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AN IMPROVED OPTIMAL IMAGE SAMPLING SCHEDULE FOR MULTIPLE

ROIS IN DYNAMIC SPECT

Lingfeng Wen····, Stefan Eber..·····, Dagan Feng..·····, Jing Raj'

* Dept. ofBiomedical Engineering, Tsinghua University, Beijing. 100084, China

** Biomedical and Multimedia Information Technology (BMIT) Group.
School ofInformation Technologies. the University ofSydney. NSW 2006. Australia
*** Dept. of PET & Nuclear Medicine, Royal Prince Alfred Hospital. Missenden Road.
Camperdown. NSW 2050, Australia
**** Centerfor Multimedia Digital Signal Processing.
Dept. ofElectronic& Information Engineering.
Hong Kong Po~vtechnic University. Hung Hom. Kowloon. Hong Kong

Abstract: Optimal image sampling schedule (OISS) has been applied successfully to
dynamic images for positron emission tomography (PET) with improved parameter
estimation precision and significantly decreased image storage and processing
requirements. OISS is usually based on one average curve for tissue, and the performance
of OISS is still unclear when multiple regions of interest are considered in clinical
diagnosis. An improved OISS is investigated with a modified objective function through a
simulated study of the tracer 5- '23 1-iodo-A-85380. The study shows that the improved
OISS is at least as efficient in providing the accuracy and precision of parameter
estimates as conventional and traditional OISS.

Keywords: Sampling Intervals, Monte Carlo Simulation, Parameter Estimation,

Physiological Model, Quantitative analysis

I. INTRODUCTION time, with the conclusion that there was a monotonic

In the traditional dynamic system identification
experiments, instantaneous measurements were
usually obtained from sampling at discrete-time
points according to empirical sampling schedules.
Since DiStefano (1979) introduced the advantage of
optimal sampling schedule (OSS), several algorithms
have been investigated to find OSS based on the
Fisher information matrix criterion for instantaneous
discrete-time sampling (Cobelli. et at. 1985;
Distefano 1981, 1982; Mori and Distefano 1979).
OSS for positron emission tomography (PET) was
investigated for temporal sampling of the glucose
model using 18-fluoro-deoxy-D-glucose (FDG) by
Hawkins. et al. (1986). Delforge. et al. (1989)
presented the general framework and various criteria
to estimate receptor-ligand reaction model
parameters with dynamic PET data. These methods
were based on D-optimal criterion and a cost
function, assuming that sample points represent
instantaneous activity concentration at the sample
improvement in the index of parameter accuracy with
increasing sampling frequency, especially in the early
stage. An optimal image sampling schedule (OISS)
was proposed by Li. et at. (1996) with a modified
cost function based on integrated activity
concentration for PET modelling. The methodology
was then successfully applied to investigate 01SS of
input function, output function and whole-body
image acquisition for PET (Feng. et at. 1997;
HoShon. et at 1996; Li. et at. 2001; Li. et at. 2000)
with the advantage of improved parameter estimation
precision and significantly decreased image storage
and processing requirements. Furthermore, OISS has
been found applicable for dynamic SPECT of TI-201
(Lau. et al. 1998).
OISS is usually derived from one tissue time activity
curve (TTAC) that is simi lar to the average of the
TTACs. The performance of OISS is still unclear for
multiple regions of interests. Therefore an improved
OISS was investigated for the nicotinic receptor
tracer 5- 123 I-iodo-A-85380 in this work, to consider

