Pub Date : 2025-08-21eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1569991
Ivo J Lutke Schipholt, Gwendolyne G M Scholten-Peeters, Meghan A Koop, Michel W Coppieters, Ronald Boellaard, Elsmarieke van de Giessen, Bastiaan C Ter Meulen, Marieke Coenen, Carmen Vleggeert-Lankamp, Paul R Depaauw, Bart N M van Berckel, Adriaan A Lammerstma, Maqsood Yaqub
Background: Animal models of nerve compression have revealed neuroinflammation not only at the entrapment site, but also remotely at the spinal cord. However, there is limited information on the presence of neuroinflammation in human compression neuropathies. The objectives of this study were to: (1) assess which tracer kinetic model most optimally quantified [11C]DPA713 uptake in the spinal cord and neuroforamina in patients with painful cervical radiculopathy, (2) evaluate the performance of linearized methods (e.g., Logan) and simplified (e.g., standardized uptake value - SUV) methods, and (3) assess the test-retest reliability of these methods. Microglia activation associated with neuroinflammation was quantified using positron emission tomography (PET) with the radiotracer [11C]DPA713, targeting the 18 kDa translocator protein (TSPO). The Akaike information criterion, visual inspection of the fits and number of outliers were used to select the optimal kinetic model. As unaffected tissue, the spinal cord and neuroforamina three cervical levels above the affected target tissue was used.
Results: The single tissue (1T2k) compartment model was the preferred model to describe [11C]DPA713 kinetics at the spinal cord and neuroforamina. Higher levels of 1T2k VT were observed in the affected neuroforamina and spinal cord compared with corresponding unaffected tissues. Logan VT (≥0.73) showed high correlation with 1T2k VT at both locations. Of the simplified methods, neuroforamina and spinal cord SUV normalized for the metabolite corrected plasma (TBR-PP) exhibited high correlations with 1T2k VT (r ≥ 0.84). Test-retest reliability varied between fair to excellent.
Conclusions: These results indicate that a 1T2k model with metabolite corrected image derived input function can be used to describe the kinetics of [11C]DPA713 in the spinal cord and neuroforamina in humans. 1T2k VT or Logan VT can be used as binding metric, while TBR-PP is the recommended choice among simplified models.
背景:神经压迫动物模型显示神经炎症不仅发生在压迫部位,而且远端发生在脊髓。然而,关于人类压迫性神经病中存在神经炎症的信息有限。本研究的目的是:(1)评估哪种示踪动力学模型最能量化疼痛性颈椎病患者脊髓和神经孔中[11C]DPA713的摄取,(2)评估线性化方法(如Logan)和简化方法(如标准化摄取值- SUV)的性能,以及(3)评估这些方法的重测可靠性。使用正电子发射断层扫描(PET)和放射性示踪剂[11C]DPA713,量化与神经炎症相关的小胶质细胞激活,靶向18 kDa转运蛋白(TSPO)。采用赤池信息准则、目视拟合检验和离群值数等方法选择最优动力学模型。作为未受影响的组织,脊髓和神经孔比受影响的目标组织高三个颈椎水平。结果:单组织(1T2k)室模型是描述脊髓和神经孔[11C]DPA713动力学的首选模型。与未受影响的相应组织相比,在受影响的神经孔和脊髓中观察到较高水平的1T2k V T。Logan V T(≥0.73)与两个部位的1T2k V T高度相关。在简化方法中,神经孔和脊髓SUV标准化代谢物校正血浆(TBR-PP)与1T2k V T呈高度相关(r≥0.84)。重测信度在一般到优异之间变化。结论:这些结果表明,具有代谢物校正图像衍生输入功能的1T2k模型可用于描述人类脊髓和神经孔中[11C]DPA713的动力学。可以使用1T2k V T或Logan V T作为绑定度量,简化模型中推荐选择TBR-PP。
{"title":"Quantification of neuroinflammation in spinal cord and neuroforamina of patients with painful cervical radiculopathy using [<sup>11</sup>C]DPA713 PET/CT.","authors":"Ivo J Lutke Schipholt, Gwendolyne G M Scholten-Peeters, Meghan A Koop, Michel W Coppieters, Ronald Boellaard, Elsmarieke van de Giessen, Bastiaan C Ter Meulen, Marieke Coenen, Carmen Vleggeert-Lankamp, Paul R Depaauw, Bart N M van Berckel, Adriaan A Lammerstma, Maqsood Yaqub","doi":"10.3389/fnume.2025.1569991","DOIUrl":"10.3389/fnume.2025.1569991","url":null,"abstract":"<p><strong>Background: </strong>Animal models of nerve compression have revealed neuroinflammation not only at the entrapment site, but also remotely at the spinal cord. However, there is limited information on the presence of neuroinflammation in human compression neuropathies. The objectives of this study were to: (1) assess which tracer kinetic model most optimally quantified [<sup>11</sup>C]DPA713 uptake in the spinal cord and neuroforamina in patients with painful cervical radiculopathy, (2) evaluate the performance of linearized methods (e.g., Logan) and simplified (e.g., standardized uptake value - SUV) methods, and (3) assess the test-retest reliability of these methods. Microglia activation associated with neuroinflammation was quantified using positron emission tomography (PET) with the radiotracer [<sup>11</sup>C]DPA713, targeting the 18 kDa translocator protein (TSPO). The Akaike information criterion, visual inspection of the fits and number of outliers were used to select the optimal kinetic model. As unaffected tissue, the spinal cord and neuroforamina three cervical levels above the affected target tissue was used.