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`"Precise rubidium-82 i11/11sio11 system for cardiac
`perft1sio11111easure111e11t using three-dime11sio11al
`positro11 emissio11 tomography"
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`Degree Date:
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`2005/M.A.Sc. Master of Applied Science
`University of Ottawa (Canada)
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`44-06M
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`NOTE TO USERS
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`ti
`mu
`u Ottawa
`uOttawa
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`L’U niversite canadieim e
`L'Universitc canadienne
`C a n ad a’s university
`Canada's university
`
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`FACULTE DES ETUDES SUPERIEURES
`FACULTE DES ETUDES SUPERIEURES
`ET POSTOCTORALES
`ET POSTOCTORALES
`
`l = = l
`U Ottawa
`uOttawa
`
`I .’U n iv e rsity c n n a riie n n e
`L'Universit('; c:mrntlicnnc
`C a n a r ia ’s u n iv e rs ity
`Cannrla's univ~r:rity
`
`FACULTY OF GRADUATE AND
`FACULTY OF GRADUATE AND
`POSDOCTORAL STUDIES
`POSDOCTORAL STUDIES
`
`Ran Klein
`Ran Klein
`AUTEUR DE LA THESE/ AUTHOR OF THESIS -
`
`M.A.Sc. (Electrical Engineering)
`M.A.Sc. (Electrical Engineering)
`- .................................
`
`-
`- · - ' - - - - - - - - - - - -
`GRADE/ DEGREE
`
`School of Information Technology and Engineering
`School o~ Information Technology and Engineering
`F^U LTiriCO LE7D fePA RT^
`FACuLWrs’CHOOLTDEPATfMENT
`.
`-------FA_C_U-LT=E,ECOLE,DEPARTEMENT/FACULTY.SCHOOL,DEPARTMENT
`
`Precise 82Rb Infusion System for Cardiac Perfusion Measurement Using 3D Positron Emission
`Precise 82Rb Infusion System for Cardiac Perfusion Measurement Using 3D Positron Emission
`Tomography
`Tomography
`
`TITRE DE LA THESE / TITLE OF THESIS
`TITRE DE LA THESE I TITLE OF THESIS
`
`A. Alder
`A. Alder
`D IR E C T E iT rW R E C T R T ceIdE LA fH ESE T THESIS SUPERVISOR
`DIRECTEUR (DIRECTRICE) DE LA THESE/ THESIS SUPERVISOR
`
`R.A. deKemp
`R.A. deKemp
`CO-DIRECTEUR (CO-DIRECTRICE) DE LA THESE-/c-=T=H=Es=1s:-;,c=o-""'su=p=ER=v=1s=oR=--------
`
`EXAMINATEURS (EXAMINATRICES) DE LA THESE / THESIS EXAMINERS
`EXAMINATEURS (EXAMINATRICES) DE LA THESE/ THESIS EXAMINERS
`
`A. Chan
`A. Chan
`
`S. Shirmohammadi
`S. Shirmohammadi
`
`Gary W. Slater
`Gary W. Slater
`'UeD OYEN DETA TA CU 7.TE"bEsTfu"D ES SUPiRIEURES’ET POSTDOCTORALES f
`LE DOYEN DE LA FACULTE DES ETUDES SUPERIEURES ET POSTDOCTORALES /
`DEAN OF THE FACULTY OF GRADUATE AND POSTDOCORAL STUDIES
`DEAN OF HIE FACULTY OF GRADUATE AND POSTDOCORAL STUDIES
`
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`PRECISE 82RB INFUSION SYSTEM FOR CARDIAC PERFUSION MEASUREMENT
`PRECISE 82RB INFUSION SYSTEM FOR CARDIAC PERFUSION MEASUREMENT
`USING 3D POSITRON EMISSION TOMOGRAPHY
`USING 3D POSITRON EMISSION TOMOGRAPHY
`
`by
`by
`
`Ran Klein B.A.Sc
`Ran Klein B.A.Sc
`
`A thesis submitted to the
`A thesis submitted to the
`
`Faculty of Graduate and Postdoctoral Studies
`Faculty of Graduate and Postdoctoral Studies
`
`in partial fulfillment o f the requirements for the degree of
`in partial fulfillment of the requirements for the degree of
`
`Master of Applied Science
`Master of Applied Science
`
`in Electrical and Computer Engineering
`in Electrical and Computer Engineering
`
`Ottawa-Carleton Institute for Electrical and Computer Engineering
`Ottawa-Carleton Institute for Electrical and Computer Engineering
`School of Information Technology and Engineering (Electrical & Computer Engineering)
`School oflnformation Technology and Engineering (Electrical & Computer Engineering)
`
`Faculty of Engineering
`Faculty of Engineering
`University of Ottawa
`University of Ottawa
`
`February, 2005
`February, 2005
`
`©2005, Ran Klein, Ottawa, Canada
`©2005, Ran Klein, Ottawa, Canada
`
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`ISBN: 978-0-494-14917-1
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`82Rb Elution System Control
`82Rb Elution System Control
`
`Ran Klein, University of Ottawa
`Ran Klein, University of Ottawa
`
`Credits
`Credits
`
`I wish to extend my gratitude to Robert deKemp and Andy Adler for guiding me
`I wish to extend my gratitude to Robert deKemp and Andy Adler for guiding me
`through this project. Their mentoring, support, and friendship have made this a memorable
`through this project. Their mentoring, support, and friendship have made this a memorable
`experience.
