{"paper_id":"4db5be71-4d31-47d8-bb40-fb57153e94ea","body_text":"Validity of a Simple Spillover Correction for Positron Emission Tomography Measurements in the Cerebrospinal Fluid Region | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Validity of a Simple Spillover Correction for Positron Emission Tomography Measurements in the Cerebrospinal Fluid Region Emi Hayashi, Shin Hibino, Mitsuhito Mase This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6415718/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Positron emission tomography (PET) measurements in the cerebrospinal fluid (CSF) region may be overestimated because of spillover artifacts from surrounding radioactivity. In this study, we proposed a simple spillover correction method (the subtraction method) and evaluated its validity. Methods A cylindrical phantom simulating brain ventricles was used to compare the subtraction method with a partial volume effect (PVE) correction method, specifically the geometric transfer matrix (GTM) approach. The subtraction method was then applied to dynamic PET images using three radiotracers, [ 18 F]fluorodeoxyglucose (FDG), [ 18 F]fluorodopa (FDOPA), and [ 11 C]raclopride (RAC), in one healthy individual, and [ 15 O]H 2 O (H 2 O) in another case. None of these tracers were expected to diffuse into the CSF within a short timeframe. The effects of spillover correction on CSF measurements were assessed. Results Both the subtraction and GTM methods effectively reduced spillover artifacts in the phantom study. In dynamic PET images, all four radiotracers showed an immediate increase in radioactivity within the CSF region following intravenous administration. FDG, FDOPA, and RAC demonstrated similar radioactivity trends in the CSF and surrounding regions, whereas H 2 O showed a distinct pattern. After spillover correction, time-activity curves for FDG, FDOPA, and RAC approached near-zero levels in the CSF, whereas H 2 O continued to show increasing activity over time. Conclusions We developed a subtraction method to correct PET signal overestimation in the CSF region attributed to spillover effects. This approach effectively reduced artifacts, comparable to the GTM method, and offers the advantages of simpler volume-of-interest (VOI) settings and straightforward calculation procedures. Spillover correction PET CSF Partial volume correction [15O]H2O Figures Figure 1 Figure 2 Figure 3 1 Introduction When measuring radioactivity in positron emission tomography (PET) images, care must be taken to avoid overestimation (spill-in) and underestimation (spill-out) because of partial volume effects (PVE) [ 1 ]. To minimize these effects, the measurement area should be at least three times larger than the spatial resolution [ 2 ]. However, in actual clinical PET examinations, small regions are often evaluated. The cerebrospinal fluid (CSF) region generally shows low radioactivity, whereas the surrounding regions exhibit higher intensity. Therefore, overestimation due to spill-in, referred to as the spillover artifact here, must be considered when measuring CSF radioactivity. To date, no reports have specifically addressed PVE correction methods focused on the CSF region. The aim of this study was to propose a simple method to correct for spillover artifacts in PET-derived radioactivity measurements in the CSF region and to evaluate the validity of this method compared with the widely used PVE correction using the geometric transfer matrix (GTM) method. This study was approved by the Ethics Committee of the Nagoya City Rehabilitation Center Hospital as \"Study on the validity of measurement method of radiotracer distribution in the cerebrospinal fluid region\" (Project No. 2022002, approved on June 6, 2022). 2 Materials and Methods 2.1 Phantom Test 2.1.1 Phantom Structure and Volume of Interest (VOI) Setting A cylindrical structure simulating the ventricles was placed at the center of the phantom to represent the ventricle (V) region. The phantom was filled with [ 18 F] fluorodeoxyglucose (FDG) solution to simulate brain parenchyma and defined as the brain (B) region. The B region had three segments with different outer diameters spaced at 50-mm intervals (Fig. 1 ). Based on the computed tomography (CT) images, VOIs were created for B1, B2, B3, V1, V2, and V3 corresponding to the three outer diameters, and radioactivity was measured. 2.1.2 PET Acquisition and Image Reconstruction PET acquisition was performed using a Biograph mCT (Siemens Healthineers, Erlangen, Germany) at three radioactivity levels: 14.6, 29.3, and 58.3 MBq. Images were reconstructed using filtered back projection with time-of-flight and a Gaussian smoothing filter (full width at half maximum: 4 mm). The matrix size was 400, pixel size 2.04 mm, and slice thickness 2.03 mm. PET images were corrected for normalization, dead time, attenuation, and scatter. 2.1.3 Resolution Calculation The spatial resolution of the PET image (R [mm]) was calculated as 6 mm, using the intrinsic resolution of the Biograph mCT scanner (R 1 = 4.4 mm) and the smoothing filter (R 2 = 4 mm), based on Eq. 1 [ 3 ]: \\(\\:R=\\sqrt{{{R}_{1}}^{2}+{{R}_{2}}^{2}}\\) (Eq. 1) 2.1.4 PVE Correction Using the GTM Method Using PMOD3.5 (PMOD Technologies, Zurich, Switzerland), PVE correction was performed with the VOI-based GTM method described by Rousset et al. [ 4 ] to obtain the corrected radioactivity (GTM_v) in the V region. 