Fast and silent MRI using nonlinear gradient fields at the ultrasonic gradient switching frequency of 20 kHz with a Point Spread Function framework reconstruction.

PURPOSE: To demonstrate the feasibility of using a nonlinear gradient field for spatial encoding at the ultrasonic switching frequency of 20 kHz and present a framework to reconstruct data acquired in this way. METHODS: Nonlinear encoding at 20 kHz was realized by using a single-axis silent gradient insert for imaging in the periphery, that, is the nonlinear region, of the gradient field. The gradient insert induces a rapidly oscillating gradient field in the phase-encode direction, which enables nonlinear encoding when combined with a Cartesian readout from the linear whole-body gradients. Data from a 2D gradient echo sequence were reconstructed using a point spread function (PSF) framework. Accelerated scans were also simulated via retrospective undersampling (R = 1 to R = 8) to determine the effectiveness of the PSF-framework for accelerated imaging. RESULTS: Using a nonlinear gradient field switched at 20 kHz and the PSF-framework resulted in images of comparable quality to images from conventional Cartesian linear encoding. At increased acceleration factors (R ≤ 8), the PSF-framework outperformed linear SENSE reconstructions by improved controlling of aliasing artifacts. CONCLUSION: Using the PSF-framework, images of comparable quality to conventional SENSE reconstructions are possible via combining traditional linear and ultrasonic oscillating nonlinear encoding fields. Using nonlinear gradient fields relaxes the demand for strictly linear gradient fields, enabling much higher slew rates with a reduced risk of peripheral nerve stimulation or cardiac stimulation, which could aid in extension to ultrasonic whole-body MRI. The lack of aliasing artifacts also highlights the potential of accelerated imaging using the PSF-framework.

A silent echo-planar spectroscopic imaging readout with high spectral bandwidth MRSI using an ultrasonic gradient axis.

PURPOSE: We present a novel silent echo-planar spectroscopic imaging (EPSI) readout, which uses an ultrasonic gradient insert to accelerate MRSI while producing a high spectral bandwidth (20 kHz) and a low sound level. METHODS: The ultrasonic gradient insert consisted of a single-axis (z-direction) plug-and-play gradient coil, powered by an audio amplifier, and produced 40 mT/m at 20 kHz. The silent EPSI readout was implemented in a phase-encoded MRSI acquisition. Here, the additional spatial encoding provided by this silent EPSI readout was used to reduce the number of phase-encoding steps. Spectroscopic acquisitions using phase-encoded MRSI, a conventional EPSI-readout, and the silent EPSI readout were performed on a phantom containing metabolites with resonance frequencies in the ppm range of brain metabolites (0-4 ppm). These acquisitions were used to determine sound levels, showcase the high spectral bandwidth of the silent EPSI readout, and determine the SNR efficiency and the scan efficiency. RESULTS: The silent EPSI readout featured a 19-dB lower sound level than a conventional EPSI readout while featuring a high spectral bandwidth of 20 kHz without spectral ghosting artifacts. Compared with phase-encoded MRSI, the silent EPSI readout provided a 4.5-fold reduction in scan time. In addition, the scan efficiency of the silent EPSI readout was higher (82.5% vs. 51.5%) than the conventional EPSI readout. CONCLUSIONS: We have for the first time demonstrated a silent spectroscopic imaging readout with a high spectral bandwidth and low sound level. This sound reduction provided by the silent readout is expected to have applications in sound-sensitive patient groups, whereas the high spectral bandwidth could benefit ultrahigh-field MR systems.

CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T-MRI.

OBJECTIVE: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. METHODS: We recruited 23 CADASIL patients (age 51.1 ± 10.1 years, 52% women) and 13 age- and sex-matched controls (46.1 ± 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. RESULTS: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference - 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference - 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood-oxygen-level dependent [BOLD] mean difference -0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference -0.29%, p = 0.02). INTERPRETATION: Multiple aspects of cerebral small vessel function on 7T-MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies. ANN NEUROL 2023;93:29-39.

A selection and targeting framework of cortical locations for line-scanning fMRI.

