System for automatic temperature regulation for an MRI-guided multi-emitter laser thermal therapy device

Abstract

The invention relates to a method for regulating temperature in a plurality of regions of interest (R1, R2, R3) of a biological tissue (T), which regions are subjected to a plurality of laser beams of predetermined wavelengths which have adjustable laser emission powers and / or durations and which originate from a multi-emitter laser apparatus (4) within a device (S) for MRI-guided thermal therapy. The method comprises steps of generating and visualising thermal images Tn(x, y, z) in said plurality of regions of interest (R1, R2, R3) by processing complex modulus and phase images originating from a device (20) for magnetic resonance imaging (MRI). This method further comprises real-time processing of the thermal images, taking into account a set of planning parameters, in order to output set values for regulating the power and / or the duration of energy emission of all or part of said laser beams which are applied to one or more of the regions of interest (R1, R2, R3).

Description

Automatic temperature control system and method for MRI-guided multi-emitter laser thermotherapy equipment FIELD OF THE INVENTION

[0001] The present invention relates to an automatic temperature control or feedback system for an MRI-guided multi-emitter laser thermotherapy device. It also relates to a temperature control method implemented in this system, as well as thermotherapy equipment implementing this automatic control system.

[0002] The field of the invention is that of laser-induced thermotherapy equipment guided by magnetic resonance imaging (MRI), also referred to as MRI-Guided Laser-Induced ThermoTherapy with the acronym MR-LITT. STATE OF THE ART

[0003] Current laser devices used during MRI-guided LITT procedures can use one or more emitter heads to create coagulation necrosis of biological tissues, but do not offer precise temperature control capabilities within biological tissues.

[0004] MRI-guided LITT is used for thermotherapy of various diseases (i.e., glioblastoma, prostate cancer, for example), as disclosed in the publication by I. Karampelas and A.E. Sloan, “Laser-Induced Interstitial Thermotherapy of Gliomas,” in Progress in Neurological Surgery, vol. 32, MF Chernov, Y. Muragaki, S. Kesari, and IE McCutcheon, Ed. S. Karger AG, 2018, pp. 14-26.

[0005] Current laser devices use one or more emitting heads to create coagulation necrosis of pathological biological tissues, as disclosed in the publication by Laganà A, Di Lascio G, Di Blasi A, Licari LC, Tufano A, Flammia RS, De Carolis A. “Ultrasound-guided SoracteLite™ transperineal laser ablation (TPLA) of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH): a prospective single-center experience” World J Urol. 2023 April.

[0006] Document WO2022248778A1 discloses a multi-laser energy emitter laser device (1) for treating a target region of a biological tissue, comprising:

[0007] - at least one sheath having a longitudinal axis and comprising a proximal end and a distal end provided with an emitting head intended to be placed opposite the target region;

[0008] - at least two optical fibers extending in the sheath between the proximal end and the emitting head, each of the optical fibers being adapted to guide a heat treatment laser beam to the target region and to deposit laser energy in the target region via their emitting head;

[0009] - the emitting heads of at least two optical fibers being configured to each emit a laser beam in a different emission direction relative to the longitudinal axis of the sheath;- a multi-emitter laser device configured to generate at least two laser beams, said at least two laser beams having different or identical wavelengths with adjustable light emission power or duration;

[0010] - a control unit of the multi-emitter laser device so as to select the wavelength, the light power, the duration of the laser energy deposition and the moment of emission of each of the laser beams guided by the optical fibers and emitted towards the target region by the emitting heads, so as to generate and dynamically adjust a 3D thermal distribution having a geometric shape adapted to the geometric shape of the target region to be treated.

[0011] However, current clinical procedures apply a predefined laser power and duration at the start of treatment and may result in insufficient or excessive heating in the targeted region.

[0012] US 2018 / 368918 A1 discloses a use of real-time thermal MRI-guided laser interstitial thermotherapy, wherein some embodiments include registering fiducial markers with an image guidance system and monitoring temperature using magnetic resonance imaging thermography.

[0013] Document US 2021 / 386478 A1 discloses a system for ablation of tumor tissue by laser energy, comprising a laser probe and a magnetic resonance (MR) temperature probe equipped with an optical sensor.

[0014] US 2023 / 397953 A1 discloses the automation of a laser ablation system for damaging target tissue by applying heat. This system includes a controller coupled to various devices, such as a magnetic resonance imaging device, a laser energy source, a laser fiber manipulation device, a laser fiber cooling device, and a tissue damage analysis computer system, via a communication interface. The controller automatically controls various functions of the coupled devices during laser ablation, while monitoring the temperature of the tissue at the ablation site.

