Torill Eidhammer Sjøbakk

Magnetic Resonance Metabolomics of Intact Tissue: A Biotechnological Tool in Cancer Diagnostics and Treatment Evaluation

Personalized medicine is increasingly important in cancer treatment for its role in staging and its potential to improve stratification of patients. Different types of molecules, genes, proteins, and metabolites are being extensively explored as potential biomarkers. This review discusses the major findings and potential of tissue metabolites determined by high-resolution magic angle spinning magnetic resonance spectroscopy for cancer detection, characterization, and treatment monitoring.

Manganese, Copper, and Zinc in Cerebrospinal Fluid from Patients with Multiple Sclerosis

The concentrations of manganese, copper, and zinc in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and patients with no known neurological disease (control group) were measured. Manganese and copper levels were determined by two different analytical methods: atomic absorption spectrometry (AAS) and high-resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS), whereas zinc levels were determined by HR-ICP-MS only. Manganese levels (mean±SEM) were significantly decreased in the CSF of MS patients (1.07±0.13 µg/L, ICP-MS; 1.08±0.11 µg/L, AAS) compared to the levels in the control group (1.78±0.26 µg/L, ICP-MS; 1.51±0.17 µg/L, AAS). Copper levels were significantly elevated in the CSF of MS patients (10.90±1.11 µg/L; ICP-MS, 11.53±0.83 µg/L, AAS) compared to the levels in the control group (8.67±0.49 µg/L, ICP-MS; 9.10±0.62 µg/L, AAS). There were no significant differences between the CSF zinc levels of MS and control patients. The physiological basis for the differences in manganese and copper concentrations between MS patients and controls is unknown, but could be related to alterations in the manganese-containing enzyme glutamine synthetase and the copper-containing enzyme cytochrome oxidase.

Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in Formalin-Fixed Brain Tissue in Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex of Guam Determined by High-Resolution ICP-MS

Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) are neurodegenerative disorders that occurred with extremely high frequency among the native population on Guam, especially in the 1950s and 1960s, but have substantially declined over the last half-century. The etiology of these diseases is unknown, but the most plausible hypothesis centers on imbalances in essential and toxic metals. We have determined the concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue collected during the period 1979–1983 from eight Guamanian patients with ALS, four with PDC, and five control subjects using high-resolution inductively coupled plasma-mass spectrometry. The concentrations of Cd are markedly and significantly elevated both in gray and white matter in ALS, but not in PDC patients. The concentrations of Zn are elevated for both patient groups, in both gray and white matter, but only the difference in gray matter for PDC is significant. For the other metals, no significant differences are found.

Short echo time 1H MRSI of the human brain at 3T with adiabatic slice-selective refocusing pulses; reproducibility and variance in a dual center setting

To assess the reproducibility of 1H‐MR spectroscopic imaging (MRSI) of the human brain at 3T with volume selection by a double spin echo sequence for localization with adiabatic refocusing pulses (semi‐LASER).

Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T

BackgroundMetastases to the central nervous system from different primary cancers are an oncologic challenge as the overall prognosis for these patients is generally poor. The incidence of brain metastases varies with type of primary cancer and is probably increasing due to improved therapies of extracranial metastases prolonging patients overall survival and thereby time for brain metastases to develop. In addition, the greater access to improved neuroimaging techniques can provide earlier diagnosis. The aim of this study was to investigate the feasibility of using proton magnetic resonance spectroscopy (MRS) and multivariate analyses to characterize brain metastases originating from different primary cancers, to assess changes in spectra during radiation treatment and to correlate the spectra to clinical outcome after treatment.MethodsPatients (n = 26) with brain metastases were examined using single voxel MRS at a 3T clinical MR system. Five patients were excluded due to poor spectral quality. The spectra were obtained before start (n = 21 patients), immediately after (n = 6 patients) and two months after end of treatment (n = 4 patients). Principal component analysis (PCA) and partial least square regression analysis (PLS) were applied in order to identify clustering of spectra due to origin of metastases and to relate clinical outcome (survival) of the patients to spectral data from the first MR examination.ResultsThe PCA results indicated that brain metastases from primary lung and breast cancer were separated into two clusters, while the metastases from malignant melanomas showed no uniformity. The PLS analysis showed a significant correlation between MR spectral data and survival five months after MRS before start of treatment.ConclusionMRS determined metabolic profiles analysed by PCA and PLS might give valuable clinical information when planning and evaluating the treatment of brain metastases, and also when deciding to terminate further therapies.

Metabolic profiles of brain metastases

Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49) were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01), irrespective of their primary origin. The principal component analysis (PCA) showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01), indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

Diffusion weighted imaging for the differentiation of breast tumors: From apparent diffusion coefficient to high order diffusion tensor imaging.

To compare “standard” diffusion weighted imaging, and diffusion tensor imaging (DTI) of 2nd and 4th‐order for the differentiation of malignant and benign breast lesions.

Differentiating diffuse World Health Organization grade II and IV astrocytomas with ex vivo magnetic resonance spectroscopy.

BACKGROUND The prognosis and treatment of astrocytomas, which are primary brain tumors, vary depending on the grade of the tumor, necessitating a precise preoperative classification. Magnetic resonance spectroscopy (MRS) provides information about metabolites in tissues and is an emerging noninvasive tool to improve diagnostic accuracy in patients with intracranial neoplasia. OBJECTIVE To investigate whether ex vivo MRS could differentiate World Health Organization grade II (A-II) and IV astrocytomas (glioblastomas; GBM) and to correlate MR spectral profiles with clinical parameters. METHODS Patients with A-II and GBM (n = 58) scheduled for surgical resection were enrolled. Tumor specimens were collected during surgery and stored in liquid nitrogen before being analyzed with high-resolution magic angle spinning MRS. The tumors were histopathologically classified according to World Health Organization criteria as GBM (n = 48) and A-II (n = 10). RESULTS Multivariate analysis of ex vivo proton high-resolution magic angle spinning spectra MRS showed differences in the metabolic profiles of different grades of astrocytomas. A-II had higher levels of glycerophosphocholine and myo-inositol than GBM. The latter had more phosphocholine, glycine, and lipids. We observed a significant metabolic difference between recurrent and nonrecurrent GBM (P < .001). Primary GBM had more phosphocholine than recurrent GBM. A significant correlation (P < .001) between lipid and lactate signals and histologically estimated percentage of necrosis was observed in GBM. Spectral profiles were not correlated with age, survival, or magnetic resonance imaging-defined tumor volume. CONCLUSION Ex vivo MRS can differentiate astrocytomas based on their metabolic profiles.

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 15×15×15 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.

Impacts of MR spectroscopic imaging on glioma patient management.

Abstract Magnetic resonance (MR) modalities are routine imaging tools in the diagnosis and management of gliomas. MR spectroscopic imaging (MRSI), which relies on the metabolic characteristics of tissues, has been developed to accelerate the understanding of gliomas and to aid in effective clinical decision making and development of targeted therapies. In this review, the potentials and practical challenges to frequently use this technique in clinical management of gliomas are discussed. The applications of new biomarkers detectable by MRSI in differential glioma diagnosis, pre- and post-treatment evaluations, and neurosurgery are also addressed.