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3D-OSEM and FP-CIT SPECT quantification: benefit for studies with a high radius of rotation?

01 Oct 2013-Nuclear Medicine Communications (Nucl Med Commun)-Vol. 34, Iss: 10, pp 971-977

TL;DR: 3D-OSEM offers a promising image quality gain but does not improve the accuracy of the putamen-to-caudate ratios, which could potentially increase the diagnostic power of dopamine transporter SPECT in patients with borderline striatal radiotracer binding.

AbstractObjectives Dopamine transporter imaging with single-photon emission computed tomography (SPECT) is a valuable tool for both clinical routine and research studies. Recently, it was found that the image quality could be improved by introduction of the three-dimensional ordered subset expectation maximization (3D-OSEM) reconstruction algorithm, which provides resolution recovery. The aim of this study was to systematically evaluate the potential benefits of 3D-OSEM in comparison with 2D-OSEM under critical imaging conditions, for example, scans with a high radius of rotation.Materials and methods Monte Carlo simulation scans of a digital brain phantom with various disease states and different radii of rotation ranging from 13 to 30 cm were reconstructed with both 2D-OSEM and 3D-OSEM algorithms. Specific striatal binding and putamen-to-caudate ratios were determined and compared with true values in the phantom.Results The percentage recovery of true striatal binding was similar between both reconstruction algorithms at the minimum rotational radius; however, at the maximum rotational radius, it decreased from 53 to 43% for 3D-OSEM and from 52 to 26% for 2D-OSEM. 3D-OSEM matched the true putamen-to-caudate ratios more closely than did 2D-OSEM in scans with high SPECT rotation radii.Conclusion 3D-OSEM offers a promising image quality gain. It outperforms 2D-OSEM, particularly in studies with limited resolutions (such as scans acquired with a high radius of rotation) but does not improve the accuracy of the putamen-to-caudate ratios. Whether the benefits of better recovery in studies with higher radii of rotation could potentially increase the diagnostic power of dopamine transporter SPECT in patients with borderline striatal radiotracer binding, however, needs to be further examined.

Summary (3 min read)

Introduction

  • Imaging of the presynaptic dopamine transporter (DAT) has evolved to be an important diagnostic tool in patients with Parkinsonian syndromes [1].
  • DAT single-photon emission computed tomography scans are used to confirm or exclude a neurodegenerative Parkinsonian syndrome [2] and, in combination with semiquantification [3,4], can detect subtle changes in DAT binding in striatal subregions and allow monitoring of disease progression [5,6].
  • Its value for clinical routine use has been demonstrated [8].
  • A superiority in low-count images enables reduction of the injected radiotracer dose or the imaging time [9–11].
  • Recently, the rotation radius dependence of I-123-FP-CIT quantification was shown for 2D-OSEM reconstructions [12].

Phantom

  • The Zubal digital brain phantom (http://noodle.med.yale.edu/ zubal/, G. Zubal, Yale University, New Haven, Connecticut, USA; [13]) was modified to simulate the typical profiles of the normal radiotracer binding status as well as neurodegeneration in Parkinsonian syndromes (loss of DAT binding [2]).
  • On the basis of previous measurements with a physical phantom [14] and patient.

Original article

  • Unauthorized reproduction of this article is prohibited.
  • Scans [15], the activity distribution within the digital phantom was chosen to reflect a realistic situation found in healthy controls and patients.
  • For simulation of normal DAT binding, the activity concentrations of I-123 ratios between the striatal structures of each hemisphere and the remaining brain were 6 to 1 [15].
  • To simulate neurodegeneration, an exponential loss of DAT binding was modeled separately for the caudate and the putamen, based on t values previously published in a long-term follow-up study on patients with idiopathic Parkinsonian syndromes [16] according to the formula: Cs¼C0 exp.

Monte Carlo simulation

  • A dual-headed MiE ECAM variable SPECTcamera (MiE, Seth, Germany) equipped with lowenergy, high-resolution parallel hole collimators (parallel hexagonal holes with cells of 1.11 mm diameter, 2.405 cm height, and 0.16 mm septal thickness) was entirely modeled in the software.
  • Apart from the original main energy window acquisitions, scatter-corrected data were calculated based on the triple energy window correction method [20,21].

SPECT processing

  • Simulated SPECT acquisition data were transferred to a real MiE ECAM variable camera acquisition workstation and reconstructed with a 2D-OSEM algorithm (OSEM implementation based on the algorithm of Richard Larkin from Macquarie University [22]) and with a 3D-OSEM algorithm (depth response OSEM) using the MiE Scintron software (MiE Medical Imaging Electronics, Seth, Germany).
  • Smoothing was performed by convolution of the projection with a filter mask in each direction.
  • For 3D-OSEM, attenuation correction was integrated into the reconstruction algorithm.
  • Three-dimensional volumes of interest (VOIs) for the striatal regions were defined based on digital phantom morphology (caudate or putamen).

