BJR https://doi.org/10.1259/bjr.

20160690
© 2018 The Authors. Published by the British Institute of Radiology under the terms
Received: Revised: Accepted: of the Creative Commons Attribution-NonCommercial 4.0 Unported License
17 August 2016 29 November 2016 22 December 2016 http://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
non-commercial reuse, provided the original author and source are credited.

Cite this article as:

Hutton BF, Occhipinti M, Kuehne A, Máthé D, Kovács N, Waiczies H, et al. Development of clinical simultaneous SPECT/MRI. Br J Radiol 2018 ;
90: 20160690.

NUCLEAR MEDICINE: PHYSICS AND INSTRUMENTATION SPECIAL

FEATURE REVIEW ARTICLE

Development of clinical simultaneous SPECT/MRI

1
BRIAN F HUTTON, PhD, 2MICHELE OCCHIPINTI, PhD, 3ANDRE KUEHNE, PhD, 4,5DOMOKOS MÁTHÉ, PhD, DVM,
4
NOÉMI KOVÁCS, MSc, 3HELMAR WAICZIES, PhD, 1KJELL ERLANDSSON, PhD, 1DEBORA SALVADO, MSc,
2
MARCO CARMINATI, PhD, 2GIOVANNI L MONTAGNANI, MD, 6SUSAN C SHORT, MBBS, PhD, 7,8LUISA OTTOBRINI, PhD,
9
PIETER VAN MULLEKOM, 10CLAUDIO PIEMONTE, PhD, 11TAMAS BUKKI, PhD, 11ZOLTAN NYITRAI, MSc, 11ZOLTAN PAPP, MSc,
11
KALMAN NAGY, PhD, 3THORALF NIENDORF, PhD, 12IRENE DE FRANCESCO, MD and 2CARLO FIORINI, PhD;
ON BEHALF OF THE INSERT CONSORTIUM
1
Institute of Nuclear Medicine, University College London (UCL), London, UK
2
Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano and Instituto Nacionale di Fisica Nucleare (INFN), Milan, Italy
3
MRI.TOOLS GmbH, Berlin, Germany
4
CROmed Ltd, Budapest, Hungary
5
Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
6
Faculty of Medicine and Health, University of Leeds, Leeds, UK
7
Department of Medical-Surgical Pathophysiology and Transplants, University of Milan, Italy
8
Institute for Molecular Bioimaging and Physiology (IBFM), National Council of Research (CNR), Milan, Italy
9
Nuclear Fields, Vortum-Mullem, Netherlands
10
Fondazione Bruno Kessler (FBK), Trento, Italy
11
Mediso Ltd, Budapest, Hungary
12
Department of Oncology, University College London Hospitals NHS Foundation Trust, London

Address correspondence to: Prof Brian F Hutton

E-mail: [email protected]

ABSTRACT
There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical
system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been
development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical
prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work
in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo
Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility
are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.

INTRODUCTION the limited literature on SPECT/MRI technology, using as an

Hybrid clinical systems with the combination of X-ray com- example the clinical design adopted in an ongoing project
puted tomography (CT) and either single-photon emission (INSERT) funded under the European Commission FP7
computed tomography (SPECT) or positron emission to- framework. In this project, the researchers aimed to construct
mography (PET) have been commercially available since the world’s first prototype clinical brain SPECT insert suitable
1999/2000 and have found important roles in clinical prac- for simultaneous use with an existing MRI. As in the case of
tice1. The combination of clinical PET with magnetic reso- the first clinical PET/MRI systems which were based on
nance imaging (MRI) was more recent, necessitating the dedicated brain PET inserts, this system is a first step towards
development of MRI-compatible components that support the potential development of a whole-body SPECT system
simultaneous acquisition.2–4 At the time of writing, however, which would have wider application.
the combination of SPECT and MRI in a simultaneous clinical
system had yet to be achieved, although work is in progress to There are some major technological challenges in achieving
produce a functional prototype. This article provides an truly simultaneous SPECT/MRI, not least the need for MRI
overview of this relatively new area of development and an compatibility and MRI safety of components and electron-
insight into the challenges faced by researchers who are ac- ics. Similar challenges have been faced by developers of PET/
tively developing these systems. The coverage will summarize MRI, with the adoption of MRI-compatible readout as
 BJR 
BJR Hutton et al