2.1.5 Spillover Correction Using the Subtraction Method The image acquired at 14.6 MBq was used as the reference to calculate the spillover correction factor (F), and the 29.3 and 58.3 MBq images were used for validation. A 6-mm band surrounding the V region was defined as the surrounding (S) region, representing the spillover source in the V region (Fig. 1 ). The correction factor F was calculated as the ratio of radioactivity in the V region (v ref ) to that in the S region (s ref ) in the reference image (Eq. 2). The corrected value in the V region (cor.v) was obtained using Eq. 3: \\(\\:F={v}_{ref}/{s}_{ref}\\) (Eq. 2) \\(\\:cor.v=v-F\\times\\:s\\) (Eq. 3) 2.1.6 Numerical Analysis The mean and standard deviation of measured radioactivity at each VOI were calculated for the three radioactivity levels. The relationships among included radioactivity, GTM_v, and cor.v were analyzed. 2.2 Application of the Subtraction Method in Brain Imaging of Healthy Subjects 2.2.1 Participant Information and Ethical Approval Data were obtained from an anonymized image database of healthy individuals previously collected at the Nagoya City Rehabilitation Center. The data were approved for secondary use under the following protocols: \"Construction of a normal database for examination using a new PET camera (mCT)\" (Ethical Review Approval: March 12, 2014) and \"Elucidation of the mechanism of spinal fluid production and absorption from the viewpoint of water turnover and its application to the diagnosis of noninvasive hydrocephalus\" (Ethical Review Approval: May 27, 2014). This was a retrospective observational study. The dynamic PET images analyzed included FDG, [ 18 F]fluorodopa (FDOPA), and [ 11 C]raclopride (RAC) from one 42-year-old man, and [ 15 O]H 2 O (H 2 O) from one 54-year-old man. Corresponding 3D-T1 and 3D-T2 magnetic resonance imaging (MRI) images were also used. 2.2.2 Imaging and Reconstruction Conditions PET data collected 15 min after intravenous administration were used. Image reconstruction followed the same parameters as those in the phantom study. For FDG, FDOPA, and RAC, the frame durations were: 5 s × 8 frames, 10 s × 2, 15 s × 4, 20 s × 3, 30 s × 6, and 60 s × 14. For H 2 O, these were: 5 s × 8, 10 s × 2, 15 s × 4, 20 s × 3, 30 s × 4, 60 s × 3, 120 s × 1, and 300 s × 1. 2.2.3 Image Analysis PET and MRI image alignment was performed using PMOD3.5 A neurosurgeon manually defined VOIs on the MRI images for three CSF regions, lateral ventricles (LV), Sylvian fissure (FS), and prepontine cistern (PPC), along with 6-mm surrounding regions (Fig. 2 ). 2.2.4 Spillover Correction Using the Subtraction Method The time-activity curves (TACs) for the LV, FS, and PPC were labeled as CSF(t), whereas those of their surrounding regions as S(t) (Fig. 2 ). Corrected radioactivity, cor.CSF(t), was calculated using Eq. 4, with the correction factor F determined at the time point when CSF(t)/S(t) was at its minimum (Eq. 5). The search interval for F was between 60 and 900 s, as radioactivity fluctuated significantly immediately after administration. \\(\\:\\text{c}\\text{o}\\text{r}.\\text{C}\\text{S}\\text{F}\\left(\\text{t}\\right)=CSF\\left(t\\right)-F\\times\\:S\\left(t\\right)\\) (Eq. 4) \\(\\:\\text{F}=\\raisebox{1ex}{$CSF\\left(t\\right)$}\\!\\left/\\:\\!\\raisebox{-1ex}{$S\\left(t\\right)$}\\right.\\) (Eq. 5) 2.2.5 Numerical Analysis TACs for CSF(t), S(t), and cor.CSF(t) were plotted for the LV, FS, and PPC across the four radiotracers. 3 Results 3.1 Phantom Test The measured radioactivity levels in the B, V, and S regions increased linearly with the included radioactivity, showing a strong correlation (R 2 = 0.99). The GTM_v values approached zero, indicating effective correction. The correction factor F calculated from the reference image was 0.22 ± 0.01. The cor.v in the validation images closely approximated those from the GTM method. Results are summarized in Table 1 . Table 1 Radioactivity measurements in each VOI from the phantom study. Inclusion Activity (MBq) Average and S.D. of radioactivity (kBq/mL) B V S GTM_v cor.v 14.6 7.98 ± 0.32 1.56 ± 0.06 7.2 ± 0.1 -0.36 ± 2.13 - 29.32 16.04 ± 0.47 3.23 ± 0.14 14.2 ± 0.23 -0.41 ± 0.21 0.16 ± 0.14 58.29 32.95 ± 0.84 6.42 ± 0.32 29.31 ± 0.44 -1.57 ± 1.09 0.07 ± 0.23 Measurements are expressed as the mean ± standard deviation (SD) in each volume of interest (VOI) from the phantom study at different inclusion activity levels. B, values for brain region; V, values for ventricular region; S, values for surrounding region; GTM_v, corrected values using the geometric transfer matrix method; cor.v, corrected values using the subtraction method. 