Depth-resolved functional magnetic resonance imaging (fMRI) is an emerging field growing in popularity given the potential of separating signals from different computational processes in cerebral cortex. Conventional acquisition schemes suffer from low spatial and temporal resolutions. Line-scanning methods allow depth-resolved fMRI by sacrificing spatial coverage to sample blood oxygenated level-dependent (BOLD) responses at ultra-high temporal and spatial resolution. For neuroscience applications, it is critical to be able to place the line accurately to (1) sample the right neural population and (2) target that neural population with tailored stimuli or tasks. To this end, we devised a multi-session framework where a target cortical location is selected based on anatomical and functional properties. The line is then positioned according to this information in a separate second session, and we tailor the experiment to focus on the target location. Anatomically, the precision of the line placement was confirmed by projecting a nominal representation of the acquired line back onto the surface. Functional estimates of neural selectivities in the line, as quantified by a visual population-receptive field model, resembled the target selectivities well for most subjects. This functional precision was quantified in detail by estimating the distance between the visual field location of the targeted vertex and the location in visual cortex (V1) that most closely resembled the line-scanning estimates; this distance was on average ~5.5 mm. Given the dimensions of the line, differences in acquisition, session, and stimulus design, this validates that line-scanning can be used to probe local neural sensitivities across sessions. In summary, we present an accurate framework for line-scanning MRI; we believe such a framework is required to harness the full potential of line-scanning and maximize its utility. Furthermore, this approach bridges canonical fMRI experiments with electrophysiological experiments, which in turn allows novel avenues for studying human physiology non-invasively.

A mechanistic computational framework to investigate the hemodynamic fingerprint of the blood oxygenation level-dependent signal.

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is one of the most used imaging techniques to map brain activity or to obtain clinical information about human cortical vasculature, in both healthy and disease conditions. Nevertheless, BOLD fMRI is an indirect measurement of brain functioning triggered by neurovascular coupling. The origin of the BOLD signal is quite complex, and the signal formation thus depends, among other factors, on the topology of the cortical vasculature and the associated hemodynamic changes. To understand the hemodynamic evolution of the BOLD signal response in humans, it is beneficial to have a computational framework available that virtually resembles the human cortical vasculature, and simulates hemodynamic changes and corresponding MRI signal changes via interactions of intrinsic biophysical and magnetic properties of the tissues. To this end, we have developed a mechanistic computational framework that simulates the hemodynamic fingerprint of the BOLD signal based on a statistically defined, three-dimensional, vascular model that approaches the human cortical vascular architecture. The microvasculature is approximated through a Voronoi tessellation method and the macrovasculature is adapted from two-photon microscopy mice data. Using this computational framework, we simulated hemodynamic changes-cerebral blood flow, cerebral blood volume, and blood oxygen saturation-induced by virtual arterial dilation. Then we computed local magnetic field disturbances generated by the vascular topology and the corresponding blood oxygen saturation changes. This mechanistic computational framework also considers the intrinsic biophysical and magnetic properties of nearby tissue, such as water diffusion and relaxation properties, resulting in a dynamic BOLD signal response. The proposed mechanistic computational framework provides an integrated biophysical model that can offer better insights regarding the spatial and temporal properties of the BOLD signal changes.

Improved Selectivity in 7 T Digit Mapping Using VASO-CBV.

Functional magnetic resonance imaging (fMRI) at Ultra-high field (UHF, ≥ 7 T) benefits from significant gains in the BOLD contrast-to-noise ratio (CNR) and temporal signal-to-noise ratio (tSNR) compared to conventional field strengths (3 T). Although these improvements enabled researchers to study the human brain to unprecedented spatial resolution, the blood pooling effect reduces the spatial specificity of the widely-used gradient-echo BOLD acquisitions. In this context, vascular space occupancy (VASO-CBV) imaging may be advantageous since it is proposed to have a higher spatial specificity than BOLD. We hypothesized that the assumed higher specificity of VASO-CBV imaging would translate to reduced overlap in fine-scale digit representation maps compared to BOLD-based digit maps. We used sub-millimeter resolution VASO fMRI at 7 T to map VASO-CBV and BOLD responses simultaneously in the motor and somatosensory cortices during individual finger movement tasks. We assessed the cortical overlap in different ways, first by calculating similarity coefficient metrics (DICE and Jaccard) and second by calculating selectivity measures. In addition, we demonstrate a consistent topographical organization of the targeted digit representations (thumb-index-little finger) in the motor areas. We show that the VASO-CBV responses yielded less overlap between the digit clusters than BOLD, and other selectivity measures were higher for VASO-CBV too. In summary, these results were consistent across metrics and participants, confirming the higher spatial specificity of VASO-CBV compared to BOLD.

