For this proof-of-concept study the 4D cardiac-gated CT scan from a 55 year-old male patient suffering from VT was used. The CT data of this VT patient has been previously used for other purposes in a work published by Gianni et al.. The treatment target for this patient had a size of 45 cm3 and it was located on the left ventricular free wall. This clinical target volume (CTV) was determined by electrophysiological mapping and contoured prior to the treatment by a medical doctor from the Texas Heart Arrhythmia Institute in Austin, USA. The left anterior descending coronary artery, the circumflex coronary arteries and the non-involved left ventricle were OARs near the target.
First, the 4D CT scan of the VT patient was loaded into the Raysearch  Raystation treatment planning system (version 10B, Raysearch Laboratories AB, Stockholm, Sweden). Subsequently, a virtual representation of the prototype version of the proprietary US probe system of EBAMed (Geneva, Switzerland) was manually inserted as volume of interest (VOI) in two locations representing the estimated position of the apical and parasternal US viewing windows. A separate study has already verified that these US viewing windows provide US images of sufficient quality for VT patients in supine position. The US probe was simulated as a cube of 2 x 2 x 2 cm. It is equipped with infra-red markers such that the probe can be localized by an optical camera (see Figure 1) and it is attached to a holder such that it can be fixed on the chest of the patient allowing for hands-free imaging during the treatment. To account for uncertainties in repositioning of the US probe during the treatment, including probe position uncertainties due to respiration and breath-hold differences, an isotropic safety margin of 10 mm has been added to the union of the US probe, holder, and optical marker.
The parasternal US probe position allowed entrance of the treatment beams from optimal directions with respect to dosimetry for this particular patient. After selection of this virtual US probe position, a pencil-beam scanned proton therapy treatment plan was generated with the treatment planning system using the CNAO (Pavia, Italy) synchrotron proton beam model adapted to the Hitachi PROBEAT gantry system with 360  range of beam angles. During planning, the solid angle was restricted to take into account the US probe, the probe holder and the localization marker. Two fields were applied both with a gantry angle of 25  and a couch rotation of 0  and 90  for beam 1 and 2, respectively. The treatment volume was planned with an internal target volume (ITV) approach in order to compensate for shape and position changes of the target due to the heartbeat. It was assumed that the motion of the heart due to respiration would be mitigated using a breath-hold technique or respiratory gating. The envisioned role of the US imaging during this treatment was real-time cardiac motion monitoring and sending an alert to the operator in case the measured motion was outside of predefined limits.
For the generation of the ITV, the heartbeat motion envelope was extracted from the 4D CT scan by deformable registration of each phase of the 4D CT scan to the planning CT scan. The resulting ITV is the union of the CTVs at all phases of the 4D CT. Finally, the planning target volume (PTV) was generated by adding a 5 mm margin to the ITV based on typical patient set-up errors which are expected when no image guidance tool like US imaging is used.
Dose constraints on dose-volume tolerances (Table 1) in agreement with prior investigators were set as planning objectives. All doses are reported in Cobalt Gray Equivalent Dose (CGyE). The plan required the ITV to be covered by the 25 CGyE isodose, which is a dose level used in prior clinical studies to achieve safe, efficacious radioablation. To achieve this, the plan was normalized so that PTV D92% = 25 CGyE. Also, in order to arrive at a satisfactory treatment plan, robust optimization with 2 mm set-up error in all directions and 2% range uncertainty was used during planning.
To verify the clinical acceptability of the generated plan, evaluation of standard target dose-volume metrics D98, D95 D50 and D2 was performed. In addition, the dose to OARs and the target dose conformity and homogeneity were evaluated.