Semiquantitative evaluation

  • Specific binding within the striatum, caudate, and putamen were calculated from the mean counts per voxel, with the occipital cortex serving as a reference [specific bindingstriatum = (striatum – occipital reference)/ occipital reference].
  • Because the underlying disease in patients with Parkinsonian syndromes often affects the caudate nucleus and putamen with a varying severity, Copyright © Lippincott Williams & Wilkins.
  • Unauthorized reproduction of this article is prohibited.
  • The putamen-to-caudate ratios (P-to-C ratios = ratio between specific putaminal and specific caudate binding) were also calculated.

Statistical analyses

  • Linear regression analyses were used to describe the relationship between specific binding ratios and radii of rotation.
  • To detect differences in the slopes of the linear regression curves, analysis of covariance was applied, investigating the significance of the interaction between the classification effect (such as the reconstruction method) and the covariate (the specific binding ratio).
  • All statistical analyses were performed using SPSS Software version 13 (SPSS Inc., Chicago, Illinois, USA).
  • For automation of digital phantom ‘filling’, multithreaded Monte Carlo simulation, file format conversions, calculation of noise with Poisson distribution, DICOM packaging, data exchange with a real MiE SPECT camera, and automation of VOI quantification, an in-house software written in VB.

Recovery

  • The measured specific striatal binding was compared with the true specific binding ratios in the phantom for both 2D-OSEM-reconstructed and 3D-OSEM-reconstructed images in the healthy state.
  • Independent of the radius of rotation, the measured striatal binding ratios were slightly higher for 3D-OSEM images than for 2D-OSEM images.
  • Table 2 shows the results of the multivariate linear regression analyses.
  • Figure 2 exemplarily shows images of the healthy state reconstructed with both 2D-OSEM and 3D-OSEM with different radii of rotation.

Putamen-to-caudate ratios

  • To estimate the potential beneficial effects of 3D-OSEM in comparison with 2D-OSEM in a clinical routine setting, the authors directly compared the P-to-C ratios between both methods of reconstruction as an objective parameter for determining the predominant putaminal binding loss typically observed in Parkinson’s disease.
  • Because low Copyright © Lippincott Williams & Wilkins.
  • Unauthorized reproduction of this article is prohibited.
  • Figure 3 exemplarily shows the correlations between the measured and true P-to-C ratios for 13 cm of rotation and 30 cm of rotation for both methods of reconstruction.

Discussion

  • Imaging of the presynaptic DAT has evolved into an important diagnostic tool for patients with Parkinsonian syndromes [1,23–25], and thus has become a routine clinical procedure.
  • Unauthorized reproduction of this article is prohibited.
  • The difference in recovery when comparing measured and true specific striatal binding using both reconstruction methods in scans with minimal rotational radii was low (1.9%); the annual loss of DAT binding in patients with idiopathic Parkinsonian syndromes is B5.2% per year [29].
  • The more prominent differences in scans with high radii of rotation (up to 19.4% at 30 cm) will most likely be related to the higher spatial resolution in 3D-OSEM images.
  • The overall measured binding values based on uncorrected data were in a typical range of about half the true activity ratios in the phantom, which can be attributed mainly to scatter and partial-volume effects.

Conclusion

  • It outperforms 2D-OSEM, particularly in studies with limited resolutions (such as scans acquired with a high radius of rotation) but does not improve the accuracy of the P-to-C ratios.
  • Whether the benefits of better recovery in studies with higher radii rotation could potentially increase the diagnostic power of DAT SPECT in patients with borderline striatal radiotracer binding, however, needs to be further examined.

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Content maybe subject to copyright    Report

