Kyle D. Weaver

A Telerobotic System for Transnasal Surgery

Mechanics-based models of concentric tube continuum robots have recently achieved a level of sophistication that makes it possible to begin to apply these robots to a variety of real-world clinical scenarios. Endonasal skull base surgery is one such application, where their small diameter and tentacle-like dexterity are particularly advantageous. In this paper, we provide the medical motivation for an endonasal surgical robot featuring concentric tube manipulators, and describe our model-based design and teleoperation methods, as well as a complete system incorporating image guidance. Experimental demonstrations using a laparoscopic training task, a cadaver reachability study, and a phantom tumor resection experiment illustrate that both novice and expert users can effectively teleoperate the system, and that skull base surgeons can use the robot to achieve their objectives in a realistic surgical scenario.

A method to track cortical surface deformations using a laser range scanner

This paper reports a novel method to track brain shift using a laser-range scanner (LRS) and nonrigid registration techniques. The LRS used in this paper is capable of generating textured point-clouds describing the surface geometry/intensity pattern of the brain as presented during cranial surgery. Using serial LRS acquisitions of the brains surface and two-dimensional (2-D) nonrigid image registration, we developed a method to track surface motion during neurosurgical procedures. A series of experiments devised to evaluate the performance of the developed shift-tracking protocol are reported. In a controlled, quantitative phantom experiment, the results demonstrate that the surface shift-tracking protocol is capable of resolving shift to an accuracy of approximately 1.6 mm given initial shifts on the order of 15 mm. Furthermore, in a preliminary in vivo case using the tracked LRS and an independent optical measurement system, the automatic protocol was able to reconstruct 50% of the brain shift with an accuracy of 3.7 mm while the manual measurement was able to reconstruct 77% with an accuracy of 2.1 mm. The results suggest that a LRS is an effective tool for tracking brain surface shift during neurosurgery.

A bimanual teleoperated system for endonasal skull base surgery

We describe transnasal skull base surgery, including the current clinical procedure and the ways in which a robotic system has the potential to enhance the current standard of care. The available workspace is characterized by segmenting medical images and reconstructing the available 3D geometry. We then describe thin, “tentacle-like” robotic tools with shafts constructed from concentric tube robots, and an actuation unit designed to robotically control them in a teleoperated setting. Lastly, we discuss the results of a proof-of-concept study in a cadaveric specimen, illustrating the ability of the robot to access clinically relevant skull base targets.

Methylated Tumor-Specific DNA as a Plasma Biomarker in Patients with Glioma

Objective: Patients with systemic malignancies have substantial quantities of tumor-specific DNA in their plasma which may serve as a potential biomarker for tumor burden. This approach has not been studied in gliomas. Methods: Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status the promoters for p16/INK4a, MGMT, p73, and RARβ within glioma tissue and plasma. Blood was collected prior to craniotomy in 10 patients with glioma. DNA was extracted from tumor and plasma samples and assayed with MSP. Total plasma DNA also was quantified. Tumor-specific plasma DNA was defined as identification of the same methylated promoter (MP) in both tumor and plasma. Results: Total plasma DNA concentration was markedly elevated (mean 6,503 ng/ml, SEM 1,400 ng/ml). Glioma tissue contained methylation of at least one promoter in 9 out of 10 (90 percent) of patients studied. Of these patients, 6 out of 9 (67 percent) demonstrated methylation of at least one of the same promoters in plasma. Five of these had one MP identified in the plasma and one had 2 MP. Overall, glioma-specific plasma DNA was present in plasma of 6 out of 10 (60 percent) of patients. Each MP DNA marker found in the plasma also was present in the intracranial tumor. Conclusions: Patients with high grade gliomas have large amounts of DNA in the plasma. Of these primary brain tumors, 90 percent contained methylated gene promoters, and in over 60 percent of these patients the same methylated promoters present in the tumor also were found in the plasma. This represents the first step to developing a quantitative plasma biomarker that could be used to monitor glioma status.

