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- Devarakonda, Sravani, et al.
(författare)
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Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
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Ingår i: EBioMedicine. - 2352-3964. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
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| 2. |
- Klintström, Eva, 1957-
(författare)
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Image Analysis for Trabecular Bone Properties on Cone-Beam CT Data
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trabecular bone structure as well as bone mineral density (BMD) have impact on the biomechanical competence of bone. In osteoporosis-related fractures, there have been shown to exist disconnections in the trabecular network as well as low bone mineral density. Imaging of bone parameters is therefore of importance in detecting osteoporosis. One available imaging device is cone-beam computed tomography (CBCT). This device is often used in pre-operative imaging of dental implants, for which the trabecular network also has great importance.Fourteen or 15 trabecular bone specimens from the radius were imaged for conducting this in vitro project.The imaging data from one dual-energy X-ray absorptiometry (DXA), two multi-slice computed tomography (MSCT), one high-resolution peripheral quantitative computed tomography (HR-pQCT) and four CBCT devices were segmented using an in-house developed code based on homogeneity thresholding. Seven trabecular microarchitecture parameters, as well as two trabecular bone stiffness parameters, were computed from the segmented data. Measurements from micro-computed tomography (micro-CT) data of the same bone specimens were regarded as gold standard.Correlations between MSCT and micro-CT data showed great variations, depending on device, imaging parameters and between the bone parameters. Only the bone-volume fraction (BV/TV) parameter was stable with strong correlations. Regarding both HR-pQCT and CBCT, the correlations to micro-CT were strong for bone structure parameters as well as bone stiffness parameters. The CBCT device 3D Accuitomo showed the strongest correlations, but overestimated BV/TV more than three times compared to micro-CT. The imaging protocol most often used in clinical imaging practice at our clinic demonstrated strong correlations as well as low radiation dose.CBCT data of trabecular bone can be used for analysing trabecular bone properties, like bone microstructure and bone biomechanics, showing strong correlations to the reference method of micro-CT. The results depend on choice of CBCT device as well as segmentation method used. The in-house developed code based on homogeneity thresholding is appropriate for CBCT data. The overestimations of BV/TV must be considered when estimating bone properties in future clinical dental implant and osteoporosis research.
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