Automatic temperature control system and method for MRI-guided multi-emitter laser thermotherapy equipment

Abstract

Method for regulating the temperature in a plurality of regions of interest (R1, R2, R3) of a biological tissue (T) subjected to a plurality of laser beams of predetermined wavelengths and adjustable laser emission powers and / or durations from a multi-emitter laser device (4) within an MRI-guided thermotherapy equipment (S), comprising steps of generating and visualizing temperature images Tn(x, y, z) in said plurality of regions of interest (R1, R2, R3), by processing complex module and phase images from magnetic resonance imaging (MRI) equipment (20). This method further comprises real-time processing of the temperature images, taking into account a set of planning parameters, to deliver instructions for adjusting the power and / or the duration of energy emission of all or part of said laser beams applied to one or more of the regions of interest (R1, R2, R3). See Figure 1

Description

Title of the invention: System and method for automatic temperature control 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 MRl-Guided Laser-Induced ThermoTherapy with the acronym MR-LITT. STATE OF THE ART

[0003] Current laser devices used during MRI-guided LITT procedures may use one or more emitter heads to create coagulation necrosis of biological tissues, but do not offer possibilities for precise temperature control in 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 Chemov, 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 an end proximal 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 emit each 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 emission power and duration at the start of treatment and may result in insufficient or excessive heating in the targeted region.

[0012] The aim 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. Statement of the invention

[0013] This objective is achieved with a method for regulating the temperature in a plurality of regions of interest of a biological tissue subjected to a plurality of laser beams of predetermined wavelengths and adjustable emission powers or durations emitted from a multi-emitter laser device within MRI-guided thermotherapy equipment, comprising steps of generating and visualizing temperature images in said plurality of regions of interest, by processing complex module and phase images from magnetic resonance imaging (MRI) equipment.

[0014] This provides a multi-emitter laser device whose power or emission duration of each emitter is automatically adjusted during treatment for force the temperature of biological tissue measured by real-time MRI thermometry to follow a predefined profile.

[0015] This regulation method further comprises real-time processing of said temperature images, taking into account a set of planning parameters, to deliver instructions for adjusting the power or the emission duration of all or part of said laser emitters applied in one or more of said one or more regions of interest using emitting heads.

[0016] The set of planning parameters may advantageously comprise a temperature time setpoint curve (Tci(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 Sj of the emitting head of each optical fiber Fj.

[0017] The real-time processing of the temperature images preferably implements a Proportional-Integral-Derivative (PID) type regulation algorithm integrating the resolution of the heat equation after fast Fourier transformation (FFT) of the temperature images on the spatial coordinates.

[0018] The regulation algorithm can be arranged to, in a first step, calculate after each temperature image “n” for each region of interest R; the temperature difference x in each region between the instant “n” and the instant n+An

[0019] so that the temperature of each region follows the set temperature Tci(n+An)

[0020] associated with each region, of the type: ^(n-> n+An) = PID (TJRJ, Tci(n+An), a, D, <ot>)

[0021] with:

[0022] n representing the time, representing the duration in seconds between two temperature measurements by MRI thermometry,

[0023] Tn representing the temperature measured by MRI thermometry at iteration n,

[0024] R; representing a region of interest to be controlled in temperature,

[0025] Te; representing a temperature setpoint time curve defined for the region of interest R;,

[0026] a, D and wb representing thermal parameters of the targeted biological tissue (absorption, thermal diffusivity, perfusion),

[0027] The regulation algorithm can be arranged to, in a second step, deliver for each laser beam “j” after the calculation of the “ ” at iteration “n”, an energy setpoint Ej(n) of the type: Ej(n) = Pj x Atj = Q(R is x i( Sj)

[0028] with:

[0029] n representing time,

[0030] j representing each laser transmitter,

[0031] Pj representing the laser power delivered by the laser transmitter “j” during the interval At R' rcPæscntant a region of interest to be controlled in temperature,

[0032] Xi representing the evolution of the temperature necessary in each region R; between the instant “n” and the instant n+An

[0033] to follow the set temperature

[0034] Sj representing the spatial distribution of thermal energy delivered in the biological tissue by the emitting head Fj.

[0035] Q representing a system of equations making it possible to link the contributions of the spatial distributions of thermal energy Sj to the temperature increases Xi in each region of interest R;. This system of equations is constructed at each iteration “n” by knowing the relative contributions of each source Sj in each of the regions to be controlled R;, as well as the differences between the target temperatures to be reached in each region R; at the following iteration nl-An

[0036] and the temperature measurement obtained at iteration n. Its resolution makes it possible to determine the powers Pj to be applied to each source Sj between times “n” and n+An.

