Acute in vivo performance evaluation of the fluorescence affinity sensor in the intravascular and interstitial space in Swine.

OBJECTIVE: We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. RESEARCH DESIGN AND METHODS: The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6-7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. RESULTS: Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ± 9.6%] and 23.8% (SD = ± 19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ± 12.5%). CONCLUSIONS: The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.

MR imaging-guided focal laser ablation for prostate cancer: phase I trial.

PURPOSE: To evaluate the feasibility and safety of magnetic resonance (MR) imaging-guided laser-based thermotherapy in men with clinically low-risk prostate cancer and a concordant lesion at biopsy and MR imaging. MATERIALS AND METHODS: This HIPAA-compliant phase I prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Transperineal MR imaging-guided focal laser ablation for clinically low-risk prostate cancer was performed in patients with a Gleason score of 7 or less in three or fewer cores limited to one sextant obtained with transrectal ultrasonography (US)-guided biopsy and a concordant lesion at MR imaging. Lesions were targeted with a laser ablation system. Periprocedural complications were recorded. The International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) score were collected before and after the procedure. MR imaging-guided biopsy of the ablation zone was performed 6 months after treatment. The prostate-specific antigen level, IPSS, and SHIM score before and after ablation were compared by using the Wilcoxon signed rank test. RESULTS: Treatment was successfully completed in nine patients (procedure duration, 2.5-4 hours; mean laser ablation duration, 4.3 minutes). Immediate contrast-enhanced posttreatment MR imaging showed a hypovascular defect in eight patients. Self-resolving perineal abrasion and focal paresthesia of the glans penis each occurred in one patient. The mean (± standard deviation) IPSS and SHIM score at baseline were 5.8 ± 5.3 and 19.0 ± 8.0, respectively. Average score changes were not significantly different from zero during follow-up (P = .18-.99). MR imaging-guided biopsy of the ablation zone showed no cancer in seven patients (78%) and Gleason grade 6 cancer in two (22%). CONCLUSION: Transperineal MR imaging-guided focal laser ablation appears to be a feasible and safe focal therapy option for clinically low-risk prostate cancer.

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.

A human pilot study of the fluorescence affinity sensor for continuous glucose monitoring in diabetes.

OBJECTIVE: We report results of a pilot clinical study of a subcutaneous fluorescence affinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h). RESEARCH DESIGN AND METHODS: A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30-60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale. RESULTS: After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100-350 mg/dl] with an average correlation coefficient of 0.84 (±0.24 SD). The actual average "warm-up" time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest. CONCLUSIONS: The in vivo performance of the FAS demonstrates feasibility of the fluorescence affinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5-7 days) in people with diabetes.

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

BACKGROUND AND OBJECTIVE: 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. MATERIALS AND METHODS: Four patients, from 40 to 58 years old, were diagnosed with glioblastoma. After total resection, chemotherapy and radiation therapy, recurrence occurred. As each was ineligible for a second surgery, LITT was proposed as salvage therapy. Under stereotactic guidance, a fiberoptic applicator was inserted within the tumor LITT was performed under continuous MRTI. Real-time feedback control based on MRTI was employed to assess the quality of local tissue destruction and to prevent unwanted damage to nearby structures. RESULTS: The procedure was well tolerated with no peroperative neurological deterioration. In the short-term follow-up, one transient supplementary motor area syndrome, one epileptic seizure, and one cerebrospinal fluid leakage occurred. All were successfully managed. Post-procedure MRI showed no complication, satisfying treatment volume, and a decrease in size of the treated tumor. For all patients, recurrence was observed with a mean/median progression free survival of 37/30 days. Mean/median overall survival after LITT was 10.5/10 months. CONCLUSION: Focal tumor control was performed safely using minimally invasive LITT with real-time MRTI control. LITT could be considered as salvage therapy for high-grade recurrent gliomas if a 1-day treatment is considered useful for a few weeks gain in survival. Larger experience will be required to define indications for such infiltrative disease and accurately determine a potentially significant survival gain in good neurological condition associated with this 1-day procedure.

Laser thermal therapy: real-time MRI-guided and computer-controlled procedures for metastatic brain tumors.

BACKGROUND AND OBJECTIVE: 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. STUDY DESIGN: In patients with chemotherapy, whole-brain radiation, and radiosurgery resistant metastatic intracranial tumors, minimally invasive stereotaxic placement of a saline-cooled interstitial fiberoptic laser applicator under local anesthesia was followed by laser irradiation during continuous magnetic resonance imaging (MRI) scanning. A computer workstation extracted real-time temperature-sensitive information for feedback control over laser delivery. A total of 15 metastatic tumors were treated in 7 patients. Patients were followed with physical exam and imaging for 30 months. RESULTS: In all cases, the procedure was well tolerated, and patients were discharged home within 24 hours. Follow-up imaging at up to 30 months showed an acute increase in apparent lesion volume followed by a gradual and steady decrease. No tumor recurrence within thermal ablation zones was noted. Kaplan-Meier analysis indicated that the median survival was 19.8 months. CONCLUSION: Real-time magnetic resonance (MR) guidance of laser-induced thermal therapy (LITT) offers a high level of control. This tool therefore enables a minimally invasive option for destruction and treatment of resistant focal metastatic intracranial tumors. MR-guided LITT appears to provide a safe and potentially effective treatment for recurrent focal metastatic brain disease. A larger phase II and III series would be of interest to quantify potential median survival advantage.

