The influence of season on glutamate and GABA levels in the healthy human brain investigated by magnetic resonance spectroscopy imaging.

Seasonal changes in neurotransmitter systems have been demonstrated in imaging studies and are especially noticeable in diseased states such as seasonal affective disorder (SAD). These modulatory neurotransmitters, such as serotonin, are influencing glutamatergic and GABAergic neurotransmission. Furthermore, central components of the circadian pacemaker are regulated by GABA (the suprachiasmatic nucleus) or glutamate (e.g., the retinohypothalamic tract). Therefore, we explored seasonal differences in the GABAergic and glutamatergic system in 159 healthy individuals using magnetic resonance spectroscopy imaging with a GABA-edited 3D-MEGA-LASER sequence at 3T. We quantified GABA+/tCr, GABA+/Glx, and Glx/tCr ratios (GABA+, GABA+ macromolecules; Glx, glutamate + glutamine; tCr, total creatine) in five different subcortical brain regions. Differences between time periods throughout the year, seasonal patterns, and stationarity were tested using ANCOVA models, curve fitting approaches, and unit root and stationarity tests, respectively. Finally, Spearman correlation analyses between neurotransmitter ratios within each brain region and cumulated daylight and global radiation were performed. No seasonal or monthly differences, seasonal patterns, nor significant correlations could be shown in any region or ratio. Unit root and stationarity tests showed stable patterns of GABA+/tCr, GABA+/Glx, and Glx/tCr levels throughout the year, except for hippocampal Glx/tCr. Our results indicate that neurotransmitter levels of glutamate and GABA in healthy individuals are stable throughout the year. Hence, despite the important correction for age and gender in the analyses of MRS derived GABA and glutamate, a correction for seasonality in future studies does not seem necessary. Future investigations in SAD and other psychiatric patients will be of high interest.

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort.

Sex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals. Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, undergoing GHT, and 15 age-matched cisgender women (CW), receiving no therapy, underwent MRSI before and after at least 12 weeks. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (combination of GABA and macromolecules) and Glx (combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus). Linear mixed models analysis revealed a significant measurement by gender identity effect (pcorr. = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (pcorr. = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men. Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies. DATA AVAILABILITY STATEMENT: Due to data protection laws processed data is available from the authors upon reasonable request. Please contact rupert.lanzenberger@meduniwien.ac.at with any questions or requests.

Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm.

Impaired cognitive flexibility represents a widespread symptom in psychiatric disorders, including major depressive disorder (MDD), a disease, characterized by an imbalance of neurotransmitter concentrations. While memory formation is mostly associated with glutamate, also gamma-Aminobutyric acid (GABA) and serotonin show attributions in a complex interplay between neurotransmitter systems. Treatment with selective serotonin reuptake inhibitors (SSRIs) does not solely affect the serotonergic system but shows downstream effects on GABA- and glutamatergic neurotransmission, potentially helping to restore cognitive function via neuroplastic effects. Hence, this study aims to elaborate the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function within and between five brain regions using magnetic resonance spectroscopy imaging (MRSI). In this study, healthy subjects were randomized into four groups which underwent three weeks of an associative relearning paradigm, with or without emotional connotation, under SSRI (10mg escitalopram) or placebo administration. MRSI measurements, using a spiral-encoded, 3D-GABA-edited MEGA-LASER sequence at 3T, were performed on the first and last day of relearning. Mean GABA+/tCr (GABA+ = GABA + macromolecules; tCr = total creatine) and Glx/tCr (Glx = glutamate + glutamine) ratios were quantified in a ROI-based approach for the hippocampus, insula, putamen, pallidum and thalamus, using LCModel. A total of 66 subjects ((37 female, mean age ± SD = 25.4±4.7) for Glx/tCr and 58 subjects (32 female, mean age ± SD = 25.1±4.7) for GABA+/tCr were included in the final analysis. A significant measurement by region and treatment (SSRI vs placebo) interaction on Glx/tCr ratios was found (pcor=0.017), with post hoc tests confirming differential effects on hippocampus and thalamus (pcor=0.046). Moreover, treatment by time comparison, for each ROI independently, showed a reduction of hippocampal Glx/tCr ratios after SSRI treatment (puncor=0.033). No significant treatment effects on GABA+/tCr ratios or effects of relearning condition on any neurotransmitter ratio could be found. Here, we showed a significant SSRI- and relearning-driven interaction effect of hippocampal and thalamic Glx/tCr levels, suggesting differential behavior based on different serotonin transporter and receptor densities. Moreover, an indication for Glx/tCr adaptions in the hippocampus after three weeks of SSRI treatment could be revealed. Our findings are in line with animal studies reporting glutamate adaptions in the hippocampus following chronic SSRI intake. Due to the complex interplay of serotonin and hippocampal function, involving multiple serotonin receptor subtypes on glutamatergic cells and GABAergic interneurons, the interpretation of underlying neurobiological actions remains challenging.

