TY - JOUR

T1 - In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients

AU - Fedorova, Tatyana Dmitrievna

AU - Knudsen, Karoline

AU - Hartmann, Bolette

AU - Holst, Jens J.

AU - Mortensen, Frank Viborg

AU - Krogh, Klaus

AU - Borghammer, Per

PY - 2020

Y1 - 2020

N2 - 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 C-11-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 C-11-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 C-11-donepezil signal in the intestine of vagotomized patients, supporting that C-11-donepezil PET is a valid measure of intestinal parasympathetic denervation.

AB - 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 C-11-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 C-11-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 C-11-donepezil signal in the intestine of vagotomized patients, supporting that C-11-donepezil PET is a valid measure of intestinal parasympathetic denervation.

KW - acetylcholinesterase

KW - esophageal neoplasms

KW - parasympathetic nervous system

KW - positron emission tomography

KW - vagotomy

KW - VAGAL-SPARING ESOPHAGECTOMY

KW - QUALITY-OF-LIFE

KW - PANCREATIC-POLYPEPTIDE

KW - PARKINSONS-DISEASE

KW - ACETYLCHOLINESTERASE DENSITY

KW - PERIPHERAL ORGANS

KW - BIODISTRIBUTION

KW - DYSFUNCTION

KW - NEUROPATHY

KW - DOSIMETRY

U2 - 10.1111/nmo.13759

DO - 10.1111/nmo.13759

M3 - Journal article

C2 - 31715652

VL - 32

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 3

M1 - 13759

ER -