Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia
<p>A major challenge in chemotherapy is that the systemic delivery of drugs to both healthy tissue as well as the tumour results in unwanted side effects. Thermosensitive liposomal carriers are designed to release their payload when they are exposed to mild hyperthermia (a few degrees above b...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2018
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| _version_ | 1797069491569426432 |
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| author | Chu, BTC |
| author2 | Coussios, CC |
| author_facet | Coussios, CC Chu, BTC |
| author_sort | Chu, BTC |
| collection | OXFORD |
| description | <p>A major challenge in chemotherapy is that the systemic delivery of drugs to both healthy tissue as well as the tumour results in unwanted side effects. Thermosensitive liposomal carriers are designed to release their payload when they are exposed to mild hyperthermia (a few degrees above body temperature). If a tumour can be locally heated, thermosensitive liposomes can provide triggered and localised delivery of the drug which should reduce systemic toxicity. Ultrasound is a noninvasive modality which can be used to produce localised heating at depth. However, most clinically approved high-intensity focused ultrasound (HIFU) systems are designed for tumour ablation and exhibit a focal volume which typically spans 1-3mm in width and 10-15mm in length, generating temperatures in excess of 50◦C for a few seconds to directly kill tissue within the focal volume. Hyperthermia-triggered drug release usually requires maintaining a tumour volume which often spans several centimetres in size at a consistent therapeutic temperature of 39.5-42◦C for durations up to an hour. This is difficult to achieve for most current HIFU transducers due to their small focal volume. The approach employed here is to design an acoustic lens that retrofits onto a clinical HIFU system to produce a focal volume better suited for mild hyperthermia. 3D printing is employed in this work to produce the lenses, and sectored lenses which enable a single-element transducer to produce acoustic fields with multiple foci in an annular pattern are investigated. Experimental measurements of the pressure and temperature using a small therapeutic transducer are consistent with simulations, and the simulated -3dB free-field focal volume of the transducer was increased from 9.6mm<sup>3</sup> to 90.9mm<sup>3</sup>. Finite element software is used to perform 3D linear full-wave simulations of an acoustic lens in a human liver target derived from a segmented CT dataset. The computational challenges with performing large 3D finite element simulations are addressed by dividing the simulation domain into several subregions. A phase-conjugate lens combined with masking transducer locations associated with ribs is explored as a solution to address aberrations in the acoustic field caused by tissue inhomogeneity. Experiments with a sectored acoustic lens on a clinical HIFU system showed the radial location of the free-field focus was shifted from 0mm to ±2.8mm in an annular pattern. This work shows that retrofitting a HIFU system with an acoustic lens is a practical approach to broadening the focal spot.</p> |
| first_indexed | 2024-03-06T22:25:15Z |
| format | Thesis |
| id | oxford-uuid:567466c1-c871-4493-a787-ca5a19c3f9f2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:25:15Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | oxford-uuid:567466c1-c871-4493-a787-ca5a19c3f9f22022-03-26T16:50:19ZDesign of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermiaThesishttp://purl.org/coar/resource_type/c_db06uuid:567466c1-c871-4493-a787-ca5a19c3f9f2Ultrasound Transducer Design3D PrintingBiomedical AcousticsPZFlexJC200Ultrasound Mediated Drug DeliveryHIFUThermosensitive LiposomesFibre Optic HydrophonesCT ImagingOnScaleTumour TargetingBiomedical EngineeringPatient Specific ModellingAcoustic LensesUltrasoundHigh Intensity Focused UltrasoundUltrasound SimulationSector Vortex TransducersTARDOXFinite Element ModellingUltrasound Mediated HyperthermiaFocused UltrasoundSonic ConceptsPatient Specific Acoustic LensesSector Vortex LensesMild HyperthermiaTumour Drug DeliveryTissue Mimicking MaterialTissue Mimicking PhantomChongqing HaifuAcoustic Hydrophone MeasurementTherapeutic UltrasoundEnglishORA Deposit2018Chu, BTCCoussios, CCCleveland, RO<p>A major challenge in chemotherapy is that the systemic delivery of drugs to