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Deadtime effects in quantification of 177Lu activity for radionuclide therapy Uribe, Carlos F; Esquinas, Pedro L; Gonzalez, Marjorie; Zhao, Wei; Tanguay, Jesse; Celler, Anna Jan 11, 2018

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ORIGINAL RESEARCH Open AccessDeadtime effects in quantification of 177Luactivity for radionuclide therapyCarlos F. Uribe1,2*, Pedro L. Esquinas1, Marjorie Gonzalez3, Wei Zhao1, Jesse Tanguay1 and Anna Celler1* Correspondence: curibe@bccrc.ca1Medical Imaging Research Group,University of British Columbia,Vancouver, BC, Canada2Department of MolecularOncology, British Columbia CancerResearch Centre, Vancouver, BC,CanadaFull list of author information isavailable at the end of the articleAbstractBackground: The aim of this study was to investigate the deadtime (DT) effects thatare present in 177Lu images acquired after radionuclide therapy injection, assessdifferences in DT based on the full spectrum and the photopeak-only measurements,and design a method to correct for the deadtime losses.A Siemens SymbiaT SPECT/CT camera with a medium energy collimator was used. A295-mL bottle was placed off-center inside a large cylinder filled with water, and177Lu activity was sequentially added up to a maximum of 9.12 GBq. The true countrates vs. observed count rates were plotted and fitted to the DT paralyzable model.This analysis was performed using counts recorded in the full spectrum and in otherenergy windows. The DT correction factors were calculated using the percentagedifference between the true and the observed count rates.Results: The DT values of 5.99 ± 0.02 μs, 4.60 ± 0.052 μs, and 0.19 ± 0.18 μs wereobtained for the primary photons (PP) recorded in the 113- and 208-keV photopeaksand for the full spectrum, respectively. For the investigated range of count rates, the DTcorrection factors of up to 23% were observed for PP corresponding to the 113-keVphotopeak, while for the 208-keV photopeak values of up to 20% were obtained. Thesevalues were almost three times higher than the deadtime correction factors derivedfrom the full spectrum.Conclusions: The paralyzable model showed to be appropriate for the investigatedrange of counts, which were five to six times higher than those observed in the patientpost-therapy imaging. Our results suggest that the deadtime corrections should bebased on count losses in the scatter-corrected photopeak window and not on thedeadtime determined from the full spectrum. Finally, a general procedure that can befollowed to correct patient images for deadtime is presented.Keywords: 177Lu, Deadtime, SPECT/CT, QuantificationBackgroundPeptide receptor radionuclide therapies (PRRT) using 177Lu-labeled somatostatin ana-logues have been proven to be very effective in treatment of neuroendocrine tumors(NETs), taking advantage of the overexpression of somatostatin receptors in NET can-cer cells [1–3]. A limitation on how this treatment is delivered in many centers is thatit does not take into account differences in radiotracer uptake between individuals andall patients are injected with the same activity [4]. It is believed that treatment plansusing injections based on an individualized dose assessment, similar to what is done inEJNMMI Physics© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 InternationalLicense (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, andindicate if changes were made.Uribe et al. EJNMMI Physics  (2018) 5:2 DOI 10.1186/s40658-017-0202-7external beam therapies, could significantly improve PRRT outcomes and thereforeshould become routine practice [5, 6].In order to achieve such personalized dose assessment, the accurate quantification ofactivity within organs of interest (critical organs) and tumors must be performed andtemporal changes of this activity determined. In typical diagnostic imaging scans, theadministered activities are low, resulting in low count rates in the SPECT camera withno deadtime (DT). However, in radionuclide therapy procedures, as those performedwith 177Lu, patients are injected with high activities (of the order of GBq), which resultin high photon flux and may cause camera DT when imaging studies are performed. Inorder to accurately quantify patient’s activity in these situations, correcting images forDT losses might be necessary.Several studies have investigated DT effects in Anger cameras using high activities of99mTc and 131I [7–13]. However, to the best of our knowledge, only two studies haveexamined this effect for 177Lu. Beauregard et al. [14] investigated DT effects usingphantom acquisitions and image quantification