Peroperative sensing head adapted to be coupled to an ablation tool

ES 2 364 348 T3

DESCRIPTION

Perioperative detection head suitable to be attached to an excision tool.

The present invention relates to aiding in the surgical treatment of biological tissues, in particular cancerous tumors.

Support for the surgical treatment of cancer is currently based on several techniques.

According to a first type of techniques called "preoperative imaging techniques", the surgeon makes, before the operation, an image of the tissue area to be treated in order to locate as well as possible the tissue parts to be treated. they will be removed.

Pre-location of the tumor, with the help of X-ray tomography or MRI, allows, for example, to obtain the precise anatomical topography of the tumor volume and thus to choose the best adapted surgical accesses. Coupled with mechanical or optical stereotaxic guidance, the preoperative location allows even narrower access routes and therefore less traumatic, particularly in the case of deep injuries.

In neurosurgery, this technique can be completed by using a functional MRI imaging apparatus, which allows the precise identification of functional brain areas near the tumor before surgery. Based on this information, the surgeon can then optimize the extent of the area to be removed while minimizing the risks of postoperative morbidity.

Preoperative imaging techniques have allowed for more precise and less invasive surgical gestures.

However, these techniques have limits in terms of performance and ergonomics. In particular, these techniques are poorly adapted to operations that need to locate small tumors and their eventual metastatic dissemination.

Furthermore, the displacement of tissues throughout the surgical procedure (particularly in the brain) frequently renders the location of the lesions made before the operation obsolete.

According to a second type of technique, the surgeon performs tissue extractions during the operation and these extractions are analyzed extemporaneously, to guarantee the quality of the surgeon's surgical procedure.

These techniques, which are based on a precise pathological diagnosis of the extracted tissues, have the advantage of being reliable.

However, these techniques are very expensive.

In addition, the time required to obtain a diagnosis from extractions can sometimes significantly increase the duration of surgery.

Taking into account the drawbacks associated with preoperative imaging techniques and tissue extraction techniques, a third type of technique called “peroperative techniques” has emerged. These techniques use control tools that can function in the operating room and thus replace external imaging instruments helping the physician to define more precisely and in real time the margins of a tumor resection or biopsy.

Two families of peroperative techniques are currently being studied. The first family of techniques, called "anatomical perioperative techniques", is based on conventional anatomical imaging systems, such as optical endoscopy, ultrasound ultrasound, X-ray tomography or MRI systems. The second family of techniques, called “functional peroperative techniques”, is based on the detection of signals emitted by the tissues thanks to miniaturized systems. The signals are particles or radiation emitted by radioactive indicators or fluorescent molecules present in the tissues and specific to the tumor lesions sought.

According to the anatomical perioperative techniques, the surgeon uses to guide his gesture an apparatus for obtaining anatomical images of identical principle to those used in clinical diagnostic services but whose characteristics, in terms of volume and ergonomics, have been adapted to use in the operating room.

In addition to preoperative scans, low-field MRI and X-ray tomography are used primarily in the operating room to correct localization errors associated with tissue displacement during surgery and to guide biopsy procedures. Anatomical imaging systems allow, in fact, to renew in real time the images taken before the

ES 2 364 348 T3 intervention and therefore control in real time the distortion of the anatomical structures. The evaluation of perioperative MRI for glioma surgery has therefore shown that these techniques allow to improve the extent of tumor resection with respect to interventions in which only stereotaxic guidance based on preoperative images was used.

Ultrasound sonography is also used in the operating room to aid in the surgical treatment of tumors. This technique has the advantage of being much less cumbersome and costly to implement than low-field MRI or X-ray tomography. The main field of application of perioperative ultrasound ultrasound is the localization of non-palpable breast tumors and of liver tumors. More generally, this technique is particularly adapted to the precise localization of deep lesions.

According to functional perioperative techniques, the surgeon uses a miniaturized detection device that can detect radioactive indicators or light radiations specific to the histology or the physiological or metabolic behavior of the tumor lesions sought. As the function of an organ is frequently altered rather than its structure, these techniques are therefore in theory more sensitive and specific than anatomical perioperative techniques for differentiating healthy tissues from cancerous tissues.

Thus, it is possible to optimize the extent of tumor resection beyond the margins demonstrated by preoperative examinations and without having to wait for the results of extemporaneous tissue extraction analysis.

