Ann Nucl Med (2014) 28:512–522
DOI 10.1007/s12149-014-0841-x

ORIGINAL ARTICLE

Effect of surrounding materials on iterative reconstruction-basedline-source response function, and annihilations outside the source
assessed by a small animal PET scanner
Yoshiharu Miyazaki • Masato Kobayashi • Ryoko Komatsu •Akiko Hayashi • Shoko Yonezawa • Keiichi Kawai •Masamichi Matsudaira • Jun Shiozaki • Ichiro Matsunari

Received: 23 July 2013 / Accepted: 13 March 2014 / Published online: 29 March 2014
Ó The Japanese Society of Nuclear Medicine 2014

Abstract
Objective The aims of this study were (1) to evaluate theeffect of surrounding materials on the iterative reconstruction-based line-source response function (IR-RF) of
18
F, 11C, 13N, and 15O using a preclinical PET system, and(2) to determine whether and how annihilation outside thesource can be visualized experimentally.
Methods We performed all the measurements using the
LabPET-8 PET/CT subsystem built-in the Triumph II
platform (TriFoil Imaging, Inc., Northridge, CA, USA). IRRF was measured for 18F, 11C, 13N, and 15O, and was
expressed as full-width at half-maximum (FWHM) and
full-width at tenth maximum (FWTM) using a glass capillary phantom mounted in materials of various densities,
which were chosen to cover the wide range of real tissues.
To determine whether and how annihilation outside thesource can be visualized, we designed a concentric ring
paper phantom, which consisted of a source at the centerwith 4 ring-like paper layers.
Results When the radionuclides were placed in air(material density 0 g/cm3), IR-RFs were similar among theY. Miyazaki  R. Komatsu  A. Hayashi  S. Yonezawa 
M. Matsudaira  I. Matsunari (&)
Clinical Research Department, The Medical andPharmacological Research Center Foundation, Wo 32, Inoyama,
Hakui, Ishikawa 925-0613, Japane-mail: matsunari@mprcf.or.jp
M. Kobayashi  K. Kawai
School of Health Sciences, College of Medical, Pharmaceuticaland Health Sciences, Kanazawa University, Kodatsuno 5-11-80,
Kanazawa, Ishikawa 920-0942, Japan
J. Shiozaki
Department of Nuclear Medicine, Noto General Hospital,
Abu 6-4, Fujihayashi-machi, Nanao, Ishikawa 926-0816, Japan123

radionuclides tested. As the surrounding material density
increased, IR-RFs for higher energy-emitting radionuclides(11C, 13N, and 15O) became worse, whereas those of 18F
remained relatively constant over the range of surrounding
material densities (0–2.17 g/cm3). Both FWHM and
FWTM values were closely correlated with mean energy ofradionuclides at middle to high material densities (material
density 0.94–2.17 g/cm3). The FWTM/FWHM ratio ofhigh energy-emitting radionuclides such as 15O increased
as a function of material density, which was followed bysubsequent decrease at high material densities (1.2–2.17 g/
cm3). Using a concentric ring paper phantom, annihilations
outside the source were visible and measurable. The
innermost layer was visible with all radionuclides, whereas
the outer layers only with high energy positron emitters.
Conclusions The results indicate that surrounding material affects IR-RF particularly for high energy positron
emitters. Furthermore, annihilation outside the radio-active
source can be visualized with some circumstances such as
those seen with a concentric ring paper phantom.
Keywords Iterative reconstruction-based spatial
resolution  Positron range  Surrounding materials  PET 
Annihilation

Introduction
Preclinical molecular imaging such as PET using small
animals is increasingly being recognized as an important
tool for biomedical research and new drug development [1,2]. Although the state-of-the-art preclinical PET systems
have reportedly achieved near millimeter spatial resolutions [3], it is still a limiting factor to image very small
structures such as those encountered in mouse organs.