Towards functional spin-echo BOLD line-scanning in humans at 7T.

OBJECTIVE: Neurons cluster into sub-millimeter spatial structures and neural activity occurs at millisecond resolutions; hence, ultimately, high spatial and high temporal resolutions are required for functional MRI. In this work, we implemented a spin-echo line-scanning (SELINE) sequence to use in high spatial and temporal resolution fMRI. MATERIALS AND METHODS: A line is formed by simply rotating the spin-echo refocusing gradient to a plane perpendicular to the excited slice and by removing the phase-encoding gradient. This technique promises a combination of high spatial and temporal resolution (250 µm, 500 ms) and microvascular specificity of functional responses. We compared SELINE data to a corresponding gradient-echo version (GELINE). RESULTS: We demonstrate that SELINE showed much-improved line selection (i.e. a sharper line profile) compared to GELINE, albeit at the cost of a significant drop in functional sensitivity. DISCUSSION: This low functional sensitivity needs to be addressed before SELINE can be applied for neuroscientific purposes.

Comparing BOLD and VASO-CBV population receptive field estimates in human visual cortex.

Vascular Space Occupancy (VASO) is an alternative fMRI approach based on changes in Cerebral Blood Volume (CBV). VASO-CBV fMRI can provide higher spatial specificity than the blood oxygenation level-dependent (BOLD) method because the CBV response is thought to be limited to smaller vessels. To investigate how this technique compares to BOLD fMRI for cognitive neuroscience applications, we compared population receptive field (pRF) mapping estimates between BOLD and VASO-CBV. We hypothesized that VASO-CBV would elicit distinct pRF properties compared to BOLD. Specifically, since pRF size estimates also depend on vascular sources, we hypothesized that reduced vascular blurring might yield narrower pRFs for VASO-CBV measurements. We used a VASO sequence with a double readout 3D EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the visual cortex while participants viewed conventional pRF mapping stimuli. Both VASO-CBV and BOLD images show similar eccentricity and polar angle maps across all participants. Compared to BOLD-based measurements, VASO-CBV yielded lower tSNR and variance explained. The pRF size changed with eccentricity similarly for VASO-CBV and BOLD, and the pRF size estimates were similar for VASO-CBV and BOLD, even when we equate variance explained between VASO-CBV and BOLD. This result suggests that the vascular component of the pRF size is not dominating in either VASO-CBV or BOLD.

Accelerating Brain Imaging Using a Silent Spatial Encoding Axis.

PURPOSE: To characterize the acceleration capabilities of a silent head insert gradient axis that operates at the inaudible frequency of 20 kHz and a maximum gradient amplitude of 40 mT/m without inducing peripheral nerve stimulation. METHODS: The silent gradient axis' acquisitions feature an oscillating gradient in the phase-encoding direction that is played out on top of a cartesian readout, similarly as done in Wave-CAIPI. The additional spatial encoding fills k-space in readout lanes allowing for the acquisition of fewer phase-encoding steps without increasing aliasing artifacts. Fully sampled 2D gradient echo datasets were acquired both with and without the silent readout. All scans were retrospectively undersampled (acceleration factors R = 1 to 12) to compare conventional SENSE acceleration and acceleration using the silent gradient. The silent gradient amplitude and the readout bandwidth were varied to investigate the effect on artifacts and g-factor. RESULTS: The silent readout reduced the g-factor for all acceleration factors when compared to SENSE acceleration. Increasing the silent gradient amplitude from 31.5 mT/m to 40 mT/m at an acceleration factor of 10 yielded a reduction in the average g-factor (gavg ) from 1.3 ± 0.14 (gmax  = 1.9) to 1.1 ± 0.09 (gmax  = 1.6). Furthermore, reducing the number of cycles increased the readout bandwidth and the g-factor that reached gavg  = 1.5 ± 0.16 for a readout bandwidth of 651 Hz/pixel and an acceleration factor of R = 8. CONCLUSION: A silent gradient axis enables high acceleration factors up to R = 10 while maintaining a g-factor close to unity (gavg  = 1.1 and gmax  = 1.6) and can be acquired with clinically relevant readout bandwidths.

