The use of pyrophosphate scintigraphy to measure the heart-to-contralateral lung ratio in the presence of rib fractures overlapping the heart

The use of pyrophosphate scintigraphy to measure the heart-to-contralateral lung ratio in the presence of rib fractures overlapping the heart | 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 The use of pyrophosphate scintigraphy to measure the heart-to-contralateral lung ratio in the presence of rib fractures overlapping the heart JUMPEI SUYAMA, Chieko Takakuwa, Muneyuki Kawada, Yuya Shirakawa, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4556923/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: Tc-99m-pyrophosphate has been used to evaluate amyloid transthyretin (ATTR) cardiac amyloidosis. Quantitative evaluation is widely performed by calculating the heart-to-contralateral lung (H/CL) ratio, but bone lesions may reduce measurement accuracy. We investigated the accuracy of the PYP-ROI software, developed by our group, in addressing the errors caused by bone lesions when measuring the H/CL ratio. Methods: This retrospective study comprised 17 patients (mean age: 70.7 ± 13.9 years; male:female ratio 13:4) who underwent pyrophosphate scintigraphy to diagnose cardiac amyloidosis during March 2021–November 2021 and in whom cardiac amyloidosis was excluded clinically. None of the participants had rib fractures or other bone lesions. Simulated rib fractures were created, and the H/CL ratio was determined for various pathologies. The differences between these values and the H/CL ratios obtained from the original images were compared. Results: Based on our findings, which confirmed the software’s utility, we recommend the following steps for imaging analysis. First, the accumulation in the fracture should be eliminated, by manual calculations in the absence of a removal function. Second, compensation for the removed part should be calculated using the average count of the surrounding area. Third, if the fracture accumulation is weaker than the sternal accumulation, the fracture should be included in the measurement. Fourth, if fracture uptake is clearly higher than sternal uptake, the impact is significant. Conclusions: This study supports the utility of removing or compensating for the accumulation in rib fractures using PYP-ROI software. However, verification in larger clinical studies is required. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Recently, cardiac amyloidosis has attracted increasing interest as a cause of chronic heart failure [ 1 ]. Cardiac amyloidosis is traditionally classified into the amyloid light chain (AL) and amyloid transthyretin (ATTR) types. Tc-99m-pyrophosphate (PYP) is traditionally used for bone scintigraphy preparation, but is also useful for diagnosing myocardial infarction. However, it also accumulates in ATTR cardiac amyloidosis lesions and is useful for ATTR amyloidosis diagnosis and differentiation of ATTR and AL amyloidosis [ 2 ]. In daily clinical practice, quantitative evaluation using the heart-to-contralateral lung (H/CL) ratio, which measures the ratio of heart uptake to contralateral lower lung field uptake in planar images at 1 and 3 h after intravenous nuclide injection, has been widely used to evaluate ATTR amyloidosis. Its utility has been described in the 2020 Cardiac Amyloidosis Clinical Practice Guidelines (Japanese Circulation Society) [ 3 ]. Currently, dedicated software for performing this measurement is not widely available, and the measurement results cannot be easily displayed as images. Accordingly, our hospital developed its own analysis software for use as an auxiliary diagnostic tool and has been applying it in clinical practice since August 2021. However, given that certain nuclides accumulate in bones, if a bone lesion, such as a fracture, exists in the area that corresponds to the heart, high accumulation will appear, which may cause errors in the measured values. Our software was thus designed to remove abnormal accumulations in bones and to compensate for the removed area by using the average value of the surrounding accumulation in the heart (hereinafter referred to as the bone lesion removal function). When a fracture occurs in ribs that overlap the heart, the H/CL ratio is assumed to be significantly affected. This effect can theoretically be reduced by setting a region of interest (ROI) to avoid fractures. However, the effectiveness of this approach has not been confirmed to date. Furthermore, the optimal method for establishing the ROI has not been described in the literature. The method involving the removal of rib-PYP accumulation from clinical images is considered to be the most effective; however, image processing to perform this is complicated when using the console of the gamma camera and has not been performed in routine clinical practice. We hypothesized that software developed to address this issue would provide accurate measurements of the H/CL ratio. This study thus investigated the accuracy of our software in addressing errors caused by bone lesions when measuring the H/CL ratio, including a clinical example to demonstrate the utility of the software in the clinical setting. MATERIALS AND METHODS Study population This retrospective study included all patients who underwent PYP scintigraphy to diagnose cardiac amyloidosis between March 2021 and November 2021, and in whom cardiac amyloidosis was excluded by clinical diagnosis. Seventeen participants (mean age: 70.7 ± 13.9 years; male:female ratio 13:4) met these criteria. All the participants experienced cardiac failure (Table 1). No participants had rib fractures or other bone lesions. Instead, the DRIP software (version 3.1.0.0; FUJIFILM Toyama Chemical Co., Ltd., Tokyo, Japan) was used to simulate rib fractures. Subsequently, the H/CL ratio was determined for various pathologies, including pseudofractures, and the difference between these values and the H/CL ratio obtained in the original image was