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Seong-Gi Kim

Publications and source records attributed to Seong-Gi Kim.

At least 19 recordsLinked to original sources

Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI.

Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI.

Animals↗

Improved spatial localization of post-stimulus BOLD undershoot relative to positive BOLD.

The negative blood oxygenation level-dependent (BOLD) signal following the cessation of stimulation (post-stimulus BOLD undershoot) is observed in functional magnetic resonance imaging (fMRI) studies. However, its spatial characteristics are unknown. To investigate this, gradient-echo BOLD fMRI in response to visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T. Since the middle cortical layer (layer 4) is known to have the highest metabolic and cerebral blood volume (CBV) responses, images were obtained to view the cortical cross-section. Robust post-stimulus BOLD undershoot was observed in all studies, and lasted longer than 30 s after the cessation of 40-60 s stimulation. The magnitude of post-stimulus BOLD undershoot was linearly dependent on echo time with little intercept when extrapolating to TE = 0, indicating that the T2* change is the major cause of the BOLD undershoot. The post-stimulus BOLD undershoot was observed within the cortex and near the surface of the cortex, while the prolonged CBV elevation was observed only at the middle of the cortex. Within the cortex, the largest post-stimulus undershoot was detected at the middle of the cortex, similar to the CBV increase during the stimulation period. Our findings demonstrate that, even though there is significant contribution from pial vessel signals, the post-stimulus undershoot BOLD signal is useful to improve the spatial localization of fMRI to active cortical sites.

Animals↗

Mapping iso-orientation columns by contrast agent-enhanced functional magnetic resonance imaging: reproducibility, specificity, and evaluation by optical imaging of intrinsic signal.

Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.

Animals↗

Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations.

Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and -24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information.

Algorithms↗

Relationship between neural, vascular, and BOLD signals in isoflurane-anesthetized rat somatosensory cortex.

Functional magnetic resonance imaging (fMRI) in anesthetized rodents has been commonly performed with alpha-chloralose, which can be used only for terminal experiments. To develop a survival fMRI protocol, an isoflurane (ISO) -anesthetized rat model was systematically evaluated by simultaneous measurements of field potential (FP) and cerebral blood flow (CBF) in the somatosensory cortex. A conventional forepaw stimulation paradigm with 0.3 ms pulse width, 1.2 mA current, and 3 Hz frequency induced 54% less evoked FP and 84% less CBF response under ISO than alpha-chloralose. To improve stimulation-induced responses under ISO, 10-pulse stimulations were performed with variations of width, current, and frequency. For widths of 0.1-5.0 ms and currents of 0.4-2.0 mA, evoked FP and CBF increased similarly and reached a plateau. The evoked FP increased monotonically for intervals from 50 to 500 ms, but the CBF peaked at an interval of 83 ms (approximately 12 Hz frequency). These data suggest that different anesthetics profoundly affect FP and CBF responses in different ways, which requires optimizing stimulation parameters for each anesthetic. With the refined stimulation parameters, fMRI consistently detected a well-localized activation focus at the primary somatosensory cortex in ISO-anesthetized rats. Thus, the ISO-anesthetized rat model can be used for cerebrovascular activation studies, allowing repeated noninvasive survival experiments.

Anesthetics, Inhalation↗

Cortical layer-dependent BOLD and CBV responses measured by spin-echo and gradient-echo fMRI: insights into hemodynamic regulation.

Spatial specificity of functional magnetic resonance imaging (fMRI) signals to sub-millimeter functional architecture remains controversial. To investigate this issue, high-resolution fMRI in response to visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T using conventional gradient-echo (GE) and spin-echo (SE) techniques; blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV)-weighted data were acquired without and with injection of 10 mg Fe/kg monocrystalline iron oxide nanoparticles (MION), respectively. Studies after MION injection at two SE times show that the T2' contribution to SE fMRI is minimal. GE and SE BOLD changes were spread across the cortical layers. GE and SE CBV-weighted fMRI responses peaked at the middle cortical layer, which has the highest experimentally-determined microvascular volume; full-width at half-maximum was <1.0 mm. Parenchymal sensitivity of GE CBV-weighted fMRI was approximately 3 times higher than that of SE CBV-weighted fMRI and approximately 1.5 times higher than that of BOLD fMRI. It is well known that GE CBV-weighted fMRI detects a volume change in vessels of all sizes, while SE CBV-weighted fMRI is heavily weighted toward microvascular changes. Peak CBV change of 10% at the middle of the cortex in GE measurements was 1.8 times higher than that in SE measurements, indicating that CBV changes occur predominantly for vasculature connecting the intracortical vessels and capillaries. Our data supports the notion of laminar-dependent CBV regulation at a sub-millimeter scale.