Ann Nucl Med (2014) 28:512–522

Spatial resolution is known to be affected by several factors
such as positron range, non-colinearity of annihilating
photons, and intrinsic properties of the PET scanner. The
overall spatial resolution of the systems is a convolution ofthese components. Tissue surrounding the radioactive
source is another important factor that affects spatial resolution as demonstrated in a MonteCarlo simulation study
by Sanchez-Crespo et al. [4]. To date, however, the effectof surrounding materials on spatial resolution for positron
emitters with different flight ranges has not yet been
investigated systematically in experimental studies, except
for one by Kemerink et al. [5] who investigated the effectof positron range of 18F, 68Ga and 124I on PET in lungequivalent materials.
Apart from possible spatial resolution deterioration due
to positron range, annihilation outside the source may
create hot regions where the radioactive source does notexist. If this is true, such a phenomenon could be a problem
in image interpretation, because the positron range of someradionuclides such as 11C, 13N, or 15O exceeds the spatial
resolution of modern preclinical PET scanners [3]. However, whether such annihilation outside the source can bevisualized has not been well documented in literature.
The aims of this study were (1) to evaluate the effect ofsurrounding materials on the iterative reconstruction-basedline-source response function (IR-RF) of 18F, 11C, 13N, and15
O positron emitters using a preclinical PET system, and(2) to determine whether and how annihilation outside thesource can be visualized experimentally. We used IR-RF asa term referring to spatial resolution obtained in the present
study, because we used iterative reconstruction rather thanfiltered back projection (FBP). We chose 18F, 11C, 13N, and15
O as radionuclides to be tested in this study because they
are commonly used, have different positron ranges, and are
pure or near pure positron emitters. To address the second
issue, we designed a concentric ring paper phantom as
detailed in a later section.

Methods

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7.5 cm. The scintillation crystals were composed of anassembly of Lu0.4Gd1.6SiO5 (LGSO) and Lu1.9Y0.1SiO5(LYSO) with dimensions of 2 2 14 mm. All PET studies wereacquired using a 250–650 keV energy window and 22 ns
coincidence-timing window.
Reconstruction settings
The list-mode data were binned into three-dimensional(3D) histograms or sinograms. The images were reconstructed using the 3D ordered subset expectation maximization (OSEM) algorithm with 1 subset and 100 iterations
according to the recommendations by the manufacturer.
The voxel size was set to the smallest one available in thissystem (0.25, 0.25, 0.5 mm) using a high-resolution mode
option. The use of 3D OSEM rather than FBP in this study
was because of two reasons. Firstly, FBP in our system hadvery limited capability in that it provided no options forfilter selection and filter parameters. Secondly, the highresolution option was not available for FBP in our system;
the voxel size was always set to 0.5, 0.5, 0.5 mm with FBP
instead of 0.25, 0.25, 0.5 mm with 3D OSEM. For thesereasons, the use of iterative reconstruction rather than FBP
is recommended for routine imaging by the manufacturer.
The acquired data were not corrected for attenuation or
scatter and reconstructed without post-reconstructionsmoothing unless specified. However, CT-based attenuation with or without scatter correction was performed for
iterative reconstruction-based spatial resolution measurements with the high density material as mentioned later.

Positron emitting radionuclides
Radionuclides were provided as a form of 18F-fluorodeoxyglucose, 11C-acetate, 13N-ammonia, or 15O-water.
Physical characteristics of the radionuclides are summarized in Table 1.
Table 1 Physical characteristics of 18F, 11C, 13N, and 15O
18

F

System description
We performed all the measurements using the LabPET-8
PET/CT subsystem built-in the Triumph II platform (TriFoil
Imaging, Inc., Northridge, CA, USA), which is a preclinicalimaging system dedicated for small animal imaging. The
features and performance of this imaging system were
described in detail elsewhere [6]. In brief, the detector arrayconsisted of 6144 crystals arranged in contiguous rings with aring diameter of 16.2 cm and an axial field of view (FOV) of

11

C

13

N

15

O

Half-life (min)

109.8

20.4

9.98

2.03

Decay mode

97 % b?

100 % b?

100 % b?

100 % b?

Maximum energy
(MeV)

0.69

0.96

1.19

1.7

Mean energy (MeV)

0.250

0.386

0.492

0.735

Maximum range
in water (mm)

2.4

4.1

5.4

8.0

The physical characteristics of radionuclides are based on data from
Health Physics Society [7] and International Commission on Radiation Units and Measurements [8]

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Fig. 1 Phantoms simulating surrounding tissue of various densities (a); the EP resolution phantom (b); a concentric ring paper phantom (c)Iterative reconstruction-based line-source response
function measurements
For IR-RF measurements with various surrounding materials, a glass capillary of inner diameter 0.14 mm (outer
diameter 0.55 mm) was filled with solution of 18F-fluorodeoxyglucose (mean ± standard deviation of 35 acquisitions for each radionuclide: 227 ± 111 MBq/mL), 11Cacetate (239 ± 120 MBq/mL), 13N-ammonia (316 ± 171
MBq/mL), or 15O-water (1801 ± 500 MBq/mL) at thestart of acquisition. The glass capillary line source was thenplaced in air (material density 0 g/cm3) or one of the 6cylindrical tissue phantoms (30-mm in length and 25.4-mm
in diameter) (Hokuriku EP, Hakui, Japan) (Fig. 1a) in thecenter of FOV. The cylindric tissue phantoms were madeof compressed cork (material density 0.48 g/cm3), polyethylene (material density 0.94 g/cm3), mixture of paraffin,
polyethylene, pine resin, magnesium oxide, and titanium
dioxide (material density 1.01 g/cm3), polycarbonate(material density 1.20 g/cm3), polyacetal (material density
1.41 g/cm3), or polytetrafluoroethylene (material density
2.17 g/cm3). These materials were chosen to cover thewide range of real tissues (e.g., air 0 g/cm3, adipose tissue