evaluated statistically. In addition to the above participants, clinical data were also sourced from a 77-year-old male patient with ATTR amyloidosis. Ethical approval and informed consent This study was approved by our hospital’s institutional review board (approval number: R05-160), which waived the need for obtaining written informed consent from the participants due to the retrospective study design. The study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and all subsequent revisions. Imaging acquisition During dual-radionuclide myocardial scintigraphy acquisition, the doses of thallium and Tc-99m-PYP administered were 111 MBq and 370 MBq, respectively. Both isotopes were administered intravenously. The gamma camera used for acquisition was the GCA-9300R (Canon Medical Systems Corporation, Otawara, Japan). Images were acquired 3 hours following intravenous infusion. Analysis technique The software we developed, PYP-ROI version 1, was used on Microsoft Windows 10 and 11 (Microsoft Corporation, Redmond, WA, USA). The software was run independently, without any other software, in a Windows environment. Many facilities, including our hospital, perform simultaneous collection using two nuclides: myocardial infarction scintigraphy (Tc-99m-PYP) and myocardial perfusion scintigraphy (201-Tl-Chloride) [ 4 ]. When an ROI was set for the entire left ventricle in myocardial perfusion scintigraphy, the same ROI was set in the myocardial infarction scintigraphy image (ROI-Main). The same ROI was automatically set in the contralateral lung field (ROI-BKG). An example is shown in Fig. 1 . As shown in Fig. 2 , the fracture site was excluded from the ROI and was filled with pixels containing the average values of the surrounding pixels. The H/CL ratio was automatically measured using the following formula: H/CL ratio = (average ROI-Main count) / (average ROI-BKG count) The intensity of Tc-99m-PYP accumulation was generated as one of two possible conditions: a) the same as the average sternum count or b) twice the average sternum count (to replicate what is observed in the presence of an acute fracture). It is important to note that the accumulation in the sternum is high under normal physiological conditions, because the sternum is thick and physically close to the detector during the examination. Normal accumulation in the ribs was much lower than that in the sternum. However, the accumulation of lesions increased in the presence of rib fractures. As normal accumulation in the sternum is high, abnormal accumulation associated with rib fractures rarely exceeds it. Accordingly, we simulated the presence of a rib fracture with counts as high as those of the sternum, which could occur in clinical practice. In addition, we simulated the accumulation of counts associated with strong rib fractures, with counts twice as high as the rib count, suggesting the presence of severe acute fractures, which are not frequently encountered in clinical settings. The pseudo-rib fractures were generated as follows: First, an ROI was established as large as possible on the sternum. The average count of each pixel in the ROI was measured. Subsequently, a normal rib overlying the heart was selected, and an ROI of the same width as the rib was set at the junction of the ribs and cartilage (costochondral junction). Finally, an accumulation of the same average count (twice the average count) as the sternal accumulation was created within the ROI setting. The ROI was set at the costochondral junction to mimic the clinical reality closely, as this is the main site of rib fractures. Furthermore, a simulated anomalous uptake of radiopharmaceuticals with twice the intensity of the sternum was created to simulate a fresh fracture, which usually exhibits strong anomalous uptake. The abnormal accumulation of radiopharmaceuticals in fractures decreases with time after injury. A simulated abnormal accumulation of radiopharmaceuticals equivalent to that in the sternum was created to mimic a chronic fracture. In routine clinical practice, the abnormal accumulation in chronic fractures is typically high; therefore, we set the pseudo-accumulation equivalent to that of the sternum. Statistical analyses All statistical analyses, including t- tests, were performed using the IBM SPSS Statistics software (version 29.0; IBM Corp., Armonk, NY, USA). Statistical significance was set at p < 0.05. Independent data access and analysis J.S. and C.T. had full access to all data in the study and take responsibility for its integrity and data analysis. RESULTS Among the 17 cases in our study in which the DRIP software was used to create abnormal accumulations artificially in areas that overlapped with the heart, no rib fractures were present in the same area as the heart to result in the accumulation of Tc-99m-PYP. The mean number of lesions (rib fractures) in the sternum did not exceed the physiological rate. In the study participants, we examined changes in the H/CL ratio using the following four steps: First, when accumulation in the rib fractures was included (Fig. 2 ), significantly higher H/CL ratios were obtained than the original values at the fracture sites. Second, when the accumulation at the rib fractures was removed, either by using software (Fig. 3 a) or manually on a computer monitor (Fig. 3 b), the H/CL ratios obtained were not significantly different from the original values. Third, when the area corresponding to the rib fracture was removed and compensated by filling in the average accumulation value from the entire ROI (Fig. 4 a), the H/CL ratio of the original image and that of the ROI in the cardiac region was significantly different. Finally, when a small ROI was set to avoid rib fractures (Fig. 4 b), the H/CL ratio of the contralateral lung field in the original image differed significantly from that in the pseudo-lesions. Figure 5 shows the H/CL ratio in the original images of the 17 study participants before the pseudo-rib