Wilson Z. Ray

Bioresorbable silicon electronic sensors for the brain

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body’s abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy.

Since its introduction in the late 1870’s, surgical restoration of function following peripheral nerve injury has made significant progress (Naff and Ecklund, 2001). The development of the operating microscope, improved microsurgical techniques, and a greater understanding of the internal topography of perpheral nerves has greatly improved functional outcomes. In addition, advances in basic science and clinical research have furthered our understanding of the pathophysiology of nerve injury, recovery, and repair. There are several factors that influence recovery following a nerve injury: time elapsed, patient age, mechanism, proximity of the lesion to distal targets, and associated soft tissue or vascular injuries (Gilbert, et al., 2006, Hentz and Narakas, 1988, Slutsky, 2006). All these factors must be carefully considered in order to optimize the operative approach used in each unique patient. Prompt repair of nerve injuries leads to improved outcomes by allowing for earlier distal motor end plate and sensory receptor reinnervation. In younger patients, the more robust regenerative capacity typically results in better outcomes compared to the elderly. Mechanism of damage is an important determinant of the longitudinal extent of the injury. More proximal lesions must traverse longer distances to reinnervate the distal target. And finally, concomitant soft tissue or vascular injuries can result in significant distortion and scarring, seriously complicating exploration of the affected area. The ultimate goal of any peripheral nerve reconstruction is the restoration of function as promptly and completely as possible, while minimizing donor site and systemic morbidity. In cases where a tension-free primary end-to-end neurorrhaphy is not possible, several alternatives exist. This review summarizes these options for repair including interpositional nerve grafting, transfers and end-to-side neurorrhaphy (Fig. 1). Open in a separate window Figure 1 Summarizes the various options for nerve repair. Nerve allografts are utilized for large, otherwise irreparable injuries. Nerve transfer use redundant nerve fibers for a proximal nerve injury. The autograft is used to reconstruct a nerve gap. Direct repair is used when there is no intervening nerve gap to create tension. Both end-to-side and nerve conduits are used for noncritical sensory injuries.

Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics

In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (μ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.

Radially Aligned, Electrospun Nanofibers as Dural Substitutes for Wound Closure and Tissue Regeneration Applications

This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The type I collagen exhibited a high degree of organization on the scaffolds of radially aligned fibers and a haphazard distribution on the scaffolds of random fibers. Taken together, the scaffolds based on radially aligned, electrospun nanofibers show great potential as artificial dural substitutes and may be particularly useful as biomedical patches or grafts to induce wound closure and/or tissue regeneration.

Acellular nerve allografts in peripheral nerve regeneration: A comparative study

Introduction: Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods: Three established models of acellular nerve allograft (cold‐preserved, detergent‐processed, and AxoGen‐processed nerve allografts) were compared with nerve isografts and silicone nerve guidance conduits in a 14‐mm rat sciatic nerve defect. Results: All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent‐processed allografts were similar to isografts at 6 weeks postoperatively, whereas AxoGen‐processed and cold‐preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent‐processed allografts promoted isograft‐equivalent levels of motor recovery 16 weeks postoperatively. All acellular allografts promoted greater amounts of motor recovery compared with silicone conduits. Conclusion: These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. Muscle Nerve, 2011

Incidence of deep venous thrombosis after subarachnoid hemorrhage : Clinical article

OBJECT The aim of this study was to determine the efficacy of venous ultrasonography in screening for deep venous thrombosis (DVT) after subarachnoid hemorrhage (SAH). A large cohort of patients who had suffered SAH was evaluated with the primary end points of ascertaining the incidence of asymptomatic DVT with venous Doppler ultrasonography screening and of identifying risk factors for the development of DVT and subsequent pulmonary embolism. METHODS Data from patients with aneurysmal SAH who had been admitted to the neurosurgical intensive care unit (ICU) between December 2002 and October 2006 were retrospectively evaluated. Patients who had undergone surgical or endovascular treatment of an aneurysm following SAH and survived > or = 15 days were included in the study. RESULTS The overall incidence of DVT among the entire study cohort was 18%. A subgroup analysis identified all patients, with or without symptoms for DVT, who had undergone venous Doppler ultrasonography screening. The incidence of asymptomatic DVT was 24%. Univariate analysis of all patients revealed a significant correlation between the risk of DVT and Hunt and Hess grade (r = 0.38, p < 0.0001), Fisher grade (r = 0.31, p < 0.0001), total hospital stay (r = 0.49, p < 0.0001), and number of days in the ICU (r = 0.48, p < 0.0001). Multivariate analysis demonstrated that the total hospital stay and number of days in the ICU were significant predictors of DVT in all patients (p < 0.0001 and p < 0.0002, respectively). In the subgroup of screened patients, Hunt and Hess grade, total hospital stay, and number of days in the ICU were significant predictors of DVT. Although screened patients were more likely to have DVT (chi(2) = 6.0976, p < 0.02), there was no significant difference in the incidence of DVT or pulmonary embolism between patients who did and those who did not undergo routine lower-extremity Doppler ultrasonography screening. CONCLUSIONS Routine compressive venous Doppler ultrasonography is an efficient, noninvasive means of identifying DVT as a screening modality in both symptomatic and asymptomatic patients following aneurysmal SAH. The ability to confirm or deny the presence of DVT in this patient population allows one to better identify the indications for chemoprophylaxis. Prophylaxis for venous thromboembolism in neurosurgical patients is common. Emerging literature and anecdotal experience have exposed risks of complications with prophylactic anticoagulation protocols. The identification of patients at high risk-for example, those with asymptomatic DVT-will allow physicians to better assess the role of prophylactic anticoagulation.

Combined endovascular embolization and stereotactic radiosurgery in the treatment of large arteriovenous malformations: Clinical article

OBJECT Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series. METHODS Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS. RESULTS The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases). CONCLUSIONS Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.

Clinical outcomes following median to radial nerve transfers.

PURPOSE To evaluate the clinical outcomes in patients with radial nerve palsy who underwent nerve transfers using redundant fascicles of median nerve (innervating the flexor digitorum superficialis and flexor carpi radialis muscles) to the posterior interosseous nerve and the nerve to the extensor carpi radialis brevis. METHODS This was a retrospective review of the clinical records of 19 patients with radial nerve injuries who underwent nerve transfer procedures using the median nerve as a donor nerve. All patients were evaluated using the Medical Research Council (MRC) grading system. The mean age of patients was 41 years (range, 17-78 y). All patients received at least 12 months of follow-up (range, 20.3 ± 5.8 mo). Surgery was performed at a mean of 5.7 ± 1.9 months postinjury. RESULTS Postoperative functional evaluation was graded according to the following scale: grades MRC 0/5 to MRC 2/5 were considered poor outcomes, whereas an MRC grade of 3/5 was a fair result, 4/5 was a good result, and 4+/5 was an excellent outcome. Postoperatively, all patients except one had good to excellent recovery of wrist extension. A total of 12 patients recovered good to excellent finger and thumb extension, 2 had fair recovery, and 5 had poor recovery. CONCLUSIONS The radial nerve is commonly injured, causing severe morbidity in affected patients. The median nerve provides a reliable source of donor nerve fascicles for radial nerve reinnervation. The important nuances of both surgical technique and motor reeducation critical for the success of this transfer have been identified and are discussed. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Double fascicular nerve transfer to the biceps and brachialis muscles after brachial plexus injury: clinical outcomes in a series of 29 cases

OBJECT The clinical outcomes of patients with brachial plexus injuries who underwent double fascicular transfer (DFT) using fascicles from the median and ulnar nerves to reinnervate the biceps and brachialis muscles were evaluated. METHODS The authors conducted a retrospective chart review of 29 patients with brachial plexus injuries that were treated with DFT for restoration of elbow flexion. All patients underwent pre- and postoperative clinical evaluation using the Medical Research Council grading system. RESULTS The mean patient age was 37 years (range 17-68 years), and there was a mean follow-up of 19 ± 12 months (range 8-68 months). At the most recent follow-up, all but 1 patient (97%) had regained elbow flexion. Eight patients recovered Grade M5, 15 patients recovered Grade M4, and 4 patients recovered Grade M3 elbow flexion strength. There was no evidence of functional deficit in the donor nerve distributions. CONCLUSIONS Study results demonstrated the reliable restoration of M4-M5 elbow flexion following double fascicular transfer in patients with brachial plexus injuries.

Magnetic resonance imaging-guided focused laser interstitial thermal therapy for subinsular metastatic adenocarcinoma: technical case report.

BACKGROUND AND IMPORTANCE: To describe the novel use of the AutoLITT System (Monteris Medical, Winnipeg, Manitoba, Canada) for focused laser interstitial thermal therapy (LITT) with intraoperative magnetic resonance imaging (MRI) and stereotactic image guidance for the treatment of metastatic adenocarcinoma in the left insula. CLINICAL PRESENTATION: The patient was a 61-year-old right-handed man with a history of metastatic adenocarcinoma of the colon. He had previously undergone resection of multiple lesions, Gamma Knife radiosurgery, and whole-brain radiation. Despite treatment of a left insular tumor, serial imaging revealed that the lesion continued to enlarge. Given the refractory nature of this tumor to radiation and the deep-seated location, the patient elected to undergo LITT treatment. The center of the lesion and entry point on the scalp were identified with STEALTH (Medtronic, Memphis, Tennessee) image-guided navigation. The AXiiiS Stereotactic Miniframe (Monteris Medical) for the LITT system was secured onto the skull, and a trajectory was defined to achieve access to the centroid of the tumor. After a burr hole was made, a gadolinium template probe was inserted into the AXiiiS base. The trajectory was confirmed via an intraoperative MRI, and the LITT probe driver was attached to the base and CO2-cooled, side-firing laser LITT probe. The laser was activated and thermometry images were obtained. Two trajectories, posteromedial and anterolateral, produced satisfactory tumor ablation. CONCLUSION: LITT with intraoperative MRI and stereotactic image guidance is a newly available, minimally invasive, and therapeutically viable technique for the treatment of deep seated brain tumors. ABBREVIATION: LITT, laser interstitial thermal therapy