</p><p><strong>Results: </strong>The single tissue (1T2k) compartment model was the preferred model to describe [<sup>11</sup>C]DPA713 kinetics at the spinal cord and neuroforamina. Higher levels of 1T2k <i>V</i> <sub>T</sub> were observed in the affected neuroforamina and spinal cord compared with corresponding unaffected tissues. Logan <i>V</i> <sub>T</sub> (≥0.73) showed high correlation with 1T2k <i>V</i> <sub>T</sub> at both locations. Of the simplified methods, neuroforamina and spinal cord SUV normalized for the metabolite corrected plasma (TBR-PP) exhibited high correlations with 1T2k <i>V</i> <sub>T</sub> (r ≥ 0.84). Test-retest reliability varied between fair to excellent.</p><p><strong>Conclusions: </strong>These results indicate that a 1T2k model with metabolite corrected image derived input function can be used to describe the kinetics of [<sup>11</sup>C]DPA713 in the spinal cord and neuroforamina in humans. 1T2k <i>V</i> <sub>T</sub> or Logan <i>V</i> <sub>T</sub> can be used as binding metric, while TBR-PP is the recommended choice among simplified models.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1569991"},"PeriodicalIF":1.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-12eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1671281
Amir Jabbarpour, Eric Moulton, Sanaz Kaviani, Siraj Ghassel, Wanzhen Zeng, Ramin Akbarian, Anne Couture, Aubert Roy, Richard Liu, Yousif A Lucinian, Nuha Hejji, Sukainah AlSulaiman, Farnaz Shirazi, Eugene Leung, Sierra Bonsall, Samir Arfin, Bruce G Gray, Ran Klein
[This corrects the article DOI: 10.3389/fnume.2025.1632112.].
[这更正了文章DOI: 10.3389/ funme .2025.1632112.]。
{"title":"Correction: On the construction of a large-scale database of AI-assisted annotating lung ventilation-perfusion scintigraphy for pulmonary embolism (VQ4PEDB).","authors":"Amir Jabbarpour, Eric Moulton, Sanaz Kaviani, Siraj Ghassel, Wanzhen Zeng, Ramin Akbarian, Anne Couture, Aubert Roy, Richard Liu, Yousif A Lucinian, Nuha Hejji, Sukainah AlSulaiman, Farnaz Shirazi, Eugene Leung, Sierra Bonsall, Samir Arfin, Bruce G Gray, Ran Klein","doi":"10.3389/fnume.2025.1671281","DOIUrl":"https://doi.org/10.3389/fnume.2025.1671281","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnume.2025.1632112.].</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1671281"},"PeriodicalIF":1.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1655419
Katherine N Haugh, Alexis M Sanwick, Ivis F Chaple
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms characterized by their overexpression of somatostatin receptors (SSTRs), which can be utilized for peptide receptor radionuclide therapy. This review provides a comprehensive update on the clinical trials of radiolabeled SSTR-targeting radiopharmaceuticals since 2020, with a focus on somatostatin receptor agonists and antagonists radiolabeled with 68Ga, 18F, 99mTc, 177Lu, 161Tb, 212Pb, 67Cu, and 225Ac. Head-to-head clinical trials demonstrate that radiolabeled SSTR antagonists such as [68Ga]Ga-DOTA-JR11 and [68Ga]Ga-DOTA-LM3 offer improved lesion detection and tumor-to-background ratios (particularly in liver metastases) compared to radiolabeled agonists like [68Ga]Ga-DOTA-TOC and [64Cu]Cu-DOTA-TATE. Additionally, 18F-labeled agents offer logistical and dosimetric advantages over 68Ga, due to 18F's longer half-life and cyclotron production, allowing for delayed imaging and increased availability to a wider range of patients. Emerging targeted alpha therapy agents, including [225Ac]Ac-DOTA-TATE, show promising results in treating disease resistant to conventional therapies due to the high linear energy transfer of alpha particles, which leads to improved localized cytotoxicity. Collectively, these developments support a shift toward more precise, receptor-specific theragnostics, emphasizing the need for further head-to-head clinical trials and integration of dosimetry-driven, personalized treatment planning in the management of NETs.
