In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients

Abstract

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.

Radionuclide Imaging of the Gut–Brain Axis in Parkinson Disease

“…Indeed, the 11 C-donepezil SUV was lower in both colon and small intestine in this patient group (Fig. 1) (8). Interestingly, the colonic SUV reduction was most prominent in the proximal part of the colon, mirroring the vagal parasympathetic projections.…”

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway

“…As increased vagal afferent input is provided, the gastric network expands to reflect heightened integration across modalities, leading to changes in the awareness of the metabolic state of the body which may facilitate deliberate adaptations of goal-directed behavior, such as foodseeking. Crucially, the higher-order integration of the transmodal cortex during taVNS is in line with a boost in parasympathetic activity due to increased vagal signaling, whereas the baseline gastric network seems to underlie sympathetic regulation (Fedorova et al, 2020;Levinthal and Strick, 2020;.…”

Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives

“…The scan is performed without bowel preparation in near-normal conditions. The validity of this imaging method to detect intestinal parasympathetic denervation is confirmed by a significantly decreased 11 C-donepezil intestinal signal in patients after truncal vagotomy [133]. Patients with early PD have a significant signal loss of 11 C-donepezil within the intestine as the result of cholinergic denervation [134].…”