A silent gradient axis for soundless spatial encoding to enable fast and quiet brain imaging.

PURPOSE: A novel silent imaging method is proposed that combines a gradient insert oscillating at the inaudible frequency 20 kHz with slew rate-limited gradient waveforms to form a silent gradient axis that enable quiet and fast imaging. METHODS: The gradient insert consisted of a plug-and-play (45 kg) single axis z-gradient, which operated as an additional fourth gradient axis. This insert was made resonant using capacitors and combined with an audio amplifier to allow for operation at 20 kHz. The gradient field was characterized using field measurements and the physiological effects of operating a gradient field at 20 kHz were explored using peripheral nerve stimulation experiments, tissue heating simulations and sound measurements. The imaging sequence consisted of a modified gradient-echo sequence which fills k-space in readout lanes with a width proportional to the oscillating gradient amplitude. The feasibility of the method was demonstrated in-vivo using 2D and 3D gradient echo (GRE) sequences which were reconstructed using a conjugate-gradient SENSE reconstruction. RESULTS: Field measurements yielded a maximum gradient amplitude and slew rate of 40.8 mT/m and 5178T/m/s at 20 kHz. Physiological effects such as peripheral nerve stimulation and tissue heating were found not to be limiting at this amplitude and slew rate. For a 3D GRE sequence, a maximum sound level of 85 db(A) was measured during scanning. Imaging experiments using the silent gradient axis produced artifact free images while also featuring a 5.3-fold shorter scan time than a fully sampled acquisition. CONCLUSION: A silent gradient axis provides a novel pathway to fast and quiet brain imaging.

Can 7T MPRAGE match MP2RAGE for gray-white matter contrast?

Ultra-High Field (UHF) MRI provides a significant increase in Signal-to-Noise Ratio (SNR) and gains in contrast weighting in several functional and structural acquisitions. Unfortunately, an increase in field strength also induces non-uniformities in the transmit field (B1+) that can compromise image contrast non-uniformly. The MPRAGE is one of the most common T1 weighted (T1w) image acquisitions for structural imaging. It provides excellent contrast between gray and white matter and is widely used for brain segmentation. At 7T, the signal non-uniformities tend to complicate this and therefore, the self-bias-field corrected MP2RAGE is often used there. In both MPRAGE and MP2RAGE, more homogeneous image contrast can be achieved with adiabatic pulses, like the TR-FOCI inversion pulse, or special pulse design on parallel transmission systems, like Universal Pulses (UP). In the present study, we investigate different strategies to improve the bias-field for MPRAGE at 7T, comparing the contrast and GM/WM segmentability against MP2RAGE. The higher temporal efficiency of MPRAGE combined with the potential of the user-friendly UPs was the primary motivation for this MPRAGE-MP2RAGE comparison. We acquired MPRAGE data in six volunteers, adding a k-space shutter to reduce scan time, a kt-point UP approach for homogeneous signal excitation, and a TR-FOCI pulse for homogeneous inversion. Our results show remarkable signal contrast improvement throughout the brain, including regions of low B1+ such as the cerebellum. The improvements in the MPRAGE were largest following the introduction of the UPs. In addition to the CNR, both SNR and GM/WM segmentability were also assessed. Among the MPRAGEs, the combined strategy (UP + TR-FOCI) yielded highest SNR and showed highest spatial similarity between GM segments to the MP2RAGE. Interestingly, the distance between gray and white matter peaks in the intensity histograms did not increase, as better pulses and higher SNR especially benefitted the (cerebellar) gray matter. Overall, the gray-white matter contrast from MP2RAGE is higher, with higher CNR and higher intensity peak distances, even when scaled to scan time. Hence, the extra acquisition time for MP2RAGE is justified by the improved segmentability.

