Abstract:
The percutaneous probe, made in MRI-compatible materials, comprises: a body percutaneously inserted into the tissue of a patient&#39;s body organ ( 8 ) having a region ( 10 ) to be analyzed, treated and monitored during a single medical procedure; at least one information collection sensing device ( 30,33,34 ); treatment application transducers ( 30 ) 360° disposed to emit focused or defocused therapeutic ultra-sound waves. The computerized system comprises a parametrizable command device ( 50 ) adapted to simulate then command a generation of the therapeutic ultra-sound waves, and to monitor the treatment by thermal MRI images.

Description:
FIELD OF THE INVENTION 
       [0001]    The instant invention relates to medical systems comprising percutaneous probes, and to uses of such medical systems. 
       BACKGROUND OF THE INVENTION 
       [0002]    Low intensity ultrasounds are widely used in medicine for diagnostic procedures, i.e. echography. For 10 years, high intensity ultra-sounds have shown to be an efficient means to induce tissue necrosis by hyperthermia for treatment procedures. Various therapeutic probes have been designed for minimally invasive therapeutic procedures and can be classified in two groups: external probes and internal probes. 
         [0003]    External probes are designed to mimic the shape of the surface of the patient&#39;s body. Ultrasound transmitters are displayed in a concentric fashion to optimise the ultrasound waves focalization. 
         [0004]    Internal/interstitial probes are inserted inside the body of the patient. There are three main categories: endo-cavity, endovascular or percutaneous probes. 
         [0005]    A. Endocavity Probes 
         [0006]    Endocavity probes are designed to be introduced in natural body holes such as the rectum, the vagina or the oesophagus. For example, US 2007/239,011 describes a medical probe for the delivery of high intensity focused ultra-sound (HIFU) energy to a patient&#39;s organ. Such a probe comprises a plane-shaped probe body inserted through a natural cavity of a patient, and a plurality of leaves to be applied to the surface of the organ, to deliver ultra-sound energy to the inside of the organ. 
         [0007]    B. Endovascular Probes 
         [0008]    Endovascular flexible probes are in development to treat cardiac atrial fibrillation or venous insufficiency. 
         [0009]    C. Percutaneous Interstitial Probes 
         [0010]    Percutaneous interstitial probes have initially received poor interest since they require a tissue penetration whereas previous probes don&#39;t penetrate the tissue. Nevertheless such percutaneous interstitial probes have been proposed for treating deep-seated tumours that cannot be reached with extra-corporeal, endocavity or endovascular high-intensity focused ultrasound probe. The ultrasound source is brought as close as possible to the target in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. Most-described ultrasound percutaneous probes are sideview emission probes whose active element is water-cooled and operates at a rather high frequency (above 3 MHz) in order to promote heating. Most described ultrasound percutaneous probes are not MRI compatible so that treatment monitoring is somewhat hazardous. 
         [0011]    For clinicians, ultrasounds are a promising technology. To extend the applicability of ultra-sound therapy to a broad variety of medical treatments, there is a need to solve the following inconveniences: 
         [0012]    In particular, external probes, although non intrusive, have shown consistent inconvenient: ultrasound attenuation, phase aberration and ultrasound defocalization by tissue structure (bone, tissue interfaces . . . ), targeting limits do to the constant body movement (respiratory, diaphragm . . . ), long treatment duration, unknown consequences on crossed normal tissue by the ultrasounds pathway, complexity of the probes with nowadays hundreds of ultrasound transducers, complexity to make the system MRI compatible and MRI adaptable. 
         [0013]    In particular, sideview interstitial/internal probes require clinician manipulation of the probe during treatment such as a 360° rotation or a longitudinal translation to treat the whole lesion leading to a lack of precision and reproducibility. 
         [0014]    In particular for all existing probes, none can perform histological characterisation or tissue biopsy, meaning that a biopsy procedure is necessary days before treatment. For all existing probes, none can perform a tissue resection after the thermal treatment. Indeed, hyperthermia treatment of a tumour will gender a serious tumour volume increase (mass effect) as shown in a previous clinical trial (Carpentier &amp; al., “Real-time Magnetic Resonance-Guided Laser Thermal Therapy of Metastatic Brain Tumors”, Neurosurgery, 63 ONS Suppl 1:21-29, 2008). Such volume increase is most of the time incompatible with preservation of the normal surrounding tissue and can limit the development of such minimally invasive ultrasound therapy systems. 
