Assessment of the intrinsic radiosensitivity of glioma cells and monitoring of metabolite ratio changes after irradiation by 14.7-T high-resolution¹H MRS

Abstract

Gliomas are the most common type of primary brain tumor. Radiation therapy (RT) is the primary adjuvant treatment to eliminate residual tumor tissue after surgery. However, the current RT guided by conventional imaging is unsatisfactory. A fundamental question is whether it is possible to further enhance the effectiveness and efficiency of RT based on individual radiosensitivity. In this research, to probe the correlation between radiosensitivity and the metabolite characteristics of glioma cells in vitro, a perchloric acid (PCA) extracting method was used to obtain water-soluble metabolites [such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and succinate (Suc)]. Spectral patterns from these processed water-soluble metabolite samples were acquired by in vitro 14.7-T high-resolution ¹H MRS. Survival fraction analysis was performed to test the intrinsic radiosensitivity of glioma cell lines. Good ¹H MRS of PCA extracts from glioma cells was obtained. The radiosensitivity of glioma cells correlated positively with the Cho/Cr and Cho/NAA ratios, but negatively with the Suc/Cr ratio. Irradiation of the C6 cell line at different X-ray dosages led to changes in metabolite ratios and apoptotic rates. A plateau phase of metabolite ratio change and a decrease in apoptotic rate were found in the C6 cell line. We conclude that in vitro high-resolution ¹H MRS possesses the sensitivity required to detect subtle biochemical changes at the cellular level. ¹H MRS may aid in the assessment of the individual radiosensitivity of brain tumors, which is pivotal in the identification of the biological target volume.

Diagnostic performance between contrast enhancement, proton MR spectroscopy, and amide proton transfer imaging in patients with brain tumors

“…APT imaging is designed to detect endogenous mobile proteins and peptides in tissues . Both MRS and APT imaging provide metabolic information that can be exploited to study the biological behaviors of tumors …”

“…13 Both MRS and APT imaging provide metabolic information that can be exploited to study the biological behaviors of tumors. 14,15 We assumed that APT imaging and metabolites identified on MRS would show similarities and correlations and would provide important oncologic information. To date, several studies have demonstrated that these advanced techniques have the potential to characterize brain tumors.…”

Exogenous Amino Acid‐Loaded Nanovehicles: Stepping across Endogenous Magnetic Resonance Spectroscopy

“…Moreover, the MRS spectrum of AMSNs is identical as that of free ALA without apparent peak position shift (Figure d,e). It is well known that the area of the metabolite peak is proportional to the corresponding metabolite's concentration, so the standard curve can be obtained via MRS imaging of various concentrations of ALA . As shown in Figure S6b in the Supporting Information, the calculated formula of ALA standard curve is: y = −0.22 + 9.14 x ( n = 3), which can be used to semiquantify the in vivo AMSNs' targeting efficiency to glioma.…”

“…The peak of Cho in glioma region was much higher than that detected in the normal brain, presumably due to the fast cellular proliferation of glioma cells, while the peak of NAA is much lower because of the destruction of neuron ( Figure a,b). [13a] The results showed that a peak at 2.562 ppm was detected in the glioma region 1 h post‐injection and could even persist up to 2 h post‐injection, while no peak could be observed in the pre‐injection spectra at 2.562 ppm (Figure b). Despite a small accumulated amount in the region of the glioma, the targeted AMSNs can be sensitively detected by using MRS.…”

Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas

“…For example, the concentrations of Cho (a marker of membrane turnover and cell density) and creatine (Cr, levels of which are related to cellular energy state) can be measured in normal and tumor tissues; they appear to be distinctively distributed in high-grade brain tumors, which have significantly higher Cho/Cr ratios than benign lesions 13,14. Although proton MRS ( 1 H-MRS) imaging of Cho and other metabolites has been used for decades in the diagnosis and staging of gliomas,15 grading of tumors,16,17 and following treatment,18,19 the relationship between biochemical metabolic heterogeneity within gliomas and CSC niches has yet to be established. A recent study reported that 1 H-MRS integrated with the use of a neuronavigation system can facilitate intraoperative planning and maximal resection, based on the metabolic activities of gliomas, leading to a better patient prognosis 20.…”