Roger J. McNichols

Optical glucose sensing in biological fluids: an overview.

Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. This article reviews many of the recent advances in optical glucose sensing including optical absorption spectroscopy, polarimetry, Raman spectroscopy, and fluorescent glucose sensing. In addition a review of calibration and data processing methods useful for optical techniques is presented.

MR-guided stereotactic laser ablation of epileptogenic foci in children☆

OBJECTIVE For about 30% of epilepsy patients, pharmaceutical therapy fails to control their seizures. MR-guided laser interstitial thermal therapy (MRgLITT) allows for real-time thermal monitoring of the ablation process and feedback control over the laser energy delivery. We report on minimally invasive surgical techniques of MRgLITT and short-term follow-up results from the first five pediatric cases in which this system was used to ablate focal epileptic lesions. METHODS We studied the patients with MRI of the brain, localized the seizure with video-EEG and used the Visualase Thermal Therapy 25 System for laser ablation of their seizure foci. RESULTS All 5 patients are seizure free and there were no complications as of 2-13-month follow-up. CONCLUSION MR-guided laser interstitial thermal therapy has a significant potential to be a minimally invasive alternative to more conventional techniques to surgically treat medically refractory epilepsy in children.

Real-time magnetic resonance-guided laser thermal therapy for focal metastatic brain tumors.

OBJECTIVE We report the initial results of a pilot clinical trial exploring the safety and feasibility of the first real-time magnetic resonance-guided laser-induced thermal therapy of treatment-resistant focal metastatic intracranial tumors. METHODS Patients with resistant metastatic intracranial tumors who had previously undergone chemotherapy, whole-brain radiation therapy, and radiosurgery and who were recused from surgery were eligible for this trial. Under local anesthesia, a Leksell stereotactic head frame was used to insert a water-cooled interstitial fiberoptic laser applicator inside the cranium. In the bore of a magnetic resonance imaging (MRI) scanner, laser energy was delivered to heat the tumor while continuous MRI was performed. A computer workstation extracted temperature-sensitive information to display images of laser heating and computed estimates of the thermal damage zone. Posttreatment MRI scans were used to confirm the zone of thermal necrosis, and follow-up was performed at 7, 15, 30, and 90 days after treatment. RESULTS In all cases, the procedure was well tolerated without secondary effect, and patients were discharged to home within 14 hours after the procedure. Follow-up imaging showed an acute increase in apparent lesion volume followed by a gradual and steady decrease. No tumor recurrence within thermal ablation zones was noted. CONCLUSION In this ongoing trial, a total of four patients have had six metastatic tumors treated with laser thermal ablations. Magnetic resonance-guided laser-induced thermal therapy appears to provide a new, efficient treatment for recurrent focal metastatic brain disease. This therapy is a prelude to the future development of closed-head interventional MRI techniques in neurosurgery.

Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model

We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)-absorbing, 150-nm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 +/- 4.1 degrees C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 +/- 1.1 degrees C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

MR‐guided laser‐induced thermal therapy (LITT) for recurrent glioblastomas

Laser‐induced thermal therapy (LITT), coupled with magnetic resonance thermal imaging (MRTI) guidance, provides a minimally invasive and safe approach to treat brain tumors, especially metastases. We report here our experience using this treatment for recurrent glioblastomas.

Laser thermal therapy: Real‐time MRI‐guided and computer‐controlled procedures for metastatic brain tumors

We report the final results of a pilot clinical trial exploring the safety and feasibility of real‐time magnetic resonance‐guided laser‐induced thermal therapy (MRgLITT) for treatment of resistant focal metastatic intracranial tumors.

Multispectral polarimetric glucose detection using a single Pockels cell

The preliminary design of a noninvasive glucose sensor developed in this investigation was based on the polarization rotation of light produced by optically active molecules. The polarimeter developed for this investigation was unique when compared to previous investigations in that it utilized a single Pockels cell to both modulate the signal and provide feedback within the system. The intended application of this polarimeter is to measure glucose concentrations within the aqueous humor of the eye. The purpose of this investigation was to elucidate whether the theory of superposition and multispectral analysis can be applied to the measurement of glucose in the presence of ascorbic acid and albumin, the most significant rotatory confounders found in the aqueous humor. The results of this investigation indicate that superposition of rotation at different wavelengths due to the above optically active molecules was valid for the in vitro experiments conducted. Utilizing two wavelengths of light, the concentration of hyperglycemic levels of glucose were derived in the presence of physiological concentrations of the optically active confounders ascorbic acid and albumin. It was found, except for one outlier, that the model predicted glucose concentrations to within 23%.

Fluorescence Resonance Energy Transfer-Based Near-Infrared Fluorescence Sensor for Glucose Monitoring

A novel near-infrared (NIR) fluorescence affinity sensor for continuous glucose monitoring was developed and characterized. The sensor operates by fluorescence resonance energy transfer between a NIR chromophore linked to concanavalin A (ConA) and an NIR fluorophore linked to free dextran. The binding of dextran with ConA in the absence of glucose results in low fluorescence due to quenching; however, the quenching is reversed by competitive displacement of dextran from ConA by glucose. In order to increase thermodynamic stability and the lifetime of the sensor, ConA was immobilized within a macroporous bead matrix. The sensor was contained within a sealed hollow dialysis fiber (o.d. 215 microm, wall thickness 20 microm), preventing the macromolecules from leaking out and enabling glucose to rapidly enter the fiber lumen. A glucose-insensitive reference fluorophore was also incorporated to allow for ratiometric measurements, resulting in a robust sensor output that is independent of positional and/or light intensity changes. The response of the fluorescence affinity sensor to glucose was tested continuously in an automated test chamber at 37 degrees C. The sensor showed good dynamic range within physiologically relevant glucose concentration range (15% change over 2.5-30 mM, no hysteresis), fast response time (2-4 min), and a remarkable long-term stability (6 months). We interpret the improved longevity of this sensor to be the result of an optimized photo exposure regime and immobilization of ConA to the matrix. Its small size, ratiometric output, and NIR fluorescence make this sensor well suited for dermal implantation and continuous transdermal monitoring.

Magnetic Resonance Guided, Focal Laser Induced Interstitial Thermal Therapy in a Canine Prostate Model

PURPOSE We evaluated a newly Food and Drug Administration cleared, closed loop, magnetic resonance guided laser induced interstitial thermal therapy system for targeted ablation of prostate tissue to assess the feasibility of targeting, real-time monitoring and predicting lesion generation in the magnetic resonance environment. MATERIALS AND METHODS Seven mongrel dogs (University of Texas Health Science Center, Houston, Texas) with (2) and without (5) canine transmissible venereal tumors in the prostate were imaged with a 1.5 T magnetic resonance imaging scanner. Real-time 3-dimensional magnetic resonance imaging was used to accurately position water cooled, 980 nm laser applicators to predetermined targets in the canine prostate. Destruction of targeted tissue was guided by real-time magnetic resonance temperature imaging to precisely control thermal ablation. Magnetic resonance predictions of thermal damage were correlated with posttreatment imaging results and compared to histopathology findings. RESULTS Template based targeting using magnetic resonance guidance allowed the laser applicator to be placed within a mean ± SD of 1.1 ± 0.7 mm of the target site. Mean width and length of the ablation zone on magnetic resonance imaging were 13.7 ± 1.3 and 19.0 ± 4.2 mm, respectively, using single and compound exposures. The damage predicted by magnetic resonance based thermal damage calculations correlated with the damage on posttreatment imaging with a slope near unity and excellent correlation (r(2) = 0.94). CONCLUSIONS This laser induced interstitial thermal therapy system provided rapid, localized tissue heating under magnetic resonance temperature imaging control. Combined with real-time monitoring and template based planning, magnetic resonance guided, laser induced interstitial thermal therapy is an attractive modality for prostate cancer focal therapy.

A Cost-Based Availability Allocation Algorithm

This paper develops a cost-based procedure for allocating the availability parameters (repair times and failure rates) to the various components that make up a system. The allocation is handled as a cost minimization problem, subject to the constraint of meeting a system availability requirement. The problem is solved using Lagrange multipliers and an example is stated and solved. This technique is applicable in the early stages of system design to determine the detailed component availability specifications (repair times and failure rates) that will allow a system requirement to be met. Furthermore, the technique is useful in the latter stages of system design when initial specifications have fallen short of the required goal, and modifications and improvements are required. The technique points out the problem components and defines the amount of improvement necessary.