WO2025141538A1

WO2025141538A1 - Microwave treatment system

Info

Publication number: WO2025141538A1
Application number: PCT/IB2024/063284
Authority: WO
Inventors: Alberto Angelo CONTI; Maria Michela COCCHI BIANCHI; Manuela BETTERA; Andrea Giacomini
Original assignee: Three Sys Srl; Three Tech Srl
Current assignee: Three Sys Srl; Three Tech Srl
Priority date: 2023-12-29
Filing date: 2024-12-30
Publication date: 2025-07-03
Anticipated expiration: 2026-06-29

Abstract

A microwave treatment system is described. The system (10) comprises an antenna array (110) including a plurality of antennas (112) and a driver circuit (114) configured to drive each of the antennas (112) with a respective driving signal (S), such that the antenna array (110) generates an electromagnetic field at a focal point (FP). The driver circuit (114) includes at least one oscillator (1140) configured to generate, for each antenna, a respective oscillating signal (C), wherein the oscillating signals (C) have the same frequency. A modulation circuit (1144) generates, for each antenna (112), a respective modulated signal (M) by enabling and disabling a respective oscillating signal (C) based on an enable signal (EN). An amplification circuit (1146) generates the driving signals (S) by amplifying the modulated signals (M). In particular, a control circuit (1148) is configured to periodically repeat driving intervals (P), wherein the control circuit (1148) generates the enable signal (EN) to sequentially enable a plurality of the oscillating signals (M) during each driving interval (P) for a multiple of the period of the oscillating signal (C).

Description

"Microwave Treatment System"

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TEXT OF THE DESCRIPTION

Technical Field

Various embodiments of the present description relate to solutions for treating solid tumors with microwaves.

Background

Microwave ablation (MW A) is a form of thermal ablation that uses electromagnetic waves to treat solid tumors. Thermal ablation is a technique that destroys tumor cells by exposing them to high temperatures, causing cell death through coagulative necrosis. MWA is a minimally invasive technique requiring the insertion of a needle into the tumor, typically guided by ultrasound, computed tomography, or magnetic resonance imaging. MWA can be used to treat tumors in various locations, such as the liver, lungs, kidneys, bones, and thyroid.

MWA operates on the principle that electromagnetic waves can induce molecular rotation of water molecules in tissues, generating heat through friction and causing cell death by coagulative necrosis. Electromagnetic waves used for MWA typically have a frequency range between 300 MHz and 300 GHz.

The needle used for MWA acts as an antenna connected to a microwave generator that produces and delivers electromagnetic waves. The antenna has a tip that emits electromagnetic waves in one direction, creating a spherical or ellipsoidal ablation zone around the tip. The size and shape of the ablation zone depend on various factors, such as the power and duration of microwave emission, the type and shape of the antenna, the distance and angle between the antenna and the tumor, the electrical and thermal properties of the tissues, blood flow, and heat dissipation in tissues. The power and duration of microwave emission are usually controlled by the operator, who can adjust them based on the desired outcome and the safety of the procedure.

The MWA procedure is typically performed under local anesthesia and sedation and can be conducted in an outpatient or inpatient setting. The patient is positioned on a table, and the tumor is located using ultrasound, computed tomography, or magnetic resonance imaging. The operator inserts the antenna into the tumor through the skin, using imaging guidance to ensure correct placement and alignment of the antenna. The operator then activates the microwave generator and delivers electromagnetic waves to the tumor, creating an ablation zone around the antenna tip. To achieve this, the operator typically monitors the temperature and dimensions of the ablation zone and adjusts the power and duration of microwave emission accordingly. The operator may repeat the procedure with multiple antennas or different positions of the same antenna, depending on the size and shape of the tumor. The antenna is then removed from the tumor.

The outcome of MWA is evaluated through imaging studies, such as ultrasound, computed tomography, or magnetic resonance imaging, performed immediately after the procedure or at a later time. Imaging studies can show the size and shape of the ablation zone, the presence or absence of residual tumor, and the presence or absence of complications, such as bleeding, infection, or damage to adjacent organs. The effectiveness of MWA is measured by the rate of complete ablation, defined as the absence of residual tumor or recurrence within the ablation zone. The safety of MWA is measured by the rate and severity of complications, which can be classified as minor or major. Minor complications do not require additional treatments or hospitalizations, such as pain, fever, nausea, vomiting, or skin burns. Major complications require further treatment or hospitalization, such as bleeding, infections, damage to adjacent organs, or systemic effects.