139
 15()J· .....---,..- ~-'--
PTAC
00 20 «l 60 80 100 120
Tme(mn)
Fig.1 the plasma tissue activity curve (PTAC) and
TTACs for cerebellum, frontal cortex and
thalamus
the overall effccts of multiple regions of interests
with a modified objective function. Monte Carlo
simulations were perfonned to generate dynamic
projection sets from a brain phantom with different
Poisson noise levels in line with the kinetics of the
selected tracer. Kinetic parameters of interest were
estimated and compared to the known values used in
the simulation to evaluate the different sampling
schedules.
2. METHODS
2.1 Optimum Image Sampling Schedule
OISS aims to minimize the covariance matrix of the
estimated parameters by rearranging the sample
intervals. According to D-optimality criterion and
Cramer-Rao theorem. minimization of the objective
function (/J,(p) is approximately equivalent to
maximizing the detenninant of the Fisher
infonnation matrix M, which is a measure for
parameter infonnation in the data (Li. et al. 2001).
CI>,(pl = Min (COVAR ( p) '" Max (IMI)
Here p is an unbiased estimate of the parameter
vector p. OISS depends on the particular shape of
TTAC. Usually there are mUltiple regions of interest
in clinical diagnosis. which may have distinctly
different TTACs, e.g., cerebellum, thalamus and
frontal cortex for the tracer 5-[1231]-iodo-A-85380
(Kassiou. et at. 200 I) as shown in Figure I. Thus a
modified objective function (/Je(P) was proposed to
consider the effect of the information matrix for all
the regions of interest with the adjustment of
sampling intervals as follows,
<l>,(p) = Max (~]M.I)
,.1
Therefore OISS was investigated through iterative
adjustment of sampling schedule in order to
maximize the objective function. starting from the
conventional sampling schedule (CSS) which has a
relatively large number of frames and short frame
durations initially and increasingly longcr frame
durations during the later parts of the study. Each
.•- .-~.~-
interval is adjusted in turn in the direction which
increases the determinant sum of the information
matrices with the TTAC resampled with the adjusted
interval. When the interval k is adjusted, the adjacent
interval k+ I is adjusted by the same amount in the
oppositc direction to maintain the same total
collection time. The interval will be merged with the
next interval if the determinant for the merged
interval keeps increasing and the duration of it falls
below the lower bound for intervals (10 s in this.
study). If the determinant decreases during the
140 160 180 200
adjustment, a simple local search is carried out for a
maximum with adjustment of interval k and k+ I.
2.2 Evaluation
Dynamic projection data were generated from high-
count Monte Carlo simulations of a mathematical
human brain phantom and using the kinetic
parameters listed in the Table I, which were derived
from the experiments of neuronal nicotinic
acetylcholine receptor (nAChR) tracer 5_[,23I]_iodo_
A-85380 (Kassiou. et al. 200 I). The projections were
scaled and Poisson noise was added to generate
projections sets without noise and with eight levels of
noise based on experimental count levels, with
maximum pixel count for a similar 5 min frame,
ranging from 15 to 50 counts. Images were then
reconstructed using Ordered Subsets Expectation
Maximization (OS EM) with moderate number of
subsets and iterations equivalent to 40 traditional
iterations and attenuation correction, but without any
post-reconstruction filtering (Wen. et al. 2002). The
TTACs were derived from the reconstructed data,
which was resampled according to the respective
optimum sampling schedules.
Table 1 The reference parameter sets for the regions
of interests
(I) Cortex
Cerebellum 0.275 0.063 0.029 0.035
Frontal cortex 0.277 0.059 0.038 0037
Thalamus 0.284 0.061 0.143 0.041
The TTAC were fitted with a four-parameter, three-
compartment model (Figure 2) using non-linear least
squares fitting. Bias and reliability of the kinetic
parameters (K I -k4 ) for thalamus, cerebellum and
frontal cortex were estimated. Bias was calculated by
comparing the estimated values with the known
parameters in Table 1. The coefficient of variation
(CV) was calculated from the standard deviation
derived from the fitting, and divided by the known
parameters in Table I.
(2)
Fig 2. Definition of rate constants for 3-compartment
model used in the curve filling
140
 cerebellum. OlSS3 generally displayed the highest
3. RESULTS bias for the frontal cortex. For the thalamus, the
OlSS techniques performed as well as CSS, except
3. J Optimum Sampling Schedule for k4 in the thalamus, where OISS techniques
showed higher bias.
OISS I, OlSS2, OlSS3 were based on the individual
TTAC respectively for cerebellum. frontal cortex and CV for the OlSS techniques (see Figure 4) was again
thalamus using the traditional objective function similar to CSS, with again OlSS3 demonstrating
l/>,(p). OlSS4 was searched for with the modified overall slightly higher CVs. A similar trend for bias
objective function l/>;>(p), which considered all the and reliability was also found for the estimated
regions of interest for nAChR study. Table 2 shows parameters at the other noise levels. Considering the
the results of OISS as well as the conventional overall effects on the bias and reliability of estimated
sampling schedule (CSS). parameters (Kt -k4 ) as compared with CSS, the OISS
based on the modified objective function (OISS4)
Table 2. Results of sampling schedule provides improved parameter estimates over those
based on traditional function.
Protocol Sampling schedule (min)
CSS* 15 x I min, 9x 5 min, l2x 10 min
OISSI 7.9,20.3,85.5,66.3 3.3 Effect ofnoise
OISS2 7.0, 15.6,84.9,72.5
OlSS3 6.8,15.7,87.3,70.2 The effect of noise for the sampling schedule was
OlSS4 7.3, 21.8, 81.3, 69.7 investigated between the conventional and optimal
*CSS: Conventional Sampling Schedule, 15 x I min sampling schedule, i.e. CSS and OISS4, for the
represents 15 frames, I min each etc parameter K/, which is one of primary interests for
the nAChR study.