These techniques can also be used to improve the diagnostic accuracy of biopsies by guiding the surgeon to relevant tissue regions to determine the histological nature of the tumor.

In general, the miniaturization of the detection devices used also allows an easier use of the functional perioperative technique in the operating room since it only modifies the surgical protocol very little with respect to the heavier and more limiting anatomical perioperative techniques.

To effectively assist the surgeon in locating tumor tissues, the miniaturized detection device must present a millimeter spatial resolution compatible with the precision of the tumor excision gesture, which is of the order of a few cubic millimeters (mm³). Tumor excision is carried out for example by fragmentation of biological tissues by means of an ultrasound device.

In addition, the detection device must have a sensitivity adapted to the localization of small lesions (of the order of approximately 1 mm³) for acquisition times suitable for surgical practice (typically less than 10 seconds per measurement).

US 5,651,783 describes a fiber optic assembly for receiving a surgical instrument, such as an intraocular surgical instrument. The assembly comprises a sleeve in whose body a bundle of optical fibers extends, and connection means for connecting the bundle of optical fibers contained in the sleeve to an external optical cable connected to a light source. The fiber optic cuff allows the transmission of irrigation solution to the treatment site while transmitting light to the surgical site.

An object of the invention is to allow the surgeon to ablate with better precision and faster than with prior art devices.

This problem is solved within the framework of the present invention thanks to a peroperative probe to guide an exeresis tool, which comprises a detection head, said detection head comprising:

- at least one optical fiber suitable for receiving and guiding a signal emitted by a tissue zone towards an analysis equipment,

- fixing means to fix the head on the exeresis tool, so that the exeresis tool is suitable for extracting a part of tissues in the area of ​​tissues that emits the signal.

The detection head is suitable to be coupled to an excision tool so that the surgeon can perform tumor detection and ablation operations in a single gesture, without moving the probe.

In this way, a more precise localization of the tumor tissues is obtained since the correlation errors between the position of the tumor obtained from the signal measured by the probe and its real position in the operative wound are eliminated.

ES 2 364 348 T3

The possibility of simultaneously measuring the concentration of radioactive indicators and fluorescent molecules also makes it possible to benefit from the complementarity of the information using these two procedures and therefore to reinforce the specificity of the detection of tumors.

Advantageously, a probe according to the invention that measures a signal emitted by fluorescent molecules in an area of ​​tissues, in response to an excitation light signal, also measures a light signal originating from the reflection of the excitation light signal by tissues . The specificity is further increased.

Thanks to the detection head, which records the signals emitted by the tissues, the surgeon can observe the treated tissue area in real time.

Advantageously, the probe can be coupled to a neuronavigation system to allow the surgeon to visualize the position of the probe relative to the tumor and the different brain structures identified during the preoperative MRI.

Furthermore, the detection head can easily be replaced by a detection head of different characteristics in order to adapt the probe to the specific limitations of different surgical protocols as well as to the different signals emitted by the tissues.

The probe is particularly suitable for surgical excision of tumors of the central nervous system, including the brain and spinal cord. Indeed, the precision of the surgical treatment of this pathology determines, more than for any other cancer, the vital and functional prognosis of the patient.

The probe may have the features of claims 2 to 9.

The invention also relates to a transmission and analysis tool for a peroperative probe according to the previous definition, the tool being according to claim 10.

The tool may have the features of claims 11 to 23.

Other characteristics and advantages will become more apparent from the following description, which is purely illustrative and not limiting and which should be read with reference to the attached figures, in which:

figure 1 schematically represents a set for surgical treatment of biological tissues according to an embodiment of the invention,

figure 2 schematically represents in front view, a detection head of a peroperative probe according to an embodiment of the invention,

figure 3 schematically represents in a side view and in section, a detection head of a peroperative probe according to an embodiment of the invention,

figure 4 schematically represents in a side view and in section, a detection head of a peroperative probe according to a variant of the embodiment of figure 3,

Figures 5A and 5B schematically represent in side and sectional view, connection elements intended to allow a connection between optical fibers of the probe's detection head and transmission optical fibers towards analysis means.

In FIG. 1, the biological tissue surgical treatment set shown comprises an excision tool 1, a peroperative probe 2 and transmission and analysis means 3.