protocol in which the dual energy win-dow (DEW) scatter correction method was applied. The effects of DT on the countsrecorded in the full spectrum and in the photopeak window were measured, and thedata were fitted to the Sorenson’s paralyzable model [8]. The authors designed a correc-tion scheme where they created lookup tables relating the DT corrections values forthe reconstructed image with the count rates observed in the full energy spectrum.Celler et al. [15] proposed a marker-based method for the determination of the DTcorrection. The counts losses in the image of a small marker placed in the field of view(FOV) of the camera and imaged simultaneously with the patient, relative to the samemarker counts without the patient, were used to determine the DT correction factor.This procedure, however, is quite cumbersome, and tests were performed for low-energy high-resolution (LEHR) collimator which presents additional challenges (needto account for high scatter and septal penetration) relative to the typically recom-mended medium-energy (ME) collimator [14, 16, 17].The aim of our study was to investigate the DT effects that are present in imagingstudies of the 177Lu radionuclide therapy patients, performed according to the guide-lines outlined in MIRD 26 [18]. Our objective was to design an accurate DT correctionmethod to be used in these studies.Since quantification of activity for dosimetry purposes is done using images recon-structed from primary photons (PP) recorded in the photopeak window(s), the dead-time correction method must correct for count losses that affect only these primaryphotopeak photons. Therefore, the proposed DT correction method is based on theanalysis of primary counts, i.e., counts that are collected in the photopeak window(s)and have the scatter/background component(s) removed. Additionally, we assesseddifferences between the DT values and the correction factors determined using ourprimary photon-based method for 113-keV, 208-keV photopeaks and those obtainedfrom the analysis of count loses in the full spectrum.A similar study to ours was performed by Guy et al. [13], but they used 131I while inour case, it is 177Lu. They found large differences between the deadtime correction fac-tor which was based on the analysis of the primary photon count losses and that basedon the count losses in the full spectrum. The full-spectrum correction factor would beunderestimated by up to 20% when compared to the DT correction based only on PP.Uribe et al. EJNMMI Physics  (2018) 5:2 Page 2 of 16Sorenson [8] suggested that gamma cameras behave as having a combination ofparalyzable and non-paralyzable components. Several studies from the second half ofthe last century [7, 19] have found that, at least for the range of count rates encoun-tered in medical procedures, the camera behavior could be accurately approximated bya paralyzable model. More recently, Silosky et al. [12] analyzed modern cameras andalso concluded that for count rates below 375 kcps, the cameras behaved as paralyzablesystems. Guirado et al. [11] found that for a Symbia camera (Siemens Medical,Germany), a sharp change in camera response can be observed at very high count rates,but in the region below this change, both paralyzable and non-paralyzable modelsaccurately fit the data. A study by Guy et al. [13] suggests that modern cameras aredominated by the paralyzable component.Based on our experience with patients treated by our collaborators at the L’Hôtel-Dieu de Québec site of the CHU de Québec – Université Laval center (Quebec City,Canada), the total count rates observed (full spectrum) during the first imaging scanafter the therapeutic 177Lu injection (which occurs between 1 and 4 h after the injec-tion) are typically of the order of 70–100 kcps. This corresponds to the low range ofthe count rates observed in the experiments performed in this study, which for the fullspectrum, were equal to about 400 kcps.MethodsSPECT camera, collimators, and energy window setupThe experiments were performed using a Siemens SymbiaT (Siemens Medical, Germany)SPECT/CT camera with a medium-energy low-penetration (MELP) collimator. Twophotopeak energy windows (PW) were specified; one for the 113-keV and another one forthe 208-keV photopeaks of 177Lu (Table 1). Additionally, lower scatter window (LSW) andupper scatter window (USW) were defined for each of the photopeaks (four in total) to beused in triple energy window (TEW) scatter correction [18]. We have been using suchthree-energy-window acquisitions in all our research and clinical studies, and thisapproach has been shown to lead to accurate activity quantification [20]. Furthermore,the counts in the full energy spectrum (i.e., 0 keV to 400 keV) were also collected.Planar acquisitionsIn order to measure the camera DT, its response has to be determined over a widerange of activities. A total of 9.12 ± 0.91 GBq of 177Lu (in the form of 177LuCl3, obtainedfrom Polatom, Poland) was diluted in water to obtain a solution with a concentrationTable 1 Energy window limits for the two photopeaks of 177Lu. Additional energy windows wereused to collect data for the entire spectrumWindow name Lower limit [keV] Center [keV] Upper limit [keV]LSW113 88.4 95.0 101.7PW113 101.7 113.0 124.3USW113 125.0 139.0 152.9LSW208 153.0 170.0 187.0PW208 187.2 208.0 228.8USW208 229.5 255.0 280.5Uribe et al. EJNMMI Physics  (2018) 5:2 Page 3 of 16of 35.7 ± 1.4 MBq/mL and distributed equally into twenty-five 10-mL syringes. Theactivity contained in each syringe was measured using an Atomlab100 plus (Biodex,USA) dose calibrator. The syringes were sequentially emptied into a 295-mL bottlelocated 5 cm off-center inside a large cylinder (21.6-cm diameter) filled with water. Thecylinder was placed on the camera bed between the detectors, so that the center of thebottle was positioned at 35 and 25 cm from the collimator surface of detector 1 anddetector 2, respectively (see Fig. 1). Since the routine quality control tests of the cameraensure that the behavior of both detectors is very similar, the 10 cm of additional waterthickness for detector 1 allowed us to investigate the effects of attenuation and scatteron the count rate and camera DT. Activity residues in each emptied syringe were mea-sured again in the dose calibrator and the net activity which was added to the bottlewas calculated for all 25 syringes.A series of 26 planar scans was performed. In order to determine background counts,the first planar scan was performed with no activity in the bottle. The subsequent scanswere performed after emptying each consecutive syringe into the bottle. The acquisi-tion time of the scans varied from 3 min for very high activity to 5 min for lower activ-ity points.Additionally, the energy spectra were collected for both detectors at low (17.3 kcps),medium (101.5 kcps), and high (306.3 kcps) count rates.Data analysisIn the analysis of the DT effects, the counts collected over the entire field of view(FOV) of each of the detectors were used and the corresponding count rates wereobtained by dividing these counts by the scan acquisition times.Since we did not see any sharp changes in the camera behavior (mentioned byGuirado et al. [11]) and a similar work by Guy et al. [13] also suggested that moderncameras follow a paralyzable model, we decided to fit our data to the Sorenson’s paral-yzable model [8] using the following equation:Ro ¼ Rte−Rtτ ð1ÞFig. 1 Coronal view of the positioning of the phantom and the bottle inside it with respect to thetwo detectorsUribe et al. EJNMMI Physics  (2018) 5:2 Page 4 of 16where Rt represents the true count rate, Ro is the observed count rate obtained fromthe experiment, and τ is the paralyzable DT parameter. In order to estimate the truecount rates Rt in each of the analyzed energy windows, a linear fit was made to the datapoints corresponding to acquisitions where the activity in the phantom was lower than2.1 GBq (< 80 kcps). We assumed that no deadtime was present at these low countrates. The parameter τ was determined by fitting the data to Eq. (1) using the total leastsquare algorithm.In the analysis of the DT effects for each detector, the following three methods wereused (summarized in Fig. 2):A. DT estimated using count rates in the full spectrumFor each acquisition, the observed and the true count rates for photons recorded inthe full energy spectrum were used to determine the value of τf. True count rates wereestimated using the extrapolation method previously described.Fig. 2 Flow charts of the three methods used to calculate the camera deadtimeUribe et al. EJNMMI Physics  (2018) 5:2 Page 5 of 16B. DT estimated for counts acquired in each energy windowIn order to compare the photopeak window DT values with the primary photons DT(obtained after correcting PW photons for scatter using TEW), the observed (mea-sured) and the true (obtained from extrapolation) count rates were determined inde-pendently for each of the two photopeak windows (PW113 and PW208) and all fourscatter windows (LSW113, USW113, LSW208, and USW208). For each energy window,the corresponding DT values (i.e., τPW208 ; τPW113 ; τLSW208 ; τLSW113 ; τUSW208 ; τUSW113Þ wereindependently calculated, in a similar way as done for the full spectrum.C. DT estimated for primary photons count