Background and Purpose: Stereotactic body radiation therapy delivered using MR-guided radiotherapy (MRgRT) and automatic breathold gating has shown to improve overall survival for locally advanced pancreatic cancer (LAPC) patients. The goal of our study was to evaluate feasibility of treating LAPC patients using abdominal compression (AC) and impact of potential intrafraction motion on planned dose on a 1.5T MR-linac. Methods & Materials: Ten LAPC patients were treated with MRgRT to 50 Gy in 5 fractions with daily online plan adaptation and AC. Three orthogonal plane cine MRI were acquired to assess stability of AC pressure in minimizing tumor motion. Three sets of T2w MR scans, pre-treatment (MRI pre ), verification (MRI ver ) and posttreatment (MRI post ) MRI, were acquired for every fraction. A total of 150 MRIs and doses were evaluated. Impact of intrafraction organ motion was evaluated by propagating pre-treatment plan and structures to MRI ver and MRI post , editing contours and recalculating doses. Gross tumor volume (GTV) coverage and organs-at-risk (OARs) doses were evaluated on MRI ver and MRI post . Results: Median total treatment time was 75.5 (49-132) minutes. Median tumor motion in AC for all fractions was 1.7 (0.7-7), 2.1 (0.6-6.3) and 4.1 (1.4-10.0) mm in anterior-posterior, left-right and superior-inferior direction. Median GTV V50Gy was 78.7%. Median D5cm 3 stomach_duodenum was 24.2 (18.4-29.3) Gy on MRI ver and 24.2 (18.3-30.5) Gy on MRI post . Median D5cm 3 small bowel was 24.3 (18.2-32.8) Gy on MRI ver and 24.4 (16.0-33.6) Gy on MRI post . Conclusion: Dose-volume constraints for OARs were exceeded for some fractions on MRI ver and MRI post . Longer follow up is needed to see the dosimetric impact of intrafraction motion on gastrointestinal toxicity.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (Ktrans) for tracer exchange across the barrier. BBB permeability was 67% higher in cortical pHGGs relative to brainstem pHGGs (t-test, p=0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p=0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean Ktrans was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

Purpose: Dynamic contrast-enhanced (DCE) MRI has been widely used as a quantitative imaging method for monitoring tumor response to therapy. The simultaneous challenges of increasing temporal and spatial resolution in a setting where the signal from the much smaller voxel is weaker have made this MR technique difficult to implement in small-animal imaging. Existing protocols employed in preclinical DCE-MRI acquire a limited number of slices resulting in potentially lost information in the third dimension. This study describes and compares a family of four-dimensional (3D spatial + time), projection acquisition, radial keyhole-sampling strategies that support high spatial and temporal resolution. Methods: The 4D method is based on a RF-spoiled, steady-state, gradient-recalled sequence with minimal echo time. An interleaved 3D radial trajectory with a quasi-uniform distribution of points in k-space was used for sampling temporally resolved datasets. These volumes were reconstructed with three different k-space filters encompassing a range of possible radial keyhole strategies. The effect of k-space filtering on spatial and temporal resolution was studied in a 5 mM CuSO 4 phantom consisting of a meshgrid with 350-μm spacing and in 12 tumors from three cell lines (HT-29, LoVo, MX-1) and a primary mouse sarcoma model (three tumors/group). The time-to-peak signal intensity was used to assess the effect of the reconstruction filters on temporal resolution. As a measure of heterogeneity in the third dimension, the authors analyzed the spatial distribution of the rate of transport (K trans ) of the contrast agent across the endothelium barrier for several different types of tumors. Results: Four-dimensional radial keyhole imaging does not degrade the system spatial resolution. Phantom studies indicate there is a maximum 40% decrease in signal-to-noise ratio as compared to a fully sampled dataset. T1 measurements obtained with the interleaved radial technique do not differ significantly from those made with a conventional Cartesian spin-echo sequence. A bin-by-bin comparison of the distribution of the time-to-peak parameter shows that 4D radial keyhole reconstruction does not cause significant temporal blurring when a temporal resolution of 9.9 s is used for the subsamples of the keyhole data. In vivo studies reveal substantial tumor heterogeneity in the third spatial dimension that may be missed with lower resolution imaging protocols. Conclusions: Volumetric keyhole imaging with projection acquisition provides a means to increase spatiotemporal resolution and coverage over that provided by existing 2D Cartesian protocols. Furthermore, there is no difference in temporal resolution between the higher spatial resolution keyhole reconstruction and the undersampled projection data. The technique allows one to measure complex heterogeneity of kinetic parameters with isotropic, microscopic spatial resolution.

Purpose: Quantitative in vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in small animals. The purpose of this work is to demonstrate 4D micro-CT for perfusion imaging in rodents at heartbeat temporal resolution and isotropic spatial resolution. Methods: We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that similar time density curves can be reproduced in a number of consecutive, small volume injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system with a microinjector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LABVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a graphic processor unit. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats. Results: We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution ͑approximately 150 ms͒ and isotropic 3D reconstruction with a voxel size of 88 m based on sampling using 16 injections of 50 L each. The total volume of contrast agent injected during the experiments ͑0.8 mL͒ was less than 10% of the total blood volume in a rat. This volume was not injected in a single bolus, but in multiple injections separated by at least 2 min interval to allow for clearance and adaptation. We assessed the reproducibility of the time density curves with multiple injections and found that these are very similar. The average time density curves for the first eight and last eight injections are slightly different, i.e., for the last eight injections, both the maximum of the average time density curves and its area under the curve are decreased by 3.8% and 7.2%, respectively, relative to the average time density curves based on the first eight injections. The radiation dose associated with our 4D micro-CT imaging is 0.16 Gy and is therefore in the range of a typical micro-CT dose. Conclusions: 4D micro-CT-based perfusion imaging demonstrated here has immediate application in a wide range of preclinical studies such as tumor perfusion, angiogenesis, and renal function. Although our imaging system is in many ways unique, we believe that our approach based on the multiple injection paradigm can be used with the newly developed flat-panel slip-ring-based micro-CT to increase their temporal resolution in dynamic perfusion studies.