Biomedical subjects

Kamil Ugurbil

Publications and source records attributed to Kamil Ugurbil.

At least 19 recordsLinked to original sources

PubMed2007

Assessment of brain iron and neuronal integrity in patients with Parkinson's disease using novel MRI contrasts.

Postmortem demonstration of increased iron in the substantia nigra (SN) is a well-appreciated finding in Parkinson's disease (PD). Iron facilitates generation of free radicals, which are thought to play a role in dopamine neuronal loss. To date, however, magnetic resonance imaging (MRI) has failed to show significant in vivo differences in SN iron levels in subjects with PD versus control subjects. This finding may be due to the limitations in tissue contrasts achievable with conventional T(1)- and T(2)-weighted MRI sequences that have been used. With the recent development of novel rotating frame transverse (T(2rho)) and longitudinal (T(1rho)) relaxation MRI methods that appear to be sensitive to iron and neuronal loss, respectively, we embarked on a study of 8 individuals with PD (Hoehn & Yahr, Stage II) and 8 age-matched control subjects. Using these techniques with a 4T MRI magnet, we assessed iron deposits and neuronal integrity in the SN. First, T(2rho) MRI, which is reflective of iron-related dynamic dephasing mechanisms (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities), demonstrated a statistically significant difference between the PD and control group, while routine T(2) MRI did not. Second, T(1rho) measurements, which appear to reflect upon neuronal count, indicated neuronal loss in the SN in PD. We show here that sub-millimeter resolution T(1rho) and T(2rho) MRI relaxation methods can provide a noninvasive measure of iron content as well as evidence of neuronal loss in the midbrain of patients with PD.

Aged↗

PubMed2006

Noninvasive and three-dimensional imaging of CMRO(2) in rats at 9.4 T: reproducibility test and normothermia/hypothermia comparison study.

Ability to image cerebral metabolic rate of oxygen (CMRO(2)) is essential for studying the fundamental role of oxidative metabolism in brain function and disease. We have demonstrated recently that three-dimensional (3D) CMRO(2) images can be obtained in the rat brain during a 2-min (17)O(2) inhalation using the (17)O MR spectroscopic imaging (MRSI) approach at high field. The feasibility for establishing a completely noninvasive approach for imaging CMRO(2) has also been demonstrated. In this study, we further explored the feasibility of (17)O MRSI approach for performing repeated CMRO(2) measurements within a short period of time and evaluated the reproducibility of the repeated measurements. Subsequently, we applied the (17)O MRSI approach to measure CMRO(2) and cerebral blood flow (CBF) values at two brain temperatures in the alpha-chloralose anesthetized rat brain at 9.4 T. Finally, we tested the validity of simplified model for noninvasively determining CMRO(2) in normothermic and hypothermic rat brain. The results show (i) an excellent reproducibility among repeated measurements of 3D CMRO(2) images under the same physiologic condition; (ii) a 44% decrease of CMRO(2) across the rat brain at mild hypothermic (32 degrees C) condition as compared with normothermic (37 degrees C) condition; and (iii) a close correlation between CMRO(2) and CBF within a relatively wide physiologic range. This study demonstrates the capability of (17)O MRSI approach for noninvasively imaging CMRO(2) and its changes caused by physiologic perturbation. This approach, thus, should provide a promising neuroimaging modality for studying oxidative metabolism and bioenergetics associated with brain functions and diseases.

Animals↗

PubMed2006

Spatial resolution dependence of DTI tractography in human occipito-callosal region.

Diffusion tensor imaging (DTI) and fiber tracking have been used to measure the fiber structural connectivity in humans in a non-invasive manner. However, low sensitivity is a principal limitation of these methods, causing a large number of possibly missing fiber tracts (FTs). Here we studied how the spatial resolution affects the sensitivity of the fiber tracing by rescaling data to different resolutions. Our data suggest that the spatial resolution can change the degree of the asymmetric cross-callosal connections in the lower visual field (loVF) compared to the upper visual field (upVF). Among connections from loVF, a larger voxel size resulted in a smaller number of FTs that was not commensurate to the number of seed points, while the number of connections from upVF was not significantly affected by variation in seeding point numbers. We conclude from our study that the spatial resolution of the acquired data will have to be taken into consideration in interpreting DTI fiber tracking data. Our results further suggest that the acquisition resolution of around 2 mm iso-voxel in the conventional DTI scheme can reconstruct the asymmetric upper and lower white matter structure in occipito-callosal region.

Adult↗

PubMed2006

T1rho MRI contrast in the human brain: modulation of the longitudinal rotating frame relaxation shutter-speed during an adiabatic RF pulse.