lossesAs already mentioned, the activity quantification is done using images reconstructedfrom primary photons only. In order to determine the number of primary photons (andprimary photons count rate) detected during each of the 26 scans in the two photopeakwindows, the TEW correction method was applied. The method estimates the scatteredcounts (Cs) collected in each of the PW windows from the counts collected in thecorresponding LSW (Cls) and USW (Cus) using Eq. (2).Cs ¼ Clsωlsþ Cusωus ωpw2ð2ÞThe widths of the LSW, PW, and USW are given by ωls, ωpw, and ωus, respectively.The primary counts (Cprim) for the two photopeaks (113 and 208 keV) are calculatedby removing scattered counts from the total counts recorded in the correspondingphotopeak window (CPW).Cprim ¼ CPW−Cs ð3ÞCount rates are calculated by dividing (Cprim) by the duration of each scan.A similar procedure as described in methods A and B was followed to determinethe DT values for primary photons only. First, the true and observed count rates,for each of the six energy windows, were determined (method B). The observedcount rates were measured experimentally, while the true count rates for eachenergy window were calculated using Eq. 1 and the corresponding value of τ (de-termined in Method B). Alternatively, the true count rates can be estimated byextrapolation, as in method B. Next, these observed and true count rates wereseparately entered into Eq. 2 to determine the observed and the true scatter com-ponents. Finally, the observed and the true primary photons count rates wereestimated using Eq. 3.In the last step, the observed and true primary photons count rates were fitted to Eq.1 to obtain the primary photons DT value τPP for each of the two photopeaks.With the known camera deadtime values, it is possible to calculate deadtimecorrection factors (DTCFs) for the full spectrum, for each of the energy windows, andfor the primary photons only. DTCF corresponding to any particular observed countrate can be calculated as the percentage difference between the true and the observedcount rates:Uribe et al. EJNMMI Physics  (2018) 5:2 Page 6 of 16DTCF ¼ Rt−RoRt 100 ð4ÞTo perform the correction, the values of the count rates observed in the experiment(or patient scan) should be used, while the values of the true count rates can be calcu-lated using Eq. 1 and the corresponding τ values. These τ values must be determinedexperimentally using phantoms.ResultsFigure 3 shows the spectra collected for both detectors at low, medium, and high countrates. For display purposes, the spectra were normalized so that the total area underthe curve was equal to one (i.e., probability density functions). In reality, due to differ-ent attenuation conditions, the number of counts collected by detector 1 was about fivetimes lower than that in detector 2. The vertical dashed lines show the positions of theenergy windows.The behavior of the observed count rates vs. true count rates for the full spectrum isshown in Fig. 4. Plots of observed count rates vs. true count rates for the LSW, USW,and PW and for the primary photons corresponding to the 113 and 208 keV photo-peaks of 177Lu are shown in Figs. 5 and 6, respectively. The curves for each detectorhave been plotted separately. The dashed lines represent the identity lines whichcorrespond to the case where no DT occurs. All the symbols in blue show the data fordetector 1, while those in black are for detector 2. The fit to the paralyzable model isdisplayed in red.In the case of detector 2, for which larger range of count rates than in detector 1were observed (due to less attenuation), the values of DT determined from PW113 andPW208 exceeded the DT values determined from the full spectrum by a factor of 7.3and 5.3, respectively. When considering only primary photons (with the TEW scattercorrection applied), the DT values exceed those obtained from the full spectrum by afactor of 31.5 and 24.2 for the 113 and 208 keV, respectively. For all the fits, theFig. 3 Measured spectra recorded at different count rates for both detectors. The count rates listed in thelegend of the plots correspond to the total full spectrum count ratesUribe et al. EJNMMI Physics  (2018) 5:2 Page 7 of 16coefficients of determination (R2) were higher than 0.95 suggesting a good fit of the ob-served count rates to the paralyzable model.Figure 7 shows the DTCF curves as a function of the observed count rates for thetwo photopeaks and the full spectrum. When considering all counts in the PW, at thecount rate of 4 × 104, the DTCF values for the PW113 and PW208 were approximately0.72 and 0.52 times lower, respectively, than those determined from the entirespectrum for the same count rate in the PW. However, when only primary photons areconsidered, the DTCF for the PW113 and PW208 were 3.6 and 2.6 times higher thanthose for the full spectrum.In our imaging studies of patients being treated with 7.4 GBq of 177Lu and scansperformed within 4 h after injection, typical count rates in the entire spectrum were atthe level of 50–70 kcps, in the 208-keV photopeak window were equal to about 6–8 kcps, and the count rates for the primary photons were almost always below 2 kcps.