The excision tool 1 comprises a gripping part 11 and an excision part 12. The excision tool 1 is for example an ultrasound aspirator, in particular used throughout the surgical treatment of gliomas to excise tumor tissues. In the case of an ultrasound aspirator, the cleavage part 12 comprises a tube 1212 for ultrasound emission and aspiration of the sprayed tissues.

The peroperative probe 2 comprises a detection head 21 that forms a single-use part. The detection head 21 is in the form of a tip suitable to be inserted over the excision tool 1.

The detection head 21 comprises a body 211 of generally cylindrical shape, a bundle 212 of detection optical fibers extending inside the body 211 and a connecting element 219.

The transmission and analysis means 3 comprise a light source 30, a reusable transmission element 31 and an analysis equipment 32.

ES 2 364 348 T3

The light source 30 comprises a laser or lamp 301 and an excitation filter 302. The laser or lamp 301 is suitable for emitting light in the form of continuous radiation or light pulses having a controlled duration. The filter 302 is suitable for filtering the light generated by the laser or the lamp 301 to transmit an excitation signal containing photons having suitable wavelengths to excite fluorescent molecules contained in the tissues to be treated. The fluorescent molecules then emit a fluorescent light signal, the wavelength of which is different from the wavelength of the excitation signal. Fluorescence is in effect electromagnetic radiation, usually in the form of visible or infrared light, originating from emitting fluorescent molecules excited by a shorter wavelength excitation light signal. Fluorescent radiation abruptly ceases when excitation ceases.

The transmission element 31 comprises a body 311, a bundle 312 of transmission optical fibers extending into the body 311 and a connection element 319. The connection element 319 is suitable to cooperate with the connection element 219 to connecting each beam sensing optical fiber 212 of sensing head 21 to a beam transmitting optical fiber 312 of transmitting element 31.

As illustrated in Figures 1 to 3, the detection head 21 comprises a body 211 and a bundle 212 of detection optical fibers that extend inside the body 211, in a longitudinal direction thereof.

The body 211 has a general tubular shape. The body 211 comprises a cylindrical wall 2111 made of metal, for example stainless steel, or any other material compatible with a surgical procedure, and a central channel 2112. The wall 2111 encloses the bundle 212 of detection optical fibers. The optical fibers of the bundle 212 are distributed around the central channel 2112 and extend substantially parallel to the central channel 2112.

The optical fiber bundle 212 comprises a plurality of light radiation detection fibers 2121, an excitation fiber 2122, a plurality of radioactive indicator detection fibers 2123, and a plurality of control fibers 2124.

The fibers 2121, 2122 and 2123 extend between an end surface 2113 of the body 211 and the connecting element 219. More precisely, the ends of the fibers 2121, 2122 and 2123 project to the surface 2113.

The light radiation detection fibers 2121 are made up of light fibers. These fibers 2121 are suitable for receiving and guiding a light signal emitted by biological tissues.

The excitation fiber 2122 is also made up of a clear fiber. This fiber 2122 is suitable for guiding an excitation light signal generated by source 30 in the direction of biological tissues to excite fluorescent molecules contained in those tissues.

The radioactive indicator detection fibers 2123 comprise a scintillating end portion 2125 and a clear main portion 2126, the scintillating end portion 2125 being fused for example by heating to the clear main portion 2126. The scintillating end portion 2125 is suitable for interacting with particles radioactive β (β particles⁺ or particles (β^-) emitted by tissues previously marked by radioactive indicators and to convert them into a light signal. The main part 2126 is suitable to guide the light signal emitted by the end part 2125.

The sparkling portion 2125 typically has a length of about 1mm and the clear portion 2126 typically has a length of about 10cm. The sparkling 2125 and clear 2126 portions typically have a diameter of the order of 1.5 mm.

The control fibers 2124 are identical to the radioactive indicator detection fibers 2123, except that the control fibers 2124 are blinded to the β particles. More precisely, the control fibers 2124 extend below the end surface 2113 of the body 211, so that the end of the control fibers 2124 is obstructed by a metal layer of thickness approximately equal to 400 µm.

Radioactive indicator detection fibers 2123 and control fibers 2124 are sensitive to γ-radiation of 511 electron volts (eV) emitted by tissues after β-particle annihilation.⁺. These γ radiations represent a background noise for the detection of β particles⁺. The control fibers 2124 make it possible to quantify the γ radiation in order to subtract it from the signals measured by the fibers 2123 and thus obtain a signal due only to the β particles⁺.