(2 + 1)D-CAIPIRINHA accelerated MR spectroscopic imaging of the brain at 7T.

PURPOSE: To compare a new parallel imaging (PI) method for multislice proton magnetic resonance spectroscopic imaging (1 H-MRSI), termed (2 + 1)D-CAIPIRINHA, with two standard PI methods: 2D-GRAPPA and 2D-CAIPIRINHA at 7 Tesla (T). METHODS: (2 + 1)D-CAIPIRINHA is a combination of 2D-CAIPIRINHA and slice-CAIPIRINHA. Eight healthy volunteers were measured on a 7T MR scanner using a 32-channel head coil. The best undersampling patterns were estimated for all three PI methods. The artifact powers, g-factors, Cramér-Rao lower bounds (CRLB), and root mean square errors (RMSE) were compared quantitatively among the three PI methods. Metabolic maps and spectra were compared qualitatively. RESULTS: (2 + 1)D-CAIPIRINHA allows acceleration in three spatial dimensions in contrast to 2D-GRAPPA and 2D-CAIPIRINHA. Thus, this sequence significantly decreased the RMSE of the metabolic maps by 12.1 and 6.9%, on average, for 4 < R < 11, compared with 2D-GRAPPA and 2D-CAIPIRINHA, respectively. The artifact power was 22.6 and 8.4% lower, and the CRLB were 3.4 and 0.6% lower, respectively. CONCLUSION: (2 + 1)-CAIPIRINHA can be implemented for multislice MRSI in the brain, enabling higher accelerations than possible with two-dimensional (2D) parallel imaging methods. An eight-fold acceleration was still feasible in vivo with negligible PI artifacts with lipid decontamination, thus decreasing the measurement time from 120 to 15 min for a 64 × 64 × 4 matrix. Magn Reson Med 78:429-440, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Diffusion-weighted imaging of breast tumours at 3 Tesla and 7 Tesla: a comparison.

OBJECTIVES: To compare bilateral diffusion-weighted MR imaging (DWI) at 3 T and 7 T in the same breast tumour patients. METHODS: Twenty-eight patients were included in this IRB-approved study (mean age 56 ± 16 years). Before contrast-enhanced imaging, bilateral DWI with b = 0 and 850 s/mm(2) was performed in 2:56 min (3 T) and 3:48 min (7 T), using readout-segmented echo planar imaging (rs-EPI) with a 1.4 × 1.4 mm(2) (3 T)/0.9 × 0.9 mm(2) (7 T) in-plane resolution. Apparent diffusion coefficients (ADC), signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were assessed. RESULTS: Twenty-eight lesions were detected (18 malignant, 10 benign). CNR and SNR were comparable at both field strengths (p > 0.3). Mean ADC values at 7 T were 4-22% lower than at 3 T (p ≤ 0.03). An ADC threshold of 1.275 × 10(-3) mm(2)/s resulted in a diagnostic specificity of 90% at both field strengths. The sensitivity was 94% and 100% at 3 T and 7 T, respectively. CONCLUSION: 7-T DWI of the breast can be performed with 2.4-fold higher spatial resolution than 3 T, without significant differences in SNR if compared to 3 T. KEY POINTS: • 7 T provides a 2.4-fold higher resolution in breast DWI than 3 T • 7 T DWI has a high diagnostic accuracy comparable to that at 3 T • At 7 T malignant lesions had 22 % lower ADC than at 3 T (p < 0.001).