       SUMMARY OF THE INVENTION 
       [0015]    The instant invention aims to solve at least some of those cited inconvenients. 
         [0016]    To this aim, it is provided a medical system comprising a percutaneous probe and a computerized system, the percutaneous probe, made in MRI-compatible materials, comprising:
       a body having an insertion end, shaped to be percutaneously inserted into tissue of a patient&#39;s body organ having a region to be analyzed, treated and monitored during a single medical procedure,   an optical head of an endo-confocal digital microscope,   at least one information collection sensing device, adapted to collect information about the region of the organ,   a plurality of treatment application transducers, operable as a phased-array, adapted to emit both focused and not-focused therapeutic ultra-sound waves to the region of the organ,       
 
         [0021]    the computerized system comprising a parametrizable command device and associated equipment adapted to command a generation of the therapeutic ultra-sound wave. 
         [0022]    With these features, the probe can be percutaneously inserted at a suitable location in any organ. Further, the probe can be used, during a single medical procedure, to sense organ information usable for establishing a diagnostic and characterization, and for implementing the appropriate therapy. 
         [0023]    In some embodiments, one might also use one or more of the features defined in the dependant claims. 
         [0024]    Further, it is provided a method comprising:
       providing a body organ having a region to be analyzed, treated and monitored during a single medical procedure, said organ being provided with a percutaneous probe made in MRI compliant materials, and having a body having an insertion end inserted into tissue of the body organ,   collecting information about the region of the organ with an information collection sensing device of the probe, and with an optical head of an endo confocal microscope   setting parameters of at least one of a focused and not-focused therapeutic ultra-sound wave to be emitted to the region of the organ with a plurality of treatment application transducers ( 30 ) of the probe, configured as a phase-array through a parametrizable command device ( 50 ) and associated equipment ( 56 ) of a computerized system.       
 
         [0028]    In some embodiments, one might also use one or more of the features defined in the method dependant claims. 
         [0029]    Advantages of one or more of these embodiments might include:
       real time monitoring of the therapy,   tissue histologic characterization and tissue therapeutic treatment during a single procedure,   ability to extract air bubbles from the tissue and replace them by liquid to avoid imaging artifacts,   ability to “real-time” monitor the therapeutic process and monitor security points for the treatment,   ability to perform continuous MRI and MR thermometry monitoring,   ability to perform immediate post-treatment MRI imaging sequences for monitoring the therapeutic process efficiency,   ability to treat regions either immediately around the probe and/or delocated areas,   improved focalization/defocalization of the therapeutic ultra-sound energy, by several techniques in order to best fit the lesion geometry,   ability to perform the therapeutic treatment even for a moving patient and/or organ,   ultrasounds emitters organized in a 360° fashion, thereby removing the need to rotate the probe inside the organ,   ability to treat tumors of various and complex shapes,   diminution of the post-treatment tumoral volume,   ability to acquire electro-encephalogram signals during the treatment.   ability to erase movement artefacts, ultrasound attenuations, phase aberrations and/or ultrasound defocalizations,   no requirement of a clinician manipulation during treatment, so that MRI safety and efficacy monitoring during the treatment becomes reliable,   ability to allow real time and in vivo tissue characterisation, biopsy, post thermal tissue resection preventing post-treatment mass effect,   disposable technology prevents inter patient contamination.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0047]    Other characteristics and advantages of the invention will readily appear from the following description of three of its embodiments, provided as a non-limitative examples, and of the accompanying drawings. 