3.2 Application in Brain Imaging of Healthy Subjects The TACs for CSF(t), S(t), and cor.CSF(t) for the four radiotracers are shown in Fig. 3 . For all radiotracers, CSF(t) increased immediately after tracer injection, which then changed gradually with time. FDG, FDOPA, and RAC showed similar trends between S(t) and CSF(t), whereas H 2 O demonstrated a slower washout pattern in CSF(t) compared with that in S(t). After correction, corCSF (t) was near zero for FDG, FDOPA, and RAC but showed a slight increase for H 2 O. 4 Discussion In this study, we propose a simple subtraction method to reduce spillover artifacts in PET measurements of CSF regions, specifically the LV, FS, and PPC. In the phantom study, although the CSF region ideally had zero concentration, measured values were elevated because of spillover from surrounding radioactivity. The linear relationship among B, V, and S regions and the inclusion radioactivity suggested that the artifact component can be estimated using a single coefficient. For this phantom, F = 0.21 provided good correction; however, an appropriate F should be determined depending on the size and shape of the CSF region. Based on the linear relationship observed in the phantom study, we applied the subtraction method to clinical brain PET images. CSF(t) values increased immediately after radiotracer injection, and for FDG, FDOPA, and RAC, the time-activity curves showed behavior similar to those in the surrounding region S(t). As these radiotracers are not known to enter or accumulate in the CSF within 15 min, the observed radioactivity in the CSF region was interpreted as resulting primarily from spillover artifacts. In contrast, H 2 O exhibited a slower washout in CSF(t), and its behavior differed from that of S(t), indicating a distinct pattern. The radiotracer distribution changed over time; for FDG, DOPA, and RAC, the contrast between CSF(t) and S(t) remained relatively constant, suggesting that the spillover correction factor F reached a plateau. However, for H 2 O, the correction factor F showed a gradual increase, suggesting not only spillover but also actual tracer influx into the CSF. This aligned with previous reports indicating that 90% of intravenously administered H 2 O enters brain tissue in the first pass [ 5 ] and may subsequently diffuse into the CSF compartment during the short 15-min imaging window. Further studies are warranted to clarify this behavior. Accurate delineation of the CSF region is challenging because of the close proximity of blood vessels, nerves, and the choroid plexus. Consequently, applying the GTM method using MRI-T1 images for VOI definition is often difficult. Ibaraki et al. also noted the challenges associated with separating small adjacent tissues with distinct functions when setting VOIs [ 6 ]. Although the subtraction method does not constitute a complete PVE correction technique and is less comprehensive than the GTM method, it offers practical advantages. Specifically, it avoids the need for complex VOI segmentation and allows for spillover correction using a straightforward calculation, making it useful for clinical applications. In this study, we included one case for each radiotracer; however, more cases must be examined to determine the dynamics of the tracer in CSF. In addition, assessing the reproducibility of the correction results using manual VOI settings is necessary. In conclusion, spillover artifacts affecting PET measurements in the CSF region can be effectively corrected using a simple subtraction method, offering a practical alternative when conventional GTM-based corrections are difficult to implement. Declarations Funding: Social Welfare Corporation, Nagoya City Rehabilitation Agency, Rehabilitation Research Fund References Fukuda N, Fukuda M. PET and MRS positron nuclear medicine and biological nuclear magnetic resonance spectroscopy. Volume 1. Tokyo: IPC; 1990. pp. 36–9. (in Japanese). Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932–45. https://doi.org/10.2967/jnumed.106.035774 . Koichi O. Basics of nuclear medicine technology basics of collimators in Gammma cameras (in Japanese). Nucl Med Clin. 2014;47:9–12. Rousset OG, Ma Y, Evans AC. Correction for partial volume effects in PET: principle and validation. J Nucl Med. 1998;39:904–11. Eichling JO, Raichle ME, Grubb RL Jr, Ter-Pogossian MM. Evidence of the limitations of water as a freely diffusible tracer in brain of the rhesus monkey. Circ Res. 1974;35:358–64. https://doi.org/10.1161/01.res.35.3.358 . Ibaraki M, Matsubara K, Shinohara Y, Shidahara M, Sato K, Yamamoto H, et al. Brain partial volume correction with point spreading function reconstruction in high-resolution digital PET: comparison with an MR-based method in FDG imaging. Ann Nucl Med. 2022;36:717–27. https://doi.org/10.1007/s12149-022-01753-5 . Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6415718\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":443536395,\"identity\":\"3ba41cfe-3c7b-40cd-af63-86c90342c324\",\"order_by\":0,\"name\":\"Emi Hayashi\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYFACxsYDCQwSdmzyhw8AeRIyxGhpAGqxSeaXYEsAaeEhyh6g6WmMM2fwGIA4hLXwix1uOPBwx2Fmg9s9n1/dqLHgYWA/fHQDPi2SsxMbDiSeOcxncOfsNuucY0CH8aSl3cCnxeA2SEsb0JYDuduMc9iAWiR4zPBqsYdqYdxwIOeZcc4/IrQYSIO1gLyfw/w4t40ILRIQW4CBzHPMjDm3T4KHjZBf+GenP3z4sw0YlezNjz/nfKuT42c/fAyvFmTAJgEmiVUOAswfSFE9CkbBKBgFIwcAAAZWTobVhYbpAAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0009-0004-6963-3751\",\"institution\":\"Nagoya City Rehabilitation Center\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Emi\",\"middleName\":\"\",\"lastName\":\"Hayashi\",\"suffix\":\"\"},{\"id\":443536396,\"identity\":\"fef990b5-08f9-4623-b5bb-58649613bcb1\",\"order_by\":1,\"name\":\"Shin