3D-OSEM and FP-CIT SPECT quantification: benefit for
studies with a high radius of rotation?
Walter Koch, Peter Bartenstein and Christian la Fouge
`
re
Objectives Dopamine transporter imaging with single-
photon emission computed tomography (SPECT) is a
valuable tool for both clinical routine and research studies.
Recently, it was found that the image quality could be
improved by introduction of the three-dimensional
ordered subset expectation maximization (3D-OSEM)
reconstruction algorithm, which provides resolution
recovery. The aim of this study was to systematically
evaluate the potential benefits of 3D-OSEM in comparison
with 2D-OSE M under critical imaging conditions, for
example, scans with a high radius of rotation.
Materials and methods Monte Carlo simulation scans of
a digital brain phantom with various disease states and
different radii of rotation ranging from 13 to 30 cm were
reconstructed with both 2D-OSEM and 3D -OSE M
algorithms. Specific striatal binding and putamen-to-
caudate ratios were determined and compared with true
values in the phantom.
Results The percentage recovery of true striatal binding
was similar between both reconstruction algorithms at
the minimum rotational radius; however, at the maximum
rotational radius, it decreased from 53 to 43% for
3D-OSEM and from 52 to 26% for 2D-OSEM. 3D-OSEM
matched the true putamen-to-caudate ratios more closely
than did 2D-OSEM in scans with high SPECT rotation radii.
Conclusion 3D-OSEM offers a promising image quality
gain. It outperforms 2D -OSEM, particularly in studies with
limited resolutions (such as sc ans acquired with a high
radius of rotation) but does not improve the accuracy of the
putamen-to-caudate ratios. Whether the benefits of better
recovery in studies with higher radii of rotation could
potentially increase the diagnostic power of dopamine
transporter SPECT in patients with borderline striatal
radiotracer binding, however, needs to be further
examined. Nucl Med Commun 34:971–977
c
2013 Wolters
Kluwer Health | Lippincott Williams & Wilkins.
Nuclear Medicine Communications 2013, 34:971–977
Keywords: 3D-OSEM iterative reconstruction, dopamine transporter, FP-CIT,
Monte Carlo simulation, radius of rotation
Department of Nuclear Medicine, University of Munich, Munich, Germany
Correspondence to Walter Koch, MD, Department of Nuclear Medicine,
University of Munich, Marchioninistr 15, 81377 Munich, Germany
Tel: + 49 89 7095 4646; fax: + 49 89 7095 7646;
e-mail: walter.koch@med.uni-muenchen.de
Received 17 March 2013 Revised 21 May 2013 Accepted 28 June 2013
Introduction
Imaging of the presynaptic dopamine transporter (DAT)
has evolved to be an important diagnosti c tool in patients
with Parkinsonian syndromes [1]. DAT single-photon
emission computed tomography (SPECT) scans are used
to confirm or exclude a neurodegenerative Parkinsonian
syndrome [2] and, in combination with semiquantifica-
tion [3,4], can detect subtle changes in DAT binding in
striatal subregions and allow monitoring of disease
progression [5,6].
Recently, the enhanced image reconstruction algorithm
three-dimensional ordered subset expectation maximiza-
tion (3D-OSEM) has become available for DAT imaging.
The algorithm takes the depth response of the collima-
tors into account and has been shown to provide a
superior image quality in comparison with 2D-OSEM [7].
Its value for clinical routine use has been demon-
strated [8]. A superiority in low-count images enables
reduction of the injected radiotracer dose or the imaging
time [9–11].
The potential benefits of resolution recovery (as im-
plemented in 3D-OSEM) for semiquantitative analyses,
however, have not been examined yet. An increased
resolution could particularly aid in critical imaging
conditions, such as performing a DAT SPECT scan with
a high rotational radius, as is sometimes required because
of anatomical reasons or claustrophobia. Recently, the
rotation radius dependence of I-123-FP- CIT quantifica-
tion was shown for 2D-OSEM reconstructions [12].
The aim of this study was to systematically evaluate the
potential benefits of 3D-OSEM in comparison with
2D-OSEM for semiquantitative analyses and disease
detection based on the Monte Carlo simulation of studies
with various radii of rotation and different extents of
Parkinson’s disease.
Materials and methods
Phantom
The Zubal digital brain phantom (http://noodle.med.yale.edu/
zubal/, G. Zubal , Yale University, New Haven, Connecti-
cut, USA; [13]) was modified to simulate the typical
profiles of the normal radiotracer binding status as well as
neurodegeneration in Parkinsonian syndromes (loss of
DAT binding [2]). On the basis of previous measure-
ments with a physical phantom [14] and patient
Original article
0143-3636
c
2013 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MN M.0b013e328364a9fd
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

scans [15], the activity distribution within the digital
phantom was chosen to reflect a realistic situation found
in healthy controls and patients. For simulation of normal
DAT binding, the activity concentrations of I-123 ratios
between the striatal structures of each hemisphere and
the remaining brain were 6 to 1 [15]. To simulate
neurodegeneration, an exponential loss of DAT binding
was modeled separately for the caudate and the putamen,
based on t values previously published in a long-term
follow-up study on patients w ith idiopathic Parkinsonian
syndromes [16] according to the formula: C
s
¼C
0
exp
T
t

