Application of novel technologies for the development of next generation MR compatible PET inserts

153 Pages·2017·9.21 MB·English

by  Georgios Konstantinou

TESIS DOCTORAL

Application of novel technologies for
the development of next generation MR
compatible PET inserts

Autor:
Georgios Konstantinou

Director:
Juan José Vaquero López

DEPARTAMENTO
Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de
Madrid y Hospital General Universitario Gregorio Marañon

Leganés, 22 de Junio 2017

( a entregar en la Oficina de Posgrado, una vez nombrado el Tribunal evaluador , para preparar el
documento para la defensa de la tesis)

TESIS DOCTORAL

Application of novel technologies for the development of next
generation MR compatible PET inserts

Autor: Georgios Konstantinou

Director: Juan José Vaquero López

Firma del Tribunal Calificador:

Firma
Presidente: Andrés Santos

Vocal: Giancarlo Sportelli

Secretario: Luis Hernández Corporales

Calificación:

Leganés 22 de Junio 2017

Application of novel technologies for the development of next generation MR compatible PET inserts

Multimodal imaging integrating Positron Emission Tomography and Magnetic
Resonance Imaging (PET/MRI) has professed advantages as compared to other available
combinations, allowing both functional and structural information to be acquired with
very high precision and repeatability. However, it has yet to be adopted as the standard
for experimental and clinical applications, due to a variety of reasons mainly related to
system cost and flexibility. A hopeful existing approach of silicon photodetector-based MR
compatible PET inserts comprised by very thin PET devices that can be inserted in the
MRI bore, has been pioneered, without disrupting the market as expected. Technological
solutions that exist and can make this type of inserts lighter, cost-effective and more
adaptable to the application need to be researched further.
In this context, we expand the study of sub-surface laser engraving (SSLE) for
scintillators used for PET. Through acquiring, measuring and calibrating the use of a SSLE
setting we study the effect of different engraving configurations on detection
characteristics of the scintillation light by the photosensors. We demonstrate that apart
from cost-effectiveness and ease of application, SSLE treated scintillators have similar
spatial resolution and superior sensitivity and packing fraction as compared to standard
pixelated arrays, allowing for shorter crystals to be used. Flexibility of design is
benchmarked and adoption of honeycomb architecture due to geometrical advantages is
proposed. Furthermore, a variety of depth-of-interaction (DoI) designs are engraved and
studied, greatly enhancing applicability in small field-of-view tomographs, such as the
intended inserts. To adapt to this need, a novel approach for multi-layer DoI
characterization has been developed and is demonstrated.
Apart from crystal treatment, considerations on signal transmission and processing are
addressed. A double time-over-threshold (ToT) method is proposed, using the statistics of
noise in order to enhance precision. This method is tested and linearity results
demonstrate applicability for multiplexed readout designs. A study on analog optical
wireless communication (aOWC) techniques is also performed and proof of concept
results presented. Finally, a ToT readout firmware architecture, intended for low-cost
FPGAs, has been developed and is described.
By addressing the potential development, applicability and merits of a range of
transdisciplinary solutions, we demonstrate that with these techniques it is possible to
construct lighter, smaller, lower consumption, cost-effective MRI compatible PET inserts.
Those designs can make PET/MRI multimodality the dominant clinical and experimental
imaging approach, enhancing researcher and physician insight to the mysteries of life.
Doctorate Dissertation i
Prolegomena

