Date post: | 23-Jan-2017 |
Category: |
Documents |
Upload: | joshua-medford |
View: | 57 times |
Download: | 2 times |
Copyright © by Joshua Ryan Medford 2015
All Rights Reserved
EVALUATION OF GEM DETECTOR SIGNAL AMPLIFICATION
WITH RADIO-ISOTOPES F-18 AND Cu-64 FOR USE
OF PERITONEAL CARCINOMATOSIS II
TUMOR MAPPING
by
JOSHUA RYAN MEDFORD
Presented to the Faculty of the Honors College of
The University of Texas at Arlington in Partial Fulfillment
of the Requirements
for the Degree of
HONORS BACHELOR OF SCIENCE IN BIOLOGY
THE UNIVERSITY OF TEXAS AT ARLINGTON
December 2015
ACKNOWLEDGMENTS
First and foremost, I would like to give a special thanks to my fiancé for being so
patient and understanding during the course of my research while being pregnant and
then bringing our child into this world. I wouldn’t be here if it wasn’t for her sacrifices.
I am extremely grateful for Dr. Yu for giving a student, whose degree was biology
intended, a chance to be a part of his high energy physics research team. My knowledge
and appreciation for physics has grown exponentially over the past 18 months due to
being given the opportunity to be a part of his team. I would also like to thank Dr. Jin, a
professor of medical physics, who was patient with me while learning the physics of
medicine as he worked in collaboration with us. He taught me the importance of physics
in medicine and was always there to help me when needed. I would also like to thank Dr.
Frederick, who I first met in Biology 1441, for being a great mentor and being patient and
understanding with me as well due to my circumstances outside of the university. She
aided in my confidence as a scientist and a public speaker by ensuring that we properly
performed research that we later presented on. I would also like to thank many associates
of my research team. Dr. Sosebee, thank you for aiding me when I desperately needed
access to Garfield and being a great mentor as well. Garrett Brown, thank you for aiding
me with your knowledge in C++, you made life much easier for me. Ronald Musser,
thanks for your assistance in trying to understand the LabVIEW GUIs of SRS. Yvonne
Ng, thanks for sharing all your knowledge of GEM with me and spending countless hours
iii
doing research as we plundered into GEM detector science alone with little to no
knowledge or guidance but never surrendered.
November 20, 2015
iv
ABSTRACT
EVALUATION OF GEM DETECTOR SIGNAL AMPLIFICATION
WITH RADIO-ISOTOPES F-18 AND Cu-64 FOR USE
OF PERITONEAL CARCINOMATOSIS II
TUMOR MAPPING
Joshua Ryan Medford, B.S.
The University of Texas at Arlington, 2015
Faculty Mentors: Jaehoon Yu and Lee Ann Frederick
Peritoneal carcinomatosis (PC) is one of medicine’s most malignant cancers with
a very low 5 year survival rate due to the fact that it has a very high recurrence rate.
Even after highly toxic chemotherapy dosages and cytoreductive surgery, residual tumors
cause patients to relapse and eventually die. It has been shown that tumors display a
much higher uptake of glucose and copper and therefore F-18 and Cu-64 could be used as
reliable radiolabeled biomarkers. In this study, we pursue that the use of a gas electron
multiplier (GEM) detector for more accurate, precise, and complete mapping of all
malignant PC tumors loaded with these radiotracers. GEM detectors are composed of
Kapton foil, copper foil and filled with a gaseous ratio of 80:20 Argon and CO2.
Whenever charged particles from beta decays of F-18 and Cu-64 pass through the GEM
v
detector, they ionize the gas molecules that then create electron avalanches and generate a
detectable signal with position read-out; the location of the radiation source that
represents the tumor can be identified. Both Monte Carlo simulation of beta particles
(from F-18 and Cu-64) transportation in a GEM and a 4x4 cm double GEM detector,
detecting a radiation source that resembles the said biomarkers, are conducted to show
the principles of this new application of GEM for PC treatment. It is envisioned that the
effective imaging of residual PC tumors can lead to their complete destruction and
significantly lower the fatality.