MWA offers some advantages over other thermal ablation techniques, such as radiofrequency ablation or laser ablation, as it produces higher thermal efficiency, faster ablation rates, larger necrosis zones, and less influence from the heat sink effect. Thermal efficiency is the ratio of heat generated by electromagnetic waves to heat dissipated by blood flow and tissues. Higher thermal efficiency means that a greater amount of heat is retained in tissues, resulting in higher temperatures and faster cell death.

However, MWA also has some disadvantages, such as the difficulty in predicting the shape and size of the ablation zone, the risk of damaging surrounding organs, and the need for greater operator experience and skill. The shape and size of the ablation zone depend on many factors, some of which are difficult to control or measure, such as the electrical and thermal properties of tissues, blood flow, and heat dissipation in tissues, as well as the distance and angle between the antenna and the tumor. Therefore, it is difficult to predict the exact shape and size of the ablation zone before or during the procedure, which may result in incomplete or excessive ablation. Incomplete ablation means that some tumor cells remain alive, increasing the risk of recurrence. Excessive ablation results in the destruction of some healthy cells, increasing the risk of complications. The risk of damaging surrounding organs is higher with MWA than with other thermal ablation techniques because electromagnetic waves can propagate beyond the intended ablation zone, especially if the antenna is near or in contact with adjacent organs. Therefore, it is important to avoid or minimize contact between the antenna and adjacent organs and carefully monitor the temperature and dimensions of the ablation zone.

MWA is described, for example, in U.S. Patent No. US 11,058,487 B2 or in scientific articles by M.G. Lubner, C. L. Brace, J. L. Hinshaw, F. T. Lee, "Microwave Tumor Ablation: Mechanism of Action, Clinical Results and Devices, " The Society of Interventional Radiology, 2010; J. I. Hernandez, M. F. J. Cepeda, F. Valdes, G. D. Guerrero, "Microwave Ablation: State of the Art Review, " Onco Target and Therapy, June 6, 2015; C. Kim, "Understanding the Nuances of Microwave Ablation for More Accurate Post-Treatment Assessment, " Future Medicine, February 14, 2018; Auto P. Tinguely, L. Frehner, A. Lachenmayer, V. Banz, S. Weber, D. Cardinas, M. H. Maurer - Frontiers, "Stereotactic Image- Guided Microwave Ablation for Malignant Liver Tumors - A Multivariable Accuracy and Efficacy Analysis," in Oncology, June 10, 2020; A. Radosevic, R. Quesada, C. Serlavos, J. Sanchez, A. Zugazaga, A. Sierra, S. Coll, M. Busto, G. Aguilar, J. Arce, D. Flores, J. M. Maiques, M. Garcia-Retortillo, J. A. Carrion, L. Visa, M. Villamonte, E. Pueyo, E. Barjano, M. Trujillo, P. Sanchez -Velazquez, L. Grande, F. Burdi o, "Microwave Versus Radiofrequency Ablation for the Treatment of Liver Malignancies: A Randomized Controlled Phase 2 Trial, " Nature, 2022; or A. Pfannenstiel, J. lannuccilli, F. H. Cornells, D. E. Dupuy, W. L. Beard, P. Prakash, "Shaping the Future of Microwave Tumor Ablation: A New Direction in Precision and Control of Device Performance, " International Journal of Hyperthermia, April 24, 2022.

Summary

Various embodiments of the present description provide new solutions for treating solid tumors with microwaves.

According to one or more embodiments, this objective is achieved through a microwave treatment system featuring the distinctive elements specifically outlined in the claims below.

The claims form an integral part of the technical teaching provided in this description. As mentioned before, various embodiments relate to a microwave treatment system. In particular, the system comprises an antenna array including a plurality of antennas and a driver circuit configured to drive each antenna with a respective driving signal, such that the antenna array generates an electromagnetic field at a focal point. For example, the number of antennas may range from 5 to 25. In various embodiments, the antennas are arranged on a semi-sphere.

In various embodiments, the system comprises one or more actuators configured to move the antenna array relative to a patient and a processing circuit configured to drive the actuators to selectively shift the focal point.