;
where C
s
is the activity concentration of the respective
striatal region, C
0
equals the striatal concentration in a
healthy state, T is the years of disease, and the t values
(reflecting the rate of disease progression) being derived
from the study by Schwarz et al.[16].
Monte Carlo simulation
The SIMIND Monte Carlo code [17] was used to
calculate projection data based on the digital brain
phantom (256 256 matrix with 128 slices, 1.1 1.1
1.4 mm pixel size). A dual-headed MiE ECAM variable
SPECTcamera (MiE, Seth, Germany) equipped with low-
energy, high-resolution parallel hole collimators (parallel
hexagonal holes with cells of 1.11 mm diameter, 2.405 cm
height, and 0.16 mm septal thickness) was entirely
modeled in the software. The comparability of the
simulated data of this camera type with real equipment
has been confirmed elsewhere [18]. The acquisition
parameters were based on recommendations outlined in
the procedure guidelines for neurotransmission SPECT
with DAT ligands published by the European Association
of Nuclear Medicine [3] and were applied to the Monte
Carlo simulation. All acquisitions were optimized not only
to obtain a high spatial resolution but also to reflect the
clinical use of the SPECT systems. A total of 120
projections were obtained for each simulation, with the
detector heads following a 3601 circular orbit in a
128 128 matrix with a main energy window from 143.1
to 174.9 keV. In addition, a lower (131.9–143.0 keV) and an
upper (175.0–186.1 keV) scatter window adjacent to the
main window were acquired. The pixel size was
3.0 3.0 mm. Physical effects, such as photon attenuation
and scatter in the phantom and the crystal, degradation
due to collimator resolution, septal penetration, photon
interaction in the collimator [19], and backscatter from
the detector cover material were included in the
simulations. The full energy spectrum of I-123 was
simulated. Ten million counts in the main energy window
were simulated for each acquired projection to obtain low
noise simulation data. Study counts of the main window
were then scaled to obtain total counts of 2.5 million per
acquisition, as typically acquired in true patient scans.
The scatter windows were consecutively scaled with
identical factors. Finally, Poisson-distributed noise was
added to the projection data. Apart from the original main
energy window acquisitions, scatter-corrected data were
calculated based on the triple energy window correction
method [20,21].
Simulated disease states and radii of rotation
A healthy state (T = 0 years) as well as disease states 2, 4,
6, 8, and 10 years after disease onset were simulated. The
simulations therefore covered a wide range, from entirely
normal to preclinical as well as far-progressed disease
states. Each disease state was imaged with 13, 14, 15, 16,
17, 18, 19, 20, and 30 cm radii of SPECT rotation.
SPECT processing
Simulated SPECT acquisition data were transferred to a
real MiE ECAM variable camera acquisition workstation
and reconstructed with a 2D-OSEM algorithm (OSEM
implementation based on the algorithm of Richard Larkin
from Macquarie University [22]) and with a 3D-OSEM
algorithm (depth response OSEM) using the MiE
Scintron software (MiE Medical Imaging Electronics,
Seth, Germany). For both 2D-OSEM and 3D-OSEM
reconstructions, projection data were smoothed using a
two-dimensional Gaussian filter with a full-width at half-
maximum of 5.65 mm. Smoothing was performed by
convolution of the projection with a filter mask in each
direction. The length of the filter mask is 3 with the
weighting [1, 2, 1]/4. Thus, each pixel in a projection is
first smoothed in the x-direction by a weighted sum
including twice itself and its left and right neighbor
divided by 4 in order to be count preserving. Thereafter,
the procedure is repeated in the y-direction using the
upper and lower neighbors of each pixel. Four iterations
with 16 subsets were used to reconstruct data, and the
reconstructions were corrected for attenuation (m = 0.11 /
cm, automated contour finding with separate contours for
each slice), following Chang’s method [3] for 2D-OSEM.
For 3D-OSEM, attenuation correction was integrated
into the reconstruction algorithm.
Automated VOI evaluation
Using shift transforms only, the digital phantom was
coregistered to the reconstructed transverse slices of the
13 cm rotational radius acquisition of the healthy state.
Three-dimensional volumes of interest (VOIs) for the
striatal regions were defined based on digital phantom
morphology (caudate or putamen). A large occipital
background region was added (8624 voxels), which served
as a reference for all semiquantitative analyses. The VOI
sizes are given in Table 1.
Semiquantitative evaluation
Specific binding within the striatum, caudate, and
putamen were calculated from the mean counts per
voxel, with the occipital cortex serving as a reference
[specific binding
striatum
= (striatum occipital reference)/
occipital reference]. Because the underlying disease in
patients with Parkinsonian syndromes often affects the
caudate nucleus and putamen with a varying severity,
972 Nuclear Medicine Communications 2013, Vol 34 No 10
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