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0.92 g/cm3, soft tissue 1.0 g/cm3, bone 1.85 g/cm3) [4]. A
cylindric hole (diameter, 0.6 mm) was drilled at the centerof each tissue phantom so that the capillary line source
fitted inside and in the center of FOV. Additionally, thesemeasurements were performed for a 11C-line source(150 ± 70 MBq/mL) with a radial offset of 25 mm toassess measurement stability over transaxial FOV.
PET acquisition was performed 5 times for each surrounding material, resulting in a total of 35 acquisitions foreach radionuclide. The acquisition time was 10 min for
18
F, 11C, and 13N, and 5 min for 15O. To assess the influence of attenuation/scatter correction on measurements, CT
scan for approximately 1 min was additionally performedfor 11C with the highest density surrounding material(material density 2.17 g/cm3). The full-width at half-maximum (FWHM) and full-width at tenth of maximum(FWTM) were determined by linear interpolation between
adjacent pixels at half or one-tenth of the maximum valueof the line count profile on the reconstructed transaxial
image based on the National Electrical Manufacturers
Association (NEMA) NU4-2008 recommendation [9]. The
maximum value was determined by a parabolic fit using thepeak point and its two nearest neighboring points,

Ann Nucl Med (2014) 28:512–522

respectively. The averages of radial and tangential directions were calculated over 10 transaxial slices for all 35
acquisition data for each radionuclide.

515

calculated for each layer as follows: total count of a layer/
total count of source at the center.
Statistical analysis

Resolution phantom measurements
To have an overview of how IR-RF looks like visually, we
performed imaging using the EP resolution phantom(Hokuriku EP, Hakui, Japan) (Fig. 1b). The phantom wasmade of acrylic resin (density 1.19 g/cm3) with dimensionsof 27 mm in diameter and 10 mm in height. It had 6 segments with fillable capillary rods of 0.7, 0.9, 1.0, 1.3, 1.5,
and 1.8 mm in diameter with the distances between thecapillary rods in a segment equal to the capillary diameterwithin that segment. The phantom was filled with
48.5 MBq of 18F-fluorodeoxyglucose, 109 MBq of 11Cacetate, or 133 MBq of 13N-ammonia, and was thenscanned for 60 min for 18F, 30 min for 11C, and 20 min for13
N. We could not test 15O imaging in a reliable manner
because the very short half-life (2 min) of this radionuclide
prevented us from completion of the phantom preparation,
which usually took approximately 10 min.
Concentric ring paper phantom
To determine whether and how annihilation outside thesource can be visualized, we designed a concentric ring
paper phantom as depicted in Fig. 1c. The phantom consisted of a source at the center with 4 ring-like paper layers(15, 25, 35 and 45 mm in diameter). Each layer consisted of
6 sub-layers of 90-lm thick papers. A filter paper chip,
which served as a source at the center, was infiltrated with
1.2 ± 0.5 MBq of 18F-fluorodeoxyglucose, 1.2 ± 0.5 MBq
of 11C-acetate, 1.5 ± 0.9 MBq of 13N-ammonia, or
0.5 ± 0.5 MBq of 15O-water, and was then scanned for
30 min for 18F, 20 min for 11C, 10 min for 13N, and 5 minfor 15O, followed by X-ray CT scan. PET/CT acquisition
was performed 5 times for each radionuclide. The idea
behind this experiment is that (1) in general, positrons travel
long distances (i.e., several meters) in air; (2) however, inthe presence of light materials such as paper, some positrons
might be trapped with annihilations; (3) such annihilations
could be detected using preclinical PET imaging; (4) theamount of annihilations on each layer would depend on theenergy of positron emitters and the distance between thesource and the paper layer. Furthermore, 5 additional
acquisitions were performed for 18F with the source covered
with a 3-mm-thick clay (material density 2.10 g/cm3) to see
the effect of high-density materials on annihilation. On
reconstructed transaxial images, total count of the source at
the center or each layer was obtained using AMIDE software [10] for all 5 acquisitions for each radionuclide. On thebasis of these count values, layer-to-center count ratios were

Values for repeated measurements were expressed asmean ± 1 standard deviation. Statistical analysis was
performed using JMP 10 (SAS Institute Inc. Cary, NC,
USA), or GraphPad Prism 6 (GraphPad Software, Inc. San
Diego, CA, USA), where appropriate. Comparisons ofmean values were performed using t test or analysis ofvariance (ANOVA), followed by Tukey’s multiple comparison test. Correlations of variables were analyzed bysimple linear regression, which were done only when thevariable was significantly different. Statistical significancewas defined as P \ 0.05.

