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Clinical Nuclear Medicine
Physics with MATLAB®
 Series in Medical Physics and Biomedical Engineering

Series Editors
Kwan-Hoong Ng, E. Russell Ritenour,
and Slavik Tabakov

Recent books in the series:

The Physics of CT Dosimetry: CTDI and Beyond

Robert L. Dixon

Advanced Radiation Protection Dosimetry

Shaheen Dewji, Nolan E. Hertel

On-Treatment Verification Imaging A Study Guide for IGRT

Mike Kirby, Kerrie-Anne Calder

Modelling Radiotherapy Side Effects Practical Applications

for Planning Optimisation
Tiziana Rancati, Claudio Fiorino

Proton Therapy Physics, Second Edition

Harald Paganetti (Ed)

e-Learning in Medical Physics and Engineering: Building Educational

Modules with Moodle
Vassilka Tabakova

Diagnostic Radiology Physics with MATLAB®: A Problem-Solving Approach

Johan Helmenkamp, Robert Bujila, Gavin Poludniowski (Eds)

Clinical Radiotherapy Physics with MATLAB®: A Problem-Solving Approach

Pavel Dvorak

Clinical Nuclear Medicine Physics with MATLAB®:

A Problem-Solving Approach
Maria Lyra Georgosopoulou (Ed)

For more information about this series, please visit: https://www.routledge.

com/Series-in-Medical-Physics-and-Biomedical-Engineering/book-series/
CHMEPHBIOENG
Clinical Nuclear Medicine
Physics with MATLAB®

A Problem-Solving Approach

Edited by
Maria Lyra Georgosopoulou
MATLAB® is a trademark of The MathWorks, Inc. and is used with permission. The MathWorks does
not warrant the accuracy of the text or exercises in this book. This book’s use or discussion of MATLAB®
software or related products does not constitute endorsement or sponsorship by The MathWorks of a par-
ticular pedagogical approach or particular use of the MATLAB® software.
First edition published 2022
by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742
and by CRC Press
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
© 2022 selection and editorial matter, Maria Lyra Georgosopoulou; individual chapters, the contributors
CRC Press is an imprint of Taylor & Francis Group, LLC
The right of Maria Lyra Georgosopoulou to be identified as the author of the editorial material, and of
the authors for their individual chapters, has been asserted in accordance with sections 77 and 78 of the
Copyright, Designs and Patents Act 1988.
Reasonable efforts have been made to publish reliable data and information, but the author and publisher
cannot assume responsibility for the validity of all materials or the consequences of their use. The authors
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Library of Congress Cataloging‑in‑Publication Data

Names: Lyra Georgosopoulou, Maria, editor.

Title: Clinical nuclear medicine physics with MATLAB : a problem-solving
approach / edited by Maria Lyra Georgosopoulou.
Description: First edition. | Boca Raton : CRC Press, 2021. | Series:
Series in medical physics and biomedical engineering | Includes
bibliographical references and index.
Identifiers: LCCN 2021006755 (print) | LCCN 2021006756 (ebook) | ISBN
9780367747510 (hardback) | ISBN 9780367756079 (paperback) | ISBN
9781003163183 (ebook)
Subjects: LCSH: MATLAB. | Medical physics. | Nuclear medicine--Data processing.
Classification: LCC R895 .C55 2021 (print) | LCC R895 (ebook) | DDC 610.1/53--dc23
LC record available at https://lccn.loc.gov/2021006755
LC ebook record available at https://lccn.loc.gov/2021006756

ISBN: 9780367747510 (hbk)

ISBN: 9780367756079 (pbk)
ISBN: 9781003163183 (ebk)

Typeset in Times
by KnowledgeWorks Global Ltd.
Contents
Foreword...................................................................................................................vii
Contributors...............................................................................................................ix

Chapter 1 Introduction........................................................................................... 1
Maria Lyra Georgosopoulou

Chapter 2 Image Formation in Nuclear Medicine............................................... 83

Nefeli Lagopati

Chapter 3 Nuclear Medicine Imaging Essentials............................................... 101

Nefeli Lagopati

Chapter 4 Methods of Imaging Reconstruction in Nuclear Medicine............... 127

Maria Argyrou

Chapter 5 Image Processing and Analysis in Nuclear Medicine....................... 141

Antonios Georgantzoglou

Chapter 6 3D Volume Data in Nuclear Medicine.............................................. 183

Christos Chatzigiannis

Chapter 7 Quantification in Nuclear Medicine Imaging................................... 191

Nefeli Lagopati

Chapter 8 Quality Control of Nuclear Medicine Equipment............................. 223

Maria Argyrou

Chapter 9 Introduction to MATLAB and Basic MATLAB

Processes for Nuclear Medicine........................................................ 243
Marios Sotiropoulos

v
vi Contents

Chapter 10 Morphology of Human Organs in Nuclear Medicine:

MATLAB Commands...................................................................... 275
Elena Ttofi

Chapter 11 Internal Dosimetry by MATLAB in Therapeutic Nuclear

Medicine............................................................................................ 281
Nefeli Lagopati

Chapter 12 Pharmacokinetics in Nuclear Medicine/MATLAB Use................... 303

Nefeli Lagopati

Chapter 13 Nanotechnology in Nuclear Medicine/MATLAB Use..................... 325

Nefeli Lagopati

Chapter 14 CASE Studies in Nuclear Medicine/MATLAB Approach............... 339

Stella Synefia, Elena Ttofi, and Nefeli Lagopati
List of Acronyms................................................................................................... 359
Foreword
Clinical Nuclear Medicine Physics with MATLAB®: A Problem-Solving Approach by
Professor Maria Lyra Georgosopoulou, PhD, and her team is the third in a collection of
textbooks within the Series in Medical Physics and Biomedical Engineering dedicated
to software used by clinical medical physicists. The first two books in the series are com-
panions to the present one and are dedicated to the use of MATLAB in Radiotherapy and
Diagnostic Physics [1,2]. This book will complete the three-book set.
Given the ongoing and accelerating development of medical device technology
and user protocols, fulfilling the mission and delivering the full competence pro-
file of the clinical medical physicist has become a daunting task [3,4]. However,
well-written software and programming skills can help in a multitude of ways [5-8].
Regrettably, few suitable textbooks are available, with the result that the acquisi-
tion of high-level programming skills by students and clinical scientists is often a
hit-and-miss affair. Few books include exemplar scripts illustrating application to
the clinical milieu whilst didactic approaches are insufficiently comprehensive or
low in communicative power. Clinical Nuclear Medicine Physics with MATLAB®:
A Problem-Solving Approach aims to fill this gap in the use of MATLAB in clinical
nuclear medicine.
In this textbook, the university tutor will find structured teaching text and real-
world case study examples with which to enhance presentations and to set as learn-
ing tasks. On the other hand, the student will find a pedagogically appealing and
engaging manuscript for individual study whilst the practicing clinical medical phys-
icist a learning tool for further development of own skills. Professor Georgosopoulou
and her team have put their multifarious clinical and MATLAB experience into this
book so there is something for everybody here.
Professor Georgosopoulou and her team are clinical nuclear medicine physicists
with many years of experience and I sincerely thank them for finding the time within
their busy schedules to dedicate to this important educational initiative and to share
their nuclear medicine and MATLAB expertise with the readers of this book. I am
sure it has not been easy and I appreciate their contribution.
Finally, I would like to wish the readers of this textbook many happy MATLAB
programming hours – and to remind them that programming is power! I also invite
potential authors with novel ideas regarding textbooks for other software used in
medical physics to write to me, they will find a willing ear.

Carmel J. Caruana, PhD, FIPEM

Professor and Head, Medical Physics Department, University of Malta
Past-Chair, Education and Training Committee, European Federation of
Organizations for Medical Physics
Past Associate Editor for Education and Training:
Physica Medica – European Journal of Medical Physics
Past Chair Accreditation Committee 1:
International Medical Physics Certification Board

vii
viii Foreword

REFERENCES
1. Dvorak P. (2018) Clinical Radiotherapy Physics with MATLAB: A Problem-Solving
Approach, CRC Press.
2. Helmenkamp J., Bujila R., & Poludniowski G. (2020) Diagnostic Radiology Physics
with MATLAB: A Problem-Solving Approach, CRC Press.
3. Caruana, C. J., Christofides, S., & Hartmann, G. H. (2014). European Federation of
Organizations for Medical Physics (EFOMP) policy statement 12.1: recommendations
on medical physics education and training in Europe 2014, Physica Medica – European
Journal of Medical Physics, 30 (6), 598.
4. Guibelalde E., Christofides S., Caruana C. J., Evans S., & van der Putten W. (Eds.)
(2015). European Guidelines on the Medical Physics Expert (Radiation Protection
Series 174). Publications Office of the European Union, Luxembourg: European
Commission.
5. Lyra M., Ploussi A., & Georgantzoglou A. (2011). MATLAB as a tool in nuclear medi-
cine image processing, In: Ionescu C. (Ed.) MATLAB – A Ubiquitous Tool for the
Practical Engineer InTech, DOI: 10.5772/19999.
6. Ferris M.C., Lim J., & Shepard D.M. (2005). Optimization tools for radiation treat-
ment planning in MATLAB, In: Brandeau M.L., Sainfort F., Pierskalla W.P. (Eds)
Operations Research and Health Care. International Series in Operations Research &
Management Science, vol 70. Boston, MA: Springer.
7. Nowik P., Bujila R., Poludniowski G., & Fransson A. (2015). Quality control of CT
systems by automated monitoring of key performance indicators: a two-year study, J
Appl Clin Med Phys. 16 (4): 254–265.
8. Donini B., Rivetti S., Lanconelli N., & Bertolini M. (2014) Free software for perform-
ing physical analysis of systems for digital radiography and mammography, Med Phys,
41 (5): 051903.
Contributors
Maria Argyrou Nefeli Lagopati
Department of Nuclear Medicine National Technical University of Athens
Athens Medical Center School of Chemical Engineering
Athens, Greece Laboratory of General Chemistry
National and Kapodistrian University of
Christos Chatzigiannis Athens
Imaging Centre and
Regional Medical Physics Service Department of Medicine
Royal Victoria Hospital School of Health Sciences
Belfast, UK Molecular Carcinogenesis Group
Athens, Greece
Antonios Georgantzoglou
Department of Physiology, Development Marios Sotiropoulos
and Neuroscience Unité Signalisation radiobiologie et
University of Cambridge cancer
Cambridge, UK Institut Curie/CNRS/Inserm/Université
Paris-Saclay
Maria Lyra Georgosopoulou Orsay, France
1st Department of Radiology
Radiation Physics Unit Stella Synefia
School of Medicine Metropolitan College
National and Kapodistrian University of Maroussi, Greece
Athens
Athens, Greece Elena Ttofi
Limassol, Cyprus

ix
 1 Introduction
Maria Lyra Georgosopoulou

CONTENTS
1.1 Introduction – Quality in Nuclear Medicine.....................................................2
1.2 Quality in Nuclear Medicine Focuses on Three Main Tasks............................3
1.2.1 Quality Management (QM)................................................................... 3
1.2.2 Quality Assurance (QA)........................................................................ 4
1.2.2.1 Why Do We Need a Quality Assurance (QA) Program
in Nuclear Medicine?.............................................................. 4
1.2.2.2 Education/Clinical Medical Physicists
in Nuclear Medicine................................................................5
1.2.2.3 Radioisotopes – Radiopharmaceutical Quality...................... 5
1.2.3 Quality Control (QC)............................................................................. 6
1.2.3.1 Quality Control of Radiopharmaceuticals..............................9
1.2.3.2 Quality Control/System Performance Degradation................ 9
1.2.3.3 Abnormal Distribution of the Radiopharmaceutical............ 12
1.2.4 Imaging Phantoms Are Quality Control Tools in
Nuclear Medicine................................................................................. 13
1.2.5 Hybrid Systems Quality Assurance (QA) – Fusion............................. 15
1.2.5.1 Quality of Performance and Advantages Utilizing
SPECT/CT............................................................................ 16
1.2.5.2 SPECT/CT Fusion................................................................. 16
1.2.5.3 Hybrid PET/CT..................................................................... 18
1.2.5.4 New Generation of PET/CT.................................................. 19
1.2.5.5 Comparison of Quantitative PET/CT and SPECT/CT..........20
1.2.5.6 From PET/CT to PET/MRI................................................... 21
1.2.5.7 Hybrid SPECT/MRI............................................................. 23
1.3 Quality Assurance (QA) of Imaging Systems Based
on International Standards...............................................................................26
1.4 The Quality of Scientific and Clinical Output................................................. 30
1.4.1 Data Quality........................................................................................ 30
1.4.2 Data Resolution – Noise Data.............................................................. 31
1.4.3 Attenuation Correction........................................................................ 33
1.5 Accuracy and Precision Improvement in Quantification
of Imaging Data...............................................................................................34
1.5.1 Accuracy and Precision in Nuclear Medicine..................................... 36
1.6 The Need for Mathematical Methods in Nuclear
Medicine Image Evaluation............................................................................. 37
1.6.1 MIRD Schema – MIRDOSE – OLINDA/EXM – RADAR
Software............................................................................................... 41

