Use of in Vivo Two-dimensional MR Spectroscopy to Compare the Biochemistry of the Human Brain to That of Glioblastoma

Ramadan, Saadallah; Andronesi, Ovidiu C.; Stanwell, Peter; Lin, Alexander P.; Sorensen, A. Gregory; Mountford, Carolyn E.

doi:10.1148/radiol.11101123

Cited by 35 publications

(44 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2). Similar finding have been previously reported, regarding increased lipids (19) and the presence of L-fucose in glioblastoma (20), and increased GPC in low grade glioma versus increased PC in high grade glioma (21-23). For comparison, 1D HRMAS spectra acquired on the anaplastic astrocytoma biopsy are shown in fig.…”

Section: Resultssupporting

confidence: 91%

Detection of 2-Hydroxyglutarate in IDH -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

et al. 2012

Self Cite

View full text Add to dashboard Cite

Mutations of arginine 132 (R132) in the enzyme isocitrate dehydrogenase-1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. R132 mutations in IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG non-invasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG has been found also by 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting IDH mutations.

show abstract

Section: Resultssupporting

confidence: 91%

Detection of 2-Hydroxyglutarate in IDH -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite these limitations, MRS has provided and continues to provide important insights into neurochemical alterations observed during inflammation. The development of advanced MRS methods capable of increasing the number of metabolites detected (e.g., 2D-COSY) 96 , or fast 3D spiral encoding of spatial information 97 will increase the applicability of MRS to the study of neuroinflammatory and other conditions.…”

Section: Imaging Resident Immunocompetent Cellsmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

175

146

View full text Add to dashboard Cite

Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes. The intent of this Review is to provide brief descriptions of currently available neuroimaging methods to image neuroinflammation in the human central nervous system (CNS) in vivo. Specifically, because of the relatively widespread accessibility of equipment for nuclear imaging (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) and magnetic resonance imaging (MRI), we will focus on strategies utilizing these technologies. We first provide a working definition of “neuroinflammation” and then discuss available neuroimaging methods to study human neuroinflammatory processes. Specifically, we will focus on neuroimaging methods that target (1) the activation of CNS immunocompetent cells (e.g. imaging of glial activation with TSPO tracer [11C]PBR28), (2) compromised BBB (e.g. identification of MS lesions with gadolinium-enhanced MRI), (3) CNS-infiltration of circulating immune cells (e.g. tracking monocyte infiltration into brain parenchyma with iron oxide nanoparticles and MRI), and (4) pathological consequences of neuroinflammation (e.g. imaging apoptosis with [99mTc]Annexin V or iron accumulation with T2* relaxometry). This Review provides an overview of state-of-the-art techniques for imaging human neuroinflammation which have potential to impact patient care in the foreseeable future.

show abstract

“…Metabolite alteration may also accompany the progression of chronic kidney allograft dysfunction and this may be relevant for the outcome both in terms of graft survival and health of the patient. Thus, aiming to explore the profile of metabolomic abnormalities induced by the progressive reduction of kidney function and their potential impact on kidney graft function, we took advantage of two complementary approaches: liquid chromatography-mass spectrometry (LC-MS/MS) for targeted metabolomic profiling of serum and urine [20] and two dimensional correlated spectroscopy (2D COSY) [21, 22] for the in vivo metabolomic profiling of the kidney allograft, in a population of individuals with different degrees of graft dysfunction, defined by progressively lower levels of glomerular filtration rate (GFR) and a pool of healthy non-allograft individuals controls. We thus performed an analysis of the transplant individual at the serum, urine and kidney graft level by taking advantage of the latest analytical techniques, in order to gain insights into the metabolomic abnormalities evident in individuals with failing kidney allografts.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

et al. 2017

View full text Add to dashboard Cite

BackgroundAlteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.MethodsTo explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls.ResultsLC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels.ConclusionsWe report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

show abstract

Use of in Vivo Two-dimensional MR Spectroscopy to Compare the Biochemistry of the Human Brain to That of Glioblastoma

Cited by 35 publications

References 38 publications

Detection of 2-Hydroxyglutarate in IDH -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

Detection of 2-Hydroxyglutarate in IDH -Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy

In Vivo Imaging of Human Neuroinflammation

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

Contact Info

Product

Resources

About