Comparing hand movement rate dependence of cerebral blood volume and BOLD responses at 7T.

Functional magnetic resonance imaging (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast takes advantage of the coupling between neuronal activity and the hemodynamics to allow a non-invasive localisation of the neuronal activity. In general, fMRI experiments assume a linear relationship between neuronal activation and the observed hemodynamics. However, the relationship between BOLD responses, neuronal activity, and behaviour are often nonlinear. In addition, the nonlinearity between BOLD responses and behaviour may be related to neuronal process rather than a neurovascular uncoupling. Further, part of the nonlinearity may be driven by vascular nonlinearity effects in particular from large vessel contributions. fMRI based on cerebral blood volume (CBV), promises a higher microvascular specificity, potentially without vascular nonlinearity effects and reduced contamination of the large draining vessels compared to BOLD. In this study, we aimed to investigate differences in BOLD and VASO-CBV signal changes during a hand movement task over a broad range of movement rates. We used a double readout 3D-EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the sensorimotor cortex. The measured BOLD and VASO-CBV responses increased very similarly in a nonlinear fashion, plateauing for movement rates larger than 1 Hz. Our findings show a tight relationship between BOLD and VASO-CBV responses, indicating that the overall interplay of CBV and BOLD responses are similar for the assessed range of movement rates. These results suggest that the observed nonlinearity of neuronal origin is already present in VASO-CBV measurements, and consequently shows relatively unchanged BOLD responses.

A plug-and-play, lightweight, single-axis gradient insert design for increasing spatiotemporal resolution in echo planar imaging-based brain imaging.

The goal of this study was to introduce and evaluate the performance of a lightweight, high-performance, single-axis (z-axis) gradient insert design primarily intended for high-resolution functional magnetic resonance imaging, and aimed at providing both ease of use and a boost in spatiotemporal resolution. The optimal winding positions of the coil were obtained using a genetic algorithm with a cost function that balanced gradient performance (minimum 0.30 mT/m/A) and field linearity (≥16 cm linear region). These parameters were verified using field distribution measurements by B0 -mapping. The correction of geometrical distortions was performed using theoretical field distribution of the coil. Simulations and measurements were performed to investigate the echo planar imaging echo-spacing reduction due to the improved gradient performance. The resulting coil featured a 16-cm linear region, a weight of 45 kg, an installation time of 15 min, and a maximum gradient strength and slew rate of 200 mT/m and 1300 T/m/s, respectively, when paired with a commercially available gradient amplifier (940 V/630 A). The field distribution measurements matched the theoretically expected field. By utilizing the theoretical field distribution, geometrical distortions were corrected to within 6% of the whole-body gradient reference image in the target region. Compared with a whole-body gradient set, a maximum reduction in echo-spacing of a factor of 2.3 was found, translating to a 344 µs echo-spacing, for a field of view of 192 mm, a receiver bandwidth of 920 kHz and a gradient amplitude of 112 mT/m. We present a lightweight, single-axis gradient insert design that can provide high gradient performance and an increase in spatiotemporal resolution with correctable geometrical distortions while also offering a short installation time of less than 15 min and minimal system modifications.

Double delay alternating with nutation for tailored excitation facilitates banding-free isotropic high-resolution intracranial vessel wall imaging.

