Clinical 1H magnetic resonance spectroscopy of brain metastases at 1.5T and 3T.

PURPOSE: To investigate whether improvements in signal-to-noise ratio (SNR) and spectral resolution are found in spectra from patients with brain metastases obtained at higher magnetic field strengths using standard clinical instrumentation. MATERIAL AND METHODS: Six patients with brain metastases, 13 healthy volunteers, and a phantom containing brain metabolites were examined using two clinical MR instruments operating at 1.5T (Siemens) and 3T (Philips) with standard clinical head coils. Spectra were obtained using a point resolved spectroscopy pulse sequence, echo times (TE) 32 ms and 144 ms, and repetition time 2000 ms from a volume-of-interest (VOI) of size 15 x 15 x 15 mm3. SNR and spectral resolution of the metabolites N-acetylaspartate, choline, and creatine compounds in spectra from 3T were compared to the 1.5T spectra. RESULTS: In general, spectral resolution was improved by 25-30% at higher magnetic field strength. Only minor improvements in SNR were obtained at 3T using short echo time and 20-50% at long echo time. CONCLUSION: SNR and spectral resolution were improved at higher magnetic field strength, especially with TE 144 ms, including spectra from patients with heterogeneous brain tumors. However, differences in the defined effective VOI, particularly at short echo time, reduced the expected effect of increased magnetic field strength on the measured SNR.

External standard method for the in vivo quantification of choline-containing compounds in breast tumors by proton MR spectroscopy at 1.5 Tesla.

Quantification of choline-containing compounds observed with (1)H MRS of breast tumors is of interest since such compounds have been linked to malignancy. Experiments were performed at 1.5 T with an external standard containing phosphocholine for calibration. In phantom studies, good precision was achieved after correction for T(1)/T(2) effects. T(2) values for choline were estimated for two breast cancer patients. A choline concentration of 2.0 mM was calculated for a third patient, a result comparable to in vitro findings. Magn Reson Med 46:189-192, 2001.

Classification of in vivo 1H MR spectra from breast tissue using artificial neural networks.

BACKGROUND: The study was designed in order to investigate whether artificial neural networks could be used for analysis of in vivo magnetic resonance (MR) spectra from breast cancer patients. MATERIALS AND METHODS: In vivo 1H MR spectra with three different echo times (TE 135, 350 and 450 msec) were acquired from patients with benign and malignant breast lesions and from healthy volunteers, of whom some were breast-feeding. A spectral region (4.0-1.5 ppm) was used as input for artificial neural network analysis, for the attempted classification of the data into different groups. RESULTS: Data recorded at all three echo times were necessary to obtain the best results. Furthermore, malignant tissue was differentiated from benign tumours using this approach, whereas benign tumours were poorly separated from healthy tissue. CONCLUSION: The results presented here indicate that in vivo MR spectroscopy in conjunction with neural network analysis might be useful for the evaluation of breast lesions.

[Diagnosis of breast diseases with magnetic resonance tomography]. / Brystdiagnostikk med magnetisk resonanstomografi.

Magnetic resonance imaging (MRI) of the breast is currently used for evaluation of both parenchymal disease and silicone gel implants. MRI is widely recognised as the most accurate imaging method for evaluation of breast implant integrity. Knowledge of the MRI appearance of the different types of implants and the possible complications of their use is important for diagnosis in these patients. The use of contrast-enhanced MRI in breast cancer diagnosis has been investigated thoroughly during the last decade. It is a sensitive imaging method to detect breast pathology, and may have an important diagnostic impact in carefully selected patient groups. The development of new MR techniques may improve the utility of MR in breast cancer diagnosis, treatment and research.

Metabolite composition in breast tumors examined by proton nuclear magnetic resonance spectroscopy.

BACKGROUND: In vivo characterisation of breast tumors using protein (1H) MR spectroscopy relies upon in vitro interpretation of tissue samples. The present study has investigated metabolite composition in extracts from breast tumors and non-involved breast tissue. Multivariate data analysis was used to determinate combinations of metabolites important for differentiation. MATERIALS AND METHODS: Tumor and non-involved breast tissue were obtained from 16 patients undergoing surgical treatment. 1H NMR spectra of perchloric acid tissue extracts were obtained at a BRUKER Avance DRX600 spectrometer. The data was analysed using principal component analysis and probabilistic neural networks. RESULTS: Low levels of glucose and high content of choline compounds were dominant findings in the tumor spectra. Principal component loadings demonstrated this strong association. The spectra were correctly classified using neural network analysis. CONCLUSIONS: Large differences in the metabolite composition of breast tumors and surrounding breast tissues have been documented.

Characterization of neoplastic and normal human breast tissues with in vivo (1)H MR spectroscopy.

