Reaching Deeper: Absolute In Vivo Thermal Reading of Liver by Combining Superbright Ag S Nanothermometers and In Silico Simulations

Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy.This work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2016-75362-C3-1-R, MAT2017-83111R, and MAT2017-85617-R, by the Instituto de Salud Carlos III (PI16/00812), by the Comunidad Autonoma de Madrid (B2017/BMD-3867 RENIM-CM), and cofinanced by the European Structural and investment fund. Additional funding was provided by the European Union's Horizon 2020 FET Open programme (Grant Agreement No. 801305, NanoTBTech), the Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal project IMP18_38 (2018/0265), and also by COST action CA17140. Y.S. acknowledges a scholarship from the China Scholarship Council (No. 201806870023). I.Z.G. thanks UCM-Santander for a predoctoral contract (CT63/19-CT64/19). D.O. and I.R. acknowledge financial support from the Community of Madrid under Contract No. PEJD-2017-PRE/IND-3663, and from the Spanish Ministry of Science and Innovation through the Ramon y Cajal grant RYC2018-025253-I, Research Networks grant RED2018-102626-T and the PID2019-106211RB-I00 grant as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). D.O. and I.R. also acknowledge support from the "NoCanTher" project, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 685795. E.X. is grateful for a Juan de la Cierva Formacion scholarship (FJC2018-036734-I)

Whither magnetic hyperthermia? A tentative roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia

Whither Magnetic Hyperthermia? A Tentative Roadmap

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02)

Soy Niña

Este libro pretende contribuir al reencuentro de la educación con esas finalidades que verdaderamente importan a una niña o un niño: ser feliz, jugar, vivir juntos y (no) aprender. Para ello hemos puesto el arte, nuestras experiencias y el saber acumulado al servicio del disfrute, el cuestionamiento, el análisis crítico y la construcción común de un presente deseable. Un texto colaborativo coordinado por Ignacio Calderón Almendros y realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga

In silico testing strategies for translational magnetic hyperthermia

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de Lectura: 31-05-2022Esta Tesis tiene embargado el acceso al texto completo hasta el 01-12-2023This thesis is a compilation of different improvements in magnetic hyperthermia treatments safety thanks to numerical computer simulation (in silico testing). This therapy uses the heat released by magnetic nanoparticles injected into tumours when exposed to an alternating mag-netic field, which induces cancer cell apoptosis. Magnetic hyperthermia has been and is being successfully trialed to treat different types of localised tumours. In silico analysis has shortened the time needed to obtain results, while reducing the cost for producing the results. In addition, virtual tests make it possible to predict the outcome of therapy and its safety in an almost infinite variety of scenarios, thus optimising the risk-benefit ratio. For this purpose, there exists mag-netic hyperthermia treatment planning platforms based on computer simulations. This thesis presents different contributions to increase the accuracy of this planning software, as well as to increase the personalisation of therapy for each patient. These improvements are already im-plemented in the clinical trial that has derived from the European NoCanTher project. Chapter 1 is an introduction to magnetic hyperthermia and treatment planning, including a brief review of the most commonly used parameters for safety analysis. This chapter is closely related to the next chapter, chapter 2, which describes the different components used in treatment simulation, from the development of the virtual models that reproduce the clinical scenario to the mathematical models used to predict the outcome of the therapy. This chapter also includes a brief introduction to machine and deep learning, which is used to personalise therapy as much as possible by creating hyper realistic models based on the patient. Chapter 3 includes the most relevant results obtained in the development of this thesis. This chapter is divided into two sections. The first one, focused on preclinical studies, includes the analysis of the cooling of different tissues by comparing in vivo mouse models and in silico virtual mouse models. This section also investigates the mechanisms of thermoregulation of healthy and tumour tissues based on their physiology. Within this same chapter 3, the second section includes different studies with direct translation to the clinic. In this section, the first steps taken to automatically obtain a personalised model of the patient thanks to deep learning are presented. The importance of considering the blood perfusion of the tumour when elaborating this model to achieve an accurate calculation of the thermal dosage is also studied. Finally, a methodology is presented to estimate the risk associ-ated with a particular treatment scenario, thus reformulating the exclusion criteria for magnetic hyperthermia and recovering a large number of patients who may benefit from this therapyI would like to acknowledge the COST Action MyWave (CA 17115), the NoCanTher pro-ject (grant agreement No 685795), the Regional Government of Madrid for the contract PEJD-2017-PRE/IND-3663, the Spanish Ministry of Economy and Competitiveness for the grants MAT2017-85617-R, Ramón y Cajal RYC2018-025253-I, the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686) and the support of NVIDIA Corporation through the GPU Grant Program with the donation of the Quadro P6000 GPU that was used in this thesi

Heating of metallic biliary stents during magnetic hyperthermia of patients with pancreatic ductal adenocarcinoma: an in silico study.

To investigate the eddy current heating that occurs in metallic biliary stents during magnetic hyperthermia treatments and to assess whether these implants should continue to be an exclusion criterion for potential patients. Computer simulations were run on stent heating during the hyperthermia treatment of local pancreatic tumors (5-15 mT fields at 300 kHz for 30 min), considering factors such as wire diameter, type of stent alloy, and field orientation. Maxwell's equations were solved numerically in a bile duct model, including the secondary field produced by the stents. The heat exchange problem was solved through a modified version of the Pennes' bioheat equation assuming a temperature dependency of blood perfusion and metabolic heat. The choice of alloy has a large impact on the stent heating, preferring those having a lower electrical conductivity. Only for low field intensities (5 mT) and for some of the bile duct tissue layers the produced heating can be considered safe. The orientation of the applied field with respect to the stent wires can give rise to the onset of regions with different heating levels depending on the shape that the stent has finally adopted according to the body's posture. Bile helps to partially dissipate the heat that is generated in the lumen of the bile duct, but not at a sufficient rate. The safety of patients with pancreatic cancer wearing metallic biliary stents during magnetic hyperthermia treatments cannot be fully assured under the most common treatment parameters

Dataset from "In silico assessment of collateral eddy current heating in biocompatible implants subjected to magnetic hyperthermia treatments"

This dataset from the publication entitled "Dataset from "In silico assessment of collateral eddy current heating in biocompatible implants subjected to magnetic hyperthermia treatments" contains simulated data of magnetic hyperthermia treatments for three different indications: colorectal cancer, prostate cancer and head & neck cancer. Since the aim of the study is to evaluate the risk of thermal damage caused by the collateral heating of two common types of passive prostheses (hip and dental implants), eddy currents induced in these implants upon interacting with the externally applied ac field during treatment have been computed for all the evaluated regions. Two different alloys for the implants have been considered for each case as well: Ti6Al4V and CoCrMo. At the same time, besides temperature, the specific abosorption rate (SAR) have been also computed to work out the energy deposition in tissues. Calculations have been carried out using a het exchange model with and without thermoregulation. log-log SAR vs T plots have been obtained and proposed as a quick means to pre-check treatment feasibility in each patient. These graphs are thought to be included in treatment planning prior to the clinical procedure. Other parameters taken into account have been the treatment time (5 and 30 minutes), and the maximum tolerable temperature threshold (1 or 5 ºC, as indicated by the ICNIRP commission), all for three main types of tissues, namely fat, bone and muscle. Each tissue have been simulated using three different field intensities (5, 10 and 15 mT). The field frequency has been 300 kHz in all cases. The files "Dataset_description.doc" and "file_scheme.txt" contain the structure and description of the files that make up the dataset. UPDATES FROM PREVIOUS VERSIONS: simulations of the dental implant without thermoregulation have been added