United States Patent (19)
`Barker et al.
`
`11) Patent Number:
`(45. Date of Patent:
`
`4,585,009
`Apr. 29, 1986
`
`54
`
`75)
`
`(73)
`21
`22)
`(51)
`(52)
`(58)
`
`STRONTIUM-RUBDIUM INFUSION PUMP
`WITH IN-LINE DOSMETRY
`Inventors: Samuel L. Barker, Lawrenceville;
`Michael D. Loberg, Princeton, both
`of N.J.
`Assignee: E. R. Squibb & Sons, Inc., Princeton,
`N.J.
`Appl. No.: 470,841
`Filed:
`Feb. 28, 1983
`Int. Cl." ............................................... A61N 5/00
`U.S. Cl. .................................... 128/655; 128/655;
`250/362
`Field of Search ..................... 128/655, 654, 656.8,
`128/716.1, 653,659, 1.1, 1.2; 250/362,363 S;
`604/51-53
`
`56)
`
`References Cited
`U.S. PATENT DOCUMENTS
`4,006,736 2/1977 Kranys et al. ................ 128/DEG. 1
`
`OTHER PUBLICATIONS
`Yano et al., "Visualization of . . . 82Rb . . . Positron
`Scintillation Camera', Jan., 1968, (JNM).
`Grant et al., “A 825R-82Rb Isotope Generator . . . Nu
`clear Medicine” (JNM) Nov. 1974.
`Primary Examiner-Lee S. Cohen
`Assistant Examiner-Steven Falk
`Attorney, Agent, or Firm-Lawrence S. Levinson;
`Sanford J. Asman
`ABSTRACT
`(57)
`The dosimetry system used with a strontium-rubidium
`infusion system is a very high speed circuit capable of
`measuring the radioactive dosage infused into a patient
`in real time. The dosimetry system is capable of receiv
`ing very short duration input pulses generated by a
`photomultiplier tube in response to the presence of
`radioactivity.
`
`8 Claims, 12 Drawing Figures :
`
`lo
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`70
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`tNFUSON
`PUMP
`CONTROLLER
`
`DOSMETRY
`CONTROLLER
`
`62
`
`JUBILANT EXHIBIT 1018
`Jubilant v. Bracco, IPR2018-01449
`
`

`

`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
`US. Patent Apr. 29, 1986
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`Sheet 4 of 11
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`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
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`Sheet 6 of 11
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`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
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`U.S. Patent Apr. 29, 1986
`US. Patent Apr,»29, 1986
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`U.S. Patent Apr. 29, 1986
`US. Patent Apr. 29, 1986‘
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`Sheet 10 of 11 4,585,009
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`ENDOFELUTION+5
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`

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`U. S. Patent Apr. 29, 1986
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`Sheet 11 of 11‘ 4,585,009
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`1
`
`STRONTIUM-RUBDIUM INFUSION PUMP
`WITH IN-LINE DOSMETRY
`
`5
`
`O
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`15
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`25
`
`BACKGROUND OF THE INVENTION
`The present invention relates to a strontium-rubidium
`infusion system. In particular, it relates to a strontium
`rubidium infusion system which has an in-line, real time
`dosimetry system which can be used to infuse patients
`with Rubidium-82.
`Current statistics show that approximately one-third
`of all deaths in the United States are related to coronary
`artery disease. See, for example, Pohost, G., McKusick,
`K., and Strauss, W., "Physiologic Basis and Utility of
`Myocardial Perfusion Imaging” Proceedings of the
`Second International Symposium on Radiopharmaceu
`ticals, Society of Nuclear. Medicine, New York 1979,
`pp. 465-473, and this fact has prompted extensive re
`search to more efficiently diagnose and manage this
`20
`disease. Recent advances in radiopharmaceutical devel
`opment and instrument design have established myocar
`dial scintigraphy as an important new approach for
`evaluating coronary artery disease and myocardial per
`fusion. See, for example, Pierson, R., Friedman, M.,
`Tansley, W., Castellana, F., Enlander, D., and Huang,
`P., "Cardiovascular Nuclear Medicine: An Overview',
`Sem. Nucl. Med., 9, 224-240 (1979); Leppo, J., Scheuer,
`J., Pohost, G., Freeman, L., and Strauss, H., "The Eval
`uation of Ischemic Heart Disease Thallium-201 with
`Comments on Radionuclide Angiography'; Sem. Nucl.