3.2 Effect ofoptimum sampling schedule
Figure 3 and 4 show the comparisons of the
percentage bias and CV for the estimated parameters
respectively as a function of the different sampling
schedules at the noise level of maximum pixel count
of 30 in the selected frame. The selected sampling
schedule had little effect on the bias for the
OISS achieves better estimation of parameters than
CSS for cerebellum and thalamus especially at the
higher noise levels with smaller bias, while
maintaining the same reliability (CV). While the bias
of OISS is not always less than that of CSS (see
Figure 5), it provides more consistent results and
displays less sensitivity to the noise level than CSS.

---e- cerebe'lm --a- fronal cortex ---b- thalamus

0 100

~-10

~ 20
m-
G>

'"
to
..
~
to
m
G>

'"
to
50

0
/
r
'E -30 'E
~
G>
~
G> G> -50
Q. -40 Q.

-50 -100
CSS 015S1 015S2 015S3 015S4 CSS 015S1 OlSS2 OlSS3 OlSS4
(a) (b)

150 30

j\
20
~ 100
..
.l!!
5
~
.l!!
.. 10

m m 0
G> G>

'"
to
'E 0
/ to
'E
'" -10 \,

/~
I
G> G>
~ ~ -20
G> G>
Q. -50 Q.
-30 \
'-
-100 -40
CSS 015S1 015S2 015S3 015S4 CSS 015S1 OlSS2 OlSS3 OlSS4
(C) (d)

Fig 3. Percentage bias of estimated K , (a), kc (b), k j (c) and k~ (d) as a function of varying sampling schedules

141
 ~ cerebelun -a-- fronal corte x ---i:T- thatamus

8 25
Q
1\
/ \

j~~
6 20

~ ~ 15 ! \
>
u
> /
u

8sLs----:o---
S~S---1--0:--IS~S:--2--0---IS~S---3::----0-::--:'1SS4 tss OISS2 OISS3 OISS4

(a) (b)

50r----__- - - ~ - - ~ - - _ _ , 30r---~---~--~---,

40

~30
>
u 20

10 5

O'-------~---~--~_::_::_-_____:__::'
CSS 0lSS1 0lSS2 0lSS3 01SS4 8S:.S;;-----=O:::IS:-:S:::1;-------:0I~S;:::S2;;---0I=S-:;:S:::-3
--::OI=SS4
(c) (d)

Fig 4. CV of estimated K, (a), k} (b), k J (c) and k 4 (d) as a function of varying sampling schedules

4. CONCLUSION pixel count for a similar 5 min frame in the

generation of dynamic projection
This study shows that improved OISS based on TTACs
from multiple regions promises to provide improved dynamic images compression (Ho. et at. 1997), fast
parameter estimates compared with those obtained parameter estimation (Feng. et at. 1999) and content-
from OISS of a single region. Bias and CV of based retrieval (Cai, et al. 2000).
parameter estimates are at least as good as those from
CSS, thus allowing advantage to be taken from the
reduced computational burden of the small number of ACKNOWLEDGEMENT
frames of OISS. The smaller number of longer frames
of the OISS technique implemented also reduces the This work was supported by the Australian Research
sensitivity of the parameter estimate bias to noise. Council and the University Grant Council of Hongkong.

Furthermore, OISS for 1-123 provides the possibility to

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