vi
TABLE OF CONTENTS
ACKNOWLEDGMENTS......................................................................................... iii
ABSTRACT............................................................................................................... v
LIST OF ILLUSTRATIONS..................................................................................... ix
Chapter
1. INTRODUCTION.................................................................................... 1
1.1 Nuclear Imaging.................................................................................. 1
1.2 Peritoneal Cancer................................................................................ 1
1.3 Radio-labeling..................................................................................... 3
1.4 The Gas Electron Multiplier............................................................... 4
1.5 GEM Detectors................................................................................... 5
2. METHODS AND MATERIALS.................................................................. 8
2.1 Garfield Simulation............................................................................. 8
2.2 GEM Detector Prototype Development.............................................. 9
2.3 Data Acquisition................................................................................. 12
3. RESULTS...................................................................................................... 13
3.1 Garfield............................................................................................... 13
3.2 Prototype Development....................................................................... 21
3.3 SRS Data Analysis.............................................................................. 24
vii
4. DISCUSSION................................................................................................ 27
5. CONCLUSION............................................................................................... 29
REFERENCES.......................................................................................................... 31
BIOGRAPHICAL INFORMATION......................................................................... 32
viii
LIST OF ILLUSTRATIONS
Figure Page
1.1 Axial view of the abdominal cavity with the peritoneum outlinedin blue............................................................................................................. 3
1.2 Microscopic view of a GEM foil................................................................... 5
1.3 Electric field produced by a GEM foil when voltage is applied.................... 6
2.1 (Left) Resistors in parallel; (right) resistors in series..................................... 10
2.2 Voltage checkpoints in the prototype GEM detector..................................... 10
2.3 Schematic of double GEM detector prototype regions.................................. 11
3.1 Energy loss (left) and electron production (right) of the major beta kinetic energy from Cu-64 beta decay........................................................... 14
3.2 Energy loss (left) and electron production (right) of the average beta kinetic energy from Cu-64 beta decay........................................................... 14
3.3 Energy loss (left) and electron production (right) of the major positron kinetic energy from Cu-64 beta decay........................................................... 15
3.4 Energy loss (left) and electron production (right) of the average positron kinetic energy from Cu-64 beta decay........................................................... 15
3.5 Energy loss (left) and electron production (right) of the major positron kinetic energy from F-18 beta decay............................................................. 16
3.6 Energy loss (left) and electron production (right) of the average positron kinetic energy from F-18 beta decay.............................................................. . 16
3.7 Energy loss (left) and electron production (right) of the major beta kinetic energy from Cs-137 beta decay......................................................... 17
3.8 Energy loss (left) and electron production (right) of the average beta kinetic energy from Cs-137 beta decay......................................................... 17
ix
3.9 Energy loss (left) and electron production (right) of the major positron kinetic energy from Cs-137 beta decay......................................................... 18
3.10 Energy loss (left) and electron production (right) of the average positron kinetic energy from Cs-137 beta decay......................................................... 18
3.11 Electron avalanche produced with the 25 electrons ionized from an incident particle. The orange lines represent electron drift lines and the blue lines represent ion drift lines. The upper and lower metals are blue with the Kapton green in color......................................................... 20
3.12 (Top left) Number of electrons produced per electron; (top right) number of ions produced per electron; (bottom left) location of electrons on plastic; (bottom right) location of ions on plastic...................... 21
3.13 Finished construction of the double GEM prototype detector....................... 22
3.14 Trigger from signal generation with no discrepancies................................... 23
3.15 Trigger from signal generation with minor discrepancies............................. 23
3.16 Trigger from signal generation with major discrepancies............................. 24
3.17 Modified signal input connection of prototype GEM detectorfor SRS analysis............................................................................................. 25
3.18 Cs-137 beta decay signal amplification over 12 seconds.............................. 25
3.19 (Top left) Waveform graph of signal input; (top right) fitted waveform graph of signal input; (bottom left) intensity graph of signal input; (bottom right) channel amplitude from signal input...................................... 26
x
CHAPTER 1
INTRODUCTION
1.1 Nuclear Imaging
Nuclear imaging is an important factor in the field of oncology. It provides a
means to determine whether a medical procedure has been fully effective. In oncology,
nuclear imaging, such as MRIs and PET scans, also plays a vital role in the detection of
tumors. They map radio-labeled tumors by detecting gamma pairs emitted from positron
annihilation. Although effective, the imaging resolution may not be sufficiently fine
and thus sometimes tumors are missed. If a tumor is not fully eradicated or too small to
detect, a patient can go into relapse with even more severe symptoms. This is often the
case with the peritoneal carcinomatosis (PC).
