TY - GEN
T1 - Positron Emission Tomographyin Gastrointestinal Inflammation
T2 - Studies in Paediatric Inflammatory Bowel Diseaseand Experimental Chemotherapy-induced Mucositis
AU - Dalby, Sina
PY - 2023/5/11
Y1 - 2023/5/11
N2 - Since its development in the 1970s, positron emission tomography (PET) has played acentral role in detecting and assessing oncological, infectious, and inflammatory conditions. As PET shows function rather than structure, it is often combined with computed tomography (CT) or magnetic resonance imaging (MRI) for anatomical information. The advent of these hybrid-imaging modalities has entailed new, potential applications beneficialto patients in many instances.Diagnosing and evaluating chronic inflammatory bowel diseases (IBD), such as Crohn’sdisease and ulcerative colitis, rely on a multifaceted approach, including endoscopy andcross-sectional imaging. Hybrid imaging with PET has shown promising results in detecting IBD in the gastrointestinal tract in adults. The diagnostic performance, usually coinedas the sensitivity and specificity, in IBD has both been shown to be high for PET combinedwith MRI.Gastrointestinal inflammation may occur in the course of cancer chemotherapy. Through aseries of dynamic processes, various types of chemotherapy may induce inflammation andulceration throughout the gastrointestinal tract. In the oral cavity, direct inspection sufficesto make a diagnosis and staging, while in the gastrointestinal tract, objective and feasiblemethods are lacking, both in clinical and preclinical settings.We hypothesised that PET combined with MRI was a sensitive and specific method to diagnose IBD in the gastrointestinal tract of children suspected of IBD and to monitor response to treatment. We also hypothesised that PET combined with computed tomography could detect and quantify gastrointestinal mucositis caused by doxorubicin treatmentin an experimental mucositis model.The first study of diagnostic accuracy aimed to estimate the diagnostic accuracy ofPET/MRI at the time of diagnosis of IBD in paediatric patients. The results of the scanwere compared to the findings on endoscopy and histopathology and showed a moderatediagnostic performance of each modality alone and of the combined parameter of PET andMRI.In the second study, a pilot study with a follow-up scan, we evaluated the applicability ofPET/MRI in treatment monitoring. We included patients diagnosed with Crohn’s disease inthe first study and six patients with known Crohn’s disease who initiated biological therapy. These pilot observations suggested that PET/MRI may have a potential role in treatmentmonitoring, but more research is needed.In the third experimental study, we aimed to evaluate the utility of PET/CT in assessingmucositis. We induced mucositis with doxorubicin in mice, and PET/CT scanned them sequentially to evaluate the development and resolution of mucositis. The results showed anincrease in the abdominal standardized uptake value of radioactive tracer in mice with mucositis compared to controls. Furthermore, mucositis appeared to peak on days 1 and 3and recover towards day 10. These results may prove helpful in future pharmacologic andclinical trials.Overall, the results presented in this thesis present new avenues for research investigatingthe utility of PET/MRI in paediatric IBD, especially in evaluating response to treatment, andin chemotherapy-induced mucositis.
AB - Since its development in the 1970s, positron emission tomography (PET) has played acentral role in detecting and assessing oncological, infectious, and inflammatory conditions. As PET shows function rather than structure, it is often combined with computed tomography (CT) or magnetic resonance imaging (MRI) for anatomical information. The advent of these hybrid-imaging modalities has entailed new, potential applications beneficialto patients in many instances.Diagnosing and evaluating chronic inflammatory bowel diseases (IBD), such as Crohn’sdisease and ulcerative colitis, rely on a multifaceted approach, including endoscopy andcross-sectional imaging. Hybrid imaging with PET has shown promising results in detecting IBD in the gastrointestinal tract in adults. The diagnostic performance, usually coinedas the sensitivity and specificity, in IBD has both been shown to be high for PET combinedwith MRI.Gastrointestinal inflammation may occur in the course of cancer chemotherapy. Through aseries of dynamic processes, various types of chemotherapy may induce inflammation andulceration throughout the gastrointestinal tract. In the oral cavity, direct inspection sufficesto make a diagnosis and staging, while in the gastrointestinal tract, objective and feasiblemethods are lacking, both in clinical and preclinical settings.We hypothesised that PET combined with MRI was a sensitive and specific method to diagnose IBD in the gastrointestinal tract of children suspected of IBD and to monitor response to treatment. We also hypothesised that PET combined with computed tomography could detect and quantify gastrointestinal mucositis caused by doxorubicin treatmentin an experimental mucositis model.The first study of diagnostic accuracy aimed to estimate the diagnostic accuracy ofPET/MRI at the time of diagnosis of IBD in paediatric patients. The results of the scanwere compared to the findings on endoscopy and histopathology and showed a moderatediagnostic performance of each modality alone and of the combined parameter of PET andMRI.In the second study, a pilot study with a follow-up scan, we evaluated the applicability ofPET/MRI in treatment monitoring. We included patients diagnosed with Crohn’s disease inthe first study and six patients with known Crohn’s disease who initiated biological therapy. These pilot observations suggested that PET/MRI may have a potential role in treatmentmonitoring, but more research is needed.In the third experimental study, we aimed to evaluate the utility of PET/CT in assessingmucositis. We induced mucositis with doxorubicin in mice, and PET/CT scanned them sequentially to evaluate the development and resolution of mucositis. The results showed anincrease in the abdominal standardized uptake value of radioactive tracer in mice with mucositis compared to controls. Furthermore, mucositis appeared to peak on days 1 and 3and recover towards day 10. These results may prove helpful in future pharmacologic andclinical trials.Overall, the results presented in this thesis present new avenues for research investigatingthe utility of PET/MRI in paediatric IBD, especially in evaluating response to treatment, andin chemotherapy-induced mucositis.
KW - chemotherapy-induced mucositis
KW - PET/MRI
KW - IBD
KW - PET/MRI
KW - IBD
U2 - 10.21996/b6yy-nb05
DO - 10.21996/b6yy-nb05
M3 - Ph.D. thesis
PB - Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet
ER -