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Essa Yacoub

Publications and source records attributed to Essa Yacoub.

14 recordsLinked to original sources

In vivo micro-MRI of intracortical neurovasculature.

This work describes a methodology for in vivo MR imaging of arteries and veins within the visual cortex of the cat brain. Very high magnetic fields (9.4 T) and small field-of-view 3D acquisitions were used to image the neurovasculature at resolutions approaching the microscopic scale. A combination of time-of-flight MR angiography and T*(2)-weighted imaging, using both endogenous BOLD contrast and an exogenous iron-oxide contrast agent, provided high specificity for distinguishing between arteries and veins within the cortex. These acquisition techniques, combined with 3D image processing and display methods, were used to detect and visualize intracortical arteries and veins with diameters smaller than 100 microm. This methodology can be used for visualizing the neurovasculature or building models of the vascular network and may benefit a variety of research applications including fMRI, cerebrovascular disease and cancer angiogenesis.

Animals↗

Frontiers of brain mapping using MRI.

Over the past dozen years, the use of MRI techniques to map brain function (fMRI) has sparked a great deal of research. The ability of fMRI to image several different physiological processes concurrently (i.e., blood oxygenation, blood flow, metabolism) and noninvasively over large volumes make it the ideal choice for many different areas of neuroscience research in addition to countless applications in clinical settings. Furthermore, with the advent of high magnetic fields (and other hardware advancements, i.e., parallel imaging) for both human and animal research, spatial and temporal resolutions continue to be pushed to higher levels because of increases in the sensitivity as well as specificity of MR-detectable functional signals. fMRI methodology continues to grow and has the ability to cater to many different research applications. There seems to be no foreseeable end in sight to the advancement of fMRI techniques and its subsequent use in basic research as well as in clinical settings. In this work, fMRI techniques and the ongoing development of existing techniques are discussed with implications for the future of fMRI.

Brain Mapping↗

The spatial dependence of the poststimulus undershoot as revealed by high-resolution BOLD- and CBV-weighted fMRI.

The hemodynamic response to neural activity consists of changes in blood flow, blood volume and oxygen metabolism. Changes in the vascular state after sensory stimulation have different spatial and temporal characteristics in the brain. This has been shown using imaging techniques, such as BOLD functional magnetic resonance imaging (fMRI), which monitor vascular changes once the stimulus is turned on, and the eventual return to baseline levels, once the stimulus is turned off. The BOLD fMRI signal during sensory stimulation has been well characterized and modeled in terms of the spatial and temporal characteristics of the vascular response. However, the return of the signals to baseline levels after sensory stimulation is not as well characterized. During this period, a poststimulus undershoot in the BOLD signal is observed. This poststimulus undershoot has been modeled and investigated to characterize the physiological mechanisms (cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral oxygen consumption) associated with the response. However, the data in the literature, which lack any spatially dependent information, appear to be contradictory in terms of the mechanisms associated with this poststimulus response. With a high spatial resolution cat model at 9.4 T, we show that CBV changes in the tissue persist once the stimulus is turned off, while CBV changes in the surface vessels quickly return to baseline levels, despite a concurrent undershoot in the BOLD signal in both the tissue and surface vessel areas. In addition, the BOLD data alone indicate that different physiological mechanisms regulate the poststimulus response in the tissue versus the surface vessel regions.

Animals↗

Combined imaging-histological study of cortical laminar specificity of fMRI signals.

Since the commencement of functional magnetic resonance imaging (fMRI), great effort has been put into increasing its spatial resolution and signal specificity from vessel-weighted to more tissue-specific signals. The working assumption is that the "tissue" signals closely mirror changes at the neuronal level. While great progress has been made, the basic and most fundamental questions remain unanswered: where in the gray matter do these "tissue fMRI" changes occur? Recently, the temporal correspondence of hemodynamic-based fMRI signals and neurophysiological activity was explored. The data suggest, although not conclusively, that the local field potential (LFP) response gives a better estimate of changes that accompany increased neuronal activity. LFP are thought to be generated by synaptic activity reflecting input signals into layer IV within a cortical region. If so, the spatial distribution of the fMRI signal should be specific to the corresponding cortical lamina. Here, in a combined imaging and histological study, the spatial characteristics of fMRI signals across the lamina were explored. In a high-resolution fMRI study (0.15 x 0.15 x 2 mm3), the spatial specificity of fMRI signals was correlated with the underlying cortical laminar cytoarchitectonic obtained within the same animal and tissue region. We demonstrate that when surface vessels are excluded high-resolution fMRI signals peak at cortical layer IV.

