In vivo observation of quadrupolar splitting in (39)K magnetic resonance spectroscopy of human muscle tissue.

The purpose of this work was to explore the origin of oscillations of the T(*)2 decay curve of (39)K observed in studies of (39)K magnetic resonance imaging of the human thigh. In addition to their magnetic dipole moment, spin-3/2 nuclei possess an electric quadrupole moment. Its interaction with non-vanishing electrical field gradients leads to oscillations in the free induction decay and to splitting of the resonance. All measurements were performed on a 7T whole-body MRI scanner (MAGNETOM 7T, Siemens AG, Erlangen, Germany) with customer-built coils. According to the theory of quadrupolar splitting, a model with three Lorentzian-shaped peaks is appropriate for (39)K NMR spectra of the thigh and calf. The frequency shifts of the satellites depend on the angle between the calf and the static magnetic field. When the leg is oriented parallel to the static magnetic field, the satellites are shifted by about 200 Hz. In the thigh, rank-2 double quantum coherences arising from anisotropic quadrupolar interaction are observed by double-quantum filtration with magic-angle excitation. In addition to the spectra, an image of the thigh with a nominal resolution of (16 × 16 × 32) mm(3) was acquired with this filtering technique in 1:17 h. From the line width of the resonances, (39)K transverse relaxation time constants T(*)2, fast = (0.51 ± 0.01) ms and T(*)2, slow = (6.21 ± 0.05) ms for the head were determined. In the thigh, the left and right satellite, both corresponding to the short component of the transverse relaxation time constant, take the following values: T(*)2, fast = (1.56 ± 0.03) ms and T(*)2, fast = (1.42 ± 0.03) ms. The centre line, which corresponds to the slow component, is T(*)2, slow = (9.67 ± 0.04) ms. The acquisition time of the spectra was approximately 10 min. Our results agree well with a non-vanishing electrical field gradient interacting with (39)K nuclei in the intracellular space of muscle tissue.

VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.

Transport of material within cells is mediated by trafficking vesicles that bud from one cellular compartment and fuse with another. Formation of a trafficking vesicle is driven by membrane coats that localize cargo and polymerize into cages to bend the membrane. Although extensive structural information is available for components of these coats, the heterogeneity of trafficking vesicles has prevented an understanding of how complete membrane coats assemble on the membrane. We combined cryo-electron tomography, subtomogram averaging, and cross-linking mass spectrometry to derive a complete model of the assembled coat protein complex I (COPI) coat involved in traffic between the Golgi and the endoplasmic reticulum. The highly interconnected COPI coat structure contradicted the current "adaptor-and-cage" understanding of coated vesicle formation.

A new contrast in MR mammography by means of chemical exchange saturation transfer (CEST) imaging at 3 Tesla: preliminary results.

PURPOSE: To evaluate the feasibility to detect and delineate malignant breast lesions in human patients by chemical exchange saturation transfer (CEST) as an MR imaging technique without the need for contrast agent administration. MATERIALS AND METHODS: Six female patients referred for pre-surgical staging due to histologically confirmed breast cancer were examined with MR at 3 T. The routine breast protocol included T (2w), STIR, T (1w)-DCE and contrast-enhanced T (1w) imaging with SPAIR fat suppression. For CEST imaging, a 3D RF-spoiled gradient echo (GRE) sequence with an optimized saturation pulse train was applied. To assess the diagnostic value of the technique, CEST effects observed between frequency offsets of 1.2 to 1.8 ppm from the bulk water resonance were compared to pharmacokinetic parameter maps (k (ep)) obtained by DCE-MRI. RESULTS: In 3 of 6 patients, regions with high CEST signal intensity correlated well with tumor areas as determined by DCE-MRI. Analysis of signal intensities from ROIs in tumor, fibroglandular, adipose, and muscle tissue revealed significantly higher CEST values in tumor tissue compared to fibroglandular tissue. The detection of lesions was equally well possible with DCE-MRI and CEST-MRI. In the three other patients, the tumor regions could not be delineated based on the CEST image due to artifacts, which were most likely caused by a high content of fat tissue within the ROIs. CONCLUSION: The results of this initial feasibility study indicate a significant potential of CEST-MRI to discriminate cancer from fibroglandular tissue in the human breast by a CEST contrast generated by endogenous solute molecules.