[0015] US 2015 / 265306 A1 discloses a method for thermal monitoring of tissue during thermotherapy, which may include identifying a bisection axis of the imaging plane located along at least the longitudinal axis of a thermotherapy instrument and a vector passing through a region of interest. This method may include identifying a plurality of thermal monitoring planes used for thermotherapy of the volume, each thermal monitoring plane intersecting the region of interest, a first thermal monitoring plane intersecting a second thermal monitoring plane at the bisection axis of the imaging plane, and the first thermal monitoring plane being offset from the second thermal monitoring plane by an intersection angle.This method may also include performing thermal monitoring of the thermotherapy by obtaining magnetic resonance images (MRI) obtained from the first and second monitoring planes, and calculating, from these images, volume temperature data.

[0016] CN 108836477 A discloses a magnetic resonance-guided laser hyperthermia system, comprising a workstation, laser ablation equipment, and minimally invasive surgical fiber optic components. The laser ablation equipment generates a real-time thermal image of the injured area using magnetic resonance thermal imaging technology during surgery. The laser power and cooling power are adjusted in real time based on the temperatures of the lesion and surrounding healthy tissue. The laser ablation equipment is used to generate and adjust the laser, as well as to drive and control the circulation of a cooling interstitium.

[0017] US 6542767 B1 discloses a method and system for using real-time closed-loop feedback to control thermal energy delivery. An energy delivery system may be used to deliver thermal energy to a target to modify it. The energy delivery system includes a temperature sensing system, a data processor, and a heat generating device. The temperature sensing system obtains temperature data from a target and transmits it to the data processor. The data processor may process the data to provide real-time control to the heat generating system and display the data as one or more images on a graphical user interface. The heat generating system receives commands from the data processor and modulates its heat output accordingly.

[0018] The purpose of the present invention is to propose an algorithm for automatic control of the temperature of the biological tissue combined with a multi-emitter laser device implemented in a laser thermotherapy assembly, the power or duration of emission of each emitter connected by optical fiber to an emitting head inserted into the biological tissue of which is automatically controlled or adjusted during ablation, which makes it possible to force the temperature of the biological tissue in the targeted regions to follow predefined temperature profiles.

[0019] This objective is achieved with a system for regulating the temperature in a plurality of regions of interest of a biological tissue, in each of which is inserted the emitting head of an optical fiber among a plurality of heads emitting laser beams of predetermined wavelengths and adjustable power or emission durations, produced by a multi-emitter laser source within MRI-guided thermotherapy equipment, this system comprising: means for processing images of each of said regions of interest, said images being delivered by magnetic resonance imaging equipment, so as to deliver images of temperature T n(x,y,z) of one or more of said regions of interest, comprising means for processing said temperature images in real time, taking into account a set of planning parameters, so as to deliver commands for adjusting the power and / or the duration of application of all or part of said laser beams applied to one or more of said one or more regions of interest, and means for applying said power adjustment commands or application duration adjustment commands to the multi-emitter laser device.

[0020] According to the invention, the means for real-time processing of the temperature images comprise a controller implementing a Proportional-Integral-Derivative (PID) type regulation algorithm integrating the resolution of the heat equation using a fast Fourier transform (FFT),

[0021] this regulation algorithm being arranged to deliver for each laser beam “j” after the calculation of the “x i » at iteration “n”, an energy setpoint E j (n) of the type: with :n representing time,

[0022] j representing each laser emitter,

[0023] P j representing the laser power delivered by the laser transmitter “j” during the interval ,

[0024] Q representing a system of equations allowing to link the contributions of the spatial distributions of thermal energy S j to temperature increasesx i in each region of interest R i R i representing a region of interest to be controlled in temperature,x i representing the evolution of the temperature required in each region R i between time "n" and time to follow the set temperature

[0025] S j representing the spatial distribution of thermal energy delivered in the biological tissue by the emitting head F j .

[0026] This provides a multi-emitter laser device whose power or emission duration of each emitter is automatically adjusted during treatment to force the temperature of the biological tissue measured by MRI thermometry in real time to follow a predefined profile.

[0027] The planning parameter set may advantageously include a temperature time setpoint curve (T ci (n)) for a given region of interest, as well as one or more parameters of the biological tissue to be treated and the heating characteristics S j of the emitting head of each optical fiber F j .

