Ann Nucl Med (2013) 27:271–278
DOI 10.1007/s12149-012-0681-5

ORIGINAL ARTICLE

Appropriate collimators in a small animal SPECT scannerwith CZT detector
Yusuke Higaki • Masato Kobayashi •Tomoya Uehara • Hirofumi Hanaoka •Yasushi Arano • Keiichi Kawai

Received: 31 October 2012 / Accepted: 26 December 2012 / Published online: 4 January 2013
Ó The Japanese Society of Nuclear Medicine 2013

Abstract
Objective Almost all small animal SPECT is performed
with pinhole collimators (PH), including single-PH (SPH)and multi-PH (MPH). In the clinical study, not only PH but
also parallel-hole collimator (PAH) is often used in planarand SPECT imaging. However, there have been no comparative studies on image quality with various collimatorson the small animal imaging. This study compared thebasic characteristics of PH and PAH in small animal
imaging.
Methods Performance of planar and SPECT images wasevaluated using 99mTcO4- and SPH, MPH and PAH withlow energy and high resolution on the SPECT/CT scanner
FX3200. We measured sensitivity, resolution, concentration linearity and uniformity. Planar imaging of mice with
99m
Tc-labeled mercaptoacetyltriglycine (99mTc-MAG3)
was performed using SPH and PAH. SPECT imaging with99m
Tc-methylene diphosphonate (99mTc-MDP) was performed using all collimators.
Results With SPH, MPH and PAH, sensitivity was 43.5,
211.2 and 926.5 cps/MBq, respectively, and spatial resolution was 0.60/0.56, non/0.96, 5.20/5.34 mm full-widthhalf maximum (planar/SPECT), respectively. There were
Y. Higaki  M. Kobayashi (&)  K. Kawai
Graduate School of Health Sciences, College of Medical,
Pharmaceutical and Health Sciences, Kanazawa University,
5-11-80, Kodatsuno, Kanazawa 920-0942, Japane-mail: kobayasi@mhs.mp.kanazawa-u.ac.jp
Y. Higaki  T. Uehara  H. Hanaoka  Y. Arano
Graduate School of Pharmaceutical Sciences, Chiba University,
1-8-1, Inohana, Chuo-ku, Chiba 260-8675, JapanK. Kawai
Biomedical Imaging Research Center, University of Fukui,
Fukui, Japan

marked correlations between the radioactivity counts on
images and radioactivity with all collimators. Values of %standard deviation on planar imaging showed small differences between the SPH and PAH, while the values were
the smallest on SPECT imaging with MPH. On imaging of
mice, SPH yielded high-quality 99mTc-MAG3-planar images when compared with PAH. MPH yielded sharper
99m
Tc-MDP-SPECT images than SPH and PAH.
Conclusions The characteristics of PH and PAH differedon small animal imaging. Although sensitivity was higher
with PAH, PH showed higher resolution. Among the PHcollimators, SPH was more appropriate for planar imaging,and MPH was more suitable for SPECT imaging in a small
animal imaging scanner with CZT detector.
Keywords Small animal imaging  Planar imaging 
SPECT imaging  Pinhole collimator  Parallel-holecollimator

Introduction
Single photon emission computed tomography (SPECT)
for small animal imaging is a useful molecular imaging
technique for tracer development and therapy evaluation,
as well as for pathophysiological investigations, in small
animals [1–3]. In current SPECT scanners, cadmium zinctelluride (CZT) semiconductor detectors have been applied
to improve energy and spatial resolution [4–8], as compared with sodium iodide (NaI) scintillation detectors,
which were used in conventional SPECT scanners [9–19].
Planar and SPECT projection data are acquired using
various collimators in clinical settings. Almost all small
animal SPECT is performed with pinhole collimators (PH),including single-PH (SPH) [8, 12–17] and multi-PH (MPH)

