Comprehensive dosimetric characterization of novel silicon carbide detectors with UHDR electron beams for FLASH radiotherapy.

BACKGROUND: The extremely fast delivery of doses with ultra high dose rate (UHDR) beams necessitates the investigation of novel approaches for real-time dosimetry and beam monitoring. This aspect is fundamental in the perspective of the clinical application of FLASH radiotherapy (FLASH-RT), as conventional dosimeters tend to saturate at such extreme dose rates. PURPOSE: This study aims to experimentally characterize newly developed silicon carbide (SiC) detectors of various active volumes at UHDRs and systematically assesses their response to establish their suitability for dosimetry in FLASH-RT. METHODS: SiC PiN junction detectors, recently realized and provided by STLab company, with different active areas (ranging from 4.5 to 10 mm2) and thicknesses (10-20 µm), were irradiated using 9 MeV UHDR pulsed electron beams accelerated by the ElectronFLASH linac at the Centro Pisano for FLASH Radiotherapy (CPFR). The linearity of the SiC response as a function of the delivered dose per pulse (DPP), which in turn corresponds to a specific instantaneous dose rate, was studied under various experimental conditions by measuring the produced charge within the SiC active layer with an electrometer. Due to the extremely high peak currents, an external customized electronic RC circuit was built and used in conjunction with the electrometer to avoid saturation. RESULTS: The study revealed a linear response for the different SiC detectors employed up to 21 Gy/pulse for SiC detectors with 4.5 mm2/10 µm active area and thickness. These values correspond to a maximum instantaneous dose rate of 5.5 MGy/s and are indicative of the maximum achievable monitored DPP and instantaneous dose rate of the linac used during the measurements. CONCLUSIONS: The results clearly demonstrate that the developed devices exhibit a dose-rate independent response even under extreme instantaneous dose rates and dose per pulse values. A systematic study of the SiC response was also performed as a function of the applied voltage bias, demonstrating the reliability of these dosimeters with UHDR also without any applied voltage. This demonstrates the great potential of SiC detectors for accurate dosimetry in the context of FLASH-RT.

Gadolinium-Doped Carbon Nanodots as Potential Anticancer Tools for Multimodal Image-Guided Photothermal Therapy and Tumor Monitoring.

This study focuses on the synthesis and characterization of gadolinium-doped carbon nanodots (CDs-Gd) and their potential applications in multimodal imaging and precision cancer therapy. CDs-Gd were synthesized through a solvothermal decomposition method combining citric acid, GdCl3, and urea. The incorporation of Gd3+ ions within the carbonaceous structure resulted in stable CDs-Gd with a peculiar architecture that retained optical and paramagnetic properties. Combined characterization techniques confirmed the presence of pH-sensitive COOH functions on the CDs-Gd surface along with the unique lattice structure induced by Gd3+ doping. The optical properties of CDs-Gd exhibited a tunable emission spectrum displaying blue-green emission with pH-dependent behavior. Additionally, CDs-Gd exhibited contrast-enhancing properties in T1-weighted magnetic resonance imaging (MRI) experiments. MRI acquisitions at different Gd3+ concentrations and pH values demonstrated the potential of CDs-Gd as contrast agents for monitoring pH changes in an aqueous environment. We found that the relaxivity of CDs-Gd at pH 5.5 (tumor, 11.3 mM-1 s-1) is roughly 3-fold higher than that observed at pH 7.4 (physiological, 5.0 mM-1 s-1) and outperformed clinical standards such as γ-butyrol (3.3 mM-1 s-1). Monitoring pH changes in tumor microenvironment (TME) is crucial for evaluating the effectiveness of anticancer treatments and understanding tumor progression. Furthermore, CDs-Gd demonstrated concentration-dependent photothermal conversion ability in the near-infrared (NIR) region, allowing for efficient heat generation under laser irradiation. This indicates the potential application of CDs-Gd in image-guided photothermal therapy (IG-PTT) for cancer treatment. The in vitro studies on MCF-7 (breast cancer) and 16-HBE (healthy bronchial epithelium) cell lines demonstrated that CDs-Gd exhibited high biocompatibility (cell viability >80%). However, upon NIR activation, they showed potent anticancer effects by inhibiting tumor cell proliferation and inducing apoptosis selectively in cancer cells. In conclusion, the synthesized CDs-Gd nanoparticles possess unique optical, photothermal, and MRI contrast properties, making them promising candidates for multimodal imaging-guided precision cancer therapy applications.

Improvement of neutron sensitivity for lithium formate EPR dosemeters: a Monte Carlo analysis.