`30
`Med., 10, 115-126 (1980); Vogel, R., "Quantitative As
`pects of Myocardial Perfusion Imaging', Sem. Nucl.
`Med., 10, 146-156 (1980); Chervu, R., "Radiopharma
`ceuticals in Cardiovascular Nuclear Medicine', Sem.
`Nucl. Med., 9, 241-256 (1979); and Pitt. B., and Strauss,
`H., "Cardiovascular Nuclear Medicine', Sem. Nucl.
`Med., 7, 3-6 (1977).
`Myocardial scintigraphy studies have been per
`formed with several isotopes of potassium, rubidium,
`cesium, and thallium (T1-201), although the usefulness
`of all of these nuclides is limited by their non-optimal
`physical properties. In spite of its long half-life andlow
`gamma energy, T1-201 is currently the most widely
`used agent for myocardial imaging. See, for example,
`Poe, N., "Rationale and Radiopharmaceuticals for
`Myocardial Imaging', Sem. Nucl. Med., 7, 7-14 (1977);
`Strauss, H. and Pitt, B., "Thallium-201 as a Myocardial
`Imaging Agent', Sem. Nucl. Med., 7, 49-58 (1977);
`Botvinick, E., Dunn. R., Hattner, R., and Massie, B., "A
`Consideration of Factors Affecting the Diagnostic Ac
`50
`curacy of T1-201 Myocardial Perfusion Scintigraphy in
`Detecting Coronary Artery Disease', Sem. Nucl. Med.,
`10, 157-167 (1980); and Wackers, F., "Thallium-201
`Myocardial Scintigraphy in Acute Myocardial Infarc
`tion and Ischemia', Sen. Nucl. Med., 10, 127-145
`(1980).
`In diagnostic procedures in which the heart is in
`volved, it is desirable for a diagnostician to be able to
`view a patient's heart. Heretofore, various radioactive
`materials have been used together with radiological
`procedures for viewing internal organs of patients. It
`has been difficult, however, to view a heart because the
`radioactive substances which could be used for viewing
`the heart have had a very long half-life. Thus, using
`them with patients involves an element of danger and
`65
`also reduces the number of times that a patient could be
`infused within any given time period. It would there
`fore be desirable to have a diagnostic apparatus and
`
`4,585,009
`2
`procedure which could be used with relative safety for
`viewing the heart.
`Rubidium-82 is a potassium analog. That means it acts
`similar to potassium which it is infused into a patient.
`Thus it builds up at a very rapid rate, i.e., within sec
`onds, in the patient's heart. Rubidium-82 also has the
`advantage of having a very short half-life, approxi
`mately 76 seconds. Therefore, it decays after a very
`short period of time following entry into the body,
`thereby allowing numerous procedures to be performed
`within a relatively short time period in a given patient.
`Rubidium-82 also has the advantage of being observable
`using a modified gamma camera such as a gamma cam
`era of the type manufactured by Searle Radiographics,
`Inc., called the PHO Gamma IV. A problem with using
`Rubidium-82 in a patient involves keeping track of the
`amount of radiation infused into the patient. In view of
`the very short half-life of Rubidium-82, it is impractical
`to measure the radioactivity of a particular dose and to
`then infuse it into the patient using conventional means.
`An accurate method for measuring the amount of radia
`tion being infused into the patient would be highly
`desirable for this particular application.