In various embodiments, the driver circuit includes at least one oscillator configured to generate, for each antenna, a respective oscillating signal, where the oscillating signals have the same frequency, typically between 300 MHz and 300 GHz, such as 900 MHz or 2.45 GHz. A modulation circuit is configured to generate for each antenna a respective modulated signal by enabling and disabling a respective oscillating signal based on an enable signal. An amplification circuit is configured to generate the driving signals by amplifying the modulated signals. A control circuit is configured to periodically repeat driving intervals, during which the control circuit sequentially enables a plurality of oscillating signals for a multiple of the oscillating signal's period, such as via respective PWM (modulations.

In various embodiments, the time during which each driving signal is enabled within the driving interval is shorter than the time it is disabled within the driving interval. For example, in various embodiments, the control circuit is configured to enable at most two oscillating signals simultaneously at any given time instant.

In various embodiments, the driver circuit includes a respective phaseshifting circuit with adjustable delay for one or more modulated signals.

In various embodiments, the system can regulate the energy transmitted to the focal point, as a function of data received from one or more temperature sensors. To this end, the control circuit can periodically disable the driving intervals for a given time, for instance, using additional PWM modulation. Additionally or alternatively, the gain of the amplification circuit can be adjustable for each driving signal, and the treatment system may include a processing circuit configured to modify the gain. Brief Description of the Figures

The embodiments of the present description will now be described with reference to the accompanying drawings, which are provided solely for illustrative purposes and are not limiting, wherein:

- Figure 1 illustrates an embodiment of a treatment system according to the present description;

- Figures 2A, 2B, and 2C show embodiments of antennas designed for use in the treatment system shown in Figure 1;

- Figure 3 illustrates an embodiment of an antenna array designed for use in the treatment system of Figure 1;

- Figure 4 provides an example of a focal point of the antenna array from Figure 3;

- Figure 5 shows an example of driving an antenna array;

- Figure 6 illustrates an example of the electromagnetic wave at a focal point of an antenna array;

- Figures 7A, 7B, 7C, and 7D show embodiments of driving an antenna array according to the present description;

- Figures 8A and 8B illustrate embodiments of a driver circuit for an antenna array according to the present description;

- Figures 9A and 9B show embodiments using the system of Figure 1 to treat a solid tumor with microwaves;

- Figures 10A, 10B, 10C, and 10D show embodiments of actuators configured to orient an antenna array relative to a patient; and

- Figure 11 illustrates an embodiment for regulating the energy transmitted to the focal point of an antenna array.

Detailed description

In the following description, numerous specific details are provided to offer a thorough understanding of the embodiments. The embodiments may be implemented without one or more specific details or using other methods, components, materials, etc. In some instances, well-known operations, materials, or structures are not shown or described in detail to avoid obscuring the aspects of the embodiments.

References throughout this description to “an embodiment” mean that a particular feature, element, or structure described with respect to the embodiment is included in at least one embodiment. Thus, the use of the phrase “in an embodiment” in various parts of this description does not necessarily refer to the same embodiment. Furthermore, particular features, elements, or structures can be combined in any suitable manner in one or more embodiments.

The references provided here are solely for convenience and do not define the scope or meaning of the embodiments.

As explained before, known solutions for treating tumors with microwaves require inserting a needle into the treatment area. The needle is configured to emit microwaves that heat the tissue in the treatment area. This principle is based on the fact that water molecules are polar due to the asymmetric orientation of the two hydrogen atoms relative to the oxygen atom. Therefore, when an electric field with a specific orientation is generated, each water molecule rotates to align with the field, colliding with other molecules and producing heat. The optimal frequency for transferring energy to water lies within the microwave range, particularly at 900 MHz or 2.45 GHz, commonly used in microwave ovens to heat food.

Consequently, to destroy tumor cells, the microwaves must locally reach the tumor to induce cell death by coagulative necrosis in a targeted area. For this reason, known solutions do not generate microwaves using an antenna located outside the patient’s body, as the microwaves would pass through and potentially damage other tissues. Precisely for this reason, MWA employs needles inserted into the tumor to apply microwaves locally within a specific zone.

The following describes a new solution that enables microwaves to be generated at a focal point using a plurality of antennas.

