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An integrated augmented reality (AR) surgical navigation system that potentially improves intra-operative visualization of concealed anatomical structures. Integration of real-time tracking technology with a laser pico-projector allows the surgical surface to be augmented by projecting virtual images of lesions and critical structures created by multimodality imaging. We aim to quantitatively and qualitatively evaluate the performance of a prototype interactive AR surgical navigation system through a series of pre-clinical studies. Four pre-clinical animal studies using xenograft mouse models were conducted to investigate system performance. A combination of CT, PET, SPECT, and MRI images were used to augment the mouse body during image-guided procedures to assess feasibility. A phantom with machined features was employed to quantitatively estimate the system accuracy. All the image-guided procedures were successfully performed. The tracked pico-projector correctly and reliably depicted virtual images on the animal body, highlighting the location of tumour and anatomical structures. The phantom study demonstrates the system was accurate to 0.55 ± 0.33mm. This paper presents a prototype real-time tracking AR surgical navigation system that improves visualization of underlying critical structures by overlaying virtual images onto the surgical site. This proof-of-concept pre-clinical study demonstrated both the clinical applicability and high precision of the system which was noted to be accurate to

PurposeTo evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of pulmonary vasculature in minimally-invasive thoracic surgery planning.MethodsCF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of pulmonary vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed.ResultsCF800 injection improved visualization of pulmonary vessels in both rabbit and pig models. The SBR of rabbit pulmonary vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; pConclusionCF800 provides SBR and contrast enhancement of pulmonary vasculature which may assist in pre-surgical CT planning of minimally invasive thoracic surgery.

BACKGROUND:We set out to determine the accuracy of 3D-navigated mandibular and maxillary osteotomies with the ultimate aim to integrate virtual cutting guides and 3D-navigation into ablative and reconstructive head and neck surgery. METHODS:Four surgeons (two attending, two clinical fellows) completed 224 unnavigated and 224 3D-navigated osteotomies on anatomical models according to preoperative 3D plans. The osteotomized bones were scanned and analyzed. RESULTS:Median distance from the virtual plan was 2.1 mm unnavigated (IQR 2.6 mm, ≥3 mm in 33%) and 1.2 mm 3D-navigated (IQR 1.1 mm, ≥3 mm in 6%) (P

BACKGROUND:Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis. METHODS AND FINDINGS:Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA) were isolated from each lavage. Two targeted next-generation sequencing (NGS) gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at allele fractions significantly less than 1%. Of the remaining 95 patients diagnosed with benign or non-cancer pathology, 44 had no significant cancer mutations detected. Intriguingly, 51 patients without histopathologic evidence of cancer had relatively high allele fraction (1.0%-30.4%), cancer-associated mutations. Participants with detected driver and potential driver mutations were significantly older (mean age mutated = 57.96, 95% confidence interval [CI]: 3.30-∞, mean age no mutations = 50.35; p-value = 0.002; Benjamini-Hochberg [BH] adjusted p-value = 0.015) and more likely to be post-menopausal (p-value = 0.004; BH-adjusted p-value = 0.015) than those without these mutations. No associations were detected between mutation status and race/ethnicity, body mass index, diabetes, parity, and smoking status. Long-term follow-up was not presently available in this prospective study for those women without histopathologic evidence of cancer. CONCLUSIONS:Using ultra-deep NGS, we identified somatic mutations in DNA extracted both from cell pellets and a never previously reported cfDNA fraction from the uterine lavage. Using our targeted sequencing approach, endometrial driver mutations were identified in all seven women who received a cancer diagnosis based on classic histopathology of tissue curettage obtained at the time of hysteroscopy. In addition, relatively high allele fraction driver mutations were identified in the lavage fluid of approximately half of the women without a cancer diagnosis. Increasing age and post-menopausal status were associated with the presence of these cancer-associated mutations, suggesting the prevalent existence of a premalignant landscape in women without clinical evidence of cancer. Given that a uterine lavage can be easily and quickly performed even outside of the operating room and in a physician's office-based setting, our findings suggest the future possibility of this approach for screening women for the earliest stages of endometrial cancer. However, our findings suggest that further insight into development of cancer or its interruption are needed before translation to the clinic.

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques across a variety of otolaryngological sub-specialties suggests an emerging role for rapid prototyping technology in surgical education, procedure simulation, and clinical practice.

The use of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung cancer; however, this has not been fully adapted for minimally invasive surgery (MIS). The aim of our study was to develop a minimally invasive SN mapping integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided transbronchial ICG injection and intraoperative NIR thoracoscopic imaging.A NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG concentrations and injection volumes. Transbronchial ICG injection (n=4) was assessed in comparison to a traditional transpleural approach (n=3), where after thoracotomy an ICG solution (100 μL at 100 μg/mL) was injected into the porcine right upper lobe for SN identification. For further translation into clinical use, transbronchial ICG injection prior to thoracotomy followed by NIR thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in two pigs with a pseudo-tumor.The ICG fluorescence at 10 μg/mL was the brightest among various concentrations, unchanged by the distance between the thoracoscope and ICG solutions. Injected ICG of no more than 500μ L showed a localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node within 15 minutes post-injection, with persistent fluorescence for 60 minutes. The antecedent transbronchial ICG injection succeeded in SN identification in all 3 cases at the first thoracoscopic inspection within 20 minutes post-injection. The ENB system allowed accurate ICG injection surrounding the pseudo-tumors.ENB-guided ICG injection followed by NIR thoracoscopy was technically feasible for SN mapping in the porcine lung. This promising platform may be translated into human clinical trials and is suited for MIS.