1
2 Clinical Nuclear Medicine Physics with MATLAB®

1.6.1.1 MIRD Schema...................................................................... 41

1.6.1.2 MIRDOSE............................................................................ 43
1.6.1.3 OLINDA (Organ Level INternal Dose Assessment)............44
1.6.1.4 RADAR (RAdiation Dose Assessment Resource)...............44
1.6.2 Computational Phantoms..................................................................... 45
1.6.2.1 Stylized (First-Generation) Computational Phantoms..........46
1.6.2.2 Voxel (Second-Generation) Phantoms.................................. 48
1.6.2.3 Hybrid (Third-Generation) Phantoms.................................. 49
1.6.2.4 Voxelization of Hybrid Phantoms......................................... 50
1.6.2.5 Reference Phantoms Adopted by the ICRP.......................... 51
1.6.2.6 Statistical Phantoms.............................................................. 52
1.6.3 Monte Carlo (MC) Simulation in Nuclear Medicine........................... 52
1.6.3.1 General Purpose Monte Carlo (MC) Codes......................... 53
1.6.3.2 Specific Monte Carlo (MC) Codes....................................... 55
1.6.3.3 VALIDATION of Monte Carlo (MC) Codes
in Nuclear Medicine.............................................................. 55
1.6.3.4 Quantification Accuracy in Monte Carlo (MC)
Simulation............................................................................. 56
1.6.3.5 Use of Voxel Models/Monte Carlo Simulations................... 57
1.6.3.6 Individualized Patient Dosimetry/MC Simulations.............. 58
1.6.4 MATLAB Computing Software in Nuclear Medicine........................ 58
1.6.4.1 MATLAB (The MathWorks, Inc.) in Developing
Nuclear Medicine Algorithms.............................................. 59
References................................................................................................................. 74

1.1 INTRODUCTION – QUALITY IN NUCLEAR MEDICINE

Nuclear Medicine includes measurement or imaging of radioactive samples in a tiny
size to a human adult. It is a medical specialty by which we use safe, painless, and
cost-effective techniques for the body and organ imaging as well as for treatment
of diseases.
Nuclear Medicine Imaging is unique in discovering organ function and structure
using radiopharmaceuticals for diagnostic and treatment purposes. It emerges valu-
able quantitative data as base to diagnosis and therapy and many useful parameters
and their relationship are studied.
As it has to deal with radioactivity, all scientists involved in clinical procedures
have to be well and continuously educated and must be well aware with new tech-
niques and innovation technology applied. Knowledge of fundamental physiological
data is necessary.
Radiation protection, basic protocols, quality control, and dosimetry are param-
eters and procedures that personnel of Nuclear Medicine must be familiar. New
trends by the modern technology in instruments and software bring developments
in favor of patients and workers. Children should safely undergo these procedures to
evaluate, e.g., bone pain, injuries, infection of kidneys, or bladder function.
Protocols and Guidelines for the inspection of equipment and parameters used by
the imaging systems in Nuclear Medicine will drive to the desirable qualified results.
Introduction 3

FIGURE 1.1 An example of high quality. Innovations in 3D printing lead to implantable

high Quality blood vessels. Advanced bioinks for 3D printing are rationally designed materials
intended to improve the functionality of printed scaffolds. (Extracted from Gao G. et al., 2019.)

Quality generally is referred to a specific characteristic of an object or to the

achievement of an object or a service. The meaning of quality is synonymous with
good or excellent. So, the quality of something depends on the criteria that are
applied for it and it is the completion of the characteristics of a product that it will
satisfy our steady needs; e.g., High Quality example could be the use of bioinks
formulated from smooth muscle cells from a human aorta and endothelial cells from
an umbilical vein. The artificial blood vessel is an essential tool to save patients suf-
fering from cardiovascular disease. There are products in clinical use made from
polymers, but they don’t have living cells and vascular functions. The researchers
built a high-quality biomimetic blood vessel using three-dimensional (3D) printing
techniques (Figure 1.1) (Gao G. et al., 2019). The researchers fabricated the printed
blood vessel; they used a special algorithm to print multiple concentric layers using
bioink. Tissue-engineered biomimetic blood vessels provide a promising route for
the construction of durable small-diameter vascular grafts that may be used in future
treatments of cardiovascular diseases.

1.2 QUALITY IN NUCLEAR MEDICINE

FOCUSES ON THREE MAIN TASKS
(1) Quality Management (QM), (2) Quality Assurance (QA), and (3) Quality Control
(QC)

1.2.1 Quality Management (QM)

Quality Management covers all activities that organizations use to direct, control,
and coordinate quality. These activities include formulating a quality policy and set-
ting quality objectives. They also include quality schedule, quality control, quality
assurance, and quality corrections. Continuous updating on modern techniques, such
as Artificial Intelligence and Deep learning techniques that differ in the way that
information is extracted from the input, helps toward a dynamic education necessary
for the optimum results of a patient’s health (Cook, G. J. R. and Goh, V., 2019).
Quality Management Systems (QMS) should be maintained with the intent
to continuously improve effectiveness and efficiency, enabling Nuclear Medicine
to achieve the expectations of its quality policy, satisfy its customers, and improve
4 Clinical Nuclear Medicine Physics with MATLAB®

professionalism. The Quality Management audit methodology in Nuclear Medicine

practice is published by International Atomic Energy Agency (IAEA No. 33, Quality
Management Audits in Nuclear Medicine Practices, 2015a).
Regular quality audits and assessments are essential for modern Nuclear Medicine
services. The entire Quality Management (QM) and audit process has to be sys-
tematic, patient oriented, and outcome based. The QM documentation in Nuclear
Medicine should contain documents of a quality policy and quality objectives, a
quality manual, standards of operating procedures for diagnosis and therapy man-
agement, and records of parameters and remarks.
The Quality Management (QM) Service in the Nuclear Medicine department
should also take into account multidisciplinary contributions including clinical,
technical, radiopharmaceutical, medical physics, and radiation safety procedures.
Its effectiveness should be improved according to the requirements of professional,
regulatory, standardization, or accrediting bodies. The adoption of internation-
ally recognized audits and protocols as from International Atomic Energy Agency
(IAEA), Society of Nuclear Medicine and Molecular Imaging (SNMMI), European
Association of Nuclear Medicine (EANM), International Commission on Radiation
Units (ICRU), etc. is preferable and offers the necessary homogeneity of results qual-
ity (EANM Carrio et al., 2006; EANM Cuocolo et al., 2007).

1.2.2 Quality Assurance (QA)

Quality Assurance is the function of a management system that provides confidence
for the fulfillment of specified requirements and it is a necessity in Nuclear Medicine.
Quality Assurance (QA) covers all activities as design, development, production,
installation, servicing, and documentation. All the results must be monitored ensur-
ing that appropriate action is taken when performance is outside acceptable ranges.
That is: “fit for purpose” or “do it right as the first time”.
QA standards, protocols, guidelines, preparation of radiopharmaceuticals, and
phantoms have been set by world organizations. National Electrical Manufacturers
Association (NEMA), International Atomic Energy Agency (IAEA), International
Electrotechnical Commission (IEC), Deutsches Institut fur Normung (DIN),
European Association of Nuclear Medicine (EANM), Society of Nuclear Medicine
and Molecular Imaging (SNMMI), and other scientific organizations have set down
guidelines in order to ensure that the appropriate standards in Nuclear Medicine are
met in most countries of the world. These guidelines will be acceptable as a common
denominator for the benefit of patient care on a world level (IAEA, 2006). Every
department should organize its own program according to its needs and workload,
in order to be efficient, to keep the instrumentation in good condition, and to prevent
any deterioration.

1.2.2.1 Why Do We Need a Quality Assurance (QA)

Program in Nuclear Medicine?
We wish to ensure that we get a high-quality, correct, clinical result which addresses
the patient’s clinical problem with minimal detrimental effects on the patient con-
cerning radiation dose, waiting time, and minimal errors.
Introduction 5

Nuclear Medicine product is “Diagnosis and Therapy”. This is what we wish to

guarantee, and Quality Assurance (QA) reassures that the obtained result is the best,
more probable for the available equipment and personnel.
Quality Assurance (QA) in Nuclear Medicine includes:

1. High-performance equipment
2. Staff Education (Clinical Medical Physicists)
3. Image acquisition and processing reliable software
4. Radioisotopes – Radiopharmaceutical Quality

1.2.2.2 Education/Clinical Medical Physicists in Nuclear Medicine

In 2013, a cooperation of European Association of Nuclear Medicine (EANM) and
European Federation of Organizations of Medical Physicists (EFOMP) produced the
“Curriculum for education and training of Medical Physicists in Nuclear Medicine” to
provide a guideline curriculum covering theoretical and practical aspects of education
and training for Medical Physicists in Nuclear Medicine (EANM/EFOMP Del Guerra
et al., 2013). This joint EANM/EFOMP European guideline curriculum is a further
step to harmonize specialized training of Medical Physicists in Nuclear Medicine and
is a contribution in Quality Assurance (QA) of the Nuclear Medicine departments.
The growing number and the increasing complexity of the procedures in Nuclear
Medicine require clinically qualified Medical Physicists to ensure safe and effec-
tive patient diagnosis, treatment, and management; they are health professionals
responsible of quality and safety of Nuclear Medicine applications of ionizing radia-
tion. IAEA, Human Health Reports No. 15 describes an algorithm developed for
determination of the recommended staffing levels for clinical medical physics ser-
vices in medical imaging and radionuclide therapy (IAEA, 2018b) endorsed by the
International Organization for Medical Physics (IOMP).

1.2.2.3 Radioisotopes – Radiopharmaceutical Quality

Progress in Nuclear Medicine is tightly linked to the development of new radio-
pharmaceuticals and efficient production of relevant radioisotopes. New radiophar-
maceuticals can provide extremely valuable information in the evaluation of many
diseases (cancer, brain, or heart diseases). IAEA (2015b) is a practical support for
the introduction of new radiotracers, including recommendations on the necessary
steps needed to facilitate and speed the introduction of radiopharmaceuticals in
clinical use, while ensuring that a safe and high-quality product is administered
to the patients at all times. Radiopharmaceuticals are an important tool in Nuclear
Medicine for early diagnosis of many diseases and developing effective treatments
(IAEA Bulletin, 2019).
The IAEA International Symposium on Trends in Radiopharmaceuticals (ISTR-
2019), 28 October–1 November 2019, in Vienna, Austria, provided an international
forum for scientists working in the fields of production of radioisotopes and radio-
pharmaceuticals to discuss the most recent progress in the field. Development,
production, and use of diagnostic, therapeutic, and theranostic (used for diagnosis
and therapy) radioisotopes and radiopharmaceuticals were analytically discussed
(International Symposium on Trends in Radiopharmaceuticals [ISTR], 2019).
6 Clinical Nuclear Medicine Physics with MATLAB®

By the completion of a Quality Assurance (QA) program, we should also be

harmonized with the European Union (EU) legislation against the dangers arising
from Ionizing Radiation. Requirements of Council Directives 96/29 and 97/43 of
Euratom are “Basic Safety Standards Directive (BSS) on the protection of workers
and the general population” and “Medical Exposure Directive (MED), on health
protection of individuals in relation to medical exposure”. These are included in the
new (Euratom, 2014), “Basic Safety Standards Directive Council Directive 2013/59/
Euratom”.

1.2.3 Quality Control (QC)

Quality Control (QC) is a part of Quality Management (QM) focused on fulfill-
ing quality requirements. Quality Control (QC) is referred to the actions we take to
achieve, support, and improve the quality.

• Total Quality Control is the completeness of quality characteristics of a system.