(Since in these acquisitions, only 208-keV photopeak was used, similar information for113 keV is not available). We had a very few patients where these rates were higher (upto a factor of two) and in these cases applying DT corrections would be important.Assuming these count rates, the DTCF when using only primary photons should bebelow 5%, while if the DT correction is based on the full spectrum, the value of DTCFwould be three to four times lower.DiscussionEnergy spectra at different count ratesAt high count rates, the spectra collected by the camera (see Fig. 3) show a wide rangeof effects, caused by different physical phenomena, which contribute to the observedDT. The reduction of intensity of both photopeaks (i.e., reduction of counts in PW113and PW208) as the count rates increase can be explained by two effects: (1) count lossesdue to the finite processing time of the camera electronics and (2) the pileup effectsFig. 4 Observed count rates vs. true count rates for the full spectrum. The values of τp determined for bothdetectors are shown. Crosses indicate the measured data points. Typical values of full spectrum count ratesin patient studies (indicated by an arrow) range from 50 to 70 kcps (~ 0.6 × 105 cps on this graph)Uribe et al. EJNMMI Physics  (2018) 5:2 Page 8 of 16where two or more photons which reach the detector within a very short time intervalare counted as a single photon with energy equal to the sum of the two photons’ ener-gies. Although the count loses due to electronics are rather energy-independent, thepileup effect causes the intensity to decrease in low-energy part of the spectrum andincrease in the high-energy part (Fig. 3).These effects are clearly seen in Fig. 3. The intensity of the photopeaks relative to thebackground is the highest in the spectra corresponding to the lowest count rates. Inthe scatter windows, however, it is at the highest count rates that the relative intensityof counts is the highest. Due to their high intensity, photopeak windows lose relativelymore counts than they gain. The effect is opposite in the other (background) regions,and this is why scatter windows show increased intensities at the high count rates.Detector 2 which was positioned closer to the source (with less attenuating material)experienced higher count rates shows much stronger pileup effect than detector 1. Thepileup effects have also been observed in 131I study by Guy et al. [13], similar to thosethat we are detecting in 177Lu spectrum.Fig. 5 Observed count rates as a function of true count rates for the 113-keV photopeak (a) and its scatterwindows (b, c). The TEW scatter corrected behavior for this photopeak is shown in (d)Uribe et al. EJNMMI Physics  (2018) 5:2 Page 9 of 16Comparing the spectra recorded by the two detectors, it can be seen that the inten-sity of counts in the 113-keV photopeak window is approximately 1.3 times higher inthe spectrum recorded by detector 2 than that recorded by detector 1, while the sameratio for the 208-keV peak is only 1.1. This effect can be explained by the higherattenuation of photons recorded by detector 1 due to additional 10 cm of waterbetween the source and the detector (the effect is stronger for 113 keV than for208 keV). Similarly, the intensity of characteristic Pb X-rays (peak at approximately70 keV) from the collimator with respect to the characteristic X-rays of 177Lu (peak atapproximately 50 keV) is higher for detector 1 due to more attenuation of the 50-keVphotons relative to those at 70 keV. As the energy of photons increases, the linearattenuation of water decreases thus the intensity of the higher photopeak (208 keV) isless affected.Deadtime valuesThe behavior of the curves representing observed vs. true count rates corresponding toboth detectors presented in Figs. 4, 5, and 6 is similar but not exactly the same. Due toFig. 