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.

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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

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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.

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