Whole-brain N-acetylaspartate MR spectroscopic quantification: performance comparison of metabolite versus lipid nulling.

BACKGROUND AND PURPOSE: Despite the prominent peak of N-acetylaspartate (NAA) in proton MR spectroscopy ((1)H-MR spectroscopy) of the adult brain and its almost exclusive presence in neuronal cells, the total amount of NAA, regarded as their marker, is difficult to obtain due to signal contamination from the skull lipids. This article compares the performance of 2 methods that overcome this difficulty to yield the whole-brain NAA signal, important for the assessment of the total disease load in diffuse neurologic disorders. MATERIALS AND METHODS: The heads of 12 healthy volunteers, 3 women and 9 men, 31.0 +/- 7.1 years of age, were scanned at 3T by using 2 nonlocalizing (1)H-MR spectroscopy sequences: One nulls the NAA (TI = 940 ms) every second acquisition by inversion-recovery to cancel the signals of the lipids (T1 << TI) in an add-subtract scheme. The other nulls the signal of the lipids (TI = 155 ms) directly after each acquisition, requiring half as many averages for the same signal-to-noise ratio. Each sequence was repeated 3 times back-to-back on 3 occasions, and the comparison criteria were intrasubject precision (reproducibility) and total measurement duration. RESULTS: NAA nulling is nearly twice as precise in its intrinsic back-to-back (5.8% versus 8.6%) as well as longitudinal (10.6% versus 19.7%) coefficients of variation compared with lipid nulling, but at the cost of double the acquisition time. CONCLUSION: When speed is a more stringent requirement than precision, the new lipid-nulling sequence is a viable alternative. For precision in cross-sectional or longitudinal global NAA quantification, however, NAA nulling is still the approach of choice despite its x2 ( approximately 5 minutes) time penalty compared with the lipid-nulling approach.

31P-{1H} echo-planar spectroscopic imaging of the human brain in vivo.

Echo-planar spectroscopic imaging (EPSI) is one of the fastest spectroscopic imaging (SI) methods. It has been applied to (1)H MR spectroscopy (MRS) studies of the human brain in vivo. However, to our knowledge, EPSI with detection of the (31)P nucleus to monitor phosphorus-containing neurometabolites has not yet been considered. In this work, eight different (31)P-{(1)H} EPSI sequence versions with spectral widths ranging from 313 Hz to 2.27 kHz were implemented on a clinical 1.5T whole-body MR tomograph. The sequence versions utilized the heteronuclear nuclear Overhauser effect (NOE) for (31)P signal enhancement. The sensitivity observed in experiments with model solutions was in good agreement with theoretical predictions. In vivo measurements performed on healthy volunteers (N = 16) demonstrated the feasibility of performing two-dimensional (2D) (31)P-{(1)H} EPSI in the human brain, and the technique enabled fast acquisition of well-resolved localized spectra.

Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency.

Prospective observation in a neonate with guanidinoacetate methyltransferase deficiency (GAMT-D), a severe neurometabolic disorder, revealed increased guanidinoacetate levels at birth. After 14-month treatment with creatine, high-dose ornithine, benzoate, and an arginine-restricted diet, the patient's development is normal and she does not present any symptoms of GAMT-D. The authors' observation indicates that early detection of GAMT-D is possible in the neonatal period, and presymptomatic treatment may prevent its manifestation.

[Application of (1)H MR spectroscopic imaging in radiation oncology: choline as a marker for determining the relative probability of tumor progression after radiation of glial brain tumors]. / Einsatz der (1)H-MR-spektroskopischen Bildgebung in der Strahlentherapie: Cholin als Marker für die Bestimmung der relativen Wahrscheinlichkeit eines Tumorprogresses nach Bestrahlung glialer Hirntumoren.