           [0048]    On the drawings: 
           [0049]      FIG. 1  is a schematic view of a medical apparatus, 
           [0050]      FIG. 2  is a partial sectional view of a probe inserted into a body organ, 
           [0051]      FIGS. 3   a ,  3   b  and  3   c  are perspective views illustrative of various components of a probe according to a first embodiment, 
           [0052]      FIG. 4  is a partial sectional view along line IV-IV On  FIG. 3   c,    
           [0053]      FIG. 5  is a view similar to  FIG. 4  for a variant embodiment, 
           [0054]      FIGS. 6   a ,  6   b  and  6   c  are perspective views illustrative of various components of a probe according to a second embodiment, 
           [0055]      FIGS. 7   a ,  7   b , and  7   c  are views similar to  FIGS. 6   a ,  6   b  and  6   c , respectively, for a probe according to a third embodiment, 
           [0056]      FIGS. 8   a  and  8   b  are perspective views of components of a probe according to a fourth embodiment, 
           [0057]      FIG. 9  is a sectional view along line IX-IX of  FIG. 8   a,    
           [0058]      FIG. 10  is a partial perspective view of a probe according to a fifth embodiment, 
           [0059]      FIGS. 11   a  and  11   b  are partial perspective views of probes according to a sixth and a seventh, respectively, embodiment, 
           [0060]      FIG. 12  is a schematic view of a computerized system operatively associated with the probe, 
           [0061]      FIG. 13  is a diagram showing an example of use of the medical apparatus, and 
           [0062]      FIG. 14  is a enlarged view of  FIG. 2 . 
       
    
    
       [0063]    On the different figures, the same reference signs designate like or similar elements. 
       DETAILED DESCRIPTION 
       [0064]      FIG. 1  is a schematic view of a medical apparatus  1  comprising a magnetic resonance imaging (MRI) system  2  of conventional type, suitable to be operated, in particular, in a thermal imaging mode, in which a patient  3  is introduced, for example lying on a suitable bed  4 . 
         [0065]    The medical apparatus  1  further comprises a computerized system  5  connected to the magnetic resonance imager so as to receive from the magnetic resonance imager data enabling the construction of anatomy and/or thermal magnetic resonance images of the patient  3 . 
         [0066]    The medical apparatus further comprises a MRI compatible probe  6  percutaneously inserted into the patient&#39;s body, and operatively associated to the computerized system  5 . The probe  6  is for example electrically connected to the computerized system  5  through MRI-compatible wires, for example coaxial wires, which are known per se and will therefore not be described in more details here. 
         [0067]    As schematically shown on  FIG. 2 , the probe  6  comprises a somehow cylindrical body  7  of external diameter D of 4 mm, or less, and preferably of 3 mm or less, and even more preferably of 2 mm or less, and is shaped to be introduced into the tissue of an organ  8  of the patient&#39;s body  3 . The probe body  7  is interstitial, since it can be introduced directly into the tissue of the organ  8  without the necessity to go through the cavity of the organ. The insertion tip  9  of the probe body  7  is located within, or close to a region  10  of the tissue of the organ, which is to be analyzed and/or treated. The probe  6  could be applied, for example, to malignant or benign cancers, or neuro-cognitive brain impairments, as well as for other tissular pathologies of all other organs that could be treated by monitored ultrasonic treatment, such as thermal ablation. 
         [0068]    According to a first embodiment, as shown on  FIGS. 3   a ,  3   b  and  3   c , the probe  6  comprises a plurality of components: an applicator  11  ( FIG. 3   a ), a mandrel  12  ( FIG. 3   b ), and an ultra-sound device  13  ( FIG. 3   c ). 
         [0069]    The applicator  11  comprises a proximally-located back portion  14  and a somehow cylindrical body  15  defining an internal cylindrical cavity  16  which extends throughout the body  15  to a tip in which an end opening  40  is formed. 
         [0070]    The medical system can further comprise a continuous pump  36  to be placed in fluid communication with the cavity  16  of the applicator  11 , or removed therefrom. The pump can thus be operated to collect tissue fragments which can later be analyzed, for example by the clinician, to provide tissue information. 
         [0071]    The pump  36  can be operated to extract any material to be extracted from the patient, such as, for example, air bubbles that artifact images, and/or inject into the patient suitable liquids. 
