Videomicroscopic imaging of graft mucosa for monitoring immunosuppressive therapy after small intestinal transplantation in rats

Background. Early diagnosis of rejection and effective immunosuppressive tr eatment are essential after small intestinal transplantation. To date littl e is known about microscopic alterations of the intestinal mucosa of the gr aft during rejection. We attempted to determine whether videomicroscopic im aging of the graft mucosa is a suitable method for monitoring immunosuppres sive therapy. Methods. Real-time videomicroscopic imaging of an ileostoma was performed d aily after allogeneic heterotopic small bowel transplantation in the rat (B N to LEW) with and without FK506 immunosuppression. Subsequently, the video microscopic findings were compared with the histologically determined grade of rejection. Results. A semiquantitative staging system was established for the intravit al mucosal changes during graft rejection. The earliest changes related to rejection appeared on POD 6 in the untreated allogeneic group. The mucosa d eveloped patchy paleness and the mucosal architecture was interrupted in pl aces. The crypts were slightly widened and their color turned dark red (sta ge I). These alterations spread progressively over the mucosa on POD 7 (sta ge II). On POD 9 the mucosa appeared pale, the villi were shortened, and th e crypts appeared wide and rounded (stage III). In the animals treated with FK506 similar changes were observed, but with a delayed onset. When FK506 was administered as antirejection therapy at the onset of rejection, a temp orary improvement of mucosal alterations was observed (stage II --> stage I ). The videomicroscopic stages correlated with the histological grade of re jection. Conclusions. The introduction of videomicroscopy has made computer-based hi gh resolution imaging of mucosal microarchitecture possible. With videomicr oscopy beginning rejection can be detected, although it can still be revers ed with antirejection therapy. This is a new noninvasive technique that mig ht be of high clinical relevance.