Hibino\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nagoya City Rehabilitation Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shin\",\"middleName\":\"\",\"lastName\":\"Hibino\",\"suffix\":\"\"},{\"id\":443536397,\"identity\":\"57efd0ad-d18d-40f5-b11e-7ef7ebe7bb19\",\"order_by\":2,\"name\":\"Mitsuhito Mase\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"nagoya City University Graduate School of Medhicine\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mitsuhito\",\"middleName\":\"\",\"lastName\":\"Mase\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-04-10 02:40:40\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6415718/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6415718/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":82081253,\"identity\":\"0a631558-f9aa-4b15-84a9-204eda1ff06c\",\"added_by\":\"auto\",\"created_at\":\"2025-05-06 14:30:22\",\"extension\":\"jpeg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":524200,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eStructure of the Cylindrical Phantom Simulating Brain Ventricles.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe structural schematic of the phantom (coronal section) is shown on the left, and representative PET images are shown on the right. Brain regions are labeled as B1, B2, and B3; ventricular regions as V1, V2, and V3; and surrounding regions of the ventricles as S1, S2, and S3. The brain regions (B) are structures with outer diameters differing by 50 mm intervals.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6415718/v1/eb63dfc23f14eebc6f17fe20.jpeg\"},{\"id\":82081254,\"identity\":\"1aab5495-c496-4d0f-b898-c432bceedcd3\",\"added_by\":\"auto\",\"created_at\":\"2025-05-06 14:30:22\",\"extension\":\"jpeg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":331729,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eExamples of VOI in the CSF Region and Surrounding Areas.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eVOIs for the CSF regions (upper row) and their corresponding surrounding regions (lower row) are shown on MRI-T1 images from a healthy individual. The LV is indicated in blue, the FS in orange, and the PPC in pink.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6415718/v1/2e053fd64bf7382f614a4e72.jpeg\"},{\"id\":82082207,\"identity\":\"32b3f6c0-89e1-4e93-bb69-18cf09937ca0\",\"added_by\":\"auto\",\"created_at\":\"2025-05-06 14:38:22\",\"extension\":\"jpeg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":534599,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eTACs of CSV(t), S(t), and cor.CSF(t) for Healthy Individuals using Four Radiotracers.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe left and right columns show results for the LV, FS, and PPC, respectively. Closed circles represent CSF(t), dotted lines represent S(t), and open circles represent cor.CSF(t).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6415718/v1/45844580e218e12c46db66e2.jpeg\"},{\"id\":83434488,\"identity\":\"d785be78-1f9e-4e40-ad76-60c582b8e89a\",\"added_by\":\"auto\",\"created_at\":\"2025-05-26 08:11:21\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2104365,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6415718/v1/032d3d77-e0a3-4e21-85be-4412b602eeaf.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Validity of a Simple Spillover Correction for Positron Emission Tomography Measurements in the Cerebrospinal Fluid Region\",\"fulltext\":[{\"header\":\"1 Introduction\",\"content\":\"\\u003cp\\u003eWhen measuring radioactivity in positron emission tomography (PET) images, care must be taken to avoid overestimation (spill-in) and underestimation (spill-out) because of partial volume effects (PVE) [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. To minimize these effects, the measurement area should be at least three times larger than the spatial resolution [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. However, in actual clinical PET examinations, small regions are often evaluated. The cerebrospinal fluid (CSF) region generally shows low radioactivity, whereas the surrounding regions exhibit higher intensity. Therefore, overestimation due to spill-in, referred to as the spillover artifact here, must be considered when measuring CSF radioactivity. To date, no reports have specifically addressed PVE correction methods focused on the CSF region.\\u003c/p\\u003e \\u003cp\\u003eThe aim of this study was to propose a simple method to correct for spillover artifacts in PET-derived radioactivity measurements in the CSF region and to evaluate the validity of this method compared with the widely used PVE correction using the geometric transfer matrix (GTM) method.\\u003c/p\\u003e \\u003cp\\u003eThis study was approved by the Ethics Committee of the Nagoya City Rehabilitation Center Hospital as \\\"Study on the validity of measurement method of radiotracer distribution in the cerebrospinal fluid region\\\" (Project No. 2022002, approved on June 6, 2022).