This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of predicting the increase in dose achievable by the addition of sensitizers inside the pellets. As expected, a larger amount of 6Li induces an increase of energy released because of the charged secondary particles (i.e. 3H ions and α-particles) produced after neutron capture. For small depths in water phantom and low-energy neutron spectra the dose increase due to 6Li enrichment is high (more than three orders of magnitude with respect to the case of with 7Li). In case of epithermal neutron beams the energy released in 6Li-enriched LFM compound is smaller but larger than in the case of fast neutron beams. On the other hand, the computational analysis evidenced that gadolinium is less effective than 6Li in improving neutron sensitivity of the LFM pellets. Discussion based on the features of MC transport code is provided. This result suggests that 6Li enrichment of LFM dosemeters would be more effective for neutron sensitivity improvement and these EPR dosemeters could be tested for dosimetric applications in Neutron Capture Therapy.

Does exergaming promote neurofunctional changes in Parkinson´s disease? A pilot clinical study / Os exergames promovem alterações neurofuncionais na doença de Parkinson? Um estudo clínico piloto

Abstract Introduction Previous studies have demonstrated beneficial effects in people with Parkinson´s disease trained with exergames. However, to the best of our knowledge, none of them evaluated whether these effects are sustained by neurofunctional changes. Objective To evaluate neurofunctional effects of a training, by means of functional magnetic resonance imaging, in people with Parkinson´s disease. Methods This study was a blind, randomized, and controlled pilot clinical trial with crossover design. The participants were submitted to an evaluation including cognitive performance and functional magnetic resonance imaging before and after the WiiTM or control trainings. Trainings were applied for 10 days, in two consecutive weeks. Participants starting with WiiTM training were then moved to the control training and vice versa. A wash-out period of 45 days between the trainings was respected. Results Memory, executive and visuo-spatial functions, and attention were significantly improved compared to baseline (p < 0.05). No differences were observed in cognition compared to the control training. Though not significant, results of functional magnetic resonance imaging analyses suggested that WiiTM training could promote improvements on the brain functional connectivity especially in areas involved in motor execution, planning, visual, memory and somatosensory functions. Conclusion In people with Parkinson´s disease, an intensive WiiTM training improved cognitive performance that underlined neurofunctional changes in areas involved in cognitive processing.

Resumo Introdução Estudos anteriores demonstraram efeitos bené-ficos em pessoas com doença de Parkinson treinadas com exergames. No entanto, até onde sabe-se, nenhum deles avaliou se esses efeitos são sustentados por alterações neurofuncionais. Objetivo Avaliar os efeitos neurofuncionais de um treinamento, por meio da ressonância magnética funcional, em pessoas com doença de Parkinson. Métodos Trata-se de um ensaio clínico piloto cego, randomizado e controlado com delineamento crossover. Os participantes foram submetidos a uma avaliação incluindo desempenho cognitivo e ressonância magnética funcional antes e após treinamentos com Wii® ou controle. Os treinamentos foram aplicados durante 10 dias, em duas semanas consecutivas. Os participantes que começaram o treinamento com Wii® foram depois movidos para o treinamento de controle e vice-versa. Respeitou-se um período de wash-out de 45 dias entre os treinamentos. Resultados Memória, funções executivas e visuoespaciais e atenção melhoraram significativamente em comparação com a linha de base (p < 0,05). Não foram observadas diferenças na cognição em comparação com o treinamento de controle. Embora não significativos, os resultados das análises de ressonância magnética funcional sugeriram que o treinamento com Wii® poderia promover melhorias na conectividade funcional do cérebro, especialmente em áreas envolvidas na execução motora, planejamento, funções visuais, de memória e somatossensoriais. Conclusão Em pessoas com doença de Parkinson, um treinamento intensivo com Wii® melhorou o desempenho cognitivo, que destacou mudanças neurofuncionais em áreas envolvidas no processamento cognitivo.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects.

Introduction: Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit-risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models. Methods: We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed. Results: We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system. Conclusions: PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system's role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

Hydrogels for Three-Dimensional Ionizing-Radiation Dosimetry.