the putamen-to-caudate ratios (P-to-C ratios = ratio
between specific putaminal and specific caudate binding)
were also calculated.
Statistical analyses
Linear regression analyses were used to describe the
relationship between specific binding ratios and radii of
rotation. The slopes and SE of slopes were calculated.
To detect differences in the slopes of the linear
regression curves, analysis of covariance was applied,
investigating the significance of the interaction between
the classification effect (such as the reconstruction
method) and the covariate (the specific binding ratio).
To determine the influence of rotational radii on the
measured binding values from a statistical point of view,
multivariate general linear regression was used: true
striatal binding in the phantom (as the dependent
variable) was predicted on the basis of the covariates
measured binding and radius of rotation. A high slope/
correlation coefficient of the rotational radius therefore
indicates a strong impact of this facto r, whereas a low
correlation coefficient indicates a weak influence.
All statistical analyses were performed using SPSS
Software version 13 (SPSS Inc., Chicago, Illinois, USA).
For automation of digital phantom ‘filling’, multithreaded
Monte Carlo simulation, file format conversions, calcula-
tion of noise with Poisson distribution, DICOM packa-
ging, data exchange with a real MiE SPECT camera, and
automation of VOI quantification, an in-house software
written in VB.NET 2010 (Visual Studio 2010; Microsoft
Corp., Redmond, Washington, USA) was used. VOI
quantification was performed using the MIPAV software
(Center for Information Technology, National Institutes
of Health, Bethesda, Maryland, USA). Reconstruction of
the raw acquisition data sets on Sc intron software was
controlled by an in-house automation software based on
the AutoIt scripting technology (AutoIt Consulting Ltd,
Birmingham, UK, http://www.autoitscript.com).
The results, images, and statistics presented in text,
tables, and figures are based on acquisition data without
scatter correction, if not explicitly mentioned.
Results
Recovery
The measured specific striatal binding was co mpared
with the true specific binding ratios in the phantom for
both 2D-OSEM-reconstructed and 3D -OSEM-recon-
structed imag es in the healthy state. Independent
of the radius of rotation, the measured striatal binding
ratios were slightly higher for 3D-OSEM images than for
2D-OSEM images. At the minimum radius of rotation
(13 cm), the percentage recovery was 53% for 3D-OSEM
and 52% for 2D-OSEM. At the maximum rotational
radius (30 cm), the recovery decreased to 43% for
3D-OSEM and to 26% for 2D-OSEM. Addition of
scatter correction increased the recovery at 13 cm to 63
and 60% and at 30 cm to 51 and 42% for 3D-OSEM and
2D-OSEM, respectively.
Radius dependency of the measured striatal binding
The correlations between specific binding ratios and radii
of rotation in the healthy state for 2D-OSEM and 3D-
OSEM reconstructions are shown in Fig. 1 (uncorrected
data Fig. 1a, scatter-corrected data Fig. 1b). A linear loss
of striatal binding with an increasing radius of rotation
could be observed for both methods of reconstruction,
the observation being independent of whether uncor-
rected or scatter-corrected data were used. For 3D-
OSEM, the decrease, however, was less steep compared
with that fo r 2D-OSEM (significantly different slopes: F-
test P < 0.05), which is in line with the higher recovery
values observed for 3D-OSEM in scans with larger
rotational radii. Table 2 shows the results of the multi-
variate linear regression analyses. The results clearly
demonstrate a higher influence (correlation coefficient)
of the rotational radius on striatal binding in 2D-OSEM
images than in 3D-OSEM images.
Figure 2 exemplarily shows images of the healthy state
reconstructed with both 2D-OSEM and 3D-OSEM with
different radii of rotation. 3D-OSEM images showed a
better delineation of the caudate and the putamen and
a smoother background (nonspecific binding) compared
with 2D-OSEM images. With a higher radius, the
resolution decreases, the activity spreads beyond the
true borders of the striatum, and the partial-volume
effects increase in all three dimensions, resulting in a loss
of recovery, which is more pronounced in 2D-OSEM
images. Although a horizontal, 15-mm-wide line profile
through the striatal area in an acquisition with a low
rotational radius shows a steep count increase from
unspecific binding to striatal binding, the increase
becomes shallower with an increase in the radius of
rotation, with this effect being shown equally in both
methods of reconstruction.
Putamen-to-caudate ratios
To estimate the potential beneficial effects of 3D-OSEM
in comparison with 2D-OSEM in a clinical routine
setting, we directly co mpared the P-to-C ratios between
both methods of reconstruction as an objective paramet er
for determining the predominant putaminal binding loss
typically observed in Parkinson’s disease. Because low
Table 1 Volumes of interest used for SPECT quantification
Method of analysis Region Size (ml)
Morphological VOI Striatum 6.40
Caudate 2.39
Putamen 4.01
Occipital reference VOI Occipital 132.87
SPECT, single-photon emission computed tomography; VOI, volume of interest.
3D-OSEM vs. 2D-OSEM in FP-CIT SPECT Koch et al.973
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