[0028] The expression for Q can be as follows:

[0029] Its resolution can be obtained by a matrix inversion technique or any other algorithm for solving a system of linear equations.

[0030] The temperature regulation method according to the invention may advantageously comprise an initial test firing step carried out to determine a spatial distribution of thermal energy of a source function S j attached to one or more of the F transmitter heads j .

[0031] Energy E j (n) can therefore be deposited by adjusting the power P j or the duration of the broadcast of the transmitter “j”.

[0032] In a particular embodiment, the means for processing the temperature images are integrated into the magnetic resonance imaging (MRI) equipment.

[0033] In another embodiment, the temperature image processing means are integrated into an image reconstruction unit downstream of the magnetic resonance imaging (MRI) equipment.

[0034] According to yet another aspect of the invention, there is provided an MRI-guided laser thermotherapy equipment, comprising means for emitting a plurality of laser beams of determined wavelengths and adjustable powers and / or emission durations and means for applying said laser beams respectively in a plurality of regions of interest of a biological tissue, and magnetic resonance medical imaging equipment arranged to deliver and display temperature images of one or more of said one or more regions of interest.

[0035] This MRI-guided laser thermotherapy equipment further comprises a system for regulating the temperature in the one or more regions of interest according to the invention.

[0036] The means for applying the laser beams may advantageously be a plurality of optical fibers whose respective emitting heads are arranged to be inserted into a region of interest of a biological tissue and to emit there a laser beam of determined wavelength and of adjustable power or duration. These emitting heads may advantageously have a source function adapted to be used as input data for the temperature regulation system according to the invention.

[0037] In a first configuration, at least one of the optical fibers comprises an emitting head arranged to diffuse the laser light within the biological tissue in which this at least one emitting head is inserted.

[0038] In a second configuration, at least one of the optical fibers comprises an emitting head arranged to axially emit the laser light within the biological tissue in which said at least one emitting head is inserted.

[0039] In a third configuration, at least one of the optical fibers comprises an emitting head arranged to radially emit the laser light within the biological tissue in which said at least one emitting head is inserted.

[0040] In a fourth configuration, at least one of the optical fibers comprises an emitting head arranged to emit the laser light at a predetermined angle relative to the axis of said optical fiber within the biological tissue in which said at least one emitting head is inserted. It should be noted that these different optical fibers terminated with emitting heads can be combined with each other to create an adjustable volumetric light energy distribution. The invention is also compatible with any other emitting head.

[0041] The present invention thus proposes a solution for precise and rapid volume temperature control combined with a multi-emitter laser device to create ablation volumes that conform to the region to be treated and are different from those obtained with a single optical fiber terminated by an emitting head.

[0042] Fast, multi-slice thermometric data are processed on-the-fly to achieve efficient volumetric temperature control of biological tissue around multiple laser energy emitting heads simultaneously.

[0043] This provides real-time automatic temperature regulation simultaneously in all previously defined regions of interest during MRI / MRI-guided laser-induced thermotherapy.

[0044] Automatic volume regulation of biological tissue temperature induced by a multi-emitter laser device, combined with real-time multi-slice MRI thermometry, allows better control of local thermotherapies in the biological tissue to be treated.

[0045] The thermal regulation method according to the invention has the following technical advantages over the methods of the prior art: 3D control: it is possible to regulate the temperature in 3D in the biological tissue; Multi-emitters: it is possible to create conformable treatments (i.e. adaptable, modular and complex shapes) by modulating the energy deposition of several laser energy emitters simultaneously; Independent setpoints: it is possible to independently control the temperature over time in several regions of interest. FFT-based algorithms: deterministic calculation time independent of the number of sources to be controlled, taking into account a realistic physical model of the evolution of the temperature in biological tissues.If properly tuned, the algorithm should allow for accurate regulation of the temperature of the biological tissue in each predefined region of interest, even with a delay of several seconds between successively obtaining two temperature images of the same region. This relaxes the constraint on MRI thermometry and allows more time to be used to prioritize a large spatial coverage of 3D thermometry between two successive measurements, rather than a very frequent measurement on a very limited number of slices.

[0046] This is the whole point of a PID controller integrating the heat equation. If we do not integrate the latter, then we neglect cooling by diffusion and perfusion. To ensure that the feedback is effective, then it is necessary to have a measurement with a very short update time for the temperature measurement compared to the characteristic times of heat transport in the tissues, which limits the spatial coverage of MRI thermometry.