fractures were created, and the extent to which the H/CL ratio changed with each measurement method. The mean rate of change (standard deviation) in the H/CL ratio relative to the preceding step/image was as follows: avoided H/CL 1.0 = 5.16 ± 4.89 (p < 0.001), avoided H/CL 2.0 = 3.58 ± 5.20 (p = 0.005), artificial accumulation 1.0 = 1.69 ± 1.44 (p < 0.001), artificial accumulation 2.0 = 7.35 ± 1.44 (p < 0.001), removal 1.0 and 2.0 = -0.08 ± 1.46 (p = -0.393), and embed 1.0 and 2.0 = -0.54 ± 0.73 (p = 0.003). Imaging of the clinical case study is shown in Fig. 6 . This individual, a 77-year-old male with ATTR amyloidosis, underwent plain computed tomography imaging of the chest, which demonstrated post-fracture osteosclerotic changes in the left-sided anterior 7th and 8th ribs (Fig. 6 a, 6 b). The H/CL ratio, when calculated using the standard technique, was 1.776 (Fig. 6 c). When utilizing the software and the fracture uptake removal function, the H/CL ratio was lower, at 1.718 (Fig. 6 d). This value is considered the most reliable. When calculating the H/CL ratio by completely avoiding the fracture uptake region, the value was most deranged from the real value, at 1.814 (Fig. 6 e). DISCUSSION This study evaluated the accuracy of the PYP-ROI software in addressing errors caused by bone lesions when measuring the H/CL ratio in a study of 17 participants with simulated bone fractures, with further corroboration through a demonstration of the use of the software in a clinical case. Our findings confirmed the utility of the software. Based on our findings, we recommend the following order when proceeding with imaging analysis. First, the accumulation in the fracture should be eliminated. In the absence of a software-based removal function, manual calculations are required. Second, the compensation for the removed part should be calculated using the average count of the surrounding area. Third, if the fracture accumulation was weaker than the sternal accumulation, the fracture was included in the measurement. Fourth, if the fracture uptake was clearly higher than the sternal uptake, the impact was considered significant. Finally, in order to set the target ROI to avoid fractures, the ROI should be as large as possible to avoid poor reproducibility. It has previously been shown that, in patients with suspected ATTR amyloidosis, the quantitative and semi-quantitative uptake intensity of TcPYP is associated with all-cause mortality and all-cause mortality or heart failure hospitalization [ 5 ]. However, the use of Tc99m-PYP varies across and even within countries, such as the USA [ 6 ]. The use of this imaging modality in patients with acute bone lesions has traditionally been limited due to concerns regarding measurement errors. Thus, a method to “remove” abnormal accumulation within bones and provide accurate measurements to facilitate optimal diagnostic processes and patient management is needed. Accordingly, the current study described the use of dedicated software to address the measurement errors associated with bone lesions. Our preliminary data indicated that it can facilitate accurate measurement of the H/CL ratio in individuals with acute bone lesions. The limitations of this study include the small sample size and the use of artificial fractures to generate data. The findings of this study warrant follow-up in a larger multicenter study of patients with rib fractures to verify and validate our findings. New knowledge gained and clinical implications This study showed that, when performing myocardial infarction scintigraphy to examine ATTR amyloidosis, if a fracture occurs in an area that overlaps with the myocardium, it is better to remove (or calculate) the accumulation in the fractures. One of the clinical implications of the current study is that the use of PYP-ROI software can allow accurate measurement of the H/CL ratio in the presence of acute bone lesions. This could improve the diagnostic ability and subsequently facilitate optimized management of patients with rib lesions and other acute bone pathologies who require examinations for ATTR amyloidosis. Conclusions This study’s findings supported the utility of removing or compensating for the accumulation of rib fractures using PYP-ROI software to measure the H/CL ratio. Larger studies performed on clinical populations with genuine bone pathologies are required to corroborate the findings of the present study. Abbreviations AL, amyloid light-chain ATTR, amyloid transthyretin EF, ejection fraction H/CL, heart-to-contralateral lung LV, left ventricular NM, nuclear medicine PYP, Tc-99m-pyrophosphate ROI, region of interest SD, standard deviation US, ultrasound Declarations Acknowledgments: Editorial support, in the form of medical writing, assembling tables, creating high-resolution images based on authors’ detailed directions, collating author comments, copyediting, fact-checking, and referencing, was provided by Editage, Cactus Communications. The authors declare no conflicts of interest. References Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac amyloidosis: Evolving diagnosis and management: A scientific statement from the American Heart Association. Circulation. 2020;142:e7–22. 10.1161/CIR.0000000000000792 . Koh Y. AL amyloidosis: Advances in diagnosis and management. Blood Res. 2020;55(S1):S54–7. 10.5045/br.2020.S009 . Kitaoka H, Izumi C, Izumiya Y, Inomata T, Ueda M, Kubo T, et al. JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis. Circ J. 2020;84:1610–71. 10.1253/circj.CJ-20-0110 . Tamarappoo B, Otaki Y, Manabe O, Hyun M, Cantu S, Arnson Y, et al. Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT myocardial imaging in patients with suspected cardiac amyloidosis. J Nucl Cardiol. 2020;27:28–37. 10.1007/s12350-019-01753-5 . Vranian MN, Sperry BW, Hanna M, Hachamovitch R, Ikram A, Brunken RC, et al. Technetium pyrophosphate uptake in transthyretin cardiac amyloidosis: Associations with echocardiographic disease severity and outcomes. J Nucl Cardiol. 