state free precession in terms of signal stability.

B0-field dependence of MRI T1 relaxation in human brain.

Tissue longitudinal relaxation characterized by recovery time T1 or rate R1 is a fundamental MRI contrast mechanism that is increasingly being used to study the brain's myelination patterns in both health and disease. Nevertheless, the quantitative relationship between T1 and myelination, and its dependence on B0 field strength, is still not well known. It has been theorized that in much of brain tissue, T1 field-dependence is driven by that of macromolecular protons (MP) through a mechanism called magnetization transfer (MT). Despite the explanatory power of this theory and substantial support from in-vitro experiments at low fields (<3 â€‹T), in-vivo evidence across clinically relevant field strengths is lacking. In this study, T1-weighted MRI was acquired in a group of eight healthy volunteers at four clinically relevant field strengths (0.55, 1.5, 3 and 7 â€‹T) using the same pulse sequence at a single site, and jointly analyzed based on the two-pool model of MT. MP fraction and free-water pool T1 were obtained in several brain structures at 3 and 7 â€‹T, which allowed distinguishing between contributions from macromolecular content and iron to tissue T1. Based on this, the T1 of MP in white matter, indirectly determined by assuming a field independent T1 of free water, was shown to increase approximately linearly with B0. This study advances our understanding of the T1 contrast mechanism and its relation to brain myelin content across the wide range of currently available MRI strengths, and it has the potential to inform design of T1 mapping methods for improved reproducibility in the human brain.

Background suppressed magnetization transfer MRI.

PURPOSE: Up to 30% of the hydrogen atoms in brain tissue are part of molecules ("semisolids") other than water. In MRI, their magnetization is typically not observed directly, but can influence the water magnetization through magnetization transfer (MT). Comparison of MRI scans differentially sensitized to MT allows estimation of the semisolid fraction and potential changes with disease. Here, we present an approach designed to improve this estimate by measuring the size of the MT effect in a single scan. METHODS: A stimulated echo sequence was used to generate a spatial pattern in the longitudinal water magnetization, which was then given time to exchange with semisolids. After saturating the remaining water magnetization, reverse exchange was allowed to partly re-establish the original water magnetization pattern. The third excitation pulse then formed a stimulated echo out of this pattern. RESULTS: MT data were obtained on 10 human subjects at 7 T with varying exchange times. The images showed the expected time dependence of signal associated with the forward and reverse exchange processes. Excellent suppression of non-exchanging background signal was achieved. As expected, this suppression came at the price of a substantial reduction in exchange-related signal (by ~75% compared to the signal in saturation recovery MT), in part because of the reliance on a 2-step exchange process. CONCLUSION: The results demonstrate an MT signal can be observed in a single acquisition without subtraction. This may be advantageous for MT measurements when signal instabilities related to motion and physiological variations exceed thermal noise sources.

Reducing motion sensitivity in 3D high-resolution T2*-weighted MRI by navigator-based motion and nonlinear magnetic field correction.

T2*-weighted gradient echo (GRE) MRI at high field is uniquely sensitive to the magnetic properties of tissue and allows the study of brain and vascular anatomy at high spatial resolution. However, it is also sensitive to B0 field changes induced by head motion and physiological processes such as the respiratory cycle. Conventional motion correction techniques do not take these field changes into account, and consequently do not fully recover image quality in T2*-weighted MRI. Here, a novel approach was developed to address this by monitoring the B0 field with a volumetric EPI phase navigator. The navigator was acquired at a shorter echo time than that of the (higher resolution) T2*-weighted GRE imaging data and accelerated with parallel imaging for high temporal resolution. At 4 â€‹mm isotropic spatial resolution and 0.54 â€‹s temporal resolution, the accuracy for estimation of rotation and translation was better than 0.2° and 0.1 â€‹mm, respectively. The 10% and 90% percentiles of B0 measurement error using the navigator were -1.8 and 1.5 Hz  at 7 T, respectively. A fast retrospective reconstruction algorithm correcting for both motion and nonlinear B0 changes was also developed. The navigator and reconstruction algorithm were evaluated in correcting motion-corrupted high-resolution T2*-weighted GRE MRI on healthy human subjects at 7 â€‹T. Excellent image quality was demonstrated with the proposed correction method.

Sympathetic activity contributes to the fMRI signal.