Animals↗

Signal and noise characteristics of Hahn SE and GE BOLD fMRI at 7 T in humans.

At very high magnetic fields, GE BOLD fMRI is expected to contain nonspecific contributions and behave differently than HSE fMRI data. Similarly, the two approaches can conceivably suffer from different contributions to temporal instabilities in a times series that ultimately determine the contrast-to-noise ratio (CNR). We investigate the signal and signal fluctuation characteristics in GE and HSE fMRI data with the imaging parameters separately optimized for each contrast at 7 T. In HSE fMRI, activation-induced fractional signal change (DeltaS/S) decreased rapidly, and the ratio of standard deviations of image-to-image fluctuations due to physiological processes (sigmaPhys) to thermal noise (sigmaTherm) remained constant with increasing voxel volume. In contrast, DeltaS/S as well as volume of activated voxels was virtually independent of voxel size for GE BOLD, and sigma(Phys)/sigmaTherm increased with increasing voxel size. The ratio of BOLD signal changes (GE/HSE) was much closer to 1 in tissue areas compared to vessel areas. These observations led to the conclusions that the spatial extent of the activation-induced DeltaS/S was much broader in the GE data, and that the physiological processes that give rise to the temporal fluctuations lost coherence over millimeter distances in HSE compared to GE fMRI data. While further studies are needed to characterize it fully, sigmaPhys in HSE data was clearly different than in GE data. It was concluded that HSE imaging yields a significantly reduced amount of nonspecific signals compared to GE imaging, and, would be the method of choice (over GE) for high-resolution applications in humans.

Adult↗

Design of an MRI-compatible robotic stereotactic device for minimally invasive interventions in the breast.

The objective of this work was to develop a robotic device to perform biopsy and therapeutic interventions in the breast with real-time magnetic resonance imaging (MRI) guidance. The device was designed to allow for (i) stabilization of the breast by compression, (ii) definition of the interventional probe trajectory by setting the height and pitch of a probe insertion apparatus, and (iii) positioning of an interventional probe by setting the depth of insertion. The apparatus is fitted with five computer-controlled degrees of freedom for delivering an interventional procedure. The entire device is constructed of MR compatible materials, i.e. nonmagnetic and non-conductive, to eliminate artifacts and distortion of the MR images. The apparatus is remotely controlled by means of ultrasonic motors and a graphical user interface, providing real-time MR-guided planning and monitoring of the operation. Joint motion measurements found probe placement in less than 50 s and sub-millimeter repeatability of the probe tip for same-direction point-to-point movements. However, backlash in the rotation joint may incur probe tip positional errors of up to 5 mm at a distance of 40 mm from the rotation axis, which may occur for women with large breasts. The imprecision caused by this backlash becomes negligible as the probe tip nears the rotation axis. Real-time MR-guidance will allow the physician to correct this error Compatibility of the device within the MR environment was successfully tested on a 4 Tesla MR human scanner

Algorithms↗

Spin-echo fMRI in humans using high spatial resolutions and high magnetic fields.

