Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T.

Mapping of the longitudinal relaxation time (T1) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T2-dependent variation of the adiabatic inversion efficiency were investigated by single slice T1 mapping with inversion recovery EPI measurements, quantitative T2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T1 estimates at high field, the proposed correction methods resulted in an improved precision, with test-retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%.

Cerebral processing of linguistic and emotional prosody: fMRI studies.

During acoustic communication in humans, information about a speaker's emotional state is predominantly conveyed by modulation of the tone of voice (emotional or affective prosody). Based on lesion data, a right hemisphere superiority for cerebral processing of emotional prosody has been assumed. However, the available clinical studies do not yet provide a coherent picture with respect to interhemispheric lateralization effects of prosody recognition and intrahemispheric localization of the respective brain regions. To further delineate the cerebral network engaged in the perception of emotional tone, a series of experiments was carried out based upon functional magnetic resonance imaging (fMRI). The findings obtained from these investigations allow for the separation of three successive processing stages during recognition of emotional prosody: (1) extraction of suprasegmental acoustic information predominantly subserved by right-sided primary and higher order acoustic regions; (2) representation of meaningful suprasegmental acoustic sequences within posterior aspects of the right superior temporal sulcus; (3) explicit evaluation of emotional prosody at the level of the bilateral inferior frontal cortex. Moreover, implicit processing of affective intonation seems to be bound to subcortical regions mediating automatic induction of specific emotional reactions such as activation of the amygdala in response to fearful stimuli. As concerns lower level processing of the underlying suprasegmental acoustic cues, linguistic and emotional prosody seem to share the same right hemisphere neural resources. Explicit judgment of linguistic aspects of speech prosody, however, appears to be linked to left-sided language areas whereas bilateral orbitofrontal cortex has been found involved in explicit evaluation of emotional prosody. These differences in hemispheric lateralization effects might explain that specific impairments in nonverbal emotional communication subsequent to focal brain lesions are relatively rare clinical observations as compared to the more frequent aphasic disorders.

Identification of emotional intonation evaluated by fMRI.

During acoustic communication among human beings, emotional information can be expressed both by the propositional content of verbal utterances and by the modulation of speech melody (affective prosody). It is well established that linguistic processing is bound predominantly to the left hemisphere of the brain. By contrast, the encoding of emotional intonation has been assumed to depend specifically upon right-sided cerebral structures. However, prior clinical and functional imaging studies yielded discrepant data with respect to interhemispheric lateralization and intrahemispheric localization of brain regions contributing to processing of affective prosody. In order to delineate the cerebral network engaged in the perception of emotional tone, functional magnetic resonance imaging (fMRI) was performed during recognition of prosodic expressions of five different basic emotions (happy, sad, angry, fearful, and disgusted) and during phonetic monitoring of the same stimuli. As compared to baseline at rest, both tasks yielded widespread bilateral hemodynamic responses within frontal, temporal, and parietal areas, the thalamus, and the cerebellum. A comparison of the respective activation maps, however, revealed comprehension of affective prosody to be bound to a distinct right-hemisphere pattern of activation, encompassing posterior superior temporal sulcus (Brodmann Area [BA] 22), dorsolateral (BA 44/45), and orbitobasal (BA 47) frontal areas. Activation within left-sided speech areas, in contrast, was observed during the phonetic task. These findings indicate that partially distinct cerebral networks subserve processing of phonetic and intonational information during speech perception.

Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare hereditary disorder of the CNS catabolism of gamma-aminobutyric acid (GABA), leading to accumulation of the metabolite 4-hydroxybutyrate (GHB). Here the authors report on 1.5 and 3.0 T proton MR spectroscopy in a patient with SSADH deficiency. A characteristic pattern with clearly elevated GABA levels and traces of GHB was found in both the white and the gray matter of the brain. In vivo spectroscopy may be useful for diagnosis and monitoring SSADH deficiency.

Validation of an ESI-MS/MS screening method for acylcarnitine profiling in urine specimens of neonates, children, adolescents and adults.

BACKGROUND: Acylcarnitine (AC) profiling in dried blood spots by means of electrospray ionisation tandem mass spectrometry (ESI-MS/MS) has proven to be a useful method in neonatal screening, able to detect inborn errors of fatty acid oxidation, amino acid, organic acid and carnitine metabolism. Furthermore, this method is becoming increasingly applied in selective screening and in prenatal and postmortal diagnostics of inborn metabolic disorders, where urine is commonly used as specimen of interest. We therefore developed and validated a butylation method of acylcarnitine profiling in urine by ESI-MS/MS without previous chromatographic separation. METHODS: Random urine specimens were used for investigation of the analytical imprecision of the method. Recovery, precision and linearity were determined using methanolic standard solutions of free carnitine, octanoylcarnitine and palmitoylcarnitine at various concentrations. RESULTS: The mean coefficients of variation of within-run and run-to-run analysis of these analytes were found between 10% and 20% and demonstrated that the method fulfills the analytical requirements within the relevant ranges of concentration. Creatinine-related and age-related reference values of free carnitine and the ACs (C2-C18) were established. The definite discrimination was possible between patients with fatty acid oxidation disorders, organic acidurias, and healthy controls. The AC profiles from patients with various specific disorders were diagnostically helpful during acute deterioration and even during conditions of well-compensated metabolic state. CONCLUSION: The method used in this study is suitable both for selective screening and for confirmation of diagnosis with the advantage of high-throughput quantitative measurement.