A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking

AbstractPurposeA study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.Methods and materialsTen institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.ResultsFor all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.ConclusionsThe investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods

Long term safety and visibility of a novel liquid fiducial marker foruse in image guided radiotherapy of non-small cell lung cancer

Safety and clinical feasibility of injecting a novel liquid fiducial marker for use in image guided radiotherapy in 15 patients with non-small cell lung cancer are reported. No major safety or toxicity issues were encountered. Markers present at start of radiotherapy remained visible in cone beam computed tomography and fluoroscopy images throughout the treatment course and on computed tomography images during follow-up (0–38 months). Marker volume reduction was seen until 9 months after treatment, after which no further marker breakdown was found. No post-treatment migration or marker related complications were found. Keywords: Liquid fiducial marker, Image-guided radiotherapy, NSCLC, Endoscopic ultrasound, EBU

Diffusion-encoded MRI for assessment of structure and microcirculation : Aspects of q-space imaging and improved IVIM modelling

Diffusion and perfusion MRI are valuable methods for investigating the microstructure and viability of tissue. One pure diffusion study was included in this thesis, with the purpose of studying microstructure and carrying out size estimations with the q-space diffusion imaging method. This is a method that has predominantly been explored with NMR spectrometers. In our study, a biological phantom consisting of asparagus stems was investigated using a clinical MRI unit to gain further knowledge about the q-space methodology in a setting where gradient performance is limited. Even though the q-space method showed limited possibilities, retrieval of some structural information was shown to be feasible.In the remaining three doctoral thesis projects, the intravoxel incoherent motion (IVIM) imaging concept was explored, allowing for extraction of combined diffusion and perfusion information from a given dataset. IVIM imaging is a non-invasive technique for acquiring diffusivity as well as microvascular and perfusion-related parameters using a diffusion-weighted pulse sequence. The model used in this technique is often limited because no relaxation properties are incorporated, and also because the signal component from blood is contaminated by cerebrospinal fluid/free water.One study was dedicated to exploring the IVIM parameters at different field strengths and the influence of relaxation and signal-to-noise ratio (SNR) was observed. Although the repeatability was generally better at higher magnetic field strength, it was shown that the relaxation properties and an unexpectedly low SNR at high field strengths resulted in erroneous blood volume estimates. The model commonly used for IVIM data analysis was then modified to compensate for relaxation effects, based on literature values. When this correction was performed, results from the lower field strengths showed lower discrepancy from expected values, while the results from higher field strength were still erroneous, likely due to physiological noise.In a following project, relaxation times were actually measured during the data collection, and incorporated to compensate for relaxation and improve the fitting procedure. The model was also upgraded to a three-compartment model to better describe the underlying tissue by including the cerebrospinal fluid component. Compared to a non-relaxation-compensated model, the three-compartment model with relaxation-compensated data modified the obtained results and reduced the CSF contamination.The last IVIM project also included a three-compartment model, but in this case the purpose of the third compartment was to improve the quantification of the fraction of free water. The free water fraction has been established as a source of clinically useful image contrast, pointing at pathologies that affect the extracellular space, for example, atrophy and neuroinflammation. With our model, the bias from microcirculation was reduced in the free water estimate. A model where extracellular and microvascular effects can be separated might enable new diagnostic possibilities

Separating Blood and Water: Perfusion and Free Water Elimination from Diffusion MRI in the Human Brain.

The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b-shells, demonstrated an expected non-zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b-shells