The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study

The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study

Physica Medica 69 (2020) 120–125 Contents lists available at ScienceDirect Physica Medica journal homepage: www.elsevier.com/locate/ejmp Technical ...

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Physica Medica 69 (2020) 120–125

Contents lists available at ScienceDirect

Physica Medica journal homepage: www.elsevier.com/locate/ejmp

Technical note

The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study

T

Emmanouil Papanastasioua, , Christina Katsivaa, Argyrios Doumasb, Georgios Gerasimoub, Anastasios Siountasa ⁎

a b

Medical Physics Laboratory, AHEPA University Hospital, Aristotle University of Thessaloniki, 541 24, Greece 2nd Nuclear Medicine Laboratory, AHEPA University Hospital, Aristotle University of Thessaloniki, 541 24, Greece

ARTICLE INFO

ABSTRACT

Keywords: 123 I-FP-CIT imaging Specific Binding Ratio Radius of rotation Scatter correction

Purpose: The high energy emissions of 123I and the suboptimal radius of rotation affect the semiquantitative measurements performed during 123I-FP-CIT tomographic imaging. An in-house extra low cost striatum phantom with brain and striatum compartments was constructed and was used to study the effects of Triple Energy Window scatter correction (TEW-SC) and radius of rotation on the Specific Binding Ratio (SBR) measurements. Materials and methods: The phantom compartments were filled with radioactive 123I solutions with varying concentrations, in a series of experiments. Tomographic images were acquired at six different radii of rotation, with and without TEW-SC and the SBRs were calculated using appropriate regions of interest, as in clinical imaging. Results: SBRs decreased with increasing radius of rotation in both non-SC and TEW-SC images, the decrease being more pronounced in the latter. The application of TEW-SC increases SBR values by 40% on average. A maximum %Recovery of 42.7% of the true SBR value was achieved in the non-SC images, which increased to 64.6% after TEW-SC. Appropriate correction factors (CF) were calculated in order to make the SBR values independent on the radius of rotation, which could be used to correct SBR values obtained from tomographic acquisitions with suboptimal radius of rotation. Conclusion: The use of appropriate CF can provide more consistent SBR values and a more meaningful comparison between SBRs calculated from images acquired at different radii of rotation.

1. Introduction One of the modern tools in imaging of neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, Lewy body dementia, essential, pharmacological and dystonic or juvenile tremor is 123I-FP-CIT (123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane). Imaging of presynaptic dopamine transporters with 123I-FPCIT single-photon emission computed tomography (SPECT) has the advantage of a relatively easy determination of the dopaminergic deficit, by visual assessment of the images. Semiquantitative evaluation for 123 I-FP-CIT SPECT, such as determination of the striatum Specific Binding Ratio (SBR), is a widely used diagnostic parameter and is particularly useful in equivocal cases, or when an assessment of disease progression is required [1–3]. In general, 123I-FP-CIT SPECT image quality and quantification are influenced by the performance characteristics of the gamma camera,

the acquisition parameters, the reconstruction methods and the corrections applied [4,5]. One acquisition parameter that is of high importance, due to its dramatic effect on image spatial resolution, is the detector radius of rotation. It is well known, that for parallel hole collimators, the spatial resolution deteriorates with the increase of the radius of rotation [6,7]. This is the reason why all the guidelines for SPECT tomographic imaging recommend that the radius of rotation must be kept as small as possible. For 123I-FP-CIT SPECT imaging the recommendation is that the radius of rotation must be lower than 15 cm [8]. However, this is not always clinically achievable, due to patients’ somatometric characteristics and/or feeling of discomfort due to claustrophobia. SPECT imaging with a larger radius of rotation will not only affect the image quality and the visual appearance of the images, but will also affect the semiquantitative measurements of the SBR, jeopardizing the interpretation of the whole examination, especially for patients whose measured SBR values lie close to the lower normal

⁎ Corresponding author at: Medical Physics Laboratory, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. E-mail address: [email protected] (E. Papanastasiou).