[0037] The expression for Q is as follows: ' Pi(n) • crSifRj 3------F Pj(n) • aSyfRj 4- + P^n) ■ aSjyfRi] = Xi(n) < Pi(n) ■ a$i[Rj + —I- Pj(n) ■ + P^(n) ■ aS^fRj - x,(n) < ^i(«) ■ + Py(n) ■ «^[Rm] + - + PN(n) ■ = xM(n)

[0038] Its resolution can be obtained by a matrix inversion technique or any other algorithm for solving a system of linear equations.

[0039] 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 Sj attached to one or more of the emitting heads Fj.

[0040] The energy Ej(n) can therefore be deposited by adjusting the power Pj or the emission duration Atj

[0041] of the transmitter “j”.

[0042] According to another aspect of the invention, there is provided a system for regulating the temperature in a plurality of regions of interest of a biological tissue, in each of which is inserted an optical fiber terminated by an emitting head chosen from a plurality of emitting heads and delivering a laser beam of predetermined wavelength and adjustable power or emission duration supplied by a multi-emitter laser device within MRI-guided thermotherapy equipment, this system implementing the temperature regulation method according to the invention and comprising means for processing images of each of said regions of interest, said images being delivered by magnetic resonance imaging (MRI) equipment, so as to deliver temperature images of one or more of said regions of interest repeatedly throughout the duration of the treatment.

[0043] The regulation system according to the invention further comprises (i) means for processing said temperature images in real time, taking into account a set of planning parameters, so as to determine commands for adjusting the energy of all or part of said laser beams applied to one or more of said one or more regions of interest, and (ii) means (6) for applying said energy adjustment commands to the multi-emitter laser device (33).

[0044] The means for real-time processing of temperature images can advantageously comprise a Proportional-Integral-Derivative controller, or a Proportional-Integral controller or even a Proportional controller.

[0045] In a particular embodiment, the means for processing the temperature images are integrated into the magnetic resonance imaging (MRI) equipment.

[0046] In another embodiment, the temperature image processing means are integrated into an image reconstruction unit downstream of the magnetic resonance imaging (MRI) equipment.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] This provides automatic temperature regulation in real time simultaneously in all previously defined regions of interest, during laser-induced thermotherapy guided by MRI / MRI.

[0057] Automatic volume regulation of the temperature of biological tissue 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.

[0058] 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 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.

[0059] 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.

[0060] 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 towards 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 a, D and wb and their possible changes during treatment. For example, perfusion goes as far as canceling itself out when coagulation necrosis is induced by sufficient heat deposition.

[0061] The proposed algorithm provides an accurate and rapid solution for controlling 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 a multi-emitter laser device can make it possible 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

[0062] [Fig.l] [Fig.l] schematically illustrates an MRI-guided laser thermotherapy system implementing a temperature regulation system according to the invention;

[0063] [Fig.2] [Fig.2] schematically illustrates MRI thermometry sections positioned on regions of interest associated with three optical fibers terminated by a transmitter head inserted into a biological tissue to be treated by MRI-guided laser thermotherapy;

[0064] [Fig.3] [Fig.3] schematically illustrates several examples of optical fiber emitting heads used in an MRI-guided laser thermotherapy system according to the invention;

[0065] [Fig.4] [Fig.4] is a block diagram of an exemplary embodiment of the automatic temperature regulation method according to the invention;

[0066] [Fig.5] [Fig.5] shows two examples of automatic in vivo temperature regulation of a pig muscle;

[0067] [Fig.6] [Fig.6] shows temperature and thermal dose images for a set of MRI slices as a function of time;

[0068] [Fig.7] [Fig.7] is a schematic 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

[0069] [Fig.8] [Fig.8] 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 [Fig.7], with a region to be preserved near the second emitting head (F2) whose limit temperature not to be exceeded is specified before the treatment, with different options for implementing the automatic temperature regulation method according to the invention. DETAILED DESCRIPTION

[0070] An MRI-guided laser thermotherapy set S comprises, with reference to [Fig.l], (i) a laser multi-emitter device intended to emit three laser beams via optical fibers 7, 8, 9 terminated by emitting 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 regulation system 1.

[0071] 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 terms of power or adjustable emission duration by a control unit 6.

[0072] 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.