striatal binding values result in statistical noise, these
analyses were confined to a disease progression of up to a
maximum of 10 years. Figure 3 exemplarily shows the
correlations between the measured and true P-to-C ratios
for 13 cm of rotation and 30 cm of rotation for both
methods of recon struction.
At 30 cm of rotation, the 3D -OSEM seems to outperform
2D-OSEM, with better reproduction of the true P-to-C
ratios. On defining an arbitrary threshold for disease
detection at a P-to-C ratio of 0.7 (30% relative loss of
putaminal binding), at 13 cm of rotation, di sease could be
detected 3.5 years after onset using 2D-OSEM and 3D-
OSEM; however, at 30 cm of rotation, the disease would
have had to have progressed 5.3 years in order to be
detected on 3D-OSEM images, but would have had to
have progressed to at least 8.0 years for detection with
2D-OSEM reconstructions.
This presumed difference between the reconstruction
methods, however, could only be observed on comparing
the minimum and maximum rotational radii. Across all
radii of rotation, no significant benefit of 3D-OSEM in
terms of P-to-C ratio reproduction could be shown (F-test
P = 0.782).
Discussion
Imaging of the presynaptic DAT has evolved into an
important diagnostic tool for patie nts with Parkinsonian
syndromes [1,23–25], and thus has become a routine
clinical procedure. Visual assessment of DAT SPECT
studies in many cases enables clinicians to decide
whether neurodegeneration of presynaptic neurons has
occurred and to confirm or exclude a neurodegenerative
Parkinsonian syndrome [2]. In particular, for an early
diagnosis, that is, the detection of subtle changes in DAT
binding in striatal subregions, and for monitoring disease
progression [5,6,26] or the beneficial effects of putative
neuroprotective drugs [5,6,16,27,28], additional semi-
quantitative measurements are essential [3].
3D-OSEM is assumed to have the potential to outper-
form filtered backprojection and 2D-OSEM in terms of
image quality [9–11].
Fig. 1
2.8
(a) (b)
3D-OSEM
2D-OSEM
Fit line for 3D-OSEM
Fit line for 2D-OSEM
Reconstruction method
3D-OSEM scatter corrected
2D-OSEM scatter corrected
Fit line for 3D-OSEM scatter corrected
Fit line for 2D-OSEM scatter corrected
Reconstruction method
2.6
2.4
Specific striatal binding
2.2
2.0
1.8
10 15 20 25 30
Radius of rotation
10
2.0
2.2
2.4
2.6
2.8
3.0
3.2
15 20 25 30
Radius of rotation
Correlations between the specific binding ratios and radii of rotation in the healthy state in 2D-OSEM-reconstructed and 3D-OSEM-reconstructed
images for (a) uncorrected simulation data and (b) scatter-corrected data. OSEM, ordered subset expectation maximization.
Table 2 Relation between the radius of rotation and the measured striatal binding for 2D-OSEM and 3D-OSEM: results of the multivariate
linear regression analyses
Regression coefficient
Method of reconstruction Measured striatal binding±SE Radius of rotation±SE Constant±SE
2D-OSEM 2.146±0.026 0.320±0.004 0.643±0.76
3D-OSEM 2.027±0.016 0.180±0.002 0.331±0.48
OSEM, ordered subset expectation maximization.
97 4 Nuclear Medicine Communications 2013, Vol 34 No 10
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

