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Parameters calculated from diffusion magnetic resonance imaging data are informative of cognitive performance. (A) Although fractional anisotropy (FA) was not different between sham and the 2 irradiated groups, white matter volume and fiber length, only in the proton group, both showed significantly higher values compared with sham (P = .03). The photon group has the highest apparent diffusion coefficient (ADC) which is significantly different from sham (P = .04) but not proton (P = .61; proton vs. sham P = .370. Data are shown as box-and-whisker plot: box extends from the 25th to 75th percentiles, median value marked by line and whiskers extend from min to max, n = 7-9/group. (B) Correlation of the connectomic metrics and 5-choice serial reaction time task testing at 12 months postirradiation. *P < .05 and **P < .01.
Source publication
Purpose
Compared to photon radiation therapy (X-CRT), proton cranial radiotherapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional MR and PET imaging markers and molecular differences between the radiation modalities.
Methods
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Contexts in source publication
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... .0001) were significantly lighter and shorter than sham animals. This phenotype persisted for the duration of the study. In addition, the proton irradiated group was significantly lighter than the photon irradiated group at 6 (P = .018) and 12 months post-CRT (P = .046) as well as significantly shorter in stature at 12 months post-CRT (P = .0272) (Fig. E3). Brain growth was also stunted, irradiated brains were lighter (P-CRT: P = .02, X-CRT: P = .03) and shorter (P-CRT: P < .0001, X-CRT: P = .0015) compared with sham animals with no significant differences between the 2 radiation modalities (Fig. E4). ...
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... < .01, and ***P < .001 significant difference between the groups (Table E1). Both white matter volume and fiber length showed significantly higher values compared with sham (P = .03), but only in the P-CRT group. The X-CRT group had the highest ADC which was significantly different from sham (P = .04), but P-CRT ADC was not different from sham (Fig. ...
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... at 12 months. Significant negative correlations were found between 5-CSRTT Percent Correct and Local efficiency, fiber length, and white matter volume. Correlation was also found between Percent Incorrect and fiber length. In addition, Percent Omission was found to be significantly correlated with both fiber length and white matter volume (Fig. ...
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... We and others have shown that the increase in brain glucose consumption coincides with an increase in brain inflammation. 12,35 These findings are in agreement with the ADC data presented in Figure 3 which show a greater change in the X-CRT group's apparent diffusion compared with the P-CRT group. Immunohistochemistry further confirms these imaging results, however statistical significance was not established between P-CRT and X-CRT. ...
Citations
... At the early stage of space exploration, the amount of radiation exposure was limited, but its impacts have increased as space mission expanded to Mars (expected dose: 350mSv/year for 3 years) [9,10]. In general, the heavy ions, such as hydrogen ( 1 H 1 ), carbon ( 12 C 6 ), silicone ( 28 S 14 ), titanium ( 48 Ti 22 ), and iron ( 56 Fe 26 ), damage DNA by producing lesion-speci c enzymes to break its double-strand [2]. Once the series of damages are initiated, the radiation-induced effects sequentially expand to the damages at upper biological levels, like chromosomal aberrations [11], cell kinetics [12], mitotic death [13], peripheral blood lymphocytes [14]. ...
... Proton, which is the dominant type in space radiation as mentioned, has been mainly used for the medical purpose, speci cally cancer therapy [21][22][23]. The repeated treatment by proton exposure raised the concerns of cognitive impairment, and some studies demonstrated the relation between the proton exposure and the cognition-related functional decline [21,22,[24][25][26]. ...
... Proton, which is the dominant type in space radiation as mentioned, has been mainly used for the medical purpose, speci cally cancer therapy [21][22][23]. The repeated treatment by proton exposure raised the concerns of cognitive impairment, and some studies demonstrated the relation between the proton exposure and the cognition-related functional decline [21,22,[24][25][26]. However, the cognition-related behavioral alteration as the functional endpoint after proton exposure is still ambiguous while the neurochemical [27,28], neurophysiological [25] and functional images [22,29] have indicated the protoninduced damages in the brain. ...
A long-term space exploration faces extremely hazardous environmental stresses, and the exposure to space radiation has been considered as one of the most dangerous factors in Space. For the safety of astronauts, even a low amount of proton exposure in space radiation is necessary to be understood to protect their body systems and maintain the functional balance. However, the endpoint test based on behavioral responses lead to an undetermined consequence in the functional declines by producing the inconsistent results despite of the accumulated proofs in the molecular and the cellular damages by proton. To clarify the systemic link between the proton exposure and the cognitive decline in behaviors, some fundamental behavioral tests, such as rota-rod, open field test, and novel object recognition, were revisited, and the proton-induced alteration was examined by computing behavioral markers in time basis. A portion out of total population (28 SD rats) involved for each test, and the relevant behavioral markers in time were calculated to assess the proton-induced effects in emotion, locomotion and memory. The examination in 3 months of behavioral responses after the different amount of exposure (control, 30cGy-, and 1Gy-exposed animals) identified the emotional and locomotive alterations while few memory-related changes were observed. The computed behavioral markers suggested a quantitative approach to demonstrate the cognitive behavioral effects by a low amount of proton (30cGy) as well as the direct relation between the proton exposure and the cognitive alteration.
Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures.
Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses.
Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures.
Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.
Purpose
Proton beam radiation therapy reduces dose to healthy brain tissue and thereby decreases the risk of treatment-related decline in neurocognition. Considering the paucity of prospective data, this study aimed to evaluate neurocognitive performance in an adult patient population with intracranial tumors.
Methods and Materials
Between 2017 and 2021, patients enrolled in the MedAustron registry study and irradiated for intracranial tumors were eligible for neurocognitive assessment. Patients with available 1-year follow-up data were included in the analysis. The test battery consisted of a variety of standardized tests commonly used in European Organization for Research and Treatment of Cancer trials. Scores were transformed into z scores to account for demographic effects, and clinically relevant change was defined as a change of ≥1.5 standard deviations. Binary logistic regression analysis and the χ² test were conducted for clinical parameters and dosimetric hippocampal parameters to evaluate the relationship with overall cognitive decline and changes in memory.
Results
One hundred twenty-three patients with mostly nonprogressive, extra-axial tumors and neurocognitive assessment at baseline and treatment end as well as 3, 6, and 12 months after completion of proton beam radiation therapy were analyzed. Overall, 7 test scores revealed stability in neurocognitive function with minimal positive changes 1 year after treatment completion (statistically significant in 6 of 7 tests), whereas the majority had no or minimal baseline deficits. At 1-year follow-up, 89.4% of all patients remained stable in their overall cognitive functioning without clinically relevant deterioration in 2 or more tests. None of them showed disease progression. Of the patients, 8.1% presented with radiation-induced brain lesions and exhibited a higher percentage of overall cognitive deterioration without reaching statistical significance. Multivariate binary logistic regression analysis revealed higher age at baseline as the only independent parameter to be associated with an overall clinically relevant cognitive decline. There was no significant correlation of hippocampal doses and memory functioning.
Conclusions
One year after proton therapy, we observed preservation of cognitive functioning in the vast majority of our patients with intracranial tumors.
