Application of Proton Chemical Shift Imaging in Monitoring of Gamma Knife Radiosurgery on Brain Tumors

doi:10.1016/S0730-725X(97)00255-5

Magnetic Resonance Imaging

Volume 16, Issue 2, February 1998, Pages 197-204

https://doi.org/10.1016/S0730-725X(97)00255-5 Get rights and content

Abstract

Our objective was to assess proton chemical shift imaging for potential clinical application in monitoring response to gamma knife radiosurgery. Twenty-five proton chemical shift imaging studies and conventional magnetic resonance images were performed on six patients with intracranial tumors. The peak areas of N-acetylaspartate, choline-containing compounds (Cho), creatine, and lipids were calculated and normalized to N-acetylaspartate in the contralateral hemisphere. The spectra from the lesion before treatment showed a relatively high Cho peak, reported as a characteristic spectrum of tumors. Tumor size and Cho level after radiosurgery did not increase except in two cases. In these cases, radiation necrosis was observed with elevated Cho and a mobile lipid peak. Stable or decreased Cho seems to suggest a loss of tumor viability, and changes in Cho indicate the effectiveness of radiosurgery. Increasing Cho and the appearance of the mobile lipid peak may distinguish radiation necrosis from recurrent tumors, which cannot be distinguished by magnetic resonance imaging.

Introduction

Gamma knife radiosurgery is a stereotactic radiation therapy using a multicobalt unit supplied by Elekta (Stockholm, Sweden).[1] It enables us to irradiate intracranial targets sharply and accurately with high dosages.[2] This treatment was started with relief of pain caused by thalamic lesions[3] and has been applied to many benign brain tumors and arteriovenous malformations.4, 5, 6, 7, 8, 9, 10 It has also been applied to malignant tumors such as metastases11, 12 or malignant glioma[13] with good results.

In spite of its effectiveness, there remains some difficulty in evaluating change in the treated lesion. With conventional computed tomography or magnetic resonance imaging (MRI), the lesion may seem to increase in size after treatment, and it is difficult to determine whether it is tumor recurrence or radiation necrosis. There are some reports that differentiation between radiation necrosis and tumor recurrence in gamma knife treatment can be made by positron emission tomography with [¹⁸F] fluorodeoxyglucose,14, 15 although currently this is available at only a limited number of facilities.

Proton chemical shift imaging (¹H-CSI) is performed with a conventional magnetic resonance (MR) unit, which is a noninvasive and more popular modality than positron emission tomography. ¹H-CSI has been applied to many brain lesions, such as ischemia, tumors, and degenerative diseases, but not yet proved its utility in the clinic. In this study, we assessed the efficacy of ¹H-CSI in monitoring radiosurgery.

Section snippets

Materials and Methods

Six patients (three women, three men; age range, 13–63 years; mean, 50 ± 18 years) underwent radiosurgery. The patient population comprised four patients with metastases, one patient with astrocytoma, and one patient with meningioma. The histology and origin were confirmed by clinical findings and open surgery. The tumor volume at the time of treatment varied from 3.3 to 12.7 cm³ (8.7 cm³ ± 3.2). The marginal radiation dose was 12–30 Gy (22.0 ± 6.0 Gy), and the maximum dose was 24-60 Gy (41.5 ±

Results

In Case 1, tumor size decreased from 9.4 cm³ to 5.9 cm³, and severe headache disappeared 1 month after radiosurgery. The cystic portion of the lesion gradually increased in size and the tumor grew to a size of 4.1 cm³ 2 months after treatment. There was no tumor regrowth for 25 months after treatment. A markedly increased Cho signal was seen from the tumor center before radiosurgery, and it decreased in level 1 month after treatment. The normalized Cho showed a statistically significant

Discussion

¹H-CSI is a noninvasive method of observing in vivo metabolism in the human brain. The major resonances observed are Cho, Cr, and NAA.[19] This Cho peak consists of many compounds such as glycerylphosphorylcholine and phosphorylcholine, with a relatively small contribution from free choline.20, 21 Cho is believed to reflect membrane constituents[22] and to participate in membrane synthesis and degeneration. Typical spectra from brain tumors demonstrate very high Cho, which therefore may reflect

Conclusion

¹H-CSI is a noninvasive technique performed with a popular MR system. Cho from this ¹H-CSI study has a correlation with loss of tumor viability. ¹H-CSI can be use to differentiate between radiation necrosis and recurrent tumor. Further, ¹H-CSI is very helpful in monitoring of the radiosurgery on brain tumors.

Acknowledgements

Acknowledgment—We are very grateful to Hiroaki Asano, Department of Hygiene, Kyoto Prefectural University of Medicine, for all his help with the statistical analysis.