Results
Iterative reconstruction-based line-source response
function
The IR-RFs expressed as FWHM/FWTM for 18F, 11C, 13N,
and 15O in relation to surrounding material density aresummarized in Table 2. When the radionuclides wereplaced in air (material density 0 g/cm3), IR-RFs weresimilar among the radionuclides tested. In particular,
FWHM values were below 1 mm for all the radionuclides
when the sources were placed at the center of FOV. As thematerial density increased, IR-RFs for higher energyemitting radionuclides (11C, 13N, and 15O) became worse,
whereas those of 18F remained relatively constant over therange of surrounding material densities tested (0–2.17 g/
cm3). The worst FWHMs were observed at material densityof 0.94 g/cm3 for 18F, 1.01 g/cm3 for 11C, 2.17 g/cm3 for
13
N, and 2.17 g/cm3 for 15O, whereas the worst FWTMs
were at material density of 0.94 g/cm3 for 18F, 1.20 g/cm3
for 11C, 0.94 g/cm3 for 13N, and 1.01 g/cm3 for 15O. The
use of attenuation and scatter correction slightly but significantly improved FWHM and FWTM in the presence ofhigh density surrounding material, whereas the use of
attenuation correction alone did not. When the 11C source
was placed 25 mm off-center, both FWHM and FWTM
were significantly but only modestly (e.g., 20 ± 6 % in
FWHM) worse than those obtained at the center of FOV
with most surrounding materials tested. The FWTM/
FWHM ratios are plotted for each radionuclide as a function of material density in Fig. 2. At low to middle material
density (0–1.01 g/cm3), the FWTM/FWHM ratio of highenergy-emitting radionuclides such as 15O increased as afunction of material density, which was followed by subsequent decrease at high material densities (1.2–2.17 g/

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Ann Nucl Med (2014) 28:512–522

Table 2 Full-width at half-maximum (FWHM) and full-width at tenth of maximum (FWTM) (parenthesis) values for 18F, 11C, 13N, and 15O in
relation to surrounding material density
18

F

11

13

15

P value by
ANOVA

11

C

N

O

C off-center(25 mm)Material density (g/cm3)
00.765 ± 0.053

0.779 ± 0.050

0.780 ± 0.058

0.807 ± 0.025

0.580

0.952 ± 0.056

0.48(1.532 ± 0.067)
0.843 ± 0.017(1.591 ± 0.078)
0.902 ± 0.024(1.620 ± 0.082)
1.015 ± 0.049*(1.572 ± 0.063)
1.003 ± 0.054*(0.319)\0.0001(1.935 ± 0.119 )1.168 ± 0.044(1.779 ± 0.040)(1.953 ± 0.115)(2.294 ± 0.181*)(2.325 ± 0.151*)(\0.0001)(2.600 ± 0.051 )0.94

0.893 ± 0.045

1.008 ± 0.047

1.124 ± 0.018

1.235 ± 0.038\0.0001

1.224 ± 0.071(1.867 ± 0.131 )(2.325 ± 0.094 )(2.785 ± 0.153 )(4.105 ± 0.166 )(\0.0001)(2.610 ± 0.164 )1.01

0.869 ± 0.037

1.050 ± 0.032*

1.105 ± 0.044*

1.285 ± 0.045\0.0001

1.239 ± 0.048(1.793 ± 0.063 )(2.343 ± 0.050 )(2.746 ± 0.134 )(4.465 ± 0.107 )(\0.0001)(2.683 ± 0.100 )0.892 ± 0.071

1.026 ± 0.021*

1.097 ± 0.042*

1.280 ± 0.031\0.0001

1.247 ± 0.031(1.862 ± 0.169 )(2.353 ± 0.033 )(2.748 ± 0.102 )(4.033 ± 0.237 )(\0.0001)(2.615 ± 0.066 )1.41

0.868 ± 0.041

1.046 ± 0.016*

1.097 ± 0.063*

1.317 ± 0.040\0.00011.180 ± 0.063(1.795 ± 0.119 )(2.316 ± 0.033 )(2.607 ± 0.182 )(3.969 ± 0.099 )(\0.0001)(2.412 ± 0.117)