`expenence.
`
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`82Rb Elution System Control
`82Rb Elution System Control
`
`Ran Klein, University of Ottawa
`Ran Klein, University of Ottawa
`
`_________________________ Abstract_________________________
`Abstract
`Introduction: Quantitative myocardial perfusion measurements using positron
`Introduction: Quantitative myocardial perfusion measurements usmg positron
`emission tomography (PET) can be improved by introducing diagnostic tracers at a constant
`emission tomography (PET) can be improved by introducing diagnostic tracers at a constant
`S')
`S’?
`87
`rate of activity. 82Rb can be produced cost effectively by eluting a 82Sr/82Rb generator with
`rate of activity. Rb can be produced cost effectively by eluting a Sr/ Rb generator with
`saline; however, it exhibits an undesirable, but reproducible, activity rate variation.
`saline; however, it exhibits an undesirable, but reproducible, activity rate variation.
`Previously, a threshold-comparison algorithm controlled saline flow through either generator
`Previously, a threshold-comparison algorithm controlled saline flow through either generator
`or bypass line using an on/off valve, to simulate constant-activity elutions. Methods: hi this
`or bypass line using an on/off valve, to simulate constant-activity elutions. Methods: In this
`
`work a mechanical system and control software is developed to control tracer infusion. The work a mechanical system and control software is developed to control tracer infusion. The
`valve is cycled at 5Hz and its duty-cycle controlled by a predictive-corrective algorithm in
`valve is cycled at 5Hz and its duty-cycle controlled by a predictive-corrective algorithm in
`order to reduce measurable activity rate fluctuations. Results: Precision increases (RMS
`order to reduce measurable activity rate fluctuations. Results: Precision increases (RMS
`error improves from >40% to -14% ) as does the range of relative activities that can be eluted
`error improves from >40% to -14%) as does the range of relative activities that can be eluted
`from the generator. Conclusion: The proposed method demonstrates superior precision and
`from the generator. Conclusion: The proposed method demonstrates superior precision and
`flexibility. However, further tests must be conducted to ensure that the precision of the
`flexibility. However, further tests must be conducted to ensure that the precision of the
`system does not deteriorate over time.
`system does not deteriorate over time.
`
`87
`87
`Key Words: Rubidium-82, 82Sr/82Rb generator, cardiac, perfusion, positron emission
`Key Words: Rubidium-82, Sr/ Rb generator, cardiac, perfusion, positron emission
`tomography, PET, predictive control.
`tomography, PET, predictive control.
