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Alyami AS, Madkhali Y, Majrashi NA, Alwadani B, Elbashir M, Ali S, Ageeli W, El-Bahkiry HS, Althobity AA, Refaee T. The role of molecular imaging in detecting fibrosis in Crohn's disease. Ann Med 2024; 56:2313676. [PMID: 38346385 PMCID: PMC10863520 DOI: 10.1080/07853890.2024.2313676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
Fibrosis is a pathological process that occurs due to chronic inflammation, leading to the proliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM). The process of long-term fibrosis initiates with tissue hypofunction and progressively culminates in the ultimate manifestation of organ failure. Intestinal fibrosis is a significant complication of Crohn's disease (CD) that can result in persistent luminal narrowing and strictures, which are difficult to reverse. In recent years, there have been significant advances in our understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD). Significant progress has been achieved in the fields of pathogenesis, diagnosis, and management of intestinal fibrosis in the last few years. A significant amount of research has also been conducted in the field of biomarkers for the prediction or detection of intestinal fibrosis, including novel cross-sectional imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Molecular imaging represents a promising biomedical approach that enables the non-invasive visualization of cellular and subcellular processes. Molecular imaging has the potential to be employed for early detection, disease staging, and prognostication in addition to assessing disease activity and treatment response in IBD. Molecular imaging methods also have a potential role to enabling minimally invasive assessment of intestinal fibrosis. This review discusses the role of molecular imaging in combination of AI in detecting CD fibrosis.
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Affiliation(s)
- Ali S. Alyami
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Yahia Madkhali
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Naif A. Majrashi
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Bandar Alwadani
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Meaad Elbashir
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Sarra Ali
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Wael Ageeli
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Hesham S. El-Bahkiry
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdullah A. Althobity
- Department of Radiological Sciences and Medical Imaging, College of Applied Medical Sciences, Majmaah University, Majmaah, Saudi Arabia
| | - Turkey Refaee
- Department of Diagnostic Radiography Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
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2
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Bhattaru A, Pundyavana A, Raynor W, Chinta S, Werner TJ, Alavi A. 18F-FDG-PET and other imaging modalities in the diagnosis and management of inflammatory bowel disease. AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 2024; 14:295-305. [PMID: 39583912 PMCID: PMC11578808 DOI: 10.62347/yxqt2560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 08/22/2024] [Indexed: 11/26/2024]
Abstract
Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal (GI) tract that presents complex diagnostic and management challenges. Early detection and treatment of IBD is paramount, as IBD can present with serious complications, including bowel perforation, arthritis, and colorectal cancer. Most forms of diagnosis and therapeutic management, like ileocolonoscopy and upper endoscopy are highly invasive and require extensive preparation at great discomfort to patients. 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging can be a potential solution to the current limitations in imaging for IBD. This review explores the utility and limitations of various imaging modalities used to detect and manage IBD including ileocolonoscopy, magnetic resonance enterography (MRE), gastrointestinal ultrasound (IUS), and 18F-FDG-PET/computed tomography (18F-FDG-PET/CT) and magnetic resonance imaging (18F-FDG-PET/MR). This review has an emphasis on PET imaging and highlights its benefits in detection, management, and monitoring therapeutic response of UC and CD.
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Affiliation(s)
- Abhijit Bhattaru
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - Anish Pundyavana
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - William Raynor
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
| | - Sree Chinta
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
- Department of Medicine, Rutgers New Jersey Medical SchoolNewark, New Jersey, The United States
| | - Thomas J Werner
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
| | - Abass Alavi
- Department of Radiology, University of PennsylvaniaPhiladelphia, Pennsylvania, The United States
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Lin CY, Chang MC, Kao CH. Comparing the Diagnostic Value of FDG PET or PET/CT With FDG PET/MR in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis. Clin Nucl Med 2024; 49:e492-e500. [PMID: 38973081 DOI: 10.1097/rlu.0000000000005379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
BACKGROUND The aim of this study was to compare the diagnostic value of 18 F-FDG PET or PET/CT with FDG PET/MR in patients with inflammatory bowel disease (IBD). METHODS A comprehensive search was performed in PubMed for studies reporting the diagnostic performance of FDG PET (PET/CT) and FDG PET/MR in IBD from the inception of the database to March 14, 2024, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fourteen studies were included in this systematic review and meta-analysis. Pooled estimates of segment-based sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for FDG PET (PET/CT) and FDG PET/MR were calculated alongside 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were plotted, and the area under the SROC curve was determined alongside the Q * index. RESULTS The segment-based pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve of FDG PET (PET/CT) for diagnosing IBD (9 studies) were 0.81, 0.86, 5.76, 0.22, 31.92, and 0.92, respectively. Those of FDG PET/MR (5 studies) were 0.78, 0.92, 10.97, 0.25, 51.79, and 0.95. There was no significant difference in the abilities of detecting or excluding IBD between FDG PET (PET/CT) and FDG PET/MR. CONCLUSIONS For diagnostic value in patients with IBD, there was no significant difference between FDG PET (PET/CT) and FDG PET/MR. Both FDG PET (PET/CT) and FDG PET/MR have demonstrated high diagnostic performance for accurate diagnosing in patients with IBD.
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Affiliation(s)
- Chun-Yi Lin
- From the Department of Nuclear Medicine, Changhua Christian Hospital, Changhua
| | - Ming-Che Chang
- From the Department of Nuclear Medicine, Changhua Christian Hospital, Changhua
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Rezazadeh F, Kilcline AP, Viola NT. Imaging Agents for PET of Inflammatory Bowel Disease: A Review. J Nucl Med 2023; 64:1858-1864. [PMID: 37918865 PMCID: PMC10690123 DOI: 10.2967/jnumed.123.265935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/27/2023] [Indexed: 11/04/2023] Open
Abstract
Inflammatory bowel disease (IBD), which encompasses ulcerative colitis and Crohn disease, is a chronic inflammatory disorder resulting from an aberrant immune response, though its exact cause is unknown. The current mainstay standard of care for the diagnosis and surveillance of IBD is endoscopy. However, this methodology is invasive and images only superficial tissue structures, revealing very little about the molecular drivers of inflammation. Accordingly, there is an unmet need for noninvasive imaging tools that provide reliable and quantitative visualization of intestinal inflammation with high spatial and molecular specificity. In recent years, several PET agents for imaging IBD have been reported. Such agents allow noninvasive visualization and quantification of dynamic molecular inflammatory processes in vivo. This review focuses on recent advancements in the development of PET tracers for imaging biomarkers of interest in IBD pathogenesis, such as cell-surface molecules that are overexpressed on immune cells and cytokines that perpetuate inflammatory signaling.
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Affiliation(s)
- Farzaneh Rezazadeh
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Aidan P Kilcline
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
| | - Nerissa T Viola
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
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Sun B, Liu J, Li S, Lovell JF, Zhang Y. Imaging of Gastrointestinal Tract Ailments. J Imaging 2023; 9:115. [PMID: 37367463 DOI: 10.3390/jimaging9060115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/20/2023] [Accepted: 05/25/2023] [Indexed: 06/28/2023] Open
Abstract
Gastrointestinal (GI) disorders comprise a diverse range of conditions that can significantly reduce the quality of life and can even be life-threatening in serious cases. The development of accurate and rapid detection approaches is of essential importance for early diagnosis and timely management of GI diseases. This review mainly focuses on the imaging of several representative gastrointestinal ailments, such as inflammatory bowel disease, tumors, appendicitis, Meckel's diverticulum, and others. Various imaging modalities commonly used for the gastrointestinal tract, including magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT), and photoacoustic tomography (PAT) and multimodal imaging with mode overlap are summarized. These achievements in single and multimodal imaging provide useful guidance for improved diagnosis, staging, and treatment of the corresponding gastrointestinal diseases. The review evaluates the strengths and weaknesses of different imaging techniques and summarizes the development of imaging techniques used for diagnosing gastrointestinal ailments.