PURPOSE: To determine the relative signal intensity ratios of choline (Cho), phosphocreatine (CR) and N-acetyl-aspartate (NAA) in MR spectroscopic imaging (proton-MRSI) for differentiating progressive tumors (PT) from non-progressive tumors (nPT) in follow-up and treatment planning of gliomas. Threshold values to indicate the probability of a progressive tumor were also calculated. MATERIAL AND METHODS: Thirty-four patients with histologically proven gliomas showing a suspicious brain lesion in MRI after stereotactic radiotherapy were evaluated on a 1.5 Tesla unit (Magnetom Vision, Siemens, Erlangen, Germany) using 2D proton MRSI (repetition time/echo time = 1500/135 msec, PRESS; voxel size 9 x 9 x 15 mm (3)). A total of 274 spectra were analyzed (92 voxel were localized within the suspicious brain lesion). Relative signal intensities Cho, Cr and NAA were measured and their ability to discern between PT and nPT was assessed using the linear discrimination method, logistic regression, and the cross-validation method. PT and nPT were differentiated between on the basis of clinical course and follow-up by MRI, CT and positron emission tomography. RESULTS: The Cho parameter and the relative signal intensity ratios of Cr and NAA were most effective in differentiating between PT and nPT. The logistic regression method using the parameter ln(Cho/Cr) and ln(Cho/NAA) had the best predictive results in cross-validation. A sensitivity of 93.8 % and specificity of 85.7 % were achieved in the differentiation of PT from nPT by proton-MRSI. CONCLUSION: (1)H-MRSI has a high sensitivity and specificity for differentiating between therapy-related effects and the relapse of irradiated gliomas. This method allows for assessment of the probability of radiotherapy response or failure.

Optimal classification of long echo time in vivo magnetic resonance spectra in the detection of recurrent brain tumors.

We describe the optimal high-level postprocessing of single-voxel (1)H magnetic resonance spectra and assess the benefits and limitations of automated methods as diagnostic aids in the detection of recurrent brain tumor. In a previous clinical study, 90 long-echo-time single-voxel spectra were obtained from 52 patients and classified during follow-up (30/28/32 normal/non-progressive tumor/tumor). Based on these data, a large number of evaluation strategies, including both standard resonance line quantification and algorithms from pattern recognition and machine learning, were compared in a quantitative evaluation. Results from linear and non-linear feature extraction, including ICA, PCA and wavelet transformations, and also the data from resonance line quantification were combined systematically with different classifiers such as LDA, chemometric methods (PLS, PCR), support vector machines and ensemble methods. Classification accuracy was assessed using a leave-one-out cross-validation scheme and the area under the curve (AUC) of the receiver operator characteristic (ROC). A regularized linear regression on spectra with binned channels reached 91% classification accuracy compared with 83% from quantification. Interpreting the loadings of these regressions, we find that lipid and lactate signals are too unreliable to be used in a simple machine rule. Choline and NAA are the main source of relevant information. Overall, we find that fully automated pattern recognition algorithms perform as well as, or slightly better than, a manually controlled and optimized resonance line quantification.

[Metabolic imaging to follow stereotactic radiation of gliomas -- the role of 1H MR spectroscopy in comparison to FDG-PET and IMT-SPECT]. / Metabolische Bildgebung zur Verlaufskontrolle stereotaktisch bestrahlter Gliome -- Wertigkeit der 1H-MR-Spektroskopie im Vergleich zur FDG-PET und IMT-Spect.

