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1.
Proton magnetic resonance spectroscopy of human cervical spondylosis at 3T.
Salamon, N, Ellingson, BM, Nagarajan, R, Gebara, N, Thomas, A, Holly, LT
Spinal cord. 2013;(7):558-63
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Abstract
STUDY DESIGN A single-center magnetic resonance imaging and spectroscopic study involving 21 patients with advanced cervical spondylosis and 11 healthy controls. OBJECTIVE We assessed the utility of magnetic resonance spectroscopy (MRS) to quantify biochemical changes within the spinal cord and serve as a potential biomarker in patients with cervical spondylosis with or without T2 hyperintensity within the cord. SETTING Los Angeles, California, USA. METHODS Twenty-one patients with cervical spondylosis and eleven healthy controls were evaluated. Single-voxel MRS was performed in the cervical cord. Morphometry of the spinal canal space was measured. N-Acetyl aspartylglutamic acid (NAA), choline (Cho), myo-inositol (Myo-I), glutamine-glutamate complex (Glx) and lactate metabolite concentration ratios with respect to total creatine (Cr) were quantified using an LC model algorithm and compared between healthy controls and spondylosis patients. Correlation of MRS metabolites with modified Japanese Orthopaedic Association (mJOA) score was also performed. RESULTS The spinal canal space was significantly different between patients and controls (analysis of variance (ANOVA), P<0.0001). Total Cho-to-Cr ratio was significantly elevated in patients with spondylosis and T2-hyperintensity compared with healthy controls (ANOVA, P<0.01). A significantly higher Cho-to-NAA ratio was observed in spondylosis patients compared with healthy controls (ANOVA, P<0.01). Slightly elevated Glx and Myo-I were encountered in patients with stenosis without T2 hyperintensity. A linear correlation between Cho-NAA ratio and mJOA was also observed (P<0.01). CONCLUSION MRS appears sensitive to biochemical changes occurring in advanced cervical spondylosis patients. The Cho/NAA ratio was significantly correlated with the mJOA score, providing a potentially clinically useful radiographical biomarker for the management of advanced cervical spondylosis patients.
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Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy.
Kesler, SR, Watson, C, Koovakkattu, D, Lee, C, O'Hara, R, Mahaffey, ML, Wefel, JS
Brain imaging and behavior. 2013;(4):501-10
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Abstract
Breast cancer survivors are at increased risk for cognitive dysfunction, which reduces quality of life. Neuroimaging studies provide critical insights regarding the mechanisms underlying these cognitive deficits as well as potential biologic targets for interventions. We measured several metabolite concentrations using (1)H magnetic resonance spectroscopy as well as cognitive performance in 19 female breast cancer survivors and 17 age-matched female controls. Women with breast cancer were all treated with chemotherapy. Results indicated significantly increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N-acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared to controls. The breast cancer group reported reduced executive function and memory, and subjective memory ability was correlated with mI and Cho levels in both groups. These findings provide preliminary evidence of an altered metabolic profile that increases our understanding of neurobiologic status post-breast cancer and chemotherapy.
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Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis.
Innis, SM, Davidson, AG, Bay, BN, Slack, PJ, Hasman, D
The American journal of clinical nutrition. 2011;(3):564-8
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Abstract
BACKGROUND Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown. OBJECTIVE We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF. DESIGN This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC-tandem mass spectrometry. RESULTS Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/10(6) cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05). CONCLUSIONS A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown. This trial was registered at clinicaltrials.gov as NCT01150136.
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Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study.
