In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the ... more In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the cortical surfaces of brain specimens. This provided the first account of a rare anatomical variation - bridges across the central sulci in both hemispheres connecting the forward and backward facing central convolutions in one of the brains. The serendipitous rediscovery of the preserved historic brain specimen in the collections at Göttingen University, being mistaken as the brain of the mathematician C.F. Gauss, allowed us to further investigate the morphology of the bridges Wagner had described with magnetic resonance imaging (MRI). On the historic lithograph, current photographs and MRI surface reconstructions of the brain, a connection across the central sulcus can only be seen in the left hemisphere. In the right hemisphere, contrary to the description of Wagner, a connecting structure is only present across the post-central sulcus. MRI reveals that the left-hemispheric bridge exte...
Quantitative magnetic imaging Magnetization transfer R1 Voxel-based morphometry Voxel-based quant... more Quantitative magnetic imaging Magnetization transfer R1 Voxel-based morphometry Voxel-based quantification Basal ganglia Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer -MT, from healthy subjects (n = 96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* -a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.
Magnetic Resonance in Medicine - MAGN RESON MED, 2010
Due to an unauthorized modification of the proofs, Eq. 9b has been incorrectly rendered in the pu... more Due to an unauthorized modification of the proofs, Eq. 9b has been incorrectly rendered in the published issue. The equation states the signal amplitude, A app in arbitrary units, as calculated from two FLASH signals S 1 and S 2 measured at flip angles a 1 and a 2 , respectively, in units of radians. The correct equation reads
Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo... more Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85 years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.
Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological a... more Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological and neuropsychiatric disorders. Currently available structural T1-weighted (T1w) magnetic resonance images do not provide sufficient contrast for reliable automated segmentation of various subcortical grey matter structures. We use a novel, semi-quantitative magnetization transfer (MT) imaging protocol that overcomes limitations in T1w images, which are mainly due to their sensitivity to the high iron content in subcortical grey matter. We demonstrate improved automated segmentation of putamen, pallidum, pulvinar and substantia nigra using MT images. A comparison with segmentation of high-quality T1w images was performed in 49 healthy subjects. Our results show that MT maps are highly suitable for automated segmentation, and so for multi-subject morphometric studies with a focus on subcortical structures.
A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This... more A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19e75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.
Magnetization transfer effects represent a major source of contrast in multislice turbo spin echo... more Magnetization transfer effects represent a major source of contrast in multislice turbo spin echo sequences (TSE)/fast spin echo sequences. Generally, low refocusing flip angles have become common in such MRI sequences, especially to mitigate specific absorption rate problems. Since the strength of magnetization transfer effects is related to the radiofrequency power and therefore specific absorption rate applied, magnetization transfer induced signal attenuations are investigated for a variety of TSE sequences with low constant and variable flip angles. Noticeable differences between the sequences have been observed. In particular, fewer signal attenuations are observed for TSE with low flip angles such as hyperecho-TSE and smooth transitions between pseudo steady states-TSE, leading to contrast that is less dependent on the number of slices. It is shown that the strength of the magnetization transfer-induced signal attenuations can be understood and described by a physical framework, which is based on the mean square flip angle of a given TSE sequence. Magn Reson Med 63:230 -234, 2010.
A novel linear parameterization for the variable flip angle method for longitudinal relaxation ti... more A novel linear parameterization for the variable flip angle method for longitudinal relaxation time T 1 quantification from spoiled steady state MRI is derived from the half angle tangent transform, t, of the flip angle. Plotting the signal S at coordinates x 5 St and y 5 S/t, respectively, establishes a line that renders signal amplitude and relaxation term separately as yintercept and slope. This representation allows for estimation of the respective parameter from the experimental data. A comprehensive analysis of noise propagation is performed. Numerical results for efficient optimization of longitudinal relaxation time and proton density mapping experiments are derived. Appropriate scaling allows for a linear presentation of data that are acquired at different short pulse repetition times, TR << T1 thus increasing flexibility in the data acquisition by removing the limitation of a single pulse repetition time. Signal bias, like due to slice-selective excitation or imperfect spoiling, can be readily identified by systematic deviations from the linear plot. The method is illustrated and validated by 3T experiments on phantoms and human brain. Magn Reson Med 66:669-677, 2011. V C 2011 Wiley-Liss, Inc.
