The effect of radiation on normal human CNS as detected by NMR spectroscopy

doi:10.1016/0360-3016(93)90018-Q

International Journal of Radiation OncologyBiologyPhysics

Volume 25, Issue 4, 15 March 1993, Pages 695-701

https://doi.org/10.1016/0360-3016(93)90018-Q Get rights and content

Abstract

In a prospective study, proton (¹H) and phosphorus (³¹P) nuclear magnetic resonance spectroscopy were used to search for effects of brain tumor radiotherapy on normal human central nervous system. Phosphorus spectroscopy data at 1.5 T seems to suggest that any radiation induced damage that may occur as a result of therapeutic brain irradiation, does not alter the relative concentrations of phosphorus metabolites or the intracellular pH beyond the limits of normal variation (approximately ±20%). Proton spectroscopy, on the other hand, detects post radiation changes in the ratios of certain nuclear magnetic resonance visible metabolites following radiotherapy, particularly choline/N-acetylaspartate, and especially in regions of brain receiving high doses of radiation. Such changes may be indicative of the release of membrane bound choline during radiation induced demyelination of brain. Of interest, we have found elevated metabolite ratios of ³¹P in normal central nervous system prior to radiotherapy, which persisted throughout the time span of the study in both the ipsilateral and contralateral cerebral hemispheres.

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Cited by (49)