`The availability of improved instrumentation has
`stimulated interest in the use of the positron emitter,
`Rubidium-82, for myocardial imaging. See for example,
`Beller G., and Smith, T., "Radionuclide Techniques in
`the Assessment of Myocardial Ischemia and Infarc
`tion," Circulation, 53 (3, Supp. 1) 123-125 (1976); Bud
`inger, T., Yano, Y., Derenzo, S., et al., "Myocardial
`Uptake of Rubidium-82. Using Positron Emission To
`mography,” J., Nucl. Med. 20, 603 (1979); Budinger, T.,
`Yano, Y., Derenzo, S., et al., "Infarction Sizing and
`Myocardial Perfusion Measurements. Using Rb-82 and
`Positron Emission Tomography,” Amer. J. Cardiol, 45,
`399 (1980). Rubidium-82, an analog of the alkali metal
`potassium, is rapidly cleared from the blood and con
`centrated by the myocardium. The short half-life of the
`Rubidium-82 (76 sec) offers the unique advantage of
`permitting repeat perfusion and blood flow studies in
`patients whose clinical status is rapidly changing.
`Rubidium-82 is produced by the decay of its parent,
`strontium-82. E. R. Squibb and Sons, Inc. has developed
`a Rubidium-82 generator and infusion system which
`yields an isotonic saline solution of Rubidium-82 at
`physiological pH for rapid administration. In animal
`experiments, the safety and myocardial uptake of
`Rubidium-82 has been demonstrated. Therefore this
`agent has been selected as a candidate for clinical trials,
`BRIEF DESCRIPTION OF THE DRAWING
`In the Drawing:
`FIG. 1 is an overall schematic diagram of the stronti
`um-rubidium infusion system of the present invention;
`FIG. 2 is a front view of the infusion pump control
`used with the strontium-rubidium infusion system;
`FIG. 3 is a front view of the dosimetry control used
`with the strontium-rubidium infusion system;
`FIG. 4 is a graph of radioactivity measured (on the
`y-axis) by the dosimeter probe versus time (on the x
`axis);
`FIG. 5 is a perspective view of the dosimetry probe;
`FIG. 6 is a schematic diagram of the interface be
`tween the dosimetry probe of FIG. 4 and the dosimetry
`control circuitry;
`
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`56, the minimum radioactivity which must be present in
`FIG. 7 is a schematic diagram of the circuit for the
`the tubing 30 before any eluate is infused into the patient
`Single Channel Analyzer used to convert and shape the
`raw pulses from the dosimetry probe of FIG. 4;
`56, the total volume to be infused (Note: The total vol
`FIG. 8 is a schematic diagram of the circuit for the
`ume eluted may differ from the total volume infused
`Multiply-Divide circuit used to carry out the formula
`into the patient 56 as some volume is likely to be di
`which converts pulses from the Single Channel Analy
`verted to waste.
`zer into radioactivity present in front of the dosimetry
`The foregoing parameters may be altered from the
`probe;
`front panel of two different controllers shown in FIGS.
`FIG. 9 is a schematic diagram of one of the Display
`2 and 3. These are the infusion pump controller 60 and
`the dosimetry controller 62, respectively. The infusion
`Controller circuits used to interface the switches and
`the displays to the other circuitry;
`pump controller 60 controls the mechanical movement
`FIG. 10 is a schematic diagram of the Dose Rate
`of the syringe's plunger 66 via a stepping motor 64
`circuit used to provide a display of the amount of radia
`which is connected to the plunger 66.
`tion present in the eluate;
`In the preferred embodiment of the invention, the
`FIG. 11 is a schematic diagram of the Control Circuit
`syringe 18 is a sterile, disposable plastic syringe of the
`which oversees the operation of the remainder of the
`type made by Sherwood Medical and designated as
`circuitry; and
`Part. No. 881-514031. The infusion pump controller 60
`FIG. 12 is a schematic diagram of a valve driver
`limits the movement of the syringe plunger 66 based
`circuit.
`upon optical limit detectors 68, 70 which limit the fully
`displaced and fully extended positions of the plunger 66,
`DETALED DESCRIPTION OF THE
`respectively. The volume control function performed
`PREFERRED EMBODIMENT
`by the infusion pump controller 60 is accomplished by
`Referring now to FIG. 1, a saline bag 10 is connected,
`counting the number of pulses sent to the stepping
`through a bullet nose fitting 12 and a piece of tubing 14,
`motor 64.