both healthy tissue as well as the tumour results in unwanted side effects. Thermosensitive liposomal carriers are designed to release their payload when they are exposed to mild hyperthermia (a few degrees above body temperature). If a tumour can be locally heated, thermosensitive liposomes can provide triggered and localised delivery of the drug which should reduce systemic toxicity. Ultrasound is a noninvasive modality which can be used to produce localised heating at depth. However, most clinically approved high-intensity focused ultrasound (HIFU) systems are designed for tumour ablation and exhibit a focal volume which typically spans 1-3mm in width and 10-15mm in length, generating temperatures in excess of 50◦C for a few seconds to directly kill tissue within the focal volume. Hyperthermia-triggered drug release usually requires maintaining a tumour volume which often spans several centimetres in size at a consistent therapeutic temperature of 39.5-42◦C for durations up to an hour. This is difficult to achieve for most current HIFU transducers due to their small focal volume. The approach employed here is to design an acoustic lens that retrofits onto a clinical HIFU system to produce a focal volume better suited for mild hyperthermia. 3D printing is employed in this work to produce the lenses, and sectored lenses which enable a single-element transducer to produce acoustic fields with multiple foci in an annular pattern are investigated. Experimental measurements of the pressure and temperature using a small therapeutic transducer are consistent with simulations, and the simulated -3dB free-field focal volume of the transducer was increased from 9.6mm<sup>3</sup> to 90.9mm<sup>3</sup>. Finite element software is used to perform 3D linear full-wave simulations of an acoustic lens in a human liver target derived from a segmented CT dataset. The computational challenges with performing large 3D finite element simulations are addressed by dividing the simulation domain into several subregions. A phase-conjugate lens combined with masking transducer locations associated with ribs is explored as a solution to address aberrations in the acoustic field caused by tissue inhomogeneity. Experiments with a sectored acoustic lens on a clinical HIFU system showed the radial location of the free-field focus was shifted from 0mm to ±2.8mm in an annular pattern. This work shows that retrofitting a HIFU system with an acoustic lens is a practical approach to broadening the focal spot.</p> |
| spellingShingle | Ultrasound Transducer Design 3D Printing Biomedical Acoustics PZFlex JC200 Ultrasound Mediated Drug Delivery HIFU Thermosensitive Liposomes Fibre Optic Hydrophones CT Imaging OnScale Tumour Targeting Biomedical Engineering Patient Specific Modelling Acoustic Lenses Ultrasound High Intensity Focused Ultrasound Ultrasound Simulation Sector Vortex Transducers TARDOX Finite Element Modelling Ultrasound Mediated Hyperthermia Focused Ultrasound Sonic Concepts Patient Specific Acoustic Lenses Sector Vortex Lenses Mild Hyperthermia Tumour Drug Delivery Tissue Mimicking Material Tissue Mimicking Phantom Chongqing Haifu Acoustic Hydrophone Measurement Therapeutic Ultrasound Chu, BTC Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title | Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title_full | Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title_fullStr | Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title_full_unstemmed | Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title_short | Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia |
| title_sort | design of a defocused transducer for targeted cancer drug delivery by ultrasound mediated hyperthermia |
| topic | Ultrasound Transducer Design 3D Printing Biomedical Acoustics PZFlex JC200 Ultrasound Mediated Drug Delivery HIFU Thermosensitive Liposomes Fibre Optic Hydrophones CT Imaging OnScale Tumour Targeting Biomedical Engineering Patient Specific Modelling Acoustic Lenses Ultrasound High Intensity Focused Ultrasound Ultrasound Simulation Sector Vortex Transducers TARDOX Finite Element Modelling Ultrasound Mediated Hyperthermia Focused Ultrasound Sonic Concepts Patient Specific Acoustic Lenses Sector Vortex Lenses Mild Hyperthermia Tumour Drug Delivery Tissue Mimicking Material Tissue Mimicking Phantom Chongqing Haifu Acoustic Hydrophone Measurement Therapeutic Ultrasound |
| work_keys_str_mv | AT chubtc designofadefocusedtransducerfortargetedcancerdrugdeliverybyultrasoundmediatedhyperthermia |