PURPOSE: To evaluate the clinical value of 1H MR spectroscopy (1H MRSI) for follow-up of irradiated glioma compared to positron emission tomography (PET) with [18F]-2-fluoro-deoxy-D-glucose (FDG-PET) and single photon emission tomography with [123I]-a-methyl-L-tyrosine (IMT-SPECT). MATERIALS AND METHODS: Twenty-four patients with irradiated gliomas were examined using 1H MRSI (2D spectroscopic imaging; PRESS; TE = 135 msec; 1.5T Magnetom Vision, Siemens; Voxel size 9 x 9 x 15 mm (3)). MR spectra (n = 233) were evaluated in areas suspicious of tumor (n = 86) as well as in healthy appearing brain tissue (n = 147). Relative signal intensity ratios of choline (Cho), creatine (Cr) and N-acetyl-aspartate (NAA) were calculated. PET scans (n = 19) were performed with 200 - 250 MBq FDG, IMT-SPECT examinations (n = 14) with 200 - 250 mBq IMT. Based on clinical and MRI/CT, follow-up lesions were classified as either neoplastic [PT] or non-neoplastic [nPT]. RESULTS: True positive results for the diagnosis of PT/nPT were 88/89 % (1H MRSI), 73/100 % (PET) and 100/75 % (SPECT). Cho/Cr showed highly significant changes for PT. Determinating a correlation between Cho, Cr, NAA and IMT-SPECT as well as FDG-PET was not possible because of different location of maximum tracer uptake and acquired 2D 1H MRSI. CONCLUSION: IMT-SPECT seems to be superior to detect tumor progression in irradiated gliomas. 1H MRSI was more suitable than FDG-PET to differentiate between recurrence and radiation-induced changes. FDG-PET plays a role as sensitive method for detecting high-grade tumors. PET and SPECT allowed the examination of the entire tumor including surrounding brain tissue with higher spatial resolution than the acquired 2D 1H MRSI. A main limitation of our study was that only 2D 1H MRSI was used, with only parts of the tumor evaluated. The use of 3D MR spectroscopic imaging may further increase the diagnostic accuracy.

[Magnetic resonance spectroscopy. Part 2: Application in diagnosis and clinical research]. / Magnetresonanzspektoskopie. Teil 2: Anwendung in Diagnostik und klinischer Forschung.

MR spectroscopy creates a noninvasive window into the metabolism of normal and diseased tissue in vivo. The physics and the measurement techniques being described in part I, this contribution presents the potential use of MRS in patient healthcare and clinical research. We discuss applications of MRS to neurooncology, to oncology outside the central nervous system and to nononcological diseases.

Monitoring individual response to brain-tumour chemotherapy: proton MR spectroscopy in a patient with recurrent glioma after stereotactic radiotherapy.

Since antineoplastic activity varies, sensitive methods for individual assessment of efficacy are needed. We demonstrate the clinical value of MR spectroscopy in monitoring chemotherapy in a patient with recurrent glioma after stereotactic radiotherapy. Diagnostic imaging before and after chemotherapy included contrast-enhanced MRI, single-voxel proton MR spectroscopy ((1)H MRS), (1)H MR spectroscopic imaging ((1)H SI), and fluorodeoxyglucose (FDG) positron-emission tomography (PET). A significant decrease in choline signal intensity was observed 2 months after chemotherapy indicating tumour chemosensitivity, in line with tumour shrinkage on MRI and decreased uptake of FDG. Assessment of early response by MRS may help to improve treatment protocols in other patients.

Signal enhancement through heteronuclear polarisation transfer in in-vivo 31P MR spectroscopy of the human brain.

Significant (31)P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the (31)P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from (1)H to (31)P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the (31)P NMR signal of metabolites with scalar (1)H-(31)P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of eta=(29+/-3)% for methylene diphosphonic acid (MDPA) and eta=(56+/-1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo (31)P signal enhancement of the same order was obtained in studies of the human brain.

[Monitoring of irradiated brain metastases using MR perfusion imaging and 1H MR spectroscopy]. / Verlaufsbeobachtung bestrahlter Hirnmetastasen mittels MR-Perfusionsbildgebung und 1H-MR-Spektroskopie.

