Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Occupational exposure to electromagnetic fields: risk assessment of operators performing Transcranial Magnetic Stimulation (TMS) treatments

The assessment of the risk from occupational exposure to electromagnetic fields (EMF) has attracted the attention of those involved in safety in the workplace, in particular after the updating of European legislation, with the publication for EMFs, of Directive 2013/35/EU1 of the European Parliament and of the Council, which made the risk assessment mandatory for this type of physical agents. The issue is made even more relevant by the proliferation of industrial and health applications using EMF even of considerable intensity. However, the rapid technological development has not always been accompanied by adequate growth in the culture of prevention and safety. Many devices expose both operators and persons of the general public to significant risks, but often, these risks are not adequately reported by the manufacturer, nor mentioned in the instruction manual, as would be expressly required by the harmonized standards. In this general framework is placed this Ph.D. research project, whose aim is to analyze possible conditions of risk in the workplace, considering only the environment where the EMF sources potentially expose the operator to risk. The research project involves a joint collaboration between two Institutions: the National Institute for Insurance against Accidents at Work - INAIL and of course Sapienza University of Rome. The project is developed in a multidisciplinary manner, providing experimental and numerical investigations to achieve the required goals, also considering the literature review and comparison for a more realistic analysis of the risk, in terms of human exposure to EMF. The work is based on a multiphysics approach to obtain a complete evaluation of the risk in the workplace, with the prospective to improve the current approach in the assessment of the risk and eventually suggest some indications to the operator for better use of the device under test. Therefore, the starting point has been a review of the workplaces to identify any gaps and critical issues in relation to the risk assessment and therefore for which it is considered necessary to deepen the protectionist issues. A literature analysis of the state of the art on the risk in the workplace is first carried out. This has been followed by numerical and accurate modeling of the device under test as well as the workers in a real reproduced work condition of exposure. Of paramount importance is the understanding of all the parameters that can affect the distribution of the induced EM quantities, which are essential for the risk assessment and the verification of compliance with the regulations system. To do this, it was necessary to study human exposure in-depth, also using different human body models available for dosimetric analysis on dedicated software. All the research has traveled on two parallel tracks, on the one hand, the need to fill the scientific gaps in the research area of exposure assessment of workers and on the other one to take into account the regulatory aspects, essential for a correct evaluation of professional exposure. Therefore, as a last step of the overall work, a possible new protocol of risk assessment analysis is proposed to move forward on the improvement of safety and security in the workplace

Influence of posture and coil position on the safety of a WPT system while recharging a compact EV

In this study, the human exposure to the magnetic field emitted by a wireless power transfer (WPT) system during the static recharging operations of a compact electric vehicle (EV) is evaluated. Specifically, the influence of the posture of realistic anatomical models, both in standing and lying positions, either inside or outside the EV, is considered. Aligned and misaligned coil configurations of the WPT system placed both in the rear and front position of the car floor are considered as well. Compliance with safety standards and guidelines has proven that reference levels are exceeded in the extreme case of a person lying on the floor with a hand close to the WPT coils, whereas the system is always compliant with the basic restrictions, at least for the considered scenarios

Tumor bed brachytherapy for locally advanced laryngeal cancer: a feasibility assessment of combination with ferromagnetic hyperthermia

Purpose. To assess the feasibility of adding hyperthermia to an original method of organ-preserving brachytherapy treatment for locally advanced head and neck tumors. Methods and materials. The method involves organ-preserving tumor resection and adjunctive high-dose-rate (HDR) brachytherapy delivered via afterloading catheters. These catheters are embedded in a polymeric implant prepared intraoperatively to fill the resection cavity, allowing precise computer planning of dose distribution in the surrounding at-risk tumor bed tissue. Theoretical and experimental analyzes address the feasibility of heating the tumor bed implant by coupling energy from a 100 kHz magnetic field applied externally into ferromagnetic particles, which are uniformly distributed within the implant. The goal is to combine adjuvant hyperthermia (40 °C–45 °C) to at-risk tissue within 5 mm of the resection cavity for thermal enhancement of radiation and chemotherapy response. Results. A five-year relapse free survival rate of 95.8% was obtained for a select group of 48 male patients with T3N0M0 larynx tumors, when combining organ-preserving surgery with HDR brachytherapy from a tumor bed implant. Anticipating the need for additional treatment in patients with more advanced disease, a theoretical analysis demonstrates the ability to heat at-risk tissue up to 10 mm from the surface of an implant filled with magnetically coupled ferromagnetic balls. Using a laboratory induction heating system, it takes just over 2 min to increase the target tissue temperature by 10 °C using a 19% volume fraction of ferromagnetic spheres in a 2 cm diameter silicone implant. Conclusion. The promising clinical results of a 48 patient pilot study demonstrate the feasibility of a new organ sparing treatment for laryngeal cancer. Anticipating the need for additional therapy, theoretical estimations of potential implant heating are confirmed with laboratory experiments, preparing the way for future implementation of a thermobrachytherapy implant approach for organ-sparing treatment of locally advanced laryngeal cancer