\\u003c/p\\u003e\"},{\"header\":\"2 Materials and Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.1 Phantom Test\\u003c/h2\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.1 Phantom Structure and Volume of Interest (VOI) Setting\\u003c/h2\\u003e \\u003cp\\u003eA cylindrical structure simulating the ventricles was placed at the center of the phantom to represent the ventricle (V) region. The phantom was filled with [\\u003csup\\u003e18\\u003c/sup\\u003eF] fluorodeoxyglucose (FDG) solution to simulate brain parenchyma and defined as the brain (B) region. The B region had three segments with different outer diameters spaced at 50-mm intervals (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Based on the computed tomography (CT) images, VOIs were created for B1, B2, B3, V1, V2, and V3 corresponding to the three outer diameters, and radioactivity was measured.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.2 PET Acquisition and Image Reconstruction\\u003c/h2\\u003e \\u003cp\\u003ePET acquisition was performed using a Biograph mCT (Siemens Healthineers, Erlangen, Germany) at three radioactivity levels: 14.6, 29.3, and 58.3 MBq. Images were reconstructed using filtered back projection with time-of-flight and a Gaussian smoothing filter (full width at half maximum: 4 mm). The matrix size was 400, pixel size 2.04 mm, and slice thickness 2.03 mm. PET images were corrected for normalization, dead time, attenuation, and scatter.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.3 Resolution Calculation\\u003c/h2\\u003e \\u003cp\\u003eThe spatial resolution of the PET image (R [mm]) was calculated as 6 mm, using the intrinsic resolution of the Biograph mCT scanner (R\\u003csub\\u003e1\\u003c/sub\\u003e\\u0026thinsp;=\\u0026thinsp;4.4 mm) and the smoothing filter (R\\u003csub\\u003e2\\u003c/sub\\u003e\\u0026thinsp;=\\u0026thinsp;4 mm), based on Eq.\\u0026nbsp;1 [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]:\\u003c/p\\u003e \\u003cp\\u003e \\u003cspan class=\\\"InlineEquation\\\"\\u003e \\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\:R=\\\\sqrt{{{R}_{1}}^{2}+{{R}_{2}}^{2}}\\\\)\\u003c/span\\u003e \\u003c/span\\u003e (Eq.\\u0026nbsp;1)\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.4 PVE Correction Using the GTM Method\\u003c/h2\\u003e \\u003cp\\u003eUsing PMOD3.5 (PMOD Technologies, Zurich, Switzerland), PVE correction was performed with the VOI-based GTM method described by Rousset et al. [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e] to obtain the corrected radioactivity (GTM_v) in the V region.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.5 Spillover Correction Using the Subtraction Method\\u003c/h2\\u003e \\u003cp\\u003eThe image acquired at 14.6 MBq was used as the reference to calculate the spillover correction factor (F), and the 29.3 and 58.3 MBq images were used for validation. A 6-mm band surrounding the V region was defined as the surrounding (S) region, representing the spillover source in the V region (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The correction factor F was calculated as the ratio of radioactivity in the V region (v\\u003csub\\u003eref\\u003c/sub\\u003e) to that in the S region (s\\u003csub\\u003eref\\u003c/sub\\u003e) in the reference image (Eq.\\u0026nbsp;2). The corrected value in the V region (cor.v) was obtained using Eq.\\u0026nbsp;3:\\u003cdiv class=\\\"BlockQuote\\\"\\u003e\\u003cp\\u003e \\u003cspan class=\\\"InlineEquation\\\"\\u003e \\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\:F={v}_{ref}/{s}_{ref}\\\\)\\u003c/span\\u003e \\u003c/span\\u003e (Eq.\\u0026nbsp;2)\\u003c/p\\u003e\\u003cp\\u003e \\u003cspan class=\\\"InlineEquation\\\"\\u003e \\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\:cor.v=v-F\\\\times\\\\:s\\\\)\\u003c/span\\u003e \\u003c/span\\u003e (Eq.\\u0026nbsp;3)\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec9\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.1.6 Numerical Analysis\\u003c/h2\\u003e \\u003cp\\u003eThe mean and standard deviation of measured radioactivity at each VOI were calculated for the three radioactivity levels. The relationships among included radioactivity, GTM_v, and cor.v were analyzed.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec10\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e2.2 Application of the Subtraction Method in Brain Imaging of Healthy Subjects\\u003c/h2\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.2.1 Participant Information and Ethical Approval\\u003c/h2\\u003e \\u003cp\\u003eData were obtained from an anonymized image database of healthy individuals previously collected at the Nagoya City Rehabilitation Center. The data were approved for secondary use under the following protocols: \\\"Construction of a normal database for examination using a new PET camera (mCT)\\\" (Ethical Review Approval: March 12, 2014) and \\\"Elucidation of the mechanism of spinal fluid production and absorption from the viewpoint of water turnover and its application to the diagnosis of noninvasive hydrocephalus\\\" (Ethical Review Approval: May 27, 2014). This was a retrospective observational study. The dynamic PET images analyzed included FDG, [\\u003csup\\u003e18\\u003c/sup\\u003eF]fluorodopa (FDOPA), and [\\u003csup\\u003e11\\u003c/sup\\u003eC]raclopride (RAC) from one 42-year-old man, and [\\u003csup\\u003e15\\u003c/sup\\u003eO]H\\u003csub\\u003e2\\u003c/sub\\u003eO (H\\u003csub\\u003e2\\u003c/sub\\u003eO) from one 54-year-old man. Corresponding 3D-T1 and 3D-T2 magnetic resonance imaging (MRI) images were also used.