Biomedical subjects
Publications and source records attributed to Gregor Adriany.
In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.
Gradient-echo EPI, blood oxygenation level-dependent (BOLD) functional MRI (fMRI) using parallel imaging (PI) is demonstrated at 7 Tesla with 16 channels, a fourfold 1D reduction factor (R), and fourfold maximal aliasing. The resultant activation detection in finger-tapping fMRI studies was robust, in full agreement with expected activation patterns based on prior knowledge, and with functional maps generated from full field of view (FOV) coverage of k-space using segmented acquisition. In all aspects the functional maps acquired with PI outperformed segmented coverage of full k-space. With a 1D R of 4, fMRI activation based on PI had higher statistical significance, up to 1.6-fold in an individual case and 1.25+/-.25 (SD) fold when averaged over six studies, compared to four-segment/full-FOV data in which the square root R reduction in the image signal-to-noise ratio (SNR) due to k-space undersampling was compensated for by acquiring additional repetitions of the undersampled k-space. When this compensation for loss in SNR was not performed, the effect of PI was determined by the ratio of physiologically induced vs. intrinsic (thermal) noise in the fMRI time series and the extent to which physiological "noise" was amplified by the use of segmentation in the full-FOV data. The results demonstrate that PI is particularly beneficial at this ultrahigh field strength, where both the intrinsic image SNR and temporal signal fluctuations due to physiological processes are large.
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.
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.
The ability to detect individual Alzheimer's amyloid plaques in vivo by magnetic resonance microimaging (MRI) should improve diagnosis and also accelerate discovery of effective therapeutic agents for Alzheimer's disease (AD). Here, we perform in vivo and ex vivo MRI on double transgenic AD mice as well as wild-type mice at varying ages and correlate these with thioflavin-S and iron staining histology. Quantitative counts of individual plaques on MRI increase with age and correlate with histologically determined plaque burden. Plaques 20 microm in diameter can be detected in AD mice as young as 3 months of age with ex vivo MRI. Plaques 35 microm in diameter can be detected by 9 months of age with in vivo MRI. In vivo MRI of individual Alzheimer's amyloid plaques provides a noninvasive estimate of plaque burden in transgenic AD mice that might be useful in assessing the efficacy of amyloid reduction therapies.
Transceive array coils, capable of RF transmission and independent signal reception, were developed for parallel, 1H imaging applications in the human head at 7 T (300 MHz). The coils combine the advantages of high-frequency properties of transmission lines with classic MR coil design. Because of the short wavelength at the 1H frequency at 300 MHz, these coils were straightforward to build and decouple. The sensitivity profiles of individual coils were highly asymmetric, as expected at this high frequency; however, the summed images from all coils were relatively uniform over the whole brain. Data were obtained with four- and eight-channel transceive arrays built using a loop configuration and compared to arrays built from straight stripline transmission lines. With both the four- and the eight-channel arrays, parallel imaging with sensitivity encoding with high reduction numbers was feasible at 7 T in the human head. A one-dimensional reduction factor of 4 was robustly achieved with an average g value of 1.25 with the eight-channel transmit/receive coils.
RF behavior in the human head becomes complex at ultrahigh magnetic fields. A bright center and a weak periphery are observed in images obtained with volume coils, while surface coils provide strong signal in the periphery. Intensity patterns reported with volume coils are often loosely referred to as "dielectric resonances," while modeling studies ascribe them to superposition of traveling waves greatly dampened in lossy brain tissues, raising questions regarding the usage of this term. Here we address this question experimentally, taking full advantage of a transceiver coil array that was used in volume transmit mode, multiple receiver mode, or single transmit surface coil mode. We demonstrate with an appropriately conductive sphere phantom that destructive interferences are responsible for a weak B(1) in the periphery, without a significant standing wave pattern. The relative spatial phase of receive and transmit B(1) proved remarkably similar for the different coil elements, although with opposite rotational direction. Additional simulation data closely matched our phantom results. In the human brain the phase patterns were more complex but still exhibited similarities between coil elements. Our results suggest that measuring spatial B(1) phase could help, within an MR session, to perform RF shimming in order to obtain more homogeneous B(1) in user-defined areas of the brain.
One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop "human-like" plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI-ex vivo MRI-in vitro histologic correlations are provided. Histologically verified plaques as small as 50 microm in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent.
