Melanie A. McWade

Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.

Purpose To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis. Methods Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue. Results All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses. Conclusions Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

Label-free Intraoperative Parathyroid Localization With Near-Infrared Autofluorescence Imaging

CONTEXT The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. OBJECTIVE The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. SETTING The study was conducted at the Vanderbilt University endocrine surgery center. SUBJECTS AND METHODS Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. MAIN OUTCOME MEASURE The detection rate of parathyroid glands was measured. RESULTS The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. CONCLUSION NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

Establishing the clinical utility of autofluorescence spectroscopy for parathyroid detection

BACKGROUND The inability of surgeons to identify parathyroid glands accurately during cervical endocrine surgery hinders patients from achieving postoperative normocalcemia. An intrinsic, near-infrared fluorescence method was developed for real-time parathyroid identification with high accuracy. This study assesses the clinical utility of this approach. METHODS Autofluorescence measurements were obtained from 137 patients (264 parathyroid glands) undergoing parathyroidectomy and/or thyroidectomy. Measurements were correlated to disease state, calcium levels, parathyroid hormone, vitamin D levels, age, sex, ethnicity, and body mass index. Statistical analysis identified which factors affect parathyroid detection. RESULTS High parathyroid fluorescence was detected consistently and showed wide variability across patients. Near-infrared fluorescence was used to identify 256 of 264 (97%) of glands correctly. The technique showed high accuracy over a wide variety of disease states, although patients with secondary hyperparathyroidism demonstrated confounding results. Analysis revealed body mass index (P < .01), disease state (P < .01), vitamin D (P < .05), and calcium levels (P < .05) account greatly for variability in signal intensity. Age, sex, parathyroid hormone, and ethnicity had no effect. CONCLUSION This intrinsic fluorescence-based intraoperative technique can detect nearly all parathyroid glands accurately in real time. Its discrimination capacity is largely unlimited by patient variables, but several factors affect signal intensity. These results demonstrate potential clinical utility of optical guidance for parathyroid detection.

Epidemiology and mapping of serious and fatal road traffic injuries in Guyana: results from a cross-sectional study

Objective To describe the epidemiology of Guyanas road traffic injuries and perform the first geocoding of road traffic injuries in this setting. Methods This was a registry-based retrospective cross-sectional study investigating collisions resulting in serious and fatal injuries. Police reports from two police divisions were used to identify victim, second party (ie, non-victim) and collision characteristics of all serious and fatal collisions between January 2012 and June 2015. Collisions with available location data were geocoded using Geographic Information Systems. Distributions of characteristics were compared for urban and rural areas. Multivariable logistic regression was used to assess variables associated with fatal collisions. Results The study included 751 collisions, resulting in 1002 seriously or fatally injured victims. Fatally injured victims tended to be older, male and either pedestrians or cyclists. Fatal collisions tended to take place in rural areas, occur on weekends and involve speeding. Fifty-three per cent of fatalities occurred due to non-motorised road users being struck by motorised road users, and the most common fatal collision type was between pedestrians and motor vehicles (35%). The distribution of collisions was similar for urban (43.8%) and rural (56.2%) areas. Fatal collisions were more likely to occur in rural settings. Conclusions Road traffic injuries pose a considerable public health burden in Guyana. These results suggest a pattern of high mortality in rural collisions and a disproportionate burden of injuries on vulnerable road users. The spatial distribution of collisions should be considered in order to target interventions and improve road traffic safety.

A portable near-infrared fluorescence image overlay device for surgical navigation (Conference Presentation)

A rise in the use of near-infrared (NIR) fluorescent dyes or intrinsic fluorescent markers for surgical guidance and tissue diagnosis has triggered the development of NIR fluorescence imaging systems. Because NIR wavelengths are invisible to the naked eye, instrumentation must allow surgeons to visualize areas of high fluorescence. Current NIR fluorescence imaging systems have limited ease-of-use because they display fluorescent information on remote display monitors that require surgeons to divert attention away from the patient to identify the location of tissue fluorescence. Furthermore, some systems lack simultaneous visible light imaging which provides valuable spatial context to fluorescence images. We have developed a novel, portable NIR fluorescence imaging approach for intraoperative surgical guidance that provides information for surgical navigation within the clinician’s line of sight. The system utilizes a NIR CMOS detector to collect excited NIR fluorescence from the surgical field. Tissues with NIR fluorescence are overlaid with visible light to provide information on tissue margins directly on the surgical field. In vitro studies have shown this versatile imaging system can be applied to applications with both extrinsic NIR contrast agents such as indocyanine green and weaker sources of biological fluorescence such as parathyroid gland tissue. This non-invasive, portable NIR fluorescence imaging system overlays an image directly on tissue, potentially allowing surgical decisions to be made quicker and with greater ease-of-use than current NIR fluorescence imaging systems.

Imaging system design for surgical guidance with near-infrared autofluorescence

We present a study to evaluate and compare three near-infrared (NIR) fluorescence imaging systems designed to provide intraoperative guidance around anatomical structures. The three systems adapted specifically for the application of endogenous NIR fluorescence detection were (1) a photomultiplier tube based NIR viewer, (2) a thermoelectrically cooled electron-multiplying charge-coupled device (CCD) camera, and (3) a clinical endoscope CCD camera system. Each system was evaluated on the basis of ease-of-use, cost, and system performance. The cooled CCD camera showed the highest contrast ratio, but is limited in utility by its bulk interface and high cost. The clinical endoscope camera showed flexibility in its field-of-view and provides the benefit of being sterilized to allow easy integration into the surgical suite; however, it exhibits signal nonlinearity that would distort quantitative analysis. The NIR viewer shows optimal performance, exhibiting high spatial resolution, linearity, and sufficient contrast to differentiate between tissue types. This low-cost design proves to be the optimal system for parathyroid detection, offering ease-of-use in a surgical setting while meeting system performance requirements.