The interpretation of functional magnetic resonance imaging (fMRI) studies of brain activity is often hampered by the presence of brain-wide signal variations that may arise from a variety of neuronal and non-neuronal sources. Recent work suggests a contribution from the sympathetic vascular innervation, which may affect the fMRI signal through its putative and poorly understood role in cerebral blood flow (CBF) regulation. By analyzing fMRI and (electro-) physiological signals concurrently acquired during sleep, we found that widespread fMRI signal changes often co-occur with electroencephalography (EEG) K-complexes, signatures of sub-cortical arousal, and episodic drops in finger skin vascular tone; phenomena that have been associated with intermittent sympathetic activity. These findings support the notion that the extrinsic sympathetic innervation of the cerebral vasculature contributes to CBF regulation and the fMRI signal. Accounting for this mechanism could help separate systemic from local signal contributions and improve interpretation of fMRI studies.

White matter intercompartmental water exchange rates determined from detailed modeling of the myelin sheath.

PURPOSE: Magnetization exchange (ME) between hydrogen protons of water and large molecules (semisolids [SS]) in lipid bilayers is an important factor in MRI signal generation and can be exploited to study white matter pathology. Current models used to quantify ME in white matter generally consider water to reside in 1 or 2 distinct compartments, ignoring the complexities of the myelin sheath's multicompartment structure of alternating myelin SS and myelin water (MW) layers. Here, we investigated the effect of this by fitting ME data obtained from human brain at 7 T with a multilayer model of myelin. METHODS: A multi-echo acquisition for a T2* -based separation of MW from other water signals was combined with various preparation pulses to change the (relative) state of the SS and water pools and analyzed by fitting with a multilayer exchange model. RESULTS: The estimated lifetime within a single MW layer was 260 µs, corresponding to a lipid bilayer permeability of 6.7 µm/s. The magnetization lifetime of the aggregate of all MW was estimated at 13 ms, shorter than previously reported values in the range of 40 to 140 ms. CONCLUSION: Contrary to expectations and previous reports, ME between protons in myelin SS and water is not limited by the myelin sheath but rather by the exchange between SS and water protons. The analysis of ME contrast should account for the relatively short MW lifetime and affects the interpretation of tissue compartmentalization from MRI contrasts such as T1 - and diffusion-weighting.

All-night functional magnetic resonance imaging sleep studies.

BACKGROUND: Previous functional magnetic resonance imaging (fMRI) sleep studies have been hampered by the difficulty of obtaining extended amounts of sleep in the sleep-adverse environment of the scanner and often have resorted to manipulations such as sleep depriving subjects before scanning. These manipulations limit the generalizability of the results. NEW METHOD: The current study is a methodological validation of procedures aimed at obtaining all-night fMRI data in sleeping subjects with minimal exposure to experimentally induced sleep deprivation. Specifically, subjects slept in the scanner on two consecutive nights, allowing the first night to serve as an adaptation night. RESULTS/COMPARISON WITH EXISTING METHOD(S): Sleep scoring results from simultaneously acquired electroencephalography data on Night 2 indicate that subjects (n = 12) reached the full spectrum of sleep stages including slow-wave (M = 52.1 min, SD = 26.5 min) and rapid eye movement (REM, M = 45.2 min, SD = 27.9 min) sleep and exhibited a mean of 2.1 (SD = 1.1) nonREM-REM sleep cycles. CONCLUSIONS: It was found that by diligently applying fundamental principles and methodologies of sleep and neuroimaging science, performing all-night fMRI sleep studies is feasible. However, because the two nights of the study were performed consecutively, some sleep deprivation from Night 1 as a cause of the Night 2 results is likely, so consideration should be given to replicating the current study with a washout period. It is envisioned that other laboratories can adopt the core features of this protocol to obtain similar results.

Impulse response timing differences in BOLD and CBV weighted fMRI.