Figure 1 shows an embodiment of a treatment system 10 according to the present description. In particular, in the embodiment considered, the system 10 includes an antenna array 110 comprising a plurality of antennas 112i .. . 112_n. The antenna array 110 is associated with a driver circuit 114 configured to drive the antennas 1121 . . . 112n. Specifically, the driver circuit 114 is configured to generate for each antenna 112 a respective driving signal S, i.e., signals Si... S_n, such that each antenna 112 emits a corresponding electromagnetic radiation, particularly in the microwave range, between 300 MHz and 300 GHz.

For example, Figure 2A shows a first embodiment of an antenna 112. Specifically, in the embodiment considered, the antenna 112 is made of a wire with two terminals T1 and T2, where the wire is wound as a spiral or solenoid. However, other forms for the antennas can also be used. In general, each antenna 112 has a specific radiation pattern. For example, in various embodiments, the antennas 112 are flat, made of a copper wire wound in a spiral, with an internal diameter ranging between 15 mm and 50 mm, e.g., 18 mm or 36 mm, and an external diameter ranging between 100 mm and 250 mm, e.g., 180 mm. For instance, with an internal diameter of 36 mm and an external diameter of 180 mm, the antenna may have 72 turns. Alternatively, with an internal diameter of 18 mm and an external diameter of 180 mm, the antenna may have 81 turns. Based on the supply current, such an antenna is typically capable of generating a magnetic field between 50 and 500 pT (micro-Tesla) at a distance of 25 cm.

As shown in Figure 2B, in various embodiments, the antenna may consist of multiple concentric single turns 1120, e.g., turns 1120i.. . 1120k arranged in a single layer. For example, the number k of turns may range from 3 to 50. In various embodiments, the turns 1120i .. . 1120k are electrically connected in parallel.

Moreover, as shown in Figure 2C, in various embodiments, the turns 1120i ... 1120k may be arranged in one or more layers, e.g., one layer for each of the turns 1120i. . . 1120k.

In various embodiments, the lengths of the individual turns 1120 (intended as a geometric path) are all equal. To achieve this, since the internal diameters are smaller than the external ones, an additional segment is added to each turn 1120 to make them equal in length.

In various embodiments, the length of each turn 1120 corresponds to a multiple of the wavelength of the electromagnetic signal to be emitted.

As shown in Figure 3, in various embodiments, the antennas 112 are arranged as an array 110. For example, Figure 3 shows nine antennas 112i, 1122, . . . , 1129. The number n of antennas 112 may range from 3 to 50, preferably from 5 to 25, e.g., 9 or 17 antennas. In various embodiments, the antennas 112 are arranged on a hemisphere with a given radius.

Thus, as shown in Figure 4, based on the arrangement of the antennas 112 and their respective radiation patterns, the antenna array 110 is configured to generate an electromagnetic field focused at a given focal point FP.

For example, in various embodiments, the focal point FP is fixed relative to the antenna array 110. For example, the focal point FP may correspond to the center of the hemisphere on which antennas 112 are arranged. In general, the focal point FP may also vary depending on the dielectric properties of the material traversed by the electromagnetic waves. In various embodiments, the driver circuit 114 may be configured to adjust the phase and/or amplitude of the driving signals of antennas 112 to control a beamforming. This operation is well known in the context of antenna arrays.

In particular, non-invasive solutions already exist, often identified as focused microwave hyperthermia therapy (FMHT), where an antenna array is used. For instance, this solution is described in the documents Lyu C, Li W, Yang B, "Differential Evolution Optimization of Microwave Focused Hyperthermia Phased Array Excitation for Targeted Breast Cancer Heating ," Sensors, 2023, 23(8):3799, https://doi.org/10.3390/s23083799; or Nguyen, Phong Thanh, "Focusing microwave hyperthermia in realistic environment for breast cancer treatment," PhD Thesis, School of Information Technology and Electrical Engineering, The University of Queensland, 2016, https://doi.org/10.14264/uql.2016.522, whose contents are incorporated herein by reference.

Substantially, in this solution, as shown in Figure 5, the driver circuit 114 is configured to drive each antenna 112 with a respective driving signal S, e.g., driving signals Si, S2, S3, ... for antennas 112i, 1122, 1123, where each driving signal S corresponds to a sinusoidal wave with a given frequency f. For example, in various embodiments, each driving signal S has a frequency f of 900 MHz or 2.45 GHz, i.e., the resonant frequencies of water. Preferably, all signals S have the same frequency.