The purpose of this study was to evaluate whether the detection of choline-containing compounds in in vivo (1)H magnetic resonance spectroscopy (MRS) of breast lesions is specific for carcinomas, whether a choline peak in in vivo (1)H MRS can be detected under physiological conditions of increased metabolism in breast parenchyma, and whether analysis of lipid signals can differentiate between various breast lesions and tissues. Forty patients and volunteers were examined with in vivo (1)H MR spectroscopy. Three spectra with identical localization but increasing echo times were obtained. Choline-containing compounds were detected in 9 of 11 carcinomas and in 2 of 11 benign lesions. A choline signal was also detected in five of seven volunteers who were breast-feeding at the time of examination, demonstrating that choline compounds can be detected by in vivo (1)H MRS in breast tissue under physiological conditions. Analysis of lipid signals did not contribute to differentiation between various breast lesions and tissues. J. Magn. Reson. Imaging 1999;10:159-164.

Applications of neural network analyses to in vivo 1H magnetic resonance spectroscopy of epilepsy patients.

A total of 67 in vivo water-suppressed proton magnetic resonance spectra of the temporal lobes were recorded from 15 patients with long standing temporal lobe epilepsy and 13 healthy volunteers. Conventional data analysis indicated slightly lower N-acetyl aspartate levels in epileptic patients compared with controls. For further analysis of data, a spectral region (4.0-1.5 ppm) was used as input for artificial neural network analysis. Correct classification of spectra was obtained in 66 out of 67 cases, disregarding from which side of the brain the spectra were recorded. The ability of the trained network to recognize spectra recorded both contalaterally and ipsilaterally to the epileptic focus strongly indicates bilateral metabolic changes. Artificial neural networks could also be trained to recognize whether the spectra were recorded from the ipsilateral or contralateral side of the epileptic focus, indicating that neural network analysis of in vivo proton MR spectra can be used as an additional tool for pre-surgical lateralization of seizure foci.

In vivo 1H MRS of normal breast and breast tumors using a dedicated double breast coil.

Image-guided localized proton MR spectroscopy (MRS) of normal breasts and breast tumors (ductal and undifferentiated carcinomas) was performed using a dedicated double breast coil. In vivo 1H MR spectra from 10 normal volunteers showed signals from water and lipids only, even in breasts with small contribution of fatty breast tissue. In the spectra from 6 of the 12 examined patients, an intense signal assigned to choline compounds was detected. The signal was also detected at lower levels in the remaining patients. This study shows that in vivo 1H MRI/MRS examinations of breast tumors can be performed within an examination time of 45 to 60 minutes. Signals from breast tumor metabolites may be detected using in vivo 1H MRS.

Dexamethasone and dexamethasone phosphate detected by 1H and 19F NMR spectroscopy in the aqueous humour.

To apply nuclear magnetic resonance (NMR) spectroscopy to study the penetration of dexamethasone phosphate into the aqueous humour from rabbit following topical administration. After topical administration of 0.1%, 1.0% and 10% dexamethasone phosphate solutions, respectively, samples of aqueous humour were aspirated, freeze-dried, redissolved in deuterium oxide and analyzed by high resolution 1H and 19F NMR spectroscopy. In order to study the lipophilic and hydrophilic metabolites of the drug, samples obtained after application of 1% dexamethasone phosphate were extracted with methanol/chloroform, and then extracted with perchloric acid. In all samples obtained from eyes denuded of the corneal epithelium prior to administration of dexamethasone, signals corresponding to the chemical shifts of the drug were identified in 19F NMR spectra. In the experiments performed with 1% dexamethasone phosphate, both dexamethasone and dexamethasone phosphate were detected in the aqueous humour. Using 10% dexamethasone phosphate solutions, signals from the drug were detected in 1H NMR spectra simultaneously with signals from about twenty other substances present in the aqueous humour. NMR spectroscopy appears to be a valuable method for studying dexamethasone metabolism and penetration into ocular tissues. It provides simultaneous detection of both the drug metabolites and other substances in the sample and might offer a complementary approach to other analytical methods.

[Magnetic tomography in diagnosis of breast implant rupture]. / Magnettomografi i påvisningen av brystimplantatruptur.

At least 20,000 Norwegian women have silicone breast implants, either for breast augmentation or for reconstruction. One of the complications associated with breast implants is rupture of the implants. Magnetic resonance imaging (MRI) has been shown to be the most accurate imaging modality for evaluating the integrity of breast implants. Recognition of the different types of implants and the appearance of normal implants on MRI is very important for distinguishing these from intracapsular and extracapsular ruptures. Examples are shown of MRI findings in normal and ruptured implants.

Metabolic analysis of the rabbit cornea by proton nuclear magnetic resonance spectroscopy.