1.2 Peritoneal Carcinomatosis
PC is a secondary cancer in which tumors metastasize from other organs into the
peritoneum. There are two types of PC. The secondary PC (PC II) is the most common
form, and it develops from other cancer types in the abdomen or cervix (ovarian, gastric,
colorectal, etc.) that have metastasized into the peritoneum [1]. Doctors are often
unaware of these metastasized tumors in the peritoneum due to their small sizes and that
the symptoms of PC II often take longer to appear. The rarer, primary form of this cancer
usually begins in the peritoneum itself and is often linked to women who are known to be
at risk for ovarian cancer [1]. Once chemotherapy or radiation therapy is complete after a
surgical removal of the tumor, the patient must be scanned for residual tumor cells.
1
Residual tumor cells, however, are often missed due to their small sizes and lack
of detecting technology. About 35% of gastrointestinal patients suffer from secondary
PC. Those diagnosed with PC II have, on average, a 30% chance of a five-year survival
rate and those who are treated have a 32% chance [2]. Currently there are two ways this
form of cancer is treated, cytoreductive surgery and hyperthermic intraperitoneal
chemotherapy (HIPEC). The use of cytoreductive surgery and HIPEC slightly increases
the survival rate of patients but HIPEC is extremely toxic itself, causing a significant side
effect after the treatment [2].
PC II is usually scored by the peritoneal carcinomatosis index (PCI) and is based
on 13 different regions in the abdomen and the size of the tumor. Tumor sizes range
from less than 0.5 cm to larger than 5.0 cm and are broken into categories that give lesion
scores from 0 to 3. The score range is designated as follows; a score of 0 for no lesion in
that region, a score of 1 for lesions less than 0.5 cm, a score of 2 for lesions up to 5.0 cm
and finally, a score of 3 for lesions larger than 5.0 cm [3]. When tumor size score is
numerically added to the designated region numbers of the abdomen, 0-12, and then
added together, the scores result in a range from 0-39. The survival rate is then
determined by the score given to the patient; e.g. colon cancer patients suffering from
carcinomatosis that have a score range from 11-20 roughly means a 20% five-year
survival rate compared to that of a patient with a score of ten or less who has a five-year
survival rate of 50% [3].
2
The peritoneum itself is very thin, with a thickness of only one to two cells. It is
categorized by two separate sections; the parietal and visceral peritoneum. For the sake
of this study and due to how PCII is treated with HIPEC, only the properties of the
parietal peritoneum will be taken into account for data analysis. The parietal peritoneum
is a smooth transport membrane that forms the lining of the abdominal cavity and the
organs within (Figure 1.1). It serves as a conduit for blood vessels, lymph vessels and
nerves. The peritoneum lies underneath the skin, subcutaneous adipose tissue and rectus
abdominis muscles at an average depth of 2.7-3.7cm [4, 5].
Figure 1.1: Axial view of the abdominal cavity with the peritoneum outlined in blue
1.3 Radio-labeling
3
Positron emission tomography (PET) currently produces images by detecting
511KeV gamma pairs emitted from positron annihilation of positron emitters.
Radiopharmaceuticals, such as fluorodeoxyglucose (FDG), are biologically active
molecules (glucose) that are tagged with radio-isotopes (F-18). FDG is an FDA approved
tracer due to the nature of tumors having a high affinity and absorption rate of glucose in
order to support its rapid growth rate. The isotope F-18 has a half-life of 110 minutes and
97% positron emission rate, making it an optimal for human ingestion and nuclear
imaging [6].
Other radiopharmaceuticals have been explored for the use of nuclear imaging
due to similar beta decay properties. The radio-isotope Cu-64 also creates indirect
gamma pairs that can be detected with nuclear imaging devices [7]. Cu is naturally taken
in by cells for cell proliferation and tumor cells exhibit a high intake of Cu-64 in order to
maintain a rapid growth rate. Cu-64 has a half-life of 12.7 hours and beta decay rate of
39% and positron emission rate of 17.9%. Cu-64 can be produced using desktop reactors,
compared F-18 whose production needs a cyclotron.
Both F-18 and Cu-64 can be label with radiotracers that specifically target
peritoneal tumors. During the surgery, in a close range small tumors can be detected by
portable radiation detectors, such as Gas Electron Multiplier (GEM) detectors, and thus
make a complete removal of residual tumors possible.
1.4 The Gas Electron Multiplier
4
A new method for radioactive particle detection has been introduced to the field
of physics. Instead of mapping tracers by detecting indirect gamma pair production, this
tool, the gas electron multiplier (GEM) foil, can instead directly detect the beta particle
through amplification. The GEM foil was created at CERN by Fabio Sauli in 1996 [8].