`to a T-shaped two-way check valve 16 having three
`25
`With reference to FIG. 2, the front panel of the infu
`arms. A first arm 20 includes a one-way valve which
`sion pump controller 60 is shown. The infusion pump
`permits saline to enter the check valve 16, but does not
`controller 60 includes an on/off power switch 72 which
`allow it to exit back into the tubing 14. A second arm 22
`is used to turn on the power to the unit.
`includes a check valve which permits saline to exit from
`A set of thumbwheel switches 74 is used to select the
`the check valve 16 into a filter 24 through a tube 26, but
`30
`total volume (ml) to be eluted. An LED display 76
`does not allow it to re-enter the check valve 16 from the
`shows the total volume (ml) which has been eluted. A
`tube 26. A syringe 18, connected to the check valve 16
`momentary contact push-button switch 78 is used to
`fills from the saline bag 10 and pumps out through the
`start and to stop the movement of the plunger 66 in the
`tubing 26 into the filter 24. Saline pumped through the
`forward (inject) direction.
`filter 24 enters a strontium-rubidium generator 28 which
`35
`A set of push-button potentiometers comprise the
`is of the type described more fully in U.S. patent appli
`Flow Rate Control 80 which is used to determine the
`cation Ser. No. 156,285, entitled 82RB GENERATING
`volume per unit time which is infused. The Flow Rate
`METHOD AND ELUENT, filed on June 4, 1980 by
`Control 80 sets the pulse rate into the stepping motor
`Rudi D. Neirinckx, et al.
`64. An LED 82 lights when the end of travel of the
`Saline pumped through the strontium-rubidium gen
`40
`plunger 66, as indicated by the optical limit detectors
`erator 28 exits the generator 28 through tubing 30 con
`68, 70 is reached. A pair of momentary contact push
`taining Rubidium-82. The tubing 30 is connected to a
`button switches 84, 86 are used to control the purge and
`diverter valve 32 having a first arm 34 which leads
`refill functions, respectively, of the syringe 18. Thus, if
`through tubing 38, an antibacterial filter 40, and ulti
`the purge control switch 84 is pushed, and held, the
`mately to waste 42. A second arm 35 of the diverter
`45
`plunger 66 continues to move in the forward direction
`valve 32 is connected through tubing 44, an antibacte
`until it reaches the forward limit detector 68. Similarly,
`rial filter 48, additional tubing 50, and into an infusion
`while the refill control switch 84 is pressed and held, the
`needle 52. The infusion needle 52 is typically inserted
`plunger 66 continues to move toward the rear limit
`into the arm 54 of a patient 56.
`detector 70. The speed of movement of the plunger 66
`In the preferred embodiment of the invention, the
`during purge and refill operations are controlled by
`check valve 16 is a dual back check valve of the type
`adjustable screw-type potentiometers 88, 90, respec
`made by Beckton Dickenson Inc., and the antibacterial
`tively.
`filters are of the type made by Schleicher & Schull as
`The infusion pump controller 60 is comprised of a
`their type FP030/3.
`Superior Electric Company STM103 Translator Mod
`In the operation of the device, the amount of radioac
`ule which is interfaced to provide signals representative
`tivity in the saline eluted from the strontium-rubidium
`of flow rate, volume eluted, and injection. It is also
`generator 28 must be measured as it is introduced into
`interfaced to be remotely controlled. A pulse called
`the patient 56. Accordingly, a dosimetry 58 is placed
`“INIT' indicates that the Translator Module has been
`adjacent to the tubing 30 where it measures the radioac
`powered. The “INIT" pulse is used to reset the displays
`tivity of the rubidium-containing saline as it leaves the
`60
`on the dosimetry module. An "INJECT signal indi
`generator 28 and enters the diverter valve 32.
`cates that the pump is injecting. Output pulses, corre
`In order to use the infusion system, various proce
`sponding to 0.1 ml steps of the syringe 18, are provided.
