Non-invasive detection of IDH-1 mutation in brain gliomas based on proton MR spectroscopy

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Abstract

Mutations of isocitrate dehydrogenase (IDH) have important prognostic significance for patients with glial brain tumor. The method of proton MR spectroscopy makes it possible to non-invasively determine the metabolic properties of the tumor tissue at the preoperative stage.

The aim of this work was to study the possibility of determining the IDH status, by using magnetic resonance spectroscopy (MRS) to detect the 2-hydroxyglutarate (2HG), a metabolic product of the IDH enzyme.

We examined 33 patients with glial tumors varying degrees of malignancy (Gr. 2–4), followed by identification of IDH mutations. IDH mutation identified in 20 cases, according to proton magnetic resonance spectroscopy, was confirmed by immunohistochemistry. Peak of 2HG did not detect in 13 cases on the MR spectrum, and the analysis for IDH did not reveal mutations.

Using of proton magnetic resonance spectroscopy showed a high sensitivity of this technique in predicting the mutational status of glial brain tumors, which makes this method an important in preoperative diagnostics.

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About the authors

A. N. Tyurina

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Author for correspondence.
Email: alfa.net@list.ru
Russian Federation, Moscow

A. I. Batalov

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Email: alfa.net@list.ru
Russian Federation, Moscow

N. E. Zakharova

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Email: alfa.net@list.ru
Russian Federation, Moscow

L. M. Fadeeva

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Email: alfa.net@list.ru
Russian Federation, Moscow

D. B. Kalaeva

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Email: alfa.net@list.ru
Russian Federation, Moscow

I. N. Pronin

N. N. Burdenko National Medical Research Center of Neurosurgery, Ministry of Healthcare of Russia

Email: alfa.net@list.ru
Russian Federation, Moscow

References

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Supplementary files

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2. Fig. 1. MR images of a diffuse glioma in the right frontotemporal region. In T2 and T2 Flair, the tumor has a hyperintense signal and fuzzy contours.

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3. Fig. 2. MR spectrum for Press (a) and Mega (б) sequences. The blue arrow at a frequency of 2.25 ppm indicates the 2HG peak, which indicates the presence of an IDH mutation in the tumor tissue.

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4. Fig. 3. (a) – T2-weighted MRI in axial view. Diffuse tumor of the left frontotemporal region; (б) – The spectrum obtained from the tumor site (indicated by a yellow square): there is a decrease in the NAA peak, a decrease in the NAA/Cho, NAA/Cr ratio, a high mI peak, the Cho/Cr ratio is slightly changed.

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5. Fig. 4. MR spectrum after processing using the LC Model. At a resonant frequency of 2.25 ppm, a 2HG peak is detected (red arrow). Histological diagnosis – Astrocytoma Gr.2, IDH1-mutant.

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6. Fig. 5. MR spectrum after processing on the LC module. At a resonant frequency of 2.25 ppm, the 2HG peak is not detected (red arrow). IDH analysis revealed no mutations. The histological diagnosis was Glioblastoma, wild type.

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