It is composed of three layers; two metal layers, usually copper, on the top and the
bottom of an acid etched Kapton foil with perforated holes (Figure 1.2). The metal layers
are typically 5µm thick with holes that are 70µm in diameter and the Kapton foil is 50µm
thick with the hole pitch 140µm and diameter 50µm [8]. The GEM foil has been
modified to these dimensions to allow for the most optimal electric field when voltage is
applied.
Figure 1.2: Microscopic view of a GEM foil
1.5 GEM Detectors
5
The GEM detector technology is used in many fields of detection of radiation
from high energy particle physics to medical physics. The significance of the GEM is its
ability to amplify a signal detected through the use of the ionization electrons. As a
charged particle enters the GEM detector it ionizes the gaseous mixture (usually 80:20 of
Argon and CO2) creating a cluster of electrons that are drawn to the electric field created
by the GEM foils through the applied voltage and accelerate the electrons through the
high electric field, causing an avalanche of electrons (Figure 1.3) [8]. These electrons are
then guided to a readout chip that produces a signal that can be recorded and
reconstructed through various imaging software.
6
Figure 1.3: Electric field produced by a GEM foil when voltage is applied
The high rate of relapse for secondary PC patients experience is the primary
cause of the low five year survival rate. The existing PET, MRI and SPECT scanners
does not have sufficiently fine image resolution and are too far away from the patient,
due to their sizes, to detect the particles irradiating from the radio markers in the tumors
[2]. Therefore, a compact, portable device that could be used at the sight of treatment
and in a closer range than that of the existing medical imaging devices would significant
7
improve the rate of detection of the residual tumors and help irradiating them. A gas
electron multiplier (GEM) detector [8, 9] is highly efficient and can detect the faintest
radiation signals emitted from radiolabeled tumors of all sizes, thanks to the flexibility of
the GEM detector to be easily modified and high signal amplification capability.
In this study, various steps will be taken in order justify the use of a GEM
detector in the field of oncology. In order to study for the detector parameters such as
gain, various types of software are used to simulate the performance of the GEM
detector. In particular, the simulation software known as Garfield, studies events such as
charged particle interaction in GEM detectors and will be used to analyze the ionization
properties of Cu-64, F-18 and Cs-137. Cs-137 will be the radioactive source used in this
study due to its longer half-life and similar properties to that of F-18 and Cu-64. Garfield
will determine if the ionization properties are similar amongst these radioisotopes in
order to conduct further studies and will also determine if beta decay from these isotopes
are sufficient enough to generate a signal. Once verified, development of a double GEM
detector will commence followed by source runs to determine detector functionality and
perform data analysis. Data analysis will be performed by the Scalable Readout System
(SRS). SRS will measure signal amplification generated by the incident particle.
8
CHAPTER 2
METHODS AND MATERIALS
2.1 Garfield
Garfield is a computer simulation program that generates detailed two- and three-
dimensional drift chambers. It allows for the interface of programs that solve for separate
components that make up a GEM detector. It pulls from the libraries of programs such as
Heed and Magboltz that compute ionization in gaseous fields and also computes files
generated from field solvers, such as ANSYS and Elmer, in order to produce accurate
simulations of real time events. Garfield calls for the Monte Carlo simulation method in
order to produce the most probable events.
In this study, Garfield will be used to generate two different simulations. The
first simulation will identify the most probable value of electrons produced and energy
loss/transferred within a simulated drift chamber of the prototype by each different
kinetic energy of Cu-64, F-18 and Cs-137 and their beta decays. This is referred to as
charged particle ionization. After this data is collected, the average of the most probable
values for each radio-isotope in electron production will be implemented into a
simulation that generates a GEM with an applied electric field. This will verify that the
electron production is enough to produce an electron avalanche that will in turn lead to
signal generation. It will also provide extra information such as ion and electron
production, electrons lost on Kapton (plastic) and metal (copper), and ions lost on
Kapton.
9
2.2 GEM Detector Prototype Development
Before construction of the detector itself, voltage must be applied across the two
GEM foils to check for the quality of the foil, including shorts across the foil. This shall
be done by taking a power cord that has been preassembled with two alligator clips that
have been wrapped in copper taping around the teeth, and attaching one clip to a
soldering point on one GEM foil and the other to a soldering point on the other GEM foil.
Then, a connection must be made between the GEM foils through the remaining
soldering points. Once this is done, a voltage range of 0-200V can be applied and
verified by measuring the current flowing across the two different soldering points of the
GEM foils. Current drops down exponentially to the value close to 0A if the quality of
the foil is good. Once the current check has been verified and the quality of the GEM foil
is assured, assembly of the detector can begin.