2018;25:1247–56. 10.1007/s12350-016-0768-9 . Harb SC, Haq M, Flood K, Guerrieri A, Passerell W, Jaber WA, et al. National patterns in imaging utilization for diagnosis of cardiac amyloidosis: A focus on Tc99m-pyrophosphate scintigraphy. J Nucl Cardiol. 2017;24:1094–7. 10.1007/s12350-016-0478-3 . Supplementary Files placeholderimage.png Graphical abstract. Measurement of the H/CL ratio in patients with rib fractures that overlap the myocardium during myocardial infarction scintigraphy using Tc-99m-PYP. Abbreviations: H/CL, heart-to-contralateral lung; PYP, Tc-99m-pyrophosphate; ROI, region of interest 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-4556923","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":313010195,"identity":"15dc8a9c-932c-49ca-be22-6e3c0c76841b","order_by":0,"name":"JUMPEI SUYAMA","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYPACGyBOYGBGEmEjpCWNdC2HMbTgBvIzcgw/3ag5H83PnsD8uaDisDyDRALjhx8MfHm4tBjcyDGWzjl2O3dmzwM26RlnDhs2SCQwS/YwsBXj1CKRYyCdw3Y7d8ONBDZm3rbbjPtvJDBIA/2S2IDbYca/c/6dywWqZP4M1GIPsuU3Pi0MN3LMpHPbDuRukAAaDtSSCNTChtcWgzPPyqxz+5JzZ5x52CbNc+Z/cgPPwzbLHgPcfpFvT958O+ebXW5/e/LhzzwVabYN7MmHb/yoOIYzxBgYOAygDMYGJIbBsQTcWtgfYBWuwaNlFIyCUTAKRhgAAJ62VeB6QOb7AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2589-2992","institution":"Kyorin University","correspondingAuthor":true,"prefix":"","firstName":"JUMPEI","middleName":"","lastName":"SUYAMA","suffix":""},{"id":313010196,"identity":"13d5ca81-336f-4980-ba70-e2eed315f82d","order_by":1,"name":"Chieko Takakuwa","email":"","orcid":"","institution":"Kyorin University","correspondingAuthor":false,"prefix":"","firstName":"Chieko","middleName":"","lastName":"Takakuwa","suffix":""},{"id":313010197,"identity":"b6288895-2f64-4261-b4ff-9f4bc2570454","order_by":2,"name":"Muneyuki Kawada","email":"","orcid":"","institution":"Kyorin University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Muneyuki","middleName":"","lastName":"Kawada","suffix":""},{"id":313010198,"identity":"ce57a768-3833-4d83-958b-9d1e7cec04ec","order_by":3,"name":"Yuya Shirakawa","email":"","orcid":"","institution":"Kyorin University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuya","middleName":"","lastName":"Shirakawa","suffix":""},{"id":313010199,"identity":"f5915679-8d8a-42fa-876b-5e653d6e8620","order_by":4,"name":"Kenichi Yokoyama","email":"","orcid":"","institution":"Kyorin University","correspondingAuthor":false,"prefix":"","firstName":"Kenichi","middleName":"","lastName":"Yokoyama","suffix":""}],"badges":[],"createdAt":"2024-06-10 09:03:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4556923/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4556923/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59870196,"identity":"a55c1845-4440-492a-a48c-f18d97d57345","added_by":"auto","created_at":"2024-07-08 16:56:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1047418,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eAscertainment of the H/CL ratio through the determination of ROI-BKG and ROI-Main\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb \u003c/strong\u003eA demonstration of the process of excluding a fracture site from the region of interest and filling the fracture site with pixels containing the average values from the surrounding pixels\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/24b5ed99c562a7ba8601f9bb.png"},{"id":59870195,"identity":"df947605-87ed-45aa-b02c-e5ceed7bee25","added_by":"auto","created_at":"2024-07-08 16:56:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":959679,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement technique for the H/CL ratio incorporating rib fractures with accumulation equivalent (middle image) or double (right-side image) the intensity of the sternum. The values provided are the H/CL ratio values. Data from a representative case are presented.\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/30e4cb4d677ee959329fd72f.png"},{"id":59870199,"identity":"f1a0432b-aa28-4a1f-9d9e-26a1be342351","added_by":"auto","created_at":"2024-07-08 16:56:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1516718,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eSimple calculation following removal of the rib fracture area to generate the H/CL ratio (using the removal function of the software)\u003c/p\u003e\n\u003cp\u003e. Data from a representative case are presented.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb \u003c/strong\u003eRemoval of the accumulation in an artificial fracture performed as a manual calculation on a computer monitor. Data from a representative case are presented.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/bf0f79353f2b8e2213943891.png"},{"id":59870198,"identity":"be23b1e7-83a2-4da1-9327-de1de0df3f68","added_by":"auto","created_at":"2024-07-08 16:56:42","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1781047,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eRemoval of the fracture accumulation and compensation through filling with the average bone accumulation count. Data from a representative case are presented.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb\u003c/strong\u003e Calculations based on avoiding the fracture site when setting the region of interest. Data from a representative case are presented.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/8a8fee93bf7df195fe211706.png"},{"id":59870188,"identity":"01e2c352-0793-4486-b606-b0b934c1a0e9","added_by":"auto","created_at":"2024-07-08 16:56:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":89705,"visible":true,"origin":"","legend":"\u003cp\u003eGroup-level summary of the rate of change in the H/CL ratio between the different stages across the 17 study participants. The y-axis represents the rate of change in the H/CL ratio.