3.0T MR-guided laser ablation of a prostate cancer recurrence in the postsurgical prostate bed.

Biochemical recurrence of prostate cancer after definitive therapy with radical prostatectomy occurs in 25%-30% of cases. The first known case of magnetic resonance (MR) imaging-guided ablation using laser interstitial thermal therapy (LITT) for locally recurrent prostate cancer after radical prostatectomy is presented. Using 3.0T MR guidance, two laser applicators were placed via a transperineal approach. Laser ablation was performed using MR thermometry to determine the ablation endpoint and lesion coverage. Dynamic contrast-enhanced MR imaging after the procedure showed no definitive abnormal enhancement. The patient had no change in continence or potency after the procedure.

In vivo evaluation of a MR-guided 980nm laser interstitial thermal therapy system for ablations in porcine liver.

PURPOSE: To evaluate the use of a 980-nm diode laser for magnetic resonance-guided laser interstitial thermal therapy (MR-guided LITT) ablations in liver tissue in an in vivo porcine model. MATERIALS AND METHODS: MR-guided guided LITT was performed on nine juvenile pigs placed under general anesthesia. Target ablation sites were selected in the left and right lobes of the liver. Laser applicators were placed in the liver using intermittent MR guidance. Up to four separate ablations were performed in each animal using a 15 or 30 W laser generator using one or two applicators. During the ablations, continuous MR-based temperature mapping (MR-thermal mapping), using a proton resonance frequency technique, was performed to monitor the size of the ablation in real-time. Extent of thermal tissue damage was continuously estimated based on Arrhenius model. Two-minute ablations were performed at each site. MR-thermal mapping of ablations within the posteroinferior liver were accomplished with continuous breathing at low tidal volume. In the mid right lobe of the liver, due to motion artefacts, MR-thermometry was performed intermittently during breath hold periods. In the left lobe of the liver, ablations were performed with ventilation using positive end expiratory pressure (PEEP) of 10 cm of water. Upon completion, MR imaging with gadolinium contrast was performed to assess the extent of treatment. Thermal lesions were subsequently measured using both, MR-thermal dose and MR gadolinium images, for comparison. Following the animal euthanasia, the liver was harvested and subjected to formalin fixation and paraffin embedding for histological examination. RESULTS: Between one and four focal liver ablations (total 24 ablations) were successfully performed in nine animals with either a 15 or 30 W laser generator. For the 15-W laser generator, the average single applicator ablation size was (2.0 ± 0.5) × (2.6 ± 0.4) cm(2) , as measured by magnetic resonance (MR) thermometry, or (1.7 ± 0.4) × (2.2 ± 0.6) cm(2) , as measured with gadolinium contrast, with the difference being not statistically significant. For the 30-W laser generator, the average single applicator ablation size was (2.4 ± 0.3) × (3.3 ± 0.5) cm(2) by MR thermometry and (2.1 ± 0.4) × (2.9 ± 0.3) cm(2) by gadolinium enhancement, with no statistically significant difference. Simultaneously activating two applicators with the 15 W generator demonstrated ablation sizes of (3.7 ± 0.9) × (3.2 ± 0.1) cm(2) using MR thermometry and (2.3 ± 0.6) × (2.4 ± 0.3) cm(2) with gadolinium contrast, while using two applicators in the 30-W laser generator, yielded (4.5 ± 0.6) × (3.9 ± 0.2) cm(2) using MR thermometry and (4.4 ± 1.1) × (3.6 ± 0.5) cm(2) with gadolinium contrast enhancement. CONCLUSION: In our experience, we found that liver ablations performed with a MR-guided 980-nm diode LITT system through the saline cooled catheter applicator could be performed throughout the liver. Additionally, liver ablations were safe and produced a clinically applicable ablation zone. These results suggest the 980-nm diode laser MR-guided LITT system could be effective in treatments of hepatic tumors.

Quantitative comparison of thermal dose models in normal canine brain.

PURPOSE: Minimally invasive thermal ablative therapies as alternatives to conventional surgical management of solid tumors and other pathologies is increasing owing to the potential benefits of performing these procedures in an outpatient setting with reduced complications and comorbidity. Magnetic resonance temperature imaging (MRTI) measurement allows existing thermal dose models to use the spatiotemporal temperature history to estimate the thermal damage to tissue. However, the various thermal dose models presented in the literature employ different parameters and thresholds, affecting the reliability of thermal dosimetry. In this study, the authors quantitatively compared three thermal dose models (Arrhenius rate process, CEM43, and threshold temperature) using the dice similarity coefficient (DSC). METHODS: The DSC was used to compare the spatial overlap between the region of thermal damage as predicted by the models for in vivo normal canine brain during thermal therapy to the region of thermal damage as revealed by contrast-enhanced T1-weighted images acquired immediately after therapy (< 20 min). The outer edge of the hyperintense rim of the ablation region was used as the surrogate marker for the limits of thermal coagulation. The DSC was also used to investigate the impact of varying the thresholds on each models' ability to predict the zone of thermal necrosis. RESULTS: At previously reported thresholds, the authors found that all three models