Perchloric acid extracts of the rabbit cornea were analyzed by high-resolution 1H NMR spectroscopy, including the two-dimensional shift-correlated (COSY) technique. Numerous metabolites including leucine/isoleucine, 3-hydroxybutyrate, valine, lactate, alanine, lysine, acetate, glutamate, creatine/phosphocreatine, taurine, glycine, inositol, glucose, tyrosine, phenylalanine, histidine, adenosine and formate have been simultaneously detected and identified in the NMR spectra. Concentrations of some of these were also determined. Of particular importance are the detection and identification of hypotaurine in the corneal tissue. Hypotaurine is a precursor of the synthesis of taurine and may act as an antioxidant. Moreover, the presence of choline, a precursor for acetylcholine, was established. This novel metabolite profile of the cornea obtained by high-resolution 1H NMR spectroscopy may be of value in the study of pathologic and toxic disorders.

High-resolution 1H NMR spectroscopy of aqueous humour from rabbits.

BACKGROUND: Detection of different substances in aqueous humour is important for evaluation of the disorders affecting the eye. The purpose of the present study was to apply high-resolution proton (1H) nuclear magnetic resonance (NMR) spectroscopy for extensive characterisation of the metabolites in the aqueous humour from rabbits. METHODS: High-resolution 1H NMR spectroscopy, including two-dimensional shift correlated (COSY) technique, was performed on aqueous humour from rabbits. RESULTS: More than 20 metabolites were simultaneously detected and identified in high-resolution 1H NMR spectra of aqueous humour from rabbits. Some of these were also quantified. CONCLUSION: High-resolution 1H NMR spectroscopy is a valuable method for simultaneous detection of many different metabolites in aqueous humour.

1H NMR spectroscopic characterization of perchloric acid extracts from breast carcinomas and non-involved breast tissue.

High-resolution 1H NMR spectra were obtained from perchloric acid extracts of breast tumor specimens and adjacent non-involved tissue. Two-dimensional shift-correlated and homonuclear J-resolved spectroscopy were used to identify coupled resonances in the spectra. Chemical shifts, multiplicities and spin-spin coupling constants of several non-resolved resonances in the one-dimensional spectra could be determined by the two-dimensional methods. Several differences in the metabolite content of the two types of extracts were established. The spectra of extracts from non-involved tissue were dominated by signals from glucose and other carbohydrates, while most of the tumors had very low or no detectable levels of glucose. High concentrations of lactate, taurine and succinate, an increase of the phosphocholine level, and a very low phosphocreatine level were characteristic findings in the 1H spectra of tumor extracts. The variation in the level of myo-inositol follows the variation in glucose for the two types of tissue. Scyllo-inositol was for the first time observed in the NMR spectra from breast tissue. Uridine 5'-diphospho-N-acetylglucosamine and uridine 5'-diphospho-N-acetylgalactosamine have been identified and there is an increased level of these two hexoses in the tumor tissue. These results provide insight into breast tumor metabolism, by simultaneously detecting a large number of metabolites and demonstrate the potential for using 1H NMR spectroscopy for studying different metabolic pathways in breast tumors. At the same time they provide useful information for interpretation of in vivo 1H NMR spectra of breast tumors.

Comparative signal intensity measurements in dynamic gadolinium-enhanced MR mammography.

Increases in signal intensity enhancement were measured in defined regions of interest (ROIs) to allow distinction between malignant and benign tumors with dynamic gadolinium-enhanced magnetic resonance (MR) mammography. Twenty patients with palpable breast lesions (15 malignant, five benign) underwent MR mammography. The dynamic gradient-echo sequence was performed with intravenous bolus injection of gadopentetate dimeglumine and consisted of 25 images with a time resolution of 30 seconds. Contrast enhancement was calculated by comparing user-defined ROIs on pre- and postcontrast images. An increase in signal intensity of 70% or more on the 1-minute postcontrast image was used as the criterion of malignancy. MR mammographic results correlated with histopathologic findings in all patients when the defined ROI was in the most enhancing part of the tumor. For the ROI in areas of submaximal enhancement or when the ROI surrounded the whole lesion, only five and nine tumors, respectively, fulfilled the malignancy criterion. All malignant tumors showed large variations in signal intensity enhancement that depended on the position of the ROI in the tumor. Dynamic, gadolinium-enhanced MR mammography allows distinction of benign from malignant breast tumors when the selected ROI is in the most enhancing part of the lesion.

UDP-N-acetylhexosamines and hypotaurine in human glioblastoma, normal brain tissue and cell cultures: 1H/NMR spectroscopy study.