The GEM foils and cathode will be installed in a pre-constructed casing
consisting of resistors, gas tubing and a readout chip (anode). Ten resistors are laid in a
series while five resistors are in parallel; these serve as a connection point for the cathode
and the two GEM foils. The ten resistors laid in a series, from the high voltage port to
the anode, have the following values; 5MΩ, 10 MΩ, 5 MΩ, 10 MΩ, 5 MΩ, 10 MΩ,
5MΩ, 10MΩ, 10MΩ and 5MΩ (Figure 2.1). The resistors, which serve as a connection
point for the cathode and the GEM foils, each measure 5MΩ and are protected from the
casing by plastic tubing that has been cut to allow for soldering (Figure 2.1). The readout
chip outputs signal via a BNC coax port. Teflon spacers, that are 1mm thick, must be
modified to properly fit into the detector in order to server as the drift, transfer and
10
induction regions. After soldering the cathode and the GEM foils to their respective
attachment points, voltage must be applied again to verify the integrity of the circuit.
Figure 2.1: (Left) Resistors in parallel; (right) resistors in series
To do this, connect a high voltage cable is connected to the high voltage port and
a range of voltages is applied from 0-200V. The checkpoints, to ensure voltage is being
applied, are at the base of each connection point, the anode, and the connection points on
the foils and cathodes (Figure 2.2). At each checkpoint there should be a difference in
voltage from that is being applied and this pattern should apply to all voltages applied.
The anode should measure 0V.
Figure 2.2: Voltage checkpoints in the prototype GEM detector
11
Once verified, two Teflon spacers will be placed at the bottom of the detector on
top of the anode (induction gap), followed by laying down the GEM foil that is closest to
the anode. Then another spacer (transfer gap) will be placed on top of GEM 1 followed
by laying down the second GEM foil on top of that spacer. Then, five spacers (drift gap)
will be placed on top of GEM 2 followed by laying down the cathode on top of them.
The layout of the chamber should mirror the schematic in Figure 2.3 with a 5:1:2; from
the drift region, to the transfer region and the induction region. One piece of Kapton will
be cut 1mm greater than the chamber and then placed over and secured with Kapton tape.
After this is complete, the top of the casing can be secured.
Figure 2.3: Schematic of double GEM detector prototype regions
The system must now be checked higher voltage integrity as well as for gas leaks.
1900V must be applied to ensure the system will operate correctly. Two gas tubes, one
for input and the other for output, must be inserted to their respective ports and adjusted
to a rate that indicates gas is flowing in and out. The detector will then be submerged
12
into a container filled with ethyl alcohol to observe for leaks. After this check is
performed, the detector must sit for one day in order to have adequate time to dry. Once
configuration of the prototype is complete, source runs must be performed in order to
verify that the GEM detector is working properly.
The radioactive source that will be used to verify if the detector is working
properly is Cs-137. The setup consists of a 600 MHz LeCroy oscilloscope, an amplifier,
a power source (for the amplifier), a gaseous connection that supplies an 80:20 of argon
and CO2, high voltage power supply, a collimator and the GEM detector prototype. Two
runs will be performed; one with the amplifier and one without.
2.3 Scalable Readout System
The scalable readout system (SRS) was developed by the RD51 group at CERN
as a complete readout system for gaseous electron multiplier (GEM) detectors. SRS
provides conventional situations by providing a choice of ASICs, APV25 hybrids, digital
readout and more that are then connected to a customizable DAQ system. GEM
detectors transmit data through an APV25 hybrid chip that consists of 128 channels. This
data is then converted from analog to digital and displayed through the interface of
LabVIEW programs. The prototype will only use one of the 128 channels the APV25
chip due to the simplicity of the readout chip and will therefore have to be modified by
hard wiring a coax cable to the Panasonic pin connector on the APV25 master chip.
After modification, a signal generator will be connected to the APV25 chip to verify
which channel has been connected. After channel verification, this hardware and
LabVIEW will produce fine and precise analyses of Cs-137 beta decay patterns from the
readout chip of the detector.
13
CHAPTER 3
RESULTS
3.1 Garfield
Ten separate simulations with 10,000 entries each were generated and fitted to
find the most probable value (MPV) to reflect the precise and accurate ionization patterns
of Cu-64, F-18 and Cs-137 and their respective beta decay kinetic energies. The major
beta of Cu-64, 578 KeV, produced 20 electrons and lost 547 eV of energy (Figure 3.1).