[0073] As illustrated in [Fig. 2], once the emitting heads are positioned, the imaging equipment performs a plurality of Cl-CIO temperature MRI slices, 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 (e.g. 3x3 pixel dimensions) on each imaging slice corresponding to the maximum heating previously identified, this region of interest being centered on the pixel of maximum heating, - propagate each 2D region of interest over all temperature imaging slices, to obtain 3D regions of interest RI, R2, R3 used by the temperature feedback algorithm around each of the emitting heads F1, F2, F3 - estimate the thermal parameters of biological tissues around each emitting head: absorption (a), thermal diffusivity (D) and perfusion (wd), using the analysis method described in the article “Non-invasive determination of tissue thermal parameters from high intensity focused ultrasound treatment monitored by volumetry MRI thermometry” by I. Dragonu et al, NMR Biomed. 2009; 22: 843-851.

[0074] For example, these test shots can be carried out under rapid and volume thermometry, with 10 Cl-CIO sections per second. A determined light power is applied to the region of interest RI via the first emitting head Fl 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.

[0075] With reference to [Fig. 3], 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. An optical fiber can also be provided 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 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.

[0076] 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.

[0077] 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.

[0078] The automatic regulation algorithm 31 comprises: - a module 34 to determine the temperature difference in each region of interest R; from the planning data, - A module 35 to solve the system of equations Q allowing to link the contributions of the spatial distributions of thermal energy Sj to the temperature rises x; in each region of interest Ri, - A module 36 to determine the energy instructions Ej(n) to be applied to each of the optical fiber sources, from the resolution of the system of equations Q(R;, X;,Sj).

[0079] [Fig.5] shows two examples of automatic temperature regulation guided by MRI with several laser emitting heads carried out on a pig leg in vivo, in an experiment A corresponding to an identical target heating profile at +30°C above the initial temperature Tcl>2>3 applied to three regions of interest RI, R2 and R3; and in an experiment B corresponding to two different heating profiles Tcij2 and Tc3j, i.e. 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.

[0080] The maximum temperature increases Tmaxi, Tmax2, Tmax3 measured in each region of interest RI, R2, R3 are indicated in graph (i) and the power used for each transmitter is displayed in graph (ii) for each region of interest RI, R2 and R3.

[0081] The average difference (+0) 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 RI, R2, R3 in experiment A and [0.24+1.18 °C, -0.02+1.22 °C] for the regions of interest RI, R2 in experiment B, respectively. These performances illustrate the technical advantage of the invention combining PID controller and heat equation.

[0082] [Fig.6] shows the temperature (AT in °C) and thermal dose (dose equivalent to constant heating at 43°C for 240 minutes, noted CEM43) images for a set of 10 temperature MRI slices, for experiments A and B presented in [Fig.3], at the end of regulation, i.e. at times t=430 s (A) and t=305 s (B) of graphs (i) of [Fig.5]. The regions of interest RI, R2 and R3 used for automatic regulation are represented on slice number 5 and extend over the 10 slices.

[0083] 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 81 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. It can also define a limit temperature TUm (set at 50°C in this example) not to be exceeded in the contact zone 45 between the rectum 42 and the external wall of the prostate 40 and located near the emitting head F2.Automatic regulation of laser energy combined with thermometry on a volume encompassing the tumor and the rectum can therefore force the temperature Ia and Ib to follow the predefined profiles TF1 and TF2 in the pathological biological tissue around the emitting heads Fl and F2 in the preselected regions 43 and 44, while actively monitoring the temperature near the rectum (45 in [Fig.7], temperature curve noted T45 in [Fig.8]) using a display of the temperature evolution over time. If the latter does not exceed the predefined limit temperature, as illustrated in Figure 811, 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 ([Fig.5] 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 deposited energy regulation algorithm. 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 Fl 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 around the emitting head Fl. In the case of continuation of the treatment, (Figure 8IV), the temperature regulation is maintained on the emitting heads Fl 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 transmitter heads are inserted.

[0084] We will now describe, with reference to Figures 1 and 2, a practical example of implementation of the automatic temperature regulation 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 temperature, using a rapid 2D (or volumetric) multi-slice acquisition sequence (collection of the entire 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 cuts (e.g.: 20 cuts to cover 6 cm in the 3rd dimension) but with a refresh period increased to 2 seconds.

[0085] The 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 Sprensen, “Gadgetron: An open source framework for medical image reconstruction: Gadgetron,” Magn. Reson. Med., vol. 69, no. 6, pp. 1768-1776, June 2013.

[0086] The thermotherapy assembly S comprises, by way of non-limiting example, three 400 qm optical fibers terminated by an emitting head equipped with a radial glass diffuser which have been inserted into a pig thigh muscle in vivo 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 (laser diode with a wavelength of 976 nm, 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.