Recent advances in BOLD fMRI scan techniques have substantially improved spatial and temporal resolution, currently reaching to sub-millimeter and sub-second levels respectively. Unfortunately, there remain physiological barriers that prevent achieving this resolution in practice. BOLD contrast relies on the hemodynamic response to neuronal activity, whose associated cerebral blood oxygenation (CBO) changes may spread over several millimeters and last several seconds. Recent reports have suggested that significant improvements may be possible with cerebral blood volume (CBV)-weighted fMRI, which highlights the CBV changes rather than the BOLD changes associated with the hemodynamic response. Nevertheless, quantitative comparisons between CBV and BOLD are sparse, in particular regarding their temporal characteristics in human brain. To address this, we studied a cohort of subjects that received injection of ferumoxytol, an intravascular iron-oxide based contrast agent that introduces strong CBV contrast. An event-related visual stimulus paradigm was used to compare the impulse response (IR) for CBV and BOLD contrast, obtained with and without ferumoxytol, respectively. Experiments performed at 7 T (n = 5) at 1.2-1.5 mm spatial and 1 s temporal resolution showed that the onset time and time-to-peak of the CBV IR averaged 0.8 and 3.5 s respectively, both 0.6 s shorter than the BOLD IR. While significant, these improvements are relatively small and not expected to lead to practical advantages for the extraction of temporal information about neural activity. Nonlinearities in the observed IR were also compared and found to be similar between the CBV and BOLD, indicating that these are likely not caused by a 'ceiling' effect in the CBO response, but rather support a previously proposed model of vascular compliance, in which changes in vascular tone elicited by a preceding stimulus affect the IR.

Effect of head motion on MRI B0 field distribution.

PURPOSE: To identify and characterize the sources of B0 field changes due to head motion, to reduce motion sensitivity in human brain MRI. METHODS: B0 fields were measured in 5 healthy human volunteers at various head poses. After measurement of the total field, the field originating from the subject was calculated by subtracting the external field generated by the magnet and shims. A subject-specific susceptibility model was created to quantify the contribution of the head and torso. The spatial complexity of the field changes was analyzed using spherical harmonic expansion. RESULTS: Minor head pose changes can cause substantial and spatially complex field changes in the brain. For rotations and translations of approximately 5 º and 5 mm, respectively, at 7 T, the field change that is associated with the subject's magnetization generates a standard deviation (SD) of about 10 Hz over the brain. The stationary torso contributes to this subject-associated field change significantly with a SD of about 5 Hz. The subject-associated change leads to image-corrupting phase errors in multi-shot T 2 * -weighted acquisitions. CONCLUSION: The B0 field changes arising from head motion are problematic for multishot T 2 * -weighted imaging. Characterization of the underlying sources provides new insights into mitigation strategies, which may benefit from individualized predictive field models in addition to real-time field monitoring and correction strategies.

Contribution of systemic vascular effects to fMRI activity in white matter.

To investigate a potential contribution of systemic physiology to recently reported BOLD fMRI signals in white matter, we compared photo-plethysmography (PPG) and whole-brain fMRI signals recorded simultaneously during long resting-state scans from an overnight sleep study. We found that intermittent drops in the amplitude of the PPG signal exhibited strong and widespread correlations with the fMRI signal, both in white matter (WM) and in gray matter (GM). The WM signal pattern resembled that seen in previous resting-state fMRI studies and closely tracked the location of medullary veins. Its temporal cross-correlation with the PPG amplitude was bipolar, with an early negative value. In GM, the correlation was consistently positive. Consistent with previous studies comparing physiological signals with fMRI, these findings point to a systemic vascular contribution to WM fMRI signals. The PPG drops are interpreted as systemic vasoconstrictive events, possibly related to intermittent increases in sympathetic tone related to fluctuations in arousal state. The counter-intuitive polarity of the WM signal is explained by long blood transit times in the medullary vasculature of WM, which cause blood oxygenation loss and a substantial timing mismatch between blood volume and blood oxygenation effects. A similar mechanism may explain previous findings of negative WM signals around large draining veins during both task- and resting-state fMRI.

Optically controlled on-coil amplifier with RF monitoring feedback.

PURPOSE: To develop a new optically controlled on-coil amplifier that facilitates safe use of multi-channel radiofrequency (RF) transmission in MRI by real-time monitoring of signal phase and amplitude. METHODS: Monitoring was carried out with a 4-channel prototype system by sensing, down sampling, digitizing, and optically transmitting the RF transmit signal to a remote PC to control the amplifiers. Performance was evaluated with benchtop and 7 T MRI experiments. RESULTS: Monitored amplitude and phase were stable across repetitions and had standard deviations of 0.061 µT and 0.0073 rad, respectively. The feedback system allowed inter-channel phase and B1 amplitude to be adjusted within two iterations. MRI experiments demonstrated the feasibility of this approach to perform safe and accurate multi-channel RF transmission and monitoring at high field. CONCLUSION: We demonstrated a 4-channel transceiver system based on optically controlled on-coil amplifiers with RF signal monitoring and feedback control. The approach allows the safe and precise control of RF transmission fields, required to achieve uniform excitation at high field. Magn Reson Med 79:2833-2841, 2018. © 2017 International Society for Magnetic Resonance in Medicine.