Substantially, as shown in Figure 6, the focal point FP corresponds to the location where the electromagnetic waves generated by the antennas 112 overlap, creating a sinusoidal wave with maximum amplitude. For this reason, the driver circuit 114 can vary the position of the focal point FP by adjusting the phase and/or amplitude of the various driving signals.

For instance, in the absence of a beamforming operation, the electromagnetic field created at the focal point FP approximately corresponds to a multiple of the electromagnetic field generated by each individual antenna at their respective distances. This multiple corresponds to the number n of antennas 112. Thus, the electromagnetic field can be concentrated at the focal point FP, and the surrounding tissue is traversed by an electromagnetic wave of lower intensity. Consequently, in this case, the antenna array 110 should be oriented such that the focal point FP is located within a solid tumor 20 to be treated.

However, the inventors observed that the electromagnetic field generated by a single antenna 112 still produces a heating effect in the tissue traversed by the electromagnetic wave. Therefore, to reduce this effect, the number n of antennas should be increased, and antennas 112 should be spaced apart. For this reason, FMHT has primarily been tested for breast tumors, where a high number of antennas radially surround the breast. However, this solution is not easily applicable to other types of tumors. In addition to the heating effect, without precise phase control, variations in distance among numerous antennas or other factors can easily introduce phase shifts that result in a reduction of the signal at the focal point instead of a constructive sum, thus achieving the opposite effect.

Conversely, in various embodiments of the present description, the driver circuit 114 is configured to drive each antenna 112 in a pulsed manner. Specifically, as previously explained, the antenna array 110 should generate an electromagnetic wave at the focal point FP with a given frequency f, and a corresponding period T = 1/f.

In the embodiment considered, as shown in Figure 7A, the driver circuit 114 is configured to periodically repeat driving intervals with a duration P. In various embodiments, the duration P corresponds to a multiple of the period T of the electromagnetic wave, i.e., P = m • T. For example, in various embodiments, the multiple m is at least 5.

Specifically, the driver circuit 114 is configured to generate the driving signals S such that:

- at least one driving signal S is activated at every time instant t within the interval P; and

- each driving signal S is activated during each interval P for a time equal to or greater than the period T but less than the duration P.

For example, in various embodiments, the driver circuit 114 is configured to activate each driving signal S within each interval P for a multiple k of the period T, where k is at least one and less than the multiple m, i.e., 1 < k < m.

For instance, in the embodiment shown in Figure 7A, the multiple k equals 1, and at any given moment, only a single driving signal S is activated. In this case, the multiple m corresponds to the number n of antennas.

However, as shown in Figure 7B, the multiple k can also be greater and may be chosen, for example, between 2 and 100, such as 3, 4, 5, 10, 15, 20, 25, 30, 40, 50, or 100. For example, in various embodiments, the multiple k is chosen between 25 and 50. In the embodiment shown in Figure 7B, the multiple k equals 3. Thus, in the embodiments shown in Figures 7A and 7B, the driver circuit 114 is configured to sequentially activate each driving signal S for a multiple k of the duration T, where the duration of the driving interval corresponds to P = k • n • T, i.e., m = k • n, and the signals are phase-shifted by k • T.

As shown in Figures 7C and 7D, one or more driving signals S may also be activated simultaneously. For example, in Figure 7C, the signals SI and S3 are activated during the same interval with durations k • T, and similarly, signals S2 and S4 are activated during the same interval with durations k • T. In contrast, in Figure 7D, each signal S is activated for its respective duration k • T, but the signals are phase-shifted relative to each other by less than k • T.

Thus, when multiple signals S are activated simultaneously, their respective electromagnetic fields overlap, generating a signal with greater amplitude (as described with reference to Figures 5 and 6). However, in various embodiments of the present description, the signals S are pulsed, i.e., activated for a duration that preferably corresponds to k • T, which is shorter than the duration of the interval P, which preferably corresponds to m • T. Preferably, all signals S are activated for the same duration, and the signals are phase-shifted relative to each other.