• Statistical Quality Control is the collection and analysis of Total Quality
Controls.

Though much has been done to improve the stability of Nuclear Medicine systems
performance, their components will drift from the initial specifications, causing a
gradual deterioration in performance over a period of time (e.g., fluctuations in the
electrical power supply and environmental conditions may cause changes in system
performance). Quality Control (QC) of imaging system and radiopharmaceuticals is
a necessity for reliable results in Nuclear Medicine.
For best image quality in Nuclear Medicine examination performance, Quality
Control (QC) of the imaging system is a necessity. Quality Control (QC) of the imag-
ing system requires special choice of:

• System characteristics (e.g., Resolution-Uniformity-Linearity-COR)

• Proper examination time-interval or quite enough counts collection to
increase statistics
• Low level of scattered radiation
• Optimum patient position (minimum distance of patient from imaging system)
• Suitable imaging size

Acceptance testing – The first Quality Control (QC) procedure has as scope to test
newly installed systems with proper phantoms to provide sufficient data for evalua-
tion of a new system’s specification and obtain relevant results. These results should
be used as reference data for annual survey of the system. The annual survey of the
system performance will be a part of an imaging Quality Assurance (QA) program.
The following examples present a few images obtained by the Quality Control
(QC) approach:

• System characteristics (Resolution-Uniformity-Linearity; Figure 1.2)

• Image quality as a function of counts
Introduction 7

FIGURE 1.2 Resolution-Uniformity-Linearity phantom imaging in a planar γ-camera qual-

ity control (QC).

Right examination time interval or proper counts collection to increase sta-

tistics (Figure 1.3).
• Low level of scattered radiation (Figure 1.4)
• Suitable imaging size
The spatial resolution of a digital image is governed by the size of the pixels
used to represent the digitized image. The pixel size is smaller as the num-
ber of pixels and the matrix size are larger.

Data collection matrix size depends on the number and size of the contained pixels.
A pixel represents the smallest sampled 2D element in an image. It has dimensions
given along two axes in millimeters, dictating in-plane spatial resolution.
Digital images are characterized by matrix size and pixel depth. Matrix size
refers to the number of discrete picture elements (pixels) in the matrix. This affects
the degree of spatial detail that can be presented. Larger matrices provide more
detail. Matrix sizes used in Nuclear Medicine images typically range from 64 × 64
to 512 × 512 pixels. The larger the matrix size, the smaller the pixels and the more
detail that is visible in the image (Figure 1.5) (Radiology Key, 2016).

FIGURE 1.3 Choice of termination of image acquisition (time or counts) is crucial for the
optimum statistics in improvement of image quality.
8 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.4 By determination of an asymmetric energy window, scattered radiation is

avoided, thereby improving the quality of acquisition.

A smaller pixel size can display more image detail; though there is no further
improvement at a certain point because of resolution limitations of the imaging device.
Most Nuclear Medicine images consist of multidimensional datasets of counts
(pixels or counts/voxel). A voxel represents a value on a regular grid in three-
dimensional space; in the word voxel, [vo] represents volume and [el] represents
element; similar formation with [el] for element includes the word pixel.
The dataset directly reflects regional concentration of radioactivity. Thus, Nuclear
Medicine is a quantitative technique for the detection of molecular interaction of a radio-
pharmaceutical with the endogenous target. However, its quantitative power for clinical
research can only become productive when there is strict standardization of imaging
protocols. Quality Control (QC) and Quality Assurance (QA) procedures of the imaging
system must be in use so that optimal quantitative images and data are obtained.

FIGURE 1.5 Matrix size. (Top) Small matrix registers the three events as one. (Bottom) In
a larger matrix the three events are recorded clearly.
Introduction 9

1.2.3.1 Quality Control of Radiopharmaceuticals

Radiopharmaceuticals are another important quality factor under consideration in
Nuclear Medicine. Benefits of high-quality radiopharmaceuticals include accurate
diagnosis and secure therapy for the patient.
Principal properties affecting labeling of radiopharmaceuticals are:

• Radioisotope concentration
• Radioisotope purity
• Radiochemical purity
• Specific concentration
• Sterility

Radiopharmaceuticals must be prepared within a reliable Quality Control (QC) sys-

tem that considers materials, personnel, accurate documentation, and improvement
of renewal results. Guidelines and best practices for the Quality Control (QC) of
medical radioisotopes and radiopharmaceuticals written by a group of experts with
experience of a large range of radiopharmaceuticals are published by the IAEA.
These guidelines support professionals in preparing radiopharmaceuticals of good
quality and high safety (IAEA, 2018a).
During preparation of radiopharmaceuticals for injection, regulations on radia-
tion protection as well as appropriate rules of working under aseptic conditions
ought to be adhered to, strictly. Particular attention must be paid to the prevention
of cross-contamination and to waste disposal. A continuous assessment of the effec-
tiveness of the Quality Assurance (QA) system is essential to prove that the proce-
dures applied in the Radiopharmacy section of the Nuclear Medicine department
lead to the expected quality (EANM, 2007, Radiopharmacy Committee, cGRPP-
guidelines, version2).
1.2.3.2 Quality Control/System Performance Degradation
In Nuclear Medicine Quality Control (QC), sources of system performance degrada-
tion must be carefully indicated. Some of them are:

• Collimator damage; photomultiplier tube (PMT) drift; energy peak drift;

electronic offsets drift; mechanical COR change; electronic noise; crystal
or light coupling degradation; contamination and background; variations
with angle of rotation.

The following images/examples of system deterioration emerged during the Quality

Control (QC) procedures are useful in training:

• Collimator damage (Figure 1.6)

• Photomultiplier tube drift (Figure 1.7)
• Photomultipliers out of order (Figure 1.8)
• Effect of large radius of rotation (Figure 1.9A)
Acquisition of striatum SPECT tomography (Figure 1.9B)
• Truncation on a SPECT myocardial perfusion study; a patient example
(Figure 1.10) (IAEA, 2003)
10 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.6 Collimator destruction during transportation. (a) Distorted cells made of foils.
(b) Collimator cells in proper condition. (c) flood source image completed by destructed
collimator a. Inhomogeneities on the image caused by destructed collimator cells

FIGURE 1.7 Uniformity checks of a planar γ-camera by Co57 Flood Source. Left: Peripheral
photomultiplier (PMT) defect. Middle: Photomultipliers PMTs voltage deficiency; see rings
of low intensity. Right: Non-uniformed image because of wrong energy window selection
(20% in Tc-99m photopeak [140 keV] instead of energy window at Co57 photopeak [122 keV]
as well as a peripheral photomultiplier (PMT) defect.

FIGURE 1.8 Left: A cold circular region completing a scintigraphy image before the daily
Quality Control (QC). Right: A uniformity control test shows that a group of photomultipliers
(PMTs) is out of order. Consequence is the cold region in the patient’s scintigraphy image.
Introduction 11

FIGURE 1.9A The patient was extremely claustrophobic and an acquisition by I-123-
Ioflupane (DATSCAN) for Striatum study was done with γ-camera heads at full radius. No
clear distinction of the imaged striatum. As a result, the obtained tomographic slices were
nondiagnostic – very bad quality images. (Images supplied courtesy of GE Healthcare.)

FIGURE 1.9B Properly acquired striatum images by DATSCAN. Left: Diagnosed as nor-
mal. Right: Characterized as abnormal.
12 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.10 (a) Transaxial image with no truncation. All 64 rows of the matrix were used
for the data. (b) Transaxial slice from severe truncation, which has been simulated by using
a row of ±10 pixels from the axis of rotation. (IAEA Quality Control Atlas for Scintillation
camera Systems, 2003.)

With truncation, the myocardium is still defined but is severely distorted.

During myocardial perfusion scintigraphy, truncation can occur when a
patient is too large to fit entirely within the Field of View (FOV) or is positioned
in such a way that a part of the body is outside the FOV. Missing emission data
are clinically acceptable as long as the entire heart is kept within the FOV.

1.2.3.3 Abnormal Distribution of the Radiopharmaceutical

Improvement of Quality in Nuclear Medicine demands best biological distribution of
Radiopharmaceutical in the patient body by: Optimum activity dose; the most suit-
able radiopharmaceutical; and proper chemical and physical form.
Two image examples of the impact of abnormal distribution of radiopharmaceuti-
cals in the Quality of the results are shown in Figure 1.11.

FIGURE 1.11 Degradation of image due to abnormal distribution of radiopharmaceutical.

(a) Image of a series of dynamic renal study. Radiopharmaceutical abnormal concentration to liver
and spleen is observed. (b) Unsuccessful labeling of Tc-99m and red blood cells. Abnormal con-
centration in skeleton and other organs is acquired due to presence of high percentage of alumina.
Introduction 13

1.2.4 Imaging Phantoms Are Quality Control

Tools in Nuclear Medicine
Phantoms are Quality Control tools in Nuclear Medicine. Three variations of them
depending to the scope of use are for:

Calibration – Ideal geometrical characteristics

Imaging – Tissue equivalent of known geometry
Dosimetry – Radioactive sources of standard dimensions

Calibration phantoms are used in procedures employing or measuring radio-

active material to evaluate performance. Phantoms often have properties simi-
lar to human tissue. Water demonstrates absorbing properties similar to normal
tissue; hence, water-filled phantoms are used to map radiation levels (Iturralde
P. M., 1990.
Imaging phantom in Nuclear Medicine is a specially designed object that is
scanned or imaged to evaluate, analyze, and tune the performance of imaging
devices used. A phantom is more readily available and provides more consistent
results than the use of a living subject and avoids subjecting a living individual to
direct risk. Phantoms are either employed for use in 2D-based imaging techniques in
planar γ-camera evaluation and phantoms with desired imaging characteristics have
been developed for 3D techniques such as SPECT, PET, CT, MRI, and hybrid imag-
ing methods or modalities.
A phantom used to evaluate an imaging device should respond in a simi-
lar manner to how human tissues and organs would act in that specific imag-
ing modality. Single Photon Emission Computed Tomography (SPECT) and
Positron Emission Tomography (PET) systems require periodic performance
testing. A modular phantom can be used to collect the data for the Quality
Control (QC) completeness of SPECT or PET systems. It permits measurements
of the resolution of radioactive (hot) lesions in a cold (clear background) field
and (cold) lesions in a radioactive (hot) field; uniformity of response to a uni-
form field, linearity, and a simple way to find the center of rotation. A more
sophisticated test suitable for acceptance testing may be done by measuring the
Point Spread Function (PSF), from which the Modulation Transfer Function
(MTF) may be calculated. Imaging phantoms are used for Quality Control (QC)
of diagnostic imaging systems in Nuclear Medicine as well as for training stu-
dents about used techniques.
Dosimetric phantoms are used to measure absorbed dose at the surface or at a
depth within their irradiated volume. Actually they are radioactive sources of stan-
dard dimensions.
Some of the phantoms used in Quality Control (QC) procedures of PET, SPECT,
and CT systems are shown in Figure 1.12.
AAPM CT performance phantom meets guidelines in American Association of
Physicists in Medicine (AAPM) Report No. 1, Performance Evaluation and Quality
Assurance of CT Scanners. It offers the user a single test object that measures ten
14 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.12 (a) National Electrical Manufactures Association (NEMA) sensitivity PET
phantom. Six concentric aluminum tubes used to detect camera sensitivity in PET. (b)
NEMA PET scatter fraction phantom. Made of four sections for ease of carrying/storage.
(c) Elliptical PET and SPECT Phantom™ Model ECT/ELP/P Deluxe ECT phantom with
elliptical body shape: Use with high spatial resolution SPECT and PET systems for evalu-
ation of data acquisition using noncircular orbit. (Data Spectrum Corporation, http://www.
spect.com/products.html.)

distinct CT performance parameters. Quality measurements are also useful in

Quality Control of hybrid systems SPECT/CT and PET/CT (Figure 1.13).
By NEMA IEC PET body phantom Image Quality (IQ), a test can be com-
pleted to simulate whole-body imaging with hot and cold lesions. Body phantom
(IQ) is used with different fillable spheres for imaging parameters determination
in PET and PET/CT. It is designed in accordance with the recommendations
by the International Electro-technical Commission (IEC) and modified by the
National Electrical Manufacturers Association (NEMA). It is recommended for
use in the evaluation of reconstructed image quality in whole-body PET imaging
(Figure 1.14).