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Affiliation(s)
- Boyang Sun
- Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Jingang Liu
- Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Silu Li
- Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Jonathan F Lovell
- Department of Biomedical Engineering, The State University of New York at Buffalo, Buffalo, NY 14260, USA
| | - Yumiao Zhang
- Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
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6
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Noriega-Álvarez E, Martín-Comín J. Molecular Imaging in Inflammatory Bowel Disease. Semin Nucl Med 2023; 53:273-286. [PMID: 36702729 DOI: 10.1053/j.semnuclmed.2022.12.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 01/26/2023]
Abstract
Inflammatory bowel diseases (IBD) are chronic immune-mediated inflammatory diseases affecting the gastrointestinal tract. Classically, two subtypes of IBD are recognized: Ulcerative colitis and Crohn's disease. There is not a single and reliable test for IBD diagnosis but the nuclear medicine techniques like 99mTc-HMPAO autologous labelled leukocytes scintigraphy (WBCS) and PET/CT plays a role in the management of IBD. Leukocytes can be labelled "in vitro" (using 99mTc-HMPAO in Europe or 111In-oxine in America) or "in vivo" using antigranulocyte monoclonal antibodies. Nuclear medicine techniques are not the first choice to investigate IBD. Ultrasonography and magnetic resonance (radiation free) are probably the first option, and the diagnosis is commonly established by endoscopic biopsies. Nevertheless, WBCS is highly sensitive and accurate and represent a real option when other methods cannot used for whatever reason. In fact, a normal scan discards the presence of active IBD. The test is also useful to measure the extension and severity of the diseases and to evaluate the response to treatment. PET/CT imaging using 18F-FDG has recently been introduced and studied in both children and adults showing an excellent sensitivity for detecting active intestinal inflammation, but poor specificity in some studies. PET alone appears to be sufficient for the evaluation of ulcerative colitis, but PET/CT provides considerably more information than PET alone in the evaluation of Crohn's disease. Current clinical applications of PET in IBD include its use in the early evaluation of IBD, especially in children who may not tolerate an invasive test such as colonoscopy. Many questions remain to be answered, but PET appears to be a promising tool in the non-invasive evaluation of IBD. On the other hand, PET/MR could become in the near future a powerful tool in the evaluation of IBD patients. In addition, immuno-PET with antibodies targeting innate immune markers is also being investigated to detect colonic inflammation. The development of these technologies in humans could offer a less invasive method than endoscopy for the diagnosis and monitoring of IBD.
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Affiliation(s)
- Edel Noriega-Álvarez
- Nuclear Medicine Department, University General Hospital of Ciudad Real, Ciudad Real, Spain.
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7
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Utility of PET Scans in the Diagnosis and Management of Gastrointestinal Tumors. Dig Dis Sci 2022; 67:4633-4653. [PMID: 35908126 DOI: 10.1007/s10620-022-07616-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/27/2022] [Indexed: 12/14/2022]
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Lovinfosse P, Hustinx R. The role of PET imaging in inflammatory bowel diseases: state-of-the-art review. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:206-217. [PMID: 35708600 DOI: 10.23736/s1824-4785.22.03467-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Inflammatory bowel diseases (IBD), i.e. Crohn disease and ulcerative colitis, are autoimmune processes of undetermined origin characterized by the chronic inflammation of the digestive tract. There is no single gold-standard to diagnose IBD which is therefore carried out through the combination of endoscopy, biopsy, radiological and biological investigations; and the development of non-invasive technique allowing the assessment and monitoring of these diseases is necessary. In this state-of-the-art review of the literature, we present the results of PET imaging studies for the diagnosis and staging of IBD (suspected or known), response evaluation to treatment and evaluation of one the main complication, i.e. strictures; explain the reasons why this examination is currently not considered in the IBD guidelines, e.g. radiation exposure, lack of standardization and not validated performances; and finally discuss the perspectives that could possibly allow it to find a place in the future, e.g. digital PET-CT, dynamic PET images acquisition, new radiopharmaceuticals, use of radiomics and use of artificial intelligence for automatically characterize and quantify digestive [18F]FDG uptake.
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Affiliation(s)
- Pierre Lovinfosse
- Division of Nuclear Medicine and Oncological Imaging, University Hospital CHU of Liège, Liège, Belgium -
- GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium -
| | - Roland Hustinx
- Division of Nuclear Medicine and Oncological Imaging, University Hospital CHU of Liège, Liège, Belgium
- GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium
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9
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Sepehrizadeh T, Jong I, DeVeer M, Malhotra A. PET/MRI in paediatric disease. Eur J Radiol 2021; 144:109987. [PMID: 34649143 DOI: 10.1016/j.ejrad.2021.109987] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 12/17/2022]
Abstract
Nuclear medicine and molecular imaging have a small but growing role in the management of paediatric and neonatal diseases. During the past decade, combined PET/MRI has emerged as a clinically important hybrid imaging modality in paediatric medicine due to diagnostic advantages and reduced radiation exposure compared to alternative techniques. The applications for nuclear medicine, radiopharmaceuticals and combined PET/MRI in paediatric diagnosis is broadly similar to adults, however there are some key differences. There are a variety of clinical applications for PET/MRI imaging in children including, but not limited to, oncology, neurology, cardiovascular, infection and chronic inflammatory diseases, and in renal-urological disorders. In this article, we review the applications of PET/MRI in paediatric and neonatal imaging, its current role, advantages and disadvantages over other hybrid imaging techniques such as PET/CT, and its future applications. Overall, PET/MRI is a powerful imaging technology in diagnostic medicine and paediatric diseases. Higher soft tissue contrasts and lower radiation dose of the MRI makes it the superior technology compared to other conventional techniques such as PET/CT or scintigraphy. However, this relatively new hybrid imaging has also some limitations. MRI based attenuation correction remains a challenge and although methodologies have improved significantly in the last decades, most remain under development.
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Affiliation(s)
| | - Ian Jong
- Department of diagnostic imaging, Monash Health, Melbourne, Australia
| | - Michael DeVeer
- Monash Biomedical Imaging, Monash University, Melbourne, Australia
| | - Atul Malhotra
- Monash Newborn, Monash Children's Hospital, Melbourne, Australia; Department of Paediatrics, Monash University, Melbourne, Australia
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10
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Bonfiglio R, Galli F, Varani M, Scimeca M, Borri F, Fazi S, Cicconi R, Mattei M, Campagna G, Schönberger T, Raymond E, Wunder A, Signore A, Bonanno E. Extensive Histopathological Characterization of Inflamed Bowel in the Dextran Sulfate Sodium Mouse Model with Emphasis on Clinically Relevant Biomarkers and Targets for Drug Development. Int J Mol Sci 2021; 22:2028. [PMID: 33670766 PMCID: PMC7923003 DOI: 10.3390/ijms22042028] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/04/2021] [Accepted: 02/16/2021] [Indexed: 12/12/2022] Open
Abstract
This study aims to develop a reliable and reproducible inflammatory bowel disease (IBD) murine model based on a careful spatial-temporal histological characterization. Secondary aims included extensive preclinical studies focused on the in situ expression of clinically relevant biomarkers and targets involved in IBD. C57BL/6 female mice were used to establish the IBD model. Colitis was induced by the oral administration of 2% Dextran Sulfate Sodium (DSS) for 5 days, followed by 2, 4 or 9 days of water. Histological analysis was performed by sectioning the whole colon into rings of 5 mm each. Immunohistochemical analyses were performed for molecular targets of interest for monitoring disease activity, treatment response and predicting outcome. Data reported here allowed us to develop an original scoring method useful as a tool for the histological assessment of preclinical models of DSS-induced IBD. Immunohistochemical data showed a significant increase in TNF-α, α4β7, VEGFRII, GR-1, CD25, CD3 and IL-12p40 expression in DSS mice if compared to controls. No difference was observed for IL-17, IL-23R, IL-36R or F480. Knowledge of the spatial-temporal pattern distribution of the pathological lesions of a well-characterized disease model lays the foundation for the study of the tissue expression of meaningful predictive biomarkers, thereby improving translational success rates of preclinical studies for a personalized management of IBD patients.
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Affiliation(s)
- Rita Bonfiglio
- Department of Experimental Medicine, University “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.B.); (M.S.); (S.F.)
| | - Filippo Galli
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00161 Rome, Italy; (F.G.); (M.V.); (G.C.); (A.S.)
| | - Michela Varani
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00161 Rome, Italy; (F.G.); (M.V.); (G.C.); (A.S.)
| | - Manuel Scimeca
- Department of Experimental Medicine, University “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.B.); (M.S.); (S.F.)
- San Raffaele University, via di Val Cannuta 247, 00166 Rome, Italy
- Saint Camillus International University of Health Sciences, via di Sant’Alessandro, 8, 00131 Rome, Italy
| | - Filippo Borri
- UOC Anatomia Patologica, Department of Oncology, USL Toscana Sud-Est, San Donato Hospital, 52100 Arezzo, Italy;
| | - Sara Fazi
- Department of Experimental Medicine, University “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.B.); (M.S.); (S.F.)
| | - Rosella Cicconi
- Interdepartmental Center for Comparative Medicine, Alternative Techniques and Aquaculture (CIMETA), University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.C.); (M.M.)
| | - Maurizio Mattei
- Interdepartmental Center for Comparative Medicine, Alternative Techniques and Aquaculture (CIMETA), University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.C.); (M.M.)