Beheshti, M, Vali, R, Waldenberger, P, Fitz, F, Nader, M, Loidl, W, Broinger, G, Stoiber, F, Foglman, I, Langsteger, W
European journal of nuclear medicine and molecular imaging. 2008;(10):1766-74
Abstract
PURPOSE The aim of this prospective study was to compare the potential value of (18)F fluorocholine (FCH) and (18)F fluoride positron emission tomography (PET)-CT scanning for the detection of bony metastases from prostate cancer. METHODS Thirty-eight men (mean age, 69+/-8 years) with biopsy-proven prostate cancer underwent both imaging modalities within a maximum interval of 2 weeks. Seventeen patients were evaluated preoperatively, and 21 patients were referred for post-operative evaluation of suspected recurrence or progression based on clinical algorithms. The number, sites and morphological patterns of bone lesions on (18)F FCH and (18)F fluoride PET-CT were correlated: Concordant lesions between the two modalities with corresponding changes on CT were considered to be positive for malignancy; discordant lesions were verified by follow-up examinations. The mean follow-up interval was 9.1 months. RESULTS Overall, 321 lesions were evaluated in this study. In a lesion-based analysis, a relatively close agreement was found between these two imaging modalities for detection of malignant bone lesions (kappa=0.57), as well as in a patient-based analysis (kappa=0.76). Sixteen malignant sclerotic lesions with a high density were negative in both (18)F FCH and (18)F fluoride PET-CT [mean Hounsfield unit (HU), 1,148+/-364]. There was also a significant correlation between tracer intensity by SUV and density of sclerotic lesions by HU both in (18)F FCH PET-CT (r= -0.28, p < 0.006) and (18)F fluoride PET-CT (r= -0.20, p<0.05). The sensitivity, specificity and accuracy of PET-CT in the detection of bone metastases in prostate cancer was 81%, 93% and 86% for (18)F fluoride, and 74% (p=0.12), 99% (p=0.01) and 85% for FCH, respectively. (18)F FCH PET-CT led to a change in the management in two out of 38 patients due to the early detection of bone marrow metastases. (18)F fluoride PET-CT identified more lesions in some patients when compared with (18)F FCH PET-CT but did not change patient management. CONCLUSION FCH PET-CT may be superior for the early detection (i.e. bone marrow involvement) of metastatic bone disease. In patients with FCH-negative suspicious sclerotic lesions, a second bone-seeking agent (e.g. (18)F fluoride) is recommended. (18)F fluoride PET-CT demonstrated a higher sensitivity than (18)F FCH PET-CT, but the difference was not statistically significant. Furthermore, (18)F fluoride PET could be also negative in highly dense sclerotic lesions, which presumably reflects the effect of treatment. It will be important to clarify in future studies whether these lesions are clinically relevant when compared with metabolically active bone metastases.
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Contrast/Noise ratio on conventional MRI and choline/creatine ratio on proton MRI spectroscopy accurately discriminate low-grade from high-grade cerebral gliomas.
Fayed, N, Morales, H, Modrego, PJ, Pina, MA
Academic radiology. 2006;(6):728-37
Abstract
RATIONALE AND OBJECTIVES Histopathology is the gold standard to establish the grade of brain tumors but biopsy and/or surgery are not always possible. The aim of this study is to determine whether histological grade of tumors may be predicted by means of conventional gadolinium-enhanced MRI and proton magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS In this study, we included 35 consecutive patients with single brain tumors and final histopathological verification: 12 had low-grade glioma, 16 had high-grade glioma, and 7 had single metastasis. Initially, we carried out T1 and T2 MRI paying attention to the following features: border definition, mass effect, heterogeneity of signal, perilesional edeme, hemorrhage, necrosis, and corpus callosum invasion. Gadolinium-enhancement was evaluated with the contrast-to-noise ratio (CNR). Next, single-voxel proton MRS was carried out to measure the absolute values of metabolites (N-acetyl-aspartate, creatine, choline, and myo-inositol) and their ratios in the area of maximum contrast enhancement. RESULTS We found that gadolinium-enhancement measured with the CNR (CNR > 35.86) predicted malignancy at 82.6% sensitivity and 91.7% specificity (area under the curve, 0.88; 95% confidence interval [CI], 0.73-0.97). With regard to MRS a choline/creatine ratio higher than 1.56 predicted malignancy at 88.9% sensitivity and 91.7% specificity (area under the curve, 0.94; 95% CI, 0.78-0.99). When we combined the CNR value, the choline/creatine ratio, and the presence of lactates in a model of discriminant analysis the predictive power improved significantly with an area under the curve of 0.99% (95% CI, 0.87-1). However, the used techniques were unable to distinguish metastases from high-grade gliomas accurately. CONCLUSIONS The intensity of contrast enhancement measured with the CNR, the choline/creatine ratio, and the presence of lactate were the most powerful variables to predict malignancy in brain tumors. The CNR is a simple, objective, and useful tool in the initial assessment of gliomas and metastases.
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Magnetisation transfer ratio of choline is reduced following epileptic seizures.