Longitudinal relaxation in the rotating frame (T1rho) is the dominant mechanism during a train of adiabatic full passage (AFP) RF pulses with no interpulse intervals, placed prior to an excitation pulse. Asymptotic apparent time constants (T1rho') were measured for human occipital lobe 1H2O at 4T using brief imaging readouts following such pulse trains. Two members of the hyperbolic secant (HSn) AFP pulse family (n=1 or 4; i.e., arising from different amplitude- and frequency-modulation functions) were used. These produced two different non-monoexponential signal decays during the pulse trains. Thus, there are differing contrasts in asymptotic T1rho' maps derived from these data. This behavior is quite different than that of 1H2O signals from an aqueous protein solution of roughly the same macromolecular volume fraction as tissue. The ROI-averaged decays from the two acquisitions can be simultaneously accommodated by a two-site-exchange model for an equilibrium isochronous process whose exchange condition is modulated during the pulse. The model employs a two-spin description of dipolar interaction fluctuations in each site. The intrinsic site R1rho(identical with T1rho(-1)) value is sensitive to fluctuations at the effective Larmor frequency (omegaeff) in the rotating frame, and this is modulated differently during the two types of AFP pulses. Agreement with the data is quite good for site orientation correlation time constants characteristic of macromolecule-interacting water (site A) and bulk-like water (site B). Since R1rhoA is significantly modulated while R1rhoB is not, the intrinsic relaxographic shutter-speed for the process (identical with /R1rhoA-R1rhoB/), and thus the exchange condition, is modulated. However, the mean residence time (67 ms) and intrinsic population fraction (0.2) values found for site A are each rather larger than might be expected, suggesting a disproportionate role for the water molecules known to be "buried" within the large and concentrated macromolecules of in vivo tissue.

Brain Mapping↗

PubMed2006

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↗

PubMed2006

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.

Adolescent↗

PubMed2006

Investigation of multicomponent diffusion in cat brain using a combined MTC-DWI approach.

In this study, multiple-component water diffusion in the cat brain is investigated using an approach that combines diffusion-weighted images using multiple b values with magnetization transfer contrast (MTC). The MTC allows filter of signal originating from water molecules that rapidly exchange with binding sites on large macromolecular structures, and in brain white matter, it is assumed that a significant portion of the MTC is due to the interaction of water with the extraaxonal myelin sheath. Henceforth, multicomponent analysis of diffusion curves with and without MTC may shed light on the contribution of the extraaxonal water to the diffusion signal and on the relationship between diffusion components and tissue compartments in the brain. When a biexponential model was applied to the data, the volume fractions of the two diffusion components changed significantly in white matter with the application of the MTC. These changes are then discussed in the frame of tissue components and the possible interaction with the myelin sheath.

Animals↗

PubMed2006

Anatomical correlates of the functional organization in the human occipitotemporal cortex.

The connectivity between functionally distinct areas in the human brain is unknown because of the limitations posed by current postmortem anatomical labeling techniques. Diffusion tensor imaging (DTI) has previously been used to define large white matter tracts based on well-known anatomical landmarks in the living human brain. In the present study, we used DTI coupled with functional magnetic resonance imaging (fMRI) to assess neuronal connections between human striate and functionally defined extrastriate ventral cortical areas. Functional areas were identified with conventional fMRI mapping procedures and then used as seeding points in a DTI analysis to ascertain connectivity patterns between cortical areas, thus yielding the pattern of connections between human occipitoventral visual areas in vivo.

Adult↗

PubMed2006

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↗

PubMed2006

Manipulation of image intensity distribution at 7.0 T: passive RF shimming and focusing with dielectric materials.

PURPOSE: To investigate the effects of high dielectric material padding on RF field distribution in the human head at 7.0 T, and demonstrate the feasibility and effectiveness of RF passive shimming and focusing with such an approach. MATERIALS AND METHODS: The intensity distribution changes of gradient-recalled-echo (GRE) and spin-echo (SE) images of a human head acquired with water pads (dielectric constant = 78) placed in specified configurations around the head at 7.0 T were evaluated and compared with computer simulation results using the finite difference time domain (FDTD) method. The contributions to the B(1) field distribution change from the displacement current and conductive current of a given configuration of dielectric padding were determined with computer simulations. RESULTS: MR image intensity distribution in the human head with an RF coil at 7.0 T can be changed drastically by placing water pads around the head. Computer simulations reveal that the high permittivity of water pads results in a strong displacement current that enhances image intensity in the nearby region and alters the intensity distribution of the entire brain. CONCLUSION: The image intensity distribution in the human head at ultra-high field strengths can be effectively manipulated with high permittivity padding. Utilizing this effect, the B(1) field inside the human head of a given RF coil can be adjusted to reduce the B(1) field inhomogeneity artifact associated with the wave behavior (RF passive shimming) or to locally enhance the signal-to-noise ratio (SNR) in targeted regions of interest (ROIs; RF field focusing).

Brain↗

PubMed2006

Signal-to-noise ratio and spectral linewidth improvements between 1.5 and 7 Tesla in proton echo-planar spectroscopic imaging.