Clinical application of bilateral high temporal and spatial resolution dynamic contrast-enhanced magnetic resonance imaging of the breast at 7 T.

OBJECTIVE: The objective of our study was to evaluate the clinical application of bilateral high spatial and temporal resolution dynamic contrast-enhanced magnetic resonance imaging (HR DCE-MRI) of the breast at 7 T. METHODS: Following institutional review board approval 23 patients with a breast lesion (BIRADS 0, 4-5) were included in our prospective study. All patients underwent bilateral HR DCE-MRI of the breast at 7 T (spatial resolution of 0.7 mm(3) voxel size, temporal resolution of 14 s). Two experienced readers (r1, r2) and one less experienced reader (r3) independently assessed lesions according to BI-RADS®. Image quality, lesion conspicuity and artefacts were graded from 1 to 5. Sensitivity, specificity and diagnostic accuracy were assessed using histopathology as the standard of reference. RESULTS: HR DCE-MRI at 7 T revealed 29 lesions in 23 patients (sensitivity 100 % (19/19); specificity of 90 % (9/10)) resulting in a diagnostic accuracy of 96.6 % (28/29) with an AUC of 0.95. Overall image quality was excellent in the majority of cases (27/29) and examinations were not hampered by artefacts. There was excellent inter-reader agreement for diagnosis and image quality parameters (κ = 0.89-1). CONCLUSION: Bilateral HR DCE-MRI of the breast at 7 T is feasible with excellent image quality in clinical practice and allows accurate breast cancer diagnosis. KEY POINTS: • Dynamic contrast-enhanced 7-T MRI is being developed in several centres. • Bilateral high resolution DCE-MRI of the breast at 7 T is clinically applicable. • 7-T HR DCE-MRI of the breast provides excellent image quality. • 7-T HR DCE-MRI should detect breast cancer with high diagnostic accuracy.

Coil combination of multichannel MRSI data at 7 T: MUSICAL.

The goal of this study was to evaluate a new method of combining multi-channel (1)H MRSI data by direct use of a matching imaging scan as a reference, rather than computing sensitivity maps. Seven healthy volunteers were measured on a 7-T MR scanner using a head coil with a 32-channel array coil for receive-only and a volume coil for receive/transmit. The accuracy of prediction of the phase of the (1)H MRSI data with a fast imaging pre-scan was investigated with the volume coil. The array coil (1)H MRSI data were combined using matching imaging data as coil combination weights. The signal-to-noise ratio (SNR), spectral quality, metabolic map quality and Cramér-Rao lower bounds were then compared with the data obtained by two standard methods, i.e. using sensitivity maps and the first free induction decay (FID) data point. Additional noise decorrelation was performed to further optimize the SNR gain. The new combination method improved significantly the SNR (+29%), overall spectral quality and visual appearance of metabolic maps, and lowered the Cramér-Rao lower bounds (-34%), compared with the combination method based on the first FID data point. The results were similar to those obtained by the combination method using sensitivity maps, but the new method increased the SNR slightly (+1.7%), decreased the algorithm complexity, required no reference coil and pre-phased all spectra correctly prior to spectral processing. Noise decorrelation further increased the SNR by 13%. The proposed method is a fast, robust and simple way to improve the coil combination in (1)H MRSI of the human brain at 7 T, and could be extended to other (1)H MRSI techniques.

Combined contrast-enhanced magnetic resonance and diffusion-weighted imaging reading adapted to the "Breast Imaging Reporting and Data System" for multiparametric 3-T imaging of breast lesions.

