Ulrike Dydak

GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI

The human anterior cingulate cortex (ACC) is part of the default-mode network that shows predominant negative blood oxygen level–dependent (BOLD) responses in functional magnetic resonance imaging (fMRI). We combined fMRI during emotional processing and resting-state magnetic resonance spectroscopy measurements and observed that the concentration of GABA in the ACC specifically correlated with the amount of negative BOLD responses in the very same region. Our findings show that default-mode network negative BOLD responses during emotions are mediated by GABA.

The Relationship Between Aberrant Neuronal Activation in the Pregenual Anterior Cingulate, Altered Glutamatergic Metabolism, and Anhedonia in Major Depression

CONTEXTnMajor depressive disorder (MDD) is characterized by diverse metabolic and functional abnormalities that occur in, among other regions, the pregenual anterior cingulate cortex (pgACC), a cortical region linked to anhedonia.nnnOBJECTIVESnTo contextualize metabolic, functional, and clinical parameters and thus to reveal cellular mechanisms related to anhedonia.nnnDESIGNnThe pgACC was investigated using a combined functional magnetic resonance imaging and magnetic resonance spectroscopic approach. Negative blood oxygenation level-dependent (BOLD) activations in the pgACC were assessed during emotional stimulation. Quantitative J-resolved magnetic resonance spectroscopy in the pgACC enabled simultaneous determination of glutamine, glutamate, N-acetylaspartate, glucose, and gamma-aminobutyric acid concentrations. Subjective emotional intensity ratings as well as various clinical parameters were determined.nnnSETTINGnThe patients were recruited and evaluated in the Department of Psychiatry, University of Zurich, while the measurements were performed in the Institute of Biomedical Engineering, University of Zurich and the Technical University Zurich.nnnPARTICIPANTSnNineteen unmedicated patients with MDD and 24 healthy subjects.nnnMAIN OUTCOME MEASURESnReduced glutamine levels and lower functional responses in pgACC in anhedonic depressed patients were expected to be the predominant effect of abnormal glutamatergic transmission. It was further tested if, among patients, the ratings of emotional intensity on visual stimulation predicted the amount of metabolic and functional alterations in terms of reduced relative metabolite concentrations and BOLD changes.nnnRESULTSnPatients with highly anhedonic MDD show decreased glutamine but normal glutamate and gamma-aminobutyric acid concentrations, with glutamine concentrations being dissociated from glucose concentrations. Glutamate and N-acetylaspartate concentrations in pgACC correlate with negative BOLD responses induced by emotional stimulation in MDD; whereas in healthy subjects, negative BOLD responses correlate with gamma-aminobutyric acid instead. Negative BOLD responses as well as glutamate and N-acetylaspartate concentrations correlate with emotional intensity ratings, an anhedonia surrogate, in those with MDD but not in healthy subjects.nnnCONCLUSIONnAberrant neuronal activation patterns of the pgACC in anhedonic depression are related to deficits of glutamatergic metabolism.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

Sensitivity-encoded spectroscopic imaging.

Sensitivity encoding (SENSE) offers a new, highly effective approach to reducing the acquisition time in spectroscopic imaging (SI). In contrast to conventional fast SI techniques, which accelerate k‐space sampling, this method permits reducing the number of phase encoding steps in each phase encoding dimension of conventional SI. Using a coil array for data acquisition, the missing encoding information is recovered exploiting knowledge of the distinct spatial sensitivities of the individual coil elements. In this work, SENSE is applied to 2D spectroscopic imaging. Fourfold reduction of scan time is achieved at preserved spectral and spatial resolution, maintaining a reasonable SNR. The basic properties of the proposed method are demonstrated by phantom experiments. The in vivo feasibility of SENSE‐SI is verified by metabolic imaging of N‐acetylaspartate, creatine, and choline in the human brain. These results are compared to conventional SI, with special attention to the spatial response and the SNR. Magn Reson Med 46:713–722, 2001.

Hypoxia-Induced Acute Mountain Sickness is Associated with Intracellular Cerebral Edema: A 3 T Magnetic Resonance Imaging Study

Acute mountain sickness is common among not acclimatized persons ascending to high altitude; the underlying mechanism is unknown, but may be related to cerebral edema. Nine healthy male students were studied before and after 6-h exposure to isobaric hypoxia. Subjects inhaled room air enriched with N2 to obtain arterial O2 saturation values of 75 to 80%. Acute mountain sickness was assessed with the environmental symptom questionnaire, and cerebral edema with 3 T magnetic resonance imaging in 18 regions of interest in the cerebral white matter. The main outcome measures were development of intra- and extracellular cerebral white matter edema assessed by visual inspection and quantitative analysis of apparent diffusion coefficients derived from diffusion-weighted imaging, and B0 signal intensities derived from T2-weighted imaging. Seven of nine subjects developed acute mountain sickness. Mean apparent diffusion coefficient increased 2.12% (baseline, 0.80±0.09; 6 h hypoxia, 0.81 ± 0.09; P = 0.034), and mean B0 signal intensity increased 4.56% (baseline, 432.1 ±98.2; 6 h hypoxia, 450.7 ± 102.5; P < 0.001). Visual inspection of magnetic resonance images failed to reveal cerebral edema. Cerebral acute mountain sickness scores showed a negative correlation with relative changes of apparent diffusion coefficients (r = 0.83, P = 0.006); there was no correlation with relative changes of B0 signal intensities. In conclusion, isobaric hypoxia is associated with mild extracellular (vasogenic) cerebral edema irrespective of the presence of acute mountain sickness in most subjects, and severe acute mountain sickness with additional mild intracellular (cytotoxic) cerebral edema.