2.17

0.879 ± 0.030

1.016 ± 0.035

1.152 ± 0.056

1.343 ± 0.061\0.0001

1.131 ± 0.046(2.138 ± 0.083 )(2.536 ± 0.075 )(3.578 ± 0.091 )(\0.0001)(2.332 ± 0.126 )

1.20(1.781 ± 0.062 )2.17 (AC)0.993 ± 0.029

2.17 (AC + SC)

0.951 ± 0.036**(1.983 ± 0.080**)(2.079 ± 0.097)

Data are expressed as mean ± 1 standard deviation (mm) of 5 measurements
ANOVA analysis of variance, AC attenuation correction, SC scatter correction* P \ 0.05 vs. 18F
P \ 0.05 vs. other radionuclides
P \ 0.05 vs. 11C at the center of field of view by t test** P \ 0.05 vs. 11C FWHM or FWTM value with material density of 2.17 g/cm3

cm3). By contrast, the FWTM/FWHM ratio of low energyemitting radionuclides such as 18F was stable over theentire range of material density tested. The 11C source
placed 25 mm off-center showed FWTM/FWHM ratios
similar to those obtained at the center of FOV. The relationship between FWHM/FWTM and mean energy of the 4radionuclides are plotted for various surrounding materials
in Figs. 3 and 4. The FWHM values were not different
among the radionuclides at low material densities (material
density 0–0.48 g/cm3), but showed close correlations at
middle to high material densities (material density
0.94–2.17 g/cm3). Essentially similar results were observed
for the FWTM values (Fig. 4).
EP resolution phantom study
Figure 5 depicts EP resolution phantom images for 18F,
C, and 13N. By visual inspection, 1.8, 1.5, and 1.3 mmrods were clearly visible for 18F, whereas 1.0 mm or
smaller rods were difficult to identify. The rod visibility for11
C was slightly worse than that for 18F. For 13N, even11123

1.8 mm or 1.5 mm rods were blurred as compared withthose for 18F or 11C.
Concentric ring paper phantom
CT and PET images of a concentric ring paper phantom arepresented in Fig. 6. For 18F, the most inner layer (layer 1),
which was approximately 7.5-mm apart from the 18F
source, was clearly visualized, whereas outer layers (layers
2–4) were only faintly or not visible. When the 18F source
was covered with 3-mm thick clay, none of the layers was
visible. For 11C and 13N, the second inner layer (layer 2)
was faintly visible in addition to the more clearly visible
layer 1. For 15O, even the outer layers (layers 3 and 4) werevisible in addition to layers 1 and 2. These visual observations were confirmed by quantitative analysis of layer-tocenter count ratios summarized in Table 3. When the 18F
source was placed in air without the clay cover, the countratio in layer 1 was 0.279 ± 0.093 and decreased as afunction of layer number. With the clay cover, the countratio was only 0.003 ± 0.001 in layer 1 and dropped to 0 in

Ann Nucl Med (2014) 28:512–522

1

*

1

2.
17

1.
2

1.
41

1.
41

1.
2

2.
17

Material Density (g /cm3)

*

*

1.
41

2.
17

3
2
1

Material Density (g /cm3)

0

2.
17

1.
41

1.
2

1.
01

0.
94

0

0

0.
48

0

*

1.
2

1

*

1.
01

2

*

0.
94

*

*

0.
48

*

FWTM / FWHM Ratio

*

*

15O

4

*

1.
01

0.
94

0

0.
48

2.
17

1.
41

1.
2

1.
01

0.
94

0

13N

*

*
2

0

Material Density (g /cm3)

4
3

3

1.
01

2

Material Density (g /cm3)

FWTM / FWHM Ratio

*

0

0.
48

0

*

0.
94

1

*

0

*

3

*

11C off-center (25 mm)

4

0.
48

FWTM / FWHM Ratio

3
2

11C

4

FWTM / FWHM Ratio

18F

4

FWTM / FWHM Ratio

517

Material Density (g /cm3)

Fig. 2 The full-width at tenth of maximum to full-width at halfmaximum (FWTM/FWHM) ratios plotted for 18F (upper left), 11C(upper middle), off-centered 11C by 25 mm (upper right), 13N (lowerleft), and 15O (lower middle) as a function of surrounding material
density (g/cm3). Error bar indicates standard deviation. *P \ 0.05 vs.
FWTM/FWHM ratio at material density 0 g/cm3

outer layers. Significantly higher layer-to-center ratios thanfor 18F were observed in outer layers for 15O.
The relationships between mean energy of positron
emitters and mean of layer-to-center count ratios in eachlayer are plotted in Fig. 7. The inner layers (layers 1 and 2)
did not show significant correlations with energy of radionuclides, whereas the outer layers (layers 3 and 4)
showed significant correlations between the twoparameters.