Animals↗

Quantification of cerebral arterial blood volume using arterial spin labeling with intravoxel incoherent motion-sensitive gradients.

Quantification of cerebral arterial blood volume (CBVa) is important for understanding vascular regulation. To enable measurement of CBVa with diffusion-weighted (DW) arterial spin labeling (ASL), a theoretical framework was developed using the effects of intravoxel incoherent motion (IVIM). The pseudo-diffusion coefficient (D*) in the IVIM model was evaluated at 9.4 T in DW-ASL of rat brain under isoflurane anesthesia by variations of both post-labeling delay (w) and magnetization transfer ratio (MTR). D* and its volume fraction decreased at values of w>or=0.3 s, and the normalized apparent diffusion coefficient (ADC) increased with MTR, suggesting that D* is closely correlated with CBVa. Thus, the difference between ASL measurements with and without DW gradients is related to CBVa. The CBVa values measured by this approach were compared with values obtained using the modulation of tissue and vessel (MOTIVE) technique with ASL, which varies MT levels without changing spin labeling efficiency. CBVa values from both methods were highly correlated. The measured CBVa values were linearly correlated with cerebral blood flow (CBF) for a PaCO2 range of 25-50 mmHg; DeltaCBVa (ml/100 g)=0.007 (min-1)xDeltaCBF (ml/100 g/min). The DW-ASL approach is simple and easy to implement for human and animal CBVa studies.

Algorithms↗

Source of nonlinearity in echo-time-dependent BOLD fMRI.

Stimulation-induced changes in transverse relaxation rates can provide important insight into underlying physiological changes in blood oxygenation level-dependent (BOLD) contrast. It is often assumed that BOLD fractional signal change (DeltaS/S) is linearly dependent on echo time (TE). This relationship was evaluated at 9.4 T during visual stimulation in cats with gradient-echo (GE) and spin-echo (SE) echo-planar imaging (EPI). The TE dependence of GE DeltaS/S is close to linear in both the parenchyma and large vessel area at the cortical surface for TEs of 6-20 ms. However, this dependence is nonlinear for SE studies in the TE range of 16-70 ms unless a diffusion-weighting of b = 200 s/mm(2) is applied. This behavior is not caused by inflow effects, T(2)* decay during data acquisition in SE-EPI, or extravascular spin density changes. Our results are explained by a two-compartment model in which the extravascular contribution to DeltaS/S vs. TE is linear, while the intravascular contribution can be nonlinear depending on the magnetic field strength and TE. At 9.4 T, the large-vessel IV signal can be minimized by using long TE and/or moderate diffusion weighting. Thus, stimulation-induced relaxation rate changes should be carefully determined, and their physiological meanings should be interpreted with caution.

Animals↗

Sources of functional apparent diffusion coefficient changes investigated by diffusion-weighted spin-echo fMRI.

The mechanism behind previously observed changes in the apparent diffusion coefficient (ADC) during brain activation is not well understood. Therefore, we investigated the signal source and spatial specificity of functional magnetic resonance imaging (fMRI) ADC changes systematically in the visual cortex of cats using diffusion-weighted (DW) spin-echo (SE) fMRI with b-values of 2, 200, and 800 s/mm(2), and echo times (TE) of 16, 28, and 60 ms at 9.4 T. For b > or = 200 s/mm(2), no ADC changes were detected in brain parenchyma, suggesting a minimal tissue contribution to the ADC change. For b < or = 200 s/mm(2), TE-dependent ADC increases were observed. When the venous blood contribution was minimized, the ADC change was higher at the middle cortical layer than at the cortical surface, which is mainly attributed to a functional elevation in arterial blood volume. At TE = 16 ms, the highest ADC changes occurred at the cortical surface with its large draining veins, which can mainly be explained by an additional contribution from the venous blood oxygenation changes. Our TE-dependent ADC results agree with computer simulations based on a three-compartment model. The contribution of arterial blood volume changes in ADC fMRI offers an improvement in spatial localization for SE-BOLD fMRI studies.