[0047] One could also implement a PI or P controller integrating the heat equation, but the proposed implementation of a PID controller leads to the situation where the difference between the set temperature and the measured temperature always converges to 0 (equation of a damped oscillator with zero discriminant), which is the objective of an efficient controller. The interest of a PID controller is above all to be robust to errors in the determination of α, D and w band their possible changes during treatment. For example, perfusion is even cancelled when coagulation necrosis is induced by sufficient heat deposition.

[0048] The proposed algorithm provides a precise and rapid solution to control the temperature rise of biological tissues during LITT procedures using a multi-emitter laser device, with the aim of creating ablation zones different from those obtained with a single optical fiber. Such automatic control of multi-emitter laser device can allow to produce conformable thermal ablation in biological tissues and / or to choose different target profiles to avoid overheating of critical biological tissues to be preserved. DESCRIPTION OF FIGURES

[0049] Schematically illustrates an MRI-guided laser thermotherapy system implementing a temperature regulation system according to the invention;

[0050] Schematically illustrates MRI thermometry sections positioned on regions of interest associated with three optical fibers terminated by a transmitter head inserted into biological tissue to be treated by MRI-guided laser thermotherapy;

[0051] Schematically illustrates several examples of fiber optic emitting heads used in an MRI-guided laser thermotherapy system according to the invention;

[0052] This is a block diagram of an exemplary embodiment of the automatic temperature regulation method according to the invention;

[0053] Lamontre shows two examples of automatic in vivo temperature regulation of a pig muscle;

[0054] Shows temperature and thermal dose images for a set of MRI slices as a function of time;

[0055] This is a schematic cross-sectional view of an organ in which pathological biological tissue is subjected to treatment by an MRI-guided laser thermotherapy system according to the invention; and

[0056] Illustrates time control curves of the temperature around two optical fibers terminated with emitting heads inserted in a region to be treated as shown in the, with a region to be preserved near the second emitting head (F2) whose limit temperature not to be exceeded is specified before treatment, with different options for implementing the automatic temperature regulation method according to the invention. DETAILED DESCRIPTION

[0057] An MRI-guided laser thermotherapy set S comprises, with reference to, (i) a laser multi-emitter device intended to emit three laser beams via optical fibers 7,8,9 terminated with emitter heads onto regions of interest (ROI: for "Region of Interest") R1,R2,R3 of a target region R of a biological tissue, (ii) magnetic resonance imaging equipment 20 surrounding the biological tissue to be treated, and (iii) an automatic temperature control system 1.

[0058] The three laser beams are generated by a laser multi-emitter device 4 and guided via optical fibers 7, 8, 9 which are each provided at their ends F1, F2, F3 with a light-emitting head. The laser multi-emitter device 4 comprises three laser emitters electrically powered from an electrical energy source 5 and controlled in power or in adjustable emission duration by a control unit 6.

[0059] A practitioner can insert each of the three emitting heads F1, F2, F3 each associated with a predetermined wavelength into regions of interest R1, R2, R3 of a pathological biological tissue, such as for example a tumor. The insertion can be monitored, for example using medical imaging equipment 20 or be assisted by a robotic system or carried out using a stereotaxic device.

[0060] As illustrated, once the emitting heads are positioned, the imaging equipment performs a plurality of MRI slices of temperature C1-C10 for example every second, simultaneously with the sequential activation of each low-power emitter (the emission durations and the powers of these test shots are chosen to be sufficiently low so as to clearly distinguish the increase in temperature around each emitting head compared to the uncertainty of the thermometry while avoiding inducing destructive heating of the biological tissue). The thermometry data produced during these test shots are analyzed using dedicated processing software connected to the imaging equipment 20 designed to: find in the temperature images the hottest pixels in the vicinity of each emitting head to locate the zone of maximum heating around each emitting head F1, F2, F3 in the region R of the biological tissue O to be treated,automatically or manually draw a 2D region of interest (for example, 3x3 pixel dimensions) on each imaging slice corresponding to the previously identified maximum heating, this region of interest being centered on the pixel of maximum heating,propagate each 2D region of interest over all the temperature imaging slices, to obtain 3D regions of interest R1, R2, R3 used by the temperature feedback algorithm around each of the emitting heads F1,F2,F3estimate the thermal parameters of the biological tissues around each emitting head: absorption (α), thermal diffusivity (D) and perfusion (w, d ), using the analysis method described in the article “Non-invasive determination of tissue thermal parameters from high intensity focused ultrasound treatment monitored by volumetric MRI thermometry” by I. Dragonu et al, NMR Biomed. 2009; 22: 843–851.