Encapsulated Contrast Agent Markers for MRI-based Post-implant Dosimetry

Low-dose-rate prostate brachytherapy involves the implantation of tiny radioactive seeds into the prostate to treat prostate cancer. The current standard post-implant imaging modality is computed tomography (CT). On CT images, the radioactive seeds can be distinctively localized but delineation of the prostate and surrounding soft tissue is poor. Magnetic resonance imaging (MRI) provides better prostate and soft tissue delineation, but seed localization is difficult. To aid with seed localization, MRI markers with encapsulated contrast agent that provide positive-contrast on MRI images (Sirius MRI markers; C4 Imaging, Houston, TX) have been proposed to be placed adjacent to the negative-contrast seeds. This dissertation describes the development of the Sirius MRI markers for prostate post-implant dosimetry. First, I compared the dose-volume histogram and other dosimetry parameters generated by MIM Symphony (a brachytherapy treatment planning system that allow the use of MRI images for treatment planning; MIM Software Inc., Cleveland, OH) and VariSeed (a widely used brachytherapy treatment planning system; Varian Medical Systems, Inc., Palo Alto, CA), and found the dosimetry between both brachytherapy treatment planning systems to be comparable. To gain more insight into the MRI contrast characteristics of the Sirius MRI markers, I measured the Sirius MRI marker contrast agent\u27s spin-lattice and spin-spin relaxivities, and studied the relaxation characteristics\u27 dependence on MRI field strength, temperature, and orientation. From the Sirius MRI marker\u27s contrast agent relaxation characteristics, I systematically studied the effect of varying MRI scan parameters such as flip angle, number of excitations, bandwidth, field of view, slice thickness, and encoding steps, on the Sirius MRI markers\u27 signal and contrast, as well as image noise, artifact and scan time. On patients implanted with Sirius MRI markers, I evaluated the visibility of the Sirius MRI markers and image artifacts. Lastly, I semi-automated the localization of markers and seeds to more enable the efficient incorporation of Sirius MRI markers as part of the clinical post-implant workflow. Ultimately, the Sirius MRI markers may change the paradigm from CT-based to MRI-based post-implant dosimetry, for a more accurate understanding of dose-response relationships in patients undergoing low dose rate prostate brachytherapy

Tools for improving high-dose-rate prostate cancer brachytherapy using three-dimensional ultrasound and magnetic resonance imaging

High-dose-rate brachytherapy (HDR-BT) is an interstitial technique for the treatment of intermediate and high-risk localized prostate cancer that involves placement of a radiation source directly inside the prostate using needles. Dose-escalated whole-gland treatments have led to improvements in survival, and tumour-targeted treatments may offer future improvements in therapeutic ratio. The efficacy of tumour-targeted HDR-BT depends on imaging tools to enable accurate dose delivery to prostate sub-volumes. This thesis is focused on implementing ultrasound tools to improve HDR-BT needle localization accuracy and efficiency, and evaluating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for tumour localization. First, we implemented a device enabling sagittally-reconstructed 3D (SR3D) ultrasound, which provides sub-millimeter resolution in the needle insertion direction. We acquired SR3D and routine clinical images in a cohort of 12 consecutive eligible HDR-BT patients, with a total of 194 needles. The SR3D technique provided needle insertion depth errors within 5 mm for 93\% of needles versus 76\% for the clinical imaging technique, leading to increased precision in dose delivered to the prostate. Second, we implemented an algorithm to automatically segment multiple HDR-BT needles in a SR3D image. The algorithm was applied to the SR3D images from the first patient cohort, demonstrating mean execution times of 11.0 s per patient and successfully segmenting 82\% of needles within 3 mm. Third, we augmented SR3D imaging with live-2D sagittal ultrasound for needle tip localization. This combined technique was applied to another cohort of 10 HDR-BT patients, reducing insertion depth errors compared to routine imaging from a range of [-8.1 mm, 7.7 mm] to [-6.2 mm, 5.9 mm]. Finally, we acquired DCE-MRI in 16 patients scheduled to undergo prostatectomy, using either high spatial resolution or high temporal resolution imaging, and compared the images to whole-mount histology. The high spatial resolution images demonstrated improved high-grade cancer classification compared to the high temporal resolution images, with areas under the receiver operating characteristic curve of 0.79 and 0.70, respectively. In conclusion, we have translated and evaluated specialized imaging tools for HDR-BT which are ready to be tested in a clinical trial investigating tumour-targeted treatment

Simplified modeling of implanted medical devices with metallic filamentary closed loops exposed to low or medium frequency magnetic fields

Background and objectives: Electric currents are induced in implanted medical devices with metallic fila-mentary closed loops (e.g., fixation grids, stents) when exposed to time varying magnetic fields, as those generated during certain diagnostic and therapeutic biomedical treatments. A simplified methodology to efficiently compute these currents, to estimate the altered electromagnetic field distribution in the bio-logical tissues and to assess the consequent biological effects is proposed for low or medium frequency fields.Methods: The proposed methodology is based on decoupling the handling of the filamentary wire and the anatomical body. To do this, a circuital solution is adopted to study the metallic filamentary implant and this solution is inserted in the electromagnetic field solution involving the biological tissues. The Joule losses computed in the implant are then used as a forcing term for the thermal problem defined by the bioheat Pennes' equation. The methodology is validated against a model problem, where a reference solution is available.Results: The proposed simplified methodology is proved to be in good agreement with solutions provided by alternative approaches. In particular, errors in the amplitude of the currents induced in the wires re-sult to be always lower than 3%. After the validation, the methodology is applied to check the interactions between the magnetic field generated by different biomedical devices and a skull grid, which represents a complex filamentary wire implant.Conclusions: The proposed simplified methodology, suitable to be applied to closed loop wires in the low to intermediate frequency range, is found to be sufficiently accurate and easy to apply in realistic exposure scenarios. This modeling tool allows analyzing different types of small implants, from coronary and biliary duct stents to orthopedic grids, under a variety of exposure scenarios.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/