Animals↗

Increases in oxygen consumption without cerebral blood volume change during visual stimulation under hypotension condition.

The magnitude of the blood oxygenation level-dependent (BOLD) signal depends on cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2). Thus, it is difficult to separate CMRO2 changes from CBF and CBV changes. To detect the BOLD signal changes induced only by CMRO2 responses without significant evoked CBF and CBV changes, BOLD and CBV functional magnetic resonance imaging (fMRI) responses to visual stimulation were measured under normal and hypotension conditions in isoflurane-anesthetized cats at 4.7 T. When the mean arterial blood pressure (MABP) decreased from 89+/-10 to 50+/-1 mm Hg (mean+/-standard deviation, n=5) by infusion of vasodilator sodium nitroprusside, baseline CBV in the visual cortex increased by 28.4%+/-8.3%. The neural activity-evoked CBV increase in the visual cortex was 10.8%+/-3.9% at normal MABP, but was negligible at hypotension. Positive BOLD changes of +1.8%+/-0.5% (gradient echo time=25 ms) at normal MABP condition became prolonged negative changes of -1.2%+/-0.3% at hypotension. The negative BOLD response at hypotension starts approximately 1 sec earlier than positive BOLD response, but similar to CBV change at normal MABP condition. Our finding shows that the negative BOLD signals in an absence of CBV changes are indicative of an increase in CMRO2. The vasodilator-induced hypotension model simplifies the physiological source of the BOLD fMRI signals, providing an insight into spatial and temporal CMRO2 changes.

Animals↗

Spatial specificity of the enhanced dip inherently induced by prolonged oxygen consumption in cat visual cortex: implication for columnar resolution functional MRI.

Since changes in oxygen consumption induced by active neurons are specific to cortical columns, the small and transient "dip" of deoxyhemoglobin signal, which indicates an increase in oxygen consumption, has been of great interest. In this study, we succeeded in enhancing and sustaining the dip in the deoxyhemoglobin-weighted 620-nm intrinsic optical imaging signals from a 10-s orientation-selective stimulation in cat visual cortex by reducing arterial blood pressure with sodium nitroprusside (a vasodilator) to mitigate the contribution of stimulus-induced blood supply. During this condition, intact spiking activity and a significant reduction of stimulus-induced blood volume changes (570-nm intrinsic signals) were confirmed. The deoxyhemoglobin signal from the prolonged dip was highly localized to iso-orientation domains only during the initial approximately 2 s; the signal specificity weakened over time although the domains were still resolvable after 2 s. The most plausible explanation for this time-dependent spatial specificity is that deoxyhemoglobin induced by oxygen consumption drains from active sites, where spiking activity occurs, to spatially non-specific downstream vessels over time. Our results suggest that the draining effect of pial and intracortical veins in dHb-based imaging techniques, such as blood oxygenation-level dependent (BOLD) functional MRI, is intrinsically unavoidable and reduces its spatial specificity of dHb signal regardless of whether the stimulus-induced blood supply is spatially specific.

Animals↗

Spatial specificity of cerebral blood volume-weighted fMRI responses at columnar resolution.

The spatial specificity of functional magnetic resonance imaging (fMRI) signals to columnar architecture remains uncertain. At columnar resolution, the specificity of intrinsic cerebral blood volume (CBV) response to orientation-selective columns in isoflurane-anesthetized cats was determined for CBV-weighted fMRI signals after injection of iron oxide at a dose of 10 mg Fe/kg. CBV-weighted fMRI data were acquired at 9.4 T with an in-plane resolution of 156 x 156 microm(2) in area 18 during visual stimulation at two orthogonal orientations. A 1-mm-thick imaging slice was selected tangential to the cortical surface. Regions with large CBV changes in response to two orthogonal orientation gratings were highly complementary. Maps of iso-orientation domains in response to these gratings were highly reproducible, suggesting that CBV-weighted fMRI has high sensitivity and specificity. The average distance between iso-orientation domains was 1.37+/- 0.28 mm (n=10 orientations) in an anterior-posterior direction. CBV-weighted fMRI signal change in the iso-orientation domains induced by preferred orientation was 1.69+/- 0.24 (n=10) times larger than that induced by orthogonal orientation. Our data demonstrate that CBV regulates at a submillimeter columnar scale and CBV-weighted fMRI has sufficient specificity to map columnar organization in animals.

