MRI-only based radiotherapy treatment planning for the rat brain on a Small Animal Radiation Research Platform (SARRP)

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences were: T1-weighted, T2-weighted, zero-echo time (ZTE), and two ultra-short echo time sequences with 20 mu s (UTE1) and 2 ms (UTE2) echo times. CT data were manually segmented into air, soft tissue, and bone to obtain the RTP reference. Bias field corrected MR images were automatically segmented into the same tissue classes using a fuzzy c-means segmentation algorithm with multiple images as input. Similarities between segmented CT and automatic segmented MR (ASMR) images were evaluated using Dice coefficient. Three ASMR images with high similarity index were used for further RTP. Three beam arrangements were investigated. Dose distributions were compared by analysing dose volume histograms. The highest Dice coefficients were obtained for the ZTE-UTE2 combination and for the T1-UTE1-T2 combination when ZTE was unavailable. Both combinations, along with UTE1-UTE2, often used to generate ASMR images, were used for further RTP. Using 1 beam, MR based RTP underestimated the dose to be delivered to the target (range: 1.4%-7.6%). When more complex beam configurations were used, the calculated dose using the ZTE-UTE2 combination was the most accurate, with 0.7% deviation from CT, compared to 0.8% for T1-UTE1-T2 and 1.7% for UTE1-UTE2. The presented MR-only based workflow for RTP on a SARRP enables both accurate organ delineation and dose calculations using multiple MR sequences. This method can be useful in longitudinal studies where CT's cumulative radiation dose might contribute to the total dose

Image Aquisition Order and Input Order of BOLD-fMRI Data for Slice Time Correction in fMRI Data Processing Tools

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Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure, increases intraperitoneal chemotherapy drug penetration, and impedes tumor growth in a mouse colorectal carcinomatosis model

Cytoreductive surgery combined with intraperitoneal chemotherapy (IPC) is currently the standard treatment for selected patients with peritoneal carcinomatosis of colorectal cancer. However, especially after incomplete cytoreduction, disease progression is common and this is likely due to limited tissue penetration and efficacy of intraperitoneal cytotoxic drugs. Tumor microenvironment-targeting drugs, such as VEGF(R) and PDGFR inhibitors, can lower the heightened interstitial fluid pressure in tumors, a barrier to drug delivery. Here, we investigated whether tumor microenvironment-targeting drugs enhance the effectiveness of intraperitoneal chemotherapy. A mouse xenograft model with two large peritoneal implants of colorectal cancer cells was developed to study drug distribution and tumor physiology during intraperitoneal Oxaliplatin perfusion. Mice were treated for six days with either Placebo, Imatinib (anti-PDGFR, daily), Bevacizumab (anti-VEGF, twice) or Pazopanib (anti-PDGFR, -VEGFR; daily) followed by intraperitoneal oxaliplatin chemotherapy. Bevacizumab and Pazopanib significantly lowered interstitial fluid pressure, increased Oxaliplatin penetration (assessed by laser ablation inductively coupled plasma mass spectrometry) and delayed tumor growth of peritoneal implants (assessed by MRI). Our findings suggest that VEGF(R)-inhibition may improve the efficacy of IPC, particularly for patients for whom a complete cytoreduction might not be feasible

Characterizing microstructural alterations in a ratmodel of mild traumatic brain injury

1. INTRODUCTION Traumatic brain injury (TBI) is an acquired brain injury that contributes to a substantial number of deaths (mortality rate: 15 per 100 000 in Europe) and a high number of cases of permanent disability (incidence rate: 235 per 100 000 in Europe). Most of the TBI patients have mild TBI (mTBI), a condition that shows no abnormalities on conventional imaging but can result in persisting cognitive defects. Diffusion imaging is an MRI technique sensitive to diffusion of water molecules in the brain and can detect subtle changes in white matter organization. The aim of this study is to investigate whether advanced diffusion MRI scanning can be used to detect microstructural changes in a rat model of mTBI. 2. MATERIALS AND METHODS 2.1 Animal model Nine female Wistar rats weighing 250 ± 19.6 g obtained mTBI utilizing the Marmarou weight drop model [1]. In brief, in anesthetized rats a steel helmet was fixed on the skull 1/3 before and 2/3 behind bregma. The rat was positioned under a 450 g brass weight on a foam bed. The weight was dropped from a height of 1m guided through a plexiglass column. The foam bed together with the rat was rapidly removed away from the column to prevent a second injury. Rats were allowed to recover for one week. 2.2 Imaging and data analysis MRI data was acquired on a 7T MRI scanner (PharmaScan, Bruker, Ettlingen) before and 1 week after injury. T2-weighted images were acquired for anatomical reference. Multishell diffusion data was acquired with multiple directions (b=800, 1500 and 2000; 32, 46 and 64 directions, respectively). Diffusion weighted images were corrected for EPI, motion and eddy current distortions and quantitative maps were calculated for the diffusion tensor and diffusion kurtosis model in ExploreDTI [2]. Furthermore diffusion kurtosis tensor estimation was done using weighted linear least squares method and maps for white matter metrics were calculated using the model of Fieremans et al. [3]. The maps were co-registered in SPM12 with a template based on the local population and a volume-of-interest analysis was performed in the hippocampus, cingulum and corpus callosum using Amide toolbox [4]. Differences between the two time points were calculated for each map using the Wilcoxon signed-rank test in SPSS. P < 0.05 was considered significant. 3. RESULTS AND DISCUSSION The DTI and DKI metrics were not significantly different between the two time points. The axonal water fraction (AWF) was significantly increased in the cingulum, corpus callosum and hippocampus after mTBI and could be explained by axonal swelling. To verify this hypothesis, histological analysis is currently ongoing. Sections will be stained for synapses, astrocytes, neurons and myelin. References Marmarou, A. et al. A new model of diffuse brain injury in rats: Part I. J Neuroscience, 80, 291-300, 1994. Leemans, A. et al. ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. In: 17th Annual Meeting of Intl Soc Mag Reson Med, p. 3537, Hawaii, USA, 2009 Fieremans, E. et al. White matter characterization with diffusional kurtosis imaging, Neuroimage 58(1): 177-188, 2011. Loening, AM. et al. AMIDE: A Free Software Tool for Multimodality Medical Image Analysis. Molecular Imaging, 2(3):131-137, 2003