In vivo validation of a system for haptic feedback of tool vibrations in robotic surgery.

BACKGROUND: Robotic minimally invasive surgery (RMIS) lacks the haptic (kinesthetic and tactile) cues that surgeons are accustomed to receiving in open and laparoscopic surgery. We previously introduced a method for adding tactile and audio feedback of tool vibrations to RMIS systems, creating sensations similar to what one feels and hears when using a laparoscopic tool. Our prior work showed that surgeons performing box-trainer tasks significantly preferred having this feedback and believed that it helped them concentrate on the task, but we did not know how well our approach would work in a clinically relevant setting. This study constituted the first in vivo test of our system. METHODS: Accelerometers that measure tool vibrations were mounted to the patient-side manipulators of a da Vinci S surgical system. The measured vibrations were recorded and presented to the surgeon through vibrotactile and audio channels while two transperitoneal nephrectomies and two mid-ureteral dissections with uretero-ureterostomy were completed on a porcine model. We examined 30 minutes of resulting video to identify and tag manipulation events, aiming to determine whether our system can measure significant and meaningful tool vibrations during in vivo procedures. RESULTS: A total of 1,404 manipulation events were identified. Analysis of each event's accelerations indicated that 82 % of these events resulted in significant vibrations. The magnitude of the accelerations measured for different manipulation events varied widely, with hard contact causing the largest cues. CONCLUSIONS: This study demonstrates the feasibility of providing tool vibration feedback during in vivo RMIS. Significant tool vibrations were reliably measured for the majority of events during standard urological procedures on a porcine model, while real-time, naturalistic tactile and audio tool vibration feedback was provided to the surgeon. The feedback system's modules were easily implemented outside the sterile field of the da Vinci S and did not interfere with the surgical procedure.

In vivo efficacy of platelet-delivered, high specific activity factor VIII variants.

Ectopically expressed, human B-domainless (hB) factor 8 (F8) in platelets improves hemostasis in hemophilia A mice in several injury models. However, in both a cuticular bleeding model and a cremaster laser arteriole/venule injury model, there were limitations to platelet-derived (p) hBF8 efficacy, including increased clot embolization. We now address whether variants of F8 with enhanced activity, inactivation resistant F8 (IR8) and canine (c) BF8, would improve clotting efficacy. In both transgenic and lentiviral murine model approaches, pIR8 expressed at comparable levels to phBF8, but pcBF8 expressed at only approximately 30%. Both variants were more effective than hBF8 in cuticular bleeding and FeCl(3) carotid artery models. However, in the cremaster injury model, only pcBF8 was more effective, markedly decreasing clot embolization. Because inhibitors of F8 are stored in platelet granules and IR8 is not protected by binding to von Willebrand factor, we also tested whether pIR8 was effective in the face of inhibitors and found that pIR8 is protected from the inhibitors. In summary, pF8 variants with high specific activity are more effective in controlling bleeding, but this improved efficacy was inconsistent between bleeding models, perhaps reflecting the underlying mechanism(s) for the increased specific activity of the studied F8 variants.

Analysis of the spatial and temporal characteristics of platelet-delivered factor VIII-based clots.

Normally factor (F) VIII is not expressed in megakaryocytes, but when human FVIII was transgenically expressed in murine megakaryocytes, it was stored in platelet alpha-granules and released at sites of injury. This platelet FVIII (pFVIII) is effective in correcting hemostasis, even in the presence of circulating inhibitors, so it offers a potential gene therapy strategy for hemophilia A. To understand clot development by pFVIII, we have examined clot response to laser injury in both cremaster arterioles and venules in FVIII(null) mice either infused with FVIII or transgenic for pFVIII. In both sets of vessels, pFVIII is at least as effective as infused FVIII. However, there are temporal and spatial differences in fibrin and platelet accumulation within clots depending on how FVIII is delivered. These differences may be related to the temporal and spatial distribution of the alpha-granular-released FVIII within the developing clot, and may explain the increased frequency and size of embolic events seen with pFVIII. These observations may not only have implications for the use of pFVIII in gene therapy for hemophilia A, but may also have physiologic consequences, explaining why many procoagulant factors are delivered both in the plasma and in platelet alpha-granules.