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.2.2 Imaging and Reconstruction Conditions\\u003c/h2\\u003e \\u003cp\\u003ePET data collected 15 min after intravenous administration were used. Image reconstruction followed the same parameters as those in the phantom study. For FDG, FDOPA, and RAC, the frame durations were: 5 s \\u0026times; 8 frames, 10 s \\u0026times; 2, 15 s \\u0026times; 4, 20 s \\u0026times; 3, 30 s \\u0026times; 6, and 60 s \\u0026times; 14. For H\\u003csub\\u003e2\\u003c/sub\\u003eO, these were: 5 s \\u0026times; 8, 10 s \\u0026times; 2, 15 s \\u0026times; 4, 20 s \\u0026times; 3, 30 s \\u0026times; 4, 60 s \\u0026times; 3, 120 s \\u0026times; 1, and 300 s \\u0026times; 1.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec13\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.2.3 Image Analysis\\u003c/h2\\u003e \\u003cp\\u003ePET and MRI image alignment was performed using PMOD3.5 A neurosurgeon manually defined VOIs on the MRI images for three CSF regions, lateral ventricles (LV), Sylvian fissure (FS), and prepontine cistern (PPC), along with 6-mm surrounding regions (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec14\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.2.4 Spillover Correction Using the Subtraction Method\\u003c/h2\\u003e \\u003cp\\u003eThe time-activity curves (TACs) for the LV, FS, and PPC were labeled as CSF(t), whereas those of their surrounding regions as S(t) (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Corrected radioactivity, cor.CSF(t), was calculated using Eq.\\u0026nbsp;4, with the correction factor F determined at the time point when CSF(t)/S(t) was at its minimum (Eq.\\u0026nbsp;5). The search interval for F was between 60 and 900 s, as radioactivity fluctuated significantly immediately after administration.\\u003c/p\\u003e \\u003cp\\u003e \\u003cspan class=\\\"InlineEquation\\\"\\u003e \\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\:\\\\text{c}\\\\text{o}\\\\text{r}.\\\\text{C}\\\\text{S}\\\\text{F}\\\\left(\\\\text{t}\\\\right)=CSF\\\\left(t\\\\right)-F\\\\times\\\\:S\\\\left(t\\\\right)\\\\)\\u003c/span\\u003e \\u003c/span\\u003e (Eq.\\u0026nbsp;4)\\u003c/p\\u003e \\u003cp\\u003e \\u003cspan class=\\\"InlineEquation\\\"\\u003e \\u003cspan class=\\\"mathinline\\\"\\u003e\\\\(\\\\:\\\\text{F}=\\\\raisebox{1ex}{$CSF\\\\left(t\\\\right)$}\\\\!\\\\left/\\\\:\\\\!\\\\raisebox{-1ex}{$S\\\\left(t\\\\right)$}\\\\right.\\\\)\\u003c/span\\u003e \\u003c/span\\u003e (Eq.\\u0026nbsp;5)\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec15\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003e2.2.5 Numerical Analysis\\u003c/h2\\u003e \\u003cp\\u003eTACs for CSF(t), S(t), and cor.CSF(t) were plotted for the LV, FS, and PPC across the four radiotracers.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e\"},{\"header\":\"3 Results\",\"content\":\"\\u003cdiv id=\\\"Sec17\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e3.1 Phantom Test\\u003c/h2\\u003e \\u003cp\\u003eThe measured radioactivity levels in the B, V, and S regions increased linearly with the included radioactivity, showing a strong correlation (R\\u003csup\\u003e2\\u003c/sup\\u003e\\u0026thinsp;=\\u0026thinsp;0.99). The GTM_v values approached zero, indicating effective correction. The correction factor F calculated from the reference image was 0.22\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.01. The cor.v in the validation images closely approximated those from the GTM method. Results are summarized in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eRadioactivity measurements in each VOI from the phantom study.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"6\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eInclusion Activity (MBq)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c6\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eAverage and S.D. of radioactivity (kBq/mL)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eB\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eV\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eS\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eGTM_v\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003ecor.v\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e14.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e7.98\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.56\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.06\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e7.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-0.36\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.13\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e29.32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e16.04\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.47\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.23\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.14\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e14.