Radiation-sensitive gels are among the most recent and promising developments for radiation therapy (RT) dosimetry. RT dosimetry has the twofold goal of ensuring the quality of the treatment and the radiation protection of the patient. Benchmark dosimetry for acceptance testing and commissioning of RT systems is still based on ionization chambers. However, even the smallest chambers cannot resolve the steep dose gradients of up to 30-50% per mm generated with the most advanced techniques. While a multitude of systems based, e.g., on luminescence, silicon diodes and radiochromic materials have been developed, they do not allow the truly continuous 3D dose measurements offered by radiation-sensitive gels. The gels are tissue equivalent, so they also serve as phantoms, and their response is largely independent of radiation quality and dose rate. Some of them are infused with ferrous sulfate and rely on the radiation-induced oxidation of ferrous ions to ferric ions (Fricke-gels). Other formulations consist of monomers dispersed in a gelatinous medium (Polyacrylamide gels) and rely on radiation-induced polymerization, which creates a stable polymer structure. In both gel types, irradiation causes changes in proton relaxation rates that are proportional to locally absorbed dose and can be imaged using magnetic resonance imaging (MRI). Changes in color and/or opacification of the gels also occur upon irradiation, allowing the use of optical tomography techniques. In this work, we review both Fricke and polyacrylamide gels with emphasis on their chemical and physical properties and on their applications for radiation dosimetry.

Preoperative imaging findings in patients undergoing transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy.

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients' age (rho = 483, p < 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating.

Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRNAs.

The presence of a growing tumor establishes a chronic state of inflammation that acts locally and systemically. Bone marrow responds to stress signals by expanding myeloid cells endowed with immunosuppressive functions, further fostering tumor growth and dissemination. How early in transformation the cross-talk with the bone marrow begins and becomes detectable in blood is unknown. Here, gene expression profiling of the bone marrow along disease progression in a spontaneous model of mammary carcinogenesis demonstrates that transcriptional modifications in the hematopoietic compartment occurred as early as preinvasive disease stages. The transcriptional profile showed downregulation of adaptive immunity and induction of programs related to innate immunity and response to danger signals triggered by activating transcription factor 3. Transcriptional reprogramming was paralleled by the expansion of myeloid populations at the expense of erythroid and B lymphoid fractions. Hematopoietic changes were associated with modifications of the bone marrow stromal architecture through relocalization and increased density in the interstitial area of Nestin+ mesenchymal cells expressing CXCL12 and myeloid cells expressing CXCL12 receptor CXCR4. These early events were concomitant with deregulation of circulating miRNAs, which were predicted regulators of transcripts downregulated in the bone marrow and involved in lymphoid differentiation and activation. These data provide a link between sensing of peripheral cancer initiation by the bone marrow and hematopoietic adaptation to distant noxia through transcriptional rewiring toward innate/inflammatory response programs. SIGNIFICANCE: The bone marrow senses distant tissue transformation at premalignant/preinvasive stages, suggesting that circulating messengers, intercepted in the blood, could serve as early diagnostic markers.

Patient centring and scan length: how inaccurate practice impacts on radiation dose in CT colonography (CTC).

OBJECTIVE: The aim of this study was to acknowledge errors in patients positioning in CT colonography (CTC) and their effect in radiation exposure. MATERIALS AND METHODS: CTC studies of a total of 199 patients coming from two different referral hospitals were retrospectively reviewed. Two parameters have been considered for the analysis: patient position in relation to gantry isocentre and scan length related to the area of interest. CTDI vol and DLP were extracted for each patient. In order to evaluate the estimated effective total dose and the dose to various organs, we used the CT-EXPO® software version 2.2. This software provides estimates of effective dose and doses to the other various organs. RESULTS: Average value of the patients' position is found to be below the isocentre for 48 ± 25 mm and 29 ± 27 mm in the prone and supine position. It was observed that the increase in CTDI and DLP values for patients in Group 1, due to the inaccurate positioning, was estimated at about 30% and 20% for prone and supine position, respectively, while in Group 2, a decrease in CTDI and DLP values was estimated at about 16% and 18% for prone and supine position, respectively, due to an average position above isocentre. A dose increase ranging from 4 up to 13% was calculated with increasing the over-scanned region below anal orifice. CONCLUSION: Radiographers and radiologists need to be aware of dose variation and noise effects on vertical positioning and over-scanning. More accurate training need to be achieved even so when examination protocol varies from general practice.

Transcranial magnetic resonance-guided focused ultrasound surgery at 1.5T: a technical note.

Magnetic resonance-guided focused ultrasound is one of the emerging non-invasive technologies offering both image guidance and thermal monitoring. In recent years transcranial application of this technology is starting to impact heavily the neuroscience field. We present here the imaging protocol and the technological methods successfully used with a transcranial magnetic resonance-guided focused ultrasound system certified for clinical treatments of functional neurological disorders, integrated for the first time with a 1.5T magnetic resonance scanner. Compared to the body radiofrequency coil (the one commonly used with transcranial magnetic resonance-guided focused ultrasound system integrated with 3T magnetic resonance scanners), the use of a dedicated two channel coil enabled a signal-to-noise ratio gain up to five times higher.