`dures must be performed and controlled. In particular,
`An "End of Elution' signal is used to remotely disable
`the syringe 18 must be purged of air, and filled with
`the infusion pump controller 60.
`saline, and the diverter valve 32 must be positioned.
`65
`With reference now to FIG. 3, the dosimetry control
`These operations are contingent upon a number of fac
`ler 62, is comprised of a number of LED displays and
`tors including the total volume to be infused into the
`patient 56, the total dosage to be infused into the patient
`thumbwheel switch sets. In addition, the dosimetry
`
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`5
`controller 62 includes an on/off switch92 for providing
`Once eluate is infused into the patient 56, it continues
`power to the unit.
`to be infused until one of various stop indications oc
`curs. In particular, when the total patient 56 dose, set by
`The first set of thumbwheel switches 94 is used to set
`the thumbwheel switches 98, is reached, the diverter
`the volume (ml) to be infused into the patient 56. The
`valve 32 is returned to the waste position, and the step
`LED display 96, immediately above the thumbwheel
`ping motor 64 stops, thereby preventing further infu
`switches 94, displays the volume of eluate which has
`sion. Similarly, the diverter valve 32 is switched, and
`been infused into the patient 56.
`the stepping motor 64 is stopped when the patient 56
`The thumbwheel switches 98 are used to set the total
`volume, preset by the thumbwheel switches 94 reaches
`dose (mCi) which is to be infused into the patent 56 and
`its preset value or after the total volume to be eluted, set
`the LED display 100 immediately above the total dose
`by the volume thumbwheel switches 94 reaches its pre
`thumbwheel switches 98 displays the total dose which
`set value; or when the purge limit optical stop 68 of the
`has been infused into the patient 56. Similarly, the
`syringe 18 is reached; or if the start/stop inject button
`thumbwheel switches 102 are used to set the dose rate
`78 is pushed. Any of the foregoing events causes the
`(mCi/sec.) which is to be used to determine when to
`diverter valve 32 to switch to the waste position, and
`switch the diverter valve 32 from the waste position to
`causes the stepping motor 64 to stop. Note, however,
`the patient 56 position. The actual dose rate which is
`that the purge and refill switches 84, 86 are disabled as
`present in the eluate within the tube 30 in front of the
`of the time that the start/stop inject button 78 is pushed
`dosimetry probe 58 is displayed on the LED display
`to commence the infusion.
`104. The description of the dose present in the eluate at
`20
`any given time from the start of infusion will be pro
`QUANTIZING RADIOACTIVITY IN A LIQUID
`vided hereafter. The dosimetry controller 62 further
`STREAM
`comprises a pair of LEDs 106, 108 which indicate the
`In order to measure the radioactivity in the saline
`position of the diverter valve 32. Only one of these two
`solution which passes through the line 30 in front of the
`LED's 106, 108, should be on at any given time.
`dosimetry probe 58, it is necessary to count the number
`25
`While the normal position of the diverter valve 32 is
`of disintigrations which occur in front of the probe 58,
`toward waste, except when eluate is being infused into
`while at the same time keeping track of the flow rate of
`a patient 56, provision must be made to clear the tubing
`the saline through the tube 30. Given that these quanti
`44, 50 of any air prior to infusing a patient 56. Accord
`ties are known, it is possible to measure the total activity
`ingly, the dosimetry controller. 62 includes a toggle
`30
`in millicuries (mCi) in accordance with the following
`switch 110 which is used to hard wire the diverter valve
`formula:
`32 in the patient 56 position.
`The present preferred embodiment of the invention
`also includes a set of thumbwheel switches 112 which
`are used to set the flow rate which will be used in inter
`35
`nal calculations of dosimetry controller 62. It is pres
`ently anticipated by the inventor that a future version of
`the present invention will include automatic means for
`determining the flow rate based upon the settings used
`in the infusion pump controller 60.