PURPOSE: In follow-up examinations of irradiated brain metastases conventional contrast-enhanced morphological MR imaging is often unable to distinguish between transient radiation effects, radionecrosis,and tumor recurrence. To evaluate changes of relative cerebral blood flow (rCBF) in irradiated brain metastases arterial spin-labeling techniques (ASL) were applied and compared to the outcome of (1)H MR spectroscopy and spectroscopic imaging ((1)H MRS, SI). PATIENTS AND METHODS: In 2 patients follow-up examinations of irradiated brain metastases were performed on a 1.5-T tomograph (average single dose: 20 Gy/80% isodose). Relative CBF values of gray matter (GM), white matter (WM),and metastases (Met) were measured by means of the ASL techniques ITS-FAIR and Q2TIPS. (1)H MRS was performed with PRESS 1500/135. RESULTS: In both patients with initially hyperperfused metastases (Met/GM >1) the reduction of rCBF after stereotactic radiosurgery indicated response to treatment--even if the contrast-enhancing region increased--while increasing rCBF values indicated tumor progression. The findings were confirmed by (1)H MRS, SI and subsequent follow-up. CONCLUSION: The ASL techniques ITS-FAIR and Q2TIPS are able to monitor changes of rCBF in irradiated brain metastases. The two cases imply a possible role for ASL-MR perfusion imaging and (1)H MR spectroscopy in differentiating radiation effects from tumor progression.

[Magnetic resonance imaging spectroscopy. Part 1: Basics]. / Magnetresonanzspektroskopie. Teil 1: Grundlagen.

A century after the discovery of X-rays, the low-energy range of the electromagnetic spectrum also attained broad application in radiology. Radiofrequency waves allow excitation in a magnetic field of the magnetic resonance of spin-bearing nuclei in tissue. Using the intense signal of the water protons, morphological images of the human body can be obtained, while at a higher frequency resolution also endogenous metabolites as well as pharmaceuticals, which contain MR-visible nuclei (e.g., 1H, 13C, 19F, 31P), can be detected noninvasively and in vivo. Accordingly, in vivo MR spectroscopy is a technique which is sensitive to molecules and molecular properties and which can be applied to repeated examinations. Its major limitation is the low signal intensity vs noise, which implies long measurement times and poor spatial resolution. Using spectroscopic imaging, the distribution of metabolites within an organ can be monitored selectively and displayed as a molecular image.

A fully automated method for tissue segmentation and CSF-correction of proton MRSI metabolites corroborates abnormal hippocampal NAA in schizophrenia.

In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients.

Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy.

We report on a young woman who was treated by stereotactic radiotherapy for recurrence of an initially resected low-grade astrocytoma. MRI follow-up examination 7 months after radiotherapy showed a gadolinium-DTPA-enhancing mass lesion indicative of high-grade tumor progression. This assumption was also supported by positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose (FDG-PET). In contrast, proton MR spectroscopy (1H-MRS) indicated radiation necrosis, which was confirmed histopathologically in surgical specimens. Subsequent follow-up examinations up to 19 months after surgery showed no evidence of tumor recurrence.

Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy.

BACKGROUND AND PURPOSE: The radiologic assessment of suspicious brain lesions after stereotactic radiotherapy of brain tumors is difficult. The purpose of our study was to define parameters from single-voxel proton MR spectroscopy that provide a probability measure for differentiating neoplastic from radiation-induced, nonneoplastic lesions. METHODS: Seventy-two lesions in 56 patients were examined using a combined MR imaging and MR spectroscopy protocol (point-resolved spectroscopy, TE = 135 ms). Signal intensities of cholines, creatines, N-acetyl aspartate, and the presence of lactate and lipid resonances were correlated to final diagnoses established by clinical and MR imaging follow-up, positron emission tomography studies, or biopsy/surgery. Statistical analysis was performed using the t test, linear discriminant analysis, and k nearest-neighbor method. RESULTS: Significantly increased signal intensity ratios I(tCho)/I(tCr) (P <.0001) and I(tCho)/I(NAA) (P <.0001) were observed in neoplastic (n = 34) compared with nonneoplastic lesions (n = 32) and contralateral normal brain (n = 33). Analysis of I(tCho)/I(tCr) and I(tCho)/I(NAA) data yielded correct retrospective classification as neoplastic and nonneoplastic in 82% and 81% of the lesions, respectively. Neither I(NAA)/I(tCr) nor signal intensitities of lactate or lipids were useful for differential diagnosis. CONCLUSION: Metabolic information provided by proton MR spectroscopy is useful for the differentiation of neoplastic and nonneoplastic brain lesions after stereotactic radiotherapy of brain tumors.