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Ann Nucl Med (2013) 27:271–278[6, 8–10, 15], as these collimators will provide good resolution for small objects when compared with parallel holecollimators (PAH), which are more commonly used inclinical settings [20]. Although we have to select appropriate collimator to obtain high-quality images and accurate analysis results, there have been no comparative
studies on image quality with various collimators in small
animal imaging.
In this study, we compared the performance and image
quality of SPH, MPH and PAH in small animal scannerwith CZT detector. Performance was evaluated using point,line and planar sources, and Derenzo phantoms. Planar and
SPECT images were obtained using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and 99mTc-methylene diphosphonate (99mTc-MDP), respectively.
Materials and methods
System description
We used the FX-3200 (Gamma Media-Ideas Inc., CA,
USA) as a small animal SPECT/CT scanner (Table 1). The
FX-3200 has four detectors with a cadmium zinc telluride(CZT) semiconductor (20.5 9 15.5 9 9.0 cm). Threetypes of collimator could be attached: (1) SPH, single
pinhole, focal-length 90 mm; (2) MPH, five pinhole, focallength 75 mm; and (3) PAH with low energy and highresolution. Radius of rotation (ROR) is from 15 to 175 mm,
and field of view (FOV) is a maximum of 120 mm, while
detectable energy ranges from 20 to 300 keV. All imaging
data were acquired at a matrix size of 80 9 80.
Sensitivity
A 3.7 MBq 99mTcO4- point source was placed in the centerof the FOV, and planar and SPECT data were acquired for
10 min. Distances between the phantom and each detector
were reduced as far as possible. An assembly of 4 detectors

with SPH and PAH was used to obtain planar imaging data.
SPECT data were acquired using a circular orbit with stepand-shoot acquisition at 68 intervals over 3608 for all
collimators.
Spatial resolution and SPECT resolution
with Derenzo phantom
A glass capillary with an internal diameter of 0.5 mm
containing about 3.7 MBq 99mTcO4- was used as a line
source. The positioning and acquisition method was thesame as for sensitivity measurement. Spatial resolution was
obtained using full-width half maximum (FWHM) and fullwidth tenth maximum (FWTM). SPECT resolution was
also obtained using a Derenzo phantom (K.K.K. NikohCo., Shizuoka, Japan) made from acryl with four types ofrod (0.5, 0.8, 1.0 and 1.2 mm in diameter) (Fig. 1d). A totalof 74 MBq 99mTcO4- was injected into the phantom,
which was then acquired using all collimators.
Concentration linearity
The positioning and acquisition method was the same as
for sensitivity and resolution measurement for each collimator. Planar and SPECT data were acquired at various
time points and radioactivity levels (1.0, 2.0, 3.7, 7.4, 11.1,
14.8, 18.5, 27.8, 37.0, 74.0, 111, 148 and 185 MBq) usinga planar source and cylindrical phantom (300 ml),respectively.
Uniformity
A planar source with 37 MBq 99mTcO4- and a cylindricalphantom including 185 MBq 99mTcO4- were placed in thecenter of the FOV. Planar and SPECT data were acquiredfor 10 and 30 min, respectively. We calculated the %standard deviation (%STD) in the regions of interest (ROI).
Planar imaging of 99mTc-MAG3

Table 1 Features of collimators on SPECT/CT scanner FX3200
Composition

Collimators
SPH

MPH

PAH

Material

TungstenTungstenTungsten andantimony

Number of pinholes

1

5

10000

Pinhole diameter (mm)Minimum FOV for animal
imaging (mm)

0.5
26.7

0.5
46.3

1.22
120

Focal length (mm)

90

75

–

SPH single-pinhole collimator, MPH multi-pinhole collimator, PAH
parallel hole collimator for low energy, high resolution, FOV field ofview, ROR radius of rotation

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Animal studies were approved by the Animal Care Committee at Chiba University and were conducted in accordance with international standards for animal welfare andinstitutional guidelines. Adequate measures were taken tominimize pain and discomfort. Five normal male ddy mice
(29–33 g) from Japan SLC Inc. (Hamamatsu, Japan) werehoused for 1 week under a 12-h light/12-h dark cycle withfree access to food and water. Mice were fasted with nofood overnight with water supplied ad libitum before
SPECT experiments.
Five mice were anesthetized with 1.2–1.5 % isoflurane(Abbot Laboratories, Illinois, USA). A PE-10 catheter wasinserted into the femoral artery for blood, and the femoral

