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Background: Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11C‐donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. Methods: Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11C‐donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long‐term symptoms. Key Results: Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4‐7.9] vs 7.4 [4.5‐11.3], P =.01 and 1.4 [1.1‐2.1] vs 1.6 [1.4‐2.4], P <.01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P <.01 and increased volumes of the small intestine and colon (715 ccm [544‐1177] vs 443 ccm [307‐613], P <.01 and 971 ccm [713‐1389] vs 711 ccm [486‐1394], P =.01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P =.03). Conclusions and Inferences: We found significantly decreased 11C‐donepezil signal in the intestine of vagotomized patients, supporting that 11C‐donepezil PET is a valid measure of intestinal parasympathetic denervation. [ABSTRACT FROM AUTHOR]

Background: The 3D‐Transit electromagnet tracking system (Motilis Medica, SA, Lausanne, Switzerland) is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit and motility. Using this tool, we aimed to derive normative values for region‐specific colonic and GI transit times and to assess the influence of age, gender, and body mass index (BMI). Methods: Regional and total colonic transit times (CTT), gastric emptying (GET), small intestinal (SITT), and whole gut (WGTT) transit times were extracted from 111 healthy volunteers from the United Kingdom and Denmark (58 female; median age: 40 years [range: 21‐88]). The effects of age, gender, and BMI were assessed using standard statistical methods. Key Results: The ascending, transverse, descending, and rectosigmoid colon transit times accounted for 32%, 34%, 17%, and 17% of total CTT in females, and 33%, 25%, 14%, and 28% of total CTT in males. CTT and WGTT were seen to cluster at intervals separated by approximately 24 hours, providing further evidence of the non‐continuous nature of these measurements. Increasing age was associated with longer CTT (P =.021), WGTT (P <.001) ascending (P =.004), transverse (P <.001), and total right (P <.001) colon transit times, but shorter rectosigmoid (P =.004) transit time. Female gender was significantly associated with longer transverse (P =.049) and descending (P <.001) colon transit times, but shorter rectosigmoid (P <.001) transit time. Increasing BMI was significantly associated with shorter WGTT (P =.012). Conclusions and Inferences: For the first time, normative reference values for region‐specific colonic transit have been presented. Age, gender, and BMI were seen to have an effect on transit times. [ABSTRACT FROM AUTHOR]

Background: 11C‐Donepezil positron emission tomography (PET) allows non‐invasive assessment of cholinergic innervation of visceral organs. We aimed to compare cholinergic innervation in the gut in patients with diabetes mellitus (DM) and in healthy controls (HC). Methods: 11C‐Donepezil PET and computed tomography (CT) were performed in 19 patients with type 1 DM and gastrointestinal symptoms and in 19 age‐ and sex‐matched HC in a cross‐sectional design. Key Results: All patients had severe gastrointestinal symptoms when assessed by standard questionnaires. DM patients had significantly increased volume of the small intestinal wall (DM: median 557 cm3 [interquartile range [IQR] 446‐697] vs HC median: 448 cm3 [IQR; 341‐518; P <.01]), and the 11C Donepezil PET uptake was reduced in patients (DM: median 7.08 standardized uptake value [SUV] [IQR; 5.94‐8.43] vs HC: median 9.18 SUV [IQR; 8.57‐10.11; P <.01]). A similar pattern was found in colon (DM: median volume 1064 cm3 [IQR; 882‐1312] vs HC: median 939 cm3 [IQR; 785‐1081; P =.13] and DM: median 1.22 SUV (IQR; 1.08‐1.36) vs HC: median 1.42 SUV (IQR; 1.32‐1.53; P =.03). Furthermore, patients had significantly reduced pancreatic volume (DM: median 53 cm3 [IQR; 41‐69] vs HC: median 98 cm3 [IQR;82‐110; P <.01]) and reduced PET uptake of the pancreas (DM: median 13.14 SUV [IQR;9.58‐15.82] vs HC: median 21.46 SUV [IQR;18.97‐24.06; P <.01]) as well as the adrenal gland (DM: median 7.62 SUV [IQR;7.61;15.82] vs HC: median 15.51 SUV [IQR;12.22;19.49; P =.03]). Conclusion and Inferences: Assessed with 11C‐Donepezil PET/CT, patients with DM and severe bowel symptoms have reduced cholinergic innervation of the gut indicative of parasympathetic denervation. [ABSTRACT FROM AUTHOR]