Charalampopoulou Alexandra
"Comparative radiobiological characterization of multiple ion irradiation in 2D and 3D in vitro models: Assessing radioresistance profiles and metastatic processes".
Abstract:
The present project will evaluate a preclinical, multi-endpoint analysis of radiation quality across a broad panel of intrinsically radioresistant tumours, integrating photon, proton, helium, and carbon ion irradiation in both 2D monolayers and 3D tumour spheroids. The project will systematically investigate how different radiation modalities influence DNA damage induction and repair, cell survival, cell-cycle redistribution, and key hallmarks of tumour aggressiveness, including migration and invasion. By combining biologically relevant in vitro models with advanced radiobiological and imaging techniques, this research will characterize differences in relative biological effectiveness and explore the role of microenvironmental factors in shaping radiation response. Particular attention will be devoted to the comparison between conventional low-LET radiation and emerging particle beams, with the aim of identifying biological signatures associated with enhanced tumour control.
Mandas Nicla
Supervisor: Prof. Danilo Pani (University of Cagliari)
Co-supervisor: Dr. V. Vitolo (CNAO)
Thesis Title (provisional): "Conception and Design of Novel Tools to Support Ventricular Tachycardia Ablation Procedure by Hadron Therapy".
Abstract:
This PhD project aimed to contribute to the optimization of VT ablation strategies, with the possibility of using hadron therapy for this aim, from two main points of view. First, deep learning tools have been developed for the automated preprocessing of cardiac CT images, including left ventricular segmentation and anatomical landmark localization, conceived to support multimodal integration between anatomical imaging and electroanatomical mapping. Then, localization of arrhythmogenic sites from electroanatomic substrate-mapping procedures has been optimized by developing novel features and approaches to the realization of electroanatomic maps. Within this context, entropy measures were employed to characterize abnormal ventricular potentials, with SlopEn showing the highest discriminative performance, while an automated algorithm based on the Hilbert–Huang transform accurately delineated the near-field activity in pathological electrograms.
Volpi Gaia
"Radiation effect on murine sarcoma cells and tumor with focus on hypoxic conditions and complement activation".
Abstract:
The main objective of this project is to investigate the potential relationship between carbon ion irradiation and the activation of the innate immune response, with a particular focus on the complement system. Emerging evidence suggests that, under specific conditions, complement activation may contribute to a pro-tumoural microenvironment, potentially affecting treatment response. Based on this hypothesis, the project aims to characterise the mechanisms through which carbon ion irradiation may trigger complement activation and to assess its biological consequences in the context of tumour progression. The ultimate goal is to evaluate the therapeutic potential of combining carbon ion radiotherapy with complement system inhibition, with the aim of enhancing treatment efficacy and limiting undesired pro-tumoural effects. This approach may provide novel insights into the immunomodulatory effects of heavy-ion radiotherapy and support the development of innovative combination strategies for the treatment of radioresistant tumours.
Ahtasham ul Hassan Hafiz
Tentative thesis title: "Development of a conformable Multi-Sensor System for Continuous Stress Assessment".
Abstract:
As modern healthcare places increasing emphasis on prevention, early diagnosis, and continuous monitoring of physiological and psychological states, there is a growing demand for wearable biosensing technologies that are non-invasive, real-time, and seamlessly integrated into daily life. Sweat, as a readily accessible and painless biofluid, offers significant advantages for such applications because it contains a rich collection of biomarkers associated with metabolic activity, hydration status, and stress-related biochemical pathways. However, despite notable progress in wearable biosensing research, existing epidermal devices often struggle to detect low-abundance biomarkers with high accuracy, and many current fabrication methods lack the scalability required for low-cost, large-area production.
In response to these limitations, this research aims to develop a flexible epidermal patch incorporating a system of multiple sensors and electrodes designed to monitor physiological indicators associated with stress. The platform integrates extended-gate organic field-effect transistor (EG-OFET) sensors, alongside electrodermal activity (EDA) measurements electrodes, that capture changes in skin conductance linked to emotional and physiological stress on an ultrathin, skin-conformal substrate. While cortisol detection through biomolecular functionalization such as DNA aptamers serves as a key component of the system, the platform is designed to support additional sensing modalities, enabling a more comprehensive assessment of the wearer’s stress state. The use of inkjet-printed gold electrodes ensures mechanical flexibility and compatibility with mass production, while the overall architecture maintains low power consumption suitable for continuous on-skin operation.
Through this approach, the project seeks to deliver a biocompatible, scalable, and multifunctional epidermal patch capable of real-time stress monitoring. This work contributes to the development of next-generation wearable systems for personalized health management and preventive digital healthcare.
Hussain Mujahid
"Comprehensive Prostate Cancer Treatment Coupling Hadron Therapy With Advanced Theranostics".