OBJECTIVE: To develop and assess a combined reading for contrast-enhanced magnetic resonance (CE-MRI) and diffusion weighted imaging (DWI) adapted to the BI-RADS for multiparametric MRI of the breast at 3 T. METHODS: A total of 247 patients with histopathologically verified breast lesions were included in this IRB-approved prospective study. All patients underwent CE-MR and DWI at 3 T. MRIs were classified according to BI-RADS and assessed for apparent diffusion coefficient (ADC) values. A reading method that adapted ADC thresholds to the assigned BI-RADS classification was developed. Sensitivity, specificity, diagnostic accuracy and the area under the curve were calculated. BI-RADS-adapted reading was compared with previously published reading methods in the same population. Inter- and intra-reader variability was assessed. RESULTS: Sensitivity of BI-RADS-adapted reading was not different from the high sensitivity of CE-MRI (P = 0.4). BI-RADS-adapted reading maximised specificity (89.4 %), which was significantly higher compared with CE-MRI (P < 0.001). Previous reading methods did not perform as well as the BI-RADS method except for a logistic regression model. BI-RADS-adapted reading was more sensitive in non-mass-like enhancements (NMLE) and was more robust to inter- and intra-reader variability. CONCLUSION: Multiparametric 3-T MRI of the breast using a BI-RADS-adapted reading is fast, simple to use and significantly improves the diagnostic accuracy of breast MRI. KEYPOINTS : • Multiparametric breast 3-T MRI with BI-RADS-adapted reading improves diagnostic accuracy. • BI-RADS-adapted reading of CE-MRI and DWI is based on established reporting guidelines. • BI-RADS-adapted reading is fast and easy to use in routine clinical practice. • BI-RADS-adapted reading is robust to intra- and inter-reader variability.

Fully adiabatic 31P 2D-CSI with reduced chemical shift displacement error at 7 T--GOIA-1D-ISIS/2D-CSI.

A fully adiabatic phosphorus (31P) two-dimensional (2D) chemical shift spectroscopic imaging sequence with reduced chemical shift displacement error for 7 T, based on 1D-image-selected in vivo spectroscopy, combined with 2D-chemical shift spectroscopic imaging selection, was developed. Slice-selective excitation was achieved by a spatially selective broadband GOIA-W(16,4) inversion pulse with an interleaved subtraction scheme before nonselective adiabatic excitation, and followed by 2D phase encoding. The use of GOIA-W(16,4) pulses (bandwidth 4.3-21.6 kHz for 10-50 mm slices) reduced the chemical shift displacement error in the slice direction ∼1.5-7.7 fold, compared to conventional 2D-chemical shift spectroscopic imaging with Sinc3 selective pulses (2.8 kHz). This reduction was experimentally demonstrated with measurements of an MR spectroscopy localization phantom and with experimental evaluation of pulse profiles. In vivo experiments in clinically acceptable measurement times were demonstrated in the calf muscle (nominal voxel volume, 5.65 ml in 6 min 53 s), brain (10 ml, 6 min 32 s), and liver (8.33 ml, 8 min 14 s) of healthy volunteers at 7 T. High reproducibility was found in the calf muscle at 7 T. In combination with adiabatic excitation, this sequence is insensitive to the B1 inhomogeneities associated with surface coils. This sequence, which is termed GOIA-1D-ISIS/2D-CSI (goISICS), has the potential to be applied in both clinical research and in the clinical routine.

Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

OBJECTIVE: To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. METHODS: Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. RESULTS: Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). CONCLUSIONS: Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy.

High resolution MRI of the breast at 3 T: which BI-RADS® descriptors are most strongly associated with the diagnosis of breast cancer?

OBJECTIVE: To identify which breast lesion descriptors in the ACR BI-RADS® MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T. METHODS: 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS® classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS® descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference. RESULTS: The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p < 0.001), irregular margin (p < 0.001), heterogeneous enhancement (p < 0.001), Type 3 enhancement kinetics (p = 0.02), increasing patient age (p = 0.02) and larger lesion size (p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape (p = 0.06), mass margin (p < 0.001), internal enhancement pattern (p = 0.03) and Type 3 enhancement kinetics (p = 0.06). CONCLUSION: The ACR BI-RADS® breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics. KEY POINTS: • 3 Tesla breast MRI allows an accurate diagnosis of breast cancer • The BI-RADS® descriptors help provide a confident diagnosis • The shape, margin, enhancement pattern and kinetics are the most important features • An irregular shape and margin, heterogeneous enhancement and type-3 kinetics indicate malignancy.

Molecular imaging of cancer: MR spectroscopy and beyond.

Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.

High-resolution mapping of human brain metabolites by free induction decay (1)H MRSI at 7 T.