La combinación multimodal de Tomografía por Emisión de Positrones con la Imagen de
Resonancia Magnética (PET/MRI, de sus siglas en inglés) tiene clara ventajas en
comparación con otras técnicas multimodales actualmente disponibles, dada su capacidad
para registrar información funcional e información estructural con mucha precisión y
repetibilidad. Sin embargo, esta técnica no acaba de penetrar en la práctica clínica debido
en gran parte a alto coste. Las investigaciones que persiguen mejorar el desarrollo de
insertos de PET basados en fotodetectores de silicio y compatibles con MRI, aunque han
sido intensas y han generado soluciones ingeniosas, todavía no han conseguido encontrar
las soluciones que necesita la industria. Sin embargo, existen opciones todavía sin explorar
que podrían ayudar a evolucionar este tipo de insertos consiguiendo dispositivos más
ligeros, baratos y con mejores prestaciones.
Esta tesis profundiza en el estudio de grabación sub-superficie con láser (SSLE) para el
diseño de los cristales centelladores usados en los sistemas PET. Para ello hemos
caracterizado, medido y calibrado un procedimiento SSLE, y a continuación hemos
estudiado el efecto que tienen sobre las especificaciones del detector las diferentes
configuraciones del grabado. Demostramos que además de la rentabilidad y facilidad de
uso de esta técnica, los centelladores SSLE tienen resolución espacial equivalente y
sensibilidad y fracción de empaquetamiento superiores a las matrices de centelleo
convencionales, lo que posibilita utilizar cristales más cortos para conseguir la misma
sensibilidad. Estos diseños también permiten medir la profundidad de la interacción (DoI),
lo que facilita el uso de estos diseños en tomógrafos de radio pequeño, como pueden ser
los sistemas preclínicos, los dedicados (cabeza o mama) o los insertos para MRI.
Además de trabajar en el tratamiento de cristal de centelleo, hemos considerado nuevas
aproximaciones al procesamiento y transmisión de la señal. Proponemos un método
innovador de doble medida de tiempo sobre el umbral (ToT) que integra una evaluación
de la estadística del ruido con el propósito de mejorar la precisión. El método se ha
validado y los resultados demuestran su viabilidad de uso incluso en conjuntos de señales
multiplexadas. Un estudio de las técnicas de comunicación óptica analógica e inalámbrica
(aOWC) ha permitido el desarrollo de una nueva propuesta para comunicar las señales del
detector PET insertado en el gantry a un el procesador de señal externo, técnica que se ha
validado en un demostrador. Finalmente, se ha propuesto y demostrado una nueva
arquitectura de análisis de señal ToT implementada en firmware en FPGAs de bajo coste.
La concepción y desarrollo de estas ideas, así como la evaluación de los méritos de las
diferentes soluciones propuestas, demuestran que con estas técnicas es posible construir
insertos de PET compatibles con sistemas MRI, que serán más ligeros y compactos, con un
reducido consumo y menor coste. De esta forma se contribuye a que la técnica multimodal
PET/MRI pueda penetrar en la clínica, mejorando la comprensión que médicos e
investigadores puedan alcanzar en su estudio de los misterios de la vida.
ii Georgios Konstantinou
Application of novel technologies for the development of next generation MR compatible PET inserts

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Doctorate Dissertation iii
Prolegomena