As mentioned previously, it is preferable that at least one signal S is activated at any given moment within the interval P, for example, at most two signals S. In various embodiments, the maximum number of signals S activated at any given moment is less than n/2, and preferably less than n/3. This ensures that the time each driving signal is enabled within the interval P is shorter than the time the same driving signal is disabled within the interval P.

Therefore, in various embodiments, each driving signal S essentially corresponds to a signal with a given carrier frequency f, modulated with intervals T. For example, in various embodiments, each signal S corresponds to a carrier signal modulated using a Pulse-Width Modulation (PWM). For instance, in various embodiments, the on-time corresponds to k • T, and the duration of a switching cycle corresponds to P, for example, m • T.

For example, as shown in Figure 8A, the driver circuit 114 includes one or more oscillators 1140 configured to generate, for each antenna 112, a respective oscillating signal C, i.e., signals Cl, ..., Cn. Preferably, these signals have sinusoidal forms with a given frequency f. For instance, as mentioned previously, the frequency f may be 900 MHz or 2.45 GHz. In the embodiment considered, the signals Cl, ..., Cn are supplied to a modulation circuit 1144, which is configured to generate the signals SI, . . ., Sn for the antennas 112. For example, as schematically shown, in various embodiments, the circuit 1144 receives, for each signal S, a respective enable signal and is configured to:

- in response to determining that the enable signal EN is de-asserted (indicating the respective driving signal is disabled), set the corresponding driving signal S, e.g., SI, to zero; and

- in response to determining that the enable signal EN is asserted (indicating the respective driving signal is enabled), set the corresponding driving signal S, e.g., SI, to the value of the corresponding oscillating signal C, e.g., Cl.

For instance, in the embodiment considered, the modulation circuit 1144 includes, for each signal S, a respective electronic switch, such as switches 1144i ... 1144_n, where each switch connects the respective signal S to the respective signal C, and wherein the switch is configured to close when the corresponding enable signal is asserted.

Thus, in the embodiment considered, the driver circuit 114 includes a control circuit 1148 configured to generate the enable signals EN such that, during each driving interval P, each signal S is sequentially enabled for k periods T. As described before, the phase shift between the enable signals EN can be equal to or less than k • T.

In various embodiments, the driver circuit 114 also includes an amplification circuit 1146. For example, this amplification circuit 1146 may include, for each signal S, a respective amplifier, such as amplifiers 1146i. . . 1146_n. In this case, the signal provided by the modulation circuit 1144, denoted as signal M, e.g., signals Ml, ..., Mn, may be a voltage signal, and the signal S can be a voltage (with higher amplitude) or preferably a current.

In various embodiments, the gain of each amplifier 1146i . . . 1146_n may be adjustable via a signal A. As will be described in more detail later, in various embodiments, the control circuit 1148 is configured to adjust this signal A based on data received from a processing circuit 100, such as data provided by a user through a user interface 102, data received via a communication interface 104, and/or data received from one or more sensors 130. In various embodiments, the driver circuit 114 may include a phase-shifting circuit 1142, such as a delay circuit. Generally, this circuit 1142 can be placed before (upstream) or after (downstream) the modulation circuit 1144.

For instance, in the embodiment shown in Figure 8A, the phase-shifting circuit 1142, e.g., comprising multiple delay lines 11421, ..., 1142_n, is located between the modulation circuit 1144 and the amplification circuit 1146. This configuration ensures that the control circuit 1148 does not need to consider delays introduced by the circuit 1142 when generating the signals EN.

Conversely, Figure 8B illustrates an embodiment where the phase-shifting circuit 1142, e.g., comprising multiple phase-locked loops (PLLs) 1142i, . . ., 1142_n, is located between the oscillator 1140 and the modulation circuit 1144.

In particular, in various embodiments, the phase-shifting circuit 1142 is configured to introduce a delay, or phase shift, in one or more signals C or M. For example, in the embodiments considered, the phase-shifting circuit 1142 includes, for each signal M (or similarly each signal C), a respective delay line or PLL 1142i ... 1142_n. In various embodiments, the delay of each delay line 11421. . . 1142_n is adjustable based on a signal D. In various embodiments, the control circuit 1148 is configured to generate the signals D, e.g., to compensate (calibrate) propagation delays or to implement beamforming operations.