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273

Fig. 1 SPECT imaging with
the Derenzo phantom. SPECT
images of phantoms wereobtained after 20 min with
74 MBq 99mTcO4- using all
collimators. Image data wereacquired using SPH (a) andMPH (b), followed byreconstruction using the 3DOSEM algorithm (4 subsets and
20 iterations), or PAH (c),followed by reconstruction
using a filtered back-projection
algorithm. The Derenzo
phantom had four rods (0.5, 0.8,
1.0 and 1.2 mm in diameter) (d)vein for 99mTc-MAG3 (Fujifilm RI Pharma Co., Tokyo,
Japan) administration. Imaging data were acquired with the
dynamic planar protocol using the small animal SPECT/CT
scanner FX-3200. Mice were placed in the supine positionon the scanner bed, and limbs were fixed using surgicaltape. The orientation of the renal position was determinedusing a laser beam and CT imaging on the scanner. Aftersetting ROR to be maximally close to mice, dynamic scans(2 s 9 30 frames, 5 s 9 48 frames and 30 s 9 30 frames)with SPH were started with an intravenous bolus administration of about 15 MBq 99mTc-MAG3 using an microinjection pump CFX1010 (ISIS, Osaka, Japan) for 15–20 s.
On the next day, the same mice were used for experiments
using the same scanning protocol with PAH and ROR
being set maximally close to mice. For 2 further days, thesame mice were evaluated using 74 MBq 99mTc-MAG3
under the same experimental protocol as with 15 MBq
99m
Tc-MAG3. Voxel sizes were 0.53 9 0.53 9 0.37 with
SPH and 0.70 9 0.70 9 0.50 mm with PAH, respectively.
Regions of interest were placed over whole kidneys in
99m
Tc-MAG3 images.

close to mice for SPECT imaging using each collimator. At
30 min after injection, whole-body SPECT imaging data
were started for 30 min using each collimator. Voxel sizes
were 0.53 9 0.53 9 0.37 mm with SPH, 0.43 9 0.43 90.31 mm with MPH and 0.70 9 0.70 9 0.50 mm with
PAH.

SPECT imaging of 99mTc-MDP

Sensitivity

Three normal ddy mice were injected with 74 MBq of
Tc-MDP (Fujifilm RI Pharma Co., Tokyo, Japan) via
the tail vein. Positioning and scanning preparation were thesame as with 99mTc-MAG3. ROR was set to be maximallySensitivity data are summarized in Table 2. On planar
imaging, sensitivity with PAH was higher than that with
SPH. On SPECT imaging, the highest sensitivity wasachieved using PAH, followed by MPH and SPH.

99m

Reconstruction methods and image analyses
Planar and SPECT imaging data with PAH were reconstructed using a filtered back-projection algorithm with aramp filter, which is a reconstruction filter. For SPECT
imaging data with SPH and MPH, a 3D-ordered subset
expectation maximization (3D-OSEM) algorithm wasapplied using 4 subsets and 20 iterations in FLEX-RECON
software. In the all planar and SPECT imaging, pre andpost-filters were not used. Imaging data were analyzed
using amide’s medical imaging data examiner.

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Ann Nucl Med (2013) 27:271–278

Table 2 Sensitivity of collimators on planar and SPECT imaging
Collimators

Sensitivity (cps/MBq)

Table 3 Spatial resolution of collimators on planar and SPECT
imaging
Collimators

FWHM/FWTM (mm)Planar

SPECT

SPH

4.0

43.5

MPH

Non

211.2

SPH

0.60/1.09

0.56/1.03

PAH

239.1

926.5

MPH

Non/1.53

0.96/1.75

PAH

5.20/9.49

5.34/9.74

Planar

SPH single-pinhole collimator, MPH multi-pinhole collimator, PAH
parallel collimator for low energy, high resolution

SPECT

FWHM full-width half maximum, FWTM full-width tenth maximum,
SPH single-pinhole collimator, MPH multi-pinhole collimator, PAH
parallel collimator for low energy, high resolution

Spatial resolution and SPECT resolution
with Derenzo phantom
Discussion
Spatial resolution data are shown in Table 3. Resolution onplanar images was 0.60 mm with SPH and 5.20 mm with
PAH. On SPECT imaging, resolution was 0.56, 0.96 and5.34 mm using SPH, MPH and PAH, respectively. On
SPECT with the Derenzo phantom, SPH provided the best
quality images (Fig. 1).
Concentration linearity
Concentration linearity is shown in Fig. 2. Correlations
between radioactivity and radioactive counts for planar and
SPECT images showed marked linearity (about 1.0) for all
collimators.
Uniformity
Uniformity data are shown in Table 4. The %STDs on
planar imaging were 11.3 with SPH and 9.3 with PAH. On
SPECT imaging, the %STDs were 20.5, 9.2 and 16.8 using
SPH, MPH and PAH, respectively.
Planar imaging of 99mTc-MAG3
On 99mTc-MAG3 images, cortexes of the kidney with SPH
were much clearer than those with PAH (Fig. 3). Time
activity curves (TACs) for the kidney with 99mTc-MAG3
are shown in Fig. 4. TACs with SPA and PAH showed
clear peaks for radioactivity and smooth washout when
74 MBq of 99mTc-MAG3 was injected into mice. When
15 MBq of 99mTc-MAG3 was used, TACs with PAH
showed an ideal radioactivity peak and washout, while
TACs with SPH had an unclear peak and much dispersion.
SPECT imaging of 99mTc-MDP
99m

Tc-MDP images with SPH and MPH were good whencompared to those with PAH (Fig. 5). In particular, separation of the spine was clearest in the 99mTc-MDP images
with MPH.