replacement for the conventional photomultiplier tube (PMT).5,6 that a shift of the signal charge inside the detector caused by Lorentz
However, the need for compact detectors that include collimation forces takes place and this phenomenon requires correction to
and stationary tomographic acquisition impose additional con- improve the detector response so as to achieve a high resolution.9
straints on the MRI-compatible SPECT system design. A se-
quential preclinical SPECT/MRI system is already commercially An alternative for use in SPECT/MRI is the employment of
available and a number of preclinical synchronous SPECT/MRI SiPMs to read out the light emitted by inorganic scintillators.27
experimental systems have been built in recent years, but these Beyond the wide success of such detectors in MR-compatible
tend to rely on pinhole collimation with magnification, which PET systems,28–30 there are several SPECT development projects
mainly suits small objects.7–9 Developing a clinical system has reported in the literature, exploring SiPM-based gamma de-
required considerable innovation in many aspects of the design. tector modules.31–34 The goal of these researchers was to pro-
duce compact gamma cameras for use in surgery or small organ
This article is structured as follows. The options for detector imaging. These systems have not normally been developed
design are discussed, including a description of customized specifically for MRI compatibility and are not tomographic, but
silicon photomultipliers (SiPMs) designed specifically for use similar compact technology could be adapted for use in syn-
in SPECT. The possible collimator designs and overall system chronous SPECT/MRI. SiPMs show no intrinsic sensitivity to
design are discussed and MRI compatibility of components magnetic fields, an important argument for the usage of a SiPM-
including electronics is considered. Finally, the potential based gamma camera in combination with MRI.6 Although the
applications of such systems are presented along with a brief energy resolution of a scintillation-based system is typically in-
discussion on the pros and cons of such a system. ferior to that offered by CdTe and CZT, it is still adequate to
potentially allow specific clinically important multi-radionuclide
acquisitions (e.g. 99mTc and 111In, 99mTc and 201Tl).
SPECT DETECTORS FOR SIMULTANEOUS
SPECT/MRI A disadvantage of pixelated detectors is that they involve direct
In the case of the early development of PET/MRI, a compact brain readout for each pixel; the number increases as the pixel size is
PET insert was designed that could be utilized with an existing decreased. In comparison, a SiPM readout system with multi-
commercial MRI system.10 This then led to the development of plexing requires a relatively small number of direct electrical con-
more integrated systems suitable for whole body scanning.11 A nections, since the readout units are quite large compared with the
similar strategy for the development of SPECT/MRI can be resolution (at least an order of magnitude larger). This opens the
adopted. One of the major constraints to be solved in the de- possibility to reach a given spatial resolution with a significant
velopment of an integrated SPECT/MRI system is the design of reduction in the number of electronic readout channels (a factor of
a compact gamma detection module which exhibits mutual com- 100) compared with a pixelated detector with the pixel size equal
patibility with commercial MRI scanners. PMTs are the photo- to the desired resolution.38 This advantage will be particularly
detectors most commonly used in conventional SPECT systems. important in the translation of this technology for clinical appli-
Unfortunately, PMT arrays are too bulky to be fitted inside an MRI cation. For a scintillator in combination with SiPMs, sufficiently
bore and their performance is severely affected by the high mag- high intrinsic spatial resolution is achievable (approximately
netic field and the pulsed magnetic field gradients used in MRI. 1 mm) to enable compact SPECT designs, taking advantage
Several solutions have been suggested. The first approach considers of multiple apertures with minification.35–37
the placement of magnetic-sensitive devices, such as PMTs, far
enough from the MRI apparatus, with light carried from the SPECT/MRI SYSTEM DESIGN
scintillators to the photo detectors through long optical fibres.12,13 Sequential SPECT and MRI has been performed with small-
Another approach is based on the adoption of either pixelated animal SPECT adjacent to a low-field (0.1 T) MRI system,39
solid-state detectors [e.g. cadmium telluride (CdTe), cadmium zinc a solution still limited by the lack of simultaneity and by the
telluride (CdZnTe or CZT)]7,14–16 or inorganic scintillators coupled need for a low magnetic field. Several groups have designed
to solid-state photodetectors (e.g. avalanche photodiodes or MRI-compatible preclinical systems. The design of an MRI-
SiPMs).17–19 Digital SiPM technology has also been developed, compatible SPECT system for mouse brain imaging has been
where on-chip circuitry enables fast, accurate photon counting and
well-defined timing.20 In combination with compact readout Figure 1. A full preclinical ring populated with 10 gamma
electronics, these solutions provide compatibility with high mag- detection modules. The mechanical structure also supports the
netic fields and compact designs that are suitable for use within cooling distribution tubes and the power and optical commu-
MRI bore sizes of 60–70 cm commonly used in clinical practice. nication lines. The overall diameter of the insert is 20 cm.

A strong case has been made for the adoption of SPECT/MRI for
preclinical use.14 In most of the experimental synchronous pre-
clinical SPECT/MRI systems under study, arrays of CdTe or CdZnTe
(CZT) gamma detectors are employed,21,22 Similar solid-state
technology is finding increasing use in clinical SPECT systems be-
ing used for cardiac imaging,23,24 scintimammography25 and, more
recently, whole-body SPECT imaging.26 As regards compatibility
with MRI, preliminary investigations on CdTe and CZT have shown

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simultaneous SPECT/MRI
SPECT/MRI BJR

presented together with results of the effect of SPECT and MRI Figure 2. The three-side-tilable silicon photomultiplier arrays
components on each other.7 This early development led to more composing the planar detector field of view in the preclinical
recent construction of an ultrahigh-resolution stationary case. The dead detection area of the single array has been
MRI-compatible SPECT system for small animal imaging, minimized to increase the amount of luminous signal collected.
based on CdTe/CdZnTe detectors.22 Further preclinical
systems have been developed through academic/industrial
collaborations and the SPECT–MRI interaction has been
evaluated.8,40–42 A preclinical SPECT system has been
designed using Lutetium Yttrium Orthosilicate and digital
SiPM;43 the high-density detector enables use of a thin
detector for SPECT with the potential to reduce depth of
interaction effects that are common with pinhole collimation.
However, the light output is somewhat compromised for low-
energy gamma emitters. A preclinical prototype based on
SiPM readout has also been developed in the INSERT pro-
ject,44 with modular detectors that also suit a clinical SPECT
design (Figure 1). First images from the preclinical system
have been recently demonstrated. 10