Animals↗

Logarithmic transformation for high-field BOLD fMRI data.

Parametric statistical analyses of BOLD fMRI data often assume that the data are normally distributed, the variance is independent of the mean, and the effects are additive. We evaluated the fulfilment of these conditions on BOLD fMRI data acquired at 4 T from the whole brain while 15 subjects fixated a spot, looked at a geometrical shape, and copied it using a joystick. We performed a detailed analysis of the data to assess (a) their frequency distribution (i.e. how close it was to a normal distribution), (b) the dependence of the standard deviation (SD) on the mean, and (c) the dependence of the response on the preceding baseline. The data showed a strong departure from normality (being skewed to the right and hyperkurtotic), a strong linear dependence of the SD on the mean, and a proportional response over the baseline. These results suggest the need for a logarithmic transformation. Indeed, the log transformation reduced the skewness and kurtosis of the distribution, stabilized the variance, and made the effect additive, i.e. independent of the baseline. We conclude that high-field BOLD fMRI data need to be log-transformed before parametric statistical analyses are applied.

Adult↗

Quantification of cerebral arterial blood volume and cerebral blood flow using MRI with modulation of tissue and vessel (MOTIVE) signals.

Regional cerebral arterial blood volume (CBVa) and blood flow (CBF) can be quantitatively measured by modulation of tissue and vessel (MOTIVE) signals, enabling separation of tissue signal from blood. Tissue signal is selectively modulated using magnetization transfer (MT) effects. Blood signal is changed either by injection of a contrast agent or by arterial spin labeling (ASL). The measured blood volume represents CBVa because the contribution from venous blood was insignificant in our measurements. Both CBVa and CBF were quantified in isoflurane-anesthetized rats at 9.4T. CBVa obtained using a contrast agent was 1.1 +/- 0.5 and 1.3 +/- 0.6 ml/100 g tissue (N = 10) in the cortex and caudate putamen, respectively. The CBVa values determined from ASL data were 1.0 +/- 0.3 ml/100 g (N = 10) in both the cortex and the caudate putamen. The match between CBVa values determined by both methods validates the MOTIVE approach. In ASL measurements, the overestimation in calculated CBF values increased with MT saturation levels due to the decreasing contribution from tissue signals, which was confirmed by the elimination of blood with a contrast agent. Using the MOTIVE approach, accurate CBF values can also be obtained.

Animals↗

Cortical depth-dependent gradient-echo and spin-echo BOLD fMRI at 9.4T.

To examine cortical depth-related spatial specificity and signal changes in gradient-echo (GE) and spin-echo (SE) blood oxygenation level-dependent (BOLD) fMRI signals, a well-established cat visual stimulation model was used at 9.4T. The GE BOLD signal percent change is the highest at the surface of the cortex containing pial vessels, and decreases as cortical depth increases. In contrast, the SE BOLD signal is more specific to parenchyma, showing the highest signal change in the middle cortical areas. The stimulation-induced DeltaR2* to DeltaR2 ratio is dependent on the vessel size, which is related to basal susceptibility effects. The averaged ratio of DeltaR2* to DeltaR2 in all active regions, including large vessels, is 3.3 +/- 0.5 (N = 6). The averaged ratio of DeltaR2* to DeltaR2 is 8.8 +/- 1.7 (N = 4) on the surface of the cortex with large pial draining vessels, and decreases to 1.9 +/- 0.1 on the middle cortical areas with parenchymal microvessels. DeltaR2*/DeltaR2 is closely related to basal susceptibility effects and can be used to differentiate tissue from vessel regions.

Animals↗

Spatial relationship between neuronal activity and BOLD functional MRI.

Despite the ubiquitous use of functional magnetic resonance imaging (fMRI), the extent to which the magnitude and spatial scale of the fMRI signal correlates with neuronal activity is poorly understood. In this study, we directly compared single and multiunit neuronal activity with blood oxygenation level-dependent (BOLD) fMRI responses across a large area of the cat area 18. Our data suggest that at the scale of several millimeters, the BOLD contrast correlates linearly with the underlying neuronal activity. At the level of individual electrode recording sites, however, the correlation between the two signals varied substantially. We conclude from our study that T(2)*-based positive BOLD signals are a robust predictor for neuronal activity only at supra-millimeter spatial scales.

Animals↗

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.

Adult↗