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.23\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-0.41\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.21\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.16\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.14\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e58.29\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e32.95\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.84\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6.42\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e29.31\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.44\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-1.57\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.09\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0.07\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.23\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eMeasurements are expressed as the mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) in each volume of interest (VOI) from the phantom study at different inclusion activity levels.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"6\\\"\\u003eB, values for brain region; V, values for ventricular region; S, values for surrounding region; GTM_v, corrected values using the geometric transfer matrix method; cor.v, corrected values using the subtraction method.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec18\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003e3.2 Application in Brain Imaging of Healthy Subjects\\u003c/h2\\u003e \\u003cp\\u003eThe TACs for CSF(t), S(t), and cor.CSF(t) for the four radiotracers are shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e. For all radiotracers, CSF(t) increased immediately after tracer injection, which then changed gradually with time. FDG, FDOPA, and RAC showed similar trends between S(t) and CSF(t), whereas H\\u003csub\\u003e2\\u003c/sub\\u003eO demonstrated a slower washout pattern in CSF(t) compared with that in S(t). After correction, corCSF (t) was near zero for FDG, FDOPA, and RAC but showed a slight increase for H\\u003csub\\u003e2\\u003c/sub\\u003eO.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"4 Discussion\",\"content\":\"\\u003cp\\u003eIn this study, we propose a simple subtraction method to reduce spillover artifacts in PET measurements of CSF regions, specifically the LV, FS, and PPC. In the phantom study, although the CSF region ideally had zero concentration, measured values were elevated because of spillover from surrounding radioactivity. The linear relationship among B, V, and S regions and the inclusion radioactivity suggested that the artifact component can be estimated using a single coefficient. For this phantom, F\\u0026thinsp;=\\u0026thinsp;0.21 provided good correction; however, an appropriate F should be determined depending on the size and shape of the CSF region.\\u003c/p\\u003e \\u003cp\\u003eBased on the linear relationship observed in the phantom study, we applied the subtraction method to clinical brain PET images. CSF(t) values increased immediately after radiotracer injection, and for FDG, FDOPA, and RAC, the time-activity curves showed behavior similar to those in the surrounding region S(t). As these radiotracers are not known to enter or accumulate in the CSF within 15 min, the observed radioactivity in the CSF region was interpreted as resulting primarily from spillover artifacts. In contrast, H\\u003csub\\u003e2\\u003c/sub\\u003eO exhibited a slower washout in CSF(t), and its behavior differed from that of S(t), indicating a distinct pattern. The radiotracer distribution changed over time; for FDG, DOPA, and RAC, the contrast between CSF(t) and S(t) remained relatively constant, suggesting that the spillover correction factor F reached a plateau. However, for H\\u003csub\\u003e2\\u003c/sub\\u003eO, the correction factor F showed a gradual increase, suggesting not only spillover but also actual tracer influx into the CSF. This aligned with previous reports indicating that 90% of intravenously administered H\\u003csub\\u003e2\\u003c/sub\\u003eO enters brain tissue in the first pass [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e] and may subsequently diffuse into the CSF compartment during the short 15-min imaging window. Further studies are warranted to clarify this behavior.\\u003c/p\\u003e \\u003cp\\u003eAccurate delineation of the CSF region is challenging because of the close proximity of blood vessels, nerves, and the choroid plexus. Consequently, applying the GTM method using MRI-T1 images for VOI definition is often difficult. Ibaraki et al. also noted the challenges associated with separating small adjacent tissues with distinct functions when setting VOIs [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Although the subtraction method does not constitute a complete PVE correction technique and is less comprehensive than the GTM method, it offers practical advantages. Specifically, it avoids the need for complex VOI segmentation and allows for spillover correction using a straightforward calculation, making it useful for clinical applications. In this study, we included one case for each radiotracer; however, more cases must be examined to determine the dynamics of the tracer in CSF. In addition, assessing the reproducibility of the correction results using manual VOI settings is necessary.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, spillover artifacts affecting PET measurements in the CSF region can be effectively corrected using a simple subtraction method, offering a practical alternative when conventional GTM-based corrections are difficult to implement.