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In this study, we evaluated the performance of the SPECT
scanner with various collimators, and assessed planar and
SPECT imagings with mice in order to confirm the suitability of these collimators for animal imaging. There arefew commercially available small animal imaging scanners
that are able to perform both planar and SPECT imagings
using CZT detector with various collimators except ourimaging scanner. As shown in Table 2, sensitivity with
PAH on planar imaging was about 60-fold higher than thatwith SPH. These results are important because the sensitivity has not previously been reported on the SPECT
scanner with CZT detector. In other scanners, the sensitivity of planar imaging using the Inveon SPECT scannerwith NaI detector (Siemens Medical Solutions, TN, USA)was about 35 cps/MBq with SPH [12]. Thus, the sensitivity
on the Inveon SPECT scanner was about 8.8-fold higher
than that on our scanner because the imaging scanner with
NaI detector has higher sensitivity than that with CZT
detector. On SPECT imaging, sensitivity with MPH wasabout fivefold higher than that with SPH, while PAH
yielded about 21-fold higher sensitivity than SPH. The
sensitivity was lower than with other scanners with NaI
detector [10, 12, 14, 15, 17].
In our scanner, the resolution of planar and SPECT
imagings with SPH and MPH was 1 mm or less, while
PAH provided about 5 mm (Table 3). In other scanners,
SPH provided 0.6–1.4 mm FWHM with NaI detector[12–15] and 1.0 mm FWHM with CZT detector [8]. MPH
produced about 1.2 mm FWHM with NaI detector [15] and1.2–1.4 mm with CZT detector [6, 8]. PAH yielded about
8 mm FWHM with NaI detector [13]. Thus, our results of
PH were great compared with those of PAH and otherscanners. On SPECT imaging using the Derenzo phantom,
SPECT resolutions with SPH and MPH were 0.5 and
0.8 mm, respectively, and PAH could not display 1.2 mm(Fig. 1). In other scanners, SPECT resolutions with Derenzo
phantom were about 1.0 mm FWHM using CZT detector
with MPH [6] and 0.35–0.5 mm FWHM using NaI detector

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Fig. 2 Concentration linearity
was marked on planar imaging
with SPH (a) and PAH (b). On
SPECT images, linearity also
was marked with SPH (c), MPH(d) and PAH (e)Table 4 Uniformity of collimators on planar and SPECT imaging
Collimators%STD
Planar

SPECT

SPH

11.3

20.5

MPH

Non

9.2

PAH

9.3

16.8

%STD % standard deviation, SPH single-pinhole collimator, MPH
multi-pinhole collimator, PAH parallel collimator for low energy,
high resolution

with MPH [9, 10]. Our results were little changed compared with other scanners.
For concentration linearity, there were marked correlations between radioactivity from low to high and radioactive counts on planar and SPECT images, regardless ofcollimator type (Fig. 2). With regard to uniformity, %STD
values on planar imaging showed small differences
between the SPH and PAH, while the values were thesmallest on SPECT imaging with MPH (Table 4). On otherscanners, %STDs in the SPECT imaging showed smallvalues when compared with our scanners [12], as no preand post-filters were used for our SPECT images. Therefore, we further confirmed that SPH, MPH and PAH produced different performances although Mok et al. [8]examined the differences in performance between SPH and
MPH in other scanners.
On planar imaging with 99mTc-MAG3, ideal TACs wereobtained using SPH (Fig. 3c) and PAH (Fig. 3d) when
74 MBq of 99mTc-MAG3 was injected into mice. Whenusing SPH, renal cortices and calices were clearly distinguished (Fig. 3a, c). Although mouse imaging using about
37 MBq 99mTc-MAG3 was reported in previous studies,clear renal images were not obtained, as gamma camera
and clinical scanner using NaI detector with PAH wereapplied for 99mTc-MAG3 imaging with mice [18, 19]. To
our knowledge, this is the first study to obtain high-resolution images of the kidney using mice injected with
74 MBq 99mTc-MAG3 on small animal SPECT imaging.
However, on mouse imaging with 15 MBq 99mTc-MAG3,
the radioactive peak on TAC was not clear, and the