To allow a more precise quantification of the γ radiation, the plastic scintillator can be replaced by an inorganic scintillator such as, for example, cerium-doped lutetium oxorthosilicate (LSO), which has a higher density and therefore a better detection efficiency for the γ radiation.

ES 2 364 348 T3

The wall 2111 in which the optical fibers 2121, 2122, 2123 and 2124 of the detection bundle 212 are embedded constitutes a protection for the fibers. This shielding isolates the fibers from ambient light and stray β particles that could reach the scintillating parts 2125 from the sides or rear of the fibers 2123.

Figure 4 illustrates a variant of the sensing head 21. In this variant, the fibers 2121 and 2122 of the sensing head do not extend to the end surface 2113 of the body 211. More precisely, the fibers 2121 and 2122 extend below surface 2113. The detection head 21 comprises an optic 2127 associated with each fiber 2121 and 2122, which focuses the light from the tissues towards the fibers 2121 and which focuses the light from the fiber 2122 towards the tissues. Each optic 2127 comprises, for example, a microlens. Focusing the incident light makes it possible to increase the local light concentration and consequently the sensitivity of the treatment set. In addition, the collection of light from the tissues with the help of a microlens improves the spatial resolution of the treatment set.

Figures 5A and 5B schematically represent an example of connection elements 219 and 319 intended to allow a connection between the bundle 212 of detection optical fibers of the detection head 21 and the bundle 312 of transmission optical fibers of the element 31 of the transmission.

In Figure 5A the connecting elements 219 and 319 are detached from each other.

The connecting element 219 comprises a body 2191 in which the detection fibers 2121, 2122, 2123 and 2124 are embedded. Body 2191 comprises a flat connecting surface 2192. The ends of the fibers 2121, 2122, 2123, and 2124 project into the connecting surface 2192.

In the same way, the connection element 319 comprises a body 3191 in which the transmission fibers 3121, 3122, 3123 and 3124 are embedded. The body 3191 comprises a flat connection surface 3192. The ends of the fibers 3121, 3122, 3123, and 3124 project to the connecting surface 3192.

Body 2191 comprises connecting legs 2193 projecting from connecting surface 2192. The body 3191 comprises connection holes 3193 that extend from the connection surface 3192. Legs 2193 are suitable for inserting into holes 3193 to engage connecting elements 219 and 319. Furthermore, the legs 2193 and the holes 3193 are arranged so that when the legs 2193 are inserted into the holes 3193, the connection surface 2192 comes into contact with the connection surface 3192 and the ends of the fibers 2121, 2122, 2123 and 2124 respectively contact the ends of the fibers 3121, 3122, 3123 and 3124 to connect the fibers together.

The surgical treatment assembly may further comprise locking elements 419 for keeping the connection elements 219 and 319 engaged. Each locking element is U-shaped and comprises two branches 4191 and 4192. Each branch 4191 and 4192 respectively has a level of a free end a shoulder 4194 and 4195.

Each of the connecting elements 219 and 319 respectively comprises notches 2194 and 3195.

The locking elements 419 are suitable for tightening the connecting elements 219 and 319 when they are mutually coupled. To do this, the elements 219 and 319 are inserted between the branches 4191 and 4192 of the locking elements 419. The presence of the projections 4194 and 4195 causes the branches 4191 and 4192 to be separated by elastic deformation. The projections 4194 and 4195 are then suitable to be inserted into the notches 2194 and 3195 by elastic return of the branches 4191 and 4192.

In Figure 5B, the connecting elements 219 and 319 are mutually engaged and the locking elements 419 hold the connecting elements 219 and 319 engaged.

As seen in Figure 1, the single-use detection head 21 is suitable to be removably attached to the excision tool 1. For this, the excision part 12 of the tool 1 is suitable to be inserted into the sensing head 21. More precisely, the aspiration tube 1212 of the exeresis tool 1 is suitable to be inserted into the channel 2112 of the sensing head 21 such that the aspiration end of the aspiration tube 1212 protrudes into the end surface 2113 of the sensing head 21.