FP-CIT semiquantification shows an acquisition radius
dependence that is attributed to partial-volume effects
due to a drop in the resolution with increasing radius, as
was recently shown by Larsson et al. [12]. With an
increase in the full-width at half-maximum of the spatial
resolution in reconstructed images, activity from within
the stri atum spreads over an increasing area as shown
in Fig. 2, resulting in a loss of counts within the
quantification VOIs (spill-out).
Radius dependence was less prominent when a three-
dimensional cone beam model was incorporated in
the iterative recon struction algorithm (3D-OSEM). The
resulting enhanced resolution recovery led to higher
binding ratios in scans with high radii of rotation.
The difference in recovery when comparing measured
and true specific striatal binding using both reconstruc-
tion methods in scans with minimal rotational radii was
low (1.9%); the annual loss of DAT binding in patients
with idiopathic Parkinsonian syndromes is B5.2% per
year [29]. It could also be attributed to the slight
differences in attenuation correction or filtering. The
more prominent differences in scans with high radii
of rotation (up to 19.4% at 30 cm) will most likely be
related to the higher spatial resolution in 3D-OSEM
images. 3D-OSEM therefore seems more robust to the
influence of the radius of rotation. The overall measured
binding values based on uncorrected data were in a
typical range of about half the true activity ratios in the
phantom, which can be attributed mainly to scatter and
partial-volume effects. Scatter correction led to a general
increase in recovery, in studies with both low and high
radii of rotation, but did not have an effect on the radius
dependence of the binding values. Scatter correction,
however, is typically not applied in a routine setting. If
further reduction of partial-volume effects is required,
the ‘Southampton semiquantification method proposed
by Fleming and colleagues [30,31] would provide a
promising method to overcome the influence of rotational
radius effects.
We would have expected that an increased spatial
resolution also has beneficial effects on the accuracy of
the P-to-C ratios. Parkinson’s disease typically affects the
putamen earlier, given the more prominent nigrostriatal
degeneration in that region [32,33] and the particular
degeneration of the ventrolateral substantia nigra pars
compacta [34], which innervates the posterior puta-
men [35]. P-to-C ratios therefore offer diagnostic informa-
tion, independent of total specific striatal binding [36].
Fig. 2
(c)(b)(a)
2D-
OSEM
2D-
OSEM
3D-
OSEM
3D-
OSEM
Examples for the effects of rotational radii on the image quality. Below each example, a 15 mm horizontal line profile centered on the striatal region is
shown. 2D-OSEM (first row), 3D-OSEM (second row), (a) a 13 cm radius of rotation, (b) a 20 cm radius of rotation, and (c) a 30 cm radius of
rotation. OSEM, ordered subset expectation maximization.
3D -OSEM vs. 2D-OSEM in FP -CIT SPECT Koch et al.975
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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Journal ArticleDOI
TL;DR: The ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them.
Abstract: [123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation. BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction. Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the “true” values (p < 0.001). Calibration provided, in fact, “first order” camera-dependent corrections, but could not include “second order” subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (−0.2%, p = 0.44). The ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an “index” rather than a “true” value.

28 citations


Journal ArticleDOI
TL;DR: A new robust and reliable rating scale for 123I-Ioflupane brain images in Lewy body disease that encompasses appearances seen in dementia with Lewy bodies, demonstrated high accuracy in autopsy confirmed cases and offers advantages over the existing visual rating scale.
Abstract: Background Dopaminergic loss on 123I-Ioflupane brain imaging is a recognised biomarker for dementia with Lewy bodies It is usually assessed using a visual rating scale developed for Parkinson's disease, which may not be optimal for dementia with Lewy bodies, as patterns of dopaminergic loss can be different Objectives We aimed to develop a new visual rating scale for 123I-Ioflupane brain images in Lewy body disease that encompasses appearances seen in dementia with Lewy bodies, and validate this against autopsy diagnosis Methods Four experienced observers developed and tested a new scale consisting of two metrics, reflecting overall loss and heterogeneity of loss 66 subjects were used during development including clinical diagnoses of Alzheimer's disease (n = 14), Parkinson's disease (n = 9), Parkinson's disease dementia (n = 9), dementia with Lewy bodies (n = 15) and normal controls (n = 19) The scale was then tested on an independent group of 46 subjects with autopsy confirmed diagnosis: Alzheimer's disease (n = 11), Parkinson's disease (n = 3), Parkinson's disease dementia (n = 15), dementia with Lewy bodies (n = 12), normal controls (n = 4) and Frontotemporal dementia (n = 1) Results In the autopsy validation the sensitivity and specificity of the new scale for Lewy body disease was 97% and 100% respectively, compared with the standard scale which had the same sensitivity (97%), but lower specificity (80%) The new scale had excellent inter rater reliability (intra-class correlation coefficient 093) Conclusion A new robust and reliable rating scale is described that straightforwardly captures the visual appearance of 123I-Ioflupane brain images It demonstrated high accuracy in autopsy confirmed cases and offers advantages over the existing visual rating scale