FIGURE 1.13 An imaging phantom for determining computed tomography (CT) perfor-
mance in SPECT/CT and PET/CT Nuclear Medicine imaging systems, AAPM Report No.
1, 1977, CT Performance Phantom. (CIRS Model 610 AAPM CT Performance Phantom,
Universal Medical, https://www.universalmedicalinc.com/aapm-ct-performance-phantom.
html.)
Introduction 15

FIGURE 1.14 NEMA IEC PET Body Phantom Set™, The body phantom with a lung insert
and an insert of six spheres with various sizes.

1.2.5 Hybrid Systems Quality Assurance (QA) – Fusion

In addition to stand-alone imaging modalities, integrated dual-modality imaging
methods by the hybrid imaging systems SPECT/CT, PET/CT, and PET/MRI are
used to provide more diagnostic information.
Single Photon Emission Tomography (SPECT) or Positron Emission Tomography
(PET) and Computed Tomography (CT) differ in that SPECT or PET evaluates phys-
iology and CT gives anatomy information.
The clinical application of hybrid technology includes the ability to register
or “fuse” a CT or a magnetic resonance imaging (MRI) data with an emission
tomography data (SPECT or PET) to add anatomy information to the physiology
imaging.
Hybrid systems of SPECT/CT or PET/CT allow the combined assessment of anat-
omy and function. Furthermore, Integrated PET/MRI can provide complementary
functional and anatomical information about a specific organ or body system at the
molecular level.
Hybrid SPECT/CT cameras are well accepted for improved attenuation correc-
tion and accurate localization. The potential of SPECT/CT imaging for lesion char-
acterization increases by the use of diagnostic CT. Recent technological advances
will also enhance the role to be played by quantitative SPECT/CT for dosimetry
estimates in individualized radionuclide therapy (Israel. O. et al., 2019).
In (AAPM, 2019c), recommendations for performing acceptance tests and annual
physics surveys of γ-camera and SPECT and SPECT/CT systems are made. SPECT
and CT spatial alignment and attenuation correction accuracy for optimum image
quality are the recommendations for SPECT/CT hybrid system.
The tests described in the AAPM Report No. 177, 2019 are categorized into four
sections: Physical Inspection, γ-Camera Planar Tests, SPECT Tests, and SPECT/CT
16 Clinical Nuclear Medicine Physics with MATLAB®

Tests. The tests include recommendations for both acceptance testing and an annual
physics survey.

1.2.5.1 Quality of Performance and Advantages Utilizing SPECT/CT

Image registration is defined as the transfer of two image datasets into one common
coordinate system. A distinction can be made between:

• Software-based registration of datasets acquired independently one from

each other by two different imaging devices; and
• Hardware-based registration where the two datasets are obtained by hybrid
equipment in a single imaging session.

A high-quality SPECT/CT study requires a reliable, well-functioning hybrid sys-

tem which has met acceptance testing criteria and which is regularly monitored for
Quality of Performance.
The acquisition and processing protocols must be carefully followed and:

• The technical staff (doctors and Medical Physicists as well) of the Nuclear
Medicine department should be well trained to perform and monitor both
components of the study according to a well-defined protocol.
• Workstations that allow integrated viewing of the functional and anatomic
data should be used for the interpretation of the SPECT/CT images.
• The images must be reviewed for technical and diagnostic quality before
the patient leaves the department.

Precise image registration in the hybrid imaging study by SPECT/CT makes the
interpretation of high signal-to-background (S/B) functional images – combined
with better anatomic information – more credible.
Anatomical accuracy of image registration in SPECT/CT hybrid imaging
is a high advantage of the system. Increased specificity is achieved through a
more precise localization by CT and characterization of functional findings by
SPECT.
The use of the CT component of a SPECT/CT patient examination, for correct-
ing the SPECT data for attenuation and scatter is crucial, for proper estimation
of radioactivity concentration in specific organs or tissues on a volumetric basis
(IAEA, 2008).

1.2.5.2 SPECT/CT Fusion

Skeletal SPECT/CT is the new imaging gold standard when searching for osseous
metastases. The improved diagnostic accuracy of SPECT/CT is associated with
greater diagnostic confidence.
Two relative cases are shown in Figures 1.15 and 1.16.
Through hybrid imaging by SPECT/CT (Figure 1.17), the Nuclear Medicine
expert contributes to better health care by clinical interventions to the individual
patient’s needs (Israel O. et al., 2019).
Introduction 17

FIGURE 1.15 (a) Fused SPECT/CT image of a lumbar vertebra in a patient with breast
cancer is shown. Increased uptake of Tc-99m-MDP into the arthrosis of the facet joint is
observed. (b) A similar image in another breast cancer patient is depicted. Although the
SPECT appearance of the lesion is quite similar to that in patient A, the CT overlay proves
it to be a small osteolysis Fused images also indicate that SPECT/CT is a clinically relevant
component of the diagnostic process in patients with non-oncological disease referred for
bone scintigraphy. (Extracted from IAEA, TECDOC 1597, 2008.)

FIGURE 1.16 A 74-year-old patient after recent trauma showing enhanced uptake of
Tc-99m-MDP in a vertebral body of the lower thoracic spine. (a) 3D-volume rendering of
the SPECT/CT fusion shows that a lesion is in the 12th vertebral body. The inspection of the
fused tomogram proves it to be a fracture; moreover, the examination discloses it to be unsta-
ble since (b) the posterior cortical is involved, thus motivating immediate surgery. (Extracted
from IAEA, TECDOC 1597, 2008.)
18 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.17 A 6-year-old child with newly diagnosed neuroblastoma was referred for
staging. I-123-mIBG SPECT/CT localizes abnormal tracer uptake to the primary lesion in a
large mass in the right adrenal. (Courtesy of Israel O. et al., 2019.)

1.2.5.3 Hybrid PET/CT

A Quality Assurance (QA) program for a hybrid PET/CT system is necessary to
complete an initial evaluation of the performance of the system so that a baseline
of measurements could be established. Then periodic assessment of system perfor-
mance on an annual, quarterly, weekly, and daily basis should follow.

1.2.5.3.1 PET/CT Acceptance Testing and Quality Assurance

The American Association of Physics in Medicine (AAPM) published in October
2019 the Report No. 126, which is referred to PET/CT Acceptance Testing and
Quality Assurance (AAPM, Report No. 126, 2019b). A rigorous Quality Assurance
(QA) program for PET/CT is recommended.
Other international, European, or American organizations have published rec-
ommendations in relative reports or guidelines, such as: as International Atomic
Energy Agency (IAEA), International Electrotechnical Commission (IEC), National
Electrical Manufacturers Association (NEMA), American College of Radiology
(ACR), Society of Nuclear Medicine and Molecular Imaging (SNMMI), or European
Association of Nuclear Medicine (EANM).

1.2.5.3.2 PET/CT Image Quality by NEMA IEC PET Body Phantom Set™
The evaluation of PET system requires standard and reliable methods to allow the com-
parison of different PET systems using accepted measurement standards for the system.
NEMA provides guidelines to measure the performance of the PET component of a
PET/CT system by the body phantom with a lung insert and an insert of six spheres with
various sizes (Figure 1.14); NEMA organization has published a series of procedures
to evaluate the physical performance of PET systems. This NEMA standard is revised
periodically, and the latest update of this publication resulted in the NEMA NU2-2018.
The NEMA NU2-2012 quality control tests have been performed to evaluate this
system on site before clinical use (Jha A. K. et al., 2019). Performance measurements
of the PET component were made using the NEMA NU2-2012 procedures for spatial
Introduction 19

FIGURE 1.18 PET/CT image quality calibrations by NEMA body phantom. Schematically,
in this figure, we see the cold, hot spheres and background Region of Interests (ROIs).

resolution, scatter fraction, sensitivity, count rate loss and random coincidence esti-
mation, Noise Equivalent Count Rate (NECR), and image quality.
Image quality test for contrast recovery, background variability met all
specifications. Overall PET performance of whole-body system was satisfac-
tory and all the performance specifications required by NEMA NU2-2012
were satisfied.
In Positron emission tomography body phantom, the middle pipe represents
lungs, six fillable spheres with inner diameters of 10, 13, 17, 2, 28, and 37 mm.
Background activity concentration of the body phantom (Figure 1.18), hot lesions,
and cold lesions should be filled accordingly.
The analysis can be made on transverse sections (Demir M. et al., 2018) in which a
circular region of interest (ROI) is drawn as close as possible to the dense inner diam-
eter of every cold and hot sphere. For background, ROIs of the same size of the hot
and cold sphere ROIs, drawn around and are outlined near the edge of the phantom.

1.2.5.4 New Generation of PET/CT

New generation of PET/CT has been introduced using silicon (Si) PM-based tech-
nology. In PET/CT devices, conventional analog PMs are replaced by the solid-state
technology aiming to improve time resolution, event collection (improvement of sys-
tem sensitivity), localization, and counting efficiency.
One limiting factor in the development of efficient and accurate PET systems is the
sensor technology in the PET detector. There are generally four types of sensor tech-
nologies employed: Photomultiplier Tubes (PMTs), Avalanche photodiodes (APDs),
Silicon Photon Multipliers (SiPMs), and Cadmium Zinc Telluride (CZT) detectors.
PMTs were widely used for PET applications due to their excellent performance
parameters of high gain, low noise, and fast timing. However, their sensitivity to mag-
netic fields turns the interest of technology to solid-state photodetectors applied to PET
systems. The two most promising types are SiPMs and CZT (Jiang W. et al., 2019).
20 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.19 Transversal images of the phantom obtained from (a) a SiPM-based PET-CT
and (b) a PET/CT scanner with a conventional Photon Multipliers (PMs) detector, with a
sphere-to-background activity ratio of 4:1. Image acquisitions and reconstructions were per-
formed as in the patient study. (Courtesy by Oddstig J. et al., 2019.)

• SiPMs have been employed to both PET/CT and PET/MRI systems due
to their high timing resolution, low operation voltage, and their features
of compactness and immunity for coexistence with magnetic fields.
However, efforts are still needed to improve the performance of SiPMs
for lower noise, higher photo-detection efficiency (PDE), and even better
timing resolution.
It is predicted that digital silicon photomultipliers (dSiPMs) might over-
take analog SiPMs in future PET systems.
• Cadmium Zinc Telluride (CZT) detectors show excellent position and
energy resolution, but their PET applications are limited due to their poor
timing resolution performance.
A comparison of measurements performed in analog PET/CT equipped
with conventional PMTs with the signal recovery obtained from digital
PET systems, in hot sphere inserts of the NEMA/IEC NU2 phantom high-
lighted the improved signal-to-noise ratios achievable with the new digital
PET devices compared to conventional ones (Gnesin S. et al., 2020).

To compare the image quality and diagnostic performance of a SiPM-based PET/

CT with a PET/CT system with a detector that uses conventional Photo Multipliers,
imaging (Figure 1.19) of the National Electrical Manufacturers Association NEMA-
IEC body phantom and 16 patients was carried out by (Oddstig J. et al., 2019).
Results indicate that the new generation of PET/CT scanners might provide better
diagnostic performance; though further quality studies are needed.

1.2.5.5 Comparison of Quantitative PET/CT and SPECT/CT

Quality Control for quantitative SPECT will require a regular check of agreement
between the dose calibrator and reconstructed SPECT values for radioactivity.
For PET systems, cross-calibration is slightly simpler than for SPECT, as in PET
all the radiation has the same photon energy and characteristics, 2 × 511-keV annihi-
lation photons, independent of the radiotracer. Various radiotracers used by SPECT,
with different photon energies, require separate calibrations and checking.
Introduction 21

FIGURE 1.20 Comparison of quantitative PET/CT (F-18) and SPECT/CT (Tc-99m) images
in IEC body phantom containing six fillable spheres. T:B indicates actual target to back-
ground ratio for each experiment between concentration of radioactivity in spheres and in
general compartment of phantom. Quantitative results are obtained for single slice through
phantom corresponding to central section through largest sphere. (Extracted from Bailey
D. L. et al., 2013.)

In Figure 1.20, a comparison of the NEMA/IEC phantom quantitative images is shown.

In this example, PET Standardized Uptake Values (SUV) is slightly overesti-
mated by about 8% whereas SPECT images are underestimated by about 11% prob-
ably because of Partial-Volume-Effect losses caused by poorer spatial resolution in
SPECT than in PET. The absolute differences between the SUVs of SPECT and PET
were generally very small.