\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/19fa01483d6a5eb932b8f0ce.png"},{"id":59870197,"identity":"453c76f4-af1b-41ab-8214-ba64aa722216","added_by":"auto","created_at":"2024-07-08 16:56:42","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":872588,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003ePlain computed tomography imaging of the chest demonstrating post-fracture osteosclerotic changes in the left-sided anterior 7\u003csup\u003eth\u003c/sup\u003e rib.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb \u003c/strong\u003eThe same computed tomography scan demonstrating similar appearances in the anterior left-sided 8\u003csup\u003eth\u003c/sup\u003e rib.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ec \u003c/strong\u003eTc-99m-PYP scintigraphy demonstrating H/CL ratio calculation through the standard technique.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ed \u003c/strong\u003e\u0026nbsp;\u0026nbsp;Tc-99m-PYP scintigraphy demonstrating H/CL ratio calculation through the use of the software described in this study, with the use of the fracture uptake removal function.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ee \u003c/strong\u003eTc\u003cstrong\u003e-\u003c/strong\u003e99m-PYP scintigraphy demonstrating H/CL ratio calculation through complete avoidance of the area around the fractured ribs.\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/85886d70bc0fa12f80da730b.png"},{"id":60540409,"identity":"eb7551fa-5575-440a-b07c-17ed128f1e1a","added_by":"auto","created_at":"2024-07-18 02:10:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":11796582,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/a11c7795-b4b1-4ca9-95c7-c55df54f7d72.pdf"},{"id":59870187,"identity":"1da373e4-9a61-49e7-8c93-d6b0fd001023","added_by":"auto","created_at":"2024-07-08 16:56:39","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraphical abstract.\u003c/strong\u003e Measurement of the H/CL ratio in patients with rib fractures that overlap the myocardium during myocardial infarction scintigraphy using Tc-99m-PYP. Abbreviations: H/CL, heart-to-contralateral lung; PYP, Tc-99m-pyrophosphate; ROI, region of interest\u003c/p\u003e","description":"","filename":"placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-4556923/v1/9de09a3041451bd7ed9d4e64.png"}],"financialInterests":"","formattedTitle":"The use of pyrophosphate scintigraphy to measure the heart-to-contralateral lung ratio in the presence of rib fractures overlapping the heart","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRecently, cardiac amyloidosis has attracted increasing interest as a cause of chronic heart failure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Cardiac amyloidosis is traditionally classified into the amyloid light chain (AL) and amyloid transthyretin (ATTR) types. Tc-99m-pyrophosphate (PYP) is traditionally used for bone scintigraphy preparation, but is also useful for diagnosing myocardial infarction. However, it also accumulates in ATTR cardiac amyloidosis lesions and is useful for ATTR amyloidosis diagnosis and differentiation of ATTR and AL amyloidosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn daily clinical practice, quantitative evaluation using the heart-to-contralateral lung (H/CL) ratio, which measures the ratio of heart uptake to contralateral lower lung field uptake in planar images at 1 and 3 h after intravenous nuclide injection, has been widely used to evaluate ATTR amyloidosis. Its utility has been described in the 2020 Cardiac Amyloidosis Clinical Practice Guidelines (Japanese Circulation Society) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, dedicated software for performing this measurement is not widely available, and the measurement results cannot be easily displayed as images. Accordingly, our hospital developed its own analysis software for use as an auxiliary diagnostic tool and has been applying it in clinical practice since August 2021. However, given that certain nuclides accumulate in bones, if a bone lesion, such as a fracture, exists in the area that corresponds to the heart, high accumulation will appear, which may cause errors in the measured values. Our software was thus designed to remove abnormal accumulations in bones and to compensate for the removed area by using the average value of the surrounding accumulation in the heart (hereinafter referred to as the bone lesion removal function).\u003c/p\u003e \u003cp\u003eWhen a fracture occurs in ribs that overlap the heart, the H/CL ratio is assumed to be significantly affected. This effect can theoretically be reduced by setting a region of interest (ROI) to avoid fractures. However, the effectiveness of this approach has not been confirmed to date. Furthermore, the optimal method for establishing the ROI has not been described in the literature. The method involving the removal of rib-PYP accumulation from clinical images is considered to be the most effective; however, image processing to perform this is complicated when using the console of the gamma camera and has not been performed in routine clinical practice. We hypothesized that software developed to address this issue would provide accurate measurements of the H/CL ratio. This study thus investigated the accuracy of our software in addressing errors caused by bone lesions when measuring the H/CL ratio, including a clinical example to demonstrate the utility of the software in the clinical setting.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThis retrospective study included all patients who underwent PYP scintigraphy to diagnose cardiac amyloidosis between March 2021 and November 2021, and in whom cardiac amyloidosis was excluded by clinical diagnosis. Seventeen participants (mean age: 70.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9 years; male:female ratio 13:4) met these criteria. All the participants experienced cardiac failure (Table\u0026nbsp;1). No participants had rib fractures or other bone lesions. Instead, the DRIP software (version 3.1.0.0; FUJIFILM Toyama Chemical Co., Ltd., Tokyo, Japan) was used to simulate rib fractures. Subsequently, the H/CL ratio was determined for various pathologies, including pseudofractures, and the difference between these values and the H/CL ratio obtained in the original image was evaluated statistically. In addition to the above participants, clinical data were also sourced from a 77-year-old male patient with ATTR amyloidosis.