This work describes a new approach for high-spatial-resolution (1)H MRSI of the human brain at 7 T. (1)H MRSI at 7 T using conventional approaches, such as point-resolved spectroscopy and stimulated echo acquisition mode with volume head coils, is limited by technical difficulties, including chemical shift displacement errors, B(0)/B(1) inhomogeneities, a high specific absorption rate and decreased T(2) relaxation times. The method presented here is based on free induction decay acquisition with an ultrashort acquisition delay (TE*) of 1.3 ms. This allows full signal detection with negligible T(2) decay or J-modulation. Chemical shift displacement errors were reduced to below 5% per part per million in the in-slice direction and were eliminated in-plane. The B(1) sensitivity was reduced significantly and further corrected using flip angle maps. Specific absorption rate requirements were well below the limit (~20 % = 0.7 W/kg). The suppression of subcutaneous lipid signals was achieved by substantially improving the point-spread function. High-quality metabolic mapping of five important brain metabolites was achieved with high in-plane resolution (64 × 64 matrix with a 3.4 × 3.4 × 12 mm(3) nominal voxel size) in four healthy subjects. The ultrashort TE* increased the signal-to-noise ratio of J-coupled resonances, such as glutamate and myo-inositol, several-fold to enable the mapping of even these metabolites with high resolution. Four measurement repetitions in one healthy volunteer provided proof of the good reproducibility of this method. The high spatial resolution allowed the visualization of several anatomical structures on metabolic maps. Free induction decay MRSI is insensitive to T(2) decay, J-modulation, B(1) inhomogeneities and chemical shift displacement errors, and overcomes specific absorption rate restrictions at ultrahigh magnetic fields. This makes it a promising method for high-resolution (1)H MRSI at 7 T and above.

In vivo 31P spectroscopy by fully adiabatic extended image selected in vivo spectroscopy: a comparison between 3 T and 7 T.

An improved image selected in vivo spectroscopy (ISIS) sequence for localized (31)P magnetic resonance spectroscopy at 7 T was developed. To reduce errors in localization accuracy, adiabatic excitation, gradient offset independent adiabatic inversion pulses, and a special extended ISIS ordering scheme were used. The localization accuracy of extended ISIS was investigated in phantoms. The possible spectral quality and reproducibility in vivo was explored in a volunteer (brain, muscle, and liver). A comparison between 3 T and 7 T was performed in five volunteers. Adiabatic extended ISIS provided high spectral quality and accurate localization. The contamination in phantom experiments was only ∼5%, even if a pulse repetition time ∼ 1.2·T(1) was chosen to maximize the signal-to-noise ratio per unit time. High reproducibility was found in the calf muscle for 2.5 cm isotropic voxels at 7 T. When compared with 3 T, localized (31)P magnetic resonance spectroscopy in the human calf muscle at 7 T provided ∼3.2 times higher signal-to-noise ratio (as judged from phosphocreatine peak amplitude in frequency domain after matched filtering). At 7 T, extended ISIS allowed the performance of high-quality localized (31)P magnetic resonance spectroscopy in a short measurement time (∼3 to 4 min) and isotropic voxel sizes of ∼2.5 to 3 cm. With such short measurement times, localized (31)P magnetic resonance spectroscopy has the potential to be applied not only for clinical research but also for routine clinical practice.

Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease.

OBJECTIVE: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. METHODS: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. RESULTS: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). CONCLUSIONS: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

[Functional and molecular imaging of breast tumors]. / Funktionelle und molekulare Bildgebung bei Brusttumoren.

Molecular imaging is concerned with the presentation, description and quantification of biological and physiological processes at the cellular and molecular level. Most recently molecular imaging has started to become established in breast diagnostics. This review article will give an overview of procedures which are either in the preclinical development stage or which have already become clinically established. Molecular nuclear medicine breast imaging (breast-specific gamma imaging [BSGI] and positron emission mammography [PEM]) together with specific radiotracers and contrast media will be discussed. The possibilities for magnetic resonance imaging in functional (DWI) and metabolic (MRSI) imaging of breast lesions and the combined application of nuclear medicine and magnetic resonance imaging (PET/MRI) will be explained. Furthermore, an overview on the preclinical procedure and the possible clinical applications of optical and photoacoustic imaging will be given.

In vivo quantification of intracerebral GABA by single-voxel (1)H-MRS-How reproducible are the results?