`40
`Referring now to FIG. 4, a graph of the radioactive
`dosage present in the tubing 30 in front of the dosimetry
`probe 58, is shown. In the graph, the dosage is measured
`on the y-axis and time is measured on the x-axis. The
`time is referenced with zero being the time that the
`45
`start/stop inject button 78 on the infusion controller 60
`is pushed to commence infusion.
`For approximately 10 seconds there will be no radio
`activity present in the eluate from the strontium
`rubidium generator 28. Thereafter, the dose rate rises at
`a rapid rate up to a maximum, after which the dose rate
`falls to a level value indicative of the steady state regen
`eration rate of the Sr-Rb generator 28. Thus, when the
`infusion starts, there is a delay initially as the dose rate
`builds up, a reduction in dosage after the generator 28 is
`55
`partially eluted, and then there is a dosage representa
`tive of the steady state regeneration rate of the genera
`tor 28.
`The setting of the dose rate thumbwheel switches 102
`tells the dosimetry controller 62 at what point along the
`60
`upward slope of the dosage curve to switch the diverter
`valve 32 from the waste position to the patient 56 posi
`tion whereby the eluate will be infused into the patient
`56. At that point the dose indicated by the LED's 100
`will start accumulating from zero, where it had been
`65
`until that point. Similarly, the patient 56 volume indi
`cated by the LED's 96 will start to accumulate as of that
`time.
`
`Where,
`A=total activity (in millicuries);
`C=net counts (from probe);
`F= the flow rate; and
`K= the calibration factor.
`As noted, the calibration factor, K, takes into account
`the volume in the detector's view, the net efficiency of
`the probe, the conversion factor in terms of disintigra
`tions per minute to milliCuries, and the net yield of
`photons. These factors are substantially constant for
`any given probe and tubing combination for a reason
`able amount of time. Accordingly, provision is made on
`the circuit board to adjust the calibration factor, K,
`when the instrument is serviced. However, the calibra
`tion factor, K, is not user adjustable in the normal
`course of operation.
`DOSMETRY PROBE
`Referring now to FIG. 5, the dosimetry probe 58 is
`comprised of a photomultiplier tube 120, such as the
`
`Where,
`A=total activity (mCi);
`C=net counts;
`F=flow rate (ml/min);
`V= volume in detector view (ml);
`E=net efficiency (counts per minute/disintegration
`per minute);
`CM=disintegrations/minute to millicurie conver
`sion factor; and p1 Y=net yield of photon.
`In the case of the present invention, the above for
`mula can be simplified to:
`
`50
`
`

`

`
`
`4,585,009
`8
`7
`or other suitable very high speed comparator, must be
`RCA C83009E 14 mm diameter 10-stage photomulti
`plier tube manufactured by the Electro Optics Division
`used.
`A biasing network 141 consisting of a series of resis
`of RCA Corporation in Lancaster, Pa. The photomulti
`tors and capacitors is used as one input to the compara
`plier tube 120 has a face 122 through which input sig
`tor 142. In view of the fact that the pulses which are
`nais in the form of light are received. On the face 122, a
`handled by the comparator 142 are of very short dura
`plastic scintillator 124, such as a Nuclear Enterprises
`tion, a one-shot circuit 144, comprised in the preferred
`Type 102A manufactured in Edinburgh, Scotland, is
`embodiment of the invention, of a Motorola Type 1670
`mounted. In the preferred embodiment of the invention,
`master-slave flip-flop integrated circuit, is used to
`the plastic scintiliator 124 is glued or bonded to the face
`stretch the pulse width up to a uniform pulse width of
`22 of the photomultiplier tube 120. After the plastic
`approximately 50 nanoseconds. The output signal from
`scintillator 124 has been bonded to the face 122 of the
`the one-shot 144 is fed into a programmable divide-by
`photomultiplier tube 120, an aluminum foil covering
`N circuit 146, which in the preferred embodiment of the
`(not shown) is placed over the face end of the photo
`invention is comprised of a Motorola Type 10136 uni
`multiplier tube 120, including the plastic scintillator 124.
