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BackgroundThe loss of tactile feedback in minimally invasive robotic surgery remains a major challenge to the expanding field. With visual cue compensation alone, tissue characterization via palpation proves to be immensely difficult. This work evaluates a bimodal vibrotactile system as a means of conveying applied forces to simulate haptic feedback in two sets of studies simulating an artificial palpation task using the da Vinci surgical robot.MethodsSubjects in the first study were tasked with localizing an embedded vessel in a soft tissue phantom using a single-sensor unit. In the second study, subjects localized tumor-like structures using a three-sensor array. In both sets of studies, subjects completed the task under three trial conditions: no feedback, normal force tactile feedback, and hybrid vibrotactile feedback. Recordings of correct localization, incorrect localization, and time-to-completion were used to evaluate performance outcomes.ResultsWith the addition of vibrotactile and pneumatic feedback, significant improvements in the percentage of correct localization attempts were detected (p = 0.0001 and p = 0.0459, respectively) during the first experiment with phantom vessels. Similarly, significant improvements in correct localization were found with the addition of vibrotactile (p = 2.57E-5) and pneumatic significance (p = 8.54E-5) were observed in the second experiment involving tumor phantoms.ConclusionsThis work demonstrates not only the superior benefits of a multi-modal feedback over traditional single-modality feedback, but also the effectiveness of vibration in providing haptic feedback to artificial palpation systems.

As robotic surgery has increased in popularity, the lack of haptic feedback has become a growing issue due to the application of excessive forces that may lead to clinical problems such as intraoperative and postoperative suture breakage. Previous suture breakage warning systems have largely depended on visual and/or auditory feedback modalities, which have been shown to increase cognitive load and reduce operator performance. This work catalogues a new sensing technology and haptic feedback system (HFS) that can reduce instances of suture failure without negatively impacting performance outcomes including knot quality. Suture breakage is common in knot-tying as the pulling motion introduces prominent shear forces. A shear sensor mountable on the da Vinci robotic surgical system's Cadiere grasper detects forces that correlate to the suture's internal tension. HFS then provides vibration feedback to the operator as forces near a particular material's failure load. To validate the system, subjects tightened a total of four knots, two with the Haptic Feedback System (HFS) and two without feedback. The number of suture breakages were recorded and knot fidelity was evaluated by measuring knot slippage. Results showed that instances of suture failure were significantly reduced when HFS was enabled (p = 0.0078). Notably, knots tied with HFS also showed improved quality compared to those tied without feedback (p = 0.010). The results highlight the value of HFS in improving robotic procedure outcomes by reducing instances of suture failures, producing better knots, and reducing the need for corrective measures.

BackgroundWith the development of laser-assisted platforms, the outcomes of cataract surgery have been improved by automating several procedures. The cataract-extraction step continues to be manually performed, but due to deficiencies in sensing capabilities, surgical complications such as posterior capsule rupture and incomplete cataract removal remain.MethodsAn optical coherence tomography (OCT) system is integrated into our intraocular robotic interventional surgical system (IRISS) robot. The OCT images are used for preoperative planning and intraoperative intervention in a series of automated procedures. Real-time intervention allows surgeons to evaluate the progress and override the operation.ResultsThe developed system was validated by performing lens extraction on 30 postmortem pig eyes. Complete lens extraction was achieved on 25 eyes, and "almost complete" extraction was achieved on the remainder due to an inability to image small lens particles behind the iris. No capsule rupture was found.ConclusionThe IRISS successfully demonstrated semiautomated OCT-guided lens removal with real-time supervision and intervention.

Purpose of reviewThe quantity of tissue removed during an oncologic surgical procedure is not standardized and there are numerous reports of local recurrence despite histologically adequate resection margins. The oral cavity is one of the sites in the head and neck with high chances of recurrence following negative margins. To address this need, this article reviews the recent applications of Dynamic Optical Contrast Imaging (DOCI) towards both oral screening and the intraoperative evaluation of tumor margins in head and neck surgery.Recent findingsHuman ex-vivo and in-vivo trials suggest DOCI is well tolerated, low-cost, and sensitive for differentiating cancerous from normal tissues throughout the head and neck, in addition to the oral cavity. Ex-vivo imaging of OSCC specimens generated histologically verified image contrast. Furthermore, in-vivo intraoperative results demonstrate significant potential for image-guided detection and resection of oral cavity squamous cell carcinoma (OSCC).SummaryDOCI augments tissue contrast and may enable surgeons to clinically screen patients for oral cancer, make histologic evaluations in vivo with fewer unnecessary biopsies, delineate clinical margins for tumor resection, provide guidance in the choice of biopsy sites, and preserve healthy tissue to increase the postoperative functionality and quality of life of the patient.

Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and dielectric windows used to flatten the imaging field. Herein, we present an optical design for non-contact THz imaging of cornea. A beam scanning methodology performs angular, normal incidence sweeps of a focused beam over the corneal surface while keeping the source, detector, and patient stationary. A quasioptical analysis method is developed to analyze the theoretical resolution and imaging field intensity profile. These results are compared to the electric field distribution computed with a physical optics analysis code. Imaging experiments validate the optical theories behind the design and suggest that quasioptical methods are sufficient for designing of THz corneal imaging systems. Successful imaging operations support the feasibility of non-contact in vivo imaging. We believe that this optical system design will enable the first, clinically relevant, in vivo exploration of CTWC using THz technology.

Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.

ObjectiveIn vivo visualization and quantification of edema, or 'tissue swelling' following injury, remains a clinical challenge. Herein, we investigate the ability of reflective terahertz (THz) imaging to track changes in tissue water content (TWC)-the direct indicator of edema-by comparison to depth-resolved magnetic resonance imaging (MRI) in a burn-induced model of edema.MethodsA partial thickness and full thickness burns were induced in an in vivo rat model to elicit unique TWC perturbations corresponding to burn severity. Concomitant THz surface maps and MRI images of both burn models were acquired with a previously reported THz imaging system and T2-weighted MRI, respectively, over 270 min. Reflectivity was analyzed for the burn contact area in THz images, while proton density (i.e., mobile TWC) was analyzed for the same region at incrementally increasing tissue depths in companion, transverse MRI images. A normalized cross correlation of THz and depth-dependent MRI measurements was performed as a function of time in histologically verified burn wounds.ResultsFor both burn types, strong positive correlations were evident between THz reflectivity and MRI data analyzed at greater tissue depths (>258 μm). MRI and THz results also revealed biphasic trends consistent with burn edema pathogenesis.ConclusionThis paper offers the first in vivo correlative assessment of mobile TWC-based contrast and the sensing depth of THz imaging.SignificanceThe ability to implement THz imaging immediately following injury, combined with TWC sensing capabilities that compare to MRI, further support THz sensing as an emerging tool to track fluid in tissue.

BackgroundThe principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator.MethodsWe asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded.ResultsCompared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p

Background and objectivesBacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy.Study design/materials and methodsStaphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 μg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay.ResultsWith gentamicin monotherapy, CFU density (CFU/mm2 ) at 31, 62, and 124 μg/ml were (282 ± 84) × 104 , (185 ± 34) × 104 , and (113 ± 9) × 104 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 104 , (89 ± 24) × 104 , and (43 ± 3) × 104 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 μg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities.ConclusionLGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc.

Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.

Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.

Accurate and early prediction of tissue viability is the most significant determinant of tissue flap survival in reconstructive surgery. Perturbation in tissue water content (TWC) is a generic component of the tissue response to such surgeries, and, therefore, may be an important diagnostic target for assessing the extent of flap viability in vivo. We have previously shown that reflective terahertz (THz) imaging, a non-ionizing technique, can generate spatially resolved maps of TWC in superficial soft tissues, such as cornea and wounds, on the order of minutes. Herein, we report the first in vivo pilot study to investigate the utility of reflective THz TWC imaging for early assessment of skin flap viability. We obtained longitudinal visible and reflective THz imagery comparing 3 bipedicled flaps (i.e. survival model) and 3 fully excised flaps (i.e. failure model) in the dorsal skin of rats over a postoperative period of 7 days. While visual differences between both models manifested 48 hr after surgery, statistically significant (p < 0.05, independent t-test) local differences in TWC contrast were evident in THz flap image sets as early as 24 hr. Excised flaps, histologically confirmed as necrotic, demonstrated a significant, yet localized, reduction in TWC in the flap region compared to non-traumatized skin. In contrast, bipedicled flaps, histologically verified as viable, displayed mostly uniform, unperturbed TWC across the flap tissue. These results indicate the practical potential of THz TWC sensing to accurately predict flap failure 24 hours earlier than clinical examination.

IntroductionThe aims of this study were to evaluate (1) grasping forces with the application of a tactile feedback system in vivo and (2) the incidence of tissue damage incurred during robotic tissue manipulation. Robotic-assisted minimally invasive surgery has been shown to be beneficial in a variety of surgical specialties, particularly radical prostatectomy. This innovative surgical tool offers advantages over traditional laparoscopic techniques, such as improved wrist-like maneuverability, stereoscopic video displays, and scaling of surgical gestures to increase precision. A widely cited disadvantage associated with robotic systems is the absence of tactile feedback.Methods and procedureNineteen subjects were categorized into two groups: 5 experts (six or more robotic cases) and 14 novices (five cases or less). The subjects used the da Vinci with integrated tactile feedback to run porcine bowel in the following conditions: (T1: deactivated tactile feedback; T2: activated tactile feedback; and T3: deactivated tactile feedback). The grasping force, incidence of tissue damage, and the correlation of grasping force and tissue damage were analyzed. Tissue damage was evaluated both grossly and histologically by a pathologist blinded to the sample.ResultsTactile feedback resulted in significantly decreased grasping forces for both experts and novices (P  0.05 in all subjects).ConclusionThe in vivo application of integrated tactile feedback in the robotic system demonstrates significantly reduced grasping forces, resulting in significantly less tissue damage. This tactile feedback system may improve surgical outcomes and broaden the use of robotic-assisted minimally invasive surgery.

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.

Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and/or systemic immunosuppressive factors, thus creating a host environment more amenable to immunotherapy. This article reviews the immunotherapeutic approaches being evaluated in patients with MPM and discusses how immunotherapy might be rationally combined with conventional tumor cytoreductive therapies for this disease.

Robot-assisted surgery is characterized by a total loss of haptic feedback, requiring surgeons to rely solely on visual cues. A compact, flexible, and lightweight pneumatic balloon tactile display has been developed suitable for mounting on robotic surgical master controls. The tactile display consists of a molded polydimethylsiloxane substrate with cylindrical channels and a spin-coated silicone film that forms the array of balloons. Human perceptual studies were conducted to determine the optimal diameter, spatial resolution, and temporal resolution of the balloon actuator design. A balloon diameter of 3.0 mm provided the highest average accuracy ([greater than or equal to] 95%) while offering five detectable inflation levels. Spatial accuracy in a two-actuator discrimination task reached 100% with 1.5 mm edge-to-edge spacing, and the accuracy of determining the order of two successive stimuli was greater than 90% when the time separation was 100 ms. Design optimization based on the results from this study enables the described tactile display to provide the effective tactile feedback that is otherwise unavailable during robotic surgery. Index Terms--Haptic feedback, haptic perception, robot tactile systems.