DCE-MRI detected vascular permeability changes in the rat spinal cord do not explain shorter latency times for paresis after carbon ions relative to photons

Author(s):  
Alina L. Bendinger ◽  
Thomas Welzel ◽  
Lifi Huang ◽  
Inna Babushkina ◽  
Peter Peschke ◽  
...  
2020 ◽  
Author(s):  
Thomas Welzel ◽  
Alina Leandra Bendinger ◽  
Christin Glowa ◽  
Inna Babushkina ◽  
Manfred Jugold ◽  
...  

Abstract Background Radiation-induced myelopathy is a severe and irreversible complication that occurs after a long symptom-free latency time if the spinal cord was exposed to a significant irradiation dose during tumor treatment. As carbon ions are increasingly investigated for tumor treatment in clinical trials, their effect on normal tissue needs further investigation to assure safety of patient treatments. Magnetic resonance imaging (MRI)-visible morphological alterations could serve as predictive markers for medicinal interventions to avoid severe side effects. Thus, MRI-visible morphological alterations in the rat spinal cord after high dose photon and carbon ion irradiation and their latency times were investigated.MethodsRats whose spinal cords were irradiated with iso-effective high photon (n = 8) or carbon ion (n = 8) doses as well as sham-treated control animals (n=6) underwent frequent MRI measurements until they developed radiation-induced myelopathy (paresis II). MR images were analyzed for morphological alterations and animals were regularly tested for neurological deficits. In addition, histological analysis was performed of animals suffering from paresis II compared to controls.ResultsFor both beam modalities, first morphological alterations occurred outside the spinal cord (bone marrow conversion, contrast agent accumulation in the musculature ventral and dorsal to the spinal cord) followed by morphological alterations inside the spinal cord (edema, syrinx, contrast agent accumulation) and eventually neurological alterations (paresis I and II). Latency times were significantly shorter after carbon ions as compared to photon irradiation.Conclusions Irradiation of the rat spinal cord with photon or carbon ion doses that lead to 100% myelopathy induced a comparable fixed sequence of MRI-visible morphological alterations and neurological distortions. However, at least in the animal model used in this study, the observed MRI-visible morphological alterations in the spinal cord are not suited as predictive markers to identify animals that will develop myelopathy as the time between MRI-visible alterations and the occurrence of myelopathy is too short to intervene with protective or mitigative drugs.


2020 ◽  
Vol 32 (7) ◽  
Author(s):  
Juan Herrera ◽  
Kurt Bockhorst ◽  
Deepa Bhattarai ◽  
Karen Uray

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Maria Saager ◽  
Christin Glowa ◽  
Peter Peschke ◽  
Stephan Brons ◽  
Rebecca Grün ◽  
...  

Abstract Background To determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations. Material and methods The rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV). Results At six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range. Conclusions This study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Thomas Welzel ◽  
Alina L. Bendinger ◽  
Christin Glowa ◽  
Inna Babushkina ◽  
Manfred Jugold ◽  
...  

Abstract Background Radiation-induced myelopathy is a severe and irreversible complication that occurs after a long symptom-free latency time if the spinal cord was exposed to a significant irradiation dose during tumor treatment. As carbon ions are increasingly investigated for tumor treatment in clinical trials, their effect on normal tissue needs further investigation to assure safety of patient treatments. Magnetic resonance imaging (MRI)-visible morphological alterations could serve as predictive markers for medicinal interventions to avoid severe side effects. Thus, MRI-visible morphological alterations in the rat spinal cord after high dose photon and carbon ion irradiation and their latency times were investigated. Methods Rats whose spinal cords were irradiated with iso-effective high photon (n = 8) or carbon ion (n = 8) doses as well as sham-treated control animals (n = 6) underwent frequent MRI measurements until they developed radiation-induced myelopathy (paresis II). MR images were analyzed for morphological alterations and animals were regularly tested for neurological deficits. In addition, histological analysis was performed of animals suffering from paresis II compared to controls. Results For both beam modalities, first morphological alterations occurred outside the spinal cord (bone marrow conversion, contrast agent accumulation in the musculature ventral and dorsal to the spinal cord) followed by morphological alterations inside the spinal cord (edema, syrinx, contrast agent accumulation) and eventually neurological alterations (paresis I and II). Latency times were significantly shorter after carbon ions as compared to photon irradiation. Conclusions Irradiation of the rat spinal cord with photon or carbon ion doses that lead to 100% myelopathy induced a comparable fixed sequence of MRI-visible morphological alterations and neurological distortions. However, at least in the animal model used in this study, the observed MRI-visible morphological alterations in the spinal cord are not suited as predictive markers to identify animals that will develop myelopathy as the time between MRI-visible alterations and the occurrence of myelopathy is too short to intervene with protective or mitigative drugs.


1979 ◽  
Vol 169 (1) ◽  
pp. 163-167 ◽  
Author(s):  
William B. Stewart ◽  
Franklin C. Wagner

Author(s):  
V. Kriho ◽  
H.-Y. Yang ◽  
C.-M. Lue ◽  
N. Lieska ◽  
G. D. Pappas

Radial glia have been classically defined as those early glial cells that radially span their thin processes from the ventricular to the pial surfaces in the developing central nervous system. These radial glia constitute a transient cell population, disappearing, for the most part, by the end of the period of neuronal migration. Traditionally, it has been difficult to definitively identify these cells because the principal criteria available were morphologic only.Using immunofluorescence microscopy, we have previously defined a phenotype for radial glia in rat spinal cord based upon the sequential expression of vimentin, glial fibrillary acidic protein and an intermediate filament-associated protein, IFAP-70/280kD. We report here the application of another intermediate filament-associated protein, IFAP-300kD, originally identified in BHK-21 cells, to the immunofluorescence study of radial glia in the developing rat spinal cord.Results showed that IFAP-300kD appeared very early in rat spinal cord development. In fact by embryonic day 13, IFAP-300kD immunoreactivity was already at its peak and was observed in most of the radial glia which span the spinal cord from the ventricular to the subpial surfaces (Fig. 1). Interestingly, from this time, IFAP-300kD immunoreactivity diminished rapidly in a dorsal to ventral manner, so that by embryonic day 16 it was detectable only in the maturing macroglial cells in the marginal zone of the spinal cord and the dorsal median septum (Fig. 2). By birth, the spinal cord was essentially immuno-negative for this IFAP. Thus, IFAP-300kD appears to be another differentiation marker available for future studies of gliogenesis, especially for the early stages of radial glia differentiation.


Sign in / Sign up

Export Citation Format

Share Document