A miniature HIFU excitation scheme to eliminate switching-induced grating lobes and nullify hard tissue attenuation

Phased array transducers are increasingly prevalent in a therapeutic contex as they facilitate precise control of the beam intensity and focus. To produce enough acoustic energy for ablation, large and costly amplifiers are required. Miniaturised switched circuits provide an alternative that is both more cost effective and more efficient. However, the high Q factor and curved geometry of a therapeutic transducer lends itself to grating lobes that deposit energy in undesirable areas when driven with switched circuitry. In this work, harmonic reduction pulse with modulation (HRPWM) is applied to a simulation of a therapeutic array. An array was simulated along with a skull that varied in attenuation. A number of switching schemes were tested and where possible, their amplitude was adjusted to reduce pressure variation in the acoustic field after propagation through the skull. Of the switched schemes tested, HRPWM performed best; reducing harmonically induced grating lobes by 12 dB and limiting pressure field variance to 0.1 dB which increases intensity at the focal point and makes therapy more efficient

Gallium Nitride Based High-Power Switched HIFU Pulser with Real-Time Current/Voltage Monitoring

High-Intensity Focussed Ultrasound (HIFU) techniques make use of ultrasound transducers capable of delivering high powers to be delivered at high frequencies. Real-time monitoring of power delivered can avoid damage to the transducer and injury to patients due to overexposure. This paper demonstrates the real-time current and voltage monitoring capabilities of a new Gallium-Nitride (GaN) based switched mode transmit pulser developed for the University of Leeds High-Intensity Focussed Ultrasound Array Research Platform (HIFUARP) system, which uses a novel approach of using an Analog Front End (AFE) floating on the transmitter output to provide high bandwidth current measurement

Ultrasound Guided Robot for Human Liver Biopsy using High Intensity Focused Ultrasound for Hemostasis

Percutaneous liver biopsy is the gold standard among clinician\u27s tool to diagnose and guide subsequent therapy for liver disease. Ultrasound image guidance is being increasingly used to reduce associated procedural risks but post–biopsy complications still persist. The major and most common complication is hemorrhage, which is highly unpredictable and may sometimes lead to death. Though the risk of mortality is low, it is too high for a diagnostic procedure. Post-biopsy care and additional surgical intervention to arrest hemorrhage make liver biopsy a costly procedure for health care delivery systems. Non-invasive methods to stop bleeding exist like electro–cautery, microwave, lasers, radio frequency, argon–beam, and High Intensity Focused Ultrasound (HIFU). All the methods except HIFU require direct exposure of the needle puncture site for hemostasis. HIFU is an ultrasound modality and uses mechanical sound waves for focused energy delivery. Ultrasound waves are minimally affected by tissue attenuation and focus internal targets without direct exposure. Human error in focusing HIFU renders it unusable for a medical procedure especially when noninvasive. In this project we designed and developed an ultrasound guided prototype robot for accurate HIFU targeting to induce hemostasis. The robotic system performs percutaneous needle biopsy and a 7.5 cm focal length HIFU is fired at the puncture point when the needle tip retracts to the liver surface after sample collection. The robot has 4 degrees of freedom (DOF) for biopsy needle insertion, HIFU positioning, needle angle alignment and US probe image plane orientation. As the needle puncture point is always in the needle path, mechanically constraining the HIFU to focus on the needle reduced the required functionality significantly. Two mini c-arms are designed for needle angle alignment and US probe image plane orientation. This reduced the contact foot print of the robot over the patient providing a greater dexterity for positioning the robot. The robot is validated for HIFU hemostasis by a series of experiments on chicken breasts. HIFU initiated hemorrhage control with robotic biopsy ensures arrest of post-biopsy hemorrhage and decreases patient anxiety, hospital stay, morbidity, time of procedure, and cost. This can also be extended to other organs like kidneys, lungs etc. and has widespread implications such as control of hemorrhage in post-biopsies in patients with reduced ability for hemostasis. This research opens a greater scope for research for automation and design making it a physician friendly tool for eventual clinical use

An integrated ultrasound transducer driver for HIFU applications

This thesis proposes an MRI-compatible integrated CMOS ampli er that is capable of di- rectly driving an ultrasound transducer for HIFU applications. The output stage of the integrated amplifier operates in class DE mode with its output directly connected to a shunt capacitor and an ultrasound transducer without the need for an inductor. This design was simulated with Spectre simulator using the 0:8 m 5/20 V CMOS process data available from Teledyne-DALSA Semiconductor. The proposed integrated ampli er has an e ciency of 80% with 1 W of output power at 1 MHz and achieves an acceptable level of third harmonic. A layout of the integrated ampli er was prepared. The integrated ampli er occupies a die area of approximately 2:5 mm by 1:6 mm including input-output pads