6 Observed count rates as a function of true count rates for the 208-keV photopeak (a) and its scatterwindows (b, c). The TEW scatter corrected behavior for this photopeak is shown in (d)Uribe et al. EJNMMI Physics  (2018) 5:2 Page 10 of 16different attenuation and scatter conditions for the two detectors, the count rates mea-sured by detector 1 and also DT were much lower than those for detector 2. Therefore,in the subsequent discussion only detector 2 will be considered.The USW of the 113-keV photopeak as well as both LSW and USW of the 208-keVphotopeak show negative values of DT for detector 2. The interpretation of this effectis that, although in principle, the camera DT should remove counts from the spectrum,the pileup effect counteracts loses related to limited electronics processing time andadds more photons to these scatter energy windows. Since the intensity of the spectrumat low energies is high (due to large contribution from scattered photons), the probabil-ity of two such low-energy photons simultaneously arriving at the detector and beingdetected as a single high-energy photon is also high. The role of the DT correction is tore-create the correct spectrum shape by removing pileup and compensating for thecount loses due to limited processing time of electronics.When TEW scatter correction is performed for both detectors (after correcting eachenergy window for its own DT), both detectors behave similarly (Fig. 5d and Fig. 6d). Thisshows that the effects of scatter and attenuation have been accurately accounted for.The differences in DT values determined using counts in the photopeak windows andin the entire spectrum, although high, are not surprising. Silosky et al. [12] analyzingFig. 7 Deadtime correction factors as a function of the observed count rate. For figures a, b, and c, theobserved count rates are those which were recorded in the energy window corresponding to thepresented curve (see legend). d DTCF corresponding to PP. Typical values of full spectrum count rates inpatient studies (indicated by an arrow) range from 50 to 70 kcps (~ 0.6 × 105 cps on this graph)Uribe et al. EJNMMI Physics  (2018) 5:2 Page 11 of 1699mTc spectra also found a factor of 20 difference between the DT determined basedon the entire spectrum and on the photopeak only. Guy et al. [13] in their study of 131Ifound discrepancy amounting to 20%. The main causes for these differences are thepileup effect and the scatter. While the DT in the entire spectrum corresponds to thecount losses mostly due to the camera electronics, the PWs are additionally affected bythe pileup effects. Due to energy summing, some photopeak photons are detected in ahigh-energy part of the spectrum (outside the photopeak window) which effectivelydecreases counts in PW and results in its higher DT.After scatter correction, the DT effect is higher for the lower energy photopeak,PW113 (Fig. 7d), most likely due to the fact that high intensity of the low-energyphotons in the spectrum provides more opportunity for them to be not processed bythe electronics and to pileup as compared to the 208 keV peak.Previous studies [18] suggest that better quantification of 177Lu activity is achievedwhen data from the PW208 is used for image reconstruction. The fact that we haveobserved less deadtime for the 208 keV photopeak provides additional support that itshould be used for quantification of 177Lu.Considering differences in DT determined using the full spectrum and the PWcounts only, a method allowing user to determine the DT for the PW if the DT for theentire spectrum is known has been proposed [7, 21]. The method involves calculatingthe window fraction and relating it to DT estimated from the full spectrum τfs.Window fraction wf is defined as a fraction of counts detected within the specifiedwindow, relative to the total number of counts recorded in the full energy spectrum. Ithas been proposed that the observed DT for the specified energy window τw should berelated to the full spectrum deadtime by the following relation:τw ¼ τfswηfð5Þwhere η is a positive constant. Cherry et al. [22] propose a value of η = 1, while Siloskyet al. [12] report values of η = 1.4.Window fractions for the different energy windows and for both detectors arepresented in Table 2. These values were calculated using all the 25 time points and takingthe average window fraction with its corresponding standard deviation. We then used Eq.5 with the values of η = 1 and η = 1.4 and compared the resulting τw with those obtainedin our experiments (Table 3). None of the DT values for the six energy windows was cor-rectly predicted based on the measured full spectrum DT and the corresponding windowfraction. Moreover, the model cannot predict negative values of DT so it does not takeTable 2 Window fractions (in percentage) for the two photopeaks and detectorsWf [%] Detector 1 Detector 2LSW113 [%] 8.73 ± 0.10 8.06 ± 