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e \u003cb\u003eand informed consent\u003c/b\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003e This study was approved by our hospital\u0026rsquo;s institutional review board (approval number: R05-160), which waived the need for obtaining written informed consent from the participants due to the retrospective study design. The study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and all subsequent revisions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eImaging acquisition\u003c/h2\u003e \u003cp\u003eDuring dual-radionuclide myocardial scintigraphy acquisition, the doses of thallium and Tc-99m-PYP administered were 111 MBq and 370 MBq, respectively. Both isotopes were administered intravenously. The gamma camera used for acquisition was the GCA-9300R (Canon Medical Systems Corporation, Otawara, Japan). Images were acquired 3 hours following intravenous infusion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis technique\u003c/h2\u003e \u003cp\u003eThe software we developed, PYP-ROI version 1, was used on Microsoft Windows 10 and 11 (Microsoft Corporation, Redmond, WA, USA). The software was run independently, without any other software, in a Windows environment. Many facilities, including our hospital, perform simultaneous collection using two nuclides: myocardial infarction scintigraphy (Tc-99m-PYP) and myocardial perfusion scintigraphy (201-Tl-Chloride) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. When an ROI was set for the entire left ventricle in myocardial perfusion scintigraphy, the same ROI was set in the myocardial infarction scintigraphy image (ROI-Main). The same ROI was automatically set in the contralateral lung field (ROI-BKG). An example is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the fracture site was excluded from the ROI and was filled with pixels containing the average values of the surrounding pixels. The H/CL ratio was automatically measured using the following formula:\u003c/p\u003e \u003cp\u003eH/CL ratio = (average ROI-Main count) / (average ROI-BKG count)\u003c/p\u003e \u003cp\u003eThe intensity of Tc-99m-PYP accumulation was generated as one of two possible conditions:\u003c/p\u003e \u003cp\u003ea) the same as the average sternum count or b) twice the average sternum count (to replicate what is observed in the presence of an acute fracture). It is important to note that the accumulation in the sternum is high under normal physiological conditions, because the sternum is thick and physically close to the detector during the examination. Normal accumulation in the ribs was much lower than that in the sternum. However, the accumulation of lesions increased in the presence of rib fractures. As normal accumulation in the sternum is high, abnormal accumulation associated with rib fractures rarely exceeds it. Accordingly, we simulated the presence of a rib fracture with counts as high as those of the sternum, which could occur in clinical practice. In addition, we simulated the accumulation of counts associated with strong rib fractures, with counts twice as high as the rib count, suggesting the presence of severe acute fractures, which are not frequently encountered in clinical settings.\u003c/p\u003e \u003cp\u003eThe pseudo-rib fractures were generated as follows: First, an ROI was established as large as possible on the sternum. The average count of each pixel in the ROI was measured. Subsequently, a normal rib overlying the heart was selected, and an ROI of the same width as the rib was set at the junction of the ribs and cartilage (costochondral junction). Finally, an accumulation of the same average count (twice the average count) as the sternal accumulation was created within the ROI setting. The ROI was set at the costochondral junction to mimic the clinical reality closely, as this is the main site of rib fractures. Furthermore, a simulated anomalous uptake of radiopharmaceuticals with twice the intensity of the sternum was created to simulate a fresh fracture, which usually exhibits strong anomalous uptake. The abnormal accumulation of radiopharmaceuticals in fractures decreases with time after injury. A simulated abnormal accumulation of radiopharmaceuticals equivalent to that in the sternum was created to mimic a chronic fracture. In routine clinical practice, the abnormal accumulation in chronic fractures is typically high; therefore, we set the pseudo-accumulation equivalent to that of the sternum.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eAll statistical analyses, including \u003cem\u003et-\u003c/em\u003etests, were performed using the IBM SPSS Statistics software (version 29.0; IBM Corp., Armonk, NY, USA). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eIndependent data access and analysis\u003c/h2\u003e \u003cp\u003eJ.S. and C.T. had full access to all data in the study and take responsibility for its integrity and data analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAmong the 17 cases in our study in which the DRIP software was used to create abnormal accumulations artificially in areas that overlapped with the heart, no rib fractures were present in the same area as the heart to result in the accumulation of Tc-99m-PYP. The mean number of lesions (rib fractures) in the sternum did not exceed the physiological rate.\u003c/p\u003e \u003cp\u003eIn the study participants, we examined changes in the H/CL ratio using the following four steps:\u003c/p\u003e \u003cp\u003eFirst, when accumulation in the rib fractures was included (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), significantly higher H/CL ratios were obtained than the original values at the fracture sites.