Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids
Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This w...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/9/2540 |
| _version_ | 1797602907123613696 |
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| author | Diana Andrés Ian Rivens Petros Mouratidis Noé Jiménez Francisco Camarena Gail ter Haar |
| author_facet | Diana Andrés Ian Rivens Petros Mouratidis Noé Jiménez Francisco Camarena Gail ter Haar |
| author_sort | Diana Andrés |
| collection | DOAJ |
| description | Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets. The system is designed with the aim of treating several 3D cell aggregates contained in an International Electrotechnical Commission (IEC) tissue-mimicking phantom with multiple wells, each holding a single tumor spheroid, with real-time temperature and thermal dose monitoring. System performance was validated using acoustic and thermal methods, ultimately yielding thermal doses in three wells that differed by less than 4%. The system was tested in vitro for delivery of thermal doses of 0–120 cumulative equivalent minutes at 43 °C (CEM<sub>43</sub>) to spheroids of U87-MG glioma cells. The effects of ultrasound-induced heating on the growth of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermocycler. Results showed that exposing U87-MG spheroids to an ultrasound-induced thermal dose of 120 CEM<sub>43</sub> shrank them by 15% and decreased their growth and metabolic activity more than seen in those exposed to a thermocycler-induced heating. This low-cost approach of modifying a HIFU transducer to deliver ultrasound hyperthermia opens new avenues for accurately controlling thermal dose delivery to complex therapeutic targets using tailored acoustic holograms. Spheroid data show that thermal and non-thermal mechanisms are implicated in the response of cancer cells to non-ablative ultrasound heating. |
| first_indexed | 2024-03-11T04:22:09Z |
| format | Article |
| id | doaj.art-4ef2c4ed1ce1442f933fa67fab93620b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T04:22:09Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4ef2c4ed1ce1442f933fa67fab93620b2023-11-17T22:41:08ZengMDPI AGCancers2072-66942023-04-01159254010.3390/cancers15092540Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor SpheroidsDiana Andrés0Ian Rivens1Petros Mouratidis2Noé Jiménez3Francisco Camarena4Gail ter Haar5Instituto de Instrumentación para Imagen Molecular (I3M), CSIC—Universitat Politècnica de València, Camino de Vera S/N, 46011 Valencia, SpainInstitute for Cancer Research (ICR), London SM2 5NG, UKInstitute for Cancer Research (ICR), London SM2 5NG, UKInstituto de Instrumentación para Imagen Molecular (I3M), CSIC—Universitat Politècnica de València, Camino de Vera S/N, 46011 Valencia, SpainInstituto de Instrumentación para Imagen Molecular (I3M), CSIC—Universitat Politècnica de València, Camino de Vera S/N, 46011 Valencia, SpainInstitute for Cancer Research (ICR), London SM2 5NG, UKHyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets. The system is designed with the aim of treating several 3D cell aggregates contained in an International Electrotechnical Commission (IEC) tissue-mimicking phantom with multiple wells, each holding a single tumor spheroid, with real-time temperature and thermal dose monitoring. System performance was validated using acoustic and thermal methods, ultimately yielding thermal doses in three wells that differed by less than 4%. The system was tested in vitro for delivery of thermal doses of 0–120 cumulative equivalent minutes at 43 °C (CEM<sub>43</sub>) to spheroids of U87-MG glioma cells. The effects of ultrasound-induced heating on the growth of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermocycler. Results showed that exposing U87-MG spheroids to an ultrasound-induced thermal dose of 120 CEM<sub>43</sub> shrank them by 15% and decreased their growth and metabolic activity more than seen in those exposed to a thermocycler-induced heating. This low-cost approach of modifying a HIFU transducer to deliver ultrasound hyperthermia opens new avenues for accurately controlling thermal dose delivery to complex therapeutic targets using tailored acoustic holograms. Spheroid data show that thermal and non-thermal mechanisms are implicated in the response of cancer cells to non-ablative ultrasound heating.https://www.mdpi.com/2072-6694/15/9/2540acoustic hologramsacoustic lensesultrasound hyperthermiatumor spheroidsthermal dose |
| spellingShingle | Diana Andrés Ian Rivens Petros Mouratidis Noé Jiménez Francisco Camarena Gail ter Haar Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids Cancers acoustic holograms acoustic lenses ultrasound hyperthermia tumor spheroids thermal dose |
| title | Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids |
| title_full | Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids |
| title_fullStr | Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids |
| title_full_unstemmed | Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids |
| title_short | Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids |
| title_sort | holographic focused ultrasound hyperthermia system for uniform simultaneous thermal exposure of multiple tumor spheroids |
| topic | acoustic holograms acoustic lenses ultrasound hyperthermia tumor spheroids thermal dose |
| url | https://www.mdpi.com/2072-6694/15/9/2540 |
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