The purpose of this study was to evaluate the use of a double delay alternating with nutation for tailored excitation (D-DANTE)-prepared sequence for banding-free isotropic high-resolution intracranial vessel wall imaging (IC-VWI) and to compare its performance with regular DANTE in terms of signal-to-noise ratio (SNR) as well as cerebrospinal fluid (CSF) and blood suppression efficiency. To this end, a D-DANTE-prepared 3D turbo spin echo sequence was implemented by interleaving two separate DANTE pulse trains with different RF phase-cycling schemes, but keeping all other DANTE parameters unchanged, including the total number of pulses and total preparation time. This achieved a reduction of the banding distance compared with regular DANTE enabling banding-free imaging up to higher resolutions. Bloch simulations assuming static vessel wall and flowing CSF spins were performed to compare DANTE and D-DANTE in terms of SNR and vessel wall/CSF contrast. Similar image quality measures were assessed from measurements on 13 healthy middle-aged volunteers. Both simulation and in vivo results showed that D-DANTE had only slightly lower vessel wall/CSF and vessel wall/blood contrast-to-noise ratio values compared with regular DANTE, which originated from a 10%-15% reduction in vessel wall SNR but not from reduced CSF or blood suppression efficiency. As anticipated, IC-VWI acquisitions showed that D-DANTE can successfully remove banding artifacts compared with regular DANTE with equal scan time or DANTE preparation length. Moreover, application was demonstrated in a patient with an intracranial aneurysm, indicating improved robustness to slow flow artifacts compared with clinically available 3D turbo spin echo scans. In conclusion, D-DANTE provides banding artifact-free IC-VWI up to higher isotropic resolutions compared with regular DANTE. This allows for a more flexible choice of DANTE preparation parameters in high-resolution IC-VWI protocols.

Automated Assessment of Cerebral Arterial Perforator Function on 7T MRI.

BACKGROUND: Blood flow velocity and pulsatility of small cerebral perforating arteries can be measured using 7T quantitative 2D phase contrast (PC) MRI. However, ghosting artifacts arising from subject movement and pulsating large arteries cause false positives when applying a previously published perforator detection method. PURPOSE: To develop a robust, automated method to exclude perforators located in ghosting artifacts. STUDY TYPE: Retrospective. SUBJECTS: Fifteen patients with vascular cognitive impairment or carotid occlusive disease and 10 healthy controls. FIELD STRENGTH/SEQUENCE: 7T/cardiac-gated 2D PC MRI. ASSESSMENT: Perforators were automatically excluded from ghosting regions, which were defined as bands in the phase-encoding direction of large arteries. As reference, perforators were manually excluded by two raters (T.A., J.J.M.Z.), based on perforator location with respect to visible ghosting artifacts. The performance of both censoring methods was assessed for the number of (Nincluded ), mean velocity (Vmean ), and pulsatility index (PI) of the included perforators. STATISTICAL TESTS: For within-method comparisons, inter- and intrarater reliability were assessed for the manual method, and test-retest reliability was assessed for both methods from repeated 2D PC scans (without repositioning). Intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CIs) were determined for Nincluded , Vmean , and PI for all within-method comparisons. The ICC to compare between the two methods was determined with the use of both (test-retest) scans using a multilevel nonlinear mixed model. RESULTS: The automated censoring method showed a moderate to good ICC (95% CI) vs. manual censoring for Nincluded (0.73 [0.58-0.87]) and Vmean (0.90 [0.84-0.96]), and a moderate ICC for PI (0.57 [0.37-0.76]). The test-retest reliability of the manual censoring method was considerably lower than the interrater and intrarater reliability, indicating that scanner noise dominates the uncertainty of the analysis. DATA CONCLUSION: The proposed automated censoring method can reliably exclude small perforators affected by ghosting artifacts. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 1.

Laminar fMRI: What can the time domain tell us?

The rapid developments in functional MRI (fMRI) acquisition methods and hardware technologies in recent years, particularly at high field (≥7 T), have enabled unparalleled visualization of functional detail at a laminar or columnar level, bringing fMRI close to the intrinsic resolution of brain function. These advances highlight the potential of high resolution fMRI to be a valuable tool to study the fundamental processing performed in cortical micro-circuits, and their interactions such as feedforward and feedback processes. Notably, because fMRI measures neuronal activity via hemodynamics, the ultimate resolution it affords depends on the spatial specificity of hemodynamics to neuronal activity at a detailed spatial scale, and by the evolution of this specificity over time. Several laminar (≤1 mm spatial resolution) fMRI studies have examined spatial characteristics of the measured hemodynamic signals across cortical depth, in light of understanding or improving the spatial specificity of laminar fMRI. Few studies have examined temporal features of the hemodynamic response across cortical depth. Temporal features of the hemodynamic response offer an additional means to improve the specificity of fMRI, and could help target neuronal processes and neurovascular coupling relationships across laminae, for example by differences in the onset times of the response across cortical depth. In this review, we discuss factors that affect the timing of neuronal and hemodynamic responses across laminae, touching on the neuronal laminar organization, and focusing on the laminar vascular organization. We provide an overview of hemodynamics across the cortical vascular tree based on optical imaging studies, and review temporal aspects of hemodynamics that have been examined across cortical depth in high spatiotemporal resolution fMRI studies. Last, we discuss the limits and potential of high spatiotemporal resolution fMRI to study laminar neurovascular coupling and neuronal processes.