Abstract:
Prostate cancer is among the most common malignancies in men worldwide, representing a leading cause of cancer-related morbidity and mortality. Advanced prostate cancer frequently metastasizes to bone (in ~90% of metastatic cases), causing debilitating pain in up to 80% of affected patients. Current treatment paradigms for high-risk and metastatic prostate cancer remain suboptimal – conventional radiotherapy and surgery control localized tumors, and systemic therapies (androgen deprivation, chemotherapy) provide temporary remission, but disease progression and relapse are common. Recent breakthroughs in theranostics – especially prostate-specific membrane antigen (PSMA) targeted PET imaging and radioligand therapy – enable precision targeting of disseminated tumor cells, while hadron therapy (proton and carbon-ion radiotherapy) offers superior dose concentration to tumors with reduced collateral damage compared to conventional X-rays. This PhD research proposal aims to develop and evaluate a comprehensive treatment strategy that couples hadron therapy with advanced theranostics for prostate cancer, integrating state-of-the-art radiation techniques with molecular diagnostics and targeted radionuclide therapy.
We will investigate the synergy of highly focused hadron beam therapy with PSMA-targeted radiotheranostic approaches in both preclinical models and translational frameworks. Key objectives include: (1) determining the therapeutic efficacy and safety of combined proton/carbon-ion irradiation and PSMA radioligand therapy in controlling local and metastatic prostate tumor models; (2) leveraging advanced diagnostics – PSMA PET imaging, liquid biopsy biomarkers – to guide patient selection, real-time treatment adaptation, and response assessment; and (3) exploring underlying mechanisms of interaction (e.g. enhanced DNA damage, tumor microenvironment modulation, immunogenic effects) that arise from this combined modality. The methodology encompasses in vitrocell experiments, in vivo animal studies, and development of a protocol for a future phase I clinical trial. We will also consider regulatory and clinical translation aspects, aligning with European Medicines Agency (EMA) and U.S. FDA guidelines for novel radiopharmaceuticals and with International Atomic Energy Agency (IAEA) standards for advanced radiotherapy deployment.
By uniting hadron therapy – a cutting-edge physical approach to ablate tumors – with theranostics – a personalized medicine strategy linking diagnostics and therapeutics – this project expects to demonstrate improved tumor control and personalized treatment efficacy for prostate cancer. The outcomes will include a validated preclinical proof-of-concept for the combined therapy, identification of predictive biomarkers of response, and a comprehensive treatment framework ready for clinical evaluation. This innovative approach addresses both local tumor eradication and systemic disease control, potentially transforming management of aggressive prostate cancer and providing a model for multimodal cancer therapy in the era of precision medicine.
Lenzi Alessandra
Tentative thesis title: "Development of a flexible biosensor for CRP detection".
Abstract:
C-reactive protein (CRP) is a pentameric protein synthesized by the liver. It is commonly used as an acute-phase indicator of inflammation, as its circulating concentrations rise in response to inflammation events caused either by infection, injury or chronic diseases. Considering the plethora of possible healthcare applications, having a device that could readily assess CRP concentration, and most of all do it on different body fluids rather than blood, could be a game changer in those clinical situations in which it is required to monitor its level over time and in a non-invasive way. A possible scenario could be that of an intensive care unit (ICU) patient, whose CRP sweat levels could be monitored over time to detect sepsis and ensure a prompt intervention from clinicians.
In this thesis, a flexible CRP biosensor based on an organic field-effect transistor (OFET) was developed. The transistor was manufactured by inkjet printing gold electrodes on top of a polyethylene naphthalate (PEN) substrate featuring a Parylene C (ParC) buffer layer, in a top gate-bottom contacts configuration. Inkjet printing was chosen to keep the manufacturing process cost effective and easily scalable, while the flexible plastic substrate could enable a wearable application. DPP:DTT was used as organic semiconductor and was spincoated on top of the transistor channel area. Different architectures and materials were tested to achieve stable and reproducible devices.
Anti-CRP antibodies and aptamers were tested as capture probes for CRP using ELISA and SPR, and the best working ones were selected to be functionalized on top of the transistor’s sensing gate. The biosensors were tested exploiting a microfluidic system in an extended gate configuration, and different running buffers were used to study the impact of Debye’s length on transistors readout.
Finally, a combined approach using electronic transduction together with SPR was used to further study the binding between CRP and the capture probe. In this dual-mode approach, a multi-periodic grating was imprinted on the transistors sensing gates, and the so obtained sensing areas were optically probed from the backside while a potential was applied through a coplanar pseudoreference AgAgCl electrode immersed in the running buffer. In this way, it was possible to get additional insights as the electronic transduction could provide information about collective charge distribution, while SPR could confirm the binding as local mass increase on the sensing surface. This approach was exploited to optimize the functionalization protocol, in order to get reliable and reproducible results.
Leva Susanna
"Characterization of novel boron-based compounds for BNCT: from cellular transporters targeting to 3D tumor models".