followed by subsequent decrease at high material densities(1.2–2.17 g/cm3); (4) both FWHM and FWTM values wereclosely correlated with mean energy of radionuclides at
middle to high material densities (material density
0.94–2.17 g/cm3); (5) EP resolution phantom images for
18
F, 11C, and 13N confirmed the observation mentioned
above; and (6) using a concentric ring paper phantom,
annihilations outside the source were visible andmeasurable.

Discussion

Iterative reconstruction-based line-source response
function and surrounding materials

To the best of our knowledge, this is the first study
reporting the effect of surrounding materials on IR-RF of 4commonly used positron emitters in experimental phantoms. The major findings of this study were that (1) when
the radionuclides were placed in air (material density 0 g/
cm3), IR-RFs expressed as FWHM or FWTM were similar
among the radionuclides tested; (2) as the material density
increased, IR-RFs for higher energy-emitting radionuclides(11C, 13N, and 15O) became worse, whereas those of 18F
remained relatively constant over the range of surrounding
material densities tested (0–2.17 g/cm3); (3) the FWTM/
FWHM ratio of high energy-emitting radionuclides such as
15
O increased as a function of material density, which was

Differences in spatial resolution due to different positron
range have been reported in 1970s [11–13]. More recently,
Disselhorst et al. [14] have reported poorer spatial resolutions for high energy positron emitters (68Ga, 124I) as
compared with those for low energy positron emitters (18F,
89
Zr). However, these measurements were mostly performed only in water. It should also be noted that organs inliving animals are rather complicated in that they often
consist of various tissues such as air, adipose, water, andbone. Our results demonstrated that, when the radioactive
source was placed in air, there were no significant differences in IR-RF expressed as FWHM or FWTM amongradionuclides tested. Furthermore, IR-RF was better in air

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Ann Nucl Med (2014) 28:512–522
Material Density = 0.48 g/cm3
y = 0.340x + 0.783, R = 0.8431, P = 0.1569

1.5

FWHM (mm)

FWHM (mm)Material Density = 0 g/cm3

1.0
18F

11C 13N

1.5

1.0

15O

18F

0.5
0.0

0.2

0.4

0.6

0.8

0.0

Mean Energy (MeV)

1.5

1.0
18F

11C 13N

0.2

0.4

0.6

0.8

Material Density = 1.01 g/cm3
y = 0.823x + 0.694, R = 0.9850, P = 0.0150
FWHM (mm)

FWHM (mm)15O

Mean Energy (MeV)

Material Density = 0.94 g/cm3
y = 0.708x + 0.735, R = 0.9811, P = 0.0189
1.5

1.0

15O

18F

0.5

11C 13N

15O

0.5
0.0

0.2

0.4

0.6

0.8

0.0

Mean Energy (MeV)

FWHM (mm)1.0
11C 13N

0.4

0.6

0.8

Material Density = 1.41 g/cm3
y = 0.893x + 0.666, R = 0.9913, P = 0.0087

1.5

18F

0.2

Mean Energy (MeV)

Material Density = 1.2 g/cm3
y = 0.788x + 0.707, R = 0.9974, P = 0.0026
FWHM (mm)11C 13N

0.5

1.5

1.0
18F

15O

0.5

11C 13N

15O

0.5
0.0

0.2

0.4

0.6

0.8

0.0

Mean Energy (MeV)

0.2

0.4

0.6

0.8

Mean Energy (MeV)

FWHM (mm)Material Density = 2.17 g/cm3
y = 0.961x + 0.650, R = 0.9951, P = 0.0049
1.5

1.0
18F

11C 13N

15O

0.5
0.0

0.2

0.4

0.6

0.8

Mean Energy (MeV)

Fig. 3 Scatter plots showing the relationship between iterative
reconstruction-based line-source response function expressed as
full-width half-maximum (FWHM) and mean energy of 18F, 11C,

N, and 15O for various surrounding materials. Solid lines indicate
regression line, dot lines 95 % confidence intervals

than in tissue materials for all radionuclides. This is different from what was expected from the results ofMonteCarlo simulation [4], where spatial resolution worsened as a function of tissue density, but is consistent withan experimental study [5], where spatial resolution in air
was better than that in water or lung simulated tissue. We
also observed that each radionuclide had different material
density which produced the worst FWHM or FWTM. As