{"title":"Targeted radionuclide therapy and diagnostic imaging of SSTR positive neuroendocrine tumors: a clinical update in the new decade.","authors":"Katherine N Haugh, Alexis M Sanwick, Ivis F Chaple","doi":"10.3389/fnume.2025.1655419","DOIUrl":"10.3389/fnume.2025.1655419","url":null,"abstract":"<p><p>Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms characterized by their overexpression of somatostatin receptors (SSTRs), which can be utilized for peptide receptor radionuclide therapy. This review provides a comprehensive update on the clinical trials of radiolabeled SSTR-targeting radiopharmaceuticals since 2020, with a focus on somatostatin receptor agonists and antagonists radiolabeled with <sup>68</sup>Ga, <sup>18</sup>F, <sup>99m</sup>Tc, <sup>177</sup>Lu, <sup>161</sup>Tb, <sup>212</sup>Pb, <sup>67</sup>Cu, and <sup>225</sup>Ac. Head-to-head clinical trials demonstrate that radiolabeled SSTR antagonists such as [<sup>68</sup>Ga]Ga-DOTA-JR11 and [<sup>68</sup>Ga]Ga-DOTA-LM3 offer improved lesion detection and tumor-to-background ratios (particularly in liver metastases) compared to radiolabeled agonists like [<sup>68</sup>Ga]Ga-DOTA-TOC and [<sup>64</sup>Cu]Cu-DOTA-TATE. Additionally, <sup>18</sup>F-labeled agents offer logistical and dosimetric advantages over <sup>68</sup>Ga, due to <sup>18</sup>F's longer half-life and cyclotron production, allowing for delayed imaging and increased availability to a wider range of patients. Emerging targeted alpha therapy agents, including [<sup>225</sup>Ac]Ac-DOTA-TATE, show promising results in treating disease resistant to conventional therapies due to the high linear energy transfer of alpha particles, which leads to improved localized cytotoxicity. Collectively, these developments support a shift toward more precise, receptor-specific theragnostics, emphasizing the need for further head-to-head clinical trials and integration of dosimetry-driven, personalized treatment planning in the management of NETs.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1655419"},"PeriodicalIF":1.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12367690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-06eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1663748
Alexis M Sanwick, Ivis F Chaple
Radiocobalt-based theranostics has emerged as a promising platform in nuclear medicine that offers dual capabilities for both diagnostic imaging and targeted radionuclide therapy. 55Co (t1/2 = 17.53 h, β+ = 77%, E γ = 931.1 keV, I γ = 75%) and 58mCo (t1/2 = 9.10 h, IC = 100%) serve as an elementally matched pair for positron emission tomography and targeted Auger electron therapy, respectively, that enable a more personalized approach to cancer management, where imaging with 55Co can help to guide and predict therapeutic outcomes for 58mCo therapy. The unique coordination chemistry of cobalt allows for stable complexation with various chelators, enhancing in vivo stability and targeting efficacy when conjugated to biomolecules such as peptides, antibodies, and small molecules. Recent developments in radiolabeling techniques, chelator design, and preclinical evaluations have significantly improved the pharmacokinetic profiles and tumor specificity of radiocobalt-based radiopharmaceuticals. The aim of this mini review is to provide an overview of the recent advancements and applications of radiocobalt isotopes with a particular focus on the production, chelation chemistry, and in vivo targeting of 55Co- and 58mCo-labelled radiopharmaceuticals over the last 5 years. While challenges still exist in production scalability, dosimetry optimization, and clinical translations, the current trajectory suggests a growing role for radiocobalt-based theranostics in precision oncology.
放射性钴基治疗已经成为核医学中一个很有前途的平台,它提供了诊断成像和靶向放射性核素治疗的双重能力。55Co (t1/2 = 17.53 h, β+ = 77%, E γ = 931.1 keV, I γ = 75%)和58mCo (t1/2 = 9.10 h, IC = 100%)分别作为正电子发射断层扫描和靶向奥格电子治疗的基本匹配对,可以实现更个性化的癌症管理方法,其中55Co成像可以帮助指导和预测58mCo治疗的治疗结果。钴独特的配位化学特性使其能够与各种螯合剂稳定络合,增强其与生物分子(如肽、抗体和小分子)结合时的体内稳定性和靶向性。放射性标记技术、螯合剂设计和临床前评估的最新发展显著改善了放射性钴基放射性药物的药代动力学特征和肿瘤特异性。这篇小型综述的目的是概述放射性钴同位素的最新进展和应用,特别关注过去5年来55Co和58mcco标记的放射性药物的生产、螯合化学和体内靶向。虽然在生产可扩展性、剂量优化和临床转化方面仍然存在挑战,但目前的发展轨迹表明,放射性钴基治疗在精确肿瘤学中的作用越来越大。
{"title":"Radiocobalt theranostic applications: current landscape, challenges, and future directions.","authors":"Alexis M Sanwick, Ivis F Chaple","doi":"10.3389/fnume.2025.1663748","DOIUrl":"10.3389/fnume.2025.1663748","url":null,"abstract":"<p><p>Radiocobalt-based theranostics has emerged as a promising platform in nuclear medicine that offers dual capabilities for both diagnostic imaging and targeted radionuclide therapy. <sup>55</sup>Co (t<sub>1/2</sub> = 17.53 h, β<sup>+</sup> = 77%, E <i><sub>γ</sub></i> = 931.1 keV, I <i><sub>γ</sub></i> = 75%) and <sup>58m</sup>Co (t<sub>1/2</sub> = 9.10 h, IC = 100%) serve as an elementally matched pair for positron emission tomography and targeted Auger electron therapy, respectively, that enable a more personalized approach to cancer management, where imaging with <sup>55</sup>Co can help to guide and predict therapeutic outcomes for <sup>58m</sup>Co therapy. The unique coordination chemistry of cobalt allows for stable complexation with various chelators, enhancing <i>in vivo</i> stability and targeting efficacy when conjugated to biomolecules such as peptides, antibodies, and small molecules. Recent developments in radiolabeling techniques, chelator design, and preclinical evaluations have significantly improved the pharmacokinetic profiles and tumor specificity of radiocobalt-based radiopharmaceuticals. The aim of this mini review is to provide an overview of the recent advancements and applications of radiocobalt isotopes with a particular focus on the production, chelation chemistry, and <i>in vivo</i> targeting of <sup>55</sup>Co- and <sup>58m</sup>Co-labelled radiopharmaceuticals over the last 5 years. While challenges still exist in production scalability, dosimetry optimization, and clinical translations, the current trajectory suggests a growing role for radiocobalt-based theranostics in precision oncology.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1663748"},"PeriodicalIF":1.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-29eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1646628
Beverley F Holman, Tamar Willson, Bruno Ferreira, Neil Davis, Hemangini Natarajan, Jannat Khan, Thomas Wagner, Daniel McCool
Purpose: Long axial field-of-view (LAFOV) PET systems like the Siemens Biograph Vision Quadra offer unprecedented sensitivity and imaging capabilities, but compliance with EARL standards across all acquisition modes remains unexplored. This study aimed to identify reconstruction parameters meeting EARL 1 and 2 compliance for static and continuous bed motion (CBM) acquisitions in High Sensitivity (HS) and Ultra-High Sensitivity (UHS) modes on the Quadra. The research focused on optimising image quality while maintaining compliance with quantitative standards.