The average beta of Cu-64, 190 KeV, produced 32 electrons and lost 681 eV of energy
(Figure 3.2). The major positron of Cu-64, 653 KeV, produced 20 electrons and lost 527
eV of energy (Figure 3.3). The average positron of Cu-64, 278 KeV, produced 27
electrons and lost 663 eV in energy (Figure 3.4). The major positron of F-18, 633 KeV,
produced 20 electrons and lost 594 eV in energy (Figure 3.5). The average positron of F-
18, 250 KeV, produced 28 electrons and lost 537 eV in energy (Figure 3.6). The major
beta of Cs-137, 512 KeV, produced 21 electrons and lost 523 eV in energy (Figure 3.7).
The average beta of Cs-137, 157 KeV, produced 36 electrons and lost 697 eV in energy
(Figure 3.8). The major positron of Cs-137, 1,173 KeV, produced 19 electrons and lost
567 eV in energy (Figure 3.9). The average positron of Cs-137, 415 KeV, produced 27
electrons and lost 574 eV in energy (Figure 3.10). The averages of electron production
within the simulated drift chamber were 24.75, 24 and 25.75 electrons for Cu-64, F-18
and Cs-137, respectively. The averages of energy lost/transferred within the simulated
14
drift chamber of the detector were 604.5 eV, 565.5 eV, and 590.25 eV for Cu-64, F-18
and Cs-137, respectively.
Figure 3.1: Energy loss (left) and electron production (right) of the major beta kinetic energy from Cu-64 beta decay
Figure 3.2: Energy loss (left) and electron production (right) of the average beta kinetic energy from Cu-64 beta decay
15
Figure 3.3: Energy loss (left) and electron production (right) of the major positron kinetic energy from Cu-64 beta decay
Figure 3.4: Energy loss (left) and electron production (right) of the average positron kinetic energy from Cu-64 beta decay
16
Figure 3.5: Energy loss (left) and electron production (right) of the major positron kinetic energy from F-18 beta decay
Figure 3.6: Energy loss (left) and electron production (right) of the average positron kinetic energy from F-18 beta decay
17
Figure 3.7: Energy loss (left) and electron production (right) of the major beta kinetic energy from Cs-137 beta decay
Figure 3.8: Energy loss (left) and electron production (right) of the average beta kinetic energy from Cs-137 beta decay
18
Figure 3.9: Energy loss (left) and electron production (right) of the major positron kinetic energy from Cs-137 beta decay
Figure 3.10: Energy loss (left) and electron production (right) of the average positron kinetic energy from Cs-137 beta decay
19
As a result from the previous simulations, the number of entries for the GEM
simulation mirrored the average of electrons produced from all three radio-isotopes, 25.
Due to poor histogram fitting, the mean values were recorded in order to analyze the data
any further. The simulation also produced a detailed image of the avalanche created by a
charged GEM foil (Figure 3.11). For each single electron, of the 25 electrons generated
from the incident particle, an additional 10.6 electrons were created during the
development of an electron avalanche (Figure 3.12). For each electron, of the 25
electrons, an additional 9.92 ions were created when the process of an electron avalanche
was developing (Figure 3.12). “Avalanche Monte Carlo” calculated that 0% of the
electrons would be lost on the upper metal of the GEM foil, 13.19% would be lost on
plastic (Kapton), 42.12% would be lost on the lower metal, 43.59% would transfer and
1.099% are uncategorized. The histogram produced also portrays the average location in
which electrons and ions were lost on the Kapton (Figure 3.12).
20
Figure 3.11: Electron avalanche produced with the 25 electrons ionized from an incident particle. The orange lines represent electron drift lines and the blue lines represent ion drift lines. The upper and lower metals are blue with the Kapton green in color
Figure 3.12: (Top left) Number of electrons produced per electron; (top right) number of ions produced per electron; (bottom left) location of electrons on plastic; (bottom right) location of ions on plastic
21
3.2 Prototype Development
The GEM foils used in the prototype were successfully verified for continuity
when 200V were applied. After installation of the GEM foils and cathode to their
respective soldering points, the second voltage check was performed at the necessary
checkpoints. There was a consistent pattern of voltage drop-offs from the input value for
checkpoints at the base of the connection points for the cathode and GEM foils when
applying 49 and 99V. At the cathode, there was a 10% drop-off, a 54% drop-off at GEM
1 and a 22% drop-off at GEM 2 and the anode measured 0V. At the checkpoints where
the foils and cathode are connected to their soldering points, the voltage drop-offs of 49
and 99V were different by 2-5%. The voltage drop-offs from a 49V were 39% at the
cathode, 57% at GEM 1 and 88% at GEM 2. When applying 99V, the drop-offs were
37% at the cathode, 55% at GEM 1 and 86% at GEM 2. After construction of the GEM
detector was complete, the high voltage and the gas leak integrity checks were performed
with no discrepancies (Figure 3.13).