https://doi.org/10.1016/j.ejmp.2019.12.009 Received 2 October 2019; Received in revised form 7 December 2019; Accepted 10 December 2019 1120-1797/ © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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limits, or for patients who are re-evaluated in a follow-up study to establish the progression of their disease. Image quality in 123I-FP-CIT SPECT imaging with low-energy collimators is also affected by the high energy (529 keV photopeak, 1.4% abundance) photons emitted by 123I, which readily penetrate the collimator septa and are downscattered inside the 123I (159 keV) photopeak acquisition window [9]. These penetration events increase the overall image counts and can also affect the semiquantitative measurements of the SBR. Their contribution to the image counts is expected to vary with the detector radius of rotation, being larger at smaller radii, where the source is closer to the detector and a larger fraction of the high energy photons have a chance to penetrate the septa and reach the crystal. The use of medium energy collimators has been proposed to moderate the effects caused by the high energy emissions [9], but their use deteriorates the spatial resolution which is also important, especially in 123I-FP-CIT SPECT imaging. Another method which has been proposed and has been shown to be helpful to overcome this problem in 123I imaging is to apply scatter correction (SC) methods (e.g. Triple Energy Window – TEW) in order to reduce the number of downscattered events detected in the 123I photopeak window [10]. The aim of this study was to construct an in-house extra low cost striatal phantom, with variable striatum concentrations, to use this phantom to acquire several 123I SPECT studies at several radii of rotation, with and without SC and to investigate the effect of the radius of rotation on the measured SBR values, in order to produce an appropriate correction factor which can be used to normalize SBR values obtained with different radii of rotation.

Table 1 Striatum to background filling ratios and the corresponding true SBR values. Filling ratio

True SBR

15.0:1 10.5:1 10.3:1 8.0:1 6.4:1 5.5:1 4.2:1

14.0 9.5 9.3 7.0 5.3 4.5 3.2

filling ratios were therefore produced, ranging from 15.0:1 to 4.2:1, as shown in Table 1. After filling, all syringe tips were sealed with parafilm and the cap was screwed tightly in place, taking special care to avoid leaks. After the completion of the each experiment the phantom was left to decay for one day, after which it was opened and 1 ml aliquots were withdrawn with a precision pipette from each compartment and were measured in a NaI(Tl) well type scintillation γ-counter (Cobra II, Packard Instrument Company, Meriden, CT) in order to obtain the nominal radioactivity concentrations and calculate the true SBR. Then the phantom would be left to decay for at least another 3 days, before the next experiment could be performed. 2.2. SPECT acquisition and processing SPECT acquisitions were performed with a dual head Discovery NM 630 γ-camera (General Electric Healthcare, Chicago IL) equipped with a 3/8′’ sodium iodide scintillation crystal and a low-energy high-resolution parallel hole collimator (LEHR). The axis of the cylindrically shaped phantom was parallel to the axis of rotation of the camera heads. For each experiment, tomographic acquisitions were performed at six different radii of rotation, namely 13, 15, 17, 19, 21 and 23 cm. All acquisitions were performed over a 360° circular orbit, using a 128x128 matrix, a zoom factor of 1.33 (pixel size: 3.32 mm) and 120 projections. The acquisition time was set between 10 and 13 s/projection, chosen properly so that every dataset had a total of at least three million counts, as recommended for clinical studies [4]. The TEW method was used for scatter and septal penetration correction, with a central energy window set at 159 ± 10% keV and two scatter windows set at 180 ± 2.8% keV (high scatter window) and 138 ± 3.6% keV (low scatter window) respectively. SPECT reconstruction was performed on a Xeleris 3 processing and review workstation (General Electric Healthcare, Chicago IL) using the vendor’s software (Volumetrix MI). Separate reconstructions were performed for TEW-SC and non-SC projection data (using only the projections from the central energy window). Projection data were reconstructed using an OS-EM iterative reconstruction algorithm, with 4 iterations and 10 subsets. A Butterworth low pass filter function with a varying cut-off frequency and an order of 8 was used for postfiltering the reconstructed data, as is routinely used in clinical practice. The cutoff frequency of the Butterworth filter was adapted to each radius of rotation, as shown in Table 2, depending on the planar spatial resolution (FWHM) at the corresponding source-to-collimator distance, which was experimentally determined using a triple line source phantom. Attenuation correction was performed in the reconstructed data using the Chang’s method. For the non-SC images the linear attenuation coefficient was set to μ = 0,110 cm−1, whereas for the TEW-SC images a higher value of μ = 0,143 cm−1 was chosen [11,12]. The Chang’s threshold for the elliptical contour definition was set to 12%.