The Hahn spin-echo (HSE)-based BOLD effect at high magnetic fields is expected to provide functional images that originate exclusively from the microvasculature. The blood contribution that dominates HSE BOLD contrast at low magnetic fields (e.g., 1.5 T), and degrades specificity, is highly attenuated at high fields because the apparent T(2) of venous blood in an HSE experiment decreases quadratically with increasing magnetic field. In contrast, the HSE BOLD contrast is believed to arise from the microvasculature and increase supralinearly with the magnetic field strength. In this work we report the results of detailed and quantitative evaluations of HSE BOLD signal changes for functional imaging in the human visual cortex at 4 and 7 T. This study used high spatial resolution, afforded by the increased signal-to-noise ratio (SNR) of higher field strengths and surface coils, to avoid partial volume effects (PVEs), and demonstrated increased contrast-to-noise ratio (CNR) and spatial specificity at the higher field strengths. The HSE BOLD signal changes induced by visual stimulation were predominantly linearly dependent on the echo time (TE). They increased in magnitude almost quadratically in going from 4 to 7 T when the blood contribution was suppressed using Stejskal-Tanner gradients that suppress signals from the blood due to its inhomogeneous flow and higher diffusion constant relative to tissue. The HSE signal changes at 7 T were modeled accurately using a vascular volume of 1.5%, in agreement with the capillary volume of gray matter. Furthermore, high-resolution acquisitions indicate that CNR increased with voxel sizes < 1 mm(3) due to diminishing white matter or cerebrospinal fluid-space vs. gray matter PVEs. It was concluded that the high-field HSE functional MRI (fMRI) signals originated largely from the capillaries, and that the magnitude of the signal changes associated with brain function reached sufficiently high levels at 7 T to make it a useful approach for mapping on the millimeter to submillimeter spatial scale.

Adult↗

Microvascular BOLD contribution at 4 and 7 T in the human brain: gradient-echo and spin-echo fMRI with suppression of blood effects.

The BOLD signal consists of an intravascular (IV) and an extravascular (EV) component from both small and large vessels. Their relative contributions are dependent on field strength, imaging technique, and echo time. The IV and EV contributions were investigated in the human visual cortex at 4 and 7 T using spin-echo and gradient-echo BOLD fMRI with and without suppression of blood effects. Spin-echo acquisition suppresses EV BOLD from large veins and reflects predominantly blood T(2) changes and EV BOLD signal from small blood vessels. At a short echo time (32 ms), diffusion gradient-based suppression of blood signals resulted in a 75% and 20% decrease in spin-echo BOLD changes at 4 T and 7 T, respectively. However, at echo times (55-65 ms) approximating tissue T(2) typically used for optimal BOLD contrast, these gradients had much smaller effects at both fields, consistent with the decreasing blood T(2) with increasing field strength. Gradient-echo BOLD percent changes, with relatively long echo times at both fields, were virtually unaffected by gradients that attenuated the blood contribution because the EV BOLD surrounding both large and small vessels dominated. These results suggest that spin-echo BOLD fMRI at 4 and 7 T, with TE approximating tissue T(2), significantly reduces nonspecific mapping signals from large vessels and significantly accentuates microvasculature contributions.

Brain↗

The evaluation of preprocessing choices in single-subject BOLD fMRI using NPAIRS performance metrics.

This work proposes an alternative to simulation-based receiver operating characteristic (ROC) analysis for assessment of fMRI data analysis methodologies. Specifically, we apply the rapidly developing nonparametric prediction, activation, influence, and reproducibility resampling (NPAIRS) framework to obtain cross-validation-based model performance estimates of prediction accuracy and global reproducibility for various degrees of model complexity. We rely on the concept of an analysis chain meta-model in which all parameters of the preprocessing steps along with the final statistical model are treated as estimated model parameters. Our ROC analog, then, consists of plotting prediction vs. reproducibility results as curves of model complexity for competing meta-models. Two theoretical underpinnings are crucial to utilizing this new validation technique. First, we explore the relationship between global signal-to-noise and our reproducibility estimates as derived previously. Second, we submit our model complexity curves in the prediction versus reproducibility space as reflecting classic bias-variance tradeoffs. Among the particular analysis chains considered, we found little impact in performance metrics with alignment, some benefit with temporal detrending, and greatest improvement with spatial smoothing.

Adult↗

Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain.