3.13: Finished construction of the double GEM prototype detector
22
The source run performed when the setup consisted of the amplifier resulted in
too much noise production and therefore was determined obsolete for verification of
GEM detector functionality. The source run performed without the amplifier allowed for
single trigger isolation. Three types of signals were observed and recorded for further
analysis; one with no discrepancies (Figure 3.14), one with minor discrepancies (Figure
3.15) and one with major discrepancies (Figure 3.16). It was also noted that the time
between triggers increased during the study.
Figure 3.14: Trigger from signal generation with no discrepancies
23
Figure 3.15: Trigger from signal generation with minor discrepancies
Figure 3.16: Trigger from signal generation with major discrepancies
3.3 SRS Data Analysis
24
Modifications for the coax cable of the GEM detector to the Panasonic pin
connector of the APV25 proved successful (Figure 3.17) due to the signal generator
properly identifying the channel selected (41 of 128). Before analysis of Cs-137 signal
amplification, analysis of noise was performed over a time period of 96 seconds. These
values were averaged their respective time slots (1-12 seconds) in order to establish error
for signal input. The signal was analyzed in a 12 second window with a peak amplitude
value of 1150 at five seconds (Figure 3.18). This was verified when extrapolating data
from four different analytical graphs with identical values (Figure 3.19).
Figure 3.17: Modified signal input connection of prototype GEM detector for SRS analysis
25
Figure 3.18: Cs-137 beta decay signal amplification over 12 seconds
Figure 3.19: (Top left) Waveform graph of signal input; (top right) fitted waveform graph of signal input; (bottom left) intensity graph of signal input; (bottom right) channel amplitude from signal input
26
CHAPTER 4
DISCUSSION
Based on the collaborated results provided by the simulation software Garfield
and the signal amplification analysis of SRS, we can conclude that the particles emitted
by beta decay of both Cu-64 and F-18 generate enough electron-ion pairs to produce a
detectable signal. The simulation results mirrored that of previously conducted studies
that measured the minimum required energy for the ionization of argon and carbon
dioxide gas. The minimum ionization energy for argon is 15.7 eV and 13.7 eV for
carbon dioxide [11]. The lowest particle energies for F-18 and Cu-64 are 250 KeV and
190 KeV, respectively. It was also noted that as the kinetic energy of the radioactive
particle decreased, the greater the electron-ion pair production. This could be due to the
increase of molecule interactions as the speed of the particle decreases; this was also
reflected in the in energy loss. As the kinetic energy of the particle decreased, the energy
loss/transfer increased.
The source runs performed with the oscilloscope in order to verify functionality
of the GEM detector indicated mixed results. The results that indicated good signal
amplification occurred more often than that of either the minor or major discrepancies.
The minor discrepancies indicated issues with the oscilloscope cutting off the top of the
signal received from the detector. The major discrepancies, which rarely occurred, could
be indications of noise, multiple signals read in close proximity, or malfunctions with the
oscilloscope.
27
The amplification results of SRS implied that signal was being generated but with
lack of knowledge on how to properly calibrate the system, the values could be off by a
greater margin than implied by the error bars (noise) in figure 3.18. Even though the
noise was evaluated before detector interface, it is not a viable method of calibration.
The signal being detected from the GEM detector through the SRS graphical user
interface (GUI) was not detected as an actual data event but as increased noise through
the channel. This is not only due to the lack of knowledge for applying calibration but
also due to being unable to properly setup a trigger. The setup did not consist of an
external trigger and therefore, during data acquisition, it had to be manually triggered by
starting and stopping data analysis repeatedly until an amplified signal was observed.
28
CHAPTER 5
CONCLUSION
While the results implied that particles emitted from the beta decay of both F-18
and Cu-64 produce enough electron-ion pairs for signal amplification, these particles do
not possess enough kinetic energy to travel through the layers of tissue from the
epidermis to the peritoneum, 2.7-3.7cm on average [4, 5]. Tissue is often referred to as
water in simulation studies, and the average travel distances for F-18 and Cu-64 in water
are 0.25cm and 0.20cm, respectively. The GEM detector could serve as another tumor
detection step alongside PET and CT imaging for patients undergoing HIPEC and
cytoreductive surgery. During these procedures, a surgical incision is made in the
abdominal cavity of the patient enabling the beta particle detection [2]. The GEM
detector could then map out any tumors missed by PET and CT scans aiding in the
reduction of relapse.