2. Materials and methods 2.1. Phantom A simplified, extra low cost, refillable and reusable striatal phantom was constructed for the purpose of this study. A cylindrically shaped plastic vessel, approximately 2100 cc in volume, was used to simulate the brain. Two sets of 4 syringes each (1x5cc, 1x2.5 cc and 2x1cc) were glued together and were properly aligned in a shape that would mimic the shape of left and right striatum, as they appear on transaxial 123I-FPCIT SPECT images. The two syringe sets were glued firmly on the inner surface of the vessel screw cap (Fig. 1). The three different phantom compartments (brain, left and right striatum) were then filled with 123I solutions of different radioactivity concentrations. Four experiments were performed: in all four, the brain compartment was filled with an 123 I solution of approximately 20 kBq/ml. In the first experiment, the left and right striatum were filled with solutions of 210 and 206 kBq/ml respectively. For the next three, the radioactive concentration of the solutions used to fill the striata compartments varied from approximately 300 to 85 kBq/ml. Left striatum in the last experiment was filled with the same 123I solution as the brain compartment. Seven different

2.3. Semiquantitative measurements Fig. 1. Photographs of the striatum phantom.

In each reconstructed image, the three transaxial slices where the 121

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Table 2 Selected cut-off values for each radius of rotation. Radius of rotation (cm)

FWHM (mm)

Cut-off frequency 1/(2 × FWHM ) (cycles/cm)

13 15 17 19 21 23

9.0 9.8 10.6 11.4 12.2 13.0

0.56 0.51 0.47 0.44 0.41 0.38

Table 3 Downscattered counts in the 159 keV photopeak energy window, as a fraction of the photopeak counts, for the six radii of rotation. Radius of rotation (cm)

% downscatter in the photopeak window

13 15 17 19 21 23

59.9 58.4 56.9 55.4 54.0 52.6

%Recovery values as a function of the radius of rotation and to compute the SBR CFs. Significant differences between SBR CFs between non-SC and TEW-SC acquisitions were examined by comparing the corresponding regression lines using ANCOVA. Statistical significance was accepted for p < 0.05. 3. Results The contribution of downscatter to the photopeak window did vary with the radius of rotation, being lower at larger radii, as expected. Table 3 lists the percentage of downscattered events that were subtracted from the photopeak window (appropriately calculated from the counts acquired at the high and the low energy scatter windows) relative to the remaining true geometric photopeak events. All the measured SBR values (SBRmeas), for all filling ratios, as a function of the tomographic radius of rotation are presented in Fig. 3a (no SC applied) and Fig. 3b (TEW-SC applied). The mean percent increase in the SBRmeas values after scatter correction is shown in Table 4. The SBRmeas for the reference rotation radius of 15 cm as a function of SBRtrue is presented in Fig. 4. SBRmeas shows excellent linearity with SBRtrue, for both TEW-SC and non-SC tomographic acquisitions (R2 = 0.995 and R2 = 0.998 respectively). The percent SBR recovery, as a function of the tomographic radius of rotation, for all filling ratios, is presented in Fig. 5, for both TEW-SC and non-SC tomographic acquisitions. The corresponding correction factors, CF(r), calculated from the average %Recovery for each rotation radius are shown in Fig. 6.

Fig. 2. A typical transaxial reconstructed section of the striatum phantom, showing the ROIs used for the semiquantitative measurements.

striatum was best visualized were identified and a composite image was formed. Three regions of interest (ROIs) were manually drawn on the first composite image, one for each striatum and one for background and these ROIs served as a template for all images. Every effort was made in order for the striatum ROIs to correspond to the geometric dimensions of the syringes. The shape of the background ROI resembled the one drawn in the occipital cortex in clinical images (Fig. 2). The average counts in each ROI were recorded and the SBRmeas for the left and right striatum was calculated using the formula [4]:

SBRmeas =

Cs

Cb Cb

4. Discussion The simplified striatum phantom constructed for this study was proven very useful for studying the effects of scatter correction and varying radius of rotation on the semiquantitative measurements in 123 I-FP-CIT imaging. It is easy to construct, using low cost materials that can be found everywhere, reusable, easy to refill and easy to manage. Despite the fact that it does not accurately represent the anatomy of the striatum, it provides a reasonable representation of the activity distribution in the tomographic plane. In this study, all four syringes that simulated each striatum were filled with the same radionuclide solution, thus yielding a homogeneous striatum activity. However, it can as easily simulate non-homogeneous striata, by using a higher radioactivity concentration solution to fill the top two syringes (representing the caudate nucleus) and a lower radioactivity concentration solution to fill the bottom two syringes (representing the putamen). One can also experiment with different syringe configurations, to alter the shape of the striatum. Based on the above, it is believed that such a phantom could be a useful alternative to other commercial striatum phantoms (for example 5220-RS901T, Capintec Inc., Florham Park, NJ) which are definitely more accurate anatomically, but are expensive and not readily available to every nuclear medicine department. SBRmeas values decrease with increasing radius of rotation, as shown in Fig. 3, mainly due to the deterioration of tomographic spatial resolution with increasing distance from the collimator. This is true for both non-SC and TEW-SC acquisitions. The average decrease in SBRmeas

(1)

where Cs is the average (left or right) striatum counts and Cb is the average background counts. The SBRmeas and the corresponding true SBR values for each experiment were used to calculate the percent SBR recovery using the formula [13]:

%Recovery =

SBRmeas × 100 SBRtrue

(2)

Using the average calculated %Recovery values for each distance from all experiments, an appropriate Correction Factor (CF) was calculated which can be used to make measured SBR values independent from the radius of rotation used during the SPECT acquisition. The % Recovery for a radius of 15 cm was used as a reference value against which all others were normalized. The following formula was used to calculate the CF as a function of the radius of rotation, r:

CF(r) =

%Recovery(15cm) %Recovery(r)

(3)

Statistical analysis of the data was performed with the SPSS v.24 software (IBM Corp. Armonk, NY). Linear regression was used to fit the 122

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Fig. 4. SBRmeas with and without the application of scatter correction as a function of SBRtrue for radius of rotation equal to 15 cm (non-SC: SBRmeas = −0.2 + 0.39 × SBRtrue, R2 = 0.998. TEW-SC: SBRmeas = −0.26 + 0.55 × SBRtrue, R2 = 0.995).

Fig. 3. Measured SBR plotted against the radius of rotation for each of the nominal filling ratios: (a) non-SC, (b) TEW-SC. Table 4 Mean percent increase in SBRmeas values after the application of TEW-SC. Radius of rotation (cm)

% increase in SBRmeas after TEW SC

13 15 17 19 21 23

49.4 40.9 38.3 35.7 38.4 36.1

Fig. 5. Percent SBR recovery as a function of the radius of rotation with and without scatter correction (non-SC: %Recovery = 53.95–1.16 × radius (cm), R2 = 0.879. TEW-SC: %Recovery = 82.72–2.02 × radius (cm), R2 = 0.805).

SC acquisitions than the TEW-SC ones. This difference can be attributed to the larger downscatter component present at small radii, which leads to a reduction in the corresponding SBR values, compared to those one would get in the absence of downscatter. The TEW-SC successfully removes most of this downscatter component and leads to a comparatively larger increase of SBR values at small radii. SBRmeas show an excellent linearity with SBRtrue values, for every radius of rotation. Fig. 4 presents the data for the radius of 15 cm, but the relationship is similar for all radii. However, as it is shown in Fig. 4, the linear slope is larger for the TEW-SC acquisitions compared to the non-SC ones. This means that, when imaging is performed with scatter correction, the same change in SBRtrue can lead to a larger change in SBRmeas compared to non-SC imaging. This could be helpful in correctly identifying a slowly progressing dopaminergic deficit in patients during follow-up imaging. Application of TEW-SC in 123I-FP-CIT imaging results in increased

from 13 cm to 23 cm is 31% (or approximately 3.1% per cm increase of the rotation radius) when no scatter correction is applied and 37% (or approximately 3.7% per cm increase of the rotation radius) when TEWSC is applied. This result is in agreement with an approximately 3% decrease per cm additional radius reported by Koch et al [7] using Monte Carlo simulation. A somewhat smaller decrease (on average 2% per cm additional radius) has been reported by Poli et al [14], but their study was performed in an anthropomorphic striatum phantom filled with Tc-99m instead of I-123. In this study, the slope of the dependence of the calculated SBR on the radius of rotation was smaller for the non123

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Fig. 6. The Correction Factor (mean value) as a function of the radius of rotation with and without scatter correction. (non-SC: CF = 0.41 + 0.04 × radius (cm), R2 = 0.982. TEW-SC: CF = 0.28 + 0.05 × radius (cm), R2 = 0.971).

