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Background: Modulation of pathological neural circuit activity in the brain with a minimum of complications is an area of intense interest. Objective: The goal of the study was to alter neurons' physiological states without apparent damage of cellular integrity using stereotactic radiosurgery (SRS). Methods: We treated a 7.5 mm-diameter target on the visual cortex of Göttingen minipigs with doses of 40, 60, 80, and 100 Gy. Six months post-irradiation, the pigs were implanted with a 9 mm-wide, eight-shank multi-electrode probe, which spanned the radiation focus as well as the low-exposure neighboring areas. Results: Doses of 40 Gy led to an increase of spontaneous firing rate, six months post-irradiation, while doses of 60 Gy and greater were associated with a decrease. Subjecting the animals to visual stimuli resulted in typical visual evoked potentials (VEP). At 40 Gy, a significant reduction of the P1 peak time, indicative of higher network excitability was observed. At 80 Gy, P1 peak time was not affected, while a minor reduction at 60 Gy was seen. No distance-dependent effects on spontaneous firing rate, or on VEP were observed. Post-mortem histology revealed no evidence of necrosis at doses below 60 Gy. In an in vitro assay comprising of iPS-derived human neuron-astrocyte co-cultures, we found a higher vulnerability of inhibitory neurons than excitatory neurons with respect to radiation, which might provide the cellular mechanism of the disinhibitory effect observed in vivo. Conclusion: We provide initial evidence for a rather circuit-wide, long-lasting disinhibitory effect of low sub-ablative doses of SRS.

BackgroundCardiac arrhythmias, such as ventricular tachycardia, are disruptions in the normal cardiac function that originate from problems in the electrical conduction of signals inside the heart. Recently, a non-invasive treatment option based on external photon or proton beam irradiation has been used to ablate the arrhythmogenic structures. Especially in proton therapy, based on its steep dose gradient, it is crucial to monitor the motion of the heart in order to ensure that the radiation dose is delivered to the correct location. Transthoracic ultrasound imaging has the potential to provide guidance during this treatment delivery. However, it has to be noted that the presence of an ultrasound probe on the chest of the patient introduces constraints on usable beam angles for both protons and photon treatments. This case report investigates the possibility to generate a clinically acceptable proton treatment plan while the ultrasound probe is present on the chest of the patient.CaseA treatment plan study was performed based on a 4D cardiac-gated computed tomography scan of a 55 year-old male patient suffering from refractory ventricular tachycardia who underwent cardiac radioablation. A proton therapy treatment plan was generated for the actual treatment target in presence of an ultrasound probe on the chest of this patient. The clinical acceptability of the generated plan was confirmed by evaluating standard target dose-volume metrics, dose to organs-at-risk and target dose conformity and homogeneity.ConclusionThe generation of a clinically acceptable proton therapy treatment plan for cardiac radioablation of ventricular tachycardia could be performed in the presence of an ultrasound probe on the chest of the patient. These results establish a basis and justification for continued research and product development for ultrasound-guided cardiac radioablation.