An Integrated Full-bridge Class-DE Ultrasound Transducer Driver for HIFU Applications

This thesis present a CMOS integrated transducer driver for high intensity focused ultrasound (HIFU) applications. Because this driver will be used in a magnetic resonance imaging (MRI) environment, no magnetic components such as inductors and transformers have been used in this design. The transducer is directly connected to the driver without a matching network. The output stage of this driver is a full-bridge Class DE RF amplifer which is able to deliver more power than the previous design that has a half-bridge Class DE amplifer. The driver was also designed to be used in a transducer array. A digital control unit was integrated with the power amplifer that allows to program the drivers phase shift and duty ratio. A strategy to drive a ultrasound transducer array using the designed driver is also presented in this thesis. This design was implemented using the AMS H35B4 CMOS technology using the Cadence suite of design tools and occupies a die area of 2mm by 1.5mm with 20 input and output pads. Simulation and initial experimental results are presented in this work. The proposed integrated CMOS driver has an efficiency of 89.4% with 3.60 W of output power. Results are little bit different for each transducer

Intraoperative Navigation Systems for Image-Guided Surgery

Recent technological advancements in medical imaging equipment have resulted in a dramatic improvement of image accuracy, now capable of providing useful information previously not available to clinicians. In the surgical context, intraoperative imaging provides a crucial value for the success of the operation. Many nontrivial scientific and technical problems need to be addressed in order to efficiently exploit the different information sources nowadays available in advanced operating rooms. In particular, it is necessary to provide: (i) accurate tracking of surgical instruments, (ii) real-time matching of images from different modalities, and (iii) reliable guidance toward the surgical target. Satisfying all of these requisites is needed to realize effective intraoperative navigation systems for image-guided surgery. Various solutions have been proposed and successfully tested in the field of image navigation systems in the last ten years; nevertheless several problems still arise in most of the applications regarding precision, usability and capabilities of the existing systems. Identifying and solving these issues represents an urgent scientific challenge. This thesis investigates the current state of the art in the field of intraoperative navigation systems, focusing in particular on the challenges related to efficient and effective usage of ultrasound imaging during surgery. The main contribution of this thesis to the state of the art are related to: Techniques for automatic motion compensation and therapy monitoring applied to a novel ultrasound-guided surgical robotic platform in the context of abdominal tumor thermoablation. Novel image-fusion based navigation systems for ultrasound-guided neurosurgery in the context of brain tumor resection, highlighting their applicability as off-line surgical training instruments. The proposed systems, which were designed and developed in the framework of two international research projects, have been tested in real or simulated surgical scenarios, showing promising results toward their application in clinical practice

Magneettikuvauksella ohjattu korkean intensiteetin kohdennettu ultraääniteknologia syöpätautien liitännäishoidoissa ja syöpälääkkeiden annostelussa