1.2.5.6 From PET/CT to PET/MRI

PET does not provide clear visualization of the anatomical structure because it has
relatively poor spatial resolution. PET/CT has been proposed to overcome this limi-
tation, and this hybrid system provides more clinically useful information than either
a PET or a CT stand-alone system.
The inability of simultaneous acquisition and the reduced soft tissue contrast in
PET/CT have led to the development of PET/MRI which offers the better soft tissue
contrast over CT. CT as synergistic modality offers anatomical details. However,
MRI combines structural and molecular imaging (Hu Z. et al., 2014).
PET/CT multimodality imaging provides both metabolic information and the ana-
tomic structure, but because of the higher soft-tissue contrast of MRI and no extra
ionizing radiation, PET/MRI imaging seems to be preferred as the method of choice.
PET/MRI, though, has many technical difficulties to overcome, such as PM tubes,
which cannot work properly in a magnetic field, and the inability to provide density
information on the object for attenuation correction (Jung J. H. et al., 2016).
Hybrid PET/MRI offers potential benefits that help in the improvement of
PET images. The combination of MR imaging – anatomic imaging and highest
resolution – with PET – metabolic imaging with high sensitivity – has a high-
clinical impact.
22 Clinical Nuclear Medicine Physics with MATLAB®

The advantage of MRI as synergistic modality in a hybrid system versus the CT

is the ability of much better soft tissue contrast. High-resolution anatomical informa-
tion from MRI can be used to enhance PET image quality and this is the desirable.
PET is a noninvasive metabolic imaging technique which traces the physio-
logical and pathophysiological process at molecular level (Boss A. et al., 2010).
However, PET does not offer any anatomical information, which is really the major
drawback of it.
MRI, though, offers an immense 3D soft tissue contrast. This enables it to be a
privileged technique as a first-line method of choice for the assessment of tumor.
By registration of high-resolution MR images, PET reconstruction improved with
information derived from MRI. MRI with higher soft-tissue contrast in comparison
with CT makes it easier to define the regions of interest in PET images that do not
provide anatomic details (Jung J. H. et al., 2016).
Integrated positron emission tomography (PET)/magnetic resonance imaging
(MRI), which can provide complementary functional and anatomical information
about a specific organ or a body system at the molecular level, has become a power-
ful imaging modality to understand the molecular biology details, disease mecha-
nisms, and pharmacokinetics.
The system produces a better performance in terms of detection and technical
possibilities. PET stability metrics demonstrated that PET quantitation was not
affected during simultaneous MRI (Musafargani S. et al., 2018).
There were various technical challenges in integrating PET and MRI in a single
system, with minimum interference between PET and MRI (Hu Z. et al., 2014).
Multicenter and multivendor Quality Control (QC) and harmonization of quanti-
tative PET/MR performance are feasible by using dedicated phantom protocols
(EANM Boellaard et al., 2015).
Simultaneous PET/MRI will be best suited for clinical situations that are disease-
specific, organ-specific, related to diseases of the children, or in those patients under-
going repeated imaging for whom cumulative radiation dose must be kept as low as
reasonably achievable.
It appears logical that PET/MRI may be the multimodality of choice in view of
less radiation exposure and all that is offered by MRI and PET for a comprehensive
structural and metabolic assessment of pediatric patients. Hybrid PET/MRI may
play a significant role in the care of children, particularly with cancer, who may need
to undergo repeated diagnostic imaging sessions, and it is desirable to minimize
their cumulative radiation exposure (Jadvar H. and Colletti P. M., 2014).
Figure 1.21 shows a fusion image of F-18 fluoroethyl-L-tyrosin registered PET/
MRI of a grade II astrocytoma. Anatomical information on MRI allows for a region
of interest definition.
Software registration with MRI is utilized in clinical applications and
allowed more accurate localization of metastatic lesions, especially in the head
and neck area.
However, software-based registration suffers from anatomical inaccuracies cause
of different positioning of the patient in the two separate imaging devices. In addi-
tion, software-based registration becomes difficult in case that a radiopharmaceuti-
cal is highly specific for a certain tissue as the images of its distribution are, with
Introduction 23

FIGURE 1.21 Image fusion following software registration. Software registered PET/MRI
image of a grade II astrocytoma. (Extracted from Slomka P. J. and Baum R. P., 2009.)

regard to anatomical detail, poorer. These limitations are greatly reduced in hard-
ware-based registration that should therefore offer a higher anatomical accuracy of
image fusion.

1.2.5.7 Hybrid SPECT/MRI

The combination of SPECT and MRI raises great expectations for further advantage
of multimodal imaging. The combination of SPECT and MRI is currently absent
from the range of clinical multimodality systems, although work is in progress to
produce the first pattern.
In medical imaging, SPECT can provide specific functional information while
magnetic resonance imaging (MRI) can provide high spatial resolution anatomical
information as well as complementary functional information.
A miniaturized dual-modality SPECT/MRI (MRSPECT) system was developed
by Hamamura M. J. et al. (2010) and shown the feasibility of simultaneous SPECT
and MRI data acquisition. In this MRSPECT system, a cadmium-zinc-telluride
(CZT) detector was interfaced with a specialized radiofrequency (RF) coil and
placed within a whole-body 4Tesla MRI system.
The metallic components of the SPECT hardware alter the B field and generate
nonuniform reduction in the signal-to-noise ratio (SNR) of the MR images. The
presence of a magnetic field creates a position shift and resolution loss in the nuclear
projection data. Various techniques were proposed to compensate for these adverse
effects. Overall, these results demonstrate that accurate, simultaneous SPECT and
MRI data acquisition is feasible, justifying the further development of MRSPECT
for either small-animal imaging or whole-body human systems by using appropriate
components.
24 Clinical Nuclear Medicine Physics with MATLAB®

The radionuclide-based SPECT imaging techniques have relatively poor resolu-

tion but, like PET, are sensitive to picomolar tracer concentrations, while MRI gives
high-resolution anatomical information but suffers from much lower sensitivity to
concentration of contrast agent. The combination of both imaging techniques can
offer synergistic advantages. With a SPECT/MRI system, simultaneous dynamic
imaging of both structure and function would be feasible, even using multiple tracers
simultaneously, providing valuable and accurate information with regard to disease
staging and therapeutic outcome. However, all the works that are currently being
executed to develop hybrid SPECT/MRI agents are applied in their preclinical stage
of development.
Recently, there has been great interest in evolving nanoparticles with dual modal-
ity SPECT/MRI properties. Nanoparticles represent very attractive candidates for
hybrid imaging due to their unique size and physical properties, allowing visualiza-
tion of biological events at subcellular levels.
Functional process of nanoparticles increases the affinity of them to the biologi-
cal target through a phenomenon known as “multivalency”, allowing for targeted
imaging of the disease. Furthermore, their large surface area permits multiple mark-
ing of imaging agents (Bouziotis P. and Fiorini C., 2014).
A major limitation in the development of simultaneous SPECT/MRI systems
is the compatibility of detectors and electronics with MRI operation. In SPECT/
MRI developments, arrays of pixelated CdTe and CdZnTe (CZT) γ-detectors are
employed as they offer the advantage of a high-energy resolution. Furthermore, the
simultaneous use of multiple radionuclides which emit γ-rays at different energies
can be enabled.
These detectors are composed of a large number of pixels which require a large
number of electronic readout channels, executed by the use of application-specific
integrated circuits (ASICs). Such detectors have shown that a shift of the signal
charge inside the detector, caused by Lorentz forces of the MRI, affects performance
and requires corrections.
MRI compatible SPECT systems can also be based on scintillators, read out by
silicon photomultiplier (SiPM) photo-detectors. This approach offers the advan-
tage of using SiPM technology, which is intrinsically compatible with MRI; but the
energy resolution offered by scintillation detectors is poorer than that achievable
using solid-state CdTe and CZT detectors, which makes multiple radionuclide acqui-
sition more challenging.
Preclinical systems have been developed, but there are several obstacles in devel-
oping a clinical model including the need for the system to be compact and station-
ary with MRI-compatible components.
There is still much to do to reach a stage of demonstrating robustness of SPECT/
MRI and evaluating its clinical utility. Whether solid-state detectors or SiPM read-
out systems will become the design of choice remains to be seen. Extension of design
ideas to permit whole-body acquisition may require a larger bore than typical of cur-
rent MRI systems. Wide bore systems are clinically appealing to improve patients’
comfort; so, the MRI system development may be dictated by clinical demands.
Clinical performance similar to that available on conventional SPECT systems
should be possible with relatively compact detector/collimator combinations, but
Introduction 25

further innovation may be needed when the Field of View (FOV) is enlarged to cover
the whole body (Hutton B. F. et al., 2018).
The dual radionuclide capability has a particular appeal. The development of
appropriate technology remains challenging, but ultimately may lead to more gen-
eral superior SPECT performance; although the clinical need for a simultaneous
SPECT/MRI acquisition remains to be demonstrated.

1.2.5.7.1 MR-Based Attenuation Correction: PET/MRI versus SPECT/MRI

In hybrid PET/MRI systems, attenuation correction (AC) algorithms based in
MRI data are used. As clinical SPECT/MRI systems are under dynamic growth,
it is important to ascertain whether MR-based AC algorithms validated for PET
can be applied to SPECT. Two imaging experiments (Marshall H. R. et al., 2011)
were performed, one by an anthropomorphic chest phantom and one by two
groups of canines to study and compare the PET/MRI and SPECT/MRI results
(Figure 1.22).
The quality of the Nuclear Medicine reconstructions using MRI-based attenua-
tion maps was compared between PET and SPECT. The sensitivity of these recon-
structions to variations in the attenuation map was ascertained. It was found that
the SPECT reconstructions were of higher fidelity than the PET reconstructions and
they were less sensitive to changes to the MRI-based attenuation map. Thus, it is
expected that MRI-based AC algorithms designed for PET/MRI to reveal better per-
formance and quantification when used for SPECT/MRI.

FIGURE 1.22 Results of the sensitivity analysis per tissue type; the black bars correspond
to SPECT and the white bars to PET. The asterisks denote statistically significant differ-
ences. The error bars represent the standard deviation (SD) of the sample. (From Marshall
H. R. et al., 2011.)
26 Clinical Nuclear Medicine Physics with MATLAB®

1.3 QUALITY ASSURANCE (QA) OF IMAGING SYSTEMS

BASED ON INTERNATIONAL STANDARDS
Many guidelines of international organizations and professional bodies for Quality
Assurance (QA) and Quality Control (QC) of the instrumentation in Nuclear
Medicine are available. Guidelines in Nuclear Medicine continue to be developed
for modern systems. World organizations generally coordinate the development of
guidelines, but they recognize the need for national guidelines.
The purpose of the guidelines is to offer to Nuclear Medicine team a framework,
to be helpful in daily practice.
QA program in Nuclear Medicine necessitates the use of QA standards, protocols,
and phantoms that have been set by the international organizations. Many world
organizations, as International Atomic Energy Agency (IAEA), have published rela-
tive guidelines; some of them include:

AAPM: American Association of Physicists in Medicine

DIN: German Institute of Standardization (Deutsches Institut fur Normung)
EANM: European Association of Nuclear Medicine
EFOMP: European Federation of Medical Physics
IAEA: International Atomic Energy Agency
ICRU: International Commission of Radiation Units and Measurements
IEC: International Electrotechnical Commission
NEMA: National Electrical Manufacturers Association
SNMMI: Society of Nuclear Medicine and Molecular Imaging; and many others
offer publications, guidelines, standards, and reports

IAEA cooperates with the World Health Organization (WHO) and the Pan American
Health Organization (PAHO) among others, in the area of radiation medicine and of
radiological safety, security, and emergencies. The arrangement covers collaboration in
quality and safety in radiation medicine (radiotherapy, diagnostic radiology, and Nuclear
Medicine); radiological safety, security, and emergencies; information sharing; and med-
ical physics. Joint activities focus particularly on Latin America and the Caribbean.
In IAEA Human Health series, guidelines relative to Nuclear Medicine Quality
Assurance of instrumentation are deposited as:

i. Guidelines concerning the Quality Assurance for PET and PET/CT Systems
in IAEA (2009) Human Health Series, No. 1; and
ii. PET/CT Atlas on Quality Control and Image Artefacts in IAEA (2014)
Human Health Series No. 27.
As well as,
iii. Quality Assurance for SPECT Systems, IAEA (2009) Human Health Series
No. 6; and
iv. SPECT/CT Atlas of Quality Control and Image Artefacts, IAEA (2019)
Human Health Series No. 36, are addressed.
• EANM networks with other associations, including EFOMP, IAEA,
SNM, World Federation of Nuclear Medicine and Biology (WFNMB;
Introduction 27

www.wfnmb.org), and WHO for Quality harmony of Nuclear Medicine

in Europe. EANM has established guidelines for instrumentation QA
taking into account the recent technological advances, the education
and training requirements (EANM, 2010b).
• Acceptance Testing for Nuclear Medicine Instrumentation (EANM,
2010a).
• Routine Quality Control Recommendations for Nuclear Medicine
Instrumentation (EANM, 2010b).
• Curriculum for education and training of Medical Physicists in Nuclear
Medicine. EANM and EFOMP recommendations (EANM, 2013).