Single cell analysis of human tissues and solid tumors with mass cytometry

Mass cytometry measures 36 or more markers per cell and is an appealing platform for comprehensive phenotyping of cells in human tissue and tumor biopsies. While tissue disaggregation and fluorescence cytometry protocols were pioneered decades ago, it is not known whether established protocols will be effective for mass cytometry and maintain cancer and stromal cell diversity.

Temporal bone encephalocele and cerebrospinal fluid fistula repair utilizing the middle cranial fossa or combined mastoid–middle cranial fossa approach

OBJECT The goals of this study were to report the clinical presentation, radiographic findings, operative strategy, and outcomes among patients with temporal bone encephaloceles and cerebrospinal fluid fistulas (CSFFs) and to identify clinical variables associated with surgical outcome. METHODS A retrospective case series including all patients who underwent a middle fossa craniotomy or combined mastoid-middle cranial fossa repair of encephalocele and/or CSFF between 2000 and 2012 was accrued from 2 tertiary academic referral centers. RESULTS Eighty-nine consecutive surgeries (86 patients, 59.3% women) were included. The mean age at time of surgery was 52.3 years, and the left side was affected in 53.9% of cases. The mean delay between symptom onset and diagnosis was 35.4 months, and the most common presenting symptoms were hearing loss (92.1%) and persistent ipsilateral otorrhea (73.0%). Few reported a history of intracranial infection (6.7%) or seizures (2.2%). Thirteen (14.6%) of 89 cases had a history of major head trauma, 23 (25.8%) were associated with chronic ear disease without prior operation, 17 (19.1%) occurred following tympanomastoidectomy, and 1 (1.1%) developed in a patient with a cerebral aqueduct cyst resulting in obstructive hydrocephalus. The remaining 35 cases (39.3%) were considered spontaneous. Among all patients, the mean body mass index (BMI) was 35.3 kg/m(2), and 46.4% exhibited empty sella syndrome. Patients with spontaneous lesions were statistically significantly older (p = 0.007) and were more commonly female (p = 0.048) compared with those with nonspontaneous pathology. Additionally, those with spontaneous lesions had a greater BMI than those with nonspontaneous disease (p = 0.102), although this difference did not achieve statistical significance. Thirty-two surgeries (36.0%) involved a middle fossa craniotomy alone, whereas 57 (64.0%) involved a combined mastoid-middle fossa repair. There were 7 recurrences (7.9%); 2 patients with recurrence developed meningitis. The use of artificial titanium mesh was statistically associated with the development of recurrent CSFF (p = 0.004), postoperative wound infection (p = 0.039), and meningitis (p = 0.014). Also notable, 6 of the 7 cases with recurrence had evidence of intracranial hypertension. When the 11 cases that involved using titanium mesh were excluded, 96.2% of patients whose lesions were reconstructed with an autologous multilayer repair had neither recurrent CSFF nor meningitis at the last follow-up. CONCLUSIONS Patients with temporal bone encephalocele and CSFF commonly present with persistent otorrhea and conductive hearing loss mimicking chronic middle ear disease, which likely contributes to a delay in diagnosis. There is a high prevalence of obesity among this patient population, which may play a role in the pathogenesis of primary and recurrent disease. A middle fossa craniotomy or a combined mastoid-middle fossa approach incorporating a multilayer autologous tissue technique is a safe and reliable method of repair that may be particularly useful for large or multifocal defects. Defect reconstruction using artificial titanium mesh should generally be avoided given increased risks of recurrence and postoperative meningitis.

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified. Their Kaplan–Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV-GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204–1.513] (OS) and 1.387 [1.225–1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35–1.85] (OS, 10 studies) and 1.41 [1.22–1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14–1.58] (OS, 6 studies) and 1.64 [0.88–3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.