\u003c/p\u003e \u003cp\u003eSecond, when the accumulation at the rib fractures was removed, either by using software (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) or manually on a computer monitor (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb), the H/CL ratios obtained were not significantly different from the original values.\u003c/p\u003e \u003cp\u003eThird, when the area corresponding to the rib fracture was removed and compensated by filling in the average accumulation value from the entire ROI (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea), the H/CL ratio of the original image and that of the ROI in the cardiac region was significantly different.\u003c/p\u003e \u003cp\u003eFinally, when a small ROI was set to avoid rib fractures (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb), the H/CL ratio of the contralateral lung field in the original image differed significantly from that in the pseudo-lesions.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the H/CL ratio in the original images of the 17 study participants before the pseudo-rib fractures were created, and the extent to which the H/CL ratio changed with each measurement method. The mean rate of change (standard deviation) in the H/CL ratio relative to the preceding step/image was as follows: avoided H/CL 1.0\u0026thinsp;=\u0026thinsp;5.16\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), avoided H/CL 2.0\u0026thinsp;=\u0026thinsp;3.58\u0026thinsp;\u0026plusmn;\u0026thinsp;5.20 (p\u0026thinsp;=\u0026thinsp;0.005), artificial accumulation 1.0\u0026thinsp;=\u0026thinsp;1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), artificial accumulation 2.0\u0026thinsp;=\u0026thinsp;7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), removal 1.0 and 2.0 = -0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46 (p = -0.393), and embed 1.0 and 2.0 = -0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73 (p\u0026thinsp;=\u0026thinsp;0.003).\u003c/p\u003e \u003cp\u003eImaging of the clinical case study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. This individual, a 77-year-old male with ATTR amyloidosis, underwent plain computed tomography imaging of the chest, which demonstrated post-fracture osteosclerotic changes in the left-sided anterior 7th and 8th ribs (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ea, \u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eb). The H/CL ratio, when calculated using the standard technique, was 1.776 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ec). When utilizing the software and the fracture uptake removal function, the H/CL ratio was lower, at 1.718 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ed). This value is considered the most reliable. When calculating the H/CL ratio by completely avoiding the fracture uptake region, the value was most deranged from the real value, at 1.814 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ee).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e This study evaluated the accuracy of the PYP-ROI software in addressing errors caused by bone lesions when measuring the H/CL ratio in a study of 17 participants with simulated bone fractures, with further corroboration through a demonstration of the use of the software in a clinical case. Our findings confirmed the utility of the software. Based on our findings, we recommend the following order when proceeding with imaging analysis. First, the accumulation in the fracture should be eliminated. In the absence of a software-based removal function, manual calculations are required. Second, the compensation for the removed part should be calculated using the average count of the surrounding area. Third, if the fracture accumulation was weaker than the sternal accumulation, the fracture was included in the measurement. Fourth, if the fracture uptake was clearly higher than the sternal uptake, the impact was considered significant. Finally, in order to set the target ROI to avoid fractures, the ROI should be as large as possible to avoid poor reproducibility.\u003c/p\u003e \u003cp\u003eIt has previously been shown that, in patients with suspected ATTR amyloidosis, the quantitative and semi-quantitative uptake intensity of TcPYP is associated with all-cause mortality and all-cause mortality or heart failure hospitalization [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the use of Tc99m-PYP varies across and even within countries, such as the USA [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The use of this imaging modality in patients with acute bone lesions has traditionally been limited due to concerns regarding measurement errors. Thus, a method to \u0026ldquo;remove\u0026rdquo; abnormal accumulation within bones and provide accurate measurements to facilitate optimal diagnostic processes and patient management is needed. Accordingly, the current study described the use of dedicated software to address the measurement errors associated with bone lesions. Our preliminary data indicated that it can facilitate accurate measurement of the H/CL ratio in individuals with acute bone lesions.\u003c/p\u003e \u003cp\u003eThe limitations of this study include the small sample size and the use of artificial fractures to generate data. The findings of this study warrant follow-up in a larger multicenter study of patients with rib fractures to verify and validate our findings.