NMR spectroscopy was used to analyse perchloric acid extracts of normal human brain, murine brain cell cultures, glioblastoma tissue and the glioblastoma cell line U-87. 1H NMR spectra revealed the presence of elevated levels of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine in glioblastoma extracts and the glioblastoma cell line U-87, in comparison with normal brain tissue and primary cell cultures of neurons and astrocytes. UDP-N-acetylhexosamines appear to accumulate in cells that are unable to differentiate. Furthermore, it was found that the culture medium had an effect on the concentration of UDP-N-acetygalactosamine in the glioblastoma cell line. Hypotaurine, previously only associated with oligodendrocytes, has been identified in astrocyte cultures and in cerebellar granule cells. In normal brain it was not observed by NMR spectroscopy, but was easily detectable in glioblastoma tissue extracts. UDP-N-acetylhexoseamines and hypotaurine might be useful markers for brain pathology and play a role in cell differentiation and cell division.

Nuclear magnetic resonance spectroscopy: biochemical evaluation of brain function in vivo and in vitro.

Nuclear magnetic resonance spectroscopy (MRS) offers a unique opportunity to monitor mmolar concentrations of high energy phosphates, glucose, lactate and amino acids. The possibility of obtaining information about chemical constituents noninvasively is of great importance. MRS and chemical shift imaging (CSI) are emerging as tools for tumor grading, monitoring of treatment, ischemia research, in pediatric research for follow-up of children with borderline mental retardation, for defining brain death and to define epileptic foci. It is important to know which cell type (neuronal or glial) shows changes as a result of external manipulations (e.g. excitotoxins) or internal changes (brain pathology). Metabolic studies have been carried out on brain cell cultures. By using 13C labeled glucose and acetate in combination with 13C MRS it was shown that astrocytes release lactate, glutamine, citrate and alanine and that cerebral cortical neurons use glutamine released from astrocytes as a precursor for GABA synthesis. An important feature in MRS is the localization of N-acetyl aspartate in neurons, since this enables monitoring of neuronal reactions, such as survival after neurotoxic insults. Recent advances have yielded high speed functional echo planar imaging (EPI) techniques that are sensitive to changes in cerebral blood volume, blood flow and blood oxygenation (Functional MRI). During cognitive task performance, local alterations in neuronal activity induce local changes in cerebral metabolism and cerebral perfusion, which can now be detected with MRI.

In vitro proton NMR spectroscopy of extracts from human breast tumours and non-involved breast tissue.

Proton (1H) nuclear magnetic resonance (NMR) spectra were obtained from perchloric acid (PCA) extracts of 11 breast tumours and non-involved breast tissue from 7 of the same patients. The spectra were correlated with histopathologic diagnosis. The tumour group consisted of 8 ductal carcinomas, 1 ductal carcinoma with an extensive intraductal component, 1 intraductal carcinoma and 1 fibroadenoma. Higher content of lactate, succinate and phosphocholine and low levels of glucose and inositol were characteristic findings in the tumour group as compared to non-involved breast tissue. 1H NMR spectra of PCA extracted breast specimens provide a comprehensive window into the metabolic activities of the tissue.

Contrast-enhanced magnetic resonance imaging of the breast.

Contrast-enhanced magnetic resonance imaging (MRI) of 28 patients with known breast tumors was compared with clinical findings and histopathology, and for 12 of the patients also with mammography. The dynamic measurements performed in 18 patients showed that signal intensity in gradient echo (FFE) images increased rapidly in malignant tumors after contrast injection and reached a plateau level at 1-3 min postcontrast. Fibroadenomas showed slower contrast enhancement continuing throughout the whole examination period of 10 min. The most enhancing parts of the tumors were selected for intensity measurements. The differentiation between malignant and benign tumors in dynamic contrast-enhanced MRI was in accordance with the histopathological findings in all cases. The tumor diameter as measured by MRI showed very good agreement with the size of the tumor specimens. Comparison of tumor size measurements in mammography and MRI showed that MRI had the most accurate correlation to the measured size of the tumor specimens.

Formation of chlorinated PAH--a possible health hazard from water chlorination.

Four PAH compounds, fluorene, anthracene, fluoranthene and benzo(a)pyrene were dissolved in humus poor (lake) and humus rich water. The samples were chlorinated, stored for three days, and extracted with cyclohexane. Chlorinated derivatives of the four compounds were synthesised and used as calibration standards for quantitative analysis of the corresponding chlorinated PAH formed during the experiment. The synthesized chlorinated PAH were tested for mutagenic activity by the Ames test, and their octanol/water partition coefficient (Pow) were determined by thin layer chromatography. Chlorinated fluorene, fluoranthene and benzo(a)pyrene were formed during chlorination of PAH polluted lake water, but not during chlorination of the humus rich water samples. All chlorinated PAH except 9,10-dichloroanthracene, acted as strong mutagens both in the presence and in the absence of metabolic activation, while benzo(a)pyrene was the only mutagen active parent PAH. The determined Pow showed high lipophilicity for all chlorinated PAH. Theoretically determined bioconcentration factors (BCF) were found to be extremely high, and increased with increasing ring number and increasing number of chlorine atoms attached to the ring.