NEMA, National Electrical Manufacturers Association, (www.nema.org) is the

“Association of Electrical Equipment and Medical Imaging Manufacturers” and has
published many standards, as:

• NEMA NU1-2018. This NEMA Standard provides a uniform criterion for

the measurement and reporting of γ-camera performance parameters for
single and multiple crystal cameras and tomographic devices that image a
section or reconstruction image volume, or both.
• NEMA NU2-2018 Performance Measurements of Positron Emission
Tomographs (PET). This Standard provides a uniform and consistent
method for measuring and reporting performance parameters of PET
systems. NU2 makes it possible to objectively compare PET systems in
purchase decision process; after delivery, tests are defined to ensure that a
quality system is included.

MITA, “Medical Imaging and Technology Alliance” is a division of NEMA. The

MITA is the collective voice of medical imaging equipment manufacturers, radio-
pharmaceuticals, innovators, and product developers. Division members interact
with health-care professionals to establish standards, reduce regulatory barriers and
for consultation of the medical imaging industry.
DICOM, “Digital Imaging and Communications in Medicine” is the interna-
tional standard to transmit, store, retrieve, print, process, and display medical imag-
ing information. It makes medical imaging information interoperable.
DICOM makes medical imaging information interoperable, integrates image-
acquisition devices, PACS, workstations from different manufacturers and is actively
developed and maintained to meet the progressing technologies and needs of medi-
cal imaging, https://www.dicomstandard.org/.
In the United States, many guidelines are available by the Society of Nuclear
Medicine and Molecular Imaging (SNMMI) and the American Society of Nuclear
Cardiology (ASNC).
The ASNC at June 21, 2018, has published an update to its guidelines for SPECT, with a
focus on advances in myocardial perfusion imaging (MPI). https://www.dicardiology.com/
channel/spect-imaging/. The new guideline features updates on new hardware, collimators,
and cadmium zinc telluride (CZT) detectors. This guideline earned the endorsement of the
Society of Nuclear Medicine and Molecular Imaging (SNMMI).
28 Clinical Nuclear Medicine Physics with MATLAB®

In Australia, courses or scientific meetings are prepared by the Australian/New

Zealand Standards (ANZSNM) about imaging systems and radiation detection,
physics, nuclear medicine technology, radiopharmaceutical sciences, radionuclide
therapy, https://www.anzsnm.org.au.
In the European Union (EU), the European Commission (EC), provides guide-
lines and reports, addresses to Member States, the needs of medical procedures
applying ionizing radiation in today’s growing use of higher-dose medical equipment
as hybrid PET/CT or SPECT/CT imaging systems.
In 2009, European Commission by No-159 “guidelines on clinical audit for medical
radiological practices (Diagnostic Radiology, Nuclear Medicine and Radiotherapy)”
provides advice and detailed guidance to responsible professionals in Member States,
on the implementation of part of the MED Directive (Council Directive 97/43/Euratom,
1997), https://ec.europa.eu/energy/sites/ener/files/documents/159.pdf.
No-175 guidelines of the EC, published in 2014, refer to radiation protection
education: “Guidelines on radiation protection education and training of medical
professionals in the European Union”, https://ec.europa.eu/energy/sites/ener/files/
documents/175.pdf.
ICRP, the International Commission on Radiological Protection, (www.icrp.
org) has developed the System of Radiological Protection which is the basis of all
standards, regulations, and practice of radiological protection worldwide.

• ICRP Publication 128, 2015 is referred to “Radiation Dose to Patients from

radiopharmaceuticals: A Compendium of Current Information Related to
Frequently Used Substances” (Ann. ICRP 44[2S]). The data presented in
this report are intended for diagnostic Nuclear Medicine and not for thera-
peutic applications.
• ICRP Publication 140, 2019. Radiological protection in therapy with radio-
pharmaceuticals. Ann. ICRP 48(1).
The recommendations and guidance of ICRP are all referred in the com-
mission’s journal, the “Annals of the ICRP”. Annals of the ICRP are the
authoritative source of recommendations and guidance of the International
Commission on Radiological Protection (ICRP).

The principal objective of ICRU, the International Commission of Radiation Units

and measurements, is the development of internationally accepted recommenda-
tions for:

1. Quantities and units of radiation and radioactivity;

2. Procedures suitable for the measurement and application of these quantities
in diagnostic radiology, radiation therapy, radiation biology, nuclear medi-
cine, radiation protection, and industrial and environmental activities; and
3. Physical data needed in the application of these procedures, the use of
which assures uniformity in reporting.

NCRP, the National Council on Radiation Protection and Measurements, has pre-
pared Report No. 176 for “Radiation safety aspects of nanotechnology” in 2017.
Introduction 29

This report is intended primarily for operational health physicists, radiation safety
officers, and internal dosimetrists responsible to establish and use radiation safety
programs involving radioactive nanomaterials. It describes the current knowledge
relating to nanotechnology that is relevant to radiation safety programs.
It considers operational health physics practices that may be modified when nano-
technology is involved and includes specific guidance for conducting internal dosim-
etry programs when nanomaterials are being handled.
AAPM, the American Association of Physicists in Medicine. Medical Physicists are
concerned with three areas of activity: Clinical Service and Consultation, Research and
Development, and Teaching. On the average, their time is distributed equally among
these three areas as it is stated in the “Definition of a Qualified Medical Physicist
Standard”, 2019, https://www.aapm.org/medical_physicist/fields.asp#nuclear.
All guidelines are referred to “procedures of good quality without needless details”,
that is “good practice through minimum requirements” and their target has to be:

• The skeleton of a local protocol

• Adapted in changes without loss of quality
• Easy to handle results in communication between different centers
• Good standards for training programs

The purpose is to provide Nuclear Medicine practitioners (physicists, technologists,

physicians) with guidelines in creating QC protocols of all instruments of a Nuclear
Medicine Department (counting devices, imaging systems) with a special focus on
new, sophisticated, digital technologies.
In order to be the “skeleton” of a local protocol, guidelines would be adapted in
changes without loss of quality.
Imaging guidelines must be established, in each country where Nuclear Medicine
applications are used, taking under consideration the recommendations of the inter-
national standards as a guide. Reports of the assessment of equipment performance,
typical patient dose, and the Image Quality compared to the standards should be
checked locally in time intervals. A suggestion of the frequency that checks have to
be done after installation is annually, monthly, at maintenance, following a service
of detectors or electronics and daily tests.
Every Nuclear Medicine department ought to organize its own program according
to its needs and workload. It must be efficient keeping the instrumentation in good con-
dition preventing any deterioration. Logbooks are suggested to be deposited in every
Nuclear Medicine department, as proper record keeping detection of gradual deterio-
ration of performance over a long time interval. Analysis of the results for degradation
and initiating the necessary corrective action is the way for good practice.
The QA program must also be harmonized with the world legislation against the
dangers arising from Ionizing Radiation.
General reference for Quality Control (QC) procedures are covered by following
summary schedule:

1. Acceptance quality control: To ensure that the performance of the system

meets the technical and performance specifications quoted by the manufacturer.
30 Clinical Nuclear Medicine Physics with MATLAB®

2. Reference quality control: At the time of system installation and repeated

annually regularly, or even after major failure of any part of the system, to
give a new set of reference data.
3. Routine quality control: Should be carried out regularly, to ensure opti-
mum performance of the system or detect any deterioration in a daily base.

1.4 THE QUALITY OF SCIENTIFIC AND CLINICAL OUTPUT

Quality of clinical output data can refer to the accuracy and precision that these data
are obtained and the criteria applied to obtain them. The optimization of results
extraction in Nuclear Medicine departments is dependent on the use of:

• optimally performing equipment; and

• successful clinical image processing.

Information Technology now plays a crucial role in Nuclear Imaging. During

the last decade, Nuclear Medicine Technology has evolved not only to hardware
systems developments, but also offers advanced informatics, quality, and quan-
tification software.
Nuclear Medicine imaging has become increasingly complex, and management
of image information requires common concepts, terminology, and measurement
methodology. This is essential for the benefit of the patient to ensure maximum diag-
nostic information with minimum potential risk.
ICRU in 1996 prepared Report No. 54 on subject related to medical imaging;
“Medical Imaging – Assessment of Image Quality”.
A theoretical framework on image quality and evaluation of medical imaging
systems, including Nuclear Medical Imaging, is provided now in Current Activities
of ICRU, 2020.
Easy to use, fast, and precise data from imaging is a necessity. Access to more
accurate data drives to improved management of Nuclear Medicine departments and
customized patient treatment.
Software to enhance image quality or automate quantification and measurements
is an assistance tool in Medical Physicists’ hands, to monitor and possibly reduce
tracer dose, offer analytics on procedures, imaging statistics, and reliable data of
equipment performance. Dedicated software in high-level analytical information is
a contributor to the Quality Management (QM) of the department (Fornell D., 2018).

1.4.1 Data Quality
Data are of high quality if they correctly represent the real world to which they refer.
Figure 1.23 refers to two examples of how to measure data or reflect data distribution.
Imaging system assessment depends on the task for which the system is intended,
so there is:

• A need to understand not only the physics of the equipment but also the way
that acquisition data affects results.
Introduction 31

FIGURE 1.23 (a) Accurate measurements in a dose calibrator or (b) an homogeneous rep-
resentation of a uniform object (homogeneous flood source of Co-57).

• Crucial to deep knowledge, of the clinical impact of equipment perfor-

mance and acquisition methods.
• Essential to ensure that data is acquired correctly.

There is no point in optimizing the resolution of the camera if the user does not
acquire clinical data in such a way as to maximize resolution (e.g., distance effects).
The ICRU Report No. 54, Medical Imaging, The Assessment of Image Quality,
1996, proposes a framework, based on statistical decision theory, within which
imaging system performance may be measured, optimized, and compared. It is pro-
posed that the analysis based on the acquired data could provide an assessment of
the potential performance of the imaging system and may link the purely objective
measures of device performance to the subjective assessment of image quality. The
analysis of the acquired data has the advantage of allowing one to investigate the
effect on performance by altering various parameters of the imaging system.

1.4.2 Data Resolution – Noise Data

Data resolution should match, at least, the imaging system resolution. When the data
are digitized, the continuous coordinates become discrete coordinates. The spatial
and temporal resolution will be lost unless the digitation is much finer than the sys-
tem resolution. Imaging devices introduce blurring in the data of the image.
Data density is low and it is based on random events (disintegrations), so the
image is subject to random noise. Random noise in the frequency domain gives a
final image equal with real data plus noise data.
Image noise is the degree of variation of pixel values caused by the statistical
nature of radioactive decay and detection processes. Even if we acquire an image of a
uniform (flat) source on an ideal γ-camera with perfect uniformity and efficiency, the
number of counts detected in all pixels of the image will not be the same (Figure 1.24)
(Moore S., 1997).
The counting noise in Nuclear Medicine is Poisson noise, so that the pixel noise
variance is equal to the mean number of counts expected in a given region of the
image. Percentage image noise is expressed by the equation:

% image noise = (σ /N ) × 100% (1.1)

32 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.24 Image noise impression (standard deviation of noise = square-root of average
pixel count N). (Courtesy of Moore S. C., 1997.)

where standard deviation σ is the square-root of the variance. N is the average pixel
count.
Variance is the expectation of the squared deviation of a random variable from
its mean. Informally, it measures how far a set of (random) numbers are spread out
from their average value. The variance is the square σ2 of the standard deviation, σ.
The noise variance is the mean number of counts expected on a certain part of the
image. It is desirable to obtain as many counts as possible to reduce the percentage
of image noise. Main limitations are:

• the selected radiopharmaceutical activity to be injected; and

• the image acquisition time.