At the time of writing, the only commercially available preclinical

SPECT/MRI system (nanoScan® SPECT/MRI 1.0 T; Mediso, (3) SiPM technology with optimal optical detection efficiency
Budapest, Hungary) was an inline system that uses a combination has been chosen, specifically adapted to the optical
of high-resolution multipinhole apertures, a PMT-based con- wavelength for CsI scintillation.
ventional SPECT detection module and a specially developed
shielding system combined with a self-shielded 1.0 T permanent At room temperature, the presence of thermal noise results in
magnet. This combination has been proven to yield a high SPECT deterioration of the energy resolution, necessitating cooling of
image quality and high-resolution imaging possibilities coupled the SiPM array. The detector module therefore incorporates
with a user-friendly and biologically relevant series of MRI a compact 8-mm-thick cooling block made of MR-compatible
sequences. However, inline SPECT/MRI still lacks the advantages thermoplastic (Coolpoly®; Cool Polymers, North Kingstown,
presented by synchronous SPECT and MRI acquisition. RI), placed between the SiPM array and the electronic readout
board and designed to ensure uniform temperature control over
At the time of writing, there was publication of only one clinical the SiPM area (Figure 3). A glycol–water mixture is circulated to
SPECT/MRI under construction (INSERT)25 dedicated to human maintain the operating temperature of 0 °C. Image quality over
brain imaging. The system has been designed using stationary the single gamma detection module has been tested with 99mTc
rings of detector modules, designed so as to minimize variation in (Figure 4). The intrinsic spatial resolution of the device is ap-
the components when translating from the preclinical to the proximately 1.0 mm full width at half maximum over a planar
clinical configuration. The electronic board, for SiPM signal field of view (FOV) of slightly greater than 4 3 4 cm2.
processing and transmission through optical fibres, also provides
mechanical support for a modular number of compact SiPM The clinical system design is illustrated in Figure 5. This is
arrays supplied by FBK, Trento, Italy.44 The SiPM arrays are based on use of 20 detector modules arranged in a partial
arranged in tiles to cover the required detector area: 5 3 5 cm2 for ring, designed to maximize the patient aperture with minimal
the preclinical configuration and 10 3 5 cm2 in the clinical case alteration to the existing patient bed. The key to development
(Figure 2). An 8-mm-thick CsI(Tl) monolithic scintillator is has been the choice of a collimator, which has been designed
optically coupled over the overall SiPM matrix surface. to provide maximum axial coverage and optimal sensitivity,
while maintaining reconstructed resolution so as to be similar
The detection module performance is mainly determined by to conventional gamma camera SPECT. The reason for this
the amount of light detected by the SiPM array. Since SPECT target was the intention to explore the use of the technology
involves use of radionuclides with relatively low emission to characterize and evaluate treatment in well-identified
energy, a low amount of light is generated for any scintillation brain tumours rather than to optimize detection of small
event. Thus, the following design principles have been abnormalities.
employed:
(1) A CsI(Tl) scintillator has been adopted. CsI has a high light COLLIMATORS FOR CLINICAL SPECT SYSTEMS
output and, although it is one of the slowest inorganic The design of a compact clinical system is markedly different
crystals, the timing performance of the camera is sufficient from the typical preclinical designs where multipinhole col-
to handle the expected clinical countrate. limators usually take advantage of magnification to achieve
(2) The gaps between SiPM cells have been minimized through superior resolution. With improvement in intrinsic resolu-
a set of smart strategies in SiPM alignment.44 As a result, loss tion, the degree of magnification can be reduced so as to
in light detection has been significantly reduced. achieve the desired compact design. Similar designs have been

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Figure 3. INSERT gamma camera configured for preclinical SPECT. In the violet box, the 36-channel application-specific integrated
circuit (ASIC) for signal readout and filtering is depicted. Digitized SPECT signals are transmitted through optical fibres.
Temperature is stabilized at 0 °C by the cooling unit (an aluminium version of the unit is depicted). SiPM, silicon photomultiplier.

adopted to achieve superior resolution for clinical brain Multiple short slits are employed to improve the angular sam-
SPECT [(G-SPECT; MiLabs, Utrecht, Netherlands) (AnyScan pling and slits are shared across detectors so as to accommodate
Trio; Mediso)]; however, these systems are not compact. the desired FOV. The resulting collimator37 demonstrates higher
Instead, the improvement of intrinsic resolution using the sensitivity than alternative multipinhole collimators and also
new technology can be used to advantage by adopting mini- improves on fan beam collimation, which is commonly used on
fication as opposed to magnification so that the resolution is conventional SPECT.
effectively traded against compactness, to achieve similar
performance to a conventional gamma camera SPECT system. A further consideration in collimator design is the choice of
material and the avoidance of features which might result in
The main challenges in collimator design are to construct induced eddy currents. The rapid switching of gradient coils
a compact system with sufficient angular sampling to permit induces spatially and temporally varying eddy currents within
stationary acquisition (avoiding detector movement is highly the conducting structures of the MRI scanner and in the colli-
desirable for simultaneous SPECT/MRI acquisition). Van mator required for SPECT, which typically has a high conduc-
Audenhaege et al45 proposed a design for a multipinhole colli- tivity. The undesired magnetic field produced by these eddy
mator for performing clinical brain SPECT studies using an currents opposes and distorts the linear gradient fields in the
existing PET scanner. The collimator was equipped with region of interest, which results in image artefacts.48 Other
a shutter mechanism, in order to eliminate the need for rotation; effects concern the thermal load in the cryostat of the super-
however, the prototype was not MR-compatible. Preclinical conducting magnet, which may lead to increased boil-off of the
systems usually utilize multipinhole collimators;46,47 but, for cryogens (can even cause magnetic quenching in extreme cases)
a compact clinical system, preference was given to utilizing and acoustic noise due to their interaction with the B0 field.49
a multislit-slat collimator (Figure 6), which incorporates several The material traditionally used for collimators and shielding is
novel features. The slits are located internal to the slats so as to lead, strengthened by various impurities that tend to be ferro-
achieve the desired minification without compromising slat magnetic. The alternative is to use tungsten and several groups
length (which controls the axial resolution/sensitivity trade-off). have developed tungsten/epoxy composites in an attempt to

Figure 4. Planar irradiation profile for a 5 3 5 cm field of view of the preclinical INSERT detector module. (a) A lead grid of holes
(0.5 mm in diameter, 2 mm pitch) is employed to collimate the gamma rays. (b) Experimental result for 99mTc: the event coordinates
were reconstructed using a maximum likelihood method. FWHM, full width at half maximum.