`versal hexadecimal counter integrated circuit. The di
`15
`The purpose of the aluminum foil covering is to reflect
`vide-by-N circuit 146 is programmable. Accordingly, a
`back into the tube 120 any light which scintillates from
`very high pulse repetition rate coming into the compar
`the plastic scintillator 124 away from the tube 120. In
`ator with very short pulse widths is reformed by the
`addition, the aluminum foil covering prevents any stray
`one-shot to have wider, uniform pulses, and the input
`light which might come into the area of the face 122
`signal is further reformed by the divide-by-N circuit to
`20
`from getting into the tube 120. Following the applica
`bring the pulse repetition rate down into any desirable
`tion of the aluminum foil, a light tight material, such as
`range. In particular, outputs of the divide-by-N circuit
`black electrical tape is wrapped over the aluminum foil
`146 are provided for N equal to 2, 4, 8, and 16.
`covered tube 120 in order to further prevent any light
`Up through this point in the circuit, the devices have
`from entering into the tube 120. The tape-wrapped tube
`all been of ECL type in order to be able to handle the
`25
`120 is then inserted into a nu metal shield 126 which is
`very high speed pulses which are detected by the do
`intended to prevent any electromagnetic radiation ef
`simetry probe 58. In view of the fact that it is conven
`fects from affecting the output of the dosimetry probe
`tional to use transistor-transistor-logic (TTL) integrated
`58. In the preferred embodiment of the invention, the
`circuits, a type 10125 ECL-to-TTL level converter
`dosimetry probe 58 is plugged into a standard photo
`circuit 150 is hooked to the output of the divide-by-N
`multiplier tube socket base 128 containing a standard
`circuit 146. Thus, the ECL-to-TTL level converter
`resistive biasing network.
`circuit 150 transforms the ECL signal levels into TTL
`signal levels for further processing. The TTL outputs
`DOSMETRY CIRCUITRY
`leave the ECL-to-TTL level converter circuit 150 on
`Referring now to FIG. 6, the photomultiplier tube
`four lines 152, 154, 156, 158, which correspond to the
`35
`socket base 128 includes a resistive network containing
`TTL level of the counts into the Single Channel Analy
`biasing resistors for placing appropriate bias voltages on
`zer divided by 2, 4, 8, and 16, respectively. The counts
`the ten dynodes in the photomultiplier tube 120. Ac
`out on the lines 152-158 will be referred to hereafter as
`cordingly, the high voltage connection to the photo
`the 'net counts'.
`multiplier tube base 128 is automatically biased to pro
`40
`vide appropriate operating voltages to the photomulti
`MULTIPLER-DIVIDER, CIRCUIT
`plier tube 120. The high voltage supply 130 used in the
`Referring now to FIG. 8, there is a Multiplier
`preferred embodiment of the invention is a 0-1000 volt,
`Divider circuit 160 which converts the net counts from
`adjustable Bertan PMT-10A-P power supply manufac
`the Single Channel Analyzer circuit, described above,
`tured by Bertan Associates, Inc., Three Aerial Way,
`into a meaningful quantity (milliCuries). The Multiplier
`Syosset, N.Y. In the present application, the high volt
`Divider circuit 160 accepts the "net counts' on an input
`age supply 130 is adjusted to provide an output voltage
`line 162 which is connected to one of the lines 152-158
`of 950 volts. The photomultiplier tube socket base 128 is
`from the Single Channel Analyzer (i.e., the raw counts
`an RCA photomultiplier tube socket base, Part No.
`converted into TTL levels and then divided by 2, 4, 8,
`AJ2273.
`or 16) and multiplies them by the eluate Flow Rate
`50
`An output signal goes from the dosimetry probe 58
`divided by 100. The result is then divided by a constant,
`on a line 132 to a coupling network comprising a pull up
`K, in order to carry out the formula:
`resistor 134, a coupling capacitor 136, and a output
`resistor 138. Accordingly, an AC signal having a peak
`to peak maximum of approximately 250 millivolts with
`55
`negative going pulses, is provided on output line 140.