Methods: The International Electrotechnical Commission (IEC) body phantom was filled with 18F-FDG in a 10:1 sphere-to-background activity ratio and scanned at five positions across the field of view (FOV) using static and CBM acquisitions in HS and UHS modes. Reconstructions used standard clinical parameters, varied with Gaussian filters (1-7 mm) and matrix sizes (440, 220, 128). EARL compliance was assessed with the EARL tool to evaluate SUV recovery coefficients (RCSUVmean, RCSUVmax, RCSUVpeak). Patient images were reconstructed using standard and EARL-compliant parameters for comparison.
Results: Reconstruction parameters achieving EARL compliance were identified for all acquisition modes, with no differences between static and CBM reconstructions. Achieving EARL compliance required significant image quality reductions, especially for EARL 1, with greater degradation in UHS mode. Patient images reconstructed with EARL-compliant parameters appeared smoother and had reduced contrast compared to clinical reconstructions.
Conclusion: While EARL compliance ensures quantitative standardisation, it significantly reduces image quality, especially on advanced LAFOV PET systems. An updated "EARL 3" standard is needed to reflect the capabilities of modern systems.
{"title":"EARL compliance on the Biograph Vision Quadra PET-CT: phantom study for static and continuous bed motion acquisitions.","authors":"Beverley F Holman, Tamar Willson, Bruno Ferreira, Neil Davis, Hemangini Natarajan, Jannat Khan, Thomas Wagner, Daniel McCool","doi":"10.3389/fnume.2025.1646628","DOIUrl":"10.3389/fnume.2025.1646628","url":null,"abstract":"<p><strong>Purpose: </strong>Long axial field-of-view (LAFOV) PET systems like the Siemens Biograph Vision Quadra offer unprecedented sensitivity and imaging capabilities, but compliance with EARL standards across all acquisition modes remains unexplored. This study aimed to identify reconstruction parameters meeting EARL 1 and 2 compliance for static and continuous bed motion (CBM) acquisitions in High Sensitivity (HS) and Ultra-High Sensitivity (UHS) modes on the Quadra. The research focused on optimising image quality while maintaining compliance with quantitative standards.</p><p><strong>Methods: </strong>The International Electrotechnical Commission (IEC) body phantom was filled with <sup>18</sup>F-FDG in a 10:1 sphere-to-background activity ratio and scanned at five positions across the field of view (FOV) using static and CBM acquisitions in HS and UHS modes. Reconstructions used standard clinical parameters, varied with Gaussian filters (1-7 mm) and matrix sizes (440, 220, 128). EARL compliance was assessed with the EARL tool to evaluate SUV recovery coefficients (RCSUVmean, RCSUVmax, RCSUVpeak). Patient images were reconstructed using standard and EARL-compliant parameters for comparison.</p><p><strong>Results: </strong>Reconstruction parameters achieving EARL compliance were identified for all acquisition modes, with no differences between static and CBM reconstructions. Achieving EARL compliance required significant image quality reductions, especially for EARL 1, with greater degradation in UHS mode. Patient images reconstructed with EARL-compliant parameters appeared smoother and had reduced contrast compared to clinical reconstructions.</p><p><strong>Conclusion: </strong>While EARL compliance ensures quantitative standardisation, it significantly reduces image quality, especially on advanced LAFOV PET systems. An updated \"EARL 3\" standard is needed to reflect the capabilities of modern systems.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1646628"},"PeriodicalIF":1.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-17eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1632112
Amir Jabbarpour, Eric Moulton, Sanaz Kaviani, Siraj Ghassel, Wanzhen Zeng, Ramin Akbarian, Anne Couture, Aubert Roy, Richard Liu, Yousif A Lucinian, Nuha Hejji, Sukainah AlSulaiman, Farnaz Shirazi, Eugene Leung, Sierra Bonsall, Samir Arfin, Bruce G Gray, Ran Klein
Introduction: Ventilation-perfusion (V/Q) nuclear scintigraphy remains a vital diagnostic tool for assessing pulmonary embolism (PE) and other lung conditions. Interpretation of these images requires specific expertise which may benefit from recent advances in artificial intelligence (AI) to improve diagnostic accuracy and confidence in reporting. Our study aims to develop a multi-center dataset combining imaging and clinical reports to aid in creating AI models for PE diagnosis.