On the other hand, the connecting elements 219 and 319 are suitable to be mutually coupled to optically couple the sensing optical fiber bundle 212 to the transmission optical fiber bundle 312. The connection elements 219 and 319 are detachable connection elements, which allow easy manual connection and disconnection.

The single-use sensing head 21 can therefore easily be replaced by another head.

ES 2 364 348 T3

The transmission element 31 normally has a length of 2 meters to route the light signals from the detection head 21 towards the analysis equipment 32 located outside the surgical field.

When the connection elements 219 and 319 are coupled, the light radiation detection fibers 2121, the excitation fiber 2122, the radioactive indicator detection fibers 2123 and the control fibers 2124, of the beam 212 of the detection head 21 they are connected respectively to transmission fibers 3121, 3122, 3123 and 3124, of the bundle 312 of the transmission element 21.

The transmission fibers 3121 are connected to the light fibers 2121 of the detection head 21 and are suitable for guiding light radiation from tissues.

The transmission fiber 3122 is connected on the one hand to the source 30 and on the other hand to the excitation fiber 2122 to guide the excitation radiation emitted by the source 30 to the tissues to be treated.

The fibers 3123 and 3124 are suitable for guiding the light signals generated by the interaction of the β particles and the γ radiation emitted by the fabrics with the scintillating parts 2125 of the fibers 2123 and 2124.

The analysis equipment 32 comprises a first photodetection unit 321, a second photodetection unit 322, a first acquisition unit 323, a second acquisition unit 324, and a PC 325.

Fibers 3123 and 3124 of bundle 312 are connected to first photodetection unit 321.

The first photodetection unit 321 comprises a multi-anode photomultiplier 3211. The multi-anode photomultiplier 3211 comprises a plurality of pixels (typically 64 pixels), each pixel or group of pixels being coupled to a fiber 3123 or 3124 of beam 312. Each Multi-anode photomultiplier pixel is suitable for converting a light signal it receives into an electrical signal.

The first acquisition unit 323 comprises a resistor network 3231, a pre-amplification electronics 3232 and an amplification electronics 3233.

The resistor network 3231 is suitable for providing, according to the principle of load division, a position of the center of gravity and an intensity of the light signal coming from fibers 3123 and 3124. This information makes it possible to determine a number of fibers reached and the quantity of energy released by a β particle or γ radiation in the scintillating parts 2125 of the fibers 2123 and 2124.

The pre-amplification electronics 3232 and the amplification electronics 3233 are suitable for integrating and then amplifying the signals generated by the resistor network 3231. Unit 323 then transmits the analog signals to PC 325 for digitization and processing.

On the other hand, the fibers 3121 of the bundle 312 are connected to the second photodetection unit 322.

The second photodetection unit 322 comprises a fiber spectrophotometer 3221, an ultra-fast detector 3222, for example a detector provided by Hamamatsu Fotonics under the reference R3805U MCP PMT, and an avalanche photodiode or a 3223 multi-anode photomultiplier comprising a Integrated analysis electronics, for example a photodiode provided by the company id QUANTIQUE with the reference id100-20. The fiber spectrophotometer 3221 is suitable for detecting an intensity of a light signal that it receives as a function of a plurality of wavelengths that make up the light signal and for converting the intensity into an electrical signal. The ultra-fast 3222 detector is suitable for measuring a time of arrival of a light signal it receives and for converting the time of arrival into an electrical signal. The avalanche photodiode or multi-anode photomultiplier 3223 is suitable for converting a light signal it receives into a conventional electrical signal.

The second acquisition unit 324 comprises a first conversion electronics 3241 and a second routing electronics 3242.

The first conversion electronics 3241 is suitable for converting the analog signals generated by the fiber spectrophotometer 3221 into digital signals, to allow direct transfer to the PC 325 via a 3243 USB cable.

The second routing electronics 3242 is suitable for connecting several parallel signals generated by one or more ultra-fast detectors 3222 to a photon counting card with their step time.

The PC 325 comprises a digitizing and calculating unit 3251 and a display screen 3252. The digitizing and computing unit 3251 is suitable for receiving and processing the signals generated by the units

ES 2 364 348 T3

323 and 324. The digitizing and computing unit 3251 is also suitable for controlling the display screen 3252.

The use and operation of the surgical treatment set just described will now be described.

Before an operation, the surgeon selects a sensing head 21 suitable for the operative wound and for the type of tumor to be treated.