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Fig. 3 Planar images with 99mTc-MAG3 using mice. Planar imagesof mice were obtained for 20 min with 15 MBq 99mTc-MAG3 using
SPH (a) and PAH (b). After decay of radioactivity, 74 MBq 99mTc-

Ann Nucl Med (2013) 27:271–278

MAG3 was injected into the mice and planar images were obtainedusing SPH (c) and PAH (d). Renal cortices were much clearer on
99m
Tc-MAG3 imaging with SPH

Fig. 4 TACs on planar imaging
with 99mTc-MAG3 using mice.
Dynamic data consisted of 108
frames, 2 s/frame for 1 min,5 s/frame for 4 min and 30 s/
frame for 15 min. When using
15 MBq 99mTc-MAG3, TACs
with PAH (b) were good, while
those with SPH showed noradioactive peaks and large
standard deviation (a). When
74 MBq 99mTc-MAG3 wasinjected into mice, TACs with
SPH (c) and PAH (d) showedradioactive peaks, followed byclear washout

washout period was not smooth when using SPH (Fig. 4a),while TAC with PAH was ideal, due to the higher sensitivity (Fig. 4b); however, the images were very indistinct(Fig. 3b). Although the ROIs were placed over the wholekidneys to assess renal function, ROIs should be placed on
the renal cortices in order to accurately determine renal
function using 74 MBq 99mTc-MAG3 imaging with SPH.
Thus, it is important to select the appropriate collimator forplanar imaging with small animals. However, there has
been little research on collimators for providing highquality images and quantification on planar imaging of
small animals.
On bone scintigraphy with 99mTc-MDP SPECT imaging, SPH and MPH provided SPECT images with higher
resolution when compared with PAH (Fig. 5). The backbone on SPECT images was clearly separated using MPH,
due to the higher sensitivity. On the other hand, PAH was123

not suitable for SPECT imaging, as it yielded SPECT
images with low resolution. Although Mok et al. [8]reported that MPH was appropriate for bone scintigraphyusing 99mTc-MDP with about 67 MBq, we expected that
SPH would be useful with higher radioactivity because thebone scintigraphy was obtained by SPH using 99mTc-MDP
with about 100 MBq [11] and 185 MBq [13], which arehigher radioactivity than in our and Mok’s study [8].
Although the PAH is often used in clinical imaging, PH
should be used to obtain high resolution images on small
animal imaging. On planar imaging with our scanner, SPH
and PAH could be used, and SPH yielded high-quality
images. However, PAH should be used for planar imaging
in order to monitor radiopharmacokinetics on whole body
imaging with radiotracers having low radioactivity. In
addition, PH was suitable for SPECT imaging using ourscanner. With PH, we should select SPH, as it yields

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Fig. 5 SPECT images of 99mTc-MDP using mice. 99mTc-MDP(74 MBq) was injected into mice, and images were acquired using
SPH (a), MPH (b) and PAH (c) for 30 min at 30 min afteradministration. The CT image was displayed using same slices as
the SPECT images (d). On 99mTc-MDP images, MPH showedsignificant separation of the backbone

high-resolution images, or MPH, as it has higher sensitivity
than SPH, depending on the gamma-emitting radionuclide
and radioactivity of radiotracers used. This study offeredinsights into the use of collimators for small animal
imaging. Although we should use the same reconstruction
method to compare performance of each collimator in the
SPECT imaging, the same reconstruction method could not
be set up in our scanner. In other scanners, researchers
should confirm whether the differences of the reconstruction methods are affected to select the collimators. In
addition, the most appropriate collimator will varydepending on scanner, gamma-emitting radionuclide,radioactivity of radiotracers, pharmacokinetics, small

animal and/or imaging acquisition method, etc. Based on
our results, we have to consider design of collimators to
obtain higher quality images.
In conclusion, the characteristics of PH and PAH weredifferent on small animal imaging. Although sensitivity
was higher with PAH, PH showed higher resolution.
Among the PH collimators, SPH was more appropriate forplanar imaging, and MPH was more suitable for SPECT
imaging in a small animal scanner with CZT detector.
Acknowledgments The author would like to thank the staff ofChiba University for their technical assistance. This study was partly
funded by a Grant-in-Aid for Scientific Research from Japan Society

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for the Promotion of Science (23659578, 23659579, 24601008, and24659558).

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