0.10PW113 [%] 16.41 ± 0.18 19.24 ± 0.26USW113 [%] 8.29 ± 0.22 8.13 ± 0.49LSW208 [%] 8.43 ± 0.09 6.77 ± 0.41PW208 [%] 12.18 ± 0.24 13.89 ± 0.15USW208 [%] 0.69 ± 0.15 1.32 ± 0.51Uribe et al. EJNMMI Physics  (2018) 5:2 Page 12 of 16into account pileup effects. We therefore do not support the use of this method to esti-mate the DT for the PW if the DT for the entire spectrum is known.Correcting patient studies for the DT effectBased on the results of our experiments and the above discussion, it is recommended thatthe procedure to correct patient’s images for the deadtime should include the following steps:A. Determination of camera DT1. Perform phantom experiments to measure the count rate performance and the DTCFof the camera. Use the same collimator, photopeak window, and two scatter windowsas will be used for patient acquisition. Set additional windows to cover the remainingparts of the spectrum. The data acquired in these windows (summed) will provide thefull spectrum count rates. The scatter conditions of the phantom used in theseexperiments should as much as possible be representative to the patient population.2. Determine the observed and the true (using extrapolation method) count rates foreach energy window (PW, LSW, and USW) independently.3. Use these true and observed count rates for each energy window and the TEWmethod to calculate the true and observed primary photon count rate.4. Determine τ for the primary photons.5. Calculate the camera DTCF to be applied for primary photons. Graph the DTCFversus observed full spectrum count rates (more detail is given below when wemention the approximations of the method).B. Performing DT corrections for patient studies1. Apply the same energy windows settings as were used in the phantom experimentsdescribed above. For each projection of the patient tomographic scan, determinethe observed count rates for the full spectrum window. Calculate the meanobserved full spectrum count rate by averaging these overall projections.2. Using the observed average full spectrum count rate, read the DTCF correspondingto primary photons only from the graph prepared in section A point 5.Table 3 Values for τw obtained with Eq. 5 using values of η available in the literature. Windowfractions obtained from detector 2 were used as it covered a larger range of count ratesη = 1 η = 1.4 True τw η required to obtain true value of τwτw113 [μs] 1.0 1.9 6.04 ± 0.23 2.1τw208 [μs] 1.4 3.0 4.79 ± 0.18 1.6The last two columns show the value of η which would be required to correctly predict the DT value determined inour experimentsUribe et al. EJNMMI Physics  (2018) 5:2 Page 13 of 163. Apply the DTCF to the quantitatively reconstructed image.In this study, we created a DTCF plot for a Siemens SymbiaT camera using a MELPcollimator (Fig. 7). It can be used to correct for deadtime losses in patient study if thesame energy windows as used in our study are employed (see Table 1).The proposed method represents a relatively simple protocol to be applied forradiotherapy patients’ scans where the deadtime has been observed (or suspected). Thetechnique is general and can be applied to any camera. However, DT values must bedetermined experimentally for any other camera, collimator, and energy windowsettings. Nevertheless, our experience (collaboration with Universite Laval and work onseveral Symbia cameras in Vancouver) shows that the values reported in this paper forSiemens SymbiaT can be used with other cameras of the same type.However, please note that the proposed method is based on the following the approx-imations: It is assumed that the scatter conditions of the phantom represent those thatwill be present in the patient study.1. It is assumed that the DT losses are the same in each projection; therefore, theDTCF can be applied to the reconstructed image.2. Since count losses due to DT depend on the scatter characteristics of a particularpatient (related to his/her body size), it is reasonable to expect that the DTCFshould be analyzed as a function of observed count rates in the full spectrum asthese will be the least affected by the size of the patient. This approach is beingused in our method as described above.In our opinion, the issue of DT correction requires further investigation using largenumber of dataset from patients with different body shapes and sizes to fully under-stand the interdependence between primary photons count losses and patient’s bodyshape, scatter, and primary photon count rates.In is important to realize that even when high activities are administered in therapyprocedures, the DT count losses are typically observed only in the first scan, doneshortly