Imaging methods used in the differential diagnosis between brain tumour relapse and radiation necrosis after stereotactic radiosurgery of brain metastases: Literature review
2016, Cancer/Radiotherapie
Après irradiation d’une métastase cérébrale en conditions stéréotaxiques, la toxicité redoutée est la radionécrose. Dans le cadre du suivi de ces patients, il est impossible de distinguer la radionécrose d’une rechute tumorale, que ce soit cliniquement ou à l’imagerie par résonance magnétique (IRM). Dans la pratique courante, de nombreux moyens d’imagerie sont utilisés, tels que des séquences particulières d’IRM (perfusion, diffusion), la spectro-RMN, la tomographie par émission de positons (TEP)-scanographie, ou de façon plus anecdotique la tomographie d’émission monophotonique (single-photon emission computed tomography [SPECT]) au thallium 201 (²⁰¹TI). Cet article est une revue de la littérature requise avant l’établissement d’un arbre décisionnel à partir d’une analyse de données rétrospectives et prospectives.
After stereotactic radiosurgery for a cerebral metastasis, one of the dreaded toxicities is radionecrosis. In the follow-up of these patients, it is impossible to distinguish radiation necrosis from tumour relapse either clinically or with MRI. In current practice, many imaging methods are designed such as special sequences of MRI (dynamic susceptibility contrast perfusion and susceptibility-weighted imaging, diffusion), proton magnetic resonance spectroscopy, positron emission tomography, or more seldom 201-thallium single-photon emission computerized tomography. This article is a required literature analysis in order to establish a decision tree with the analysis of retrospective and prospective data.
Influence of echo time in quantitative proton MR spectroscopy using LCModel
2015, Magnetic Resonance Imaging
Citation Excerpt :
Based on the above, when TE is longer than recommended, it is necessary to adjust the correction coefficient since the signal correction is insufficient. Although the ratios of quantitative values obtained using LCModel and the T2-corrected internal reference method tended to be large at long TE, there was no significant difference because the ratios differed substantially between patients (Fig. 2), owing to the large differences in T2 relaxation times of water and metabolites between individual patients [10,17–19]. In the T2-corrected internal reference method, the signal value at TE = 0 ms is extrapolated by deriving the T2 relaxation curve from three TE points.
The objective of this study was to elucidate the influence on quantitative analysis using LCModel with the condition of echo time (TE) longer than the recommended values in the spectrum acquisition specifications.
A 3 T magnetic resonance system was used to perform proton magnetic resonance spectroscopy. The participants were 5 healthy volunteers and 11 patients with glioma. Data were collected at TE of 72, 144 and 288 ms. LCModel was used to quantify several metabolites (N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds). The results were compared with quantitative values obtained by using the T2-corrected internal reference method.
In healthy volunteers, when TE was long, the quantitative values obtained using LCModel were up to 6.8-fold larger (p < 0.05) than those obtained using the T2-corrected internal reference method. The ratios of the quantitative values obtained by the two methods differed between metabolites (p < 0.05). In patients with glioma, the ratios of quantitative values obtained by the two methods tended to be larger at longer TE, similarly to the case of healthy volunteers, and large between-individual variation in the ratios was observed.
In clinical practice, TE is sometimes set longer than the value recommended for LCModel. If TE is long, LCModel overestimates the quantitative value since it cannot compensate for signal attenuation, and this effect is different for each metabolite and condition. Therefore, if TE is longer than recommended, it is necessary to account for the possibly reduced reliability of quantitative values calculated using LCModel.
Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: Statistical analysis of a large group of patients
2006, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
The CG response to irradiation is faster than that of Cho/NAA. There is agreement that the 1H MRS in vivo metabolic profile of the brain regions that are distant from the tumor site is disturbed (3, 6, 7, 13, 19, 20, 24, 26–29, 37–40). The postirradiation changes involve increase in Cho, mI, Lac, and Lip as well as a decrease in NAA as compared with the pre-RT state.
Purpose: The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using ¹H nuclear magnetic resonance (NMR) spectroscopy in vivo.
Methods and Materials: A total of 394 ¹H MR spectra were acquired from 100 patients (age 19–74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy).
Results: Ocilations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band in the range of 0.7–1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months.
Conclusions: The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.
MRI changes due to early-delayed conformal radiotherapy and postsurgical effects in patients with brain tumors
2005, International Journal of Radiation Oncology Biology Physics
Purpose: Discernment of radiotherapy (XRT) effects vs. tumor activity is difficult in brain tumor patients during the months after XRT when white matter hyperintensities sometimes emerge. We examined brain scans in XRT-treated vs. untreated patients for early-delayed post-XRT effects.
Methods and Materials: Brain regions susceptible to XRT injury were examined on magnetic resonance imaging (MRI) for T2-weighted hyperintensities and atrophy in 37 adults with low-grade primary brain tumors (13 nonirradiated and 24 irradiated). Cases evidencing recurrence/growth over the study period were censored. Interactions with age, mood, fatigue, medications, tumor type and grade, extent of resection, and laterality of MRI changes were examined.
Results: Hyperintensity and atrophy ratings over time for the treated and untreated groups were not significantly different. White matter atrophy increased unrelated to XRT. In all patients combined, white matter atrophy and hyperintensities were greater at all time points and more lateralized in surgically treated patients.
Conclusions: Radiotherapy status was not related to changes in MRI ratings during the weeks/months after XRT. Findings contradict assumptions about radiographically evidenced early-delayed XRT effects. Increases in T2-weighted hyperintensities during the 1–6-month period postconformal radiotherapy for low-grade tumors are likely not related to early-delayed XRT effects.
Differentiation among metastatic brain tumors, radiation necroses, and brain abscesses using proton magnetic resonance spectroscopy
2004, Kaohsiung Journal of Medical Sciences
Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) were evaluated for differentiating metastatic brain tumors, radiation necroses, and brain abscesses. Twelve histologically verified lesions in 12 patients were studied using preoperative MRI and proton MRS. The signal intensities of four major metabolites, N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and lactate (Lac), were observed over the region of interest. Metastatic brain tumors showed a decrease in NAA/Cr and an increase in Cho/Cr ratios. Radiation necroses showed a decrease in NAA/Cr and no change in Cho/Cr ratios. Brain abscesses showed an increase in Lac/Cr ratio. Correlation with histopathologic findings showed that a high Cho signal was suggestive of a metastatic brain tumor. Lac signals were observed in brain abscesses, presumably reflecting the anerobic glycolysis of living cells. Although more cases and studies are necessary, metabolic information provided by proton MRS combined with MRI is useful for differentiating among metastatic brain tumors, radiation necroses, and brain abscesses.
Investigation of metabolic changes in irradiated rat brain tissue by means of <sup>1</sup>H NMR in vitro relaxation study
2004, Solid State Nuclear Magnetic Resonance
The effect of irradiation on concentrations and relaxation behaviour of brain metabolites was studied by means of high-resolution ¹H NMR in vitro. The studies were performed on rat brains irradiated with the doses of 20 Gy applied in fractions of 2 Gy. Standard procedures were used to obtain HClO₄ extracts of rat brains. The ¹H NMR studies of the extracts solutions in D₂O were performed using a Varian Inova-300 NMR spectrometer. The integral intensities of the metabolite signals were found to change during the irradiation cycle and after it. These changes are accompanied by the variations in the T1 relaxation times. N-acetylaspartate, glycerophosphocholine, phosphocholine, choline, creatine and phosphocreatine, myoinositol and taurine were analysed as potential markers of irradiation injury.

