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Eosinophil-Associated Gene Pathways but not Eosinophil Numbers are Differentially Regulated between Synchrotron Microbeam Radiation Treatment and Synchrotron Broad-Beam Treatment by 48 Hours Postirradiation

Ibahim MJ, Yang Y, Crosbie JC, Stevenson A, Cann L, Paiva P, et al.

Radiat Res, 2016 Jan;185(1):60-8.
PMID: 26720800 DOI: 10.1667/RR14115.1

Synchrotron microbeam radiation treatment (MRT) is a preclinical radiotherapy technique with considerable clinical promise, although some of the underlying radiobiology of MRT is still not well understood. In recently reported studies, it has been suggested that MRT elicits a different tumor immune profile compared to broad-beam treatment (BB). The aim of this study was to investigate the effects of synchrotron MRT and BB on eosinophil-associated gene pathways and eosinophil numbers within and around the tumor in the acute stage, 48 h postirradiation. Balb/C mice were inoculated with EMT6.5 mouse mammary tumors and irradiated with microbeam radiation (112 and 560 Gy) and broad-beam radiation (5 and 9 Gy) at equivalent doses determined from a previous in vitro study. After tumors were collected 24 and 48 h postirradiation, RNA was extracted and quantitative PCR performed to assess eosinophil-associated gene expression. Immunohistochemistry was performed to detect two known markers of eosinophils: eosinophil-associated ribonucleases (EARs) and eosinophil major basic protein (MBP). We identified five genes associated with eosinophil function and recruitment (Ear11, Ccl24, Ccl6, Ccl9 and Ccl11) and all of them, except Ccl11, were differentially regulated in synchrotron microbeam-irradiated tumors compared to broad-beam-irradiated tumors. However, immunohistochemical localization demonstrated no significant differences in the number of EAR- and MBP-positive eosinophils infiltrating the primary tumor after MRT compared to BB. In conclusion, our work demonstrates that the effects of MRT on eosinophil-related gene pathways are different from broad-beam radiation treatment at doses previously demonstrated to be equivalent in an in vitro study. However, a comparison of the microenvironments of tumors, which received MRT and BB, 48 h after exposure showed no difference between them with respect to eosinophil accumulation. These findings contribute to our understanding of the role of differential effects of MRT on the tumor immune response.
Effect of iterative reconstruction algorithm levels on noise index and figure-of-merit in CT pulmonary angiography examinations

Harun HH, Karim MKA, Abbas Z, Sabarudin A, Muniandy SC, Ibahim MJ

J Xray Sci Technol, 2020;28(5):893-903.
PMID: 32741801 DOI: 10.3233/XST-200699

PURPOSE: To evaluate the influence of iterative reconstruction (IR) levels on Computed Tomography (CT) image quality and to establish Figure of Merit (FOM) value for CT Pulmonary Angiography (CTPA) examinations.
METHODS: Images of 31 adult patients who underwent CTPA examinations in our institution from March to April 2019 were retrospectively collected. Other data, such as scanning parameters, radiation dose and body habitus information from the subjects were also recorded. Six different levels of IR were applied to the volume data of the subjects. Five circles of the region of interest (ROI) were drawn in five different arteries namely, pulmonary trunk, right pulmonary artery, left pulmonary artery, ascending aorta and descending aorta. The mean Signal-to-noise ratio (SNR) was obtained, and the FOM was calculated in a fraction of the SNR2 divided by volume-weighted CT dose index (CTDIvol) and SNR2 divided by the size-specific dose estimates (SSDE).
RESULTS: Overall, we observed that the mean value of CTDIvol and SSDE were 13.79±7.72 mGy and 17.25±8.92 mGy, respectively. Notably, SNR values significantly increase with increase of the IR level (p
Synchrotron microbeam radiotherapy evokes a different early tumor immunomodulatory response to conventional radiotherapy in EMT6.5 mammary tumors

Yang Y, Swierczak A, Ibahim M, Paiva P, Cann L, Stevenson AW, et al.

Radiother Oncol, 2019 04;133:93-99.
PMID: 30935588 DOI: 10.1016/j.radonc.2019.01.006

BACKGROUND: Synchrotron microbeam radiation therapy (MRT) is a new, evolving form of radiotherapy that has potential for clinical application. Several studies have shown in preclinical models that synchrotron MRT achieves equivalent tumor control to conventional radiotherapy (CRT) but with significantly reduced normal tissue damage.
METHODS: To explore differences between these two modalities, we assessed the immune cell infiltrate into EMT6.5 mammary tumors after CRT and MRT.
RESULTS: CRT induced marked increases in tumor-associated macrophages and neutrophils while there were no increases in these populations following MRT. In contrast, there were higher numbers of T cells in the MRT treated tumors. There were also increased levels of CCL2 by immunohistochemistry in tumors subjected to CRT, but not to MRT. Conversely, we found that MRT induced higher levels of pro-inflammatory genes in tumors than CRT.
CONCLUSION: Our data are the first to demonstrate substantial differences in macrophage, neutrophil and T cell numbers in tumors following MRT versus CRT, providing support for the concept that MRT evokes a different immunomodulatory response in tumors compared to CRT.

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