Parallel spectroscopic imaging with spin-echo trains.

A reduction in scan time in spectroscopic imaging (SI) can be achieved by both fast and reduced k‐space sampling. This work presents an ultrafast SI technique that combines the two approaches. The synergy of multiple spin‐echo (MSE) acquisition and sensitivity encoding (SENSE) enables high‐resolution SI to be performed within a clinically acceptable scan time. MSE‐SENSE‐SI with echo train lengths ranging from one to four echoes is evaluated with respect to SNR and spatial response function by means of in vitro experiments. It is shown that acquiring two spin‐echoes (SEs) per acquisition yields a good practical trade‐off among scan time, SNR, and spatial response. The clinical feasibility of the technique is demonstrated in a patient with an astrocytoma, and SI data are obtained with an image matrix of 24 × 24 in just over 2 min. Magn Reson Med 50:196–200, 2003.

MR‐spectroscopic imaging during visual stimulation in subgroups of migraine with aura

Migraine pathophysiology possibly involves deficient mitochondrial energy reserve and diminished cortical habituation. Using functional magnetic resonance spectroscopic imaging (fMRSI), we studied cortical lactate changes during prolonged visual stimulation to search for different pathophysiological mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy volunteers (HV) and 10 migraine patients were investigated interictally: five with visual aura (MA) and five with visual symptoms and at least one of the following: paraesthe-sia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5 T) 1H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual and non-visual cortex, with the first and fifth measurements in darkness and the second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased only during stimulation, only in visual cortex; in MA resting lactate was high in visual cortex, without further increase during stimulation. This is compatible with an abnormal metabolic strain during stimulation in MAplus, possibly due to dishabituation, and a predominant mitochondrial dysfunction in MA.

Quantitative magnetic resonance spectroscopy in the entire human cervical spinal cord and beyond at 3T.

Quantitative magnetic resonance spectroscopy (MRS) amends differential diagnostics of neurological pathology. However, due to technical challenges, it has rarely been applied to the spinal cord and has mainly been restricted to the very upper part of the cervical spine. In this work, an improved acquisition protocol is proposed that takes technical problems as strong magnetic field inhomogeneities, pulsatile flow of the cerebrospinal fluid (CSF), and small voxel size into account. For that purpose, inner‐volume saturated point‐resolved spectroscopy sequence (PRESS) localization, ECG triggering, and localized higher‐order shimming and F0 determination, based on high‐resolution cardiac‐triggered static magnetic field B0 mapping, are combined. For inner‐volume saturation a highly selective T1‐ and B1‐insensitive outer‐volume suppression (OVS) sequence based on broadband RF pulses with polynomial‐phase response (PPR) is used. Validation is performed in healthy volunteers and patients with multiple sclerosis and intramedullary tumors. The applicability of spinal cord MRS is extended to the entire cervical spine. Spectral quality and its consistency are improved. In addition, high quality MRS patient data from a lesion that occluded the spinal canal in the thoracic spinal cord could be acquired. A quantitative analysis of patient spectra and spectra from healthy volunteers at different positions along the spinal cord underlines the diagnostic value of spinal cord MRS. Magn Reson Med 59:1250–1258, 2008.

Minimum-norm reconstruction for sensitivity-encoded magnetic resonance spectroscopic imaging

In this work we propose minimum‐norm reconstruction as a means to enhance the spatial response behavior in parallel spectroscopic MRI. By directly optimizing the shape of the spatial response function (SRF), the new method accounts for coil sensitivity variation across individual voxels and their side lobes. In this fashion, it mitigates the signal contamination and side‐lobe aliasing, to which previous techniques are susceptible at low resolution. Although the computational burden is higher, minimum‐norm reconstruction is shown to be feasible using an iterative algorithm. Benefits in terms of SRF shape and artifact suppression are demonstrated. Magn Reson Med, 2006.

Prostate spectroscopy at 3 Tesla using two‐dimensional S‐PRESS

Two‐dimensional (2D) strong‐coupling point‐resolved spectroscopy (S‐PRESS) is introduced as a novel approach to 1H MR spectroscopy (MRS) in the prostate. The technique provides full spectral information and allows for an accurate characterization of the citrate (Cit) signal. The method is based on acquiring a series of PRESS spectra with constant total echo time (TE). The indirect dimension is encoded by varying the relative lengths of the first and second TEs (TE1 + TE2 = TE). In the resulting 2D spectra, only the signal of strongly coupled spin systems is spread into the second dimension, which leads to more clearly arranged spectra. Furthermore, the spectral parameters of Cit (coupling constant J and chemical shift difference δ of the AB spin system) can be determined with high accuracy in vivo. The sequence is analytically optimized for maximal “strong coupling peaks” of Cit at 3T. 2D S‐PRESS spectra are compared with JPRESS spectra in vitro as well as in vivo. Magn Reson Med, 2006.