Most fMRI studies are based on the detection of a positive BOLD response (PBR). Here, we demonstrate and characterize a robust sustained negative BOLD response (NBR) in the human occipital cortex, triggered by stimulating part of the visual field. The NBR was spatially adjacent to but segregated from the PBR. It depended on the stimulus and thus on the pattern of neuronal activity. The time courses of the NBR and PBR were similar, and their amplitudes covaried both with increasing stimulus duration and increasing stimulus contrast. The NBR was associated with reductions in blood flow and with decreases in oxygen consumption. Our findings support the contribution to the NBR of (1) a significant component of reduction in neuronal activity and (2) possibly a component of hemodynamic changes independent of the local changes in neuronal activity.

Adult↗

Perfusion-based high-resolution functional imaging in the human brain at 7 Tesla.

Perfusion-based MRI measures cerebral blood flow (CBF) at the capillary level and can be used for functional studies based on the tight spatial coupling between brain activity and blood flow. Obtaining functional CBF maps with high spatial resolution is a major challenge because the CBF signal is intrinsically low and the SNR is critical. In the present work, CBF-based functional imaging was performed at a considerably smaller voxel size than previously reported in humans. High-resolution CBF maps were obtained with voxel sizes as small as 0.9 x 0.9 x 1.5 mm(3) in the human brain. High sensitivity was made possible by signal-to-noise gains at the high magnetic field of 7 T and by using a novel RF combination coil design. In addition, a reduction of the field-of-view was critical to achieve 0.9-mm in-plane resolution with gradient-echo echo-planar imaging in a single shot. Functional CBF data were compared with functional BOLD data to reveal that, for CBF, large contrast- to-noise gains were obtained at high spatial resolution, indicating that the functional CBF response was more localized. High-resolution functional CBF imaging is significant for neuroscience research because it provides better localization and more specific information than BOLD for monitoring brain function.

Cerebrovascular Circulation↗

High-resolution, spin-echo BOLD, and CBF fMRI at 4 and 7 T.

With growing interest in noninvasive mapping of columnar organization and other small functional structures in the brain, achieving high spatial resolution and specificity in fMRI is of critical importance. We implemented a simple method for BOLD and perfusion fMRI with high spatial resolution and specificity. Increased spatial resolution was achieved by selectively exciting a slab of interest along the phase-encoding direction for EPI, resulting in a reduced FOV and number of phase-encoding steps. Improved spatial specificity was achieved by using SE EPI acquisition at high fields, where it is predominantly sensitive to signal changes in the microvasculature. Robust SE BOLD and perfusion fMRI were obtained with a nominal in-plane resolution up to 0.5 x 0.5 mm(2) at 7 and 4 Tesla, and were highly reproducible under repeated measures. This methodology enables high-resolution and high-specificity studies of functional topography in the millimeter to submillimeter spatial scales of the human brain.

Adult↗

Zoomed functional imaging in the human brain at 7 Tesla with simultaneous high spatial and high temporal resolution.

Functional neuroimaging in the human brain using noninvasive magnetic resonance methods has the potential of providing highly resolved maps of neuronal activation. Decreasing the voxel size and obtaining simultaneously high temporal resolution is a major challenge and is mainly limited by sensitivity. Here, signal-to-noise gains at high magnetic fields (7 Tesla) and an optimized surface coil setup are combined with a novel approach for zoomed functional imaging in the visual cortex. For echoplanar imaging, the acquisition time and segmentation was shortened fourfold by using a reduced field-of-view. An adiabatic outer-volume suppression method, BISTRO, was used to obliterate signal outside the area-of-interest achieving effective suppression even for inhomogeneous B1-fields. A single-shot acquisition was performed at submillimeter resolution in the human brain, while simultaneously maintaining a high temporal resolution of 125 ms. Functional studies with and without field-of-view reduction were performed. Activation and percent change maps were compared with respect to spatial extent, t values and percentage changes of the BOLD contrast. The detection of functional activation was found to be equal within the inter-series variability for the two acquisition schemes. Thus, single-trial BOLD responses were detected for the first time robustly at a 500 x 500 microm2 in plane and 250 ms temporal resolution, significantly expanding the possibilities of event-related functional imaging in the human brain. The magnetization transfer effect induced by the outer-volume suppression pulses was investigated and found to be increased during neuronal activity.

Algorithms↗