In this work, the dependence of parallel MRI performance on main magnetic field strength is experimentally investigated. Using the general framework of electrodynamic scaling, the B0-dependent behavior of the relevant radiofrequency fields at a single physical field strength of 7 T is studied. In the chosen implementation this is accomplished by adjusting the permittivity and conductivity of a homogeneous spherical phantom. With different mixing ratios of decane, ethanol, purified water, N-methylformamide, and sodium chloride, field strengths in the range of 1.5 to 11.5 T are mimicked. Based on sensitivity maps of an eight-coil receiver array, the field-dependent performance of parallel imaging is assessed in terms of the geometry factor g, which reflects noise enhancement in parallel imaging reconstruction. At low field strengths the SNR penalty was nearly independent of B0 and favorably low for 1D reduction factors up to between 3 and 4. At higher field strengths the transition between favorable and prohibitive parallel imaging conditions was found to shift toward higher feasible reduction factors. These findings are in good agreement with previous theoretical predictions. From this agreement it is concluded that parallel MRI at high B0 benefits specifically from onsetting far-field behavior of the involved radiofrequency 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.
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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.
A high-resolution spin-echo imaging method is presented (called CP-LASER) which exploits the spin refocusing capability of an adiabatic Carr-Purcell (CP) pulse sequence to measure apparent 1H2O transverse relaxation (T2+) and generate contrast based on microscopic tissue susceptibility. High-resolution CP-LASER images of the human occipital lobe were acquired at four different echo times from six subjects at 4T and eight subjects at 7T to investigate the effect of magnetic field strength (B(0)) and the CP interpulse time (tau(cp)) on T2+. Susceptibility contrast was identified and T2+ was quantified for long tau(cp) (>10 ms) and short tau(cp) (7 ms at 4T and 6 ms at 7T) in gray matter, white matter, and cerebral spinal fluid. The 1H2O relaxation rate constants (1/T2+) of gray and white matter each increased approximately linearly with field strength and T2+ was inversely related to tau(cp). The average T2+ value of gray matter was 19% and 9% smaller than that of white matter at 4T and 7T, respectively. These results are consistent with higher levels of compartmentalized ferritin and increased blood volume in gray matter compared to white matter in this region of the brain.
Carr-Purcell and Hahn spin-echo (SE) measurements were used to estimate the apparent transverse relaxation time constant (T2) of water and metabolites in human brain at 4T and 7T. A significant reduction in the T2 values of proton resonances (water, N-acetylaspartate, and creatine/phosphocreatine) was observed with increasing magnetic field strength and was attributed mainly to increased dynamic dephasing due to increased local susceptibility gradients. At high field, signal loss resulting from T2 decay can be substantially reduced using a Carr-Purcell-type SE sequence.
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.
The RF field intensity distribution in the human brain becomes inhomogeneous due to wave behavior at high field. This is further complicated by the spatial distribution of RF field polarization that must be considered to predict image intensity distribution. An additional layer of complexity is involved when a quadrature coil is used for transmission and reception. To study such complicated RF field behavior, a computer modeling method was employed to investigate the RF field of a quadrature surface coil at 300 MHz. Theoretical and experimental results for a phantom and the human head at 7.0 T are presented. The results are theoretically important and practically useful for high-field quadrature coil design and application.
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.
Localized (13)C NMR spectroscopy provides a new investigative tool for studying cerebral metabolism. The application of (13)C NMR spectroscopy to living intact humans and animals presents the investigator with a number of unique challenges. This review provides in the first part a tutorial insight into the ingredients required for achieving a successful implementation of localized (13)C NMR spectroscopy. The difficulties in establishing (13)C NMR are the need for decoupling of the one-bond (13)C-(1)H heteronuclear J coupling, the large chemical shift range, the low sensitivity and the need for localization of the signals. The methodological consequences of these technical problems are discussed, particularly with respect to (a) RF front-end considerations, (b) localization methods, (c) the low sensitivity, and (d) quantification methods. Lastly, some achievements of in vivo localized (13)C NMR spectroscopy of the brain are reviewed, such as: (a) the measurement of brain glutamine synthesis and the feasibility of quantifying glutamatergic action in the brain; (b) the demonstration of significant anaplerotic fluxes in the brain; (c) the demonstration of a highly regulated malate-aspartate shuttle in brain energy metabolism and isotope flux; (d) quantification of neuronal and glial energy metabolism; and (e) brain glycogen metabolism in hypoglycemia in rats and humans. We conclude that the unique and novel insights provided by (13)C NMR spectroscopy have opened many new research areas that are likely to improve the understanding of brain carbohydrate metabolism in health and disease.