Thus, to transmit the same energy via an antenna, the respective driving signal S must have a significantly higher amplitude to compensate for the modulation of signal S. For instance, considering n = 9 antennas with k = 1, each driving signal should have an amplitude nine times greater than the continuous signal shown in Figure 5.

Therefore, in the embodiment considered, each signal S contains frequency components corresponding to the carrier frequency, i.e., f = 1/T, and the modulation frequency, i.e., a frequency of 1/P. Consequently, since the resonant effect at the modulation frequency 1/P is much weaker, the tissue traversed by the electromagnetic wave generated by a single antenna heats up significantly less with a pulsed signal (Figures 7A-7D) compared to a continuous signal (Figure 5).

Therefore, to transmit the same energy, the amplitude of each driving signal S is increased compared to the solution shown in Figures 5 and 6. For example, assuming the signals S are not overlapped (Figures 7A and 7B), each pulse must already have an amplitude sufficient to generate the oscillation at the focal point FP with the desired amplitude. The inventors observed that this intermittent driving approach, even though the total energy transmitted by the antenna array 110 corresponds to that of Figures 5 and 6, generates significantly less resonance. Consequently, the tissues traversed by the electromagnetic wave generated by a single antenna heat up substantially less than with the previous solution. This is also because, at the start of each pulse sequence, the molecular inertia must be overcome, like the increased initial rolling effort of a tire.

As discussed before, the focal point FP should therefore be positioned to correspond to an area within the tumor to be treated. For example, as shown in Figure 1, to achieve this, the treatment system 10 may include one or more actuators 126 to move and/or orient the antenna array 110. Additionally or alternatively, as previously mentioned, the driver circuit 114 can adjust the phase (via signal D) and/or the amplitude (via signal A) of the signals S to implement beamforming operations.

For instance, this is shown in Figures 9A and 9B, where a patient 30 is lying on a table 140. In the embodiment considered, the actuators 126 form part of a robotic arm that allows the antenna array 110 to be oriented relative to the patient 30/table 140. In this way, as shown in Figure 9B, the focal point FP of the antenna array can be positioned within the tumor 20.

For example, in various embodiments, the actuator 126 is configured to adjust at least one of the following:

- as shown in Figure 10A, the position along a longitudinal direction x relative to the patient 30/table 140;

- as shown in Figure 10B, the position along a transverse direction y relative to the patient 30/table 140;

- as shown in Figure 10C, the distance along a z-axis relative to the patient 30/table 140; and

- as shown in Figure 10D, the angular orientation relative to the patient 30/table 140, for example, in the y-z plane.

For instance, in the embodiment considered, the driver circuit 114 and optional actuators 126 are controlled by a processing circuit 100, such as a computer, or an integrated or embedded processor.

In various embodiments, the processing circuit, the driver circuit 114, and the actuators 126 may be associated with a power supply circuit 106. In various embodiments, as mentioned before, the operation of system 10 may be controlled via a user interface 102, a communication interface 104, and/or sensors 130.

Specifically, as explained before, the driver circuit 114 and the antenna array 110 are configured to generate an electromagnetic wave at the focal point. Therefore, for proper operation, it must be ensured that the focal point FP is located within the tumor mass to be treated, and the evolution of tissue temperatures should also be monitored.

Accordingly, in various embodiments, the system 10 may include a sensor 140 configured to detect the temperature of the treatment area. Generally, the sensor may be a physical sensor inserted via a needle or, preferably, a sensor capable of detecting temperature remotely.

Therefore, in various embodiments, the system 10, such as circuit 100 and/or 114, may adjust the energy transmitted by the antenna array 110. As previously described, the energy received at the focal point FP can be adjusted by controlling the amplitude of the driving signals (see amplifier 1146) and/or by varying the number k of pulses within each interval P. Moreover, as shown in Figure 11, the energy may be adjusted by activating the sequence of intervals P using a PWM modulation, where the intervals P are repeated for an on-time TON, followed by an off-time TOFF, during which all signals S are disabled. For this purpose, the control circuit 1148 may generate enable signals EN obtained via a combination of two PWM signals: one for generating bursts of pulses, for example, with k pulses, and another for regulating the energy transferred to the focal point FP.