`
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`ii
`11
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`11 of 174
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`82Rb Elution System Control
`82Rb Elution System Control
`
`Ran Klein, University of Ottawa
`Ran Klein, University of Ottawa
`
`Table of Contents
`Table of Contents
`
`....................................................................................................................... ...................................................ii
`Credits
`Credits
`........................................................................................................................................................ 11
`...................................................................................................................... ..................................................iii
`Abstract
`Abstract
`••••••••••••••.••••••••••••••••••••••••••...•••••••••••••.••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••.•••••••••••••••••••••••••••• 111
`Table of Contents................................................................................................................ ..................................................iv
`Table of Contents ................................................................................................................................................. iv
`Table of Figures.................................................................................................................. ..................................................vi
`Table of Figures ................................................................................................................................................... vi
`Table of Tables.................................................................................................................... ................................................viii
`Table of Tables ................................................................................................................................................... viii
`List of Acronyms................................................................................................................. ..................................................ix
`List of Acronyms .................................................................................................................................................. ix
`List o f Variables.................................................................................................................. ................................................... X
`List of Variables .................................................................................................................................................... x
`Introduction
`...................................................................................................................... ...................................................1
`Introduction
`........................................................................................................................................................ 1
`Chapter 1:
`Introduction to Molecular Imaging and Dynamic PE T ...................... ...................................................4
`Chapter 1:
`Introduction to Molecular Imaging and Dynamic PET ................................................................... 4
`1.1 Positron Emission Tomography......................................................................... ...................................................4
`1.1 Positron Emission Tomography ................................................................................................................ 4
`82Sr/82Rb Generator - a Cost-effective Tracer Source .............................................................................. 7
`1.2 82Sr/82Rb Generator - a Cost-effective Tracer Source................................... ...................................................7
`1.2
`Sr Breakthrough......................................................................................................... ...................................................9
`Sr Breakthrough ............................................................................................................................................ 9
`82Rb Elution Profiles ............................................................................................................................... 10
`1.3 82Rb Elution Profiles............................................................................................ .................................................10
`1.3
`1.4 Constant-Activity Elution for Quantitative Perfusion Measurement in the Left Ventricle o f the H eart. 11
`1.4 Constant-Activity Elution for Quantitative Perfusion Measurement in the Left Ventricle of the Heart. 11
`1.5 Quantitative Perfusion Measurements Using 82Rb .................................................................................. 14
`1.5 Quantitative Perfusion Measurements Using R b........................................................................................... 14
`The Second Generation 82Rb Infuser - a starting point.. ............................................................... 16
`Chapter 2:
`The Second Generation 82Rb Infuser - a starting point...................... ................................................. 16
`Chapter 2:
`2.1 The Daily Protocol and Elution Types.............................................................. .................................................17
`2.1 The Daily Protocol and Elution Types .................................................................................................... 17
`2.2 Hardware Description............................................................................................................................................19
`2.2 Hardware Description ............................................................................................................................. 19
`2.3 Prototype Performance...........................................................................................................................................25
`2.3 Prototype Performance ............................................................................................................................ 25
`2.4 Further Development of the 82Rb Elution System (RbES) ...................................................................... 26
`2.4 Further Development of the 82Rb Elution System (RbES)..............................................................................26
`System Design and Conceptual Understanding.....................................................................................28
`Chapter 3:
`Chapter 3:
`System Design and Conceptual Understanding ............................................................................ 28
`3.1 Requirements........................................................................................................ .................................................28
`3.1 Requirements .......................................................................................................................................... 28
`Functional Requirements........................................................................................................................................... 28
`Functional Requirements ............................................................................................................................. 28
`Non-Functional Requirements...................................................................................................................................29
`Non-Functional Requirements ..................................................................................................................... 29
`Other Requirements.....................................................................................................................................................30
`Other Requirements ..................................................................................................................................... 30
`3.2
`Initial Design Considerations............................................................................. ..................................................32
`3.2
`Initial Design Considerations .................................................................................................................. 32
`Safety........................................................................................................................... ..................................................32
`Safety ........................................................................................................................................................... 32
`Process Monitoring......................................................................................................................................................33
`Process Monitoring ...................................................................................................................................... 33
`Hardware Modifications.............................................................................................................................................34
`Hardware Modifications .............................................................................................................................. 34
`Software packages.......................................................................................................................................................36
`Software packages ....................................................................................................................................... 36
`3.3 Flow Hardware Layout Justification...................................................................................................................39
`3.3 Flow Hardware Layout Justification ....................................................................................................... 39
`Pump Speed Variation................................................................................................................................................40
`Pump Speed Variation ................................................................................................................................. 40
`Bypass Ratio Control................................................................................................ ..................................................41
`Bypass Ratio Control. .................................................................................................................................. 41
`3.4 Design of Physical Processes............................................................................ ..................................................43
`3.4 Design of Physical Processes .................................................................................................................. 43
`Run sequence............................................................................................................. ..................................................44
`Run sequence ............................................................................................................................................... 44
`Calibration................................................................................................................. ..................................................45
`Calibration ................................................................................................................................................... 45
`Breakthrough Activity M easurement.................................................................... ..................................................50
`Breakthrough Activity Measurement .......................................................................................................... 50
`Elution Tests.................................................................................................................................................................52
`Elution Tests ................................................................................................................................................ 52
`3.5 Software Design................................................................................................... ..................................................53
`3.5 Software Design ...................................................................................................................................... 53
`Pre-Run Stage and the GUI-Sequence.................................................................. ..................................................53
`Pre-Run Stage and the GUI-Sequence ......................................................................................................... 53
`Post-Run Stage......................................................................................................... ..................................................55
`Post-Run Stage ............................................................................................................................................ 55
`Real-Time Sequence................................................................................................ ..................................................56
`Real-Time Sequence .................................................................................................................................... 56
`Physical Sequence.................................................................................................... ..................................................58
`Physical Sequence .........................................................................................................................