Robust Optimal Power Distribution for Hyperthermia Cancer Treatment

We consider an optimization problem for spatial power distribution generated by an array of transmitting elements. Using ultrasound hyperthermia cancer treatment as a motivating example, the signal design problem consists of optimizing the power distribution across the tumor and healthy tissue regions, respectively. The models used in the optimization problem are, however, invariably subject to errors. To combat such unknown model errors, we formulate a robust signal design framework that can take the uncertainty into account using a worst-case approach. This leads to a semi-infinite programming (SIP) robust design problem, which we reformulate as a tractable convex problem that potentially has a wider range of applications

Locoregional hyperthermia of deep-seated tumours applied with capacitive and radiative systems. A simulation study

Background: Locoregional hyperthermia is applied to deep-seated tumours in the pelvic region. Two very different heating techniques are often applied: capacitive and radiative heating. In this paper, numerical simulations are applied to compare the performance of both techniques in heating of deep-seated tumours. Methods: Phantom simulations were performed for small (30 × 20 × 50 cm 3 ) and large (45 × 30 × 50 cm 3 ), homogeneous fatless and inhomogeneous fat-muscle, tissue-equivalent phantoms with a central or eccentric target region. Radiative heating was simulated with the 70 MHz AMC-4 system and capacitive heating was simulated at 13.56 MHz. Simulations were performed for small fatless, small (i.e. fat layer typically 3 cm) patients with cervix, prostate, bladder and rectum cancer. Temperature distributions were simulated using constant hyperthermic-level perfusion values with tissue constraints of 44 °C and compared for both heating techniques. Results: For the small homogeneous phantom, similar target heating was predicted with radiative and capacitive heating. For the large homogeneous phantom, most effective target heating was predicted with capacitive heating. For inhomogeneous phantoms, hot spots in the fat layer limit adequate capacitive heating, and simulated target temperatures with radiative heating were 2–4 °C higher. Patient simulations predicted therapeutic target temperatures with capacitive heating for fatless patients, but radiative heating was more robust for all tumour sites and patient sizes, yielding target temperatures 1–3 °C higher than those predicted for capacitive heating. Conclusion: Generally, radiative locoregional heating yields more favourable simulated temperature distributions for deep-seated pelvic tumours, compared with capacitive heating. Therapeutic temperatures are predicted for capacitive heating in patients with (almost) no fat

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Towards UWB microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and control in the thermal dose delivery which current systems are not able to provide. All clinical applicators available today are in fact based on a single-frequency technology. In terms of treatment planning options, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of UWB systems opens up an opportunity to overcome these limitations, as they convey the possibility to adapt the focal spot and to use multiple operating frequencies to reduce the power deposition in healthy tissues.In this thesis, we explore whether the current treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for UWB microwave hyperthermia. We analyze the most commonly used cost-functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel cost-function specifically tailored for UWB optimization (HCQ). To solve for the HCQ, we further describe a novel, time-reversal based, iterative scheme for the rapid and efficient optimization of UWB treatment plans. We show that the combined use of these techniques results in treatment plans that better exploit the benefits of UWB systems, yielding increased tumor coverage and lower peak temperatures outside the target. Next, we investigate the design possibilities of UWB applicators and introduce a fast E-field approximation scheme. The method can be used for the global optimization of the array parameters with respect to the multiple objectives and requirements of hyperthermia treatments. Together, the proposed solutions represent a step forward in the implementation of patient-specific hyperthermia treatments, increasing their accuracy and precision. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible, and motivate the efforts for further development of UWB applicators and systems

Current state of the art of regional hyperthermia treatment planning: A review

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed

Ultra wideband microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and precision in the thermal dose delivery. Current clinical applicators are not able to provide such control, partly because they are designed to operate at a single fixed frequency. In terms of treatment planning, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of ultra wide-band (UWB) systems opens up an opportunity to overcome these limitations, as they convey the possibility of adapting the focal spot and obtaining different power deposition patterns to reduce the heating of healthy tissues.In this thesis, we explore whether the current SAR-based treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for deep UWB microwave hyperthermia. We analyze the most commonly used cost functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel SAR-based cost function (HCQ) for UWB optimization that exhibits a high correlation with the resulting tumor temperature. To solve for the HCQ, we describe a novel, time-reversal-based, iterative scheme for a rapid and efficient optimization of UWB treatment plans. Next, we investigate the design possibilities of UWB brain applicators and introduce a fast E-field approximation scheme to quickly explore a large number of array configurations. The method determines the best antenna arrangement around the head with respect to the multiple objectives and requirements of clinical hyperthermia. Together, the proposed solutions manage to achieve the level of tumor coverage and hot-spot suppression that is necessary for a successful treatment. Finally, we investigate the benefit of integrating hyperthermia delivered by an optimized UWB applicator into the radiation therapy plan for a pediatric medulloblastoma patient. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible and motivate efforts for further development of UWB applicators and systems

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