Evidence map›Paper›PMID 32003035›Full record

ArticleMagnetic resonance in medicine2020

In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.

Vivek Tiwari, Tomoyuki Mashimo, Zhongxu An, Vamsidhara Vemireddy, Sara Piccirillo, Pegah Askari, Keith M Hulsey, Shanrong Zhang, Robin A de Graaf, Toral R Patel and 5 more

Open access · greenAbstract read
In one paragraph

Article in Magnetic resonance in medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 1 country.

Vivek TiwariAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Tomoyuki MashimoDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Zhongxu AnAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Vamsidhara VemireddyDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Sara PiccirilloDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Pegah AskariAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Keith M HulseyDepartment of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.
Shanrong ZhangAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Robin A de GraafDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut.
Toral R PatelDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas.
Edward PanDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas.
Bruce E MickeyAnnette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Elizabeth A MaherDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Robert M BachooDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Changho ChoiAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.ORCID 0000-0002-7135-2447
Center for Neuro-Oncology · USSouthwestern Medical Center · USThe University of Texas Southwestern Medical Center · USNeurological Surgery · USThe University of Texas at Arlington · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Understanding the role of IDH in malignant gliomasR01CA154843 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MAHER, ELIZABETH A · 2012 to 2022
$3.5M
Clinical development of cancer-specific MRS biomarkers in malignant gliomasR01CA184584 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CHOI, CHANGHO · 2014 to 2018
$1.6M
NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA154843NCI NIH HHS R01 CA184584
6 · The paper itself

Abstract

purposeTo generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients.

methodsFive patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water.

resultsThe PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients.

conclusionThe similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

Indexed as

Brain NeoplasmsGliomaAnimalsComputer SimulationGlutaratesHumansIsocitrate DehydrogenaseMagnetic Resonance SpectroscopyMiceNeoplasm Transplantationalpha-hydroxyglutarateGlutaratesIsocitrate Dehydrogenase1H magnetic resonance spectroscopy2HG2-hydroxyglutarategliomasIDH mutationisocitrate dehydrogenasemouseMRSpatient-derived xenograftPDXpoint-resolved spectroscopyPRESS

Identifiers

PMID32003035
PMCPMC7263951
OpenAlexW3003588018

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.