This study characterizes gains in sensitivity and spectral resolution of proton echo-planar spectroscopic imaging (PEPSI) with increasing magnetic field strength (B(0)). Signal-to-noise ratio (SNR) per unit volume and unit time, and intrinsic linewidth (LW) of N-acetyl-aspartate (NAA), creatine (Cr), and choline (Cho) were measured with PEPSI at 1.5, 3, 4, and 7 Tesla on scanners that shared a similar software and hardware platform, using circularly polarized (CP) and eight-channel phased-array (PA) head coils. Data were corrected for relaxation effects and processed with a time-domain matched filter (MF) adapted to each B(0). The SNR and LW measured with PEPSI were very similar to those measured with conventional point-resolved spectroscopy (PRESS) SI. Measurements with the CP coil demonstrated a nearly linear SNR gain with respect to B(0) in central brain regions. For the PA coil, the SNR-B(0) relationship was less than linear, but there was a substantial SNR increase in comparison to the CP coil. The LW in units of ppm decreased with B(0), resulting in improved spectral resolution. These studies using PEPSI demonstrated linear gains in SNR with respect to B(0), consistent with theoretical expectations, and a decrease in ppm LW with increasing B(0).

Artifacts↗

PubMed2006

9.4T human MRI: preliminary results.

This work reports the preliminary results of the first human images at the new high-field benchmark of 9.4T. A 65-cm-diameter bore magnet was used together with an asymmetric 40-cm-diameter head gradient and shim set. A multichannel transmission line (transverse electromagnetic (TEM)) head coil was driven by a programmable parallel transceiver to control the relative phase and magnitude of each channel independently. These new RF field control methods facilitated compensation for RF artifacts attributed to destructive interference patterns, in order to achieve homogeneous 9.4T head images or localize anatomic targets. Prior to FDA investigational device exemptions (IDEs) and internal review board (IRB)-approved human studies, preliminary RF safety studies were performed on porcine models. These data are reported together with exit interview results from the first 44 human volunteers. Although several points for improvement are discussed, the preliminary results demonstrate the feasibility of safe and successful human imaging at 9.4T.

Burns, Electric↗

PubMed2006

Potential and feasibility of parallel MRI at high field.

This survey focuses on the fusion of two major lines of recent progress in MRI methodology: parallel imaging with receiver coil arrays and the transition to high and ultra-high field strength for human applications. As discussed in this paper, combining the two developments has vast potential due to multiple specific synergies. First, parallel acquisition and high field are highly complementary in terms of their individual advantages and downsides. As a consequence, the joint approach generally offers enhanced flexibility in the design of scanning strategies. Second, increasing resonance frequency changes the electrodynamics of the MR signal in such a way that parallel imaging becomes more effective in large objects. The underlying conceptual and theoretical considerations are reviewed in detail. In further sections, technical challenges and practical aspects are discussed. The feasibility of parallel MRI at ultra-high field is illustrated by current results of parallel human MRI at 7 T.

Algorithms↗

PubMed2006

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↗

PubMed2005

Analysis of the distribution of diffusion coefficients in cat brain at 9.4 T using the inverse Laplace transformation.

In this work, the usefulness of the inverse Laplace transformation (ILT) in the characterization of diffusion processes in the brain has been investigated. The method has been implemented on both phantom and in vivo cat brain data acquired at high resolution at 9.4 T. The results were compared with monoexponential and biexponential analyses of the same data. It is shown that in the case of diffusion restricted by white matter axonal tracts, the resulting diffusograms are in good agreement with the biexponential model. In gray matter, however, the non-monoexponential decay does not lead to a bimodal distribution in the ILT, even though the data can be fitted to a biexponential. This finding suggests the possibility of a distribution of diffusion coefficients rather than a discrete biexponential behavior. It is shown that this distribution is sensitive, for example, to experimental parameters such as the diffusion time. Thus, the ILT offers the possibility of implementing a unique tool for the analysis of heterogeneous diffusion, that is, the analysis of the diffusion coefficient distribution, which has the yet unexplored potential of being a valuable parameter in the characterization of tissue structure.

Animals↗

PubMed2005

Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia.

OBJECTIVE: Quantitation of glutathione (GSH) in the human brain in vivo using short echo time 1H NMR spectroscopy is challenging because GSH resonances are not easily resolved. The main objective of this study was to validate such quantitation in a clinically relevant population using the resolved GSH resonances provided by edited spectroscopy. A secondary objective was to compare several of the neurochemical concentrations quantified along with GSH using LCModel analysis of short echo time spectra in schizophrenia versus control. MATERIALS AND METHODS: GSH was quantified at 4T from short echo STEAM spectra and MEGA-PRESS edited spectra from identical volumes of interest (anterior cingulate) in ten volunteers. Neurochemical profiles were quantified in nine controls and 13 medicated schizophrenic patients. RESULTS: GSH concentrations as quantified using STEAM, 1.6 +/- 0.4 micromol/g (mean +/- SD, n = 10), were within error of those quantified using edited spectra, 1.4 +/- 0.4 micromol/g, and were not different (p = 0.4). None of the neurochemical measurements reached sufficient statistical power to detect differences smaller than 10% in schizophrenia versus control. As such, no differences were observed. CONCLUSIONS: Human brain GSH concentrations can be quantified in a clinical setting using short-echo time STEAM spectra at 4T.

Adult↗

PubMed2005

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↗

PubMed2005

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Adult↗