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H(2)O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H(2)O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H(2)O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr approximately 10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

Assessment of (31)P relaxation times in the human calf muscle: a comparison between 3 T and 7 T in vivo.

Phosphorus ((31)P) T(1) and T(2) relaxation times in the resting human calf muscle were assessed by interleaved, surface coil localized inversion recovery and frequency-selective spin-echo at 3 and 7 T. The obtained T(1) (mean +/- SD) decreased significantly (P < 0.05) from 3 to 7 T for phosphomonoesters (PME) (8.1 +/- 1.7 s to 3.1 +/- 0.9 s), phosphodiesters (PDE) (8.6 +/- 1.2 s to 6.0 +/- 1.1 s), phosphocreatine (PCr) (6.7 +/- 0.4 s to 4.0 +/- 0.2 s), gamma-NTP (nucleotide triphosphate) (5.5 +/- 0.4 s to 3.3 +/- 0.2 s), alpha-NTP (3.4 +/- 0.3 s to 1.8 +/- 0.1 s), and beta-NTP (3.9 +/- 0.4 s to 1.8 +/- 0.1 s), but not for inorganic phosphate (Pi) (6.9 +/- 0.6 s to 6.3 +/- 1.0 s). The decrease in T(2) was significant for Pi (153 +/- 9 ms to 109 +/- 17 ms), PDE (414 +/- 128 ms to 314 +/- 35 ms), PCr (354 +/- 16 ms to 217 +/- 14 ms), and gamma-NTP (61.9 +/- 8.6 ms to 29.0 +/- 3.3 ms). This decrease in T(1) with increasing field strength of up to 62% can be explained by the increasing influence of chemical shift anisotropy on relaxation mechanisms and may allow shorter measurements at higher field strengths or up to 62% additional signal-to-noise ratio (SNR) per unit time. The fully relaxed SNR increased by +96%, while the linewidth increased from 6.5 +/- 1.2 Hz to 11.2 +/- 1.9 Hz or +72%. At 7 T (31)P-MRS in the human calf muscle offers more than twice as much SNR per unit time in reduced measurement time compared to 3 T. This will facilitate in vivo (31)P-MRS of the human muscle at 7 T.

The transmembrane arrangement of the ADP/ATP carrier as elucidated by the lysine reagent pyridoxal 5-phosphate.

The lysine reagent pyridoxal 5-phosphate was applied to the ADP/ATP carrier (AAC) in order to elucidate topological and functional properties of the numerous lysines within the primary structure. To establish appropriate labeling conditions, the influence of pyridoxal-P on transport and inhibitor binding to the AAC was examined. The ADP/ATP transport is sensitive to low concentrations of pyridoxal-P with a Ki = 0.4 mM. Binding of [3H]carboxyatracylate and [3H]bongkrekate is largely inhibited by pyridoxal-P treatment with Ki approximately 1 mM. [3H]Carboxyatractylate is not and [3H]bongkrekate weakly removed by pyridoxal-P, whereas [3H]atractylate is displaced to a large extent. Under optimized conditions of pyridoxal-P concentration, of pH and of time exposure, the AAC was exposed to [3H]pyridoxal-P in mitochondria, in submitochondrial particles and in the detergent-solubilized carrier. The [3H]pyridoxal-P-labeled AAC was isolated from mitochondria and particles. After citraconylation thermolysinolytic peptides were prepared. The pyridoxyl-lysine-containing peptides were purified and the pyridoxal-P incorporation to specific lysines was determined by sequencing. The pyridoxal-P incorporation into the AAC in various states was evaluated with regard to structural and functional aspects. First, by comparing pyridoxal-P incorporation in mitochondria and sonic particles, the segments of the polypeptide chain exposed to the cytosolic and matrix side of the membrane are detected. Second, the additional lysine incorporation into the isolated as compared to the membrane-bound carrier is attributed to the protein collar facing the phospholipid headgroups. Third, the difference between lysine incorporation into the carboxyatractylate-AAC and bongkrekate-AAC complexes reflect either conformational changes or lysines involved in the translocation channel through the protein. Fourth, the additional lysine labeled in the atractylate-carrier complex as compared to the carboxyatractylate-carrier complex is attributed to a cationic site in the binding center. These results are incorporated into a transmembrane folding model of the carrier.