30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

A 60 MeV proton beam-line dedicated to research and development programs.

A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical 'eye-line' used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 µA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) - 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.

In-vivo tongue stiffness measured by aspiration: Resting vs general anesthesia.

Tongue cancer treatment often results in impaired speech, swallowing, or mastication. Simulating the effect of treatments can help the patient and the treating physician to understand the effects and impact of the intervention. To simulate deformations of the tongue, identifying accurate mechanical properties of tissue is essential. However, not many succeeded in characterizing in-vivo tongue stiffness. Those who did, measured the tongue At Rest (AR), in which muscle tone subsides even if muscles are not willingly activated. We expected to find an absolute rest state in participants 'under General Anesthesia' (GA). We elaborated on previous work by measuring the mechanical behavior of the in-vivo tongue under aspiration using an improved volume-based method. Using this technique, 5 to 7 measurements were performed on 10 participants both AR and under GA. The obtained Pressure-Shape curves were first analyzed using the initial slope and its variations. Hereafter, an inverse Finite Element Analysis (FEA) was applied to identify the mechanical parameters using the Yeoh, Gent, and Ogden hyperelastic models. The measurements AR provided a mean Young's Modulus of 1638 Pa (min 1035 - max 2019) using the Yeoh constitutive model, which is in line with previous ex-vivo measurements. However, while hoping to find a rest state under GA, the tongue unexpectedly appeared to be approximately 2 to 2.5 times stiffer under GA than AR. Explanations for this were sought by examining drugs administered during GA, blood flow, perfusion, and upper airway reflexes, but neither of these explanations could be confirmed.

In vivo measurement of human brain elasticity using a light aspiration device.

The brain deformation that occurs during neurosurgery is a serious issue impacting the patient "safety" as well as the invasiveness of the brain surgery. Model-driven compensation is a realistic and efficient solution to solve this problem. However, a vital issue is the lack of reliable and easily obtainable patient-specific mechanical characteristics of the brain which, according to clinicians' experience, can vary considerably. We designed an aspiration device that is able to meet the very rigorous sterilization and handling process imposed during surgery, and especially neurosurgery. The device, which has no electronic component, is simple, light and can be considered as an ancillary instrument. The deformation of the aspirated tissue is imaged via a mirror using an external camera. This paper describes the experimental setup as well as its use during a specific neurosurgery. The experimental data was used to calibrate a continuous model. We show that we were able to extract an in vivo constitutive law of the brain elasticity: thus for the first time, measurements are carried out per-operatively on the patient, just before the resection of the brain parenchyma. This paper discloses the results of a difficult experiment and provide for the first time in vivo data on human brain elasticity. The results point out the softness as well as the highly non-linear behavior of the brain tissue.

A light sterilizable pipette device for the in vivo estimation of human soft tissues constitutive laws.

This paper introduces a new light device for the in vivo estimation of human soft tissues constitutive laws. It consists of an aspiration pipette able to meet the very severe sterilization and handling issues imposed during surgery. The simplicity of the device, free of any electronic circuitry, allows using it as an ancillary instrument. The deformation of the aspired tissue is imaged via a mirror using an external camera. The paper describes the experimental setup as well as the protocol that should be used during surgery. First feasibility measurements are shown for human tongue and forearm skin.

Framework for a low-cost intra-operative image-guided neuronavigator including brain shift compensation.

In this paper we present a methodology to address the problem of brain tissue deformation referred to as 'brain-shift'. This deformation occurs throughout a neurosurgery intervention and strongly alters the accuracy of the neuronavigation systems used to date in clinical routine which rely solely on pre-operative patient imaging to locate the surgical target, such as a tumour or a functional area. After a general description of the framework of our intra-operative image-guided system, we describe a procedure to generate patient specific finite element meshes of the brain and propose a biomechanical model which can take into account tissue deformations and surgical procedures that modify the brain structure, like tumour or tissue resection.

Intra-operative quantification of the surgical gesture in orbital surgery: application to the proptosis reduction.

BACKGROUND: Proptosis is characterized by a protrusion of the eyeball due to an increase of the orbital tissue volume. To recover a normal eyeball positioning, the most frequent surgical technique consists in the osteotomy of orbital walls combined with a loading on the eyeball to initiate tissue decompression. The first biomechanical models dealing with proptosis reduction, validated in one patient, have been previously proposed by the authors. METHODS: This paper proposed an experimental method to quantify the intra-operative clinical gesture in proptosis reduction, and the pilot study concerned one clinical case. The eyeball's backward displacement was measured by an optical 3D localizer and the load applied by the surgeon was simultaneously measured by a custom-made force gauge. Quasi-static stiffness of the intra-orbital content was evaluated. FINDINGS: The average values for the whole experiment was 16 N (SD: 3N) for the force exerted by the surgeon and 9 mm (SD: 4mm) for the eyeball backward displacement. The averaged quasi-static stiffness of the orbital content was evaluated to 2.4N/mm (SD: 1.2) and showed a global decrease of 45% post-operatively. INTERPRETATION: The protocol and the associated custom-designed devices allowed loads, induced displacements and macroscopic stiffness of the orbital content to be measured intra-operatively. The clinical relevance has been demonstrated in a pilot study. To our knowledge, no study has been published allowing the clinical gesture in proptosis reduction to be quantified intra-operatively. Associating an enlarged database and validated patient-related predictive models will reinforce the surgical efficiency and patient comfort contributing to diagnosis and intra-operative guidance.

Computer-assisted access to the kidney.

OBJECTIVES: The aim of this paper is to introduce the principles of computer-assisted access to the kidney. The system provides the surgeon with a pre-operative 3D planning on computed tomography (CT) images. After a rigid registration with space-localized ultrasound (US) data, preoperative planning can be transferred to the intra-operative conditions and an intuitive man-machine interface allows the user to perform a puncture. MATERIAL AND METHODS: Both CT and US images of informed normal volunteer were obtained to perform calculation on the accuracy of registration and punctures were carried out on a kidney phantom to measure the precision of the whole of the system. RESULTS: We carried out millimetric registrations on real data and guidance experiments on a kidney phantom showed encouraging results of 4.7 mm between planned and reached targets. We noticed that the most significant error was related to the needle deflection during the puncture. CONCLUSION: Preliminary results are encouraging. Further work will be undertaken to improve efficiency and accuracy, and to take breathing into account.

A simulator for maxillofacial surgery integrating 3D cephalometry and orthodontia.

OBJECTIVES: This paper presents a new simulator for maxillofacial surgery that gathers the dental and maxillofacial analyses together into a single computer-assisted procedure. The idea is to first propose a repositioning of the maxilla via the introduction of 3D cephalometry applied to a 3D virtual model of the patient's skull. Orthodontic data are then integrated into this model, using optical measurements of plaster casts of the teeth. MATERIALS AND METHODS: The feasibility of the maxillofacial demonstrator was first evaluated on a dry skull. To simulate malformations (and thus simulate a "real" patient), the skull was modified and manually cut by the surgeon to generate a given maxillofacial malformation (with asymmetries in the sagittal, frontal, and axial planes). RESULTS: The validation of our simulator consisted of evaluating its ability to propose a bone repositioning diagnosis that would restore the skull to its original configuration. An initial qualitative validation is provided in this paper, with a 1.5-mm error in the repositioning diagnosis. CONCLUSIONS: These results mainly validate the concept of a maxillofacial numerical simulator that integrates 3D cephalometry and guarantees a correct dental occlusion.