         [0072]    The inner mandrel  12  is made of a rigid material and is shaped so as to be inserted into the cavity  16  so as to totally obstruct this cavity. The mandrel  12  can for example have a body  25  of cylindrical shape, of external diameter equal to the internal diameter of the body  15  of the applicator  11 . Furthermore, the mandrel  12  can have a back portion  26  of cylindrical shape of outer diameter equal to the inner diameter of the back portion  14  of the applicator  11 . The mandrel  12  can further comprise a pointy tip  57 . The mandrel can comprise an internal channel  27  extending from a proximal end  27   a  in the back portion  26 , to a distal end  27   b  at the insertion end  9  of the probe and adapted to be placed in fluid communication with a fluid tank  28 , for example through the pump  36 . The pump  36  can thus be operated in connection with the mandrel  12  to insert liquid into the patient through the cavity  27  and extract air bubbles which may form artifacts on the images therefrom. 
         [0073]    In this embodiment, the body  25  comprises, at its insertion end  9 , a confocal endo-microscope head  23  which is connected through a suitable fiber extending in the cavity  27  from the confocal microscope head  23  to the back portion  14 , so as to connect the confocal microscope head  23  to the computerized system  5 , for example with a not-shown MRI-compatible wire. The confocal endo-microscope head can thus be used to collect in vivo and real-time cellular and tissular information of the organ. 
         [0074]    Such miniaturized endo-confocal microscope heads are known per se and will not be described in more detail here. Alternatively, two separate channels are provided in the mandrel  25 , one for fluid insertion, and one for the endoconfocal microscope fiber. 
         [0075]    In an alternative embodiment (not shown), the mandrel back portion  26  will contain an electro mechanical component able to generate low frequency vibrations (around 10 kHz) within the mandrel body, in order to transmit low frequency vibrations to the tissue for fragmentation. In such embodiment, the mandrel might not be MRI compatible. 
         [0076]    When the mandrel  12  is inserted through the cavity of the applicator  11 , its distal portion will extend beyond the distal end of the applicator  11 , so that the endo confocal microscope head will be brought in close proximity to the region to be treated. 
         [0077]    The MRI-compatible ultra-sound device  13  has an external shape which is globally identical to the one of the mandrel  12 , so as to be inserted into the cavity  16  of the applicator  11 . The distal portion  29   b  of the body  29  of the ultra-sound device comprises a plurality of ultra-sound transducers  30  which are, for example, spaced from each other both longitudinally and circumferentially, disposed all around the circumference and the length of the part of the ultra-sound device which is to be inserted in the region to be treated. All the transducers  30  are connected as a phased-array device to the computerized control system  5  through MRI compatible wires  31 , which extend from the back portion  32  of the ultra-sound device to the computerized control system  5 . The transducers  30  can operate as ultra-sound emitters and/or as ultra-sound receivers. Such micro ultra-sound transducers are known per se, and will not be described in more details here (piezoelectric composite technology, capacitive micromachined ultrasonic transducers technology, etc. . . . ). When they are operated to detect ultra-sounds, the transducers thus can collect information about the organ. 
         [0078]    The back portion  32  comprises an in-flow aperture  17  in fluid communication with a fluid tank  18  preferably provided outside the patient&#39;s body. As shown on  FIGS. 4 and 5 , the in-flow aperture  17  is in fluid communication with a micro circuitry of the body  29  comprising at least one in-flow channel  19  extending in the thickness of the body  29 , from the back portion  32  to the tip  9  where it is in fluid communication with at least one out-flow channel  20  which extends from the tip  9  to an out-flow aperture  21  of the back portion  32 . 
         [0079]    A suitable micro pump such as a pulsed micro-pump  22  is located in the fluid line, so as to generate a flow of fluid from the fluid tank  18  to the out-flow aperture  21 . Such pulsed micro-pumps are known per se and will not be described in more details here. 
         [0080]    The outer surface of the ultra-sound device  13  can further comprise other MRI compatible sensors, such as, for example, electro-physiological signal sensors  33  such as carbon contact electrodes for detecting electro-encephalograms, electro-metabolic bio sensors  59 , . . . . 
         [0081]    Other MRI compatible sensors can be provided at the outer surface of the body  15 , such as temperature sensors  34  adapted to locally detect the temperature. The sensors  33 ,  34  are connected to the computerized system  5  through suitable MRI compatible wires  35  extending from the back portion  32  of the ultra-sound device  13 , and are thus operable to collect information about the organ. 
         [0082]    Such micro sensors are known per se and will not be described in more details here. 
         [0083]    When the ultra-sound device  13  is inserted through the cavity  16  of the applicator  11 , its distal portion  29   b  will extend beyond the distal end of the applicator such that the ultra-sound transducers  30  are directly coupled to the tissue of the organ so as to emit and/or receive ultra-sounds to/from the tissue. 
         [0084]    In the embodiment of  FIG. 4 , the coupling is performed by way of circulating the cooling fluid in the micro-circuitry  19 ,  20 . As shown by  FIG. 5 , other configurations are possible for the flow of the cooling fluid such as having the in-flow channel  19  and the out-flow channel  20  in the centre of the probe. 
         [0085]    The transducers  30  can be configured to be operable in an operating volume  37  around the probe having an external envelope  38  located at least 20 mm from the probe (not to scale on  FIG. 3   c ) and preferably at least 30 mm from the probe. The transducers  30  can be further configurable to focus ultra-sounds to a focal area in the operation volume. For example, the transducers  30  are configurable to focus the ultra-sounds to a focal area having between 2 (or 3) and 10 mm of diameter. In another operative mode, the ultra-sounds are not focused. 
         [0086]    The transducers  30  are configurable to operate in one or a plurality of frequencies, for example chosen in the range extending from 500 kHz to 10 MHz. Indeed by modulating the ultrasound emission frequencies, different physical effects, biological effects and tissue treatment effects can be produced such as cavitation phenomenons, tissue fragmentation, sonoporation of the cell membranes and thermal tissue necrosis. For thermal tissue necrosis, an embodiment is optimal between 3 MHz to 10 Mhz frequencies. The transducers  30  are configurable to operate in a plurality of emission intensities, time durations, and pulsed or continuous modes. Additionally, they can operate in phase or out of phase, in a specific setup of synchronizations. 
         [0087]    The transducers  30  are configurable to emit sufficient energy to raise the temperature by 30 degrees Celsius, preferably by 60 degrees Celsius, within less than 2 minutes, preferably less than 20 seconds, in the whole envelope  38  (cylinder of 30 mm around the probe). Possibly, they can perform this temperature rise within less than 1 second, preferably within less than 100 milliseconds, at a focal spot of 2 mm of diameter. 
         [0088]    Thus, the probe can be set to operate in ultrasound imaging and/or elastography modes, in an ultrasound therapeutic mode or a fragmentation mode. 
         [0089]    As can be visible from the various embodiments described in the application, other arrangements and configurations are possible within the scope of the invention. For example, a second embodiment is shown on  FIGS. 6   a  to  6   c . This second embodiment differs from the first embodiment described above in relation to  FIGS. 3   a  to  5  mainly by the fact that the cooling fluid circuits are provided within the shell of the applicator  11 , as well as the sensors  33 ,  34  and  59  and the head  40  of the endo confocal microscope. Thus, in this embodiment, the ultra-sound transducer  30  are coupled to the tissue of the organ through the body  15  of the applicator  11 . 
         [0090]    According to a third embodiment, as shown on  FIGS. 7   a  to  7   c , the applicator  11  of the second embodiment is modified to incorporate the ultra-sound transducers  30  to form a combined applicator and ultra-sound device  39 . The combined device  39  further comprises a plurality of openings  40  formed on the lateral face of the body  15  and in a fluid communication with the internal cavity  16 . 
         [0091]    In this third embodiment, the probe can comprise a rigid mandrel  12  identical to the one of the second embodiment. 
         [0092]    The probe can further comprise a cooling mandrel  41  shaped to be introduced into the internal cavity  16  of the combined device  39 , and comprising a micro circuitry comprising an in-flow channel  19  in fluid communication with a fluid tank  18  through an in-flow aperture  17  of the back portion  42  of the cooling mandrel, and an out-flow channel  20  in fluid communication with the in-flow channel and exiting from the back portion  42  at an out-flow aperture  21 . 
         [0093]    According to a fourth embodiment, as shown on  FIGS. 8   a ,  8   b  and  9 , the probe comprises only two components. Indeed, the combined applicator and ultra-sound device  39  of the third embodiment ( FIG. 7   a ) is modified to incorporate the fluid micro circuitry which, in the third embodiment, is provided through the independent cooling mandrel  41 . Thus, in the fourth embodiment, as shown on  FIG. 8   a , in addition to the features of the combined device of the third embodiment, an in-flow channel extends from the in-flow aperture  17  provided in the head  14 , whereas the internal cavity  16  itself serves as the out-flow channel. The in-flow channel  19  is thus in fluid communication with the cavity  16  at the insertion tip  9  of the device. 
         [0094]    In this fourth embodiment, the probe still comprises the rigid mandrel  12  of the two previous embodiments. 
         [0095]    A fifth embodiment is partially shown on  FIG. 10 . This fifth embodiment differs from the third or fourth embodiment in that it has no side openings. 
         [0096]      FIG. 11   a  partially shows a sixth embodiment of a device  39 . When compared to the device of the fifth embodiment, this sixth embodiment differs by a concave arrangement of the transducers, for example in a central portion of the device  39 . For example, no sensors are found in this central portion. Thus, instead of being purely cylindrical, the body  15  has, in this embodiment, a thinned central portion. According to another embodiment, as shown on  FIG. 11   b , the central portion could be convex. 
         [0097]    Such convex or concave shapes could be used for any of the ultra-sound carrying components of the above embodiments. 
         [0098]    It is contemplated that other geometries could be used provided the ultra-sound device is still able to provide therapeutic ultra-sound energy with the required power. 
         [0099]    The ultra-sound waves  51  are schematically illustrated on these figures. 
         [0100]      FIG. 12  now describes a schematic representation of an embodiment of the computerized system  5 . This system could be embodied on one or on a plurality of programmable machines and comprise both hardware and software components. The operating system and interfaces of the computerized system can be of any conventional type, and will not be described in more details here. The system  5  comprises network corrections, data archiving and storage software and hardware, image manipulation software including metric and editing functions, . . . . 
         [0101]    The computerized system  5  can comprise an echographic and elastographic imaging software  43  of conventional type suitable for obtaining a 2D or a 3D image based on ultra-sound detection data provided from the probe  6 , and resulting from the detection by the probe  6  of ultra-sound emitted by the probe  6  and reflected by the organ. 
         [0102]    The computerized system can further comprise an EEG-reading software  44  adapted to read data provided from the probe  6 , and detected by the electro-physiological sensors  33  of the probe. 
         [0103]    The computerized system can further comprise a thermal software  47  receiving data from the temperature sensors  34  of the probe  6  and adapted to determine temperature data of the tissue based on these received signals. 
         [0104]    The computerized system can further comprise a confocal microscope image software  48  adapted to receive data from the confocal microscope head  23  of the probe  6 , and to form an image from this data. 
         [0105]    The computerized system  5  can further comprise an MRI image software  45  receiving data from the MRI system  2  and adapted to reconstruct an MRI anatomy image of the patient from this data in conventional way. 
         [0106]    The computerized system can further comprise a thermal image software  46  connected to the MRI system  2  and adapted to treat data provided from the MRI system  2  to provide the user with a thermal image and with thermal ablation image of the patient. 
         [0107]    The computerized system  5  can further comprise a planning software  49  adapted to gather information and/or data about the patient and/or the studied organ and/or region from the echographic imaging software  43 , the EEG software  44 , the MRI image software  45 , the confocal microscope image software  48 , as well as if necessary, any other patient data, or organ data, obtained by any other suitable way. The planning software  49  enables the clinician to evaluate the relevant information, and to determine the best suit of action for the patient. 
         [0108]    The computerized system can further include a simulation software  60  that can elaborate the optimal parameter settings for the treatment, based on the various information available. 
         [0109]    For example, the simulation software  60  will use a model of the probe (including its position and orientation in the patient&#39;s reference frame, for example obtained from the MRI), a model of the tumor (acoustic impedance and other relevant parameters), and the geometry of the planned ablation, to estimate the appropriate settings to use for each of the transducers. 
         [0110]    The computerized system  5  can further comprise a command software  50  adapted to gather information from the planning software  49 , the MRI thermal image software  46 , the thermal software  47 . The command software  50  comprises a setting device  55  enabling to set the probe  6  in therapeutic or fragmentation mode (see below), by setting the parameters of the ultra-sound transducers to emit the necessary ultra-sound energy, as determined from the simulation and the planning software  49 , toward the appropriate region (appropriate focal area) of the patient. The ultra-sound can be set to operate in thermal- and/or cavity-dominant modes, and the focal area can be dynamically modified, for example under MRI image guidance, or ultra-sound imaging. 
         [0111]    The command software  50  can also be used to operate the other mechanical parts of the system such as the pump  22 , through a pulsed-pump command  53 , the pump  36  through a continuous pump command  54 , and the ultra-sound device in imaging mode, through the setting device  55 . The command software  50  is connected to power amplifiers  56  which deliver the necessary power to the transducers  30 . The switch between the different operation modes of the transducers could be commanded by a foot switch operated by the clinician. 
         [0112]    In the therapeutic mode, the system can operate in a step-by-step user-commanded style, or in a computer-controlled automatic style. 
         [0113]      FIG. 13  now describes a possible application of the above described medical system. 
         [0114]    At step  101 , the applicator  11  comprising the inner rigid mandrel  12  is percutaneously inserted into the tissue of the patient&#39;s organ, either by hand or under image monitoring (external echography or MRI). Alternatively, a stereotaxis frame or a robot arm could be used, for example for cerebrally inserting the probe. 
         [0115]    At step  102 , the position of the probe relative to the organ is monitored. For example, an image of the patient is obtained from the MRI system, or from an external CT-scan or echographic system. In alternative or in addition, the image could be obtained by the probe  6  itself, operating in an “imaging” mode. To do so the mandrel has to be removed and the ultra-sound device  13  inserted. In this mode, the ultrasound transducers  30  are commanded, by the command software  50 , to operate in an imaging mode, in which they emit ultra-sounds, for example within the operation volume  37 , and to detect the reflected ultra-sounds, the obtained detection data being thus sent to the echographic imaging software  43  of the computerized system. 
         [0116]    At step  103 , the inner rigid mandrel  12  is removed while simultaneously bringing liquid through the channel  27  by the pump  36  to avoid air introduction. The continuous pump  36  is then directly connected to the internal cavity  16 , so as to perform a biopsy by aspiring through the opening(s)  40 , a part of the organ. Alternatively, a syringe head or a biopsy needle could be used. This part can be further analyzed to confirm the characteristics of the tissue. In addition or in alternative, tissue characterization could be performed by disconnecting the pump  36  and inserting the microscope optical fiber through the cavity  16  (or  27 ), so as to use the endo-confocal microscope, the data of which is provided to the confocal microscope image software  48  of the computerized system. 
         [0117]    At step  104 , data from the electro-physiologic sensors  33  is obtained and is forwarded to the electro encephalogram reading software  44  of the computerized system  5 . 
         [0118]    Using the data obtained at steps  102 ,  103 , and/or  104 , at step  105 , the target volume and the probe position in reference to the targeted volume are defined, for example by the clinician using the planning software  49 . The target volume can further be defined manually or automatically, using external images, such as MRI images or the like. 
         [0119]    Based on the location and size of the target volume, at step  105 ′, the therapeutic ultra-sound energy, phases, durations for the various ultrasound transducers are simulated and calculated. At step  106 , the ultra-sound emission parameters are set, for example using the command software  50 . The size and the location of the focal area, the ultra-sound power and frequency are set in the command software  50 . Low frequency ultra-sound waves can be used for applying therapeutic ultra-sound energy to regions remote from the probe  6 , whereas higher frequencies can be used for close regions. The probe  6  is thus set to operate in a thermal “therapeutic” treatment mode, either by non destructive (metabolism stimulation, . . . ) or destructive (coagulation, vaporization) mode. 
         [0120]    At step  107 , the ultra-sounds are delivered to the region  10  of the organ  8 . As shown on  FIG. 14 , the probe  6  could be operated in de-focused mode inside the envelope  38 . It can also be operated in a focused mode active on specific focal areas  58 . Simultaneously, cooling physiological fluid is pumped into the micro-circuitry of the probe by the pump  22 , under command of the command software  50 , so as to efficiently cool the probe. Real-time thermal MRI images are provided to the thermal image software  46  of the computerized system for monitoring the temperature rise in the probe and/or in the organ and/or security points for the treatment. Necrosis prediction could be performed by the computerized system  5  by summing in time the obtained thermal data, to obtain thermal deposited doses within the specific volume. The reflected ultra-sounds are detected by the transducers  30 , and real-time images are formed at the computerized system  5 , which enables a real-time ultra-sound monitoring. 
         [0121]    At step  108 , the efficiency of the therapy ultra-sound application is monitored, for example from the detected MRI image, or by ultra-sound imaging (echography, elastography). If the therapeutic treatment is not judged sufficient by the clinician, the process continues back from step  105 . However, if the clinician finds out that a sufficient thermal treatment was performed, the process moves to step  109 . 
         [0122]    At step  109 , the treated region  10  is mechanically fragmented by ultra-sounds. The probe  6  is set to operate in a “fragmentation” mode by emission of pulsed ultra-sound to the treated region of the organ. The “fragmentation” mode also is a therapeutic mode. This results in a fragmentation (shearing) of the region, by breaking the inter-cellular adhesions using the jet-steam/cavitation technique. Of course, the ultra-sound parameters, in this mode, can be set from the command software  50 . In this mode, the probe is continuously cooled by the pump  22 . In another method, the fragmentation of the tissue can be performed by low frequency vibration (around 10 kHz [1-50 kHz]) emitted by the electromechanical mandrel back portion  26  through the mandrel body (if reintroduced) to transmit low frequency vibration within the treated tissue, or alternatively by yet another specific mechanical-stress inducing mandrel. 
         [0123]    At step  110 , the efficiency of the fragmentation step  109  is monitored. If this step is not judged sufficiently efficient by the clinician, the process moves back to step  109  whereas, if it is judged to be sufficiently efficient, the process moves to step  111  where the fragmented tissue is aspirated outside the body. 
         [0124]    At step  111 , the optical fiber of the endo-confocal microscope is removed, the pump  36  connected to the cavity performs a soft aspiration, at controlled negative pressure, commanded by the command software  50  of the computerized system, so as to allow the decrease in volume of the treated region. 
         [0125]    At step  112 , it is monitored whether the treatment can be judged satisfactory by the clinician. If this is not the case, the process moves back to step  111 . If it is decided to end the procedure, the probe  6  is removed from the organ and the process is ended. 
         [0126]    The above description is just an exemplary description of one possible embodiment of the above described probe and system and it is within the reach of the person skilled in the art to repeat, bypass, or change the order of the above steps, or to add additional steps, dependent of the pathology to be treated. Thus, the probe could allow the treatment of the tissue lesions by the following modes and physical agents: thermal blood coagulation, thermal reversible ischemia, non-thermal mechanical jet steam and cavitation means, sonoporation or combinations thereof. 
         [0127]    Furthermore, the interstitial probe could be used in a non-interstitial way, by being placed in close proximity, but outside an organ to be treated. The probe could be disposable, or be sterilized between subsequent uses. 
         [0128]    Furthermore, in another embodiment, the probe could be permanently installed in the organ of the patient, and be remote-controlled by a suitable computer, for example implanted inside the patient, at periodical examinations. 
         [0129]    Although the above embodiments show a probe having numerous features, it should be noted that not all of these features necessarily need to be part of the inventive probe. For example, the information collection device could be comprised of only one or more of the ultra-sound transducers  30  in imaging mode, the electro physiological sensors  33 , the temperature sensors  34 , and the endo-confocal microscope head  40 .