[0087] The temperature regulation algorithm was implemented in the Gadgetron to simultaneously control the temperature evolution within the sample in the regions of interest (ROI) R; (with i=[l, M]; here 3, denoted R1,R2,R3) by automatically adjusting the power Pj 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 the laser emitters is identical and is equal to the update duration of the 10 temperature MRI slices (here 1 second).

[0088] The input parameters of the automatic temperature control 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 emitting head as well as (3) the absorption, thermal diffusivity, perfusion of the sample and (4) the characterization of the heating functions of each emitting head.

[0089] 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 [Fig.5] 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 (cob) and heating function characteristic of each emitter head Si.

[0090] The regulation algorithm uses the following input data: - regions of interest R; (I [1, M]) on 'cs temperature images - a heating function describing the 3D heat deposition of each emitting head “j”, noted Sj(ye [1, n]) - temperature instructions over time for each region of interest R;, noted Tc;(t) - an absorption coefficient (a), thermal diffusivity (D) and perfusion (wb) for the biological tissue of each region of interest R;

[0091] The PID regulation algorithm works as follows:

[0092] the temperature T^n) measured by MRI at time “n” in each region of interest Ri is compared to the temperature setpoint Tei(il} to be followed in order to determine the energy to be deposited between the last measurement "n" and the following measurement n+An

[0093] on each emitting head “j”;

[0094] To ensure the convergence of the experimental temperature towards the target value and therefore result in a difference between T and T^in) 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: dTe;(rù 3T,(n)l g2 fn "É2—É2M \Z ft l / lv j T *Q

[0095] The parameter g ensures a stable convergence towards 0 of the difference between the target temperature Tci(n) and the temperature measured in each region of interest “R;”. Its value must be adjusted so that the response time of the regulator is in line with the acquisition rate of the MRI images.

[0096] Using the heat transfer equation, it is possible to introduce into the PID controller the thermal parameters (a, D, wb) of the biological tissue and the 3D characteristics of each emitting head Sj used. Indeed, the heat equation is given by the following equation: = D • V2 TtW - + Zj a Pj^.Sj [RJ

[0097] with

[0098] D: thermal diffusivity [mm.s-1]

[0099] wb: perfusion [mg.cm-3.sec-1]

[0100] a: absorption [°CJ-1]

[0101] where Pj(n) is the power applied to the emitting head “j” whose spatial heating is characterized by the function Sj.

[0102] To keep the computation time the same regardless of the number of Regions R; of interest in which temperature control is to be performed, 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 hyperthermie 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 makes it possible to linearize the term containing the temperature Laplacian in the previous equation, since FFT(DV 2 T(r, n)) = -Dk 2 T*(k, n)

[0103] By replacing 377 (n) dn

[0104] by its expression in the equation of the Proportional-Integral-Derivative (PID) controller, we arrive at: + TF'1 [B ■ k2^(n)l + - %a PjW) ' ^[R,]] + qf^tn) - T,(n)] + L (T) _ T^idt = 0

[0105] This makes it possible to calculate, in a first step, the temperature difference xi to be compensated in the region of interest R; so that the temperature of the region R; follows the temperature setpoint Tci; Xi dTci(n) , r , TF"1 ​​C ■ dn q2 fn +q[Tci(n) - ^(n)] + [Tci(x) - 4

[0106] From Xi(n)

[0107] we then calculate the power Pj(n)

[0108] to be applied to each transmitter “j” during the interval At

[0109] by solving the following system of equations Q, knowing a and the Sf. Pi(n) ■ aSifRj + + Pj(n) ■ + P^(n) • - Xi(n) PAn) - + - + Pj(n) ■ + ■■■ + PN(n) ■ = xi(p) P^i) ■ + - + Pj(n) • + - + PN(n) ■ aSw[RM] = xM(n)

[0110] The product of this power by the laser emission time At (here identical to the delay between two successive acquisitions of temperature images) gives the energy to be deposited Ej (n) Pj (n) x At

[0111] This energy can be deposited by adjusting the power Pj or the applied emission duration (which can be shorter than the delay 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.