Ablative hyperthermia (more than 55 °C) has been used as a stand-alone treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45 °C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is noninvasive and spatially accurate, with precise and homogeneous heating limited to the target region. High-intensity focused ultrasound (HIFU) can noninvasively heat solid tumors deep within the human body. Magnetic resonance imaging (MRI) is ideal for HIFU treatment planning and monitoring in real time due to its superior soft-tissue contrast, high spatial imaging resolution, and the ability to measure temperature changes. The combination of MRI and HIFU therapy is known as magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU). Low temperature-sensitive liposomes (LTSLs) release their drug cargo in response to heat (more than 40 °C) and may improve drug delivery to solid tumors when combined with mild hyperthermia. MR-HIFU provides a way to image and control content release from imageable low-temperature sensitive liposomes (iLTSLs). This ability may enable spatiotemporal control over drug delivery - a concept known as drug dose painting. The objectives of this dissertation work were to develop and implement a clinically relevant volumetric mild hyperthermia heating algorithm, to implement and characterize different sonication approaches (multiple foci vs. single focus), and to evaluate the ability to monitor and control heating in real time using MR-HIFU. In addition, the ability of MR-HIFU to induce the release of a clinical-grade cancer drug encapsulated in LTSLs was investigated, and the potential of MR-HIFU mediated mild hyperthermia for clinical translation as an image-guided drug delivery method was explored. Finally, drug and contrast agent release of iLTSLs as well as the ability of MR-HIFU to induce and monitor the content release were examined, and a computational model that simulates MR-HIFU tissue heating and drug delivery was validated. The combination of a multifoci sonication approach and the mild hyperthermia heating algorithm resulted in precise and homogeneous heating limited to the targeted region both in vitro and in vivo. Heating was more spatially confined compared to the use of single focus sonication method. The improvement in spatial control suggests that multifoci heating is a useful tool in MR-HIFU mediated mild hyperthermia applications for clinical oncology. Using the mild hyperthermia heating algorithm, LTSL + MR-HIFU resulted in significantly higher tumor drug concentrations compared to free drug and LTSL alone. This technique has potential for clinical translation as an image-guided drug delivery method. MR-HIFU also enabled real-time monitoring and control of iLTSL content release. Finally, computational models may allow quantitative in silico comparison of different MR-HIFU heating algorithms as well as facilitate therapy planning for this drug delivery technique.Ablatiivista hypertermiaa (yli 55 °C) on perinteisesti käytetty leikkauksiin soveltumattomien kasvainten hoitoon. Lievän hypertermian (40-45 °C) on sen sijaan todettu olevan tehokas liitännäishoito syöpätautien säde- ja lääkehoidoille. Suotuisa hypertermiahoito on kajoamatonta ja täsmällisesti kohdistettua. Lämmityksen tulisi lisäksi olla tarkkaa, tasalaatuista ja kohdealueeseen rajoittunutta. Korkean intensiteetin kohdennettu ultraääni (HIFU) -hoito mahdollistaa kasvainten kajoamattoman lämmityksen. Magneettikuvauksen (MK) etuina ovat erinomainen pehmytkudoskontrasti, korkea paikkaresoluutio ja kyky mitata lämpötilan muutoksia. Näin ollen MK soveltuu erinomaisesti HIFU -hoitojen suunnitteluun ja seurantaan. MK:n ja HIFU:n yhdistelmää kutsutaan magneettikuvauksella ohjatuksi korkean intensiteetin kohdennetuksi ultraääniteknologiaksi (MR-HIFU). Lämpötilaherkät liposomit ovat suunniteltuja vapauttamaan lääkeainesisältönsä hieman normaalia ruumiinlämpötilaa korkeammissa lämpötiloissa (yli 40 °C). Yhdessä lievän hypertermian kanssa tämänkaltaiset liposomit voivat mahdollistaa kohdistetun lääkeaineen vapauttamisen. Liposomien sisällön vapautumisen tarkkailu voi myös mahdollistaa tarkan lääkemäärän kohdistetun annostelun kasvaimessa. Väitöskirjatyössä kehitettiin kliinisesti merkittävä lämmitysalgoritmi lievän hypertermian aikaansaamiseksi, toteutettiin usean samanaikaisen kohteen sonikaatio (ultraäänialtistus) menetelmä sekä arvioitiin algoritmin ja menetelmän kykyä kontrolloida kudoksen lämpötilaa käyttäen kliinistä MR-HIFU laitetta. Lisäksi tutkittiin HIFU:n kykyä vapauttaa lääkeaine lämpötilaherkistä liposomeista, karakterisoitiin lääke- ja kontrastiaineen vapautuminen kuvannettavissa olevista lämpötilaherkistä liposomeista sekä tarkasteltiin MR-HIFU:lla aikaansaadun lievän hypertermian potentiaalia kohdentaa lääkeaineen vapautuminen kasvaimeen. Tässä työssä myös validoitiin laskennallinen malli, joka simuloi MR-HIFU:lla aikaansaatua lämmitystä ja siitä johtuvaa lääkeaineen vapautumista, sekä todennettiin MR-HIFU:n sopivuus lämpöablaatioon perustuvaan kohdun pehmytkudoskasvainten hoitomenelmään kliinisessä käytössä. Lievän hypertermian lämmitysalgoritmi yhdessä usean kohteen sonikaatiomenetelmän kanssa tuotti täsmällisen, tasalaatuisen sekä paikallisesti rajoitetun lämmityksen kohdealueessa. Usean kohteen sonikaatiomenetelmä voi siis olla hyödyllinen työkalu MR-HIFU:n lievän hypertermian syöpähoidon sovelluksissa. MR-HIFU yhdessä lämpötilaherkkien liposomien kanssa sai aikaan merkittävästi korkeamman kasvaimen lääkeainekonsentraation verrokkiryhmiin nähden, ja saattaa siten soveltua kliiniseen käyttöön kuvantamisavusteisena lääkehoitona. Liposomien sisällön (lääkeaine + MK-kontrastiaine) vapautumisen kuvannettavuus merkitsee, että MR-HIFU saattaa lisäksi mahdollistaa tarkan lääkeannoksen kohdistetun vapauttamisen

HIFU Power Monitoring Using Combined Instantaneous Current and Voltage Measurement

