Spin-echo Blood Oxygenation Level-dependent Research Articles

Improved laminar specificity and sensitivity by combining SE and GE BOLD signals

The most widely used gradient-echo (GE) blood oxygenation level-dependent (BOLD) contrast has high sensitivity, but low specificity due to draining vein contributions, while spin-echo (SE) BOLD approach at ultra-high magnetic fields is highly specific to neural active sites but has lower sensitivity. To obtain high specificity and sensitivity, we propose to utilize a vessel-size-sensitive filter to the GE-BOLD signal, which suppresses macrovascular contributions and to combine selectively retained microvascular GE-BOLD signals with the SE-BOLD signals. To investigate our proposed idea, fMRI with 0.8 mm isotropic resolution was performed on the primary motor and sensory cortices in humans at 7 T by implementing spin- and gradient-echo (SAGE) echo planar imaging (EPI) acquisition. Microvascular-passed sigmoidal filters were designed based upon the vessel-size-sensitive ΔR2*/ΔR2 value for retaining GE-BOLD signals originating from venous vessels with ≤ 45 μm and ≤ 65 μm diameter. Unlike GE-BOLD fMRI, the laminar profile of SAGE-BOLD fMRI with the vessel-size-sensitive filter peaked at ∼ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity over GE-BOLD fMRI. Also, the functional sensitivity of SAGE BOLD at middle layers (0.75–1.5 mm) was improved by ∼ 80% to ∼100% when compared with SE BOLD. In summary, we showed that combined GE- and SE-BOLD fMRI with the vessel-size-sensitive filter indeed yielded improved laminar specificity and sensitivity and is therefore an excellent tool for high spatial resolution ultra-high filed (UHF)-fMRI studies for resolving mesoscopic functional units.

Improvement of sensitivity and specificity for laminar BOLD fMRI with double spin-echo EPI in humans at 7 T

Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.

Whole‐brain three‐dimensional T2‐weighted BOLD functional magnetic resonance imaging at 7 Tesla

A new acquisition scheme for T2-weighted spin-echo BOLD fMRI is introduced. It uses a T2-preparation module to induce blood-oxygenation-level-dependent (BOLD) contrast, followed by a single-shot three-dimensional (3D) fast gradient-echo readout with short echo time (TE). It differs from most spin-echo BOLD sequences in that BOLD contrast is generated before the readout, which eliminates the "dead time" due to long TE required for T2 contrast, and substantially improves acquisition efficiency. This approach, termed "3D T2prep-GRE," was implemented at 7 Tesla (T) with a typical spatial (2.5 × 2.5 × 2.5 mm(3) ) and temporal (TR = 2.3 s) resolution for functional MRI (fMRI) and whole-brain coverage (55 slices), and compared with the widely used 2D spin-echo EPI sequence. In fMRI experiments of simultaneous visual/motor activities, 3D T2prep-GRE showed minimal distortion and little signal dropout across the whole brain. Its lower power deposition allowed greater spatial coverage (55 versus 17 slices with identical TR, resolution and power level), temporal SNR (60% higher) and CNR (35% higher) efficiency than 2D spin-echo EPI. It also showed smaller T2* contamination. This approach is expected to be useful for ultra-high field fMRI, especially for regions near air cavities. The concept of using T2-preparation to generate BOLD contrast can be combined with many other sequences at any field strength.

On the numerically predicted spatial BOLD fMRI specificity for spin echo sequences

This work utilises general numerical magnetic resonance imaging MRI simulations to predict the spatial specificity of the blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal. A Monte Carlo simulation approach was utilized on a microvascular structure consisting of randomly oriented cylinders representing blood vessels. This framework was employed to numerically investigate the spatial specificity, defined as ratio of pial vessel to microvascular signal, of the spin echo BOLD fMRI signal as a function of field strength, echo time and tissue types [grey matter (GM) and cerebrospinal fluid (CSF), respectively]. Spatial specificity of spin echo BOLD fMRI signal was determined to increase with field strength up to 16 T and with maximal specificity for echo time shorter than tissue T 2. In addition, it was found that, for large pial vessels, the extravascular signal decay could not be described using the oversimplified but nevertheless commonly employed mono-exponential signal decay approximation (MEA). Consequently, a recently proposed model relying on the MEA deviates substantially from our results on the spatial specificity. A refinement of this model is proposed based on an available, more detailed signal description. Finally, the effect of CSF on the spatial specificity was investigated. While a large spatial specificity of the spin echo BOLD fMRI signal is observed if a pial vessel is surrounded by grey matter, this is greatly reduced for a pial vessel situated on a GM/CSF interface, rendering the suppression of pial vessels on the cortex surface unlikely.