The surgeon fixes the detection head 21 on the excision tool 1 by inserting the aspiration tube 1212 into the channel 2112 of the detection head 21.

The surgeon then connects bundles 212 and 312 to each other via connection elements 219 and 319.

During the operation, the surgeon excises a major visible part of the tumor.

The surgeon then inserts the end of the probe 2 into the operative wound. More precisely, the surgeon positions the probe 2 such that the end surface 2113 of the sensing head 21 faces an area of ​​the tissues to be treated. The surgeon traverses the operative wound with the aid of the detection head 21 and places the detection head 21 in a plurality of successive positions. The surgeon acquires, for each position of the head 21, a mapping of the signals emitted from the area of ​​the tissues in front of the end surface 2113. For each position of the detection head 21, the acquisition duration of the mapping does not exceed a few seconds .

The peroperative probe first makes it possible to detect particle-emitting radioactive tumor markers.

When a β particle emitted by the tissue area is received by one of the fibers 2123, the scintillating part 2125 of the fiber 2123 generates a light signal (pulse) that is guided by the clear part 2126 of the detection fiber 2123.

The light signal is guided to the photodetection unit 321 by means of a transmission fiber 3123 of the transmission element 31. The light signal is received by a pixel of the photomultiplier 3211 that generates an electrical signal (electrical pulse) proportional to the signal intensity bright.

The electrical signal is processed by the acquisition unit 323, which provides, through the resistor network 3231, a number associated with the fiber 2123 reached by the β particle and an energy transferred to the scintillating part 2125. The acquisition unit 323 amplifies and digitizes the signals generated by the photodetection unit 321 and transmits the amplified signals to the digitizing and computing unit 3251.

On the other hand, the transmission fibers 3124 guide the light signal from the control fibers 2124 sensitive only to γ-radiation generated by the tissues.

Γ radiation from the annihilation of β particles⁺ in tissues they represent a background noise for the process of localization of tumor lesions in the operative wound. These signals may indeed come from regions, specific or non-specific, of the β-reporter binding.⁺, very far from the tissue area analyzed by the probe.

To differentiate γ signals from β signals⁺, the surgical treatment set has the following characteristics.

According to a first characteristic, the scintillating parts 2125 of the fibers 2123 are made of a plastic material, not very sensitive to high-energy γ radiation. Indeed, the plastic material has a low density (normally 1.05 g / cm³) and is made up of elements that have a low atomic number (maximum equal to 6 for carbon). The simulated γ efficiency of a scintillating plastic fiber 2 mm in diameter and 1 mm in length placed 0.1 mm from a point source of¹⁸F is therefore approximately 300 strokes per second per microCurie (cps / PCi) versus an efficiency β⁺ of 1.7 · 10⁴ cps / PCi in the same configuration.

In the case of treatment of a brain tumor, these radiations can nevertheless come from the whole brain. The contribution of the background noise γ to the signal β⁺ it can therefore become very important despite the low intrinsic sensitivity of the plastic material that constitutes the scintillating part.

According to a second characteristic, the digitization and calculation unit 3251 is suitable for selecting the signals it receives as a function of the energy of the particle that has interacted with the scintillating part. The theoretical study of the energy spectrum of γ radiation that has interacted with the scintillating part shows in

ES 2 364 348 T3 effect that 40% of the detected γ radiations generate an energy between 0 and 100 keV, while the energy distribution of the β particles⁺ it is between 0 and 500 keV.

The digitizing and computing unit 3251 is therefore suitable for selecting only those signals whose energy is greater than a threshold between 50 and 100 kiloelectronvolts (keV).

According to a third characteristic, each fiber 2123 for detecting radioactive indicators is associated with a control fiber 2124. The control fibers 2124 are sensitive to γ ​​radiation but are insensitive to β particles.⁺. The 3251 unit is suitable for subtracting from the count rate corresponding to the signals generated by a radioactive indicator detection fiber 2123, the count rate γ corresponding to the signals generated by the associated control fiber 2124, in order to obtain only a measurement of the signal β⁺.

It will be noted in this regard that several fibers 2123 for detecting radioactive indicators can be associated with the same control fiber 2124 to optimize the part of the detection surface 2113 sensitive to β particles.