Nuclear Medicine imaging systems distort and suppress real data more than do with
noise. The deformation that the detector introduces in the “image” of an “object” is
described by the Point Spread Function (PSF) and results into blurring. Blurring is
caused by the relative suppression of the high-frequency components of the image in
the frequency domain. To find the shape of an “object” must deconvolute the “blur-
ring image” from the “image” of the object.
If Resolution could be better, Noise should be less than a problem. The effect of
the resolution loss depends on the processing procedure that is performed.

• Image processing endeavors for the “impossible” target of a noise-free

imaging with improved resolution but:
Introduction 33

• Noise improvement requires some averaging procedures which degrade

resolution and any attempt to improve resolution involves amplification of
high-frequency components which make the image noisier.

Nuclear Medicine images illustrate the problem of image processing due to their
relatively poor resolution and noise appearance. For example, enhancing the contri-
bution from the high-frequency components of the image selectively, the contribu-
tion of noise into the image is enhanced more.
By image processing we try to correct image parameters as exposure, contrast,
or low-count statistics, as well as we may also correct artefacts. However, Nuclear
Medicine images, often, suffer from low contrast; that is further degraded by the
noise introduced in the process of imaging (Lyra M. and Ploussi A., 2011). The
image optimization tools are:

• Filtering which is aimed at restoring the image blurred because of the

detector characteristics; and
• Smoothing (spatial and temporal) in order to reduce the effect of random
noise.

1.4.3 Attenuation Correction
The attenuation correction is dependent on a correct pixel size and attenuation fac-
tor, μ.
A cylindrical phantom, 20 cm in diameter, containing a homogeneous solution of
Technetium-99m (Tc-99m) can be used to acquire a high-count dataset. Attenuation
correction was applied using different linear attenuation coefficients. A profile
was drawn across one of the transverse slices (IAEA, Quality Control Atlas for
Scintillation camera Systems, 2003).
Figure 1.25 shows that, for the attenuation correction using μ = 0.11 cm−1, the pro-
file through the slice is essentially flat, apart from statistical fluctuations indicating
that the attenuation correction software is correct.
The attenuation correction determined by a homogeneous water-filled phantom is
not correct when applied to a nonhomogeneous patient. So, attenuation correction in
clinical imaging ought to be used carefully.
IAEA encourages and assists research development and practical use of atomic
energy and its applications for peaceful purposes throughout the world. It brings
together research institutions to collaborate on research projects of common interest,
so-called Coordinated Research Projects (CRPs). An IAEA Co-ordinated Project,
“Development and Validation of an Internet-based clinical and technical study
communication system for Nuclear Medicine” https://www.iaea.org/projects/crp/
e11013, was referred to software for imaging data communicating through the inter-
net. The participating countries included: Argentina, Austria, China, Cuba, Greece,
India, Thailand, United Kingdom of Great Britain and Northern Ireland, and United
States of America. A part of it (multimedia training package on planar γ-camera
and QC practice) is shown at http://www.medimaging.gr/cd/pages/intro.html.
34 Clinical Nuclear Medicine Physics with MATLAB®

FIGURE 1.25 Profiles to check the accuracy of attenuation correction. (a) No attenua-
tion correction. (b) Attenuation correction with μ = 0.11 cm−2. (Extracted of IAEA, Quality
Control Atlas for Scintillation Camera Systems, 2003.)

1.5 ACCURACY AND PRECISION IMPROVEMENT

IN QUANTIFICATION OF IMAGING DATA
Anyone who operates instruments will use terminology that refers to metrology.
The definition of metrology in encyclopedias and branch dictionaries is a science of
measurements covering all aspects concerning theory and practice.
Measuring instrument operators also have contact with metrology, the scientific
and technological metrology.
One basic activity referring to this type of metrology is the calibration process.
Operators are well aware of the importance of calibration results and of working in
accordance with the norms of quality systems. Results obtained from test procedures
Discovering Diverse Content Through
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Title: The Princess Athura: A romance of Iran

Author: Samuel W. Odell

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*** START OF THE PROJECT GUTENBERG EBOOK THE

PRINCESS ATHURA: A ROMANCE OF IRAN ***
 THE
PRINCESS ATHURA
A ROMANCE OF IRAN

BY
SAMUEL W. ODELL

NEW YORK
THOMAS Y. CROWELL COMPANY
PUBLISHERS
 Copyright, 1913, by
Thomas Y. Crowell Company

Published April, 1913

 CONTENTS
CHAPTER PAGE
I The Great King’s Last Battle 1
II An Oath 15
III Prexaspes 29
IV Athura 42
V Cambyses 58
VI Persepolis 76
VII “I am Cyrus, the King, the Achæmenian!” 92
VIII A Royal Council and a Royal Hunt 101
IX The Deeper Things 121
X A Farewell Feast 133
XI The Great King Introduces a Strange Custom 151
XII The Force of an Oath 165
XIII A Clash of Wills 179
XIV The War Against Egypt 198
XV The Madness of Cambyses 219
XVI The End of Oath-Keeping 235
XVII The Earless King 254
XVIII The Spider’s Web 266
XIX A Galloping To and Fro 280
XX The Overthrow of the Magi 297
XXI King of Kings 305
THE PRINCESS ATHURA
A Romance of Iran
 CHAPTER I
THE GREAT KING’S LAST BATTLE