Abstract:
Boron Neutron Capture therapy (BNCT) is an emerging radiotherapy based on the nuclear interaction between thermal neutrons and Boron-10 atoms selectively accumulated in tumor cells. This project focuses on characterizing novel boron-based compounds specifically designed to target cellular transporters that are overexpressed across various cancer types. The research involves a biological characterization of these agents, evaluating their uptake dynamics and therapeutic efficacy in combination with thermal neutrons. The study employs models of increasing complexity, from conventional 2D cultures to 3D matrix-based systems, to investigate how the extracellular matrix and the tumor microenvironment influence boron internalization and the localized biological damage. This comparative approach aims to evaluate the compounds' behavior in conditions that more closely mimic physiological tissues, providing a more reliable assessment of the overall BNCT effectiveness.
Pavanello Vittoria
"Feasibility and evaluation of treatment planning and biological modeling in Multi-Ion Radiotherapy".
Abstract:
The research project investigates the feasibility and potential of Multi-Ion RadioTherapy (MIRT), an advanced hadrontherapy technique that combines different particle species within a single treatment session. The study focuses on developing an appropriate treatment planning system (TPS) and testing innovative relative biological effectiveness (RBE) models. Through these tools, the project aims to evaluate the dosimetric and clinical implications of MIRT, as well as to identify its possible limitations when applied to real patients. The outcomes are expected to contribute to a better understanding of MIRT’s role within particle-based cancer therapy and to inform future steps toward its clinical application.
Ali Saadat
"Design, Development, and Characterisation of an Ionoacoustic Sensor for Real-Time Dosimetry in Hadron Therapy and FLASH Therapy".
Abstract:
The research focuses on exploiting radiation-induced acoustic signals as a novel method for monitoring dose deposition during ultra-high dose rate radiotherapy and hadron therapy. Real-time and accurate dosimetry is one of the critical challenges in these modalities, particularly for adaptive treatment strategies. In the initial stage of the project, a single-channel acoustic sensor has been designed and fabricated. Its performance has been characterized in an acoustic test bench, establishing the system transfer function, frequency response, sensitivity, and noise-equivalent pressure.
Subsequent phases of the research will focus on extending the design towards a multichannel sensor array, allowing for spatially resolved measurements of dose deposition. This system will then be tested and validated in hadron therapy beams, with the ultimate objective of enabling real-time, in situ dosimetry and treatment verification.
Aresta Simona
"Development and Validation of Deep Learning-Based Segmentation Methods for Brain Imaging".
Abstract:
This PhD thesis focuses on the development and validation of deep- learning models for automated segmentation in biomedical brain imaging analysis, with particular emphasis on brain tumor segmentation from magnetic resonance imaging. A central objective of the work is a systematic study of the literature on the most recent deep learning methods developed for medical image segmentation, with the aim of critically analyzing and benchmarking current approaches. Public datasets such as BraTS are used for model development and comparison, while private clinical datasets support external validation. The research addresses key challenges including imaging heterogeneity, annotation variability, and cross-center generalization. The overall goal is to contribute robust, reproducible, and clinically relevant segmentation methodologies for neuro-oncological imaging.
Asim Muhammad
"Development and Validation of Machine Learning Classification Models for Biomedical Brain Imaging Analysis".
Abstract:
This PhD thesis focuses on the development and validation of machine learning classification models for biomedical brain imaging analysis, with particular emphasis on brain tumor characterization from magnetic resonance imaging. A central objective of the research is a systematic study of the literature on state-of-the-art machine learning and deep learning methods for brain tumor classification, providing a critical overview of current approaches and open challenges. The work investigates advanced classification models for tumors such as gliomas, leveraging large public datasets including BraTS alongside private clinical datasets for external validation. Key challenges related to data heterogeneity, class imbalance, and cross-center generalization are systematically addressed. The proposed models are evaluated using rigorous validation protocols to assess robustness, interpretability, and clinical applicability, with the aim of supporting reliable decision-making in neuro-oncological imaging.
Vorster Ethan Robert
"Philosophy of Science Meets Hadron Therapy: An Exploration of Evidence, Values, and Expertise in Radiation Oncology".
Abstract:
This PhD thesis will consist of a collection of three papers at the intersection of philosophy of science and hadron therapy. The three works focus on evidence, values, and expertise, respectively. The first paper puts forward a Bayesian appraisal of mechanistic evidence in a bid to vindicate the evidential profile that hadron therapy produces, namely, strong mechanistic evidence with weak population-level evidence derived from RCTs. The second paper addresses the numerous ways in which non-epistemic values influence the design, development, and application of hadron therapy. Things such as cost, patient preferences and safety all steer hadron therapy while it simultaneously grapples with epistemic values which undergird the science and engineering that make up the treatment. This interplay between epistemic and non-epistemic values and how they play out in hadron therapy is the focus of this paper. The third paper seeks to understand the complex interrelations of the various types of experts that are at work in hadron therapy. Specifically, I will investigate how different fields come to understand important aspects like 'evidence', 'effectiveness', 'trust', etc. These concepts are at the core of hadron therapy, and parsing out how different fields use and understand them is going to be crucial. Importantly, this paper will try to uncover just how hadron therapy is so successful while relying on the work of so many different fields, which may potentially be 'talking past one another'.