On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm.

Diffusion functional magnetic resonance imaging (dfMRI) is a promising technique to map functional activations by acquiring diffusion-weighed spin-echo images. In previous studies, dfMRI showed higher spatial accuracy at activation mapping compared to classic functional MRI approaches. However, it remains unclear whether dfMRI measures result from changes in the intracellular/extracellular environment, perfusion, and/or T2 values. We designed an acquisition/quantification scheme to disentangle such effects in the motor cortex during a finger-tapping paradigm. dfMRI was acquired at specific diffusion weightings to selectively suppress perfusion and free-water diffusion, then time series of the apparent diffusion coefficient (ADC-fMRI) and of intravoxel incoherent motion (IVIM) effects were derived. ADC-fMRI provided ADC estimates sensitive to changes in perfusion and free-water volume, but not to T2 /T2 * values. With IVIM modeling, we isolated the perfusion contribution to ADC, while suppressing T2 effects. Compared to conventional gradient-echo blood oxygenation level-dependent fMRI, activation maps obtained with dfMRI and ADC-fMRI had smaller clusters, and the spatial overlap between the three techniques was below 50%. Increases of perfusion fractions were observed during task in both dfMRI and ADC-fMRI activations. Perfusion effects were more prominent with ADC-fMRI than with dfMRI but were significant in less than 25% of activation regions. IVIM modeling suggests that the sensitivity to task of dfMRI derives from a decrease of intracellular/extracellular diffusion and an increase of the pseudo-diffusion signal fraction, leading to different, more confined spatial activation patterns compared to classic functional MRI.

Phase contrast MRI measurements of net cerebrospinal fluid flow through the cerebral aqueduct are confounded by respiration.

BACKGROUND: Net cerebrospinal fluid (CSF) flow through the cerebral aqueduct may serve as a marker of CSF production in the lateral ventricles, and changes that occur with aging and in disease. PURPOSE: To investigate the confounding influence of the respiratory cycle on net CSF flow and stroke volume measurements. STUDY TYPE: Cross-sectional study. SUBJECTS: Twelve young, healthy subjects (seven male, age range 19-39 years, average age 28.3 years). FIELD STRENGTH/SEQUENCE: Phase contrast MRI (PC-MRI) measurements were performed at 7T, with and without respiratory gating on expiration and on inspiration. All measurements were repeated. ASSESSMENT: Net CSF flow and stroke volume in the aqueduct, over the cardiac cycle, was determined. STATISTICAL TESTS: Repeatability was determined using the intraclass correlation coefficient (ICC) and linear regression analysis between the repeated measurements. Repeated measures analysis of variance (ANOVA) was performed to compare the measurements during inspiration/expiration/no gating. Linear regression analysis was performed between the net CSF flow difference (inspiration minus expiration) and stroke volume. RESULTS: Net CSF flow (average ± standard deviation) was 0.64 ± 0.32 mL/min (caudal) during expiration, 0.12 ± 0.49 mL/min (cranial) during inspiration, and 0.31 ± 0.18 mL/min (caudal) without respiratory gating. Respiratory gating did not affect stroke volume measurements (41 ± 18, 42 ± 19, 42 ± 19 µL/cycle for expiration, no respiratory gating and inspiration, respectively). Repeatability was best during inspiration (ICC = 0.88/0.56/-0.31 for gating on inspiration/expiration/no gating). A positive association was found between average stroke volume and net flow difference between inspiration and expiration (R = 0.678/0.605, P = 0.015/0.037 for the first/second repeated measurement). DATA CONCLUSION: Measured net CSF flow is confounded by respiration effects. Therefore, net CSF flow measurements with PC-MRI cannot in isolation be directly linked to CSF production. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:433-444.