Methods: We established a comprehensive imaging registry encompassing patient-level V/Q image data along with relevant clinical reports, CTPA images, DVT ultrasound impressions, D-dimer lab tests, and thrombosis unit records. Data extraction was performed at two hospitals in Canada and at multiple sites in the United States, followed by a rigorous de-identification process. We utilized the V7 Darwin platform for crowdsourced annotation of V/Q images including segmentation of V/Q mismatched vascular defects. The annotated data was then ingested into Deep Lake, a SQL-based database, for AI model training. Quality assurance involved manual inspections and algorithmic validation.
Results: A query of The Ottawa Hospital's data warehouse followed by initial data screening yielded 2,137 V/Q studies with 2,238 successfully retrieved as DICOM studies. Additional contributions included 600 studies from University Health Toronto, and 385 studies by private company Segmed Inc. resulting in a total of 3,122 V/Q planar and SPECT images. The majority of studies were acquired using Siemens, Philips, and GE scanners, adhering to standardized local imaging protocols. After annotating 1,500 studies from The Ottawa Hospital, the analysis identified 138 high-probability, 168 intermediate-probability, 266 low-probability, 244 very low-probability, and 669 normal, and 15 normal perfusion with reversed mismatched ventilation defect studies. In 1,500 patients were 3,511 segmented vascular perfusion defects.
Conclusion: The VQ4PEDB comprised 8 unique ventilation agents and 11 unique scanners. The VQ4PEDB database is unique in its depth and breadth in the domain of V/Q nuclear scintigraphy for PE, comprising clinical reports, imaging studies, and annotations. We share our experience in addressing challenges associated with data retrieval, de-identification, and annotation. VQ4PEDB will be a valuable resource to development and validate AI models for diagnosing PE and other pulmonary diseases.
{"title":"On the construction of a large-scale database of AI-assisted annotating lung ventilation-perfusion scintigraphy for pulmonary embolism (VQ4PEDB).","authors":"Amir Jabbarpour, Eric Moulton, Sanaz Kaviani, Siraj Ghassel, Wanzhen Zeng, Ramin Akbarian, Anne Couture, Aubert Roy, Richard Liu, Yousif A Lucinian, Nuha Hejji, Sukainah AlSulaiman, Farnaz Shirazi, Eugene Leung, Sierra Bonsall, Samir Arfin, Bruce G Gray, Ran Klein","doi":"10.3389/fnume.2025.1632112","DOIUrl":"10.3389/fnume.2025.1632112","url":null,"abstract":"<p><strong>Introduction: </strong>Ventilation-perfusion (V/Q) nuclear scintigraphy remains a vital diagnostic tool for assessing pulmonary embolism (PE) and other lung conditions. Interpretation of these images requires specific expertise which may benefit from recent advances in artificial intelligence (AI) to improve diagnostic accuracy and confidence in reporting. Our study aims to develop a multi-center dataset combining imaging and clinical reports to aid in creating AI models for PE diagnosis.</p><p><strong>Methods: </strong>We established a comprehensive imaging registry encompassing patient-level V/Q image data along with relevant clinical reports, CTPA images, DVT ultrasound impressions, D-dimer lab tests, and thrombosis unit records. Data extraction was performed at two hospitals in Canada and at multiple sites in the United States, followed by a rigorous de-identification process. We utilized the V7 Darwin platform for crowdsourced annotation of V/Q images including segmentation of V/Q mismatched vascular defects. The annotated data was then ingested into Deep Lake, a SQL-based database, for AI model training. Quality assurance involved manual inspections and algorithmic validation.</p><p><strong>Results: </strong>A query of The Ottawa Hospital's data warehouse followed by initial data screening yielded 2,137 V/Q studies with 2,238 successfully retrieved as DICOM studies. Additional contributions included 600 studies from University Health Toronto, and 385 studies by private company Segmed Inc. resulting in a total of 3,122 V/Q planar and SPECT images. The majority of studies were acquired using Siemens, Philips, and GE scanners, adhering to standardized local imaging protocols. After annotating 1,500 studies from The Ottawa Hospital, the analysis identified 138 high-probability, 168 intermediate-probability, 266 low-probability, 244 very low-probability, and 669 normal, and 15 normal perfusion with reversed mismatched ventilation defect studies. In 1,500 patients were 3,511 segmented vascular perfusion defects.</p><p><strong>Conclusion: </strong>The VQ4PEDB comprised 8 unique ventilation agents and 11 unique scanners. The VQ4PEDB database is unique in its depth and breadth in the domain of V/Q nuclear scintigraphy for PE, comprising clinical reports, imaging studies, and annotations. We share our experience in addressing challenges associated with data retrieval, de-identification, and annotation. VQ4PEDB will be a valuable resource to development and validate AI models for diagnosing PE and other pulmonary diseases.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1632112"},"PeriodicalIF":1.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
[This corrects the article DOI: 10.3389/fnume.2025.1575026.].