`SINGLE CHANNEL ANALYZER
`Referring now to FIG. 7, the schematic diagram for
`a Single Channel Analyzer circuit is shown. The Single
`Channel Analyzer is used, because the pulses on output
`line 140 from the Dosimetry circuitry are very sharply
`defined pulses which may occur at very high frequen
`
`Where,
`A = total activity (in millicuries);
`N = net counts (from Single Channel Analyzer);
`F=Flow Rate; and
`K=the calibration factor.
`The net counts, N, are first multiplied by a two digit
`number corresponding to the eluate Flow Rate (entered
`on the Flow Rate thumbwheel switches 112A, 1.12B,
`
`10
`
`60
`
`

`

`15
`
`4,585,009
`10
`9
`Synchronous Decade Rate Multiplier circuits (F74167),
`diverter valve 32, through the valve driver circuit
`and sending their outputs through a NAND gate 168.
`which will be explained hereinafter. The Patient Vol
`The resulting output corresponds to Fout, where:
`ume can also be preset, and the infusion pump can be
`stopped at the preset limit.
`DOSE RATE CIRCUIT
`The Dose Rate circuit 200, shown in FIG. 10, pro
`vides a visual display of the amount of radiation present
`in the eluate. The Dose Rate circuit 200 employs a
`Display Controller Circuit, of the type described above.
`The Dose Rate display is constantly updated to provide
`the user with Dose Rate information. The Dose Rate
`circuit 200, with the Display Controller, is programmed
`to set a trigger level for switching the eluate from waste
`to the patient 56.
`The Dose Rate circuit 200 uses signals from the Mul
`tiplier-Divider circuit 160, described above, and from
`the Control Board which will be described hereinafter.
`The dose corrected output pulses on line 186 from the
`Multiplier-Divider circuit 160 described above (i.e., 1
`pulse/0.01/mCi) enter the Dose Rate circuit 200, and
`are double buffered by buffers 202, 204. The buffered
`pulses are then fed through one-half of a one-shot 206,
`comprised of a CD4098BE integrated circuit in the
`preferred embodiment of the invention. The output
`from the one-shot 206 is gated through NAND gate 207
`to the Dose Rate Display 104 since there are three
`Display Controller Circuits 190, which are used for
`Dose (circuit "A'). Dose Rate (circuit “B”), and Pa
`tient Volume (circuit "C"), the designation "B10" at the
`output of NAND gate 207 means pin 10 on input con
`nector 197 (see FIG. 9).
`The heart of the Dose Rate circuit 200 is an Intersil
`ICM7207A Oscillator Controller integrated circuit 208.
`This unit, along with a dual one-shot comprised of a
`CD4098BE integrated circuit 210, in the preferred em
`bodiment of the invention, provides all of the control
`necessary for gating, storing, and resetting the display.
`The outputs of the Dose Rate Display Controller
`Circuit provide an easy interface to determine when a
`predetermined count (corresponding to the dose rate
`which was set on thumbwheel switches 102) has been
`reached, and to generate a signal which is used for
`switching the diverter valve 32. The valve switching
`signal is also used to enable the Dose and Patient Vol
`ume Displays, 100, 96, respectively.
`In the preferred embodiment of the invention, the
`valve switching signal is derived from one half of a dual
`D-type flip-flop, such as a CD4013BE integrated circuit
`212. The flip-flop. 212 is only enabled during an injec
`tion, i.e., when the infusion pump is being used to either
`infuse eluate into a patient 56 or to divert it to waste.
`The enabling "INJECT" signal is generated when the
`pump is injecting. Once an injection is started and a user
`pre-set Dose Rate limit set on thumbwheel switches 102
`is met, the flip-flop. 212 latches a positive Q output to
`switch the diverter valve 32 from the waste position to
`the patient position and to enable the Dose Display and
`the Patient Volume Display.
`CONTROL CIRCUIT
`Referring now to FIG. 11, the schematic diagram of
`the Control circuit 220 is shown. The purpose of the
`Contro