after the injection. Based on our experience with therapy patients, the DTcorrection is typically less or much less than 10%. Since dosimetry calculations arebased on the time-integrated activity, the change in total organ/tumor dose due to theDT correction is expected to be relatively small.We estimated this effect considering a patient study where three scans wereperformed at 3, 24, and 72 h. In the unlikely case when the DT correction in-creased the organ activity measured at the first time point by 10%, the change inthe cumulative activity value would depend on the method used to integrate thearea under the time activity curve (TAC). Assuming analytical fit to the datapoints, such increase of activity at the first time point would create a “steeper”shape of the TAC, which will result in 5% lower total dose to the organ. If thecurve integration was performed using a “trapezoid” approach for the first threetime points and exponential tail, the total dose would increase by 0.6%. Therefore,in our opinion, the correction for DT in most cases is not significant and theapproximations used here are appropriate. The effects associated with curve fittingplay much more important role in this case.Uribe et al. EJNMMI Physics  (2018) 5:2 Page 14 of 16ConclusionsDeadtime measurements for the Siemens SymbiaT camera have been performed, andthe resulting data were fitted to the paralyzable model. The deadtime values (τ) weredetermined for each detector using counts in the entire spectrum and in the twophotopeak windows set around the 113- and 208-keV gamma emissions of 177Lu. Inorder to match the scatter correction used in quantitative imaging studies, countscorresponding to both photopeak windows were corrected for scatter using TEWscatter correction method (after each photopeak and scatter window has been individu-ally corrected for its own DT value).The paralyzable model proved to be appropriate for the range of studied count rates.The DT values and the corresponding DTCF determined using primary photons onlywere substantially higher than those obtained from the analysis of the entire spectrum.Moreover, the DT values determined in this study did not agree with those predictedby the window fraction models found in the literature. This was most likely becausethese models do not consider primary photons but use all photopeak counts (i.e., donot perform the subtraction of scatter presented here).The results of this study suggest that deadtime corrections should be performedbased on the estimates of DT losses of the primary photons only, using scatter-corrected photopeak window and not by using the deadtime determined from the fullspectrum. Additionally, since the deadtime values are lower for the 208-keV photopeak,it is recommended that 177Lu quantification should be based on acquisition of the208-keV photons. Finally, a general procedure that can be followed to correct patientimages for deadtime is presented.AbbreviationsDEW: Dual energy window; DT: Deadtime; DTCFs: Deadtime correction factors; FOV: Field of view; LEHR: Low energyhigh resolution; LSW: Lower scatter window; ME: Medium energy; NETs: Neuroendocrine tumors; PP: Primary photons;PRRT: Peptide receptor radionuclide therapies; PW: Photopeak windows; TEW: Triple energy window; USW: Upperscatter windowFundingThis project has been funded by the Natural Sciences and Engineering Research Council of Canada, award number194512-12.Availability of data and materialsThe datasets supporting the conclusions of this article are included within the article.Authors’ contributionsCU was responsible for the data acquisition and data analysis and participated in the study design with AC. PE, MG,and JT assisted with the data acquisition and discussion. WZ assisted with the count rate determinations in clinicalstudies and was involved in the discussion. All authors read and approved the manuscript.Ethics approval and consent to participateNot applicableConsent for publicationNot applicableCompeting interestsThe authors declare that they have no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Author details1Medical Imaging Research Group, University of British Columbia, Vancouver, BC, Canada. 2Department of MolecularOncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada. 3Vancouver Coastal Health Authority,Vancouver, BC, Canada.Uribe et al. EJNMMI Physics  (2018) 5:2 Page 15 of 16Received: 27 July 2017 Accepted: 7 December 2017References1. Kwekkeboom DJ, de Herder WW, van Eijck CHJ, et al. Peptide receptor radionuclide therapy in patients withgastroenteropancreatic neuroendocrine tumors. 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