Greek saying

Writing a PhD thesis has been the most diversely challenging task I ever undertook.
my gratitude to the people that accompanied me in this journey, from those that provided
the direct help and work collaboration, to those that were able to support me and relieve
the corresponding feelings and anxiety.
First, I would like to thank my supervisor, Juan José Vaquero Lopez, for giving me the
opportunity to join his team and mentoring me not only in how to build nuclear medicine
detectors, but also in fighting for my ideas and believing in myself; furthermore, for the
great experience of living in the wonderful city of Madrid, the best city in the world.
Along with him, I would like to thank the group of the laboratorio de imagen médica
(LIM), from the Hospital General Universitario Gregorio Marañón. I hope that they, under
the strain and transformation the current economic and social situation has added, will
manage to continue creating great science and develop great scientists. Particularly the
people that were there when I joined, I would like to thank for helping me land in their
city in such a graceful manner. I would also like to thank the people of the Departamento
de Bioingeniería e Ingeniería Aeroespacial of Universidad Carlos III de Madrid, especially
Miguel, Guillermo, Angélica, Carlos, Santi, Ana, Asier, Sara and Tom, for their support
and endless energy, so necessary when mine was running out (quite often). Along with
them, the whole group of Friday beers at el Puerto, for giving me the much cherished
insight in Spanish cuisine and culture.
Of course, I also would like to voice my appreciation to the international colleagues
from the INFIERI collaboration who, apart from securing the funding that I used for the
PhD, shared the experience of the numerous workshops, visits and secondments; in
particular, the groups of Pisa, both in INFN (Giancarlo, Fabrizio) and SSSA (Ernesto,
Giulio) that supported the secondments undertaken. Moreover, our coordinator Aurore,
for the impossible job of organizing such a diverse and broad collection of individuals; and
more than everything the other ESRs, especially Stamatis, Eleytheria, Wajahat, Michele
and Mateo, for making me feel that I am not alone in this madness.
iv Georgios Konstantinou
Application of novel technologies for the development of next generation MR compatible PET inserts
On a personal level, I would like to thank my great and greatly supportive family, my
parents Dionisis and Filia and my sister Thalia. In a broader scope aunts and uncles Kaiti,
Tonia, Gerasimos, Nitsa and cousins Mitsos, Maria and Katerina who have been on my
side all this time. Most importantly, my companion in life Masha Reva, who taught me
how it is really worth trying and becoming better every single day and has been there to
share the biggest and strongest happiness and most difficult melancholies.
Furthermore, all the people who were there when I needed some solace from the toils of
life. From Madrid Hara and Stathis, Tania, Laura and Giannis and from around the world
Foivos, Vaggelis, Vasilis, Panos and Elena, Nikos, Lefteris and Eliza, Matias and Naz,
Valerio, Samir, Maya, Spyros, Thanos and Eirini, Fotis, Manolis, Ilias... countless
kilometers will keep separating us from each other, but the feelings are strong and true
and when we meet, it is as if we never stopped living in the unchangeable refuge of our
common past.
Finally, I would like to thank all the innumerable great people that I have had the luck to
meet, discuss, learn from and look up to; the only reason that allows me to not relinquish
the hope that one day, this world will be a better place. This thesis is the contribution I was
able to make for that goal, during the last three years.

Doctorate Dissertation v
Prolegomena

Chapter 1: Introduction and Hypothesis
A. Medical imaging ............................................................................................................................. 1
B. Imaging approaches ...................................................................................................................... 2
C. Multimodal imaging ...................................................................................................................... 3
D. The chase for PET/MR ................................................................................................................... 4
E. Objective: What could make PET/MR the standard multimodal approach? ......................... 6
F. Hypothesis ...................................................................................................................................... 7
G. Thesis outline .................................................................................................................................. 8
References ......................................................................................................................................................... 9
Chapter 2: PET basics
A. A Historical perspective .................................................................................................................. 11
B. + Radiotracers: Physics and application ...................................................................................... 12
C. detection using scintillators ......................................................................................................... 15
D. Detection of scintillation light ......................................................................................................... 17
E. PET detector specifications ............................................................................................................. 20
F. Small animal scanners and PET inserts ......................................................................................... 24
References ....................................................................................................................................................... 25
Chapter 3: A feasibility study of Sub-Surface Laser Engraving for scintillators
I. Introduction ........................................................................................................................................... 29
II. Materials and Methods ........................................................................................................................ 32
A. SSLE process...................................................................................................................................... 32
B. Study and introduction of a cost-effective system ...................................................................... 33
C. BK-7 testing and photometric experiments .................................................................................. 35
D. Simulations ........................................................................................................................................ 36
III. Results ................................................................................................................................................ 41
A. Engraving results .............................................................................................................................. 41
B. Photometric results .......................................................................................................................... 42
C. Simulations results ........................................................................................................................... 45
IV. Conclusions ....................................................................................................................................... 46
V. References .............................................................................................................................................. 47
Chapter 4: Verification of Sub-Surface Laser Engraving for scintillators
I. Introduction ...................................................................................................................................... 49
II. Materials And Methods ................................................................................................................... 50
A. Experimental setup ...................................................................................................................... 50
B. Design verification ....................................................................................................................... 51
III. Results............................................................................................................................................ 53
A. First engravings of scintillators .................................................................................................. 53
B. Spatial resolution results ............................................................................................................. 55
C. Energy Results .............................................................................................................................. 57
vi Georgios Konstantinou