Effect of subject motion and gantry rotation speed on image quality and dose delivery in CT-guided radiotherapy.

PURPOSE: To investigate the effects of subject motion and gantry rotation speed on computed tomography (CT) image quality over a range of image acquisition speeds for fan-beam (FB) and cone-beam (CB) CT scanners, and quantify the geometric and dosimetric errors introduced by FB and CB sampling in the context of adaptive radiotherapy. METHODS: Images of motion phantoms were acquired using four CT scanners with gantry rotation speeds of 0.5 s/rotation (denoted FB-0.5), 1.9 s/rotation (FB-1.9), 16.6 s/rotation (CB-16.6), and 60.0 s/rotation (CB-60.0). A phantom presenting various tissue densities undergoing motion with 4-s period and ranging in amplitude from ±0.5 to ±10.0 mm was used to characterize motion artifacts (streaks), motion blur (edge-spread function, ESF), and geometric inaccuracy (excursion of insert centroids and distortion of known shape). An anthropomorphic abdomen phantom undergoing ±2.5-mm motion with 4-s period was used to simulate an adaptive radiotherapy workflow, and relative geometric and dosimetric errors were compared between scanners. RESULTS: At ±2.5-mm motion, phantom measurements demonstrated mean ± SD ESF widths of 0.6 ± 0.0, 1.3 ± 0.4, 2.0 ± 1.1, and 2.9 ± 2.0 mm and geometric inaccuracy (excursion) of 2.7 ± 0.4, 4.1 ± 1.2, 2.6 ± 0.7, and 2.0 ± 0.5 mm for the FB-0.5, FB-1.9, CB-16.6, and CB-60.0 scanners, respectively. The results demonstrated nonmonotonic trends with scanner speed for FB and CB geometries. Geometric and dosimetric errors in adaptive radiotherapy plans were largest for the slowest (CB-60.0) scanner and similar for the three faster systems (CB-16.6, FB-1.9, and FB-0.5). CONCLUSIONS: Clinically standard CB-60.0 demonstrates strong image quality degradation in the presence of subject motion, which is mitigated through faster CBCT or FBCT. Although motion blur is minimized for FB-0.5 and FB-1.9, such systems suffer from increased geometric distortion compared to CB-16.6. Each system reflects tradeoffs in image artifacts and geometric inaccuracies that affect treatment delivery/dosimetric error and should be considered in the design of next-generation CT-guided radiotherapy systems.

Technical assessment of a mobile CT scanner for image-guided brachytherapy.

PURPOSE: The imaging performance and dose of a mobile CT scanner (Brainlab Airo®, Munich, Germany) is evaluated, with particular consideration to assessment of technique protocols for image-guided brachytherapy. METHOD: Dose measurements were performed using a 100-mm-length pencil chamber at the center and periphery of 16- and 32-cm-diameter CTDI phantoms. Hounsfield unit (HU) accuracy and linearity were assessed using materials of specified electron density (Gammex RMI, Madison, WI), and image uniformity, noise, and noise-power spectrum (NPS) were evaluated in a 20-cm-diameter water phantom as well as an American College of Radiology (ACR) CT accreditation phantom (Model 464, Sun Nuclear, Melbourne, FL). Spatial resolution (modulation transfer function, MTF) was assessed with an edge-spread phantom and visually assessed with respect to line-pair patterns in the ACR phantom and in structures of interest in anthropomorphic phantoms. Images were also obtained on a diagnostic CT scanner (Big Bore CT simulator, Philips, Amsterdam, Netherlands) for qualitative and quantitative comparison. The manufacturer's metal artifact reduction (MAR) algorithm was assessed in an anthropomorphic body phantom containing surgical instrumentation. Performance in application to brachytherapy was assessed with a set of anthropomorphic brachytherapy phantoms - for example, a vaginal cylinder and interstitial ring and tandem. RESULT: Nominal dose for helical and axial modes, respectively, was 56.4 and 78.9 mGy for the head protocol and 17.8 and 24.9 mGy for the body protocol. A high degree of HU accuracy and linearity was observed for both axial and helical scan modes. Image nonuniformity (e.g., cupping artifact) in the transverse (x,y) plane was less than 5 HU, but stitching artifacts (~5 HU) in the longitudinal (z) direction were observed in axial scan mode. Helical and axial modes demonstrated comparable spatial resolution of ~5 lp/cm, with the MTF reduced to 10% at ~0.38 mm-1 . Contrast-to-noise ratio was suitable to soft-tissue visualization (e.g., fat and muscle), but windmill artifacts were observed in helical mode in relation to high-frequency bone and metal. The MAR algorithm provided modest improvement to image quality. Overall, image quality appeared suitable to relevant clinical tasks in intracavitary and interstitial (e.g., gynecological) brachytherapy, including visualization of soft-tissue structures in proximity to the applicators. CONCLUSION: The technical assessment highlighted key characteristics of dose and imaging performance pertinent to incorporation of the mobile CT scanner in clinical procedures, helping to inform clinical deployment and technique protocol selection in brachytherapy. For this and other possible applications, the work helps to identify protocols that could reduce radiation dose and/or improve image quality. The work also identified areas for future improvement, including reduction of stitching, windmill, and metal artifacts.

Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform.

Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior). Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. A defined, scalable, and resource-efficient cell culture platform can thus rapidly generate high quality differentiated cells, both neurons and potentially other cell types, with strong potential to accelerate both basic and translational research.