If a GEM detector could detect gamma radiation produced directly or indirectly
from beta decay of FDG and Cu-64, then tumor mapping could be performed for a
greater depth. Studies have been performed with more GEM foil layers and gold layers,
instead of copper layers, but the results were not efficient enough to be used in the
medical field [12]. The GEM detector coupled with collimator and scintillator may
enable proper detection of gamma rays. Further studies include more in depth analysis
with SRS, phantom studies, and possible GEM detector modifications for gamma
detection.
29
REFERENCES
1. W. Bleibel, O. Kozyreva, S. May, and A. Mahmood. 2014. Peritoneal Cancer.
www.emedicine.medscape.com/article/281107-overview. Medscape.
2. G. Montori, F. Coccolini, M. Ceresoli, F. Catena, N. Colaianni, E. Poletti, & L.
Ansaloni. 2014. The Treatment of Peritoneal Carcinomatosis in Advanced Gastric
Cancer: State of the Art. International Journal of Surgical Oncology. Vol: 2014:
7pgs.
3. R. Harmon and P. Sugarbaker. 2005. Prognostic indicators in peritoneal carcinomatosis
from gastrointestinal cancer. International Seminars in Surgical Oncology. Vol:
2:3: 10pgs.
4. O. Akkus, A. Oguz, M. Uzunlulu, and M. Kizilgul. 2012. Evaluation of Skin and
Subcutaneous Adipose Tissue Thickness for Optimal Insulin Injection. J Diabetes
Metab.Vol:3:8.
5. J. Kim, H. Lim, S.I. Lee, and Y.J. Kim. 2012. Thickness of Rectus Abdominis Muscle
and Abdominal Subcutaneous Fat Tissue in Adult Women: Correlation with Age,
Pregnancy, Laparotomy, and Body Mass Index. APS. Vol:39:5.
6. B. Quinn, B. Holahan, J. Aime, J. Humm, J. St. Germain, and LT. Dauer. 2012.
Measured Dose Rate Constant from Oncology Patients Administered 18F for
Positron Emission Tomography. Med Phys. 10:6071-9.
7. MA. Green. 2007. Assessment of Cu-ETS as a PET radiopharmaceutical for evaluation
of regional renal perfusion. Nuclear Medicine and Biology 34.3:247-255.
30
8. F. Sauli. 2007. Imaging with the Gas Electron Multiplier. NUCL INSTRUM
METHODS. 580: 971-973.
9. R. Bouclier, M. Capeans, W. Dominik, M. Hoch, J-C. Labbe, G. Million, L.
Ropelewski, F. Sauli, and A. Sharma. 1997. The Gas Electron Multiplier (GEM),
IEEE Trans. Nucl. Sci. NS-44, 646
10. J. Ostling. 2006. New Efficient Detector for Radiation Therapy Imaging using Gas
Electron Multipliers. Department of Medical Radiation Physics Karolinksa
Institutet & Stockholm University. 49 p.
11. A. Sharma. 1998. Properties of some Gas Mixtures Used in Tracking Detectors.
SLAC-JOURNAL-IFCA. Vol:16-3.
12. T. Koike, S. Uno, T. Uchida, M. Sekimoto, T. Murakami, M. Shoji, F. Nagashima, K.
Yamamoto, and E. Nakano. 2012. A New Gamma Camera with a Gas Electron
Multiplier. J Inst. Vol 7.
31
BIOGRAPHICAL INFORMATION
Joshua Medford was born and raised in the Dallas-Fort Worth area of Texas. He
graduated from Trinity High School in 2005 and later joined the Air Force 2006. After
six years, he decided to come home to his daughter and to pursue his dreams of obtaining
a degree in a field of science. During the course of his time at UT Arlington, he realized
that he wanted to perform studies in the field of oncology after his 14 year old sister was
diagnosed with thyroid cancer. He later discovered a research team that wanted to aid in
tumor detection in a cancer that is notorious for relapse due to missed tumors and eagerly
joined the lab. After graduation from UT Arlington, Joshua plans to attend MD
Anderson to continue studies in the field of oncology and medical dosimetry.
32