[这更正了文章DOI: 10.3389/ funme .2025.1575026.]。
{"title":"Correction: Emotional stress during the COVID-19 lockdown: how negative X/Twitter posts correlated with changes in the brain's fear network.","authors":"Eric Guedj, Jacques-Yves Campion, Tatiana Horowitz, Fanny Barthélémy, Stéphanie Khalfa, Wissam El-Hage","doi":"10.3389/fnume.2025.1655239","DOIUrl":"https://doi.org/10.3389/fnume.2025.1655239","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnume.2025.1575026.].</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1655239"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-04eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1611823
Ashish Kumar Jha, Umeshkumar Baburao Sherkhane, Nilendu C Purandare, Leonard Wee, Andre Dekker, Venkatesh Rangarajan
Background: The characterization of solitary pulmonary nodules (SPNs) as malignant or benign remains a diagnostic challenge using conventional imaging parameters. The literature suggests using combined Positron Emission Tomography (PET) and Computed Tomography (CT) to characterise a SPN. Radiomics and machine learning are other promising technologies which can be utilised to characterise the SPN.
Purpose: This study explores the potential of PET radiomics signatures and machine learning algorithms to characterise the SPN.
Methods: This retrospective study aimed to characterize solitary pulmonary nodules (SPNs) using PET radiomics. A total of 163 patients who underwent PET/CT imaging were included in this study. A total of 1,098 features were extracted from PET images using PyRadiomics. To optimize model performance two strategies i.e., (a) feature selection and (b) feature reduction techniques were employed, including hierarchical clustering, RFE in feature selection, and PCA in feature reduction. To address outcome class imbalance, the dataset was statistically resampled (SMOTE). A random forest models was developed using original training set (RF-Model-O & RF-PCA-Model-O) and balanced training dataset (RF-Model-B & RF-PCA-Model-B) and validated on the test datasets. Additionally, 5-fold cross-validation and bootstrap validation was also performed. The model's performance was assessed using various metrics, such as accuracy, AUC, precision, recall, and F1-score.
Results: Of the 163 patients (aged 36-76 years, mean age 58 ± 7), 117 had malignant disease and 46 had granulomatous or benign conditions. In Strategy (a), five radiomic features were identified as optimal using hierarchical clustering and RFE. In Strategy (b), five principal components were deemed optimal using PCA. The model accuracy of RF-Model-O and RF-Model-B in the train-test validation, 5-fold cross-validation and bootstrap validation were found to be 0.8, 0.80 ± 0.07, 0.84 ± 1.11 and 0.8, 0.83 ± 0.10, 0.80 ± 0.07 in Strategy (a). Similarly, the model accuracy of RF-PCA-Model-O and RF-PCA-Model-B in the train-test validation, 5-fold cross-validation and bootstrap validation were found to be 0.84, 0.80 ± 0.07, 0.84 ± 07 and 0.74, 0.80 ± 0.08, 0.75 ± 0.08 in Strategy (b).
Conclusion: The PET radiomics demonstrated excellent performance in characterizing SPNs as benign or malignant.
{"title":"Positron emission tomography imaging biomarker and artificial intelligence for the characterization of solitary pulmonary nodule.","authors":"Ashish Kumar Jha, Umeshkumar Baburao Sherkhane, Nilendu C Purandare, Leonard Wee, Andre Dekker, Venkatesh Rangarajan","doi":"10.3389/fnume.2025.1611823","DOIUrl":"10.3389/fnume.2025.1611823","url":null,"abstract":"<p><strong>Background: </strong>The characterization of solitary pulmonary nodules (SPNs) as malignant or benign remains a diagnostic challenge using conventional imaging parameters. The literature suggests using combined Positron Emission Tomography (PET) and Computed Tomography (CT) to characterise a SPN. Radiomics and machine learning are other promising technologies which can be utilised to characterise the SPN.</p><p><strong>Purpose: </strong>This study explores the potential of PET radiomics signatures and machine learning algorithms to characterise the SPN.</p><p><strong>Methods: </strong>This retrospective study aimed to characterize solitary pulmonary nodules (SPNs) using PET radiomics. A total of 163 patients who underwent PET/CT imaging were included in this study. A total of 1,098 features were extracted from PET images using PyRadiomics. To optimize model performance two strategies i.e., (a) feature selection and (b) feature reduction techniques were employed, including hierarchical clustering, RFE in feature selection, and PCA in feature reduction. To address outcome class imbalance, the dataset was statistically resampled (SMOTE). A random forest models was developed using original training set (RF-Model-O & RF-PCA-Model-O) and balanced training dataset (RF-Model-B & RF-PCA-Model-B) and validated on the test datasets. Additionally, 5-fold cross-validation and bootstrap validation was also performed. The model's performance was assessed using various metrics, such as accuracy, AUC, precision, recall, and F1-score.</p><p><strong>Results: </strong>Of the 163 patients (aged 36-76 years, mean age 58 ± 7), 117 had malignant disease and 46 had granulomatous or benign conditions. In <b>Strategy (a),</b> five radiomic features were identified as optimal using hierarchical clustering and RFE. In <b>Strategy (b),</b> five principal components were deemed optimal using PCA. The model accuracy of RF-Model-O and RF-Model-B in the train-test validation, 5-fold cross-validation and bootstrap validation were found to be 0.8, 0.80 ± 0.07, 0.84 ± 1.11 and 0.8, 0.83 ± 0.10, 0.80 ± 0.07 in Strategy (a). Similarly, the model accuracy of RF-PCA-Model-O and RF-PCA-Model-B in the train-test validation, 5-fold cross-validation and bootstrap validation were found to be 0.84, 0.80 ± 0.07, 0.84 ± 07 and 0.74, 0.80 ± 0.08, 0.75 ± 0.08 in Strategy (b).</p><p><strong>Conclusion: </strong>The PET radiomics demonstrated excellent performance in characterizing SPNs as benign or malignant.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1611823"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: The COVID-19 pandemic has profoundly affected mental health, with lockdown periods particularly exacerbating negative emotions such as fear, sadness, and uncertainty. This study examines brain metabolic changes associated with the psychological context of the first French COVID-19 lockdown in vulnerable individuals.