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article: Development
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BJR

Figure 5. (a) Schematic diagram of the clinical system design with a partial ring of 20 detectors. The patient aperture of 33 cm
accommodates the MRI receiver/transmitter head coil. (b) Schematic of complete SPECT insert in the MRI system.

reduce eddy currents while maintaining stopping power.50 This magnetic fields and radiofrequency (RF) power deposition.
strategy works well for radiation shielding, with attenuation Additional conditions, including specific configurations of the
approaching that of lead being possible. However, the composite SPECT device (e.g. routing of leads and power lines), may be
material tends to be brittle and easily broken and so not suitable required. MR compatibility indicates that a SPECT device, when
for fine collimator components. used in the MR environment, does not significantly reduce the
quality of the diagnostic information via the formation of MR
Various strategies can be employed in the design of pinhole signal and image artefacts and that its operation will not be
collimators to reduce the incidence of eddy currents, e.g. seg- detrimentally affected by the MR device.
menting the collimator into smaller subsections while avoiding
any possible penetration.51 Manufacturing the resulting complex Mutual SPECT/MRI safety and compatibility issues may
parts is greatly aided by recent developments in additive arise from:
manufacturing.52 In the case of already complex multicompo-
– static magnetic fields (B0): interference with the B0 spatial
nent tungsten collimators (e.g. multislit-slat collimators), in-
gradient can cause displacement and torque of objects moved
duced eddy currents appear to be acceptably small.
into the MR environment. This displacement force is
responsible for the projectile effect that continues to cause
SPECT/MRI COMPATIBILITY accidents in the MR environment. Diagnostic MRI and MR
The technical challenges of integrating a SPECT insert with spectroscopy require a B0 uniformity of #1 ppm and foreign
a clinical MRI system relate primarily to potential interferences objects such as bulk collimators, SPECT detector modules
between both modalities. These interferences might compromise and large bundles of lead placed in the MR magnet run the
MR safety and MR compatibility. The requirements of MR safety potential to perturb B0. The static magnetic field might also
are met if the SPECT device poses no known hazards in induce susceptibility effects which bear the risk of spoiling the
a specified MRI environment with specified conditions of use. MR signal and image quality if placed close to the FOV used
Conditions that define the MRI environment include static mag- for MRI. Sensitivity to B0 might also cause malfunction and
netic field strength, spatial magnetic field gradient, time-varying dysfunction of the SPECT device owing to electromagnetic
interference with its electronics and detectors.
– Switching magnetic fields (dB/dt: #200 mT/m/ms): switch-
ing magnetic fields can cause movement, frequency shift and
Figure 6. Multislit-slat collimator corresponding to three
temperature rise owing to eddy currents induced in
detector units. The collimator consists of slats in the axial
conductive system components (cables, collimator, cooling
direction and an array of short slits with their apertures internal
to the collimator surface. The figure shows a central slit (a) for
blocks, means of shielding, scintillators etc.) placed inside
each of the three subsections plus slits that are shared across the magnet bore equipped with a gradient coil. Pulsed
adjacent detectors (b). magnetic field gradients might also interfere with the
electronic circuits and detectors of the SPECT device,
disturbing the low amplitude signals within the SPECT
acquisition chain (application-specific integrated circuit,
data acquisition board etc.).
– RF energy transmission (B11): RF transmission can induce
temperature rise and functionality disturbances owing to RF
power deposition. RF might also interfere with the electronics
and detectors of the SPECT device owing to RF shielding
deficits. Any RF emission of the SPECT device (for example:
power supplies or preamplifier electronics) bears the potential