Fig. 7. Percent noise (mean value) as a function of radius of rotation before and after TEW-SC. (Non-SC: %Image noise = 14.18–0.34 × radius (cm), R2 = 0.945. TEW-SC: %Image noise = 25.02–0.72 × radius (cm), R2 = 0.971).

values of the semiquantitative measurements of the SBR. On average, a 40% increase in SBRmeas values was observed irrespective of the rotation radius used during the tomographic acquisition. A combined 40% increase in SBR values has also been reported by Tossici-Bolt et al [15] after the application of both attenuation correction and TEW scatter correction. In their study, 16% of the increase was attributed to the attenuation correction and a 24% to the scatter correction, indicating that scatter correction is more significant. In the present study, the increase in SBR was higher for smaller radii of rotation (more than 49% for a radius of 13 cm and almost 41% for a radius of 15 cm) and lower (36–38%) for larger radii. This can be attributed to the larger fraction of high energy I-123 downscattered septal penetration photons that are present at smaller source to collimator distances (Table 3). Such a behavior is not to be expected with Tc-99 m, where high energy photons are not present. Indeed, Poli et al [14], using Tc-99 m instead of I-123, have found that the application of Dual Energy Window scatter correction results in an increase in SBR values which is much lower (less than 15% on average) and does not vary with the radius of rotation. A maximum percent recovery of 42.7% was observed in our experiments without scatter correction at the smaller radius of rotation of 13 cm, which improved to a 64.6% after the application of TEW-SC (Fig. 5). This is in accordance with previous studies which have reported a maximum recovery of approximately 70% when attenuation correction and scatter correction were applied [13]. Fig. 5 also shows that the percent recoveries calculated for the seven filling ratios were in better agreement with each other in the non-SC acquisitions compared to the TEW-SC ones, especially for the small radii of rotation. This can be attributed to the increased noise present in the TEW-SC images, due to the lower total counts available for the reconstruction, after the subtraction of the downscattered events. In the phantom images, percent image noise can be estimated by dividing the standard deviation of the uniform background ROI counts by the corresponding mean. Fig. 7 shows that for all radii of rotation, percent image noise after the application of TEW-SC is significantly higher than before. The strong dependence of the SBR values on the radius of rotation denotes that an appropriate factor is necessary, in order to correct SBR values obtained from tomographic images acquired at a suboptimal rotation radius. The statistical comparison between the two regression lines in Fig. 6 indicated that different CFs are necessary, depending on whether scatter correction is used during tomographic acquisition or

not (p = 0.043). Using the 15 cm rotation radius as reference and the regression equations shown in Fig. 6, the CF for non-SC acquisitions at a radius of 17 cm was 1.09 and at a radius of 21 cm was 1.25. This shows that a slight 2 cm increase from the optimum radius of rotation of 15 cm, can lead to a 9% underestimation of the striatum SBR, unless the CF is applied. Such an underestimation can be significant in equivocal cases, or in follow up studies. The corresponding values for TEW-SC acquisitions were 1.13 and 1.33. 4.1. Limitations There are a few limitations in the present study. The in-house striatum phantom used in this study differs significantly from other, anatomically more accurate, striatum phantoms commercially available, but the results thus obtained, should, at least in principle, apply also to the other phantoms. However, there is no guarantee that the exact quantitative results, concerning the calculated correction factors with the radius of rotation, would be the same if anatomically accurate phantoms were used. A second limitation is the use of Chang’s attenuation correction method, instead of a more accurate CT-based attenuation correction that could be applied using a SPECT/CT system. A third limitation is the lack of a resolution recovery correction, since it was not available, the application of which could have altered the results of the SBR dependence on the radius of tomographic rotation. 5. Conclusion The measurement of the striatum SBR plays an important role in the diagnostic interpretation of 123I-FP-CIT images. Unfortunately, these measurements are quite sensitive on the acquisition and processing protocols used. TEW-SC results in increased SBR values which are closer to the actual ones. Appropriate CFs can be calculated to smooth out the dependence of the SBRs on the tomographic radius of rotation. Application of such CFs can provide more consistent SBR values and a more meaningful comparison between SBRs calculated from images acquired at different radii of rotation. The in-house, extra low cost, simplified striatum phantom built for this study, was proven very useful in determining such CFs. 124

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Declaration of Competing Interest

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