9 citations


References
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TL;DR: Ordered subsets EM (OS-EM) provides a restoration imposing a natural positivity condition and with close links to the EM algorithm, applicable in both single photon (SPECT) and positron emission tomography (PET).
Abstract: The authors define ordered subset processing for standard algorithms (such as expectation maximization, EM) for image restoration from projections. Ordered subsets methods group projection data into an ordered sequence of subsets (or blocks). An iteration of ordered subsets EM is defined as a single pass through all the subsets, in each subset using the current estimate to initialize application of EM with that data subset. This approach is similar in concept to block-Kaczmarz methods introduced by Eggermont et al. (1981) for iterative reconstruction. Simultaneous iterative reconstruction (SIRT) and multiplicative algebraic reconstruction (MART) techniques are well known special cases. Ordered subsets EM (OS-EM) provides a restoration imposing a natural positivity condition and with close links to the EM algorithm. OS-EM is applicable in both single photon (SPECT) and positron emission tomography (PET). In simulation studies in SPECT, the OS-EM algorithm provides an order-of-magnitude acceleration over EM, with restoration quality maintained. >

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01 Oct 1991-Brain
TL;DR: It is suggested that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of Parkinson's disease and the regional selectivity of PD is relatively specific.
Abstract: The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD.

2,914 citations


Journal ArticleDOI
TL;DR: It is proposed that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits are less marked or restricted to discrete functions only.
Abstract: Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.

1,802 citations


Journal ArticleDOI
01 Aug 1999-Brain
TL;DR: The spatiotemporal progression of neuronal loss related to disease duration can be drawn in the substantia nigra pars compacta for each Parkinson's disease patient: depletion begins in the main pocket (nigrosome 1) and then spreads to other nigrosomes and the matrix along rostral, medial and dorsal axes of progression.
Abstract: To achieve accuracy in studying the patterns of loss of midbrain dopamine-containing neurons in Parkinson's disease, we used compartmental patterns of calbindin D(28K) immunostaining to subdivide the substantia nigra with landmarks independent of the degenerative process. Within the substantia nigra pars compacta, we identified dopamine-containing neurons in the calbindin-rich regions ('matrix') and in five calbindin-poor pockets ('nigrosomes') defined by analysis of the three-dimensional networks formed by the calbindin-poor zones. These zones were recognizable in all of the brains, despite severe loss of dopamine-containing neurons. The degree of loss of dopamine-containing neurons in the substantia nigra pars compacta was related to the duration of the disease, and the cell loss followed a strict order. The degree of neuronal loss was significantly higher in the nigrosomes than in the matrix. Depletion was maximum (98%) in the main pocket (nigrosome 1), located in the caudal and mediolateral part of the substantia nigra pars compacta. Progressively less cell loss was detectable in more medial and more rostral nigrosomes, following the stereotyped order of nigrosome 1 > nigrosome 2 > nigrosome 4 > nigrosome 3 > nigrosome 5. A parallel, but lesser, caudorostral gradient of cell loss was observed for dopamine-containing neurons included in the matrix. This pattern of neuronal loss was consistent from one parkinsonian substantia nigra pars compacta to another. The spatiotemporal progression of neuronal loss related to disease duration can thus be drawn in the substantia nigra pars compacta for each Parkinson's disease patient: depletion begins in the main pocket (nigrosome 1) and then spreads to other nigrosomes and the matrix along rostral, medial and dorsal axes of progression.

1,379 citations


Journal ArticleDOI
TL;DR: A computerized 3-dimensional volume array modeling all major internal structures of the body has been created and can serve as a voxel-based anthropomorphic phantom suitable for many computer-based modeling and simulation calculations.
Abstract: Manual segmentation of 129 x-ray CT transverse slices of a living male human has been done and a computerized 3-dimensional volume array modeling all major internal structures of the body has been created. Each voxel of the volume contains a index number designating it as belonging to a given organ or internal structure. The original x-ray CT images were reconstructed in a 512×512 matrix with a resolution of 1 mm in the x,y plane. The z-axis resolution is 1 cm from neck to midthigh and 0.5 cm from neck to crown of the head. This volume array represents a high resolution model of the human anatomy and can serve as a voxel-based anthropomorphic phantom suitable for many computer-based modeling and simulation calculations.

1,046 citations


Frequently Asked Questions (2)
Q1. What have the authors contributed in "3d-osem and fp-cit spect quantification: benefit for studies with a high radius of rotation?" ?

Recently, it was found that the image quality could be improved by introduction of the three-dimensional ordered subset expectation maximization ( 3D-OSEM ) reconstruction algorithm, which provides resolution recovery. The aim of this study was to systematically evaluate the potential benefits of 3D-OSEM in comparison with 2D-OSEM under critical imaging conditions, for example, scans with a high radius of rotation. 

Whether 3D-OSEM could lead to a significant gain in diagnostic power, however, would need further evaluation in patient studies.