IT was morning on the plains of Asia. Long-legged herons stood in

the shallows of the yellow Jaxartes, bathing their feet in its sluggish
flood and warming their bodies in the first rays of the sun. They were
silently and uneasily watching a host of armed men drawn out in long
battle-lines across the lowlands bordering the southern margin of the
stream.
Where the armed host stood was a sandy plain, about two miles
wide. Beyond this was a low range of sand-hills, which trended away
to the southeast, enlarging the plain as they receded from the river.
Cutting through hills and plain to join the river-bed was a dry water-
course, where, in winters only, a torrent flowed. In it were some
stunted trees and scattered thickets of shrubs. To the north of the
river was a vast plain on which the dry, yellow grass had been
withered by summer sun and wind. Far in the east appeared dimly
through a blue haze the summits of high mountains. Westward the
river had yet to flow half its length to the Oxian swamps. Here it was
wide and shallow and its banks were low and marshy.
The rays of the sun sparkled on the brazen breastplates and shining
blades of battle-axes, on the spear-points and gilded helmets, of two
hundred thousand men, who here awaited the approach of a far
more numerous host coming down from the east along the river
towards them. The light rested softly upon the stern, bearded faces
of veterans of many wars and the softer cheeks of young men on
this, their first campaign. They were men of Iran for the most part,
though some were Assyrians, Babylonians, Arabs, Hebrews, or
Greeks from the Ionian cities. They were followers of Cyrus, the King
of Kings, the Great King, ever victorious Lord of the World.
Those about to attack them were Touranian horsemen, known to
ancient history as Scythians, Massagetæ, Sacæ, and to modern
history as Tartars, Turks, or Kalmuks. The hearts of the soldiers of
Cyrus were glad. For the long, dusty marches in pursuit of an ever
retreating enemy would now end in a riot of blood and slaughter, and
perhaps they might then set their faces homeward. No doubt of
victory entered their minds. They were led by Cyrus, the invincible. It
mattered not if the enemy outnumbered them three to one, as their
scouts had reported. There would be more killing and a greater
victory.
Racial hatred, reaching back beyond history and tradition to the
distant age when the first family of man threw off branches to
different parts of the earth and the branches immediately claimed the
pleasant places and fought each other for them, animated both
parties to the coming conflict. The folklore of the early Aryans is
largely composed of tales concerning heroes who had saved their
people from the ravages of those fierce men of the North, the
Touranians. Century after century the wandering hordes of the great
northern plains hovered, like threatening clouds, along the
boundaries of Iran, looking across the mountains from their own arid
and wind-swept abodes to the rich and pleasant hills and valleys of
the South. The children of those tribes, in the days of Tamerlane and
Mohammed, broke over all barriers, crushed Eastern civilization, and
put back the clock of progress a thousand years.
Once even before the time of Cyrus, the wild Touranians had passed
over the mountains and pushed through into Mesopotamia, bearing
woe to the nations. Then, one day, their captains sat down to a
banquet prepared by the conquered ones and instead of meats were
fed with sword-blows and dagger-thrusts. Having thus been deprived
of leaders, the Touranian conquerors had suffered disaster; and all
had been either killed, enslaved, or driven back across the
mountains. Stories of that invasion were thereafter told at every
fireside of the Bactrians, Medes, Persians, and their kindred tribes;
and the mothers in Iran frightened their children into obedience by
threatening to hand them over to the dreaded monsters of Touran.
Having conquered all civilized Asia, Cyrus had thought to rest in his
palaces at Hamadan, or Susa, Babylon, or Pasargadæ; but there
had come word from ancient Balk, or Bactra, the mother city of all
Aryans, warning him that the Touranians were gathering for war in
numbers so immense that help must be sent. The great war-king had
at once responded. With half a million men he had marched into
Bactra, to the aid of King Hystaspis, who, under him, ruled there,
and, passing through the mountains on its northern border, he had
driven back the leading troops of the enemy. The Touranians had
retreated, seeking to draw him into the great plains, where they
hoped that they might crush him with overwhelming numbers. He
had followed carefully, building forts as he advanced, that his supply-
line might be safe, and leaving strong detachments to guard them.
With less than half his army, though its best part, he had arrived at
the great river, Jaxartes, and had waited there for the enemy to
assemble and attack him. Now they were coming and he was ready.
Cyrus had chosen the battle-ground. He had marched out of his
camp, situated a mile or so down the river, and had taken position
where the narrow plain enabled him to mass his forces, with the
sand-hills to protect his right, the river his left, and the dry water-
course his front. The enemy, coming down towards him, would be
compressed into an ever narrowing field where their immense
superiority in numbers would not give them undue advantage.
Knowing that the Touranians were all mounted and were
accustomed to charge in mass at headlong speed, he hoped to draw
them into the great ditch at his front in such confusion that the
impetus of their assault would be broken. For this purpose he threw
out to the east of the ditch about one thousand paces a curtain of
light cavalry, which had orders to draw an assault, retreat rapidly
before it, and take refuge behind the infantry. The position of the
infantry was a line about halfway down the western slope of the
water-course, and it would not be perceived by the pursuers until
they should arrive at the upper margin of the eastern slope. Keeping
five thousand of his heavy cavalry, known as the Imperial Guard, in
reserve on the high ground at his extreme left near the river, he had
stationed the remainder, about fifteen thousand strong, behind the
crests of the sand-hills at his extreme right; and it would be their duty
as soon as the Touranians should join battle, to make a détour to the
right, descend from the hills upon their rear, and there attack. Thus,
by the grace of Ahura-Mazda, Cyrus hoped, the enemy would be
placed between his veteran infantry and his invincible cavalry, and
so be ground to pieces.
Near the margin of the river in front of the army was a group of men
whose dress and demeanor denoted them leaders. One of these, to
whom the others gave worshipful attention, was mounted on a noble
Nisæan stallion. He was watching the distant mass of enemies with
searching attention. He seemed indeed a king and worthy to be a
King of Kings. Historians and storytellers have surrounded him with
heroic luster. His countenance was eagle-like. His forehead was
high, his nose sharp and slightly bridged, and his chin firm. The
piercing glance of his black eyes never failed to read men nor to
impress them with the necessity of instant obedience to orders. His
demeanor was humorous and kind toward friends but fierce and
terrible to evil-doers or to an enemy. Despite his sixty years, forty of
which had been spent in war, his body was erect and soldierly. A
helmet, glittering with gold, was on his head, and from beneath it his
straight gray hair fell to the collar of his cloak. A white, silky beard
covered the lower portion of his face and lay upon the silver breast-
scales of the flexible coat-of-mail which covered his body and hips.
Brazen greaves, fastened to soft leathern breeches, protected his
limbs. His only weapon was a short sword, pendent from a belt
around his waist. The trappings of his horse were rich. Its chest and
neck were also protected by link mail.
In the group of officers surrounding the Great King, there were two of
no less royal birth than he. One was Hystaspis, King of Iran, his
cousin, one of the Achæmenides, the family that had ruled in Iran for
ages. Cyrus had been King of Fars, or Persia, before he became
King of Kings. Hystaspis had ruled in Bactra, the ancient seat of the
Aryan race. Astyages was king of Medea and grandfather of Cyrus,
whose mother was a Medean princess. He claimed suzerainty over
all Iran. Cyrus had conquered his grandfather in war and, having
dethroned him, had stepped up into the exalted position of King of
Kings. He had then placed Persia under control of Hystaspis, who
loyally supported him and acknowledged him as the overlord of all
Iran. Cyrus was a warrior. Hystaspis was a student, a lover of peace
and a mystic, though he ruled his people well as a statesman and
showed qualities of a great warrior when necessity demanded. In his
youthful days he had known the famous Zoroaster, the seer of Iran,
who had reduced to writing the ancient songs and the ritual of
religious worship of his race and had preached new life into its
creed. Hystaspis was milder, more benevolent, and less alight with
energy than Cyrus.
Prince Darius Hystaspis, son of the King of Iran, was the other royal
person in the group. He had dismounted from his war-horse and,
with folded arms, was standing at its head, also watching the enemy.
Six feet in height and well-proportioned, youthful and gallant, he was
an ideal soldier. A helmet of gold and silver leaves covered his black,
short-cropped hair save at the temples. A coat of leaf-mail protected
his chest and his limbs halfway to the knee and was confined at his
waist by a broad leather belt studded with gems set in golden
buttons. A bronze plate further protected his breast, and greaves of
the same metal were fastened to his leather riding-breeches as a
protection to his legs. High-laced leather shoes encased his feet. A
short sword hung at his belt, and a short-handled battle-ax swung
from the saddle on his horse. A soldier from boyhood and already a
veteran, having served in Cyrus’ last campaign against Babylon, yet
he was, like his father, a student, and had learned wisdom of the
greatest seer of that age, Belteshazzer, the Hebrew. His shaven
cheeks were fair and glowing with the health of right living. His eyes
were blue and clear and were set deeply beneath dark eyebrows
and a lofty forehead. He was the idol of all Aryans, and, next to
Cyrus, the hero of the army. He was commander of the Imperial
Guard, and to him had been entrusted the duty of leading the Guard
in the flank movement by which Cyrus hoped to crush the enemy.
Otanes, a giant in size, the noblest of Iran’s seven great nobles, was
another of the group. He was shield-bearer to Cyrus and commander
of his chosen body-guard. There was also Hydarnes, another of the
seven nobles, a short, heavy man whose long, upturned mustache
and beetling eyebrows were his most prominent features. He was
commander of the Persian infantry. Vomisces, one of the seven
nobles and commander of the allied infantry, the Babylonian,
Assyrian, and Hebrew levies, and Gobryas, another one of the
seven, a young man, blood-brother and closest friend of Prince
Darius, were in the group. There was also Prexaspes, a Medean
noble, commander of the light-armed cavalry, a brave, ambitious
man, richly dressed in jeweled armor and having his hair and
whiskers curled and perfumed. He was a cynical, unscrupulous, and
pleasure-loving man, but energetic, resourceful, and brave. Of him
we shall hear much in this story. A number of orderlies waited near
by to receive and transmit the Great King’s commands.
The herons in the Jaxartes have become restless but have not yet
flown. While they wait and while Cyrus is watching the enemy, we
may study the private soldiers to whose blows he will owe his victory,
if he wins. They were not of the same quality as those effeminate
men who, in later years, were unable to withstand the Greeks under
the great Alexander. This was true at least of the Aryans who
constituted the bulk of the army.
Passing along the front of the light-armed cavalry, we observe the
dusky Arab, with his curved scimiter and long javelin, his bow and
arrows. He is clothed in turban, short tunic, loose cloak, brazen
breastplate, and leathern breeches. He is mounted on the beautiful,
swift horse of the desert which he loves as his own brother. Here
also we see famous bowmen from Edom and Canaan, slingers from
the Mediterranean isles, and Syrians from Mesopotamia, severally
arrayed in their national costumes. When we pass along the lines of
infantry, we note a distinctive army dress. Each soldier wears on his
head a high, round felt cap; on his body, a stout, leathern, tight-fitting
jacket, or tunic, with skirt extending halfway to the knee, and on his
legs linen trousers, confined at the ankles by the tops of the soft
leathern shoes with which his feet are shod. A bronze breastplate
covers his chest, and bars of the same metal are on his arms and
shoulders. The front rank, as it stands in position, is protected by
wicker shields, covered with heavy leather, braced with metal bands.
These shields are about seven feet long and are placed upright with
the pointed lower ends thrust into the earth. Behind them, as a wall,
the spearmen are comparatively safe from the enemy’s javelins and
arrows. If the fight comes to close quarters, the shields may be
easily thrown down; then for his further protection, the soldier must
rely on a small, round targe held in place by straps on his left
forearm.
Each heavy-armed infantryman in the six front ranks carries a heavy
spear about seven feet long and a short sword somewhat like a long
dagger. A short-handled battle-ax with sharp, shearing blade and
pointed beak is hung by a strap over his shoulder. The soldiers in the
rear ranks, instead of the heavy spear and battle-ax, carry bundles of
light javelins, for casting at short range, and long bows with sheaths
of arrows, for fighting at long range. Protected by the wicker wall and
the hedge of spears in the fore, they will meet the assault with
showers of darts cast over the front ranks or, advancing behind the
charging spearmen, will gall the enemy thus before the shock of the
hand-to-hand fight comes.
At intervals along the lines stand the captains of hundreds and
commanders of thousands, distinguished from private soldiers only
by richer armor and plumes of horse-hair on their caps.
We next note the soldiers of the Imperial Guard. They are all large
men, none of them over forty years of age, every one of noble birth,
and all belong to the military class of Iran. They know but one calling,
that of arms. All had entered military service at the age of sixteen,
had been enrolled in the Guards at the age of twenty, and will remain
there until they shall reach their fortieth year, at which time they will
either be made civil officers or promoted and placed in command of
companies and divisions of the imperial armies. Their armor consists
of brazen helmets for their heads, chain-mail for their bodies, and
brazen greaves for their legs and arms. A round shield, held on the
left forearm in battle, will give further protection. A long, sharp javelin,
a sword, and a battle-ax are their weapons. Their horses are
protected by chain-mail on neck, forehead, and breast.
Cyrus, having satisfied himself that the Touranians were really
coming to battle, turned to his generals and said: “At last the
Touranians have decided to fight! We must not only repel this attack
but must utterly destroy them, so that hereafter the terror of our
name shall command peace! Take no prisoners! This day we shall
avenge the wrongs of Iran in the death of its ancient enemies!
Should it happen that I be slain in this battle, my cousin, the King of
Iran, will command. In case he also should fall, his son, our beloved
Prince, will command.”
His piercing black eyes rested a moment upon the Prince’s
countenance. The latter flushed with pleasure at the honor done him,
and bowed in acknowledgment. The King continued: “The King of
Iran will remain at my side. I shall need his advice. There will be no
change in the plans announced last evening. With the help of Ahura-
Mazda, this day we will fill that torrent-bed with Touranian dead! You,
Prince of Iran, have the most important duty. Ride down upon their
rear as soon as you see their front ranks engaged with our infantry.
Officers, go to your places! Let the skirmishers advance farther into
the plain!”
The group scattered, each officer riding to his place. Cyrus and the
King of Iran retired across the torrent-bed to the eminence at the rear
of the left wing of the army. The Prince of Iran mounted and hurried
to his command. Trumpets sounded. The light cavalry of the skirmish
line moved briskly out upon the plain. The Touranians came on, a
vast throng with but little semblance of order. Their leaders rode in
advance at intervals, and the front ranks only preserved an irregular
alignment. The two opposing forces slowly drew near each other.
The shaggy coats made of hairy skins, the tall, peaked caps, and the
fierce, dark faces of the Touranians soon became plainly visible to
their opponents. The former were surprised at the apparent
weakness of the latter and began to utter shouts of derision and
defiance. These shouts presently blended into a great roar as the
soldiers demanded of their leaders the right to charge.
But the Touranian leaders were wary. They thought that but a
fraction of the Persian army was here, possibly an advance guard
sent out to delay their progress. They were puzzled and hesitated.
But when the enemy halted at long bowshot distance and sent a
flight of arrows into their crowded battalions, they lost control of their
men. Screams of agony arose, and a roar of angry shouts. Another
flight of arrows and a third smote the Touranians. Their own bowmen
sought to reply, but their bows were weak and their arrows fell short.
Then came a vast forward movement of the mass. Leaders were
swallowed up in the midst of galloping squadrons. The skirmishers of
Iran retreated, but turned in their saddles and shot backwards with
fatal effect. Eager to overtake the flying archers, the Touranians
threw caution to the winds and urged their horses to full speed. The
earth shook with the beat of a million hoofs, and the air was rent by
the terrific volume of savage war-cries. No line of infantry ever
formed could have withstood the impetus of that charge if
unprotected by ditch or wall.
The herons, affrighted, spread their broad wings, sprang out of the
yellow waters of the Jaxartes, and hastily flapped away. The conflict
had begun.
After pausing at the margin of the torrent-bed to send one last flight
of arrows into their pursuers, the skirmishers of Cyrus quickly
descended into and crossed it, passed through the ranks of the
infantry, which opened to permit their passage, and formed in line on
the ridge beyond. The Touranian leaders were surprised when the
fugitives disappeared from their view in the chasm as if the earth had
swallowed them up, and, guessing the reason, frantically screamed
orders for their men to halt. But the noise was so great that the
orders were unheard. The shaggy horses of the leading ranks came
at full speed to the margin of the torrent-bed and, unable to halt,
plunged headlong down into it. Many horses and riders went down
and were ridden over, crushed and mangled. Some retained their
footing and struggled across the bottom of the ditch and up the
opposite slope to assault the Aryan infantry. But the momentum of
their rush was lost. The gleaming hedge of spears, protruding from
behind the wicker shields, was terrible to horse and rider. The
Touranians struck at the spear-points with their curved scimiters and
endeavored to force ways between them. Masses of horsemen
poured into the great ditch and struggled forward. Pushed on from
behind, those in front could not avoid contact with the darting spears,
which, in the hands of sinewy and practiced veterans, gashed horse
and rider and threw them down in dying, struggling heaps.
The rear ranks of Cyrus’ army came into action. They hurled clouds
of javelins and arrows over the heads of the men in front upon the
confused mass of assailants. The slaughter was horrible. But the
Touranians in the front could not retreat had they desired. Those in
front were crowded on, over dead and dying, upon the darting
spears and against the wicker shields, overthrowing the shields and
pushing back the Aryan infantry by sheer weight. Especially at the
extreme left, where Cyrus was watching the struggle, did this
backward movement of his lines take place. Here the water-course
was wider and shallower than elsewhere and the advance was not
so difficult. Here and there the Touranians succeeded in getting
between the Aryan spears and with fierce strokes opened ways into
the midst of the infantry. The latter, dropping their spears, fought with
battle-ax and sword. The contest became a mad swirl of screaming,
plunging horses, shouting men, gleaming swords, and slashing axes.
Heads were crushed, limbs lopped off, bodies hurled to earth, horses
brained and hamstrung. Ever the stout veterans of Cyrus faced their
enemy, unterrified, sweating, grunting, and cursing, as they stabbed
and hewed; but they were forced back step by step.
Cyrus watched the struggle with anxiety. There seemed no end to
the on-pressing masses of the enemy. More and yet more poured
down into the vale of death and pushed across to the assault.
Javelins and arrows were becoming exhausted. The infantrymen
were fighting furiously, but were beginning to show weariness.
Casting his eyes often to the distant hills, he presently noted with
satisfaction that the Prince of Iran and his guards were passing down
into the plain at the rear of the enemy’s left. He then ordered the
light-armed cavalry to the assistance of the infantry at the center and
right, and placing himself at the head of that division of the Imperial
Guard held in reserve, he led it into the affray just as the infantry,
pressed back by sheer weight of numbers, seemed about to be
overwhelmed. The heavy horsemen of the Guard rode forward
smartly and plunged into the battle. Prodigies of valor were
performed. The infantrymen, seeing their King in their midst swinging
his battle-ax with deadly effect, renewed their efforts. Huge Otanes
with mighty strokes and protecting shield endeavored to ward off
from Cyrus all blows aimed at him. King Hystaspis of Iran rode along
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