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Purpose: Treatment of malignant tumors by either hyperthermia induced drug delivery or thermal ablation requires complete coverage of the treatment area and precise control of the thermal dose.Both can be achieved by volumetric ultrasonic heating in combination with simultaneous MR-based temperature mapping. The translation ofthese techniques to the clinic requires thorough preclinical testing in large cohorts. Mouse and rat studies are preferred over largeranimals for ethical reasons as well as the larger variety of available tumor models. Our work aims to develop temperature induced drug delivery and ablation protocols in rats and to subsequently evaluatetreatment outcome using small animal imaging methods. To this end, we adapted a clinical MR-HIFU system for the treatment of rats by utilizing a dedicated small animal setup. Methods: All animals were positioned in a HIFU dedicated small animal 4-channel MR volume coil that was used as add-on to a clinical 3T Philips Sonalleve MR-HIFU system. Hyperthermia was performed for 15 min using binary temperaturecontrol on lateral gastrocnemius muscle (n = 5) and on subcutaneousinoculated tumors on the hind limb of rats (9L rat glioma; n = 5).For thermal ablation, tumors were partly heated to T = 65 °C with continuous wave ultrasound (1.44 MHz) under MR temperature monitoring(n = 5). The treatment effect was assessed with T2-weighted imagingand dynamic contrast enhanced (DCE-) MRI using Gd-DTPA as contrast agent. Excised muscle and tumors were further evaluated with histology. Results: The target temperatures were readily achieved in hyperthermia and ablation treatments while changes in body temperature remained below 1 °C. For hyperthermia treatments, no indication of tissue damage was found on MR images. Analysis of the Gd-DTPA uptake kinetics post ablation indicated a difference in non-perfused volume inthe tumor of 371 ± 123 mm3 (Δ tissue volume with ktrans ≥ 0.04 min-1). NADH-diaphorase staining of ablated tumors showed a sharp demarcation between viable and non-viable cells. Conclusion: These results demonstrate that both controlled hyperthermia and thermal ablation treatment of malignant tumors in small animals can be performed on a clinical MR-HIFU system. This approach provides all theadvantages of clinical MR-HIFU, such as volumetric heating, temperature feedback control and a clinical software interface, while also having many of the advantages of a dedicated small animal system. Theuse of a clinical system facilitates a rapid translation of these protocols into the clinic.

Purpose: Recently, image-based computational fluid dynamic (CFD) simulations have been proposed to investigate the local hemodynamics inside human cerebral aneurysms. It is suggested that the knowledge ofthe computed three-dimensional flow fields can be used to assist clinical risk assessment and treatment decision making. Therefore, itis desired to know the reliability of CFD for cerebral blood flow simulation, and be able to provide clinical feedback. However, the validations are not yet comprehensive as they lack either patient-30 specific boundary conditions (BCs) required for CFD simulations or quantitative comparison methods. Methods: In this work, based on a recently proposed in-vitro quantitative CFD evaluation approach via virtual angiography, the CFD evaluation is extended from phantom to patient studies. In contrast to previous work, patient-specific blood flow rates obtained by transcranial color coded Doppler ultrasound measurements are used to impose CFD BCs. Virtual angiograms (VAs) are constructed which resemble clinically acquired 35 angiograms (AAs). Quantitative measures are defined to thoroughly evaluate the correspondence of the detailed flow features between the AAs and the VAs, and thus, the reliability of CFD simulations. Results: The proposed simulation pipeline provides a comprehensive validation method of CFDsimulation for reproducing cerebral blood flow, with a focus on theaneurysm region. Six patient cases are tested and close similaritiesare found in terms of spatial and temporal variations of CA distribution between AAs and VAs. For 40 patient #1 to #5, discrepancies ofless than 11% are found for the relative root mean square errors intime intensity curve comparisons from characteristic vasculature positions. For patient #6, where the CA concentration curve at vesselinlet cannot be directly extracted from the AAs and given as a BC, deviations about 20% are found. Conclusions: As a conclusion, the reliability of the CFD is well confirmed. Besides, it is shown that the45 accuracy of CFD simulations is closely related to the input BCs.

Purpose: Recent research efforts investigating dose escalation techniques for three-dimensional conformal radiation therapy (3D CRT) andintensity modulated radiation therapy (IMRT) have demonstrated great benefit when high-dose hypofractionated treatment schemes are implemented16,21. The use of these paradigms emphasizes the importanceof smaller treatment margins to avoid high dose to surrounding normal tissue or organs at risk (OARs). However, tighter margins may leadto under-dosage of the target due to the presence of organ motion.It is important to characterize organ motion and possibly account for it during treatment delivery. The need for real-time localizationof dynamic targets has encouraged the use and development of more continuous motion monitoring systems such as kilo-voltage/fluoroscopicimaging, electromagnetic tracking, and optical monitoring systems.Methods: This paper presents the implementation of an algorithm toquantify translational and rotational inter- and intra-fractional organ motion, and compute the dosimetric effects of these motion patterns. The estimated delivered dose is compared with the static plan dose to evaluate the success of delivering the plan in the presence of organ motion. The method is implemented on a commercial treatmentplanning system (Pinnacle3, Philips Radiation Oncology Systems, Philips Healthcare) and is termed Delivered Dose Investigational Tool (DiDIT). The DiDIT implementation in Pinnacle3 is validated by comparisons with previously published results13. Finally, different workflows are discussed with respect to the potential use of this tool in clinical treatment planning. Results: The DiDIT dose estimation process took approximately 5-20 minutes (depending on the number of fractions analyzed) on a Pinnacle3 9.100 research version running on a Dell M90 system (Dell Inc., Round Rock, TX, USA) equipped with an Intel Core 2 Duo processor (Intel Corporation, Santa Clara, CA, USA). The DiDIT implementation in Pinnacle3 was found to be in agreement with previously published results13, on the basis of percent dose difference (PDD) and distance to agreement (DTA) metrics. These metricswere also utilized to compare plan dose versus delivered dose, for three clinically acceptable treatment plans. Conclusion: This paper presents results from the implementation of an algorithm on a commercially available treatment planning system that quantifies the dosimetric effects of interfractional and intrafractional motion in external beam radiation therapy (EBRT) of prostate cancer. The implementation of this algorithm within a commercial treatment planning systemsuch as Pinnacle3 enables easy deployment in the existing clinical workflow. The results of the PDD and DTA tests validate the implementation of the DiDIT algorithm in Pinnacle3, in comparison with previously published results13.