To optimize contrast-to-noise and spatial resolution of a FLASH-based magnetization transfer (MT)... more To optimize contrast-to-noise and spatial resolution of a FLASH-based magnetization transfer (MT) protocol for visualization of substructures in human thalamus. Healthy adults were examined at 3 Tesla with a three-dimensional (3D) spoiled gradient-echo sequence. The signal-to-noise ratio (SNR) was increased by averaging eight bipolar echo acquisitions (mean echo time = 12.3 ms; bandwidth = 370 Hz/pixel). Three isotropic datasets with different weighting (proton density: flip angle/repetition time = 7 degrees /30 ms; T(1): 20 degrees /30 ms and MT: 10 degrees /48 ms, Gaussian MT prepulse) yielded maps of T(1), signal amplitude, MT ratio and MT saturation for comparison to MP-RAGE images. Measuring time was 23 min using partial k-space acquisition. First, the SNR of MT saturation maps in thalamus was optimized by means of the excitation flip angle. Then, noise and partial volume effects were traded off by means of the resolution. Finally, the contrast within the thalamus and to adjacent structures was compared between different maps. The optimized MT saturation maps at 0.95 mm isotropic resolution provided the highest contrast. It was most prominent between structures of high axonal content (internal medullary lamina, ventral nuclei) and those containing predominantly neuronal somata (pulvinar, mediodorsal thalamus, geniculate bodies). Semiquantitative MT saturation maps provide an enhanced intra-thalamic contrast. The borders and nuclear groups of the thalamus are reliably delineated; individual assignment of singular nuclei seems feasible.
One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance ima... more One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1-weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7%±0.4%), but no change relative to baseline in the poststimulation phase (0.2% ± 0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism.
Despite advances in understanding basic organizational principles of the human basal ganglia, acc... more Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of
Purpose: The longitudinal relaxation rate (R 1 ) measured in vivo depends on the local microstruc... more Purpose: The longitudinal relaxation rate (R 1 ) measured in vivo depends on the local microstructural properties of the tissue, such as macromolecular, iron, and water content. Here, we use whole brain multiparametric in vivo data and a general linear relaxometry model to describe the dependence of R 1 on these components. We explore a) the validity of having a single fixed set of model coefficients for the whole brain and b) the stability of the model coefficients in a large cohort. Methods: Maps of magnetization transfer (MT) and effective transverse relaxation rate (R 2 *) were used as surrogates for macromolecular and iron content, respectively. Spatial variations in these parameters reflected variations in underlying tissue microstructure. A linear model was applied to the whole brain, including gray/white matter and deep brain structures, to determine the global model coefficients. Synthetic R 1 values were then calculated using these coefficients and compared with the measured R 1 maps. Results: The model's validity was demonstrated by correspondence between the synthetic and measured R 1 values and by high stability of the model coefficients across a large cohort. Conclusion: A single set of global coefficients can be used to relate R 1 , MT, and R 2 * across the whole brain. Our population study demonstrates the robustness and stability of the model.
In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the ... more In 1860 and 1862, the German physiologist Wagner published two studies, in which he compared the cortical surfaces of brain specimens. This provided the first account of a rare anatomical variation - bridges across the central sulci in both hemispheres connecting the forward and backward facing central convolutions in one of the brains. The serendipitous rediscovery of the preserved historic brain specimen in the collections at Göttingen University, being mistaken as the brain of the mathematician C.F. Gauss, allowed us to further investigate the morphology of the bridges Wagner had described with magnetic resonance imaging (MRI). On the historic lithograph, current photographs and MRI surface reconstructions of the brain, a connection across the central sulcus can only be seen in the left hemisphere. In the right hemisphere, contrary to the description of Wagner, a connecting structure is only present across the post-central sulcus. MRI reveals that the left-hemispheric bridge exte...
Quantitative magnetic imaging Magnetization transfer R1 Voxel-based morphometry Voxel-based quant... more Quantitative magnetic imaging Magnetization transfer R1 Voxel-based morphometry Voxel-based quantification Basal ganglia Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer -MT, from healthy subjects (n = 96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* -a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.
Magnetic Resonance in Medicine - MAGN RESON MED, 2010
Due to an unauthorized modification of the proofs, Eq. 9b has been incorrectly rendered in the pu... more Due to an unauthorized modification of the proofs, Eq. 9b has been incorrectly rendered in the published issue. The equation states the signal amplitude, A app in arbitrary units, as calculated from two FLASH signals S 1 and S 2 measured at flip angles a 1 and a 2 , respectively, in units of radians. The correct equation reads
Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo... more Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18-85 years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.
Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological a... more Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological and neuropsychiatric disorders. Currently available structural T1-weighted (T1w) magnetic resonance images do not provide sufficient contrast for reliable automated segmentation of various subcortical grey matter structures. We use a novel, semi-quantitative magnetization transfer (MT) imaging protocol that overcomes limitations in T1w images, which are mainly due to their sensitivity to the high iron content in subcortical grey matter. We demonstrate improved automated segmentation of putamen, pallidum, pulvinar and substantia nigra using MT images. A comparison with segmentation of high-quality T1w images was performed in 49 healthy subjects. Our results show that MT maps are highly suitable for automated segmentation, and so for multi-subject morphometric studies with a focus on subcortical structures.
A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This... more A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19e75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.
