Computational simulation of tumour hypoxia as applied to radiation therapy applications

It has long been appreciated that hypoxia plays a significant role in tumour resistance to radiotherapy treatment, chemotherapy treatment and also in surgery. For present interests, it is noted that tumour radio-sensitivity increases with the increase of oxygen concentration across tumour regions. A theoretical representation of oxygen distribution in 2D vascular architecture using a reaction diffusion model enables relationships between tissue diffusivity, tissue metabolism, anatomical structure of blood vessels and oxygen gradients to be characterized quantitatively. We present a refinement to the work of Kelly and Brady (2006) and demonstrate the significant effect of the role of the venules supply on the microcirculation process at the intracellular level. With our representation of the two latter forces, the model is being developed to simulate the uptake of various PET reagents, such as 64Cu-ATSM, to demonstrate their potential use in radiation therapy treatment planning as an indicator of tumour hypoxic regions

SU-D-202-03: Statistical Segmentation On Quantitative CT for Assessing Spatial Tumor Response During Radiation Therapy Delivery

Purpose: Develop a method to segment regions of interest (ROIs) in tumor with statistically similar Hounsfield unit (HU) values and/or HU changes during chemoradiation therapy (CRT) delivery, to assess spatial tumor treatment response based on daily CTs during CRT delivery. Methods: Generate a three region map of ROIs with differential HUs, by sampling neighboring voxels around a selected voxel and comparing to the mean of the entire ROI using a t-test. The cumulative distribution function, P, is calculated from the t-test. The P value is assigned to be the value at the selected voxel, and this is repeated over all voxels in the initial ROI. Three regions are defined as: (1-P) \u3c 0.00001 (mid region), and 0.00001 \u3c (1-P) (mean greater than baseline and mean lower than baseline). The test is then expanded to compare daily CT sets acquired during routine CT-guided RT delivery using a CT-on-rails. The first fraction CT is used as the baseline for comparison. We tested 15 pancreatic head tumor cases undergoing CRT, to identify the ROIs and changes corresponding to normal, fibrotic, and tumor tissue. The obtained ROIs were compared with MRI-ADC maps acquired pre- and post-CRT. Results: The ROIs in 13 out of 15 patients’ first fraction CTs and pre-CRT MRIs matched the general region and slices covered, as well as in 6 out of the 9 patients with post-CRT MRIs. The high HU region designated by the t-test was seen to correlate with the tumor region in MR, and these ROIs are positioned within the same region over the course of treatment. In patients with poorly delineated tumors in MR, the t-test was inconclusive. Conclusion: The proposed statistical segmentation technique shows the potential to identify regions in tumor with differential HUs and HU changes during CRT delivery for patients with pancreas head cancer

Cumulative lifetime attributed risks for patients subjected to contrast enhanced chest CT examinations

The main aim here is to estimate the cumulative lifetime attributed risks (LARs) for patients subjected to contrast-enhanced chest computer tomography (CECCT). Further, the impact of the contrast media on the organs doses (ODs), effective dose (E*), LARs and scan acquisition parameters were assessed. The ODs, and E* of the CECCT scan for 17 patients were obtained without-contrast (S1) and with-contrast (S2) using the commercial software CT-EXPO. The LARs were calculated using age- and- gender specific risk factors. The relationship between the CT dose metrics (CTDIvol and DLP), mAs and scan-length were established using the Pearson's correlation coefficient-test. The Wilcoxon pairs t-test was used to determine the statistical differences between all quantities in both chest CT series. No significant differences were found between the CT scan series S1 and S2 in all the determined quantities including: CTDIvol (p = 0.772), DLP (p = 0.092), mAs (p = 0.450) and E* (p = 0.111). The ODs were higher with contrast media, particularly stomach and bone marrow. The LARs of developing lung cancer were particularly high for the females in their 60's about 1 in 3000 (or 0.03%). The highest LARs of all organ cancers reported were higher in females comparing to males 0.03% comparing to 0.01%). Female patients are at higher risk of developing cancers than males while undergoing CECCT wherein contrast media can contribute to increasing organ doses

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity

Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer

PURPOSE: Local recurrence is a common and morbid event in patients with unresectable pancreatic adenocarcinoma. A more conformal and targeted radiation dose to the macroscopic tumor in nonmetastatic pancreatic cancer is likely to reduce acute toxicity and improve local control. Optimal soft tissue contrast is required to facilitate delineation of a target and creation of a planning target volume with margin reduction and motion management. Magnetic resonance imaging (MRI) offers considerable advantages in optimizing soft tissue delineation and is an ideal modality for imaging and delineating a gross tumor volume (GTV) within the pancreas, particularly as it relates to conformal radiation planning. Currently, no guidelines have been defined for the delineation of pancreatic tumors for radiation therapy treatment planning. Moreover, abdominal MRI sequences are complex and the anatomy relevant to the radiation oncologist can be challenging. The purpose of this study is to provide recommendations for delineation of GTV and organs at risk (OARs) using MRI and incorporating multiple MRI sequences. METHODS AND MATERIALS: Five patients with pancreatic cancer and 1 healthy subject were imaged with MRI scans either on 1.5T or on 3T magnets in 2 separate institutes. The GTV and OARs were contoured for all patients in a consensus meeting. RESULTS: An overview of MRI-based anatomy of the GTV and OARs is provided. Practical contouring instructions for the GTV and the OARs with the aid of MRI were developed and included in these recommendations. In addition, practical suggestions for implementation of MRI in pancreatic radiation treatment planning are provided. CONCLUSIONS: With this report, we attempt to provide recommendations for MRI-based contouring of pancreatic tumors and OARs. This could lead to better uniformity in defining the GTV and OARs for clinical trials and in radiation therapy treatment planning, with the ultimate goal of improving local control while minimizing morbidity

The role of necrosis, acute hypoxia and chronic hypoxia in 18

Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure (PO2) is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 µm vs. ~4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (~20 min vs. a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of PO2 and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local PO2 of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue PO2: tracer uptake rises sharply from negligible levels in avascular tissue, peaking at ~5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing PO2 and necrotic fraction, but simulated TACs indicate that additional early-phase information may allow discrimination of hypoxic and necrotic signals. We conclude that a robust approach to FMISO interpretation (and dose-painting prescription) is likely to be based on dynamic PET analysis