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to interfere with the MR device and compromise its susceptibility would be xSPECT insert 5 xair 5 0.36 3 1026 which is
(diagnostic) functionality through RF-induced artefacts. hard to achieve in practice.64 The effects of magnetization
– Movement and flow: mechanical movement of components of induced by non-magnetic materials/objects used for the SPECT
the SPECT device can cause MR frequency shift owing to insert are largest at the surface of the object. Therefore, it is
eddy currents. Flow (for example: cooling fluids) in the FOV prudent to place all components of the SPECT system outside
to be imaged can cause MRI artefacts that present an of the FOV of the MR system for avoiding susceptibility
impediment for diagnostic image quality. The implications gradient-induced artefacts. The tests for magnetic susceptibility
feed into the (stationary) collimator design and the cooling are based on the ASTM Standard F2119-0758 and on the study
strategy used for heat extraction from the SiPMs ther- of Wendt.65 To achieve this goal, a material probe together with
mal pads. a reference probe (e.g. copper) is placed in close proximity to
an imaging phantom65 filled with a solution.58 MR scans are
The literature primarily reports on evaluation of MR compati- performed for multiple orientations to evaluate the severity
bility and safety of instruments for interventional MR and extent of magnetic field distortion and susceptibility
procedures53–56 and provides guidance for standardized test artefacts induced by the material under investigation vs the
procedures57–60 that mainly focus on passive devices. A SPECT reference probe (Figure 7).
insert is an active device that differs from interventional MR
devices/applications in many aspects. For the design of a syn- Frequency shift and free induction decay
chronous clinical setup, careful considerations need to be made attenuation due to eddy currents induced by pulsed
to reduce if not eliminate electromagnetic coupling between the magnetic field gradients
MR and SPECT device with the goal to assure SPECT/MR Local eddy currents disturb B0 homogeneity resulting in fre-
compatibility. These considerations should include legal regu- quency shift, T2* relaxation time shortening and free induction
lations61 and established norms,62,63 but should also build upon decay (FID) attenuation. For eddy current and frequency as-
a close interdisciplinary team work involving experts in electrical sessment, a reference FID/spectrum is acquired for an agarose
engineering, SPECT manufacturing, RF antenna design, MR phantom. For comparison, the object under test is placed in the
physics, nuclear medicine and radiology. As a minimum, pro- magnet (resembling its position in the SPECT insert) followed
cedures for ensuring MR safety and compatibility should include by the acquisition of a test FID/spectrum. For both sets of
the following assessments. measurements, the delay between the pulsed magnetic field
gradient and the FID acquisition is varied to determine the eddy
Hard magnetic materials current time constant (Figure 8). Eddy current considerations
Hard magnetic materials (also known as permanent magnets) have major implications for the design of the heat exchangers,
including high carbon steels, barium, ferrite, alnico, samarium– since commonly employed copper heat exchangers (which ex-
cobalt alloys etc. are not MR-safe and should be strictly hibit very good thermal conductivity 401 W/mK21) cannot
banned from any clinical SPECT design. This test can be be implemented. To overcome this limitation, thermally
conveniently performed by measuring the attraction force of conductive non-metallic materials, such as ceramic material
a piece of metal plate placed in the vicinity of the material SHAPAL™ (Precision Ceramics, Birmingham, UK) (thermal
under investigation. conductivity 92 W/mK21) or thermally conductive plastic
CoolPoly® D5506 (Cool Polymers, North Kingstown, RI)
Soft magnetic materials (thermal conductivity 10 W/mK21), are alternative candi-
Soft magnetic materials are not magnetized if not placed in the dates for the cooling block material. The latter is less costly
vicinity of a magnetic field. However, their susceptibility is very and can be easily modelled in complex forms with robust and
large and they exhibit forces and torques in the presence of reliable outcomes.
a strong magnetic field of a clinical MR scanner.64 The test for
soft magnetic materials is performed according to the American Heat extraction and spurious MR signals
Section of the International Association for Testing Materials From the MR perspective, air cooling can be considered as an
(ASTM) Standard F2052-06.57 For example, WNiFe collimator ideal candidate for heat extraction from the SiPM thermal pads,
materials (alloy 1: r 5 17.6 g cm23, W 5 93%, Ni 5 5%, since air does not induce spurious MR signals. However, air
Fe 5 2%; alloy 2: r 5 18.0 g cm23, W 5 95%, Ni 5 3.5%, cooling constitutes a severe challenge for flow and temperature
Fe 5 1.5%; Nuclear Fields International, Vortum-Mullem, stabilization needed for the SiPM performance. For this reason,
Netherlands) were found to be ferromagnetic and excluded from a water and glycol mixture (40–60%) is used for heat extraction
the collimator design. In comparison, collimator samples of from the cooling block. To reduce spurious MR signals, the RF
polyimide/tungsten (r 5 11.0 g cm23), lead 1 4% antimony coil is shielded. Also, the tubes supplying and draining the
(r 5 11.03 g cm23), lead (r 5 11.3 g cm23) and tungsten heating blocks need to be routed outside of the excitation field
(r 5 19.3 g cm 23) are non-magnetic. of the RF coil to avoid spurious signals in the MR images. The
remaining concern is spurious MR signals due to aliasing of
Non-magnetic materials the parasitic signal obtained from the cooling fluid outside of
Non-magnetic materials exhibit small magnetic susceptibility x so the FOV into the FOV. This artefact is induced by parasitic
that no forces and torques are apparent when placed in a static excitation of regions outside of the FOV owing to the non-
magnetic field. To avoid any B0 perturbation induced by the linearity of the gradient coil, and commonly called “third arm
magnetic susceptibility of the SPECT insert, the ideal magnetic artefact”. Parasitic excitation can be addressed by limiting

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instrumentation special
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feature review
review article:
article: Development
Development of
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clinical simultaneous SPECT/MRI
simultaneous SPECT/MRI BJR
BJR

Figure 7. Magnetic field distortion inside a uniform phantom due to the presence of a collimator block (polyimide/tungsten,
r 5 11.0 g cm23) tested for the clinical SPECT/MRI setup. The left image shows a uniform static magnetic field in the absence of the
collimator block. For this setup, a magnetic field dispersion (Df) of approximately 20 Hz was obtained across the slice. After placing
the collimator block in close vicinity to the phantom lower right corner, the static magnetic field is significantly distorted (right)
which manifests itself by field dispersion across the slice of Df  120 Hz.