[0112] 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 transmitting heads used implemented in an MRI-guided laser thermotherapy equipment according to the invention is not limited to three.< / ot>

Claims

Claims

1. Method for regulating the temperature in a plurality of regions of interest (R1,R2,R3;R;) of a biological tissue (T) subjected to a plurality of laser beams of predetermined wavelengths and adjustable emission powers or durations emitted from a multi-emitter laser device (4) and guided by optical fibers (7,8,9) terminated by emitting heads (F1,F2,F3;Fj) within an MRI-guided thermotherapy equipment (S), comprising steps (22,23) of generating and displaying temperature images Tn(x,y,z) in said one or more regions of interest (R1,R2,R3;Ri), by processing complex images in module and in phase (21) from magnetic resonance imaging (MRI) equipment (20), characterized in that it further comprises real-time processing (3) of said temperature images, taking into account a set of planning parameters (30), to deliver instructions (En) for adjusting the energy to be emitted by all or part of said laser beams applied in one or more of said one or more regions of interest (R1, R2, R3; R;), between two successive measurements of the temperature in all or part of said regions of interest (R1, R2, R3; RÛ.;

2. Regulation method according to the preceding claim, characterized in that the set of planning parameters (30) comprises a temperature time setpoint curve (Tci(n)) for one or more of the regions of interest (R1,R2,R3;R;).

3. Regulation method according to one of the preceding claims, characterized in that the set of planning parameters (30) comprises one or more parameters (a, D, wb) of the biological tissue being treated.

4. Regulation method according to the preceding claim, characterized in that the set of planning parameters (30) further comprises a spatial distribution (Sj) of thermal energy delivered in the biological tissue by the emitting head Fj.

5. Regulation method according to any one of the preceding claims, characterized in that the real-time processing of the temperature images (3) implements a regulation algorithm (31) of the Proportional-Integral-Derivative (PID) type integrating the solving the heat equation using a fast Fourier transform (FFT).

6. Regulation method according to the preceding claim, characterized in that the regulation algorithm is arranged to calculate after each temperature image "n" for each region of interest R; the evolution of the temperature xt necessary in each region between the instant "n" and the instant H t An So that the temperature of each region follows the setpoint temperature Tci(n+An) associated with each region, of the type: Xi(n-» n+An) - PID (Tn[Ri], Tci(n+An), a, D, ©b) with: n representing the time, representing the duration in seconds between two temperature measurements by MRI thermometry, Tn representing the temperature measured by MRI thermometry at iteration n, Ri representing a region of interest to be controlled in temperature, Te; representing a temperature setpoint time curve defined for the region of interest R;, a, D and wb representing thermal parameters of the targeted biological tissue (absorption, thermal diffusivity, perfusion).

7. Regulation method according to the preceding claim, characterized in that the regulation algorithm is arranged to deliver for each laser beam “j” after the calculation of the “Xi” at iteration “n”, an energy setpoint Ej(n) of the type: Ej(n) = Pj x Atj = Q(Ri, xj, Sj) with: n representing the time, j representing each laser emitter, Pj representing the laser power delivered by the laser emitter “j” during the interval Q representing a system of equations allowing to link the contributions of the spatial distributions of thermal energy Sj to the temperature increases Xi in each region of interest R; Ri representing a region of interest to be controlled in temperature, Xi representing the evolution of the temperature necessary in each region R; between the instant "n" and the instant n+An to follow the set temperature Tc}(n+An) Sj representing the spatial distribution of thermal energy delivered in the biological tissue by the emitting head Fj.

8. Regulation method according to any one of the preceding claims, characterized in that it further comprises a test firing step carried out to determine a spatial distribution of thermal energy of a source function attached to one or more of the emitting heads.

9. System (1) for regulating the temperature in a plurality of regions of interest (R1, R2, R3; R;) 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 (4) within an MRI-guided thermotherapy equipment (S), this system (1) implementing the temperature regulation method according to any one of the preceding claims and comprising means (3) for processing images of each of said regions of interest (R1, R2, R3; R;), said images being delivered by magnetic resonance imaging (MRI) equipment (20), so as to deliver temperature images Tn(x, y, z) of one or more of said regions of interest (R1, R2, R3; R;) characterized in that it further comprises (i) 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;Ri), and (ii) means (6) for applying said power adjustment or application duration adjustment commands to the multi-emitter laser device (33).

10. Regulation system (1) according to the preceding claim, characterized in that the real-time processing means (31) of the temperature images comprise a Proportional-Integral-Derivative controller.

11. Regulation system (1) according to one of the two preceding claims, characterized in that the means for processing the temperature images are integrated into the magnetic resonance imaging (MRI) equipment.

12. Regulation system according to one of claims 9 or 10, 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.

13. 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; Fj) for applying said laser beams respectively in a plurality of regions of interest (R1, R2, R3; R;) of a biological tissue, and magnetic resonance medical imaging equipment (20) arranged to deliver and display temperature images Tn(x, y, z) of one or more of said one or more regions of interest (R1, R2, R3; R;), 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;) according to one of the four preceding claims.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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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