Methods: As a proxy measure of the psychological context, we used a composite negative-emotion score derived from an open-source X/Twitter dataset ("The First French COVID-19 Lockdown Twitter Dataset"), designed to capture public sentiment over the 55-day lockdown. This score was day-by-day correlated with whole-brain voxel-based [18F]FDG PET imaging in 95 patients with neurological conditions, using statistical parametric mapping (SPM) (p-voxel < 0.001, k > 108).
Results: A significant negative correlation was found between daily negative-emotion scores and metabolism in the right ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC), key regions of the brain's fear circuit. Inter-regional correlation analysis (IRCA) of metabolic connectivity from the right vmPFC/ACC further revealed a right limbic-dominant network including the amygdala, hippocampus, thalamus, and basal ganglia.
Discussion: These findings highlight the sensitivity of the right vmPFC/ACC to societal emotional stressors, suggesting a potential cerebral substrate for the increase in psychological and psychiatric disorders observed during the pandemic. Further research is needed to validate these results in larger populations and to explore their longitudinal implications, to better understand the neurological impact of collective stress.
导读:2019冠状病毒病大流行深刻影响了心理健康,封锁期尤其加剧了恐惧、悲伤和不确定等负面情绪。这项研究调查了与法国首次COVID-19封锁对弱势群体的心理背景相关的大脑代谢变化。方法:作为心理背景的代理度量,我们使用了来自开源X/Twitter数据集(“第一个法国COVID-19封锁Twitter数据集”)的综合负面情绪评分,旨在捕捉55天封锁期间的公众情绪。该评分与95例神经系统疾病患者基于全脑体素的FDG PET成像逐日相关,采用统计参数映射(SPM) (p-voxel < 0.001, k > 108)。结果:日常负情绪得分与大脑恐惧回路关键区域右侧腹内侧前额叶皮层(vmPFC)和前扣带皮层(ACC)的代谢呈显著负相关。来自右侧vmPFC/ACC的代谢连通性的区域间相关分析(IRCA)进一步揭示了包括杏仁核、海马、丘脑和基底神经节在内的右侧边缘主导网络。讨论:这些发现突出了右侧vmPFC/ACC对社会情绪压力源的敏感性,表明在大流行期间观察到的心理和精神疾病增加的潜在脑基质。进一步的研究需要在更大的人群中验证这些结果,并探索其纵向影响,以更好地了解集体压力对神经系统的影响。
{"title":"Emotional stress during the COVID-19 lockdown: how negative X/Twitter posts correlated with changes in the brain's fear network.","authors":"Eric Guedj, Jacques-Yves Campion, Tatiana Horowitz, Fanny Barthélémy, Stéphanie Khalfa, Wissam El-Hage","doi":"10.3389/fnume.2025.1575026","DOIUrl":"10.3389/fnume.2025.1575026","url":null,"abstract":"<p><strong>Introduction: </strong>The COVID-19 pandemic has profoundly affected mental health, with lockdown periods particularly exacerbating negative emotions such as fear, sadness, and uncertainty. This study examines brain metabolic changes associated with the psychological context of the first French COVID-19 lockdown in vulnerable individuals.</p><p><strong>Methods: </strong>As a proxy measure of the psychological context, we used a composite negative-emotion score derived from an open-source X/Twitter dataset (\"The First French COVID-19 Lockdown Twitter Dataset\"), designed to capture public sentiment over the 55-day lockdown. This score was day-by-day correlated with whole-brain voxel-based [18F]FDG PET imaging in 95 patients with neurological conditions, using statistical parametric mapping (SPM) (<i>p</i>-voxel < 0.001, <i>k</i> > 108).</p><p><strong>Results: </strong>A significant negative correlation was found between daily negative-emotion scores and metabolism in the right ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC), key regions of the brain's fear circuit. Inter-regional correlation analysis (IRCA) of metabolic connectivity from the right vmPFC/ACC further revealed a right limbic-dominant network including the amygdala, hippocampus, thalamus, and basal ganglia.</p><p><strong>Discussion: </strong>These findings highlight the sensitivity of the right vmPFC/ACC to societal emotional stressors, suggesting a potential cerebral substrate for the increase in psychological and psychiatric disorders observed during the pandemic. Further research is needed to validate these results in larger populations and to explore their longitudinal implications, to better understand the neurological impact of collective stress.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1575026"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-05eCollection Date: 2025-01-01DOI: 10.3389/fnume.2025.1597902
Giordana Salvi de Souza, Pascalle Mossel, Joost F Somsen, Laura Providência, Anna L Bartels, Antoon T M Willemsen, Rudi A J O Dierckx, Cristiane R G Furini, Adriaan A Lammertsma, Charalampos Tsoumpas, Gert Luurtsema
Kinetic modelling of brain PET data is crucial for estimating quantitative biological parameters, traditionally requiring arterial sampling. This study evaluated whether arterial samples could be omitted to estimate the image-derived input function (IDIF) using a long axial field-of-view PET scanner. The use of internal carotid arteries (ICA) for IDIF estimation, along with venous samples for plasma-to-whole blood ratios and plasma parent fractions, was also assessed. Six healthy volunteers underwent [18F]MC225 scans with manual arterial sampling. IDIFs were derived from the aortic arch (IDIFAA) and calibrated using manual arterial samples (IDIFAA_CAL). ICA-derived IDIF was also calibrated (IDIFCA_CAL) and compared to IDIFAA_CAL. In a separate group of six volunteers, venous and arterial samples were collected to evaluate plasma-to-whole blood ratios, plasma parent fractions, and IDIF calibration (IDIFCA_CAL_VEN). Volume of distribution (VT) of different brain regions was estimated for all IDIFs techniques, corrected for plasma-to-whole blood ratio and plasma parent fraction (IDIFAA,P, IDIFAA_CAL,P, IDIFICA_CAL,P and IDIFICA_CAL_VEN_P). Our findings revealed discrepancies between IDIFAA and arterial samples, highlighting the importance of calibration. The differences between IDIFAA,P and IDIFAA_CAL,P were 9.2% for area under the curve and 4.0% for brain VT. IDIFICA_CAL,P showed strong agreement with IDIFA_CAL,P, with 1.2% VT difference. Venous sampling showed consistent agreement with arterial sampling for plasma parameters but was unreliable for IDIF calibration, leading to 39% VT differences. This study emphasises that arterial samples are still required for IDIF calibration and reliable VT estimation for [18F]MC225 PET tracer. ICA-derived IDIF, when calibrated, provides reliable VT estimates. Venous sampling is a potential alternative for estimating plasma parameters, but it is unsuitable for IDIF calibration.
{"title":"Evaluating image-derived input functions for cerebral [<sup>18</sup>F]MC225 PET studies.","authors":"Giordana Salvi de Souza, Pascalle Mossel, Joost F Somsen, Laura Providência, Anna L Bartels, Antoon T M Willemsen, Rudi A J O Dierckx, Cristiane R G Furini, Adriaan A Lammertsma, Charalampos Tsoumpas, Gert Luurtsema","doi":"10.3389/fnume.2025.1597902","DOIUrl":"10.3389/fnume.2025.1597902","url":null,"abstract":"<p><p>Kinetic modelling of brain PET data is crucial for estimating quantitative biological parameters, traditionally requiring arterial sampling. This study evaluated whether arterial samples could be omitted to estimate the image-derived input function (IDIF) using a long axial field-of-view PET scanner. The use of internal carotid arteries (ICA) for IDIF estimation, along with venous samples for plasma-to-whole blood ratios and plasma parent fractions, was also assessed. Six healthy volunteers underwent [<sup>18</sup>F]MC225 scans with manual arterial sampling. IDIFs were derived from the aortic arch (IDIF<sub>AA</sub>) and calibrated using manual arterial samples (IDIF<sub>AA_CAL</sub>). ICA-derived IDIF was also calibrated (IDIF<sub>CA_CAL</sub>) and compared to IDIF<sub>AA_CAL</sub>. In a separate group of six volunteers, venous and arterial samples were collected to evaluate plasma-to-whole blood ratios, plasma parent fractions, and IDIF calibration (IDIF<sub>CA_CAL_VEN</sub>). Volume of distribution (V<sub>T</sub>) of different brain regions was estimated for all IDIFs techniques, corrected for plasma-to-whole blood ratio and plasma parent fraction (IDIF<sub>AA,P</sub>, IDIF<sub>AA_CAL,P</sub>, IDIF<sub>ICA_CAL,P</sub> and IDIF<sub>ICA_CAL_VEN_P</sub>). Our findings revealed discrepancies between IDIF<sub>AA</sub> and arterial samples, highlighting the importance of calibration. The differences between IDIF<sub>AA,P</sub> and IDIF<sub>AA_CAL,P</sub> were 9.2% for area under the curve and 4.0% for brain V<sub>T</sub>. IDIF<sub>ICA_CAL,P</sub> showed strong agreement with IDIF<sub>A_CAL,P</sub>, with 1.2% V<sub>T</sub> difference. Venous sampling showed consistent agreement with arterial sampling for plasma parameters but was unreliable for IDIF calibration, leading to 39% V<sub>T</sub> differences. This study emphasises that arterial samples are still required for IDIF calibration and reliable V<sub>T</sub> estimation for [<sup>18</sup>F]MC225 PET tracer. ICA-derived IDIF, when calibrated, provides reliable V<sub>T</sub> estimates. Venous sampling is a potential alternative for estimating plasma parameters, but it is unsuitable for IDIF calibration.</p><p><strong>Trial registry: </strong>NCT05618119 (clinicaltrials.gov/study/NCT05618119).</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":"5 ","pages":"1597902"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}