the range of excitation and reception of the RF coil using magnetic field gradient-switching schemes used for MRI to
a dome-shaped design or by employing a bird cage design avoid strong coupling.
tailored to the brain.
Temperature changes due to pulsed magnetic
Mechanical vibration due to pulsed magnetic fields gradients
fields gradients Under normal conditions, the heating due to pulsed magnetic
The literature is short of a standardized test given by ASTM or field gradients in the kilohertz frequency range is negligible.66
other bodies that is tailored for examining mechanical vibration This may change if bulky electrically conductive objects (colli-
induced by a device incorporated or inserted in an MR scanner. mator, cooling blocks, application-specific integrated circuit
Careful considerations should include the use of pressure and etc.) are placed in the MR scanner. For temperature monitoring,
acceleration sensors. It is advised that the eigenfrequencies of the an object under test is placed either in air or in a gel
SPECT components should not match the frequencies of the phantom59,67 and positioned in the MR scanner according to its

Figure 8. An example of eddy current assessment using a reference free induction decay (FID) (black line) obtained for an agarose
phantom and pulsed magnetic field gradients placed along the read, phase and slice direction. For comparison, the object under
test [polyimide/tungsten sample (r 5 11.0 g cm23] was placed in the magnet (resembling its position in the SPECT insert) followed
by the acquisition of a test FID (blue and red lines). For assessment of the eddy current time constants, the delay between the
pulsed magnetic field gradient and the FID acquisition was varied between 0.3 and 300 ms.

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position within the SPECT system. Temperature probes are at- coil and an MRI phantom are placed inside the collimator. A
tached to the object and positioned in its vicinity. Pulsed magnetic noise scan and clinical imaging protocol are performed, while the
field gradients are applied using clinical MR protocols including component under test is in operation. These scans are bench-
fast spin-echo, fast gradient-echo and echoplanar imaging marked against reference data acquired without the component
sequences for fast and high duty cycle switching paradigms. under investigation in the bore.

Pulsed gradient fields Radiofrequency heating induced by the

Pulsed gradient fields can induce electrical voltages on the radiofrequency transmission
SPECT device components as well as on all electrical cables In current clinical MR scanners, integrated large-volume body RF
connected to them. These voltage spikes interfere with device coils are commonly used for RF excitation. The large-volume
operation and can cause measurement artefacts in the form of excitation bodes well for a uniform transmission field. Yet, this
spectral distortions and can even lead to a complete operational approach is not suitable for a clinical SPECT/MR setup owing to
failure if voltages become too high. Electromagnetic simulations the RF shielding provided by the collimator and other compo-
and bench measurements using pulsed magnetic field generators nents of the SPECT insert. Instead, a small-volume transmit
such as toroidal coils are performed to test problematic con- transmit/receive RF coil tailored to the geometry of an average
figurations and identify possible mitigation measures. head and positioned inside the SPECT insert is employed. The RF
power applied to this RF coil needs to be limited to meet the RF
power deposition and specific absorption rate limits governed by
SPECT/MR interferences due to radiofrequency
the International Electrotechnical Commission guidelines.68 For this
transmission/emission
purpose, careful electromagnetic field simulations need to be con-
This compatibility issue can be twofold: (i) interference of RF
ducted in human voxel models. For validation, transmission field
coil transmission with the functionality of the SPECT modules
distributions obtained from these simulations need to be bench-
and (ii) interference of RF emission induced by the SPECT
marked against experimental B11 maps.69,70 Since the integrated
device with the RF chain of the MR scanner. To reduce RF
SPECT module is placed outside of the RF coil, it is unlikely that the
interferences caused by the SPECT module, it needs to be
head coil of the MR scanner would induce heating into the SPECT
electromagnetic compatibility shielded. Efficiency of electro-
module that might cause a compatibility issue.
magnetic compatibility shielding can be evaluated by placing the
components of the SPECT electronics in a shielded box followed
by measurements of RF spectra outside of the box (Figure 9). Potential applications of clinical SPECT/MRI
The RF coil itself is shielded and, in addition, is separated from In general, it is the authors’ opinion that multi-radionuclide
the active components of the SPECT system by a collimator, SPECT imaging with well-established radiopharmaceutical
which reduces (if not eliminates) RF interference with the tracers of a variety of metabolic and molecular features could
SPECT device. For the evaluation of MRI/SPECT interferences, indeed provide useful synergies with function-related physi-
it is prudent to use a transmitted RF power that exceeds the ometabolic MRI and spectroscopy including X-nuclei MRI.
limits given by the International Electrotechnical Commission Owing to the massively multiarray possibilities of the resulting
guidelines by a factor of 3. For the assessment of SPECT/MRI images, synchronous SPECT/MRI realizes insights hereto im-
interference, noise figures are acquired. For this purpose, the possible for any other type of hybrid imaging methodologies
component under investigation is placed in the MR system with (including PET/MRI). As nowadays fully quantitative SPECT
the collimator (or alternative shielding) being installed. An RF reconstruction can be achieved, synchronous SPECT/MRI

Figure 9. A data acquisition board mounted inside the electromagnetic compatibility shielding test box for the evaluation of the
SPECT/MRI interference due to radiofrequency emission (left). Closed test box being fully shielded (right).

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SPECT/MRI BJR
BJR

equipped with high temporal resolution acquisition will be the can be used instead for therapy planning. The alternative use of
124
method of choice for personalized therapy guidance and I with PET is methodologically challenging and is limited by
“radiomics”-based decisions (i.e. use of imaging parameters as both general availability and dosimetric issues. One emerging
a surrogate for reading out tumour biology). example is targeted alpha therapy using 212Pb, where 203Pb is
proposed to be the surrogate dosimetry probe based on SPECT
One goal of the current synchronous SPECT/MRI development imaging.77
is to aid in the clinical management of patients with brain
tumours. Assessment of treatment response in patients with Additional applications can be envisioned in research of the
glioma is currently extremely challenging. Anatomical and central nervous system. Functional MRI brain mapping studies
contrast-enhanced MRI remains the standard imaging modality combined with complementary, simultaneous SPECT readouts
at follow-up, but is associated with well-documented problems of neuroreceptor pathways using radio-labelled receptor ligands
in ascertaining response to treatment, particularly at early time will be feasible with the system, although PET/MRI will probably
points owing to the phenomenon of pseudoprogression71 as- remain the preferred modality for these studies. In treatment of
sociated with inflammation. Currently, patients with imaging diseases of the central nervous system (especially dementia),
findings that suggest progression or pseudoprogression are intensive development of new therapies is under way. SPECT/
managed expectantly, since the only approach to confirming the
diagnosis is through continued clinical and radiological follow-
up. It is notable that fluorodeoxyglucose (18F-FDG) imaging has Figure 10. (a) 99mTc-labelled pentavalent dimercaptosuccinic
not proven useful for this indication, although amino acid acid [99mTc-DMSA(V)] and gadolinium (Gd)-enhanced
tracers may be more relevant and are still under investigation in gradient-echo three-dimensional (3D) sequence MRI visualizes
this setting.72,73 Hence, based on current imaging approaches, peripheral, more perfused regions of the tumour to express
patients who have true progression may be denied access to more transporter proteins of phosphate ions related to
alternative treatments early and patients who will have an ulti- energy metabolism. Also, the superior nature of SPECT/MRI
mately favourable outcome cannot be reassured. In the context with very high resolution and high soft-tissue details/
of pseudoprogression, the earlier the imaging is carried out MRI-related functionality of the perfusion data readout is
following treatment, the less useful the data tend to be and to presented. (b) 125I-deoxy-uridine and Gd-enhanced gradient-
date, there have been no successful approaches to monitor these echo 3D sequence MRI visualizes central, less perfused
patients during treatment. This is despite the fact that real-time regions of the tumour to express more DNA build-up
assessment of treatment response, for example during radio- (nucleoside incorporation). This image was taken synchro-
therapy or adjuvant chemotherapy, could allow for selection of nously with 99mTc-DMSA(V) images using an energy window
centred at 28 keV.
patients for treatment intensification at the time when treatment
is likely to be most effective.

The clinical use of simultaneous SPECT/MRI to directly help

assess (and thus predict) therapy monitoring will be most
prominently present in the imaging and follow-up of local or
systemic radionuclide therapy against post-surgical brain tu-
mour remnants.74–76 Dosimetry and efficacy control will be
possible with a SPECT/MRI system as opposed to PET/MRI,
given that therapeutic nuclides are mostly SPECT emitters too.
Improved dosimetry in the tumour is indispensable to optimize
radionuclide therapeutic procedures for reaching the highest
possible tumour dose. Improved regional dosimetry is necessary
to identify dose-related organ impairment risks too.

There is further potential for future use of specific radionuclide-

labelled peptides in targeted radionuclide therapy; provided that
single photon emission is present in either the therapeutic ra-
dionuclide or an available analogue, then patient-specific do-
simetry can be readily estimated. This would be an ideal use of
the SPECT/MRI combination. In the future, one can anticipate
availability of compounds that are labelled either with gamma
emitters for diagnostic purposes or with therapeutic radio-
nuclides; the ability to plan and monitor therapy with these
paired compounds has potential. If used for therapy, the com-
pound would be labelled with an alpha or beta emitter rather
than a gamma emitter; the gamma version would be used to
plan subsequent personalized therapy using the alpha or beta
emitter. One case is with 131I-labelled compounds; 123I labelling

