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    Gisela Hagberg

    The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human... more
    The superior colliculus (SC) is a layered structure located in the midbrain. We exploited the improved spatial resolution and BOLD signal strength available at 9.4 T to investigate the depth profile of visual BOLD responses in the human SC based on distortion-corrected EPI data with a 1 mm isotropic resolution. We used high resolution (350 µm in-plane) anatomical images to determine regions-of-interest of the SC and applied a semi-automated method to segment it into superficial, intermediate, and deep zones. A greater than linear increase in sensitivity of the functional signal at 9.4 T allowed us to detect a statistically significant depth pattern in a group analysis with a 20 min stimulation paradigm. Descriptive data showed consistent depth profiles also in single individuals. The highest signals were localized to the superficial layers of the right and left SC during contralateral stimulation, which was in good agreement with its functional architecture known from non-human primates. This study thus demonstrates the potential of 9.4 T MRI for functional neuroimaging even in deeply located, particularly challenging brain structures such as the SC. Hum Brain Mapp 38:574-587, 2017. © 2016 Wiley Periodicals, Inc.
    To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T. Spectra were acquired with a 9.4T whole-body scanner with the use of a... more
    To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T. Spectra were acquired with a 9.4T whole-body scanner with the use of a custom-built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee. The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish α-ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glu...
    To characterize the lipidic profile of bone marrow in the calcaneus and femoral neck of healthy, osteopenic, and osteoporotic women, by using magnetic resonance spectroscopy (MRS) at 3T. The final goal was to identify specific metabolites... more
    To characterize the lipidic profile of bone marrow in the calcaneus and femoral neck of healthy, osteopenic, and osteoporotic women, by using magnetic resonance spectroscopy (MRS) at 3T. The final goal was to identify specific metabolites with the potential ability to discriminate between healthy, osteopenic, and osteoporotic subjects. Sixty-two and thirty three postmenopausal women recruited to investigate calcaneus and femoral neck, respectively, underwent a bone mineral density (BMD) measurement to be classified as healthy subjects (n = 22), osteopenic (n = 45), or osteoporotic (n = 28) patients. MRS spectra were used to quantify and compare bone marrow fat resonances between the three BMD groups. Between-group differences were tested using a Welch analysis of variance. Multiple comparisons were made with the Games-Howell correction. Relationships between pairs of variables were assessed with linear correlation analysis. Reproducibility analysis was performed for all the lipid resonances in both sites. The reproducibility was satisfactory. In femoral neck, methylene (L13), glycerol (L41, L43), and total lipid resonances were significantly lower in healthy as compared to osteoporotic subjects. On the other hand, in calcaneus, L13/glycerol significantly discriminated between osteopenic and osteoporotic subjects whereas L13/(unsaturated lipid) discriminated between healthy and osteopenic group. However, the reproducibility of both unsaturated lipid and glycerol resonances were less optimal. MRS of bone marrow lipid profiles from peripheral skeletal sites may be a promising tool for screening of large population to identify individuals with or at risk for developing osteoporosis. Moreover, it provides information about the metabolic changes occurring in bone marrow with the development of osteoporosis, which are skeletal site dependent.
    ABSTRACT
    The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2... more
    The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque ...
    Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury (TBI), and is frequently accompanied by tissue tear hemorrhage. T2-weighted gradient-recalled echo (GRE) sequences are... more
    Diffuse axonal injury (DAI) is a common type of primary neuronal injury in patients with severe traumatic brain injury (TBI), and is frequently accompanied by tissue tear hemorrhage. T2-weighted gradient-recalled echo (GRE) sequences are more sensitive than T2-weighted spin-echo images for detection of hemorrhage. The purpose of this study is to compare turbo Proton Echo Planar Spectroscopic Imaging (t-PEPSI), an extremely fast sequence, with GRE sequence in the detection of DAI. Twenty-one patients (mean age 26.8 years) with severe TBI occurred at least 3 months earlier, underwent a brain MR Imaging study on a 1.5-T scanner. A qualitative evaluation of the t-PEPSI sequences was performed by identifying the optimal echo time and in-plane resolution. The number and size of DAI lesions, as well as the signal intensity contrast ratio (SI CR), were computed for each set of GRE and t-PEPSI images, and divided according to their anatomic location as lobar and/or deep brain. There was no s...
    Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally... more
    Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally interrogated the phase data of the fMRI time-series and used quantitative susceptibility mapping (QSM) in order to investigate the potential of functional QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data (1mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient-echo EPI collected at 7 T in single orientation (SO) and multiple orientation (MO) experiments, the latter involving 4 repetitions with the subject's head rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for magnitude, phase and QSM time-series and each was subjected to detailed analysis. Several fQSM pipelines were evaluated and compared based on the relative number of voxels that were coincidentally found to be significant in QSM and magnitude SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM relative to the magnitude data depended strongly on the arbitrary significance threshold defining "activated" voxels in SPMs, and on the efficiency of spatio-temporal filtering of the phase time-series. Sensitivity and spatial reliability depended slightly on whether MO or SO fQSM was performed and on the QSM calculation approach used for SO data. Our results present the potential of fQSM as a quantitative method of mapping BOLD changes. We also critically discuss the technical challenges and issues linked to this intriguing new technique.
    This paper describes the state of the art of tractography, a technique which enables the virtual reconstruction of axon bundles of the central nervous system using diffusion-weighted magnetic resonance images. This technique has raised... more
    This paper describes the state of the art of tractography, a technique which enables the virtual reconstruction of axon bundles of the central nervous system using diffusion-weighted magnetic resonance images. This technique has raised enthusiasm and expectations among specialists because it is the only non-invasive method for studying the three-dimensional architecture of axonal fibres in vivo. Tractography is a new technique used to assess the anatomy of the central nervous system, and it will be available for routine clinical use in the future. Understanding its potential applications and limitations is therefore important.
    Page 1. 8 Nerve Pathways with MR Tractography A. Cherubini, G. Luccichenti, F. Fasano, GE Hagberg, P. Péran, F. Di Salle, F. Esposito, T. Scarabino, U. Sabatini The neuroradiological interpretation of magnetic reso-nance ...
    Magnetic resonance (MR) is the imaging technique of choice for the study of traumatic brain injury (TBI) in clinically stable patients, both in the acute and in the chronic phase, and is beginning to erode the role of computed tomography... more
    Magnetic resonance (MR) is the imaging technique of choice for the study of traumatic brain injury (TBI) in clinically stable patients, both in the acute and in the chronic phase, and is beginning to erode the role of computed tomography (CT) also in clinically unstable trauma patients [1 –3 ]. In the latter the role of MR is still to
    By virtue of greater signal intensity, susceptibility arte-facts and chemical shift, 3.0 T MR imagers with advanced techniques have provided promising results for the study of PD that could not be obtained with standard magnets.... more
    By virtue of greater signal intensity, susceptibility arte-facts and chemical shift, 3.0 T MR imagers with advanced techniques have provided promising results for the study of PD that could not be obtained with standard magnets. Microstructural, metabolic and functional data will, as never before, contribute to the early diagnosis and follow-up of PD.
    The aim of this work was to investigate the hypothesis that multimodal MRI is able to detect the progressive disruption of volume and microstructure of subcortical structures in patients with amnestic mild cognitive impairment (a-MCI) and... more
    The aim of this work was to investigate the hypothesis that multimodal MRI is able to detect the progressive disruption of volume and microstructure of subcortical structures in patients with amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD) in comparison with healthy controls (CTRL). We combined volumetric and diffusion tensor imaging (DTI) techniques in a cross-sectional study including 30 a-MCI, 30 AD patients, and 30 age-matched CTRL. We employed a fully automated model-based segmentation algorithm on 3 Tesla MRI anatomical images and accurate coregistration of DTI to anatomical images to extract regional values of DTI parameters. Both the hippocampi significantly and progressively decreased in volume from CTRL through MCI to AD. Both the thalami showed a progressive and significant decrease in volume from CTRL to AD. Mean diffusivity (MD) values increased progressively across the three groups in the bilateral hippocampus, amygdala, and in the right caudate. No differences in fractional anisotropy (FA) values were found. Two distinct but overlapping patterns of progression of structural (i.e., atrophy) and microstructural (i.e., MD increase) damage were observed. Particularly, the pattern of atrophy was mirrored by the increasing value of the averaged MD, which provided a further indicator of subtle tissue disruption in the hippocampal structure in mild AD patients. Combining different MRI modalities can allow identifying sensitive indicators of the subtle pathogenic mechanisms that occur in subcortical areas of AD patients.
    The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]-tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography... more
    The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]-tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography (PET) for probing the second enzymatic step in the biosynthesis of serotonin. In this study, we examined the capacity of the model to track pharmacological changes in this biological process. We also investigated the potential loss of [(11)C]HTP-derived radioactivity during a PET study, since loss should be negligible not to alter quantification. Six rhesus monkeys were investigated using bolus [(11)C]HTP/PET methodology before and after pharmacological intervention. The second enzymatic step in serotonin synthesis was inhibited using the aromatic L-amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [(11)C]-derived radioactivity loss from the brain was studied by inhibition of the enzyme responsible for formation of the tissue metabolite, monoamine oxidase A, using clorgyline (2 mg/kg). After NSD1015, the uptake of [(11)C]HTP-derived radioactivity was increased in all the investigated brain regions, while the parameter used to reflect decarboxylase activity, the net accumulation rate constant (K(acc)), was decreased by 37% in the striatum, compared with baseline. Pretreatment with clorgyline did not change the brain uptake of [(11)C]HTP-derived radioactivity or K(acc). This study demonstrates that the 2TCM for [(11)C]HTP/PET is able to detect changes occurring during alteration of the biological process (i.e., the conversion of HTP to serotonin). Elimination of the radiotracer metabolite [(11)C]HIAA from the brain may be considered negligible if the PET study is limited to 60 min.
    BACKGROUND AND PURPOSE: Our aim was to investigate the presence of brain gray matter (GM) abnormalities in patients with different forms of essential tremor (ET). MATERIALS AND METHODS: We used optimized voxel-based morphometry (VBM) and... more
    BACKGROUND AND PURPOSE: Our aim was to investigate the presence of brain gray matter (GM) abnormalities in patients with different forms of essential tremor (ET). MATERIALS AND METHODS: We used optimized voxel-based morphometry (VBM) and manually traced single region-of-interest analysis in 50 patients with familial ET and in 32 healthy subjects. Thirty patients with ET had tremor of the arms (a-ET), whereas the remaining 20 patients had both arm and head tremor (h-ET). RESULTS: VBM showed marked atrophy of the cerebellar vermis in the patients with h-ET with respect to healthy subjects (Pcorrected .001). Patients with a-ET showed a trend toward a vermal GM volume loss that did not reach a significant difference with respect to healthy controls (Puncorrected .01). The region-of-interest analysis showed a reduction of the cerebellar volume (CV) in the h-ET group (98.2 13.6 mm3) compared with healthy controls (110.5 15.5 mm3, P.012) as well as in the entire vermal area (790.3 94.5 mm2...
    Research Interests:
    The relative size and relaxation of the invisible pool of bound spins (T(1b)) underlying magnetization transfer (MT) was quantified in eight subjects in vivo at 1.5 T from progressive saturation experiments using repetitive MT pulses. The... more
    The relative size and relaxation of the invisible pool of bound spins (T(1b)) underlying magnetization transfer (MT) was quantified in eight subjects in vivo at 1.5 T from progressive saturation experiments using repetitive MT pulses. The evolution of the binary spin-bath was sampled by increasing the repetition period from 8 to 200 ms. Single-shot echo-planar images at TE = 50 ms were evaluated in the central white matter. Three models were fitted: the general solution, and with constraints of equal relaxation and T(1b) = 1 s for the invisible pool. The general solution of unconstrained T(1b) provided a significantly better fit, indicating fast-to-intermediate exchange. The bound pool fraction was 17 +/- 4%, the relaxation times T(1f) = 1.6 +/- 0.2 s for free water and T(1b) = 171 +/- 22 ms for the bound pool. The constrained models did not differ from each other, since here T(1b) was similar to the observed T(1) of 1.1 +/- 0.1 s. They underestimate the bound pool fraction and its relaxation. Thus, the standard assumption of continuous-wave MT models may underestimate the relaxation via the bound pool by more than a factor of five.
    We report on a patient with left hemiparesis and peripersonal neglect after post-traumatic left frontal hemorrhage, who underwent fMRI, TMS and TCD to identify the functional abnormalities that account for his neurological symptoms, in... more
    We report on a patient with left hemiparesis and peripersonal neglect after post-traumatic left frontal hemorrhage, who underwent fMRI, TMS and TCD to identify the functional abnormalities that account for his neurological symptoms, in the absence of any detectable lesion affecting right motor areas.
    This study presents a simple approach for the noninvasive assignment of glial brain tumors according to malignancy by single-voxel proton magnetic resonance spectroscopy at short echo times (TE < or = 50 milliseconds). Based on... more
    This study presents a simple approach for the noninvasive assignment of glial brain tumors according to malignancy by single-voxel proton magnetic resonance spectroscopy at short echo times (TE < or = 50 milliseconds). Based on peak area ratios, a five-dimensional data set was obtained for each investigated subject. This vector was then projected along metabolic coordinates in a two-dimensional metabolic space. These coordinates had been determined in a previous study (Hagberg G et al., 1995, Magn Reson Med 34: 242-252). Tumor assignment was done without any knowledge of histology by comparing the location of the new cases to the features of the previous study. All 11 investigated glioblastomas multiforme, as well as 4 of 5 astrocytomas grade II, could easily be assigned to the groups of high- and low-grade tumors, respectively. Classification was more difficult in the case of a cystic astrocytoma grade II and one astrocytoma grade III. Two spectra measured in normal-appearing matter of glioblastoma patients were not classified as healthy. Using single-voxel proton magnetic resonance spectroscopy at short echo times with the knowledge of a base study, a straightforward, fast, and noninvasive differential diagnosis of glial brain tumors is possible.

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