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International Journal of Radiation OncologyBiologyPhysics

Abstract

References (30)

Localized proton spectroscopy using stimulated echoes

J. Magn. Reson.

Size dependant changes in tumor phosphate metabolism after radiation therapy as detected by ³¹p spectroscopy

Int. J. Radiation Oncology Biol. Phys.

Selective excitation in Fourier transform nuclear magnetic resonance

J. Mag. Res.

Myelin basic protein and magnetic resonance imaging for diagnostic radiation myelopathy

Int. J. Radiat. Oncol. Biol. Phys.

An in vivo phosphorus NMR study of variations with age on the phosphodiester content in human muscle

Mechan. Aging Devel.

Creatinine and creatine in the CSF: indices of brain energy metabolism in depression

J. Neural Transmission

Depth and refocusing pulses designed for multipulse NMR with surface coils

J. Mag. Res.

Brain tumor cell kinetics correlated with survival

J. Neurosurg.

Changes in intracranial pressure associated with delayed cerebral radionecrosis

Med. Phys.

The morphologic effects of radiation administered therapeutically for intracranial gliomas

Cancer

Phospholipid methylation

Experimental observations: Delayed radiation necrosis in normal monkey brain

The process of demyelination in the central nervous system II

Exp. Neural.

Brain radiation lesions: MR imaging

Radiology

Experimental radiation injury

Radiology

Cited by (49)

Imaging methods used in the differential diagnosis between brain tumour relapse and radiation necrosis after stereotactic radiosurgery of brain metastases: Literature review

Influence of echo time in quantitative proton MR spectroscopy using LCModel

Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: Statistical analysis of a large group of patients

MRI changes due to early-delayed conformal radiotherapy and postsurgical effects in patients with brain tumors

Differentiation among metastatic brain tumors, radiation necroses, and brain abscesses using proton magnetic resonance spectroscopy

Investigation of metabolic changes in irradiated rat brain tissue by means of <sup>1</sup>H NMR in vitro relaxation study

Therapeutic oncologic imagingThe effect of radiation on normal human CNS as detected by NMR spectroscopy

Abstract

J. Magn. Reson.

Int. J. Radiation Oncology Biol. Phys.

J. Mag. Res.

Int. J. Radiat. Oncol. Biol. Phys.

Mechan. Aging Devel.

Creatinine and creatine in the CSF: indices of brain energy metabolism in depression

J. Neural Transmission

Depth and refocusing pulses designed for multipulse NMR with surface coils

J. Mag. Res.

Brain tumor cell kinetics correlated with survival

J. Neurosurg.

Changes in intracranial pressure associated with delayed cerebral radionecrosis

Med. Phys.

The morphologic effects of radiation administered therapeutically for intracranial gliomas

Cancer

Phospholipid methylation

Experimental observations: Delayed radiation necrosis in normal monkey brain

The process of demyelination in the central nervous system II

Exp. Neural.

Brain radiation lesions: MR imaging

Radiology

Experimental radiation injury

Radiology

Therapeutic oncologic imaging
The effect of radiation on normal human CNS as detected by NMR spectroscopy