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al

MRI offers an outstanding opportunity for simultaneous which should be possible using techniques being developed for
blood perfusion imaging and determination of other disease PET/MRI.78–80 For example, MRI navigator techniques can
indices such as dopamine transporter or neuroinflammation- monitor and correct for motion for predefined regions such as
associated parameters. Here, Go/No-Go decisions of large the surface of the head, acquired in combination with most
investments (in pharmaceutical discovery and development) standard MRI techniques that may be selected for clinical studies
are dependent on early disease detection and the evaluation of (e.g. T1, T2). There are, however, challenges in accurately de-
treatment effect. But, as suitable therapies are developed, the termining the rigid motion based on six degrees of freedom and
demand for cost-effective tools will increase; SPECT/MRI alternative methods of motion tracking may be more appro-
may be the system of choice for wider scale screening that priate, provided these can be implemented in the practical set-
may be indicated. ting, with minimal interference to the normal clinically
indicated MRI acquisition.
DISCUSSION
There are several potential advantages offered by simulta- Much of the work on PVC has been developed for PET.
neous acquisition of MRI and SPECT images, rather than Traditionally, in the case of clinical systems, SPECT resolution
simply sequential acquisition via adjacent gantries (or totally is inferior to that of PET. PVC for SPECT is therefore
independent acquisition). The reduction of the overall scan more demanding but critical. Once again, the techniques that
time and associated improvements in patient comfort and have been developed for PET/MRI are easily adapted for the
compliance are important. The availability of registered data SPECT/MRI application. The availability of simultaneous
sets to assist localization can be helpful, as it is not always SPECT and MRI data will greatly facilitate correction using
possible with separately acquired modalities, especially with post-reconstruction methods,81 potentially reducing regis-
highly specific radiotracers where many structures may not tration errors that affect PVC accuracy.
be visualized. However, the potential to combine information
from the two modalities so as to enhance diagnostic and A distinct advantage of SPECT over PET is the potential for
prognostic information is particularly appealing. This can simultaneous acquisition of multiple radiotracers labelled with
potentially extend beyond the improvement of SPECT different radionuclides. Similar techniques in PET rely on se-
quantification via motion or partial volume correction (PVC) quential use of short half-life radionuclides and extrapolation of
to the development of joint models that might enhance both time–activity curves. The ability to combine multitracer studies
SPECT- and MRI-derived parameters. There is a strong case with multiple MRI pulse sequences extends the potential to
to evaluate the potential of this new multimodality option. better characterize tissue and evaluate treatment. A preclinical
example of combined multi-radionuclide imaging and MRI is
Both SPECT and MRI are lengthy procedures requiring patient illustrated in Figure 10. Dual radionuclide imaging does require
cooperation, but restricting motion for lengthy periods can be corrections for downscatter, scattered photons from the higher
a challenge, especially with certain brain conditions where energy emitter that are acquired in the energy window selected
movement control is affected. Motion effects can therefore be for the lower energy radionuclide. Correction is more complex
significant. Monitoring motion during SPECT acquisition is in the case of CZT, where a tail in the energy spectrum due to
therefore very important and will allow correction of motion incomplete charge collection must also be accounted for.82–84
during reconstruction; this does imply that motion can be suf- A range of radiopharmaceuticals may be of interest for dual
ficiently well monitored during the complete SPECT acquisition, radionuclide imaging (Table 1).
99m
Table 1. Possible measurements using SPECT/MRI including a range of MRI biomarkers along with Tc-labelled compounds and
additional compounds with second radionuclide, which could be used interchangeably

MRI Application SPECT1 Application 1 SPECT2 Application 2

T1, gadolinium Tumour site, blood–brain 99m Phosphate 201 Perfusion/glial activity
Tc-DMSA(V) Tl-chloride
enhancement barrier integrity transport (prognosis)

99m Blood–brain 111

T2 1 FLAIR Invasiveness Tc-DTPA In-RGD peptide Angioneogenesis
barrier integrity
MRI perfusion 1 99m 123 Histologic
Invasiveness, oedema Tc-Annexin-V Apoptosis I-CLINDE
T2 FLAIR classification
DWI 1 ADC Intracellular/extracellular 99m 111 Planning for specific
Tc-HMPAO Perfusion In-Nimotuzumab
additive: DTI oedema, pseudoprogression treatment

99m 123 Proliferation

MR spectroscopy Histologic classification Tc-HL91 Hypoxia l-iodoUracyl
post-therapy
ADC, apparent diffusion coefficient; DTI, diffusion tensor imaging; DWI, diffusion weighted imaging; FLAIR, fluid-attenuated inversion recovery; 123I-CLINDE,
123
I-labelled 6-chloro-2-(49-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide; 111In-labelled arginyl-glycyl-aspartic acid (RGD) peptide; SPECT,
single-photon emission computed tomography; 99mTc-DMSA(V), 99mTc-labelled pentavalent dimercaptosuccinic acid; 99mTc-DTPA, 99mTc-labelled
diethylenetriaminepentaacetic acid; 99mTc-HL91, 99mTc-labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; 99mTc-HMPAO, 99mTc-labelled
hexamethylpropyleneamine oxime.
Potential diversity of simultaneous measurement in the context of tumour characterization is well illustrated.

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 Physics
Physics and
and instrumentation
instrumentation special
special feature
feature review
review article:
article: Development
Development of
of clinical
clinical simultaneous
simultaneous SPECT/MRI
SPECT/MRI BJR
BJR

There is still much to do to reach a stage of demonstrating robustness MRI, the combination of SPECT and MRI is attractive to
of SPECT/MRI and evaluating its clinical utility. Whether solid-state patients who often have to undergo multiple lengthy imaging
detectors or SiPM readout systems will become the design of choice procedures. The dual radionuclide capability has particular ap-
remains to be seen. Extension of design ideas to permit whole-body peal, although the clinical need for a simultaneous SPECT/MRI
acquisition may require a larger bore than typical of current MRI acquisition remains to be demonstrated. The development of
systems. Wide bore systems are clinically appealing to ease patient appropriate technology remains challenging, but ultimately may
access and improve patient comfort; so, this MRI system de- lead to more general superior SPECT performance.
velopment may be dictated by independent clinical demands.
Early experience suggests that clinical performance similar to that
ACKNOWLEDGMENTS
available on conventional SPECT systems should be possible with
This work was supported by a European Union Seventh
relatively compact detector/collimator combinations, although fur-
Framework Program FP7/2007-2013 under project INSERT
ther innovation may be needed to address sampling issues when the
(HEALTH-F5-2012-305311). DM and NK also receive support
FOV is enlarged to accommodate the whole body.
from FP7/2007-2013 project INMiND (278850). DS is sup-
ported by the Portuguese national funding agency for science,
CONCLUSION research and technology (SFRH/BD/88093/2012). Researchers at
The combination of SPECT and MRI is currently absent from the UCL Institute of Nuclear Medicine receive support from the
the range of clinical multimodality systems, although work is in National Institute of Health Research University College London
progress to produce the first prototype. As in the case of PET/ Hospitals Biomedical Research Centre.

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 Physics and instrumentation special feature review article: Development of clinical simultaneous
simultaneous SPECT/MRI
SPECT/MRI BJR

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