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13

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519

Material Density = 0 g/cm3

Material Density = 0.48 g/cm3
y = 1.162x + 1.547, R = 0.8965, P = 0.1035
5

FWTM (mm)

FWTM (mm)

5
4
3
2
18F

1
0.0

0.2

11C 13N

0.4

15O

0.6

4
3
2
18F

1

0.8

0.0

Mean Energy (MeV)

44

FWTM (mm)

FWTM (mm)

5

3
2
1
0.0

0.2

0.4

15O

0.6

0.8

3
2
18F

1

0.8

0.0

0.2

11C 13N

0.4

15O

0.6

0.8

Mean Energy (MeV)

Mean Energy (MeV)

Material Density = 1.41 g/cm3
y = 4.482x + 0.584, R = 0.9903, P = 0.0097

Material Density = 1.2 g/cm3
y = 4.511x + 0.648, R = 0.9946, P = 0.0054
5

FWTM (mm)5FWTM (mm)0.6Material Density = 1.01 g/cm3
y = 5.557x + 0.249, R = 0.9874, P = 0.0126

5

11C 13N

0.4

15O

Mean Energy (MeV)

Material Density = 0.94 g/cm3
y = 4.681x + 0.591, R = 0.9939, P = 0.0061

18F

0.2

11C 13N

4
3
2
18F

1
0.0

0.2

11C 13N

0.4

15O

0.6

4
3
2
18F

1

0.8

0.0

Mean Energy (MeV)

0.2

11C 13N

0.4

15O

0.6

0.8

Mean Energy (MeV)

Material Density = 2.17 g/cm3
y = 3.769x + 0.753, R = 0.9944, P = 0.0056
FWTM (mm)

5
4
3
2
18F

1
0.0

0.2

11C 13N

0.4

15O

0.6

0.8

Mean Energy (MeV)

Fig. 4 Scatter plots showing the relationship between iterative
reconstruction-based line-source response function expressed as
full-width tenth maximum (FWTM) and mean energy of 18F, 11C,

13

N, and 15O for various surrounding materials. Solid lines indicate
regression line, dot lines 95 % confidence intervals

mentioned in that study, once a positron leaves the sourcein air, it is likely to escape detection because the flight
range in air is several meters. Thus, only the annihilations

within the source are detected in air. With the increase inmaterial density, however, more positrons are likely to be
trapped within the surrounding materials, but some may

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Fig. 5 EP resolution phantom images with fillable capillary rods of
0.7, 0.9, 1.0, 1.3, 1.5, and 1.8 mm in diameter for 18F, 11C, and 13N.
Images were normalized to the peak activity on each image

Fig. 6 CT (upper left) and PET images of a concentric ring paper
phantom for 18F with (upper middle) and without clay cover (upper
right), 11C (lower left), 13N (lower middle), and 15O (lower right). The
PET images are normalized to the mean of central source activity

travel long distance depending on the energy of positron
emitters, resulting in worsening in FWHM and FWTM.
Furthermore, this may result in long tail distribution of

positron range with high energy-emitting radionuclides,
and may explain the worsened FWTM/FWHM ratio at low
to middle material density (0.48–1.01 g/cm3) particularly
with 13N and 15O. When the material density is high, mostpositrons are likely to annihilate near the source, resulting
in lessened both FWHM and FWTM, which was true forlow energy-emitting radionuclides (18F and 11C). For highenergy-emitting radionuclides, some positrons may stilltravel long distance even in high density materials, which
may explain the worst FWHM observed at the material
density of 2.17 g/cm3 for 13N and 15O. However, themajority of positrons seem to be trapped near the source
even for these radionuclides, resulting in Gaussian-like
distribution rather than long tail distribution of positron
range. This was reflected by lessened FWTM and FWTM/
FWHM ratio at high density materials observed in thisstudy. Our results also showed that both FWHM and
FWTM for higher energy positron emitters were variable
depending on surrounding material density, whereas thosefor 18F remained relatively constant. This indicates thatsurrounding material affects IR-RF particularly for highenergy positron emitters. To this end, IR-RF is mainly
determined by the energy of positron emitters when thesource is surrounded by dense materials as illustrated in
Figs. 3 and 4. Thus, IR-RF as measured by a preclinical
PET is highly dependent on surrounding materials and theenergy of positron emitters. It would be worthwhile tomention on the IR-RF values reported in this study, which
seem to be better than those reported for the preclinical
PET system [3, 6, 15]. This is likely because we used avery thin (0.14-mm in inner diameter) capillary phantom,
and because we used an iterative reconstruction rather thanfiltered back projection, which reflects our routine practice.
It should also be noted that iterative reconstruction may
overestimate the resolution, which is known to occur as
described in a study by de Jong et al. [16]. The results
obtained by off-centered 11C source showed that there wasonly modest deterioration in both FWHM and FWTM as
compared to those by centered 11C source, indicating that
FWHM/FWTM values are rather stable over transaxial
FOV. This is consistent with published data [6] reporting

