Irradiation Effects on the Metabolism of Metastatic Brain Tumors: Analysis by Positron Emission Tomography and ¹H-Magnetic Resonance Spectroscopy

Abstract

To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and ¹H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4–10.1 cm³ (mean: 5.5 cm³). The marginal dose to the tumor was 24–30 Gy (mean: 26.2 Gy). The follow-up period was 5–19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. ¹⁸F-fluoroboronophenylalanine (¹⁸FBPA) or ¹⁸F-fluorodeoxyglucose (¹⁸FDG) were used as tracers for the PET study. Using ¹H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of ¹⁸FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the ¹H-MRS study, choline, which is characteristically high in metastatic brain tumors, also decreased over time. In two cases with suspected radiation injury, the enhanced region, which was decreased in size in early follow-up, enlarged progressively and was accompanied by edema. However, ¹⁸FBPA and ¹⁸FDG were not transported to the enhanced region. The peak of free lipid, which might show destruction of the cell membrane, was recognized in the enhanced region and adjacent brain in these cases. This study revealed that radiation effects on the metabolism of metastatic brain tumors occur at an early stage after radiosurgery and continue over several months. In particular, in the case of radiation injury, PET and ¹H-MRS studies made it possible to distinguish between regrowth of the tumor and radiation injury.

Dynamics of Metabolic Changes in Intracranial Metastases and Distant Normal-Appearing Brain Tissue after Stereotactic Radiosurgery: A Serial Proton Magnetic Resonance Spectroscopy Study

“…By contrast, tumor progression was associated with prominent metabolic alterations, such as decrease of NAA content, NAA/Cho ratio and Cr content, and increase of Lip/nCr ratio and Cho content. This confirms the appropriateness of 1 H-MRS for diagnosis of local recurrence of intracranial metastases after SRS 9,10,27,29,32 . Moreover, analysis of the serial metabolic data in progressing lesions revealed several subtle neurochemical alterations before volumetric changes in the neoplasm.…”

“…Previously we found that initial decreases of Cho and NAA can be identified as early as 16-18 hours after treatment 7 . Others observed decreases of Cho, Lac or Lip and increases in NAA on MR spectra of metastatic adenocarcinoma within the first week after SRS 29,30 . In the series of Kimura et al 31 the effects of irradiation were marked on 1 H-MRS of brain metastases on average 2.8±1.6 weeks after radiosurgery and were observed earlier than changes in 201 TlCl single photon emission computed tomography and gadoliniumcurrent gliomas 23,24 .…”

“…enhanced MRI. On longer follow-up responsive neoplasms usually exhibit a gradual decrease of Cho and Lac 31,32 , or show the appearance or elevation of Lip with a decrease of all other metabolites as a possible result of the radiationinduced tumor necrosis29 .…”

Cerebral Radiation Necrosis

“…Studies that compare techniques, however, are few and have conflicting results. Some authors suggested that using PET and MRS in conjunction may help distinguish tumor recurrence from necrosis (39). Others have not found significant advantages in using PET versus thallium-201 SPECT (40).…”

Proton magnetic resonance spectroscopy: clinical applications in patients with brain lesions

“…Coupled with magnetic resonance imaging techniques, it allows for the corre-lation of anatomical and physiological changes in the metabolic and biochemical processes occurring within previously-determined volumes in the brain. 13 Proton magnetic resonance spectroscopy of the brain is useful whenever biochemical or metabolic assessment may be necessary, such as in differential diagnosis of focal brain lesions (neoplastic and non-neoplastic diseases); [14][15][16][17][18][19][20] brain lesions in patients with acquired immunodeficiency syndrome; [21][22][23] diagnosis of dementia [24][25][26] and other degenerative diseases; 27 follow-up radiation therapy for patients with brain neoplasms; [28][29][30] demyelinating diseases such as multiple sclerosis [31][32][33] and leukodystrophy; 6,34 diagnosis and prognosis of brain ischemic 35,36 and traumatic lesions; [37][38][39][40][41][42] assessment of epilepsy; [43][44][45] biochemical alterations in hepatic encephalopathies; 46,47 and neuropediatric affections such as brain tumors, inborn errors of metabolism and hypoxic encephalopathy. [48][49][50] Magnetic resonance examinations, including spectroscopy, are absolutely contraindicated in patients with heart pacemakers or other electronic appliances implanted in the body, and thos...…”