Simultaneous acquisition of gradient echo/spin echo BOLD and perfusion with a separate labeling coil

Arterial spin labeling-based cerebral blood flow imaging complements blood oxygenation level dependent (BOLD) imaging with a measure that is more quantitative and has better specificity to neuronal activation. Relative to gradient echo BOLD, spin echo BOLD has better spatial specificity because it is less biased to large draining veins. Although there have been many studies comparing simultaneously acquired cerebral blood flow data with gradient echo BOLD data in fMRI, there have been few studies comparing cerebral blood flow with SE BOLD and no study comparing all three. We present a pulse sequence that simultaneously acquires cerebral blood flow data with a separate labeling coil, gradient echo BOLD, and spin echo BOLD images. Simultaneous acquisition avoids interscan variability, allowing more direct assessment and comparison of each contrast's relative specificity and reproducibility. Furthermore, it facilitates studies that may benefit from multiple complementary measures.

Retinotopic mapping with spin echo BOLD at 7T

For blood oxygenation level-dependent (BOLD) functional MRI experiments, contrast-to-noise ratio (CNR) increases with increasing field strength for both gradient echo (GE) and spin echo (SE) BOLD techniques. However, susceptibility artifacts and nonuniform coil sensitivity profiles complicate large field-of-view fMRI experiments (e.g., experiments covering multiple visual areas instead of focusing on a single cortical region). Here, we use SE BOLD to acquire retinotopic mapping data in early visual areas, testing the feasibility of SE BOLD experiments spanning multiple cortical areas at 7T. We also use a recently developed method for normalizing signal intensity in T 1-weighted anatomical images to enable automated segmentation of the cortical gray matter for scans acquired at 7T with either surface or volume coils. We find that the CNR of the 7T GE data (average single-voxel, single-scan stimulus coherence: 0.41) is almost twice that of the 3T GE BOLD data (average coherence: 0.25), with the CNR of the SE BOLD data (average coherence: 0.23) comparable to that of the 3T GE data. Repeated measurements in individual subjects find that maps acquired with 1.8-mm resolution at 3T and 7T with GE BOLD and at 7T with SE BOLD show no systematic differences in either the area or the boundary locations for V1, V2 and V3, demonstrating the feasibility of high-resolution SE BOLD experiments with good sensitivity throughout multiple visual areas.

A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

A new interpretation is proposed for stimulus-induced signal changes in diffusion-weighted functional MRI. T(2)-weighted spin-echo echo-planar images were acquired at different diffusion-weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus-correlated response and post-stimulus undershoot (PSU) in the functional time-courses were found to follow different trends as a function of b-value. Data were analysed using a three-compartment signal model, with one compartment being purely vascular and the other two dominated by fast- and slow-diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus-induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast-diffusion phase displays a substantial PSU, while the slow-diffusion phase demonstrates a highly reproducible and stimulus-correlated time-course with minimal undershoot. The decomposed responses are interpreted in terms of the spin-echo blood oxygenation level dependent (SE-BOLD) effect, and it is proposed that the signal produced by fast- and slow-diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule- and capillary-sized vessels, respectively. This interpretation suggests that diffusion-weighted SE-BOLD imaging may provide subtle information about the haemodynamic and neuronal responses.

Pain fMRI in rat cervical spinal cord: An echo planar imaging evaluation of sensitivity of BOLD and blood volume-weighted fMRI

Objective measure of pain is valuable in drug discovery research and development of analgesics. Spinal cord is an important relay of the pain pathway, and fMRI offers an excellent opportunity to quantify pain using activation in the spinal cord induced by painful stimuli. fMRI literature of cervical spinal cord with regard to the spatial extent, in both longitudinal and cross-sectional directions, of neuronal activation induced by noxious stimulation is ambiguous. This study investigates the feasibility of developing a robust pain assay using fMRI in the cervical spinal cord in α-chloralose anesthetized rats subjected to transcutaneous noxious electrical stimulation of the forepaw. Blood oxygenation level dependent (BOLD) and blood volume (BV)-weighted fMRI data were acquired without and with intravenous injection of ultra small superparamagnetic iron oxide particles (USPIO), respectively. BOLD data were acquired by gradient-echo (GE) and spin-echo (SE) echo planar imaging (EPI), while BV-weighted fMRI data were acquired only by GE EPI. Cervical spinal cord activity was robustly detected by all three fMRI techniques. The sensitivity of the fMRI signal was highest in GE BV-weighted fMRI followed in order by GE BOLD, and SE BOLD, respectively. Spatially, the fMRI signal extended ∼ 9 mm in the longitudinal direction, covering C 4–C 8 segments, coinciding with the synapse location of afferent terminals from the stimulated site. In the cross-sectional direction, the signal change is localized predominantly to the ipsilateral dorsal region. This study demonstrates that cervical spinal cord fMRI can be performed reliably in anesthetized rats offering it as a potential tool for analgesic drug development.

Neural Interpretation of Blood Oxygenation Level-Dependent fMRI Maps at Submillimeter Columnar Resolution

Whether conventional gradient-echo (GE) blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is able to map submillimeter-scale functional columns remains debatable mainly because of the spatially nonspecific large vessel contribution, poor sensitivity and reproducibility, and lack of independent evaluation. Furthermore, if the results from optical imaging of intrinsic signals are directly applicable, regions with the highest BOLD signals may indicate neurally inactive domains rather than active columns when multiple columns are activated. To examine these issues, we performed BOLD fMRI at a magnetic field of 9.4 tesla to map orientation-selective columns of isoflurane-anesthetized cats. We could not convincingly map orientation columns using conventional block-design stimulation and differential analysis method because of large fluctuations of signals. However, we successfully obtained GE BOLD iso-orientation maps with high reproducibility (r = 0.74) using temporally encoded continuous cyclic orientation stimulation with Fourier data analysis, which reduces orientation-nonselective signals such as draining artifacts and is less sensitive to signal fluctuations. We further reduced large vessel contribution using the improved spin-echo (SE) BOLD method but with overall decreased sensitivity. Both GE and SE BOLD iso-orientation maps excluding large pial vascular regions were significantly correlated to maps with a known neural interpretation, which were obtained in contrast agent-aided cerebral blood volume fMRI and total hemoglobin-based optical imaging of intrinsic signals at a hemoglobin iso-sbestic point (570 nm). These results suggest that, unlike the expectation from deoxyhemoglobin-based optical imaging studies, the highest BOLD signals are localized to the sites of increased neural activity when column-nonselective signals are suppressed.

Temporal resolving power of spin echo and gradient echo fMRI at 3T with apparent diffusion coefficient compartmentalization

The temporal resolving power of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T was investigated in the visual and auditory cortices of the human brain. By using controlled temporal delays and selective visual hemifield stimulation, regions with similar (left vs. right occipital cortex) and different (occipital cortex vs. auditory cortex) vascular architectures were compared. Estimates of the time-to-peak (TTP) of the BOLD hemodynamic response function (hrf) were obtained using a spin echo (SE) sequence and compared to those acquired using a traditional gradient echo (GE) sequence. The hrf TTP in the visual cortex was found to be 4.73 s and 4.21 s for GE and SE, respectively. The auditory cortex response was significantly delayed, with TTPs of 4.95 s and 4.51 s for GE and SE, respectively. The GE response was able to resolve visual stimuli separated by 250 ms, whereas SE could resolve stimuli 500 ms apart. Apparent-diffusion-coefficient (ADC) compartmentalization of the BOLD signal was applied to restrict the vascular sensitivity of the SE and GE sequences. Limiting the response to voxels with ADCs < 0.8 x 10(-3) mm(2)/s improved the temporal resolving power of GE and SE BOLD to 125 ms and 250 ms, respectively.

Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences

The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal response to neural stimulation is influenced by many factors that are unrelated to the stimulus. These factors are physiological, such as the resting venous cerebral blood volume (CBV(v)) and vessel size, as well as experimental, such as pulse sequence and static magnetic field strength (B(0)). Thus, it is difficult to compare task-induced fMRI signals across subjects, field strengths, and pulse sequences. This problem can be overcome by normalizing the neural activity-induced BOLD fMRI response by a global hypercapnia-induced BOLD signal. To demonstrate the effectiveness of the BOLD normalization approach, gradient-echo BOLD fMRI at 1.5, 4, and 7 T and spin-echo BOLD fMRI at 4 T were performed in human subjects. For neural stimulation, subjects performed sequential finger movements at 2 Hz, while for global stimulation, subjects breathed a 5% CO(2) gas mixture. Under all conditions, voxels containing primarily large veins and those containing primarily active tissue (i.e., capillaries and small veins) showed distinguishable behavior after hypercapnic normalization. This allowed functional activity to be more accurately localized and quantified based on changes in venous blood oxygenation alone. The normalized BOLD signal induced by the motor task was consistent across different magnetic fields and pulse sequences, and corresponded well with cerebral blood flow measurements. Our data suggest that the hypercapnic normalization approach can improve the spatial specificity and interpretation of BOLD signals, allowing comparison of BOLD signals across subjects, field strengths, and pulse sequences. A theoretical framework for this method is provided.

Venous blood effects in spin-echo fMRI of human brain.

The spin-echo response to visual activation was studied as a function of spatial resolution at a field of 1.5 T. The results showed that the increase in absolute T(2) upon activation was as large as 22.8 +/- 3.1% (P < 0.05) at the highest resolution (5.3 mm(3)), while it was as small as 3.5 +/- 0.2% (P < 0.05) at the lowest resolution (42.2 mm(3)). In addition, upon increasing resolution, the spin-echo signal decay as a function of echo time changed from monoexponential to nonexponential. These data indicate that, when using the standard resolution for fMRI studies at 1.5 T, the effects of spin-echo changes in the draining veins are of major contribution to the total blood oxygenation level-dependent (BOLD) signal changes measured in voxels encompassing the activated brain areas. The data can be quantitatively accounted for using a model based on the intravascular origin of the spin-echo effect including both macrovascular and microvascular effects. Existing theories for the spin-echo BOLD effect based on diffusion through field gradients predict negligible spin-echo effects inside the large vessels and are therefore incompatible with the data. Magn Reson Med 42:617-626, 1999.

In vivo determination of absolute cerebral blood volume using hemoglobin as a natural contrast agent: an MRI study using altered arterial carbon dioxide tension.

The ability of the magnetic resonance imaging transverse relaxation time, R2 = 1/T2, to quantify cerebral blood volume (CBV) without the need for an exogenous contrast agent was studied in cats (n = 7) under pentobarbital anesthesia. This approach is possible because R2 is directly affected by changes in CBF, CBV, CMRO2, and hematocrit (Hct), a phenomena better known as the blood-oxygenation-level-dependent (BOLD) effect. Changes in CBF and CBV were accomplished by altering the carbon dioxide pressure, PaCO2, over a range from 20 to 140 mm Hg. For each PaCO2 value, R2 in gray and white matter were determined using MRI, and the whole-brain oxygen extraction ratio was obtained from arteriovenous differences (sagittal sinus catheter). Assuming a constant CMRO2, the microvascular CBV was obtained from an exact fit to the BOLD theory for the spin-echo effect. The resulting CBV values at normal PaCO2 and normalized to a common total hemoglobin concentration of 6.88 mmol/L were 42+/-18 microL/g (n = 7) and 29+/-19 microL/g (n = 5) for gray and white matter, respectively, in good agreement with the range of literature values published using independent methodologies. The present study confirms the validity of the spin-echo BOLD theory and, in addition, shows that blood volume can be quantified from the magnetic resonance imaging spin relaxation rate R2 using a regulated carbon dioxide experiment.