The digitizing and calculating unit 3251 is suitable for comparing the count rate of the pulses corresponding to the concentration of the radioactive indicators measured at the level of the fibers 2123 of the detection head 21 with a reference count rate previously measured in a area of ​​the operative wound consisting only of healthy tissues.

When the difference between the measured count rate and the reference count rate is greater than a threshold (eg, a standard deviation greater than 3), the 3251 will identify the tissue area as tumor.

Digitizing and computing unit 3251 controls display 3252 so that the display will visually display a map of the tissue area indicating the number of β particles detected by each fiber 2123.

The surgeon can therefore visualize in real time on the screen 3252 an image of the treated tissue area that indicates the distribution of the concentration of the radioactive indicators at the level of the fibers 2123 of the detection head 21.

The peroperative probe also allows the detection of tumor tissues by fluorescent optical techniques.

Thus, the light fibers 2121 receive the fluorescent radiation emitted by fluorescent molecules present in the tissues after the molecules have been excited by an excitation light signal conducted by the fiber 2122 towards the tissues. The light signal containing the fluorescent light radiation is guided by the clear fibers 2121. The light signal is then guided through the beam transmission fibers 3121 from the beam 312 to the photodetection unit 322. For the analysis of the fluorescent signal, the light signal is processed by a filter 320 that cuts the wavelengths of the excitation radiation in order to select only the fluorescent radiation.

The fluorescent light signal is received on the one hand by the fiber spectrophotometer 3221 and on the other hand by the ultra-fast detector 3222. Fluorescent radiation can also be filtered and then received by the avalanche photodiode or photomultiplier 3223. The three devices 3221, 3222, and 3223 each generate an electrical signal.

The 3221 fiber spectrophotometer determines a spectrum of fluorescent radiation and generates an electrical signal that allows counting of the radiation, a measurement of the wavelength of the radiation, and a number that identifies the fiber that has guided the radiation.

The avalanche photodiode or multi-anode photomultiplier 3223 generates an electrical signal that is suitable for counting fluorescent radiation.

The ultrafast detector 3222 generates an electrical signal corresponding to the passage time of the fluorescence photons and a number that identifies the fiber that has guided this photon. These signals allow a measurement of the time of decay of the fluorescence radiation with respect to the moment of excitation of the tissues (that is, the moment of emission of a pulse from the light source 30).

The acquisition unit 324 digitizes the signals generated by the spectrophotometer 3221 and transmits the digitized signals to the digitization and calculation unit 3251. In addition, the unit 3242 performs a routing of the signals generated by the ultrafast detector (s) 3222 and transmits the signals to the dedicated digitizing card of the digitizing and computing unit 3251. Signals generated by detector 3223 are transferred directly to the count card in unit 3251.

ES 2 364 348 T3

The digitizing and calculating unit 3251 is suitable for comparing the counting rate of the radiation detected by the fibers 2121 with a reference counting rate, previously measured in an area of ​​the operative wound consisting only of healthy tissues. When the difference between these count rates is greater than a predetermined threshold (for example, the count rate is greater than 3 standard deviation from the baseline count rate), the 3251 will identify the tissue area as tumor. .

Furthermore, the digitizing and calculating unit 3251 is suitable for comparing a spectrum of the fluorescent radiation detected by the fibers 2121 with a reference spectrum previously measured in an area of ​​the operative wound consisting only of healthy tissues. The comparison is made for one or more wavelength ranges of the measured spectrum. For example, when the "red" contribution of the spectrum (wavelengths 600-700nm) is more than 100% greater than the reference spectrum, the 3251 unit will identify the tissue area as tumor.

In addition, digitizing and computing unit 3251 is suitable for calculating fluorescence decay times from unit 3242 signals and for comparing them with previously measured reference times in a tissue-only area of ​​the operative wound. healthy. When at least one of the measured decay times has a deviation greater than 50% from the reference time, the 3251 unit will identify the tissue area as tumor.

Lastly, the digitization and calculation unit 3251 is suitable for processing in combination the different information coming from the devices 3233, 3241, 3242 and 3223. The identification of a tumor tissue is therefore based on complementary information and leads to more detailed results. reliable than with an independent use of the different information.