Type 2 Diabetes Mellitus is an Independent Risk Factor for PostoperativeComplications in Patients Surgically Treated for Meningioma

Objectives: Increased risk of perioperative complications in patients with type 2 diabetes mellitus (DM) has previously been noted with regard to a number of different operations. We sought to study the relative rates of postoperative complications after the surgical resection of an intracranial meningioma based on a pre-existing diagnosis of diabetes. Methods: We conducted a retrospective cohort study on 259 patients who underwent a primary meningioma resection at our institution between 2001-2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM and any postoperative complications prior to discharge. The duration of postoperative hospital stay, intensive care unit (ICU) stay, perioperative changes in Karnofsky Performance Status (KPS) scores, and any postoperative emergency department (ED) presentation within 90 days of the operation were also recorded for each patient. Multivariable logistic regression models were built to determine the impact of a history of diabetes on postoperative complications and post-discharge presentation to the ED. Multivariable linear regression models were designed to assess the predictors of lengthier hospitalization and ICU stays in addition to differential postoperative changes in KPS scores. Results: Forty-one (16%) patients had diagnoses of type 2 DM prior to clinical presentation. In multivariate analyses, patients with a pre-existing history of diabetes had a higher risk of postoperative complications, postoperative ED presentation, and deterioration in functional status in addition to lengthier durations of hospitalization and ICU stay (p<0.001, p=0.008, p<0.001, p=0.007, p<0.001). Conclusions: Patients with pre-existing diagnoses of type 2 DM have a significantly increased risk of immediate postoperative complications following the resection of an intracranial meningioma. Type 2 DM also predicts increased lengths of postoperative hospital stay, decreased postoperative performance status, and increased risk of postoperative ED presentation.

An experimental feasibility study on robotic endonasal telesurgery.

BACKGROUND Novel robots have recently been developed specifically for endonasal surgery. They can deliver several thin, tentacle-like surgical instruments through a single nostril. Among the many potential advantages of such a robotic system is the prospect of telesurgery over long distances. OBJECTIVE To describe a phantom pituitary tumor removal done by a surgeon in Nashville, Tennessee, controlling a robot located approximately 800 km away in Chapel Hill, North Carolina, the first remote telesurgery experiment involving tentacle-like concentric tube manipulators. METHODS A phantom pituitary tumor removal experiment was conducted twice, once locally and once remotely, with the robotic system. Robot commands and video were transmitted across the Internet. The latency of the system was evaluated quantitatively in both local and remote cases to determine the effect of the 800-km distance between the surgeon and robot. RESULTS We measured a control and video latency of < 100 milliseconds in the remote case. Qualitatively, the surgeon was able to carry out the experiment easily and observed no discernable difference between the remote and local cases. CONCLUSION Telesurgery over long distances is feasible with this robotic system. In the longer term, this may enable expert skull base surgeons to help many more patients by performing surgeries remotely over long distances.

Endonasal Skull Base Tumor Removal Using Concentric Tube Continuum Robots: A Phantom Study

Objectives The purpose of this study is to experimentally evaluate the use of concentric tube continuum robots in endonasal skull base tumor removal. This new type of surgical robot offers many advantages over existing straight and rigid surgical tools including added dexterity, the ability to scale movements, and the ability to rotate the end effector while leaving the robot fixed in space. In this study, a concentric tube continuum robot was used to remove simulated pituitary tumors from a skull phantom. Design The robot was teleoperated by experienced skull base surgeons to remove a phantom pituitary tumor within a skull. Percentage resection was measured by weight. Resection duration was timed. Setting Academic research laboratory. Main Outcome Measures Percentage removal of tumor material and procedure duration. Results Average removal percentage of 79.8 ± 5.9% and average time to complete procedure of 12.5 ± 4.1 minutes (n = 20). Conclusions The robotic system presented here for use in endonasal skull base surgery shows promise in improving the dexterity, tool motion, and end effector capabilities currently available with straight and rigid tools while remaining an effective tool for resecting the tumor.