During HIFU therapy it is important that the electrical power delivered to the transducer is monitored to avoid under or over exposure, ensure patient safety and to protect the transducer itself. Due to ease of measurement, the transducer’s potential difference may be as an indicator of power delivery. However, even when a transducer’s complex impedance is well characterised at small amplitudes and matching networks are used, voltage-only (VO) monitoring cannot account for the presence of drive waveform distortion, changes to the acoustic path or damage to the transducer. In this study, combined current and voltage (CCV) is proposed as an MRI-compatible, miniature alternative to bi-directional power couplers that is compatible with switched amplifiers. For CCV power measurement, current probe data was multiplied by the voltage waveform and integrated in the frequency domain. Transducer efficiency was taken into account to predict acoustic power. The technique was validated with a radiation force balance (RFB). When using a typical HIFU transducer and amplifier, VO predictions and acoustic power had a maximum difference of 20%. However, under the same conditions, CCV only had a maximum difference of 5%. The technique was applied to several lesioning experiments and it was shown that when VO was used as a control between two amplifiers there was up to a 38% difference in lesion area. This greatly reduced to a maximum of 5% once CCV was used instead. These results demonstrate that CCV can accurately predict real-time electrical power delivery leading to safer HIFU treatments

Design of a 2D MRI compatible robot for performing prostate cancer treatment using therapeutic ultrasound

Therapeutic ultrasound is a promising treatment method for many common cancers, including prostate cancer. Magnetic resonance image (MRI) guidance of therapeutic ultrasound permits targeting and monitoring of therapy. In this thesis a prototype MRI compatible positioning device for the treatment of prostate cancer using therapeutic ultrasound is presented. The accuracy, MRI compatibility and functionality of the positioning device was evaluated in in vitro experiments (using gel phantoms and in vitro). The MRI was used as the imaging guidance technique. The proposed device incorporates a portable electronic system and operates in two PC controlled stages, linear and angular (X - Θ) and one manual driven stage Z (height of the probe). The device is small and portable and can be placed on the patient’s table to any commercial MRI scanner. The proposed device was tested on two clinical MRI scanners of different manufacturers. Additionally, in this thesis a software that controls an MRI guided focus ultrasound system is presented. The software was written in C sharp and consists of the following options: a) connection with DAQ device, b) tab that controls 2D device, c) tab that controls 3D device, d) tab that controls ultrasound protocol and e) operation command history list, g) MRI compatible camera, h) open and control the DICOM images captured from the MRI scanner during the therapy, i) temperature reading of the HIFU focal point. The proposed positioning device offers approximately 20μm accuracy on linear and angular stages. It incorporates MRI compatible optical encoders as mechanical motion feedback. The accuracy measurements were taken using a digital calibre. The positioning device has range of 111mm in linear stage, ±90o on angular stage and 50mm on Z stage. The design was based on measurements that were taken by a 100 patients. The MRI compatibility and motion accuracy images were taken by scanning gel phantoms using T2W FSE on 1.5T and 3T MRI scanner

Optimum switch sizing for class DE amplifier

Recently, integrated class DE ampli fiers without matching networks have been proposed as a compact solution to drive a multi-element piezoelectric ultrasound transducer array for high-intensity focused ultrasound (HIFU) therapy. These transducers produce acoustic energy that translates into heat for tissue ablation. In order to steer the focal zone, each element in the transducer array is driven at a different phase. Hence, there's a need for the power amplifi er with a digital control unit in this application. Since each element in the transducer array has a different electrical characteristic and they have to be driven at the same frequency, it is a challenge to drive all transducers in the array at their optimum conditions. This work introduces strategies to determine efficient driving parameters for an entire transducer array. In addition. a method to improve the power efficiency of the class DE amplifi er by choosing the optimum size for switching MOSFETs is also proposed. During the operation of a class DE ampli fier, losses are caused by the ON resistance and the drivers of the MOSFET gate capacitances. These parameters are directly dependent on the size of the switching MOSFETs. A wider MOSFET will have a higher gate capacitance, but lower ON resistance. With the correct sizing, these losses can be greatly reduced to improve power efficiency and prevent excessive heating. The challenge with this method is the wide selection of transducers with varying impedance. As the load impedance changes, the MOSFET size also needs to be changed to maintain the maximum power efficiency. Also, the proposed design must deliver at least 1 W output power to the transducer in order to produce enough acoustic pressure. This output requirement will limit the available technology that can be used to design the amplifi er. In addition, this work also proposes a new driving circuit that consumes less power to operate, and also allows a full 0-360 degree phase shift. The design is simulated with Spectre simulator using 0.35 m 50V CMOS process data available from Austria Micro Systems. The proposed design can deliver 1422mW of average power to 6-elements transducer array, and achieve up to 91% power efficiency