Thus, in various embodiments, the system 10 may be configured to monitor temperature changes and regulate the energy transmitted to the focal point FP, for instance, by using at least one of the following:

- a regulation of the amplitude A of the signals S;

- a regulation of the duration of the pulse bursts in each signal S, e.g., by varying the number of pulses k;

- modulating the repetition of the intervals P using a PWM modulation.

Additionally or alternatively, as described in the article by Cheng Lyu, the processing circuit 100 may store a mathematical model that enables the estimation of the focal point FP's position and, potentially, the evolution of the temperature at the focal point FP. For instance, such a model can be created during a training phase by performing multiple microwave treatments, recording temperature variations at different points, and then generating a model for the focal point position and temperature evolution using machine learning algorithms.

Of course, without prejudice to the principle of the invention, the details of construction and the embodiments may vary widely with respect to what has been described and illustrated herein purely by way of example, without thereby departing from the scope of the present invention, as defined by the ensuing claims.

Claims

1. A microwave treatment system, comprising an antenna array (110) comprising a plurality of antennas (112) and a driver circuit (114) configured to drive each of said antennas (112) with a respective driving signal (S), such that said antenna array (110) generates an electromagnetic field at a focal point (FP), wherein said driver circuit (114) comprises:

- at least one oscillator (1140) configured to generate for each antenna a respective oscillating signal (C), wherein said oscillating signals (C) have the same frequency, wherein said frequency is between 300 Mhz and 300 Ghz;

- a modulation circuit (1144) configured to generate for each antenna (112) a respective modulated signal (M) by enabling and disabling a respective oscillating signal (C) as a function of an enable signal (EN);

- an amplifier circuit (1146) configured to generate said driving signals (S) by amplifying said modulated signals (M); and

- a control circuit (1148) configured to periodically repeat driving intervals (P), wherein said control circuit (1148) is configured to generate said enable signal (EN) to enable during each driving interval (P) sequentially a plurality of said oscillating signals (M) for a multiple of the period of said oscillating signal (C).

2. The treatment system according to Claim 1, wherein, for each driving signal (S), the time that the respective driving signal is enabled in the driving interval (P) is less than the time that the respective driving signal is disabled in the driving interval (P).

3. The treatment system according to Claim 1 or Claim 2, where said control circuit (1148) is configured to disable periodically said driving intervals (P) for a given time (TOFF).

4. The treatment system according to any of the previous claims, comprising enabling at most two oscillating signals (M) at each time instant.

5. The treatment system according to any of the previous claims, wherein said frequency is 900 Mhz or 2.45 Ghz.

6. The treatment system according to any of the previous claims, wherein said driver circuit (114) comprises for one or more modulated signals a respective phase-shift circuit (1142) with adjustable delay (D).

7. The treatment system according to any of the previous claims, wherein the number of antennas is between 5 and 25.

8. The treatment system according to any of the previous claims, wherein said antennas are arranged on a semi-sphere.

9. The treatment system according to any of the previous claims, comprising one or more actuators (126) configured to move said antenna array (110) relative to a patient (30) and a processing circuit configured to drive said actuators to selectively move said focal point (FP).

10. The treatment system according to any of the previous claims, wherein the gain of said amplification circuit (1146) is settable for each driving signal (S), and wherein said treatment system comprises a processing circuit configured to vary said gain according to data received from one or more temperature sensors (130).

11. The treatment system according to any of the previous claims, wherein at least one of said driving signals (S) is activated at each time instant (t) of the driving interval (P).

12. The treatment system according to any of the previous claims, wherein said driver circuit (114) is configured to enable each driving signal (S) within each driving interval (P) for a multiple (k) of the period of said oscillating signal (C), where the multiple (k) is at least one.

13. The treatment system according to Claim 12, wherein the multiple (k) is chosen between 2 and 100.

14. The treatment system according to Claim 12 or Claim 13, wherein said driver circuit (114) is configured to sequentially activate each driving signal (S) for the multiple (k) of the period of said oscillating signal (C), and the signals are phase- shifted relative to each other by a duration equal to k • T, where k corresponds to said multiple (k) and T corresponds to the period (T) of said oscillating signal (C).

15. The treatment system according to any of the previous claims, wherein said treatment system is for focused hyperthermia therapy, and the treatment system is configured to generate an electromagnetic field at a focal point (FP) to locally induce cell death by coagulative necrosis.