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eFunding:\\u003c/h2\\u003e \\u003cp\\u003eSocial Welfare Corporation, Nagoya City Rehabilitation Agency, Rehabilitation Research Fund\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eFukuda N, Fukuda M. PET and MRS positron nuclear medicine and biological nuclear magnetic resonance spectroscopy. Volume 1. Tokyo: IPC; 1990. pp. 36\\u0026ndash;9. (in Japanese).\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSoret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932\\u0026ndash;45. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.2967/jnumed.106.035774\\u003c/span\\u003e\\u003cspan address=\\\"10.2967/jnumed.106.035774\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKoichi O. Basics of nuclear medicine technology basics of collimators in Gammma cameras (in Japanese). Nucl Med Clin. 2014;47:9\\u0026ndash;12.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRousset OG, Ma Y, Evans AC. Correction for partial volume effects in PET: principle and validation. J Nucl Med. 1998;39:904\\u0026ndash;11.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEichling JO, Raichle ME, Grubb RL Jr, Ter-Pogossian MM. Evidence of the limitations of water as a freely diffusible tracer in brain of the rhesus monkey. Circ Res. 1974;35:358\\u0026ndash;64. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1161/01.res.35.3.358\\u003c/span\\u003e\\u003cspan address=\\\"10.1161/01.res.35.3.358\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eIbaraki M, Matsubara K, Shinohara Y, Shidahara M, Sato K, Yamamoto H, et al. Brain partial volume correction with point spreading function reconstruction in high-resolution digital PET: comparison with an MR-based method in FDG imaging. Ann Nucl Med. 2022;36:717\\u0026ndash;27. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1007/s12149-022-01753-5\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s12149-022-01753-5\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Spillover correction, PET, CSF, Partial volume correction, [15O]H2O\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6415718/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6415718/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eObjective\\u003c/h2\\u003e \\u003cp\\u003ePositron emission tomography (PET) measurements in the cerebrospinal fluid (CSF) region may be overestimated because of spillover artifacts from surrounding radioactivity. In this study, we proposed a simple spillover correction method (the subtraction method) and evaluated its validity.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eA cylindrical phantom simulating brain ventricles was used to compare the subtraction method with a partial volume effect (PVE) correction method, specifically the geometric transfer matrix (GTM) approach. The subtraction method was then applied to dynamic PET images using three radiotracers, [\\u003csup\\u003e18\\u003c/sup\\u003eF]fluorodeoxyglucose (FDG), [\\u003csup\\u003e18\\u003c/sup\\u003eF]fluorodopa (FDOPA), and [\\u003csup\\u003e11\\u003c/sup\\u003eC]raclopride (RAC), in one healthy individual, and [\\u003csup\\u003e15\\u003c/sup\\u003eO]H\\u003csub\\u003e2\\u003c/sub\\u003eO (H\\u003csub\\u003e2\\u003c/sub\\u003eO) in another case. None of these tracers were expected to diffuse into the CSF within a short timeframe. The effects of spillover correction on CSF measurements were assessed.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eBoth the subtraction and GTM methods effectively reduced spillover artifacts in the phantom study. In dynamic PET images, all four radiotracers showed an immediate increase in radioactivity within the CSF region following intravenous administration. FDG, FDOPA, and RAC demonstrated similar radioactivity trends in the CSF and surrounding regions, whereas H\\u003csub\\u003e2\\u003c/sub\\u003eO showed a distinct pattern. After spillover correction, time-activity curves for FDG, FDOPA, and RAC approached near-zero levels in the CSF, whereas H\\u003csub\\u003e2\\u003c/sub\\u003eO continued to show increasing activity over time.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eWe developed a subtraction method to correct PET signal overestimation in the CSF region attributed to spillover effects. This approach effectively reduced artifacts, comparable to the GTM method, and offers the advantages of simpler volume-of-interest (VOI) settings and straightforward calculation procedures.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Validity of a Simple Spillover Correction for Positron Emission Tomography Measurements in the Cerebrospinal Fluid Region\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-05-06 14:30:18\",\"doi\":\"10.21203/rs.3.rs-6415718/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"87d1ef32-5dd3-4500-9aa5-8db2849d1e02\",\"owner\":[],\"postedDate\":\"May 6th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-05-26T08:03:13+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-05-06 14:30:18\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6415718\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6415718\",\"identity\":\"rs-6415718\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}