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Quantitative analysis of spatial averaging effect on chemical shift imaging SNR and noise coherence with k-space sampling schemes
2019, Magnetic Resonance Imaging
Citation Excerpt :
In vivo chemical shift imaging (CSI) or MRS imaging (MRSI) provides a unique imaging tool for mapping cerebral metabolites and metabolic rates, and studying neurochemistry and neuroenergetics [1–7]. In particular, with increasing recognition of complex neurological disorders/disease, CSI has been clinically useful for the improved diagnosis in the infected tissue and longitudinal monitoring of the disease progress [8], and for advancing the understanding of pathophysiological mechanisms underlying diseases [9–12]. Due to low concentration of detectable brain metabolites in a range of few mM, signal-to-noise ratio (SNR) of CSI is a key consideration for in vivo metabolite quantification that is essential for reliable neurochemical profiling in the human brain [13–16].
Spatial averaging of multiple voxels from high-resolution chemical shift imaging (hrCSI) is a common strategy for in vivo metabolic studies to achieve a better signal-to-noise ratio (SNR) for a region-of-interest. However, the mechanism about how the spatial averaging approach influences the respective spectral signal and noise and its relevance to the k-space sampling schemes remains unclear. Using three-dimension ¹⁷O CSI technique with the weighted k-space sampling method of Fourier series window, we performed quantitative SNR comparisons between a single low-resolution CSI (lrCSI) voxel (being 27 times larger than the hrCSI voxel size) and the spatially averaged hrCSI voxels with matched sampling volume and location. We demonstrated that the averaged hrCSI voxel spectrum had a large SNR loss (> 4 times) compared to the lrCSI voxel, which was resulted from unmatched increases in signal (~1.9 fold) and noise (~9.3 fold). The signal increase was caused by the spatial overlapping between the adjacent hrCSI voxels. The substantial noise increase was mainly attributed to the strong noise coherence among hrCSI voxels acquired with the weighted k-space sampling. This study presents a quantitative relation between the k-space sampling schemes to an apparent SNR penalty of the spatial averaging approach. The information could be useful for designing CSI acquisition method and determination of optimal spatial resolution for in vivo metabolic imaging studies.
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 :
This provides a unique opportunity to study the effect of radiation on the living normal human brain by means of proton magnetic resonance spectroscopy (1H MRS) in vivo. That method allows noninvasive measurement on metabolites in the brain and is widely used in monitoring treatment response of brain tumors after radiotherapy (4–24). The response of normal tissues to radiation is more predictable than for tumors, however, as the former are less heterogeneous in their cellular composition (25).
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.
Metabolite Changes in BT4C Rat Gliomas Undergoing Ganciclovir-Thymidine Kinase Gene Therapy-induced Programmed Cell Death as Studied by <sup>1</sup>H NMR Spectroscopy in Vivo, ex Vivo, and in Vitro
2003, Journal of Biological Chemistry
Citation Excerpt :
Consistent with this observation, Kizu et al. showed that in the brain tumors after radiosurgery metabolites become undetectable in the necrotic tissue. In some cases, however, macroscopically necrotic tissue showed strong signals from both lipids and CHO (33). Severe decline in CHO has also been observed in tumors responding to radiation (34).
Programmed cell death was induced by HSV-tk gene therapy in rat BT4C glioma cells, and metabolite changes associated with cell damage were monitored in vivo by ¹H NMR spectroscopy and ex vivo by high resolution magic angle spinning (HRMAS) ¹H NMR, and in vitro in perchloric acid extracts of tumors. Metabolite concentrations, as quantified in vivo using water as an internal reference and in vitro in extracts, were correlated with cell density. The results showed that both in vivo and in vitro glycine and creatine concentrations followed volume-averaged cell density, whereas that of total choline-containing compounds was unaffected by a cell loss approaching 60%. Meanwhile, both saturated and unsaturated ¹H NMR visible lipids increased. HRMAS ¹H NMR spectroscopy of the tumor samples at 14.1 tesla demonstrated the presence of nucleotide peaks from adenosine and uridine nucleotides in glioma samples ex vivo. The assignment of a doublet at 7.95 ppm to UDP was confirmed by spiking experiments of tumor extracts in conjunction with ¹H and ³¹P NMR spectroscopy. HRMAS also resolved the choline-containing peak at 3.2 ppm in vivo into resonances from choline (3.20 ppm), phosphocholine (3.22 ppm), glycerophosphocholine (3.24 ppm), and taurine (3.26 ppm). These resonances were uncorrelated with temporal progression through programmed cell death. Our results show that ¹H NMR-detected lipids and some of the small molecular weight metabolites respond to gene therapy. However, the choline-containing compounds are unaffected by severe decline in cell density. The latter observation supports the idea that triacylglycerols, rather than membrane phospholipids, are the key components of ¹H NMR visible lipids, and it also casts doubt on the validity of resonance of choline-containing compounds as a diagnostic marker of programmed cell death in vivo.
Review mr image changes of normal-appearing brain tissue after radiotherapy
2021, Cancers
MR-visible lipids and the tumor microenvironment
2011, NMR in Biomedicine
Dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain tissue after stereotactic radiosurgery: A serial proton magnetic resonance spectroscopy study
2009, Neuroradiology Journal

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Original ContributionApplication of Proton Chemical Shift Imaging in Monitoring of Gamma Knife Radiosurgery on Brain Tumors

Abstract

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusion

Acknowledgements

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

Magn. Reson. Imaging

Neurosci. Behav. Rev.

J. Biol. Chem.

Biochim. Biophys. Acta

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

The stereotaxic method and radiosurgery of the brain

Acta Chir. Scand.

Gamma knife

Jpn. J. Cancer Chemother.

Cerebral radiosurgeryGammathalamotomy in two cases of intractable pain

Acta Chir. Scand.

Stereotaxic radiosurgery for cerebral arteriovenous malformationsReport of case

Acta Chir. Scand.

Stereotactic radiosurgery for arteriovenous malformations of the brain

J. Neurosurg.

Radiosurgery of acoustic neurinomas

Cancer

Stereotactic rediosurgery for intracranial meningiomas

No Shinkei Geka

Sterotactic radiosurgery of meningiomas

J. Neurosurg.

Radiosurgical treatment of recurrent hemangiopericytomas of the meningesPreliminary results

J. Neurosurg.

Radiosurgery for venous angiomas

J. Neurosurg.

The role of stereotactic radiosurgery in the management of intracranial tumors

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The treatment of recurrent brain metastases with stereotactic radiosurgery

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Radiology

Original Contribution
Application of Proton Chemical Shift Imaging in Monitoring of Gamma Knife Radiosurgery on Brain Tumors

Work in progress[¹⁸F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain