Patent Application: US-55900600-A

Abstract:
the invention relates to a cerebral blood flow velocity monitoring system and method that comprises a transcranial doppler ultrasound device that is adapted to be implanted in the human body , an oximeter , an external handheld computer and a drug delivery system . the system provides for monitoring of microembolic signals and operatively activates the drug delivery system for infusion of medication into the blood circulation for thrombolysis and neuroprotection .

Description:
fig1 shows the schematic diagram of one embodiment of the present invention attached to a patient 1 , with the ultrasound probe housing 2 placed on the temporal bone on the head ; transcranial doppler ultrasound device including a voltage generator / gate 3 a receiver / gate 4 that allow a selection of depth at which velocity of moving red blood cells can be measured and to detect motion of microembolic signals . the microprocessor 5 processes the spectral data in the usual manner as described for pulsed and continuous wave doppler in the book by kremkau f . w ., “ diagnostic ultrasound : principles , instruments , and exercises ,” third edition , published by w . b . saunders co ., philadelphia : ( 1989 ). however , the spectral waveform and audio signals are transmitted via a radio frequency transmitter / receiver 6 to another transmitter / receiver 9 attached to an external handheld computer 10 , which displays the spectral data on the monitor 11 and plays the audio signals on the loudspeaker 12 . the patient or medical personnel can view the spectral information and listen to the audio signals . it is possible for the patient to make authorized inputs into the program of the system using the keyboard 13 , for example , to input the clinical symptoms related to a particular event . the system can be programmed to automatically access the internet 14 and use the “ file transfer procedure ” ( ftp ) to move files containing information that may include spectral data , microembolic signal rate , patient personal data , equipment serial number and lot number to the attending physician or emergency medical service personnel . conversely , the attending physician 15 can alter the program of the system including pump bolus dose discharge rate , insonation depth , new artifact exclusion criteria , and even review records on microembolic signal rate before and after each drug delivery regimen . in addition , a built - in oximeter 7 that detects oxygen saturation in blood is used to assess the respiratory status . the system on detection of microembolic signals could generate a trigger signal to activate an internally implanted infusion pump or an external infusion pump 8 . in a preferred system , the infusion is implanted and receives control signals via a direct or telemetric connection . for example , when the infusion pump is built - in with the transcranial doppler ultrasound device and placed in the subcutaneous space below the clavicle , an attached catheter could be placed at a selected in - vivo site such as the subclavian or cephalic vein . fig2 shows the flexible silicone elastomer probe housing , containing an embedded ultrasound transducer 16 placed on a contoured polypropylene base . similar silicon elastomer housing have been used for cerebrospinal fluid flow control valves and could be obtained from pudenz - schulte medical , a company in santa barbara , calif . a solid ultrasonic biomedical couplant hydrogel sheet 17 , and a thin film of hydrophilic polymer 18 provide means for transfer of ultrasound energy between the ultrasound transducer and the patient &# 39 ; s head . a reservoir 20 temporarily stores the humectant such as triethylene glycol or glycerin , which drains through an upper inlet 21 into the silicon membrane valve 22 . after drainage of the gel through the membrane valve 22 , the reservoir 20 fills with air and provides an air cushion in the probe housing , which is required for attenuation of the ultrasound beam propagation in the reverse direction . the gel is refilled via a radiopaque dot marked needle injection site 23 into a reservoir 24 . the reservoir is made of deformable silicon elastomer with pores at the base to allow a portion of the gel to flow to the surface of the probe . both ends of the probe housing have radiopaque marks 25 . the size of the probe housing vary and as shown could be of height 7 . 5 mm and diameter of 32 mm by way of example . the height of the probe housing is chosen such that it does not protrude sideways to alter the side profile of the patient &# 39 ; s head and is well within the area covered by the hairline . in effect there is no cosmetic defect produced by the implantation of the probe housing . the transducer 16 is firmly attached to the proximal end of the transducer cable 19 , while the distal end is connected to the transcranial doppler ultrasound device by means of detachable connector . the said cable could be additionally covered with silicon elastomer tubing impregnated with white barium sulfate to provide radiopacity for its entire length . the latter radiopaque cover provides means to monitor appearance of wire cable kink that may disturb the functionality of the transducer . however , the sillicon eclastomer cable cover is made of kink resistant material . fig3 shows the line of incision 26 for implantation of the transcranial doppler probe housing . after the usual patient preparation for surgery , anesthesia , and aseptic procedures for surgical field preparation on a shaved skin , the line of incision 26 is made as shown by way of example . several variations of the incision line are possible provided the superficial temporal artery is not severed . fig4 shows exposure of the temporal bone 27 by removing the overlying skin . the probe housing , transducer cable and transcranial doppler ultrasound device are packaged in a sterile pack . the probe housing 2 is aseptically removed from the pack and placed on the temporal bone above the zygomatic arc . the transcranial doppler ultrasound device is aseptically implanted in the subcutaneous pocket below the clavicle . the external handheld computer 10 , is placed at a distance from the sterile area but in eye view of the operator - surgeon . the system is then activated and the surgeon with the help of an assistant optimizes the doppler waveform signals . once the best possible spectral signals are obtained on the monitor 11 of the external handheld computer 10 the operational parameters are saved and the site of the probe housing on the temporal bone is marked . the surface area of the bone in the marked region is prepared with an abrasive operating instrument to create a rough bone surface on the marked bone region . the surface preparation instrument in some cases could be an adapted bone drill used to thin the bone if there is a poor acoustic window or when no window exists at all and the patient requires an implant . the firm polypropylene base of the probe housing 2 can be affixed to the temporal bone by means of a pre - applied adhesive surface at the polypropylene base and / or by means of application of adhesive semi - liquid glue . the said glue could be removed when required by using a variety of substances including a conventional nail polish remover by way of example . fig5 shows the side profile of the probe housing placed on the temporal bone 27 . a properly placed probe housing will have both the anterior and posterior ends of the probe stuck on the bone but the central portion free with couplant hydrogel 17 and hydrophilic polymer 18 trapped in the space between the acoustic window of the temporal bone and the transducer . to ensure that the desired probe - to - vessel angle is maintained the shape of the polypropylene base could appropriately be adapted . additionally , the area around the couplant hydrogel 17 can be sealed to prevent leaks of the gel substance into the subcutaneous tissue by applying additional glue on the outside perimeter of the circular surface of the polypropylene base around the hydrophilic polymer 18 . fig6 shows the focusing of the transducer on basal cerebral arteries . the transducer 16 can be focused on any of the basal cerebral vessels . however , the preferred insonation is on the middle cerebral artery main stem 28 or at the carotid bifurcation ( shown by arrow ). the latter ensures monitoring of microembolic signal rate in a larger vascular territory . fig7 shows the top - side view of the probe housing indicating the site of needle introduction for percutaneous refills of ultrasonic gel substance . the radiopaque dot indicating the needle injection site 23 such as a 25 - gauge needle 29 by way of example , allows for refill of the gel substance percutaneously under x - ray control . the radiopaque tantalum - impregnated arrowhead indicates the anterior end of the probe housing , and corresponds to the direction of the patient &# 39 ; s face . fig8 shows the means to expunge the gel substance into the space between the transducer and the temporal bone . the middle 30 and index 31 fingers are used to press on the reservoir to expunge the gel substance into the space between the probe and the bone , until good contact of the gel sheet with the bone is achieved during implantation . this could be repeated percutaneously after implantation . subsequently , it is not necessary to use fingers to expunge the gel substance . the system is designed such that the movement of the skin overlying the probe housing squeezes the dome of the probe housing against the temporal bone during talking and chewing or lying down on the side of the implant . this assures a regulated and continuing expunge of the gel substance via the outlets under the silicon membrane pump into the desired space between the probe and the bone . doppler flow signal quality controls are used to determine when the hydrogel should be refilled . fig9 shows the implantation of the transcranial doppler ultrasound device 32 inserted in a subcutaneous pocket below the clavicle . the components for assembly of such a transcranial doppler ultrasound device and ultrasound transducers could be obtained from dwl , a company in sipplingen , germany . the transducer cable 19 is tunneled through the path from the temporal region to the space below the clavicle where the transcranial doppler ultrasound device 32 is implanted . making a small incision below and parallel to the clavicle to allow access to the subcutaneous pocket to insert the transcranial doppler ultrasound device . when an internal infusion pump system is used , the catheter for delivery of the thrombolytic agent and / or neuroprotective agents is inserted into an in - vivo site for example the subclavian or cephalic vein . the pump could be connected directly to the transcranial doppler ultrasound device . the implant site for the pump is chosen to permit percutaneous refill of the thrombolytic and / or neuroprotective agents . however , advances in genetic engineering may permit in - vivo production of the drug substances from cell lines , purification and storage in reservoir systems , with eventual dispensing of the drug by microinjection . other modifications may include intra - peritoneal implantation with telemetric communication with the transcranial doppler ultrasound device . however , in some cases where short duration use of a drug is of essence , external programmable infusion pump such as that used for insulin infusion for example minimed 508 ( minimed inc . sylmar , calif .) could be used with telemetric control by the transcranial doppler ultrasound device . the infusion needle can be inserted into the veins of the arm such as the median antebrachial vein 33 using a catheter 34 and the infusion line 35 connected to the infusion pump 36 attached to a waist belt . fig1 shows the subcutaneous transducer cable passer . the transducer cable passer is designed to pass distally through the subcutaneous space with the polypropylene handle 37 and nylon obturator 38 in place the tubular passer shaft 39 is malleable and may be hand formed by the surge on as required during the operative procedure . tunneling of the subcutaneous space can be accomplished from either the top or bottom end as may be convenient for the surgeon . however , it is preferred that tunneling begins from behind the ear on the mastoid bone and along the stenocleidomastoid muscle to the clavicle . the passer will accept transducer cables of a definite outer diameter usually less than 3 . 0 mm by way of example . after placement of the passer , the obturator 38 is unlocked from the handle 37 and the handle removed from the passer shaft . the distal end connector ( to the transcranial doppler ultrasound device ) of the transducer cable is then placed on the obturator end fitting 40 ( that fits the transducer cable connector in a plug - to - socket arrangement ). the obturator and transducer cable are then drawn through the passer shaft by pulling the distal obturator tip . the obturator is then removed from the transducer cable . the passer shaft can now be withdrawn caudally through the incision below the clavicle . the distal end of the transducer cable is now connected to the terminal on the transcranial doppler ultrasound device . fig1 shows the program flow chart of the system of the invention . after initialization , the visualization of the operation of the transcranial doppler device is done on the handheld computer , the telemetric connection between the handheld computer and the implanted transcranial doppler device allows for telemetering of the doppler signals for spectral display on the monitor of the handheld computer . the program mode selection could be done on the handheld computer . the implanted transcranial doppler ultrasound device and the oximeter are all sensing devices for doppler flow signals and oxygen saturation respectively ; both signals are telemetered for analyses and display to the handheld computer . first , the threshold parameters 41 for mean blood flow velocity ( mbfv ) in the cerebral artery is set , the acceptable microembolic signal ( mes ) rate ( count per unit time ) is chosen and the normal oxygenation saturation level ( sao 2 ) range are selected . the program creates files 42 for storing the relevant data for these parameters . these parameters are read continually 43 and if not 44 all data are read , it proceeds to read all 43 . if all are now read the program proceeds to store the baseline values 45 for the parameters monitored . it then reads the online values 46 and compares them to the set threshold 47 , if the online values are below threshold 48 then it continues to read the online values 46 . when above the set threshold , it calculates the precise percentage change in mbfv relative to baseline 49 , if this is below the critical threshold 50 it continues with reading online values 46 . however , if above the set threshold it generates an audible alarm 51 , that cautions the patient ( by a voice prompt , by way of example ) to remain still for a few minutes , during which time it reads the files 52 and compares the online values to set threshold 53 . if below threshold 54 it proceeds to read online parameters 46 in the usual manner . if above threshold it runs an artifact subroutine 55 to exclude such artifacts as motion related artifacts , sound interference , device malfunction and other artifacts that may arise . if the artifacts are confirmed , it proceeds with continuous monitoring of online parameters 46 . if no artifacts were found , it generates the trigger “ on ” rf signal to cause the infusion to release a bolus of thrombolytic and / or neuroprotective agents such as rt - 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