Magnetization transfer effects represent a major source of contrast in multislice turbo spin echo... more Magnetization transfer effects represent a major source of contrast in multislice turbo spin echo sequences (TSE)/fast spin echo sequences. Generally, low refocusing flip angles have become common in such MRI sequences, especially to mitigate specific absorption rate problems. Since the strength of magnetization transfer effects is related to the radiofrequency power and therefore specific absorption rate applied, magnetization transfer induced signal attenuations are investigated for a variety of TSE sequences with low constant and variable flip angles. Noticeable differences between the sequences have been observed. In particular, fewer signal attenuations are observed for TSE with low flip angles such as hyperecho-TSE and smooth transitions between pseudo steady states-TSE, leading to contrast that is less dependent on the number of slices. It is shown that the strength of the magnetization transfer-induced signal attenuations can be understood and described by a physical framework, which is based on the mean square flip angle of a given TSE sequence. Magn Reson Med 63:230 -234, 2010.
A novel linear parameterization for the variable flip angle method for longitudinal relaxation ti... more A novel linear parameterization for the variable flip angle method for longitudinal relaxation time T 1 quantification from spoiled steady state MRI is derived from the half angle tangent transform, t, of the flip angle. Plotting the signal S at coordinates x 5 St and y 5 S/t, respectively, establishes a line that renders signal amplitude and relaxation term separately as yintercept and slope. This representation allows for estimation of the respective parameter from the experimental data. A comprehensive analysis of noise propagation is performed. Numerical results for efficient optimization of longitudinal relaxation time and proton density mapping experiments are derived. Appropriate scaling allows for a linear presentation of data that are acquired at different short pulse repetition times, TR << T1 thus increasing flexibility in the data acquisition by removing the limitation of a single pulse repetition time. Signal bias, like due to slice-selective excitation or imperfect spoiling, can be readily identified by systematic deviations from the linear plot. The method is illustrated and validated by 3T experiments on phantoms and human brain. Magn Reson Med 66:669-677, 2011. V C 2011 Wiley-Liss, Inc.
To optimize contrast-to-noise and spatial resolution of a FLASH-based magnetization transfer (MT)... more To optimize contrast-to-noise and spatial resolution of a FLASH-based magnetization transfer (MT) protocol for visualization of substructures in human thalamus. Healthy adults were examined at 3 Tesla with a three-dimensional (3D) spoiled gradient-echo sequence. The signal-to-noise ratio (SNR) was increased by averaging eight bipolar echo acquisitions (mean echo time = 12.3 ms; bandwidth = 370 Hz/pixel). Three isotropic datasets with different weighting (proton density: flip angle/repetition time = 7 degrees /30 ms; T(1): 20 degrees /30 ms and MT: 10 degrees /48 ms, Gaussian MT prepulse) yielded maps of T(1), signal amplitude, MT ratio and MT saturation for comparison to MP-RAGE images. Measuring time was 23 min using partial k-space acquisition. First, the SNR of MT saturation maps in thalamus was optimized by means of the excitation flip angle. Then, noise and partial volume effects were traded off by means of the resolution. Finally, the contrast within the thalamus and to adjacent structures was compared between different maps. The optimized MT saturation maps at 0.95 mm isotropic resolution provided the highest contrast. It was most prominent between structures of high axonal content (internal medullary lamina, ventral nuclei) and those containing predominantly neuronal somata (pulvinar, mediodorsal thalamus, geniculate bodies). Semiquantitative MT saturation maps provide an enhanced intra-thalamic contrast. The borders and nuclear groups of the thalamus are reliably delineated; individual assignment of singular nuclei seems feasible.
One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance ima... more One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1-weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7%±0.4%), but no change relative to baseline in the poststimulation phase (0.2% ± 0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism.
Despite advances in understanding basic organizational principles of the human basal ganglia, acc... more Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of
Purpose: The longitudinal relaxation rate (R 1 ) measured in vivo depends on the local microstruc... more Purpose: The longitudinal relaxation rate (R 1 ) measured in vivo depends on the local microstructural properties of the tissue, such as macromolecular, iron, and water content. Here, we use whole brain multiparametric in vivo data and a general linear relaxometry model to describe the dependence of R 1 on these components. We explore a) the validity of having a single fixed set of model coefficients for the whole brain and b) the stability of the model coefficients in a large cohort. Methods: Maps of magnetization transfer (MT) and effective transverse relaxation rate (R 2 *) were used as surrogates for macromolecular and iron content, respectively. Spatial variations in these parameters reflected variations in underlying tissue microstructure. A linear model was applied to the whole brain, including gray/white matter and deep brain structures, to determine the global model coefficients. Synthetic R 1 values were then calculated using these coefficients and compared with the measured R 1 maps. Results: The model's validity was demonstrated by correspondence between the synthetic and measured R 1 values and by high stability of the model coefficients across a large cohort. Conclusion: A single set of global coefficients can be used to relate R 1 , MT, and R 2 * across the whole brain. Our population study demonstrates the robustness and stability of the model.
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Papers by Gunther Helms