Challenges of Using MR Spectroscopy to Detect Neural Progenitor Cells In Vivo

Dong, Zhengchao; Dreher, Wolfgang; Leibfritz, Dieter; Peterson, Bradley S.

doi:10.3174/ajnr.a1557

Cited by 19 publications

(18 citation statements)

References 48 publications

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“…33 However, evidence for the existence of two distinct signals in the same spectral region was neither found by the cited experimental study on cell-specificity of the signal nor by our results.…”

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confidence: 89%

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Loewenbrück

Fuchs

Hermann

et al. 2011

Rejuvenation Research

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Recently, a peak at 1.28 ppm in proton magnetic resonance spectroscopy ( 1 H-MRS) of neural stem cells (NSCs) was introduced as a noninterventional biomarker for neurogenesis in vivo. This would be an urgently needed requisite for translational studies in humans regarding the beneficial role of adult neurogenesis for the structural and functional integrity of the brain. However, many concerns have risen about the validity of the proposed signal as a specific marker for NSCs. The peak has also been related to cell-type-independent phenomena such as apoptosis or necrosis. Thus, we compared the 1.28-ppm peak in various immature stem cell populations, including embryonic stem cells, mouse embryonic fibroblasts, embryonic stem cell-and induced pluripotent stem cell-derived NSCs, ex vivo isolated embryonic NSCs, as well as mature and tumor cell types from different germ layers. To correlate the integral peak intensity with cell death, we induced both apoptosis with camptothecin and necrosis with sodium azide. A peak at 1.28 ppm was found in most cell types, and in most, but not all, NSCH cultures, demonstrating no specificity for NSCs. The intensities of the 1.28-ppm resonance significantly correlated with the rate of apoptosis, but not with the rate of necrosis, cell cycle phase distribution, cell size, or type. Multiple regression analysis displayed a significant predictive value of the peak intensity for apoptosis only. In this context, its specificity for apoptosis as a major selection process during neurogenesis may suggest this resonance as an indirect marker for neurogenesis in vivo.

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confidence: 89%

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Loewenbrück

Fuchs

Hermann

et al. 2011

Rejuvenation Research

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show abstract

“…The in vivo signals are the sum of 1 H spin-coupled multiplets from several different fatty acids with slightly different chemical shifts that cannot be resolved [20]. Consequently, a single Lorentzian-Gaussian line will not properly represent the experimental lineshape, which might translate into small errors in quantification [41]. 4.…”

Section: H Mr Spectroscopic Information On Hepatic Lipid Composition mentioning

confidence: 99%

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

Danzer

Fuchs

et al. 2012

Magn Reson Mater Phy

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Object Hepatic lipid accumulation is associated with nonalcoholic fatty liver disease, and the metabolic syndrome constitutes an increasing medical problem. In vivo proton magnetic resonance spectroscopy ( 1 H MRS) allows the assessment of hepatic lipid levels noninvasively and also yields information on the fat composition due to its high spectral resolution. Materials and methods We applied 1 H MRS at 9.4T to study lipid content and composition in eight leptin-deficient ob/ob mice as a model of obesity and in four lean ob/? control mice at 24 weeks of age. PRESS sequence was used. For accurate estimation of signal intensity, differences in relaxation behavior of individual signals were accounted for each mouse individually. Also, in order to minimize spectral degrading due to motion artifacts, respiration gating was applied.Results Significant differences between ob/ob and ob/? control mice were found in both lipid content and composition. The mean chain length was found to be significantly longer in ob/ob mice with a higher fraction of monounsaturated lipids. Conclusion 1 H MRS enables accurate assessment in hepatic lipids in mice, which is attractive for mechanistic studies of altered metabolism given the large number of genetically engineered mouse models available.

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“…If confirmed, this study provides an unparalleled glimpse into the human brain with the promise to provide a truly noninvasive biomarker of adult neurogenesis. Not unexpectedly, this report has aroused a certain amount of controversy on technical and study design aspects (Friedman 2008;Hoch et al 2008;Jansen et al 2008;Dong et al 2009;Ramm et al 2009). More studies are needed to demonstrate feasibility and practicality of this approach as a tool to investigate the role of neurogenesis in a wide variety of human brain disorders.…”

Section: Translational Biomarkers Of Human Neurogenesismentioning

confidence: 99%

Role of Adult Hippocampal Neurogenesis in Cognition in Physiology and Disease: Pharmacological Targets and Biomarkers

Costa

Lugert

Jagasia

2015

Handbook of Experimental Pharmacology

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Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis.

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Challenges of Using MR Spectroscopy to Detect Neural Progenitor Cells In Vivo

Cited by 19 publications

References 48 publications

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

Role of Adult Hippocampal Neurogenesis in Cognition in Physiology and Disease: Pharmacological Targets and Biomarkers

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