Flügel, D, McLean, MA, Simister, RJ, Duncan, JS
NMR in biomedicine. 2006;(2):217-22
Abstract
The purpose of this study was to characterise the concentration and magnetisation transfer ratio (MTR) of brain metabolites following epileptic seizures. Magnetic resonance spectroscopy was performed in 10 patients with temporal or extra-temporal lobe epilepsy as soon as possible after a seizure, with a second interictal scan between 1 and 3 days after the postictal scan and 10 healthy controls were scanned twice. Voxels (26 +/- 2 mL) were placed in the frontal lobe in all patients and controls, on the side of seizure focus in the patient group. Spectra were obtained using a modified PRESS sequence (TE 30 ms, TR 3 s, with three hard pulses offset from the water frequency by 2,500 Hz for MT presaturation). Mean metabolite concentrations and median metabolite MTRs of N-acetylaspartate (NAA), creatine, choline (Cho), myo-inositol (Ins) and glutamate plus glutamine were compared between the first and second scans in each group. A significant decrease in the MTR of Cho was seen postictally in the patient group, but the metabolite concentrations showed no significant difference between interictal and postictal scans and in the control group there was no difference between the two scans. Inter-group comparison showed significantly reduced concentrations of NAA and Ins in the patients. Reduced MTR of Cho indicates a shift from a bound to a more mobile fraction. These changes might indicate membrane perturbation in areas of seizure spread.
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Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients.
Caetano, SC, Fonseca, M, Olvera, RL, Nicoletti, M, Hatch, JP, Stanley, JA, Hunter, K, Lafer, B, Pliszka, SR, Soares, JC
Neuroscience letters. 2005;(3):321-6
Abstract
The dorsolateral prefrontal cortex (DLPFC) plays an essential role in mood regulation and integration of cognitive functions that are abnormal in major depressive disorder (MDD). Few neuroimaging studies have evaluated the still maturing DLPFC in depressed children and adolescents. We conducted single voxel proton magnetic resonance spectroscopy ((1)H MRS) of the left DLPFC in 14 depressed children and adolescents (13.3 +/- 2.3 years old, 10 males) and 22 matched healthy controls (13.6 +/- 2.8 years old, 13 males). Depressed subjects had significantly lower levels of glycerophosphocholine plus phosphocholine (GPC + PC; or choline-containing compounds) and higher myo-inositol levels in the left DLPFC compared to healthy controls. In the depressed subjects, we found significant inverse correlations between glutamate levels and both duration of illness and number of episodes. In healthy controls there was a significant direct correlation between age and glutamine levels, which was not present in the patient group. Lower GPC + PC levels in pediatric MDD may reflect lower cell membrane content per volume in the DLPFC. Increased myo-inositol levels in MDD may represent a disturbed secondary messenger system. GPC + PC and myo-inositol abnormalities further demonstrate the involvement of DLPFC in pediatric MDD.
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1H MRS in stroke patients with and without cognitive impairment.
Ross, AJ, Sachdev, PS, Wen, W, Valenzuela, MJ, Brodaty, H
Neurobiology of aging. 2005;(6):873-82
Abstract
The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.
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MRS study on lentiform nucleus in idiopathic Parkinson's disease with unilateral symptoms.
Zheng, XN, Zhu, XC, Ruan, LX, Zhang, LJ, Yuan, M, Shang, DS, Liu, Y
Journal of Zhejiang University. Science. 2004;(2):246-50
Abstract
OBJECTIVE To investigate changes in magnetic resonance spectroscopy (MRS) of lentiform nucleus during the early stage of Parkinson's disease. METHODS Twenty-five patients with idiopathic Parkinson disease with unilateral symptoms (IPDUS) and 25 healthy volunteers were enrolled in this study. MRS of the lentiform nucleus in each patient was taken and then concentrations of N-acetylaspartate (NAA), Creatine (Cr) and Choline (Cho) were calculated. RESULTS Compared to that in the control, NAA/ (Cho+Cr) was significantly lower in the lentiform nucleus contralateral to symptoms and even that in the ipsilateral side in IPDUS patients (all P<0.05); while there was no difference between the two sides in the healthy volunteer (P>0.05). The ratio of NAA/(Cho+Cr) ipsilateral to the sympatomatic side of the patient was also lower than that of the control (P<0.05). CONCLUSIONS There might be some changes with MRS on the lentiform nucleus during the early stage of idiopathic Parkinson's disease with unilateral symptom. MRS may be one of the reliable methods for early or even sub-clinical diagnosis.
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Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis.
Inglese, M, Li, BS, Rusinek, H, Babb, JS, Grossman, RI, Gonen, O
Magnetic resonance in medicine. 2003;(1):190-5
Abstract
It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy.