Safety of laser-generated shockwave treatment for bacterial biofilms in a cutaneous rodent model.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

Artificial palpation in robotic surgery using haptic feedback.

BACKGROUND: The 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. METHODS: Subjects 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. RESULTS: With 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. CONCLUSIONS: This 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.

In-depth analysis of antibacterial mechanisms of laser generated shockwave treatment.

Background and Objectives Laser generated shockwave (LGS) is a novel modality for minimally invasive disruption of bacterial biofilms. The objectives of this study are to determine the mechanisms behind LGS treatment and non-biofilm effects on bacterial disruption, including (1) comparing bacterial load with and without LGS in its planktonic form and (2) estimating bacterial cell permeability following LGS. Study Design/Materials and Methods For the first study, planktonic S. epidermidis were treated with gentamicin (0, 8, 16, 32, 64 µg/ml) with and without LGS (1064 nm Nd:YAG laser, 110.14 mJ/mm2 , pulse duration 9 ns, spot size 3 mm, n = 8/group), and absorbances at 600 nm compared. For the second study, four samples of planktonic S. epidermidis were treated with LGS (same settings). Propidium iodide (PI) uptake via flow cytometry as a measure of cell permeability was measured at 0, 10, and 20 minutes following LGS. RESULTS: In comparing corresponding gentamicin concentrations within both LGS-treated samples and controls at 0 hours, there were no differences in absorbance (P = 0.923 and P = 0.814, respectively). Flow cytometry found modest PI uptake (10.4 ± 2.5%) immediately following LGS treatment, with time-dependent increase and persistence of the signal at 20 minutes (R2 = 0.449, P = 0.048). CONCLUSION: Taken together, LGS does not appear to have direct bacteriocidal properties, but rather by allowing for biofilm disruption and bacterial cell membrane permeabilization, both of which likely increase topical antibiotic delivery to pathogenic organisms. Insight into the mechanisms of LGS will allow for improved clinical applications and facilitate safe and effective translation of this technology. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Vibroacoustographic System for Tumor Identification.

Oral and head and neck squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. The primary management of OSCC relies on complete surgical resection of the tumor. Margin-free resection, however, is difficult given the devastating effects of aggressive surgery. Currently, surgeons determine where cuts are made by palpating edges of the tumor. Accuracy varies based on the surgeon's experience, the location and type of tumor, and the risk of damage to adjacent structures limiting resection margins. To fulfill this surgical need, we contrast tissue regions by identifying disparities in viscoelasticity by mixing two ultrasonic beams to produce a beat frequency, a technique termed vibroacoustography (VA). In our system, an extended focal length of the acoustic stress field yields surgeons' high resolution to detect focal lesions in deep tissue. VA offers 3D imaging by focusing its imaging plane at multiple axial cross-sections within tissue. Our efforts culminate in production of a mobile VA system generating image contrast between normal and abnormal tissue in minutes. We model the spatial direction of the generated acoustic field and generate images from tissue-mimicking phantoms and ex vivo specimens with squamous cell carcinoma of the tongue to qualitatively demonstrate the functionality of our system. These preliminary results warrant additional validation as we continue clinical trials of ex vivo tissue. This tool may prove especially useful for finding tumors that are deep within tissue and often missed by surgeons. The complete primary resection of tumors may reduce recurrence and ultimately improve patient outcomes.

Dynamic optical contrast imaging as a novel modality for rapidly distinguishing head and neck squamous cell carcinoma from surrounding normal tissue.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patient's prognosis depends heavily on complete tumor resection. Currently, the surgeon's fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes. METHODS: A total of 47 fresh ex vivo samples from 15 patients were imaged with the DOCI system immediately after surgical resection. DOCI maps were analyzed to determine the statistical significance of contrast between tumors and adjacent nonmalignant tissue. Pilot intraoperative clinical data were also acquired. RESULTS: Statistical significance (P < .05) between muscle and tumor was established for 10 of 10 emission wavelengths, between collagen and tumor for 8 of 10 emission wavelengths, and between fat and tumor for 2 of 10 wavelengths. The system extracted relative fluorescence decay information in a surgically relevant field of view in <2 minutes. CONCLUSIONS: This study demonstrates the feasibility of using DOCI to rapidly and accurately distinguish HNSCC from surrounding normal tissue. An analysis of DOCI images revealed microscopic characterization sufficient for tissue-type identification consistent with histology. Such an intraoperative tool would be transformative by allowing the rapid delineation of tumor tissue from nontumor tissue and thus maximizing the efficacy of resection and improving patient outcomes. Cancer 2017;123:879-86. © 2016 American Cancer Society.

Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use of Patient Specific Molds to Correlate Images with Whole Mount Pathology.

PURPOSE: We evaluated the accuracy of magnetic resonance imaging in determining the size and shape of localized prostate cancer. MATERIALS AND METHODS: The subjects were 114 men who underwent multiparametric magnetic resonance imaging before radical prostatectomy with patient specific mold processing of the specimen from 2013 to 2015. T2-weighted images were used to contour the prostate capsule and cancer suspicious regions of interest. The contours were used to design and print 3-dimensional custom molds, which permitted alignment of excised prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3 dimensions from digitized whole mount sections. Tumors were then matched with regions of interest and the relative geometries were compared. RESULTS: Of the 222 tumors evident on whole mount sections 118 had been identified on magnetic resonance imaging. For the 118 regions of interest mean volume was 0.8 cc and the longest 3-dimensional diameter was 17 mm. However, for matched pathological tumors, of which most were Gleason score 3 + 4 or greater, mean volume was 2.5 cc and the longest 3-dimensional diameter was 28 mm. The median tumor had a 13.5 mm maximal extent beyond the magnetic resonance imaging contour and 80% of cancer volume from matched tumors was outside region of interest boundaries. Size estimation was most accurate in the axial plane and least accurate along the base-apex axis. CONCLUSIONS: Magnetic resonance imaging consistently underestimates the size and extent of prostate tumors. Prostate cancer foci had an average diameter 11 mm longer and a volume 3 times greater than T2-weighted magnetic resonance imaging segmentations. These results may have important implications for the assessment and treatment of prostate cancer.

Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance.

PURPOSE: Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. MATERIALS AND METHODS: A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. RESULTS: Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. CONCLUSIONS: Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy.

Visual-perceptual mismatch in robotic surgery.

BACKGROUND: The 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. METHODS: We 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. RESULTS: Compared 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 < 0.001). Additionally, it was observed that addition of tactile feedback helps reduce the negative effects of visual-perceptual mismatch in some cases. Grip force data recorded from grasper-mounted sensors showed no difference between the different groups. CONCLUSIONS: The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

Tensile strength and failure load of sutures for robotic surgery.

BACKGROUND: Robotic surgical platforms have seen increased use among minimally invasive gastrointestinal surgeons (von Fraunhofer et al. in J Biomed Mater Res 19(5):595-600, 1985. doi: 10.1002/jbm.820190511 ). However, these systems still suffer from lack of haptic feedback, which results in exertion of excessive force, often leading to suture failures (Barbash et al. in Ann Surg 259(1):1-6, 2014. doi: 10.1097/SLA.0b013e3182a5c8b8 ). This work catalogs tensile strength and failure load among commonly used sutures in an effort to prevent robotic surgical consoles from exceeding identified thresholds. Trials were thus conducted on common sutures varying in material type, gauge size, rate of pulling force, and method of applied force. METHODS: Polydioxanone, Silk, Vicryl, and Prolene, gauges 5-0 to 1-0, were pulled till failure using a commercial mechanical testing system. 2-0 and 3-0 sutures were further tested for the effect of pull rate on failure load at rates of 50, 200, and 400 mm/min. 3-0 sutures were also pulled till failure using a da Vinci robotic surgical system in unlooped, looped, and at the needle body arrangements. RESULTS: Generally, Vicryl and PDS sutures had the highest mechanical strength (47-179 kN/cm2), while Silk had the lowest (40-106 kN/cm2). Larger diameter sutures withstand higher total force, but finer gauges consistently show higher force per unit area. The difference between material types becomes increasingly significant as the diameters decrease. Comparisons of identical suture materials and gauges show 27-50% improvement in the tensile strength over data obtained in 1985 (Ballantyne in Surg Endosc Other Interv Tech 16(10):1389-1402, 2002. doi: 10.1007/s00464-001-8283-7 ). No significant differences were observed when sutures were pulled at different rates. Reduction in suture strength appeared to be strongly affected by the technique used to manipulate the suture. CONCLUSIONS: Availability of suture tensile strength and failure load data will help define software safety protocols for alerting a surgeon prior to suture failure during robotic surgery. Awareness of suture strength weakening with direct instrument manipulation may lead to the development of better techniques to further reduce intraoperative suture breakage.

Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro.

BACKGROUND AND OBJECTIVES: Bacterial 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 METHODS: Staphylococcus 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. RESULTS: With 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. CONCLUSION: LGS 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.

Focal Laser Ablation of Prostate Cancer: Phase I Clinical Trial.

PURPOSE: Focal laser ablation is an investigational technique to treat prostate cancer in a region confined manner via coagulative necrosis. This phase I trial primarily examines the safety of transrectal magnetic resonance imaging guided (in-bore) focal laser ablation in men with intermediate risk prostate cancer. An exploratory end point is cancer control after 6 months. MATERIALS AND METHODS: In an institutional review board approved trial we studied focal laser ablation in 8 men with intermediate risk prostate cancer diagnosed using magnetic resonance-ultrasound fusion. Focal laser ablation was performed by inserting a cylindrically diffusing, water cooled laser fiber into magnetic resonance visible regions of interest, followed by interstitial heating at 10 to 15 W for up to 3 minutes. Secondary safety monitors (thermal probes) were inserted to assess the accuracy of magnetic resonance thermometry. Comprehensive magnetic resonance-ultrasound fusion biopsy was performed after 6 months. Adverse events and health related quality of life questionnaires were recorded. RESULTS: Focal laser ablation was successfully performed in all 8 subjects. No grade 3 or greater adverse events occurred and no changes in International Prostate Symptom Score or International Index of Erectile Function 5 were observed. Ablation zones, as measured by posttreatment magnetic resonance imaging, had a median volume of 3 cc or 7.7% of prostate volume. Prostate specific antigen decreased in 7 men (p <0.01). At followup magnetic resonance-ultrasound fusion biopsy cancer was not detected in the ablation zone in 5 men but was present outside the treatment margin in 6 men. CONCLUSIONS: Focal laser ablation of the prostate is feasible and safe in men with intermediate risk prostate cancer without serious adverse events or changes in urinary or sexual function at 6 months. Comprehensive biopsy followup indicates that larger treatment margins than previously thought necessary may be required for complete tumor ablation.

Evaluating tactile feedback in robotic surgery for potential clinical application using an animal model.

INTRODUCTION: The 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 PROCEDURE: Nineteen 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. RESULTS: Tactile feedback resulted in significantly decreased grasping forces for both experts and novices (P < 0.001 in both conditions). The overall incidence of tissue damage was significantly decreased in all subjects (P < 0.001). A statistically significant correlation was found between grasping forces and incidence of tissue damage (P = 0.008). The decreased forces and tissue damage were retained through the third trial when the system was deactivated (P > 0.05 in all subjects). CONCLUSION: The 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.

Immunotherapy for malignant pleural mesothelioma. Current status and future prospects.

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.

Effect of laser generated shockwaves 1 on ex-vivo pigskin.

INTRODUCTION: Persistent bacterial infection prolongs hospitalizations, leading to increased healthcare costs. Treatment of these infections costs several billion dollars annually. Biofilm production is one mechanism by which bacteria become resistant. With the help of biofilms, bacteria withstand the host immune response and are much less susceptible to antibiotics. Currently, there is interest in the use of laser-generated shockwaves (LGS) to delaminate biofilm from infected wound surfaces; however, the safety of such an approach has not yet been established. Of particular concern are the thermal and mechanical effects of the shockwave treatment on the epidermis and the underlying collagen structure of the dermis. The present study is a preliminary investigation of the effect of LGS on freshly harvested ex vivo porcine skin tissue samples. MATERIALS AND METHODS: Tissue samples for investigation were harvested immediately post-mortem and treated with LGS within 30 minutes. Previous studies have shown that laser fluences between 100 and 500 mJ/pulse are capable of delaminating biofilms off a variety of surfaces, thus our preliminary investigation focused on this range of laser energy. For each sample, LGS were produced via laser irradiation of a thin layer (0.5 µm) of titanium sandwiched between a 50 and 100 µm thick layer of water glass and a 0.1 mm thick sheet of Mylar. The rapid thermal expansion of the irradiated titanium film generates a transient compressive wave that is coupled through a liquid layer to the surface of the ex vivo pigskin sample. Shocked samples were immediately fixed in formalin and prepared for histological analysis. A blinded pathologist evaluated and scored each section on the basis of its overall appearance (O) and presence of linear/slit-like spaces roughly parallel to the surface of the skin (S). The scores were given on a scale of 0-3. RESULTS: The present investigation revealed no visible difference between the tissue sections of the control sample and those that were subjected to laser-generated shockwaves. There was no relationship between the scores received by the samples and the energy with which they were shocked. CONCLUSION: Preliminary investigation into the safety of the LGS treatment for biofilm delamination appears promising. Additional investigation will continue on ex vivo porcine samples, followed by an in vivo animal trial to better understand the physiological response to LGS treatment.

The role of tactile feedback in grip force during laparoscopic training tasks.

BACKGROUND: Laparoscopic minimally invasive surgery has revolutionized surgical care by reducing trauma to the patient, thereby decreasing the need for medication and shortening recovery times. During open procedures, surgeons can directly feel tissue characteristics. However, in laparoscopic surgery, tactile feedback during grip is attenuated and limited to the resistance felt in the tool handle. Excessive grip force during laparoscopic surgery can lead to tissue damage. Providing additional supplementary tactile feedback may allow subjects to have better control of grip force and identification of tissue characteristics, potentially decreasing the learning curve associated with complex minimally invasive techniques. METHODS: A tactile feedback system has been developed and integrated into a modified laparoscopic grasper that allows forces applied at the grasper tips to be felt by the surgeon's hands. In this study, 15 subjects (11 novices, 4 experts) were asked to perform single-handed peg transfers using these laparoscopic graspers in three trials (feedback OFF, ON, OFF). Peak and average grip forces (newtons) during each grip event were measured and compared using a Wilcoxon ranked test in which each subject served as his or her own control. RESULTS: After activating the tactile feedback system, the novice subject population showed significant decreases in grip force (p < 0.003). When the system was deactivated for the third trial, there were significant increases in grip force (p < 0.003). Expert subjects showed no significant improvements with the addition of tactile feedback (p > 0.05 in all cases). CONCLUSION: Supplementary tactile feedback helped novice subjects reduce grip force during the laparoscopic training task but did not offer improvements for the four expert subjects. This indicates that tactile feedback may be beneficial for laparoscopic training but has limited long-term use in the nonrobotic setting.

Development of a novel portable multi-channel near infrared spectroscopy system.

A novel light-weight multi-channel multi-wavelength ultra-low power near infrared spectroscopy (NIRS) system was designed and tested. The NIRS system was designed for clinical use to emit low power (maximum 5 mW) red and near infrared (NIR) light into human tissue and acquire, record, and display reflected light from various tissue depths. In this paper, results of initial functional tests of the system are presented. Potential clinical applications of the NIRS system include long-term non-invasive monitoring of functional activity in tissues, oxygen consumption in skeletal muscles, and tissue blood perfusion.

A prototype stimulator system for noninvasive Low Intensity Focused Ultrasound delivery.

A prototype Low Intensity Focused Ultrasound (LIFU) stimulator system was developed to evaluate non-invasive neuromodulation in a large animal model. We conducted a feasibility study on a Göttingen minipig, demonstrating reversible, targeted transcranial neuromodulation. The hypothalamus of the minipig was repeatedly stimulated with LIFU which evoked temporally correlated increases in both heart rate and blood pressure.

A transurethral catheter-based ultrasound system for multi-modal fusion.

Current methods of prostate cancer diagnosis and therapy rely on accurate imaging of the prostate using real-time ultrasound. Transurethral ultrasound (TUUS) may improve upon the current gold standard through improved 3D visualization and co-registration (fusion) with CT and MRI. A prototype transurethral ultrasound (TUUS) catheter-based transducer array and system was developed, featuring 32 elements with a diameter of 18F (6mm). A robust, multi-channel ultrasound transceiver was also developed to enable TUUS imaging using pulse-echo and frequency-based signal processing methods. The feasibility of a TUUS imaging system suitable for multi-modal image fusion and novel ultrasound signaling techniques was demonstrated.

Reducing retraction forces with tactile feedback during robotic total mesorectal excision in a porcine model.

Excessive tissue-instrument interaction forces during robotic surgery have the potential for causing iatrogenic tissue damages. The current in vivo study seeks to assess whether tactile feedback could reduce intraoperative tissue-instrument interaction forces during robotic-assisted total mesorectal excision. Five subjects, including three experts and two novices, used the da Vinci robot to perform total mesorectum excision in four pigs. The grip force in the left arm, used for retraction, and the pushing force in the right arm, used for blunt pelvic dissection around the rectum, were recorded. Tissue-instrument interaction forces were compared between trials done with and without tactile feedback. The mean force exerted on the tissue was consistently higher in the retracting arm than the dissecting arm (3.72 ± 1.19 vs 0.32 ± 0.36 N, p < 0.01). Tactile feedback brought about significant reductions in average retraction forces (3.69 ± 1.08 N vs 4.16 ± 1.12 N, p = 0.02), but dissection forces appeared unaffected (0.43 ± 0.42 vs 0.37 ± 0.28 N, p = 0.71). No significant differences were found between retraction and dissection forces exerted by novice and expert robotic surgeons. This in vivo animal study demonstrated the efficacy of tactile feedback in reducing retraction forces during total mesorectal excision. Further research is required to quantify the clinical impact of such force reduction.

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.