Ultra-high field MRI: Advancing systems neuroscience towards mesoscopic human brain function.

Human MRI scanners at ultra-high magnetic field strengths of 7 T and higher are increasingly available to the neuroscience community. A key advantage brought by ultra-high field MRI is the possibility to increase the spatial resolution at which data is acquired, with little reduction in image quality. This opens a new set of opportunities for neuroscience, allowing investigators to map the human cortex at an unprecedented level of detail. In this review, we present recent work that capitalizes on the increased signal-to-noise ratio available at ultra-high field and discuss the theoretical advances with a focus on sensory and motor systems neuroscience. Further, we review research performed at sub-millimeter spatial resolution and discuss the limits and the potential of ultra-high field imaging for structural and functional imaging in human cortex. The increased spatial resolution achievable at ultra-high field has the potential to unveil the fundamental computations performed within a given cortical area, ultimately allowing the visualization of the mesoscopic organization of human cortex at the functional and structural level.

Effect sizes of BOLD CVR, resting-state signal fluctuations and time delay measures for the assessment of hemodynamic impairment in carotid occlusion patients.

BACKGROUND AND PURPOSE: The BOLD signal amplitude as a response to a hypercapnia stimulus is commonly used to assess cerebrovascular reserve. Despite recent advances, the implementation remains cumbersome and alternative ways to assess hemodynamic impairment are desirable. Resting-state BOLD signal fluctuations (rsBOLD) have been proposed however data on its sensitivity and dependence on baseline venous cerebral blood volume (vCBV) is limited. The primary aim of this study was to compare the effect sizes of resting-state and hypercapnia induced BOLD signal changes in the detection of hemodynamic impairment. The second aim of the study was to assess the dependence of BOLD signal variability on vCBV. MATERIALS AND METHODS: Fifteen patients with internal carotid artery occlusive disease and 15 matched healthy controls were included in this study. The BOLD signal was derived from a dual-echo gradient-echo echo-planar sequence during hypercapnia (HC) and hyperoxia (HO) gas modulations. BOLD (fractional) amplitude of low frequency fluctuations ((f)ALFF) was compared to HC-BOLD, BOLD response delays derived from time delay analysis and ΔBOLD in response to progressively increasing HC. Effect sizes (i.e. the standard mean difference between patients and controls) were calculated. HO-BOLD was used to estimate vCBV, and its contribution to the variability in rsBOLD signal was evaluated. RESULTS: The effect sizes of ALFF and fALFF (0.61 and 0.72) were lower than the effect sizes related to hypercapnia-based hemodynamic assessment analysis; 1.62, 1.56 and 0.90 for HC-BOLD, BOLD response delays and ΔBOLD in response to progressively increasing HC. A moderate relation was found between (f)ALFF and HC-BOLD in controls (R2 of 0.61 and 0.42), but this relation decreased in patients (R2 of 0.33 and 0.15). (f)ALFF did not differ between patients and controls whereas HC-BOLD did (p < 0.005). The ΔBOLD response to progressively increasing HC was significantly different in between patients and controls for ΔEtCO2 values ≥ 2 mmHg (at +2  mmHg F(1, 18) = 5.85, p = 0.026). Up to 31% and 53% of the variance in the ALFF and HC-BOLD spatial distribution could be explained by HO-BOLD. CONCLUSION: ALFF and fALFF demonstrated a moderate effect size to detect hemodynamic impairment whereas the effect size was large for methods employing a hypercapnia-based vascular stress stimulus. Based on our analysis of BOLD signal change as a response to a progressively increasing hypercapnia stimulus we can argue that a hypercapnia stimulus of at least 2 mmHg above baseline EtCO2 is necessary to evaluate hemodynamic impairment. We also demonstrated that a substantial amount of information imbedded in the rsBOLD and HC-BOLD was explained by HO-BOLD. HO-BOLD can serve as a proxy for vCBV and this thus indicates that one should be careful when adopting these techniques in disease cases with compromised CBV.