[0061] For example, these test shots can be performed under rapid and volume thermometry, with 10 C1-C10 sections per second. A determined light power is applied to the region of interest R1 via the first emitting head F1 for 30 seconds, the same power level is then applied to the region of interest R2 for 30 seconds via the second emitting head F2, then the same power level is applied to the region of interest R3 for 30 seconds via the third emitting head F3 with a time long enough to allow the biological tissue to return to its initial temperature between each laser shot.

[0062] With reference to the, different types of emitting heads for optical fibers can be provided. Thus, an optical fiber can be provided at its end with an emitting head consisting of an omnidirectional optical diffuser Fa. It is also possible to provide an optical fiber whose emitting head Fb emits the laser beam in the axis of the optical fiber. In another configuration, the emitting head Fc is made up of two radial emitters, or else provided with a directional emitter Fd emitting the light in a determined angular sector. These examples of emitting heads are not limiting and any other configuration of the emitting head remains compatible with the regulation method according to the invention.

[0063] With reference to Figures 1 and 4, the control unit 6 receives the power or emission duration commands at the output of the automatic regulation system 1 which comprises a thermometry module 2 receiving the imaging signals from the MRI equipment 20 to process them and deliver temperature images Tn (x,y,z) which are displayed on a display screen 23 which can be consulted in real time by a practitioner during the deposition of thermal energy and which are entered into an automatic regulation module 3.

[0064] The automatic regulation module 3 implements a planning module 30 which gathers the treatment planning data which are entered by the practitioner and / or are previously stored in the planning module, and an automatic regulation algorithm 31 which processes the planning data and the measurement data from the MRI imaging system and delivers 32 control signals 33 of the laser emitters in real time.

[0065] The automatic regulation algorithm 31 comprises: a module 34 for determining the temperature difference in each region of interest R i from planning data,A module 35 to solve the system of equations Q allowing to link the contributions of the spatial distributions of thermal energy S j to temperature increases x i in each region of interest Ri,A module 36 to determine the energy instructions E j (n) to be applied to each of the sources of optical fibers, from the resolution of the system of equations Q(R i , x i ,S j ).

[0066] Lamontre shows two examples of MRI-guided automatic temperature regulation with multiple laser emitter heads performed on a pig leg in vivo, in experiment A corresponding to an identical target heating profile at +30°C above the initial temperature T c1,2,3applied to three regions of interest R1, R2 and R3; and in an experiment B corresponding to two different heating profiles T c1,2 and T c3, either a single plateau at +15°C for 250 s for one emitting head and two successive plateaus at +10°C and +15°C for 100 s each for the second emitting head.

[0067] Maximum temperature increases T max1 , T max2 , T max3 measured in each region of interest R1, R2, R3 are shown in graph (i) and the power used for each transmitter is displayed in graph (ii) for each region of interest R1, R2 and R3.

[0068] The average difference (±σ) between the target and experimental temperatures is [0.24±1.87 °C, 0.5±1.8 °C, 0.25±1.36 °C] for the regions of interest R1, R2, R3 in experiment A and [0.24±1.18 °C, -0.02±1.22 °C] for the regions of interest R1, R2 in experiment B, respectively. These performances illustrate the technical advantage of the invention combining PID controller and heat equation.

[0069] Shows the temperature images (ΔT in °C) and thermal dose (dose equivalent to constant heating at 43°C for 240 minutes, noted CEM 43 ) for a set of 10 temperature MRI slices, for experiments A and B presented in the, at the end of regulation, i.e. at times t=430 s (A) and t=305 s (B) of graphs (i) of the. The regions of interest R1, R2 and R3 used for automatic regulation are represented on slice number 5 and extend over the 10 slices.