In particular, for multiple measurements based on different independent parameters of the same tissue area indicating a tumor area without however exceeding the thresholds defined for a reference area, the 3251 unit will identify the area as tumor. In the opposite case, in which a significant measurement (standard deviation greater than 3) is not confirmed or if it is contradicted by other measurements, the 3251 will not propose the excision of the corresponding tissues.

Processing unit 3251 controls display 3252 so that the display displays a number of two-dimensional graphics each representing the tissue area. The first graph indicates the count rate of the β indicators at the level of each fiber 2123.

Unit 3251 may control display 3252 to display a second graph representing the intensity of fluorescent radiation as a function of the wavelength of the radiation. Previously, the surgeon will have chosen a wavelength interval and the screen 3251 will only visually present in this second graph the intensity of the fluorescent radiation at the level of the 2121 fibers whose wavelengths are between the lower limit and the upper limit of the interval chosen by the surgeon.

The unit 3251 also controls the screen 3252 so that the screen 3252 displays a third graph that represents the decay time of the radiations emitted by the fluorescent molecules detected at the level of the fibers 2121.

The surgeon can thus view in real time on screen 3252 various maps of spatial distributions of measured intensities and specific parameters of the treated tissue area.

Display 3252 can simultaneously display multiple measured cartographies and superimpose them on each other.

The screen 3252 may also display a table that compiles the results of the measurements made individually, proposing conclusions to the surgeon.

Based on the map (s) displayed on screen 3252, the surgeon may decide to remove the tissue area with the help of the excision tool 1.

It will be appreciated that the number and arrangement of the optical fibers in the sensing head 21 can be easily modified to accommodate the limitations of different surgical protocols.

The probe 2 can be made versatile by providing a range of interchangeable detection heads 21 that respond to different specifications (compactness, sensitivity, resolution).

Therefore it is possible to provide a detection head comprising only a clear fiber 2121 and an excitation fiber 2122 for the detection of fluorescent molecules present in tissues.

ES 2 364 348 T3

It is also possible to provide a detection head that only comprises a β-radioactive indicator detection fiber 2123 and a control fiber 2124. This type of detection heads is particularly suitable for surgical operations that require extreme compactness of the probe, such as excision operations with endoscope or biopsies.

At the reverse end, it is possible to provide a detection head comprising several concentric layers of detection fibers 2121 and 2123, which make it possible to map the spatial distribution of radioactive indicators and light radiation in a field of view of the order of 2 square centimeters (cm²). This type of detection head is suitable for surgical operations that require rapid exploration of the operative wound or for operations limited by significant non-specific fixation of radioactive indicators.

In contrast to a counting probe, the possibility of measuring a map of the area of ​​tissues to be treated in effect makes it possible to differentiate specific tumor signals from background noise and thus reinforce the ratio of signal to noise that can be degraded. greatly due to the heterogeneity of the fixation of the indicators in the tissues surrounding the lesion.

Between these two extreme configurations that have just been described, detection heads can also be provided that have intermediate fiber arrangements in terms of number and placement.

Advantageously, it is possible to collect and sum the information from each fiber into a single piece of information. The sum is then used as a single mono-pixel detector, in such a way that the probe has better sensitivity for faster identification of the areas to be treated.

The treatment set that has just been described allows the simultaneous measurement of the concentration of radioactive indicators and the distribution of the fluorescent molecules. This association makes it possible to benefit from the complementarity of the histological, metabolic and molecular information provided by these different measurements and therefore to reinforce the effectiveness of the perioperative detection of tumors.

The probe that has just been described has a reduced volume and manageability that allows access to narrow areas of the operative wound (cavities of the order of 3 to 5 cm for brain tumors).

In addition, the probe allows a precise and fast localization of the tissue areas to be extracted.

The coupling with the excision tool allows the surgeon to visualize in real time a map of the area of ​​tissues that are in the vicinity of the excision tool and therefore carry out an excision in a single gesture, after a location. more accurate and faster of tumor tissues.

Lastly, the probe allows more specific detection of tumors than with prior art techniques. Indeed, the combination of a detection of several types of indicators makes it possible to provide more precise and reliable information on the nature of the treated tissues.

A probe according to the invention which measures a signal emitted by fluorescent molecules in an area of ​​tissues, in response to an excitation light signal, also advantageously measures a light signal originating from the reflection of the excitation light signal by the tissues.

In the previous developments, a bundle of very small diameter optical microfibers can evidently replace each optical fiber described.