Table 3 Layer-to-center count ratios with a concentric ring paper phantom for 18F, 11C, 13N, and 15O
18

F with clay

18

F

11

C

13

N

15

P value\0.0001O

Layer 10.003 ± 0.001*

0.279 ± 0.093

0.233 ± 0.058

0.175 ± 0.062

0.266 ± 0.051

Layer 20.000 ± 0.000*

0.082 ± 0.029

0.104 ± 0.030

0.087 ± 0.033

0.150 ± 0.038\0.0001

Layer 30.000 ± 0.000

0.019 ± 0.010

0.043 ± 0.012

0.048 ± 0.020

0.098 ± 0.027*\0.0001

Layer 40.000 ± 0.000

0.002 ± 0.003

0.022 ± 0.005

0.027 ± 0.011

0.069 ± 0.020*\0.0001

Data are expressed as mean ± 1 standard deviation (mm) of 5 measurements* P \ 0.05 vs. other groups
P \ 0.05 vs. 18F

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521

Fig. 7 The relationships between mean energy of positron emitters and mean of layer-to-center count ratios in each layer. Solid lines indicate
regression line, dot lines 95 % confidence intervals

the performance of the same preclinical PET scanner toours, where relatively stable FWHM/FWTM values overtransaxial FOV were observed with the use of iterative
reconstruction.
The use of attenuation and scatter correction slightly but
significantly improved IR-RF as reflected by FWHM or
FWTM in the presence of high density surrounding material, whereas the use of attenuation correction alone did
not. This indicates that the presence of scatter may unfavorably affect IR-RF by adding counts that come frommaterials surrounding the source. Because the attenuation/
scatter correction software in the LabPET system has
become available very recently and still needs validation,
we did not systemically looked at the effects of attenuation/
scatter correction on IR-RF in the present study. Nevertheless, this issue needs to be addressed by further studies.
EP resolution phantom results with material density of
1.19 g/cm3 are essentially consistent with the observation
described above in that IR-RF for high energy-emitting
radionuclides such as 13N is worse than that for low

energy-emitting radionuclides such as 18F. At the sametime, it should be noted that, although such a resolution
phantom image gives an estimate of IR-RF in a certain situation, it does not necessarily reflect IR-RF in
reality, where a radioactive source can be surrounded byvarious tissues.
Annihilations outside the source
Theoretically, a positron emitter travels for a distancedepending on its energy before annihilation and, therefore,
annihilation may occur outside the source. As mentioned
earlier, the travel range of a positron could reach several
meters in air [5]. In the presence of light materials such as
paper layer, some positrons should be trapped by them withannihilations, which could be detected using a preclinical
PET camera. The results of the concentric ring paper
phantom study demonstrated that such annihilations outside the radio-active source are clearly visible, although theimage quality of 15O image was somewhat poor as

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compared to those of 18F or 11C, reflecting relatively lower
dose and shorter acquisition time for 15O. Furthermore,when the source was covered with clay to stop positron
flight, none of the layers was visible, which was confirmedby the quantitative analysis of layer-to-center count ratios.
This indicates that layer visibility was due to annihilationsin that layer and not the result of scattering of emitted
gamma-ray following annihilation.
Our results also showed that annihilations in layers near
the central source were visible with all radionuclides tested, whereas those in distant layers were visible only withhigh-energy radionuclides such as 15O. Moreover, theamount of annihilations in distant layers was mainly
determined by the energy level of positron emitters. Thus,
visibility of such annihilations depends on the distance
between the source and object, and type of radionuclide.
From a viewpoint of in vivo imaging, our results suggestthat annihilations outside the source may constitute an
imaging artifact in some rodent organs that contain tissue
and air in face-to-face such as those encountered in gastrointestinal system or oral cavity. However, this needs tobe addressed in further in vivo studies.

Conclusions
The results indicate that surrounding material affects IRRF particularly for high energy positron emitters. Furthermore, annihilation outside the radio-active source canbe visualized with some circumstances such as those seen
with a concentric ring paper phantom.
Acknowledgmentstural government.

This work was supported by Ishikawa prefec-

Conflict of interest

None of the authors has conflicts to disclose.

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