[0070] With reference to Figures 7 and 8, the automatic temperature regulation method allows the practitioner to safely intervene on a prostate tumor 41 40 for example, using two emitting heads F1 and F2. Once the emitting heads are inserted, the practitioner can for example define temperature time profiles TF1 and TF2 for each emitting head, as illustrated in Figure 8I with a target temperature set at 90°C for F1 and 80° for F2 with different durations and starting times. He can also define the regions of interest (43 and 44) ​​around each of the fibers F1 and F2, the two regions of interest in which the tissue temperature control will be carried out. He can also define a limit temperature T lim(set at 50°C in this example) not to be exceeded in the contact zone 45 between the rectum 42 and the outer wall of the prostate 40 and located near the emitting head F2. Automatic regulation of the laser energy associated with thermometry on a volume encompassing the tumor and the rectum can therefore make it possible to force the temperature Ia and Ib to follow the predefined profiles TF1 and TF2 in the pathological biological tissue around the emitting heads F1 and F2 in the preselected regions 43 and 44, while actively monitoring the temperature near the rectum (45 on, temperature curve noted T45 on) using a display of the evolution of the temperature over time. If the latter does not exceed the predefined limit temperature, as illustrated in Figure 8II, the regulation is continued normally.On the other hand, if the temperature T45 reaches the limit value Tlim, as illustrated in Figures 8III and 8IV by the black arrow, the information is immediately accessible to the practitioner to interrupt (III) or continue (Figure 8IV) the treatment. This choice of continuation or interruption can also be predefined by the practitioner before the treatment and be integrated into the algorithm for regulating the deposited energy. In the case of an interruption (Figure 8III), the power resulting from the PID sent to the emitting head F2 will be set to 0 regardless of the value resulting from the calculation when Tlim is reached, while that on the emitting head F1 will be maintained. This results in a decrease in the temperature Ib of the biological tissue near the emitting head F2 and T45, while the temperature is correctly regulated Ia around the emitting head F1.In the case of continued treatment, (Figure 8IV), temperature control is maintained on the emitting heads F1 and F2 simultaneously, and the temperature T45 remains above the limit Tlim. The methodology presented here in an example setting of prostate tumor treatment can be applied to any situation in which biological tissue to be preserved is located near an area to be treated in which one or more emitting heads are inserted.

[0071] We will now describe, with reference to Figures 1 and 2, a practical example of implementation of the automatic temperature control method according to the invention. The real-time MRI thermometry equipment S, configured in a pipeline, is designed to repeatedly acquire a plurality of image slices whose phase varies with the temperature, using a rapid 2D (or volume) multi-slice acquisition sequence (collection of all the slices / volume within a time of the order of a second). This can be achieved for example using a single-shot echo planar acquisition sequence [3], allowing 10 slices to be obtained every second for 300 s on a clinical MRI operating at 1.5 T with the following parameters: TE=21 ms, FOV=200x200 mm², thickness of 3 mm (voxel of 1.56x1.56x3 mm3), flip angle = 50°, acceleration by parallel imaging = 2, bandwidth / pixel=1446 Hz.In this example, the volume covered by thermometry is 20 x 20 x 3 cm. The volume covered can be increased if necessary by increasing the number of sections (e.g. 20 sections to cover 6 cm in section 3). ème dimension) but with a refresh period increased to 2 seconds.

[0072] Thermometry and thermal dose images were reconstructed in real time using an image reconstruction software tool such as Gadgetron, with reference to the publication by MS Hansen and TS Sørensen, “Gadgetron: An open source framework for medical image reconstruction: Gadgetron,” Magn. Reson. Med., vol. 69, no. 6, pp. 1768‑1776, June 2013.

[0073] The thermotherapy set S comprises, by way of non-limiting example, three 400 μm optical fibers terminated by an emitting head equipped with a radial glass diffuser which have been inserted into an in vivo pig thigh muscle in a triangular configuration, with a spacing of approximately 2 cm between each emitting head of the optical fibers. Each optical fiber is connected to a programmable laser unit and powered by an independent laser emitter (976 nm wavelength laser diode, maximum output power on each channel of 18 W). This laser unit is interfaced with the image reconstruction unit, for example the aforementioned Gadgetron, to dynamically update the power of each laser emitter with each new MRI temperature measurement.

[0074] The temperature control algorithm was implemented in the Gadgetron to simultaneously control the temperature evolution within the sample in the regions of interest (ROI) R i (with i=[1, M]; here 3, noted R1,R2,R3) by automatically adjusting the power P j of each laser emitter with j=[1, N], N being the number of laser emitters (3 here). In this example the emission duration of all laser emitters is identical and is equal to the update duration of the 10 temperature MRI slices (here 1 second).

[0075] The input parameters of the automatic temperature regulation algorithm are (1) the temperature-time profiles associated with (2) each region of interest (here a rectangular region of 3x3 voxels propagated over all 10 slices, i.e. 3x3x10 voxels) centered on the hottest voxel around each emitter head as well as (3) the absorption, thermal diffusivity, perfusion of the sample and (4) the characterization of the heating functions of each emitter head.

[0076] Before starting the automatic temperature control, a non-destructive test shot is performed. For this, a constant laser power of 6 W in the experimental setup described in is applied for 30 seconds to each emitter sequentially, with a cooling period of 50 seconds. The hottest voxel in the temperature image associated with each emitter head is automatically detected and a 3x3 pixel region of interest is centered on this voxel and then propagated to all slices. This region of interest serves as input data for the temperature control algorithm. Curve fitting of the resulting temperature data with the biological heat transfer equation is performed to estimate the absorption coefficient (a), thermal diffusivity (D), perfusion (ω b ) and the characteristic of the heating function of each emitting head S i .

[0077] The regulation algorithm uses the following input data: regions of interest R i ( ) on the temperature images a heating function describing the 3D heat deposition of each emitting head “j”, noted S j ( )temperature setpoints over time for each region of interest R i , noted Tc i (t) an absorption coefficient (a), thermal diffusivity (D) and perfusion (w b ) for the biological tissue of each region of interest R i

[0078] The PID control algorithm works as follows:

[0079] the temperature measured by MRI at time “n” in each region of interest R i is compared to the temperature setpoint to follow in order to determine the energy to be deposited between the last measurement “n” and the following measurement

[0080] on each transmitter head “j”;

[0081] To ensure the convergence of the experimental temperature towards the target value and therefore result in a difference between tending towards 0, the controller integrates a Proportional-Integral-Derivative (PID) type algorithm which sums in a weighted manner this temperature difference (proportional term), the instantaneous variation of the temperature difference (derivative term) and the history of their differences (integral term), as follows:

[0082] The parameter q ensures a stable convergence towards 0 of the difference between the target temperature and the measured temperature in each region of interest “R i ". Its value must be adjusted so that the response time of the regulator is in line with the acquisition rate of the MRI images.

[0083] Using the heat transfer equation, it is possible to introduce into the PID controller the thermal parameters (a, D, w b ) of the biological tissue and the 3D characteristics of each emitting head S j used. In fact, the heat equation is given by the following equation:

[0084] with

[0085] D: thermal diffusivity [mm.s-1]

[0086] w b : perfusion [mg.cm-3 .sec-1]

[0087] a: absorption [°CJ-1]

[0088] where P j (n) is the power applied to the emitting head “j” whose spatial heating is characterized by the function S j .

[0089] To keep the same calculation time regardless of the number of R Regions iof interest in which temperature control is desired, this equation is solved in the spatial Fourier domain, as previously proposed in the publication by B. Quesson, F. Vimeux, R. Salomir, JA de Zwart, and CTW Moonen, “Automatic control of hyperthermic therapy based on real-time Fourier analysis of MR temperature maps,” Magn. Reson. Med., vol. 47, no. 6, pp. 1065-1072, June 2002. This in fact allows the term containing the temperature Laplacian to be linearized in the previous equation, since

[0090] By replacing

[0091] by its expression in the equation of the Proportional-Integral-Derivative (PID) controller, we arrive at:

[0092] This allows us to calculate, firstly, the temperature difference to compensate in the region of interest R i so that the temperature of the region R i follow the temperature setting :

[0093] From

[0094] we then calculate the power

[0095] to be applied to each transmitter “j” during the interval

[0096] by solving the following system of equations Q, knowing and the :

[0097] The product of this power by the laser emission time Δt (here identical to the delay between two successive acquisitions of temperature images) gives the energy to be deposited

[0098] This energy can be deposited by adjusting the power P jor the emission duration applied (which can be shorter than the time between two MRI temperature map acquisitions) on each emitting head. Ideally, the number of regions of interest is identical to the number of sources (N=M). In the case where N is different from M, the system is either overdetermined or underdetermined. If the system is underdetermined, it is appropriate to add additional conditions for example.

[0099] Of course, the present invention is not limited to the examples which have just been described and many other variants can be envisaged without departing from the scope of the invitation. Thus, the number of optical fibers and emitting heads implemented in an MRI-guided laser thermotherapy equipment according to the invention is not limited to three.

Claims

System (1) for regulating the temperature in a plurality of regions of interest (R1, R2, R3; R i ) of biological tissue, in each of which is inserted the emitting head of an optical fiber among a plurality of heads emitting laser beams of predetermined wavelengths and adjustable power or emission durations, produced by a multi-emitter laser source (4) within MRI-guided thermotherapy equipment (S), this system (1) comprising: means (3) for processing images of each of said regions of interest (R1, R2, R3; R i ), said images being delivered by magnetic resonance imaging (MRI) equipment (20), so as to deliver temperature images T n (x,y,z) of one or more of said regions of interest (R1,R2,R3;R i), comprising means (31) for processing said temperature images in real time, taking into account a set of planning parameters (30), so as to deliver commands (33) for adjusting the power and / or the duration of application of all or part of said laser beams applied to one or more of said one or more regions of interest (R1, R2, R3; R i ), and means (6) for applying said power adjustment commands or application duration adjustment commands to the multi-emitter laser device (33), characterized in that the real-time processing means (31) of the temperature images comprise a controller implementing a regulation algorithm (31) of the Proportional-Integral-Derivative (PID) type integrating the resolution of the heat equation using a fast Fourier transformation (FFT), this regulation algorithm being arranged to deliver for each laser beam "j" after the calculation of the "x i » at iteration “n”, an energy setpoint E j (n) of the type: with:n representing time, j representing each laser emitter,P j representing the laser power delivered by the laser transmitter “j” during the interval ,Q representing a system of equations allowing to link the contributions of the spatial distributions of thermal energy S j to temperature increasesx i in each region of interest R i R i representing a region of interest to be controlled in temperature,x i representing the evolution of the temperature required in each region R i between time "n" and time to follow a set temperature S j representing the spatial distribution of thermal energy delivered in the biological tissue by the emitting head F j . Regulation system according to the preceding claim, characterized in that the regulation algorithm uses the following input data: regions of interest R i ( ) on the temperature images, a heating function describing the 3D heat deposition of each emitting head “j”, noted S j ( )temperature setpoints over time for each region of interest R i , noted Tc i (t) an absorption coefficient (a), thermal diffusivity (D) and perfusion (w b ) for the biological tissue of each region of interest R i. Control system according to any one of the preceding claims, characterized in that the set of planning parameters can advantageously comprise a temperature time setpoint curve (T ci(n)) for a given region of interest, as well as one or more parameters of the biological tissue to be treated and the heating characteristics S j of the emitting head of each optical fiber F j . Control system according to any one of the preceding claims, characterized in that the set of equations Q is expressed in the following form: Regulation system (1) according to any one of the preceding claims, characterized in that the means for processing the temperature images are integrated into the magnetic resonance imaging (MRI) equipment. Regulation system according to any one of claims 1 to 4, characterized in that the means for processing the temperature images are integrated into an image reconstruction unit downstream of the magnetic resonance imaging (MRI) equipment. MRI-guided laser thermotherapy equipment (S), comprising means (7, 8, 9) for emitting a plurality of laser beams of determined wavelengths and adjustable emission powers or durations and means (F1, F2, F3; F j ) to apply said laser beams respectively in a plurality of regions of interest (R1,R2,R3;R i ) of a biological tissue, and magnetic resonance medical imaging equipment (20) arranged to deliver and display temperature images T n (x,y,z) of one or more of said one or more regions of interest (R1,R2,R3;R i ), characterized in that it further comprises a system (1) for regulating the temperature in said one or more regions of interest (R1, R2, R3; R i ) according to any one of the preceding claims. MRI-guided laser thermotherapy equipment according to the preceding claim, characterized in that the means for applying the laser beams comprise a plurality of optical fibers powered by laser emitters and having respective emitting heads arranged to be inserted into a region of interest of a biological tissue and to emit therein laser light of determined wavelength and adjustable power or emission duration. MRI-guided laser thermotherapy equipment according to the preceding claim, characterized in that at least one of the optical fibers comprises an emitting head (Fa) arranged to diffuse the laser light within the biological tissue in which said at least one emitting head (Fa) is inserted. MRI-guided laser thermotherapy equipment according to one of the two preceding claims, characterized in that at least one of the optical fibers comprises an emitting head (Fb) arranged to axially emit the laser light within the biological tissue in which said at least one emitting head (Fb) is inserted. MRI-guided laser thermotherapy equipment according to one of the three preceding claims, characterized in that at least one of the optical fibers comprises an emitting head (Fc) arranged to radially emit the laser light within the biological tissue in which said at least one emitting head (Fc) is inserted. MRI-guided laser thermotherapy equipment according to one of the four preceding claims, characterized in that at least one of the optical fibers comprises an emitting head (Fd) arranged to emit laser light at a predetermined angle relative to the axis of said optical fiber within the biological tissue in which said at least one emitting head is inserted. MRI-guided laser thermotherapy equipment according to one of the five preceding claims, characterized in that the means for applying the laser beams further comprise one or more emitting heads having a source function adapted to be used as input data for the temperature regulation system according to claim 8.

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