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eNew knowledge gained and clinical implications\u003c/h2\u003e \u003cp\u003eThis study showed that, when performing myocardial infarction scintigraphy to examine ATTR amyloidosis, if a fracture occurs in an area that overlaps with the myocardium, it is better to remove (or calculate) the accumulation in the fractures. One of the clinical implications of the current study is that the use of PYP-ROI software can allow accurate measurement of the H/CL ratio in the presence of acute bone lesions. This could improve the diagnostic ability and subsequently facilitate optimized management of patients with rib lesions and other acute bone pathologies who require examinations for ATTR amyloidosis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study\u0026rsquo;s findings supported the utility of removing or compensating for the accumulation of rib fractures using PYP-ROI software to measure the H/CL ratio. Larger studies performed on clinical populations with genuine bone pathologies are required to corroborate the findings of the present study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAL, amyloid light-chain\u003c/p\u003e\n\u003cp\u003eATTR, amyloid transthyretin\u003c/p\u003e\n\u003cp\u003eEF, ejection fraction\u003c/p\u003e\n\u003cp\u003eH/CL, heart-to-contralateral lung\u003c/p\u003e\n\u003cp\u003eLV, left ventricular\u003c/p\u003e\n\u003cp\u003eNM, nuclear medicine\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePYP, Tc-99m-pyrophosphate\u003c/p\u003e\n\u003cp\u003eROI, region of interest\u003c/p\u003e\n\u003cp\u003eSD, standard deviation\u003c/p\u003e\n\u003cp\u003eUS, ultrasound\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgments:\u003c/h2\u003e \u003cp\u003eEditorial support, in the form of medical writing, assembling tables, creating high-resolution images based on authors\u0026rsquo; detailed directions, collating author comments, copyediting, fact-checking, and referencing, was provided by Editage, Cactus Communications. The authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac amyloidosis: Evolving diagnosis and management: A scientific statement from the American Heart Association. Circulation. 2020;142:e7\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIR.0000000000000792\u003c/span\u003e\u003cspan address=\"10.1161/CIR.0000000000000792\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoh Y. AL amyloidosis: Advances in diagnosis and management. 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J Nucl Cardiol. 2020;27:28\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12350-019-01753-5\u003c/span\u003e\u003cspan address=\"10.1007/s12350-019-01753-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVranian MN, Sperry BW, Hanna M, Hachamovitch R, Ikram A, Brunken RC, et al. Technetium pyrophosphate uptake in transthyretin cardiac amyloidosis: Associations with echocardiographic disease severity and outcomes. J Nucl Cardiol. 2018;25:1247\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12350-016-0768-9\u003c/span\u003e\u003cspan address=\"10.1007/s12350-016-0768-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarb SC, Haq M, Flood K, Guerrieri A, Passerell W, Jaber WA, et al. National patterns in imaging utilization for diagnosis of cardiac amyloidosis: A focus on Tc99m-pyrophosphate scintigraphy. J Nucl Cardiol. 2017;24:1094\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12350-016-0478-3\u003c/span\u003e\u003cspan address=\"10.1007/s12350-016-0478-3\" 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":"[email protected]","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":"","lastPublishedDoi":"10.21203/rs.3.rs-4556923/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4556923/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTc-99m-pyrophosphate has been used to evaluate amyloid transthyretin (ATTR) cardiac amyloidosis. Quantitative evaluation is widely performed by calculating the heart-to-contralateral lung (H/CL) ratio, but bone lesions may reduce measurement accuracy. We investigated the accuracy of the PYP-ROI software, developed by our group, in addressing the errors caused by bone lesions when measuring the H/CL ratio.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis\u003cstrong\u003e \u003c/strong\u003eretrospective study comprised 17 patients (mean age: 70.7 ± 13.9 years; male:female ratio 13:4) who underwent pyrophosphate scintigraphy to diagnose cardiac amyloidosis during March 2021–November 2021 and in whom cardiac amyloidosis was excluded clinically. None of the participants had rib fractures or other bone lesions. Simulated rib fractures were created, and the H/CL ratio was determined for various pathologies. The differences between these values and the H/CL ratios obtained from the original images were compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Based on our findings, which confirmed the software’s utility, we recommend the following steps for imaging analysis. First, the accumulation in the fracture should be eliminated, by manual calculations in the absence of a removal function. Second, compensation for the removed part should be calculated using the average count of the surrounding area. Third, if the fracture accumulation is weaker than the sternal accumulation, the fracture should be included in the measurement. Fourth, if fracture uptake is clearly higher than sternal uptake, the impact is significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis study supports the utility of removing or compensating for the accumulation in rib fractures using PYP-ROI software. However, verification in larger clinical studies is required.\u003c/p\u003e","manuscriptTitle":"The use of pyrophosphate scintigraphy to measure the heart-to-contralateral lung ratio in the presence of rib fractures overlapping the heart","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-08 16:56:34","doi":"10.21203/rs.3.rs-4556923/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","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":"458ad5ee-0037-44b7-824d-8596d9cf9b36","owner":[],"postedDate":"July 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-18T02:02:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-08 16:56:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4556923","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4556923","identity":"rs-4556923","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}