- Department of Biology, University of Rome “Tor Vergata”, via della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Giuseppe Campagna
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00161 Rome, Italy; (F.G.); (M.V.); (G.C.); (A.S.)
| | - Tanja Schönberger
- Divison of Target Discovery Research and Target Validation Technologies, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany;
| | - Ernest Raymond
- Immunology and Respiratory Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ridgefield, CT 06877, USA;
| | - Andreas Wunder
- Division of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88387 Biberach an der Riss, Germany;
| | - Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, 00161 Rome, Italy; (F.G.); (M.V.); (G.C.); (A.S.)
| | - Elena Bonanno
- Department of Experimental Medicine, University “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy; (R.B.); (M.S.); (S.F.)
- “Diagnostica Medica” and “Villa dei Platani”, Neuromed Group, 83100 Avellino, Italy
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11
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Peñate Medina T, Kolb JP, Hüttmann G, Huber R, Peñate Medina O, Ha L, Ulloa P, Larsen N, Ferrari A, Rafecas M, Ellrichmann M, Pravdivtseva MS, Anikeeva M, Humbert J, Both M, Hundt JE, Hövener JB. Imaging Inflammation - From Whole Body Imaging to Cellular Resolution. Front Immunol 2021; 12:692222. [PMID: 34248987 PMCID: PMC8264453 DOI: 10.3389/fimmu.2021.692222] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 05/12/2021] [Indexed: 01/31/2023] Open
Abstract
Imaging techniques have evolved impressively lately, allowing whole new concepts like multimodal imaging, personal medicine, theranostic therapies, and molecular imaging to increase general awareness of possiblities of imaging to medicine field. Here, we have collected the selected (3D) imaging modalities and evaluated the recent findings on preclinical and clinical inflammation imaging. The focus has been on the feasibility of imaging to aid in inflammation precision medicine, and the key challenges and opportunities of the imaging modalities are presented. Some examples of the current usage in clinics/close to clinics have been brought out as an example. This review evaluates the future prospects of the imaging technologies for clinical applications in precision medicine from the pre-clinical development point of view.
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Affiliation(s)
- Tuula Peñate Medina
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
- *Correspondence: Tuula Peñate Medina, ; Jan-Bernd Hövener,
| | - Jan Philip Kolb
- Institute of Biomedical Optics, University of Lübeck, Lübeck, Germany
| | - Gereon Hüttmann
- Institute of Biomedical Optics, University of Lübeck, Lübeck, Germany
- Airway Research Center North (ARCN), Member of the German Center of Lung Research (DZL), Gießen, Germany
| | - Robert Huber
- Institute of Biomedical Optics, University of Lübeck, Lübeck, Germany
| | - Oula Peñate Medina
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
- Institute for Experimental Cancer Research (IET), University of Kiel, Kiel, Germany
| | - Linh Ha
- Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein Lübeck (UKSH), Lübeck, Germany
| | - Patricia Ulloa
- Department of Radiology and Neuroradiology, University Medical Centers Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Naomi Larsen
- Department of Radiology and Neuroradiology, University Medical Centers Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Arianna Ferrari
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
| | - Magdalena Rafecas
- Institute of Medical Engineering (IMT), University of Lübeck, Lübeck, Germany
| | - Mark Ellrichmann
- Interdisciplinary Endoscopy, Medical Department1, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Mariya S. Pravdivtseva
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
- Department of Radiology and Neuroradiology, University Medical Centers Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Mariia Anikeeva
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
| | - Jana Humbert
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
- Department of Radiology and Neuroradiology, University Medical Centers Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Marcus Both
- Department of Radiology and Neuroradiology, University Medical Centers Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Jennifer E. Hundt
- Lübeck Institute for Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
| | - Jan-Bernd Hövener
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center, Schleswig-Holstein Kiel University, Kiel, Germany
- *Correspondence: Tuula Peñate Medina, ; Jan-Bernd Hövener,
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Abstract
FDG-PET/CT has potential in inflammatory bowel disease. The literature generally presents good sensitivity and specificity in various settings. At present, the most promising roles are assessment of early treatment response and stricture characterization, whereas general use in the initial diagnostic workup should be reserved for equivocal cases for the time being. However, it is challenging to image the moving and physiologically active bowel with FDG, and available literature is far from ideal. Thus, several issues remain unclarified, and further data are needed to make firm conclusions on the role of FDG and PET/CT in inflammatory bowel disease.
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Affiliation(s)
- Jacob Broder Brodersen
- Department of Gastroenterology, Hospital of Southwest Jutland, Finsensgade 35, Esbjerg Dk-6700, Denmark
| | - Søren Hess
- Department of Radiology and Nuclear Medicine, Hospital of Southwest Jutland, Finsensgade 35, Esbjerg Dk-6700, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
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Le Fur M, Zhou IY, Catalano O, Caravan P. Toward Molecular Imaging of Intestinal Pathology. Inflamm Bowel Dis 2020; 26:1470-1484. [PMID: 32793946 PMCID: PMC7500524 DOI: 10.1093/ibd/izaa213] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD) is defined by a chronic relapsing and remitting inflammation of the gastrointestinal tract, with intestinal fibrosis being a major complication. The etiology of IBD remains unknown, but it is thought to arise from a dysregulated and excessive immune response to gut luminal microbes triggered by genetic and environmental factors. To date, IBD has no cure, and treatments are currently directed at relieving symptoms and treating inflammation. The current diagnostic of IBD relies on endoscopy, which is invasive and does not provide information on the presence of extraluminal complications and molecular aspect of the disease. Cross-sectional imaging modalities such as computed tomography enterography (CTE), magnetic resonance enterography (MRE), positron emission tomography (PET), single photon emission computed tomography (SPECT), and hybrid modalities have demonstrated high accuracy for the diagnosis of IBD and can provide both functional and morphological information when combined with the use of molecular imaging probes. This review presents the state-of-the-art imaging techniques and molecular imaging approaches in the field of IBD and points out future directions that could help improve our understanding of IBD pathological processes, along with the development of efficient treatments.
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Affiliation(s)
- Mariane Le Fur
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Iris Y Zhou
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Onofrio Catalano
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA,The Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, MA, USA
| | - Peter Caravan
- The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, MA, USA,Address correspondence to: Peter Caravan, PhD, The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, The Institute for Innovation in Imaging, Massachusetts General Hospital and Harvard Medical School, 149 Thirteenth Street, Charlestown 02129, MA, USA. E-mail:
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Li Y, Schaarschmidt B, Umutlu L, Forsting M, Demircioglu A, Koch AK, Martin O, Herrmann K, Juette H, Tannapfel A, Langhorst J. 18F-FDG PET-MR enterography in predicting histological active disease using the Nancy index in ulcerative colitis: a randomized controlled trial. Eur J Nucl Med Mol Imaging 2019; 47:768-777. [DOI: 10.1007/s00259-019-04535-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 09/12/2019] [Indexed: 01/17/2023]
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Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals. J Acquir Immune Defic Syndr 2019; 78:450-457. [PMID: 29874201 DOI: 10.1097/qai.0000000000001693] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Alterations in the gut microbiome have been associated with inflammation and increased cardiovascular risk in HIV-infected individuals. The aim of this study was to investigate the effects of the probiotic strain Lactobacillus rhamnosus GG (LGG) on intestinal inflammation, gut microbiota composition, and systemic markers of microbial translocation and inflammation in HIV-infected individuals. METHODS This prospective, clinical interventional trial included 45 individuals [15 combination antiretroviral treatment (cART) naive and 30 cART treated] who ingested LGG twice daily at a dosage of 6 × 109 colony-forming units per capsule for a period of 8 weeks. Intestinal inflammation was assessed using F-2-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging (F-FDG PET/MRI) scans in 15 individuals. Gut microbiota composition (V3-V4 region of the 16s rRNA gene) and markers of microbial translocation and inflammation (lipopolysaccharide, sCD14, sCD163, sCD25, high-sensitive CRP, IL-6, and tumor necrosis factor-alpha) were analyzed at baseline and after intervention. RESULTS At baseline, evidence of intestinal inflammation was found in 75% of the participants, with no significant differences between cART-naive and cART-treated individuals. After LGG supplementation, a decrease in intestinal inflammation was detected on PET/MRI (-0.3 mean difference in the combined activity grade score from 6 regions, P = 0.006), along with a reduction of Enterobacteriaceae (P = 0.018) and Erysipelotrichaceae (P = 0.037) in the gut microbiome, with reduced Enterobacteriaceae among individuals with decreased F-FDG uptake on PET/MRI (P = 0.048). No changes were observed for soluble markers of microbial translocation and inflammation. CONCLUSIONS A decrease in intestinal inflammation was found in HIV-infected individuals after ingestion of LGG along with a reduced abundance of Enterobacteriaceae, which may explain the local anti-inflammatory effect in the gut.
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Palatka K, Kacska S, Lovas S, Garai I, Varga J, Galuska L. The potential role of FDG PET-CT in the characterization of the activity of Crohn's disease, staging follow-up and prognosis estimation: a pilot study. Scand J Gastroenterol 2018; 53:24-30. [PMID: 29043862 DOI: 10.1080/00365521.2017.1390600] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES FDG PET-CT is a global, noninvasive, sensitive method to determine the location and activity of inflammatory lesions. Segmental FDG uptake is proportional with immune cell infiltration of bowel. Our aim was to evaluate prospectively the role of PET in patients with active Crohn's disease (CD) before and after one year's biological therapy, and to compare simple endoscopic score for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed the prognostic value of initial PET scores. PATIENTS Twelve patients were selected: six male/six female, ages between 18 and 39, average: 24 years, with CDAI values >300. METHODS We scored the FDG uptake in the small intestine and the four colon segments (on a scale 0-3 for each), and summed them thus forming a global PET score. The scoring was based on the maximal standardized uptake value of the intestinal segment, related to the SUVmax of the liver (as a reference for normal tissue activity). The SES-CD, CDAI and global PET scores before and after treatment were statistically compared. RESULTS There were significant changes in CDAI and SES-CD after therapy, PET scores improved only in patients' subgroup with high (>4) initial PET score, indicating good prognosis of biological treatment. In active disease, PET was more informative than endoscopy to access the extent of the inflammation, and small intestine involvement. CONCLUSIONS FDG PET-CT score is a promising, noninvasive complementary method in the staging, treatment planning and follow-up of CD. Limitation of the study is the small number of patients.
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Affiliation(s)
- Károly Palatka
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - Sándor Kacska
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - Szilvia Lovas
- a Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | | | - József Varga
- c Department of Medical Imaging, Division of Nuclear Medicine, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
| | - László Galuska
- c Department of Medical Imaging, Division of Nuclear Medicine, Faculty of Medicine , University of Debrecen , Debrecen , Hungary
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18
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Chacko AM, Watanabe S, Herr KJ, Kalimuddin S, Tham JY, Ong J, Reolo M, Serrano RM, Cheung YB, Low JG, Vasudevan SG. 18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response. JCI Insight 2017; 2:93474. [PMID: 28469088 DOI: 10.1172/jci.insight.93474] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 04/04/2017] [Indexed: 01/18/2023] Open
Abstract
Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection-associated inflammation biomarker for assessing treatment response during therapeutic intervention trials.
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Affiliation(s)
- Ann-Marie Chacko
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Satoru Watanabe
- Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore
| | - Keira J Herr
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Shirin Kalimuddin
- Department of Infectious Diseases, Singapore General Hospital, Singapore
| | - Jing Yang Tham
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Joanne Ong
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Marie Reolo
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Raymond Mf Serrano
- Laboratory for Translational and Molecular Imaging, Cancer and Stem Cell Biology Programme, and
| | - Yin Bun Cheung
- Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore.,Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
| | - Jenny Gh Low
- Department of Infectious Diseases, Singapore General Hospital, Singapore
| | - Subhash G Vasudevan
- Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore
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Signore A, Glaudemans AWJM, Gheysens O, Lauri C, Catalano OA. Nuclear Medicine Imaging in Pediatric Infection or Chronic Inflammatory Diseases. Semin Nucl Med 2017; 47:286-303. [PMID: 28417857 DOI: 10.1053/j.semnuclmed.2016.12.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
In this review article, we focus on the most recent applications of nuclear medicine techniques (mainly 99mTc/111In white blood cells (WBC) scan, [18F]-FDG-PET/CT, [18F]-FDG-PET/MRI, and 99mTc-IL-2 scintigraphy) in the study of children affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel diseases, and type 1 diabetes, owing to recent important published evidences of their role in the management of these diseases. For osteomyelitis in children, both bone scintigraphy and [18F]-FDG-PET have a major advantage of assessing the whole body in one imaging session to confirm or exclude multifocal involvement, whereas WBC scan has a limited role. In children with fungal infections, [18F]-FDG-PET can help in defining the best location for biopsy and can help in evaluating the extent of the infection and organs involved (also sites that were not yet clinically apparent), although its main role is for therapy monitoring. In inflammatory bowel diseases, and Crohn disease in particular, WBC scan has been successfully used for many years, but it is now used only in case of doubtful magnetic resonance (MR) or when MR cannot be performed and endoscopy is inconclusive. By contrast, there is an accumulating evidence of the role of [18F]-FDG-PET in management of children with Crohn disease, and PET/MR could be a versatile and innovative hybrid imaging technique that combines the metabolic information of PET with the high soft tissue resolution of MR, particularly for distinguishing fibrotic from active strictures. Finally, there are several new radiopharmaceuticals that specifically target inflammatory cells involved in the pathogenesis of insulitis aiming at developing new specific immunotherapies and to select children candidates to these treatments for improving their quality of life.
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Affiliation(s)
- Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and Translational Medicine, "Sapienza" University of Rome, Rome, Italy.
| | - Andor W J M Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Olivier Gheysens
- Department of Nuclear Medicine and Molecular imaging, University Hospitals Leuven, Leuven, Belgium
| | - Chiara Lauri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and Translational Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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20
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Kim SL, Kim SH, Park YR, Liu YC, Kim EM, Jeong HJ, Kim YN, Seo SY, Kim IH, Lee SO, Lee ST, Kim SW. Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-κB Activation. Mol Cancer Res 2017; 15:141-151. [PMID: 28108625 DOI: 10.1158/1541-7786.mcr-16-0101] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 10/08/2016] [Accepted: 10/10/2016] [Indexed: 11/16/2022]
Abstract
UNLABELLED Balsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets. Apoptosis via NF-κB signaling was confirmed by detecting expression of caspases, p53 and PARP. Moreover, treatment of a CAC murine model with parthenolide and balsalazide together resulted in significant recovery of body weight and improvement in histologic severity. Administration of parthenolide and balsalazide to CAC mice also suppressed carcinogenesis as demonstrated by uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) using micro-PET/CT scans. These results demonstrate that parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-κB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation. IMPLICATIONS This study represents the first evidence that combination therapy with balsalazide and parthenolide could be a new regimen for colorectal cancer treatment. Mol Cancer Res; 15(2); 141-51. ©2016 AACR.
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Affiliation(s)
- Se-Lim Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Seong Hun Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Young Ran Park
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Yu-Chuan Liu
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Eun-Mi Kim
- Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Hwan-Jeong Jeong
- Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Yo Na Kim
- Department of Pathology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Seung Young Seo
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - In Hee Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Seung Ok Lee
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Soo Teik Lee
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea
| | - Sang-Wook Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
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Fidler JL, Goenka AH, Fleming CJ, Andrews JC. Small Bowel Imaging: Computed Tomography Enterography, Magnetic Resonance Enterography, Angiography, and Nuclear Medicine. Gastrointest Endosc Clin N Am 2017; 27:133-152. [PMID: 27908513 DOI: 10.1016/j.giec.2016.08.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Radiology examinations play a major role in the diagnosis, management, and surveillance of small bowel diseases and are complementary to endoscopic techniques. Computed tomography enterography and magnetic resonance enterography are the cross-sectional imaging studies of choice for many small bowel diseases. Angiography still plays an important role for catheter-directed therapies. With the emergence of hybrid imaging techniques, radionuclide imaging has shown promise for the evaluation of small bowel bleeding and Crohn disease and may play a larger role in the future. This article reviews recent advances in technology, diagnosis, and therapeutic options for selected small bowel disorders.
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Affiliation(s)
- Jeff L Fidler
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Chad J Fleming
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - James C Andrews
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn's Disease. Inflamm Bowel Dis 2016; 22:2619-2629. [PMID: 27753695 DOI: 10.1097/mib.0000000000000924] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Fluorine-fluorodeoxyglucose positron emission tomography (F-FDG PET) has recently attracted interest for the measurement of disease activity in Crohn's disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activity and its response to treatment in patients with CD. METHODS Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used to assess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity (Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component and underwent scanning before and 12 weeks after the initiation of anti-tumor necrosis factor alpha therapy. Patients were subcategorized on the basis of a clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took part in the test-retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures. RESULTS The sensitivity and specificity of F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measures correlated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEAN demonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt >0.80 and % variability <20%) compared with volume-dependent FDG-PET measures. A proportion of the FDG signal (10%-30%) was found to originate from the lumen of diseased segments. CONCLUSIONS F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.
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Caobelli F, Evangelista L, Quartuccio N, Familiari D, Altini C, Castello A, Cucinotta M, Di Dato R, Ferrari C, Kokomani A, Laghai I, Laudicella R, Migliari S, Orsini F, Pignata SA, Popescu C, Puta E, Ricci M, Seghezzi S, Sindoni A, Sollini M, Sturiale L, Svyridenka A, Vergura V, Alongi P, Young AIMN Working Group. Role of molecular imaging in the management of patients affected by inflammatory bowel disease: State-of-the-art. World J Radiol 2016; 8:829-845. [PMID: 27843542 PMCID: PMC5084061 DOI: 10.4329/wjr.v8.i10.829] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Revised: 06/30/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease (IBD).
METHODS A systematic review of the literature was performed in order to find important original articles on the role of molecular imaging in the management of patients affected by IBD. The search was updated until February 2016 and limited to articles in English.
RESULTS Fifty-five original articles were included in this review, highlighting the role of single photon emission tomography and positron emission tomography.
CONCLUSION To date, molecular imaging represents a useful tool to detect active disease in IBD. However, the available data need to be validated in prospective multicenter studies on larger patient samples.
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Brückner M, Lenz P, Mücke MM, Gohar F, Willeke P, Domagk D, Bettenworth D. Diagnostic imaging advances in murine models of colitis. World J Gastroenterol 2016; 22:996-1007. [PMID: 26811642 PMCID: PMC4716050 DOI: 10.3748/wjg.v22.i3.996] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/09/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
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A longitudinal study of FDG-PET in Crohn disease patients receiving granulocyte/monocyte apheresis therapy. Cytotherapy 2015; 18:291-9. [PMID: 26700210 DOI: 10.1016/j.jcyt.2015.10.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 10/13/2015] [Accepted: 10/16/2015] [Indexed: 12/30/2022]
Abstract
BACKGROUND AIMS Endoscopy is the gold standard for the diagnosis and follow-up of patients with Crohn disease (CD). However, a less invasive approach is now being sought for the management of these patients. The objective of this study was to examine whether (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) might be relevant for monitoring the disease activity in CD patients undergoing granulocyte/monocyte apheresis (GMA). METHODS This study was conducted in 12 patients with CD who were receiving treatment with 10 once-a-week GMA sessions with the Adacolumn. The response to treatment was monitored by measuring standard laboratory variables, Crohn's Disease Activity Index (CDAI) score, International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score, and regional and global bowel uptakes on FDG-PET. RESULTS In 6 of the 12 patients, significant improvement of the CDAI was observed after the final session of GMA. The patients who showed clinical response to GMA had a decrease in the regional and global bowel uptakes on FDG-PET, whereas those who did not respond showed no change. In the patients who responded to the GMA, the decrease in regional bowel uptake on FDG-PET in each disease area of the same patient varied in parallel. There was a significant correlation between decrease in the global bowel uptake on FDG-PET and improvement of the CDAI and IOIBD scores. CONCLUSIONS The longitudinal changes in FDG-PET uptakes are of potential clinical interest for assessing the regional and global bowel disease activity in CD patients undergoing GMA therapy.
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Casciani E, Vincentiis CD, Gualdi G. Small bowel imaging of inflammatory bowel disease. World J Radiol 2015; 7:198-201. [PMID: 26339463 PMCID: PMC4553251 DOI: 10.4329/wjr.v7.i8.198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/26/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
The study of the small bowel (SB) has always been challenging both for clinicians and radiologist. It is a long and tortuous tube that can be affected by various pathologies whose signs and symptoms are usually non specific and can mimic other acute abdominal disorders. For these reasons, imaging plays a central role in the diagnosis of the different pathological conditions that can occur. They are important also in the management and follow up of chronic diseases. We expose and evaluate all the radiological methods that are now available for the study of the SB with particular emphasis on the technological improvement of cross-sectional imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI). These techniques have, infact, highly improved in terms of execution times (fast acquisitions images), patients discomfort and radiation dose, for CT, with consequent reduced biological risks. Moreover, the new post-processing options with multiplanar reconstruction and isotropic images have made significant changes in the evaluation of the exams. Especially MRI scans have been improved by the advent of new sequences, such as diffusion weighted imaging and cine-MRI, parallel imaging and breath-hold sequences and can provide excellent soft-tissue contrast without the use of ionizing radiations.
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Yacoub JH, Oto A. Diagnostics: The Future. CROHN’S DISEASE 2015:131-146. [DOI: 10.1007/978-3-319-14181-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Inflammation. THE PATHOPHYSIOLOGIC BASIS OF NUCLEAR MEDICINE 2015. [PMCID: PMC7123337 DOI: 10.1007/978-3-319-06112-2_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Inflammation was described as early as 3000 BC in an Egyptian papyrus [1] and is still a common problem despite continuous advancements in prevention and treatment methods. The delineation of the site and extent of inflammation are crucial to the clinical management of infection and for monitoring the response to therapy [2].
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Hess S, Hansson SH, Pedersen KT, Basu S, Høilund-Carlsen PF. FDG-PET/CT in Infectious and Inflammatory Diseases. PET Clin 2014; 9:497-519, vi-vii. [PMID: 26050949 DOI: 10.1016/j.cpet.2014.07.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Casciani E, Vincentiis CD, Polettini E, Masselli G, Nardo GD, Civitelli F, Cucchiara S, Gualdi GF. Imaging of the small bowel: Crohn’s disease in paediatric patients. World J Radiol 2014; 6:313-328. [PMID: 24976933 PMCID: PMC4072817 DOI: 10.4329/wjr.v6.i6.313] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 05/16/2014] [Indexed: 02/06/2023] Open
Abstract
In more than 20% of all patients, the Crohn’s disease presents before the age of 18years. The diagnosis and management of Crohn’s disease in children has changed dramatically over the last decade, mainly due to increased awareness, availability of newer diagnostic modalities such as magnetic resonance imaging (MRI) and newer, more powerful treatments such as biologics. Imaging of the small bowel is needed for diagnosis, management, follow-up and also evaluation of the disease in terms of location, extent, activity and complications. We review all the methods (barium examinations, ultrasonography, computed tomography, MR, and computed tomography- positron emission tomography) commonly used for imaging the small bowel in paediatric patients with Crohn’s disease analyzing the advantages and disadvantages of each modality, with particular emphasis on MR imaging.
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Abstract
PET/CT imaging has become an important part of the evaluation of patients with many types of cancer. This imaging modality can also be used to image areas of active inflammation, such as those occurring in patients with active inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). The standard methods of determining a patient's disease activity are either indirect, such as blood and stool tests, or invasive, such as colonoscopy. FDG-PET imaging is a noninvasive, direct method of evaluating bowel inflammation and represents a significant advancement in the care of these patients. The PET/CT technique is very similar to that used for oncology imaging. Minor changes can be instituted to improve the accuracy, as well as to reduce the radiation exposure to the patient. This paper reviews the literature on the use of FDG-PET imaging in IBD in both the adult and pediatric populations. Future improvements in the technique should focus on decreasing the radiation dose to the patient and on decreasing the cost of the examination. The FDG-PET/CT technique is an excellent method for the noninvasive quantification of bowel inflammation in patients with IBD.
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Affiliation(s)
- Scott B Perlman
- The University of Wisconsin School of Medicine and Public Health, Madison, WI.
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Abstract
Radiographical modalities have become important diagnostic tools in cases of ulcerative colitis (UC). Imaging can be used non-invasively to determine the extent of involvement, severity of disease and to detect disease-related complications and extra-intestinal inflammatory bowel disease (IBD) manifestations. While abdominal X-rays and barium enemas still retain their relevance in specific clinical settings, the use of computed tomography enterography (CTE) or magnetic resonance enterography (MRE) are now used as first-line investigations to exclude active small bowel disease in IBD patients and can be utilized to detect active colonic inflammation. Additionally, CT colonography and MR colonography are emerging techniques with potential applications in UC. Ultrasonography, leukocyte scintigraphy and positron emission tomography are novel abdominal imaging modalities currently being explored for IBD interrogations. This plethora of radiological imaging options has become a vital component of UC assessments.
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Affiliation(s)
- Parakkal Deepak
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester MN, USA
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester MN, USA
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Wu YW, Tseng PH, Lee YC, Wang SY, Chiu HM, Tu CH, Wang HP, Lin JT, Wu MS, Yang WS. Association of esophageal inflammation, obesity and gastroesophageal reflux disease: from FDG PET/CT perspective. PLoS One 2014; 9:e92001. [PMID: 24642729 PMCID: PMC3958434 DOI: 10.1371/journal.pone.0092001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Accepted: 02/15/2014] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Gastroesophageal reflux disease (GERD) is associated with bothersome symptoms and neoplastic progression into Barrett's esophagus and esophageal adenocarcinoma. We aim to determine the correlation between GERD, esophageal inflammation and obesity with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). METHODS We studied 458 subjects who underwent a comprehensive health check-up, which included an upper gastrointestinal endoscopy, FDG PET/CT and complete anthropometric measures. GERD symptoms were evaluated with Reflux Disease Questionnaire. Endoscopically erosive esophagitis was scored using the Los Angeles classification system. Inflammatory activity, represented by standardized uptake values (SUVmax) of FDG at pre-determined locations of esophagus, stomach and duodenum, were compared. Association between erosive esophagitis, FDG activity and anthropometric evaluation, including body mass index (BMI), waist circumference, visceral and subcutaneous adipose tissue volumes were analyzed. RESULTS Subjects with erosive esophagitis (n = 178, 38.9%) had significantly higher SUVmax at middle esophagus (2.69±0.74 vs. 2.41±0.57, P<.001) and esophagogastric junction (3.10±0.89 vs. 2.38±0.57, P<.001), marginally higher at upper esophageal sphincter (2.29±0.42 vs. 2.21±0.48, P = .062), but not in stomach or duodenum. The severity of erosive esophagitis correlated with SUVmax and subjects with Barrett's esophagus had the highest SUVmax at middle esophagus and esophagogastric junction. Heartburn positively correlated with higher SUVmax at middle oesophagus (r = .262, P = .003). Using multivariate regression analyses, age (P = .027), total cholesterol level (P = .003), alcohol drinking (P = .03), subcutaneous adipose tissue (P<.001), BMI (P<.001) and waist circumference (P<.001) were independently associated with higher SUVmax at respective esophageal locations. CONCLUSIONS Esophageal inflammation demonstrated by FDG PET/CT correlates with endoscopic findings and symptomatology of GERD. Obesity markers, both visceral and general, are independent determinants of esophageal inflammation.
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Affiliation(s)
- Yen-Wen Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Nuclear Medicine and Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Shan-Ying Wang
- Department of Nuclear Medicine and Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hung Tu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
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Segmental "misty mesentery" on FDG PET/CT: an uncommon manifestation of mesenteric lymphoma. Clin Nucl Med 2014; 39:84-6. [PMID: 23797224 DOI: 10.1097/rlu.0b013e31829960f6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Mesenteric lymphomas are commonly seen as bulky hypermetabolic nodal masses on F-FDG PET/CT. Very rarely, these are seen as mesenteric haziness due to localized hyperattenuation of fat, known as "misty mesentery", which morphological imaging-wise has other differentials as well. We report a unique imaging finding of segmental misty mesentery with hypermetabolic mesenteric nodes on FDG PET/CT in a patient who was kept on observation due to inconclusive biopsy, which on follow-up imaging progressed to extensive lymphomatous involvement. Thus, in retrospect, this imaging feature on baseline PET/CT was diagnostic for mesenteric lymphoma.
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FDG PET/CT in Crohn's disease: correlation of quantitative FDG PET/CT parameters with clinical and endoscopic surrogate markers of disease activity. Eur J Nucl Med Mol Imaging 2013; 41:605-14. [PMID: 24253895 DOI: 10.1007/s00259-013-2625-2] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 10/31/2013] [Indexed: 02/08/2023]
Abstract
PURPOSE The aim of this study was to determine the feasibility and potential clinical utility of assessment of Crohn's disease (CD) activity by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT employing a new quantitative approach. METHODS A total of 22 subjects (mean age 37) with CD who had undergone FDG PET/CT followed by ileocolonoscopy within 1 week were included in this analysis. The CD endoscopy index of severity (CDEIS) for various bowel segments was calculated. The CD activity index (CDAI) was evaluated, and fecal calprotectin was measured. On PET, regions with increased FDG uptake in large bowel were segmented with an adaptive contrast-oriented thresholding algorithm, and metabolically active volume (MAV), uncorrected mean standardized uptake value (SUV(mean)), partial volume-corrected SUV(mean) (PVC-SUV(mean)), SUV(max), uncorrected total lesion glycolysis (TLG = MAV × SUV(mean)), and PVC total lesion glycolysis (PVC-TLG = MAV × PVC-SUV(mean)) were measured. Global CD activity score (GCDAS) was calculated as the sum of PVC-TLG over all clinically significant FDG-avid regions in each subject. Correlations between regional PET quantification measures (SUVs, TLGs) and CDEIS were calculated. Correlations between the global PET quantification measure (GCDAS, global SUVs) with CDAI, fecal calprotectin, CDEIS, and CRP level were also calculated. RESULTS SUV(max), PVC-SUV(mean), and PVC-TLG significantly correlated with segment CDEIS subscores (r = 0.50, r = 0.69, and r = 0.31, respectively; p < 0.05). GCDAS significantly correlated with CDAI and fecal calprotectin (r = 0.64 and r = 0.51, respectively; p < 0.05). CONCLUSION By employing this new quantitative approach, we were able to calculate indices of regional and global CD activity, which correlated well with both clinical and pathological disease activity surrogate markers. This approach may be of clinical importance in measuring both global disease activity and treatment response in patients with CD.
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The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. Clin Dev Immunol 2013; 2013:623036. [PMID: 24027590 PMCID: PMC3763592 DOI: 10.1155/2013/623036] [Citation(s) in RCA: 172] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 07/20/2013] [Indexed: 02/08/2023]
Abstract
FDG-PET, combined with CT, is nowadays getting more and more relevant for the diagnosis of several infectious and inflammatory diseases and particularly for therapy monitoring. Thus, this paper gives special attention to the role of FDG-PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory diseases. Enough evidence in the literature already exists about the usefulness of FDG-PET/CT in the diagnosis, management, and followup of patients with sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and fungal infections, hard evidence is lacking, but studies also point out that FDG-PET/CT could be useful. It is of invaluable importance to have large prospective multicenter studies in this field to provide clear answers, not only for the status of nuclear medicine in general but also to reduce high costs of treatment.
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Treglia G, Quartuccio N, Sadeghi R, Farchione A, Caldarella C, Bertagna F, Fania P, Cistaro A. Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in patients with chronic inflammatory bowel disease: a systematic review and a meta-analysis. J Crohns Colitis 2013; 7:345-354. [PMID: 22960135 DOI: 10.1016/j.crohns.2012.08.005] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Revised: 08/04/2012] [Accepted: 08/06/2012] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in patients with chronic inflammatory bowel disease (IBD). METHODS A comprehensive computer literature search of studies published through May 2012 regarding (18)F-FDG-PET and PET/CT in patients with IBD was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG PET and PET/CT in patients with IBD on a per segment-based analysis were calculated. The area under the ROC curve was calculated to measure the accuracy of (18)F-FDG PET and PET/CT in patients with IBD. RESULTS Nineteen studies comprising 454 patients with suspected IBD were included in the qualitative analysis (systematic review) and discussed. The quantitative analysis (meta-analysis) of seven selected studies (including 219 patients with IBD) provided the following results on a per segment-based analysis: sensitivity was 85% [95% confidence interval (95%CI) 81-88%], specificity 87% (95%CI 84-90%), LR+ 6.19 (95%CI: 2.86-13.41), LR- 0.19 (95%CI: 0.10-0.34), and DOR 44.35 (95%CI: 11.77-167.07). The area under the ROC curve was 0.933. CONCLUSIONS In patients with suspected IBD (18)F-FDG PET and PET/CT demonstrated good sensitivity and specificity, being accurate methods in this setting. Nevertheless, the literature focusing on the use of PET and PET/CT in IBD remains still limited; thus, further large multicenter studies will be necessary to substantiate the diagnostic accuracy of these methods in patients with IBD.
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Affiliation(s)
- Giorgio Treglia
- Institute of Nuclear Medicine, Catholic University of Sacred Heart, Rome, Italy.
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Bettenworth D, Reuter S, Hermann S, Weckesser M, Kerstiens L, Stratis A, Nowacki TM, Ross M, Lenze F, Edemir B, Maaser C, Pap T, Koschmieder S, Heidemann J, Schäfers M, Lügering A. Translational 18F-FDG PET/CT imaging to monitor lesion activity in intestinal inflammation. J Nucl Med 2013; 54:748-755. [PMID: 23516311 DOI: 10.2967/jnumed.112.112623] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED In patients with inflammatory bowel disease (IBD) and in murine IBD models, mucosal disease activity is routinely assessed by endoscopy and histologic evaluation. This information is valuable for monitoring treatment response, with mucosal healing being a major treatment goal. The aim of this study was to evaluate the translational potential of noninvasive (18)F-FDG PET/CT for the assessment of mucosal damage in murine dextran sodium sulfate (DSS) colitis and human IBD. METHODS After induction of DSS colitis, (18)F-FDG uptake was serially assessed from colonic volumes of interest defined on PET/CT scans and intraindividually correlated to histologic findings and to infiltrating cell types. In addition, (18)F-FDG PET/CT scans of 25 Crohn disease patients were analyzed, and colonic (18)F-FDG uptake was correlated to endoscopically assessed damage. RESULTS At days 4 and 7 after DSS induction, colonic (18)F-FDG uptake was significantly increased, with a distinct peak in the medial colon. (18)F-FDG uptake strongly correlated with histologic epithelial damage. Additionally, (18)F-FDG uptake increased in the bone marrow in the course of the disease, correlating with an increase in intestinal (18)F-FDG uptake. Histology and fluorescence-activated cell sorting analysis of the bone marrow of DSS mice revealed an increased number of immature neutrophils, whereas mucosal polymerase chain reaction suggested a correlation of (18)F-FDG uptake to T cell infiltration. In accordance with the results of (18)F-FDG PET/CT in DSS colitis, an increased (18)F-FDG uptake was found in 87% of deep mucosal ulcerations in IBD patients, whereas mild endoscopic lesions were detected only by (18)F-FDG PET/CT in about 50% of patients assessed. CONCLUSION (18)F-FDG PET/CT is a noninvasive method for evaluation of both experimental colitis and Crohn disease patients and thereby offers promising translational potential.
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Heylen M, Deleye S, De Man JG, Ruyssers NE, Vermeulen W, Stroobants S, Pelckmans PA, Moreels TG, Staelens S, De Winter BY. Colonoscopy and µPET/CT are valid techniques to monitor inflammation in the adoptive transfer colitis model in mice. Inflamm Bowel Dis 2013; 19:967-976. [PMID: 23407045 DOI: 10.1097/mib.0b013e3182802c7c] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Preclinical in vivo research on inflammatory bowel diseases requires proper animal models and techniques allowing longitudinal monitoring of colonic inflammation without the need to kill animals. We evaluated colonoscopy and μ-positron emission tomography/computed tomography (μPET/CT) as monitoring tools in a model for chronic colitis in mice. METHODS Colitis was induced by adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in immunocompromised severe combined immunodeficient mice. Three study protocols were designed. In study 1, colonoscopy and µPET/CT were performed once, 4 weeks after transfer. In study 2 and study 3, colitis was sequentially followed up through colonoscopy (study 2) or colonoscopy plus µPET/CT (study 3). Each study included postmortem evaluation of colonic inflammation (macroscopy, microscopy, and myeloperoxidase activity). RESULTS In study 1, both colonoscopy and µPET/CT detected colitis 4 weeks after transfer. Study 2 showed a gradual increase in colonoscopic score from week 2 (1.4 ± 0.6) to week 8 (6.0 ± 1.1). In study 3, colitis was detected 2 weeks after transfer by µPET/CT (2.0 ± 0.4) but not by colonoscopy, whereas both techniques detected inflammation 4 and 6 weeks after transfer. Colonoscopy correlated with µPET/CT (r = 0.812, 0.884, and 0.781, respectively) and with postmortem analyses in all 3 studies. CONCLUSIONS Adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in severe combined immunodeficient mice results in a moderate chronic colitis. Evolution of colitis could be monitored over time by both colonoscopy and µPET/CT. µPET/CT seems to detect inflammation at an earlier time point than colonoscopy. Both techniques represent reliable and safe methods without the need to kill animals.
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Affiliation(s)
- Marthe Heylen
- Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium
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Lenze F, Wessling J, Bremer J, Ullerich H, Spieker T, Weckesser M, Gonschorrek S, Kannengiesser K, Rijcken E, Heidemann J, Luegering A, Schober O, Domschke W, Kucharzik T, Maaser C. Detection and differentiation of inflammatory versus fibromatous Crohn's disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis 2012; 18:2252-60. [PMID: 22359277 DOI: 10.1002/ibd.22930] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2011] [Accepted: 02/02/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Differentiation between inflammatory and fibromatous strictures in Crohn's disease (CD) is difficult but crucial for therapeutic decisions. The aim of this study was to assess the best noninvasive imaging method for the detection and differentiation of inflammatory and fibromatous stenoses in CD in comparison to endoscopic and histologic evaluation. METHODS Patients with suspected CD strictures were included. According to a formalized endoscopic and histologic protocol, strictures were classified as inflammatory, mixed, and fibrostenotic. Strictures were further analyzed using fluorine 18-labeled fluoro-2-deoxy-D-glucose ((18) FDG) / positron emission tomography (PET) low-dose computed tomography (CT), magnetic resonance (MR) enteroclysis and transabdominal ultrasound using standardized scoring systems. RESULTS Thirty patients with 37 strictures were evaluated (inflamed n = 22; mixed n = 12, fibromatous n = 3). (18) FDG-PET/CT detected 81%, MR-enteroclysis 81%, and ultrasound 68% of the strictures. Correct differentiation rates of strictures were 57% for MRE, 53% for (18) FDG-PET/CT, and 40% for ultrasound. Differences of detection rates and differentiation rates were not statistically significant. When combining transabdominal ultrasound with (18) FDG-PET/CT or MR-enteroclysis all strictures that required invasive treatment were detected. CONCLUSIONS Detection rates of the strictures were not significantly different between (18) FDG-PET/CT, MR-enteroclysis, and ultrasound. Despite good stricture detection rates relating to our gold standard, (18) FDG-PET/CT nor MR-enteroclysis nor ultrasound can accurately differentiate inflamed from fibrotic strictures. A combination of MR-enteroclysis and ultrasound as well as a combination of (18) FDG-PET/CT and ultrasound resulted in a 100% detection rate of strictures requiring surgery or endoscopic dilation therapy, suggesting the combination of these methods as an alternative to endoscopy at least in the group of patients not able to perform an adequate bowel preparation.
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Affiliation(s)
- Frank Lenze
- Department of Medicine B, University of Muenster, Muenster, Germany.
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Cronin CG, Scott J, Kambadakone A, Catalano OA, Sahani D, Blake MA, McDermott S. Utility of positron emission tomography/CT in the evaluation of small bowel pathology. Br J Radiol 2012; 85:1211-21. [PMID: 22919004 DOI: 10.1259/bjr/64534573] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We describe the management principles and different roles of positron emission tomography (PET)/CT in the evaluation of patients with small bowel tumours (adenocarcinoma, gastrointestinal stromal tumour, lymphoma, metastases) from initial staging, monitoring response to treatment, to detection of recurrent disease. We also discuss the various non-malignant aetiologies of small bowel fludeoxyglucose (FDG) PET uptake, and other pitfalls in FDG PET/CT interpretation. Awareness of the imaging appearances of small bowel tumours, patterns of disease spread and potential PET/CT interpretation pitfalls are of paramount importance to optimise diagnostic accuracy.
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Affiliation(s)
- C G Cronin
- Department of Abdominal Imaging and Interventional Radiology, Massachusetts General Hospital, Boston, MA, USA.
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Shyn PB. 18F-FDG positron emission tomography: potential utility in the assessment of Crohn's disease. ACTA ACUST UNITED AC 2012; 37:377-86. [PMID: 21833729 DOI: 10.1007/s00261-011-9793-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Computed Tomography Enterography (CTE) and Magnetic Resonance Enterography (MRE) are currently the dominant imaging tests used in the assessment of patients with Crohn's disease. More recently, the possibility of utilizing F-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) or PET/CT has been explored in several preliminary studies. 18F-FDG PET appears to enable reliable detection of moderate to severe inflammation in bowel segments involved by Crohn's disease. Perhaps more importantly, 18F-FDG PET has the potential to provide a noninvasive, quantitative measure of inflammation that dynamically reflects changes in Crohn's disease activity. If 18F-FDG PET proves useful in monitoring responses to medical therapy within a few days of therapy initiation, an important new role for imaging in the management of patients with Crohn's disease could emerge.
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Affiliation(s)
- Paul B Shyn
- Department of Radiology, Abdominal Imaging and Intervention, Brigham and Women's Hospital, Boston, MA 02115, USA.
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Holtmann MH, Uenzen M, Helisch A, Dahmen A, Mudter J, Goetz M, Schreckenberger M, Galle PR, Bartenstein P, Neurath MF. 18F-Fluorodeoxyglucose positron-emission tomography (PET) can be used to assess inflammation non-invasively in Crohn's disease. Dig Dis Sci 2012; 57:2658-68. [PMID: 22569824 DOI: 10.1007/s10620-012-2190-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2011] [Accepted: 04/14/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND Differential therapy requires repeated diagnostic assessment for mapping and monitoring of disease activity in Crohn's disease (CD). PURPOSE The purpose of this prospective study was to evaluate the accuracy of (18)F-fluorodexyglucose positron-emission tomography (FDG-PET) for non-invasive assessment of disease activity in CD. METHODS Forty-three patients with CD underwent ileocolonoscopy and hydromagnetic resonance imaging (hydro-MRI) as reference standards. In addition, FDG-PET was performed and correlated with clinical data, hydro-MRI, and endoscopy findings. Diagnostic accuracy was determined for all methods. RESULTS Two-hundred and forty-one bowel segments could be analyzed by all methods. Of 80 endoscopically inflamed segments in CD, FDG-PET detected 72 and hydro-MRI 53 segments. Overall sensitivity was 90 % (FDG-PET) versus 66 % (hydro-MRI), and specificity was 92.6 % versus 99 %. In the proximal ileum, hydro-MRI revealed inflammation in eight out of 49 patients and FDG-PET, also, detected all of these inflamed segments. Seventeen stenoses could be identified in 43 CD patients. With regard to assessment as inflammatory or fibrotic stenosis, there was good concordance between colonoscopy, hydro-MRI, and FDG-PET. In one case only, the nature of the stenosis was assessed differently. In contrast with leukocyte numbers and CDAI, there was significant correlation of FDG-PET activity with C-reactive protein and CDEIS levels (P = 0.019 and P = 0.007, respectively). CONCLUSION FDG-PET is able to detect mucosal inflammation in CD with high sensitivity and specificity and to enable proper assessment of inflammatory activity in stenoses. FDG-PET is, thus, a promising non-invasive technique for clinical management of CD.
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Affiliation(s)
- Martin H Holtmann
- 1st Department of Medicine, Johannes Gutenberg-University, 55131 Mainz, Langenbeckstrasse 1, Mainz, Germany.
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Silindir M, Özer AY, Erdoğan S. The use and importance of liposomes in positron emission tomography. Drug Deliv 2012; 19:68-80. [PMID: 22211758 DOI: 10.3109/10717544.2011.635721] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Among different imaging modalities, Positron Emission Tomography (PET) gained importance in routine hospital practice depending on ability to diagnose diseases in early stages and tracing of therapy by obtaining metabolic information. The combination of PET with Computed Tomography (CT) forms hybrid imaging modality that gives chance to obtain better images having higher resolution by fusing both functional and anatomical images in the same imaging modality at the same time. Therefore, better contrast agents are essentially needed. The advance in research about developing drug delivery systems as specific nanosized targeted systems gained an additional importance for obtaining better diagnosis and therapy of different diseases. Liposomes appear to be more attractive drug delivery systems in delivering either drugs or imaging ligands to target tissue or organ of diseases with higher accumulation by producing in nano-scale, long circulating by stealth effect and specific targeting by modifying with specific ligands or markers. The combination of positron emitting radionuclides with liposomes are commonly in research level nowadays and there is no commercially available liposome formulation for PET imaging. However by conjugating positron emitter radionuclide with liposomes can form promising diagnostic agents for improved diagnosis and following up treatments by increasing image signal/contrast in the target tissue in lower concentrations by specific targeting as the most important advantage of liposomes. More accurate and earlier diagnosis of several diseases can be obtained even in molecular level with the use of stable and effectively radiolabeled molecular target specific nano sized liposomes with longer half-lived positron emitting radionuclides.
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Affiliation(s)
- Mine Silindir
- Department of Radiopharmacy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
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Cistaro A, Quartuccio N, Mansi L, Signore A, Dolci M, Treglia G. The Role of Positron Emission Tomography in Inflammatory Bowel Disease. EUR J INFLAMM 2012; 10:251-256. [DOI: 10.1177/1721727x1201000301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are a group of pathological conditions characterized by chronic inflammation of the gastrointestinal tract, including Crohn's disease and ulcerative colitis. To date, imaging of IBD is based on several radiological techniques such as barium studies, magnetic resonance imaging, and computed tomography (CT). Endoscopy is the gold standard for the assessment of the large bowel and proximal small intestine in patients with IBD allowing the biopsy of the visualized bowel. Positron emission tomography (PET) and PET/CT with Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is a functional imaging method used to detect abnormalities in glucose metabolism in a variety of disorders. FDG accumulates mainly in tumours, but increased uptake and retention has been shown also in lesions with a high concentration of inflammatory cells, such as granulocytes and activated macrophages. Recent literature data demonstrate that FDG-PET and PET/CT may be useful noninvasive tools for identifying and localizing active IBD. In patients with an established diagnosis of IBD, FDG-PET and PET/CT may provide information about disease activity, location and extent of the disease within the intestinal tract, allowing early recognition of disease relapse and possible complications. Furthermore, these techniques may play a role in assessing the treatment response to medical therapy in patients with IBD.
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Affiliation(s)
- A. Cistaro
- Positron Emission Tomography Centre, IRMET S.p.A., Turin, Italy
| | - N. Quartuccio
- Department of Radiological Sciences, Nuclear Medicine Unit, University of Messina, Messina, Italy
| | - L. Mansi
- Nuclear Medicine Division, Second University of Naples, Naples, Italy
| | - A. Signore
- Nuclear Medicine Unit, Faculty of Medicine and Psychology, “Sapienza” University of Rome, Rome, Italy
| | - M. Dolci
- Department of Medical, Oral and Biotechnological Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
| | - G. Treglia
- Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Rome, Italy
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Jouan Y, Venel Y, Lioger B, du Sorbier CM, Gaucher L, Marchand-Adam S, Diot P, Diot E. Tracheal involvement in ulcerative colitis: clinical presentation and potential interest of 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography (18F-FDG PET) for the management. Ann Nucl Med 2012; 26:830-4. [DOI: 10.1007/s12149-012-0646-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 07/17/2012] [Indexed: 11/29/2022]
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Di Gialleonardo V, Signore A, Glaudemans AW, Dierckx RA, De Vries EF. N-(4-18F-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes. J Nucl Med 2012; 53:679-86. [DOI: 10.2967/jnumed.111.091306] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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Hindryckx P, Staelens S, Devisscher L, Deleye S, De Vos F, Delrue L, Peeters H, Laukens D, De Vos M. Longitudinal quantification of inflammation in the murine dextran sodium sulfate-induced colitis model using μPET/CT. Inflamm Bowel Dis 2011; 17:2058-64. [PMID: 21910167 DOI: 10.1002/ibd.21578] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2010] [Accepted: 10/18/2010] [Indexed: 12/31/2022]
Abstract
BACKGROUND This study investigates whether deoxy-2-[18F]fluoro-d-glucose (FDG) micro-positron emission tomography (μPET)/computed tomography (CT) can serve as a tool for monitoring of the commonly used dextran sodium sulfate (DSS)-induced murine model of inflammatory bowel disease (IBD). METHODS DSS-colitis was induced in Sv129 mice. In a first experiment, four animals were serially scanned with CT and FDG-μPET on days 0, 3, 7, 11, and 14. The ratio of the mean voxel count of the PET images in the colon and the brain was compared with the histological inflammation score and the colonic myeloperoxidase levels. A second experiment was performed to investigate whether FDG-μPET was able to detect differences in inflammation between two DSS-treated groups, one receiving placebo (n = 4) and one receiving dimethyloxalylglycine (DMOG) (n = 4), a compound that protects against DSS-induced colitis. RESULTS The progression of the colonic/brain FDG-signal ratio (over days 0-14) agreed with the predicted histological inflammation score, obtained from a parallel DSS-experiment. Moreover, the quantification of normalized colonic FDG-activity at the final timepoint (day 14) showed an excellent correlation with both the MPO levels (Spearman's rho = 1) and the histological inflammation score (Spearman's rho = 0.949) of the scanned mice. The protective action of DMOG in DSS colitis was clearly demonstrated with FDG-μPET/CT (normalized colonic FDG-activity DMOG versus placebo: P < 0.05). CONCLUSIONS FDG-μPET-CT is a feasible and reliable noninvasive method to monitor murine DSS-induced colitis. The implementation of this technique in this widely used IBD model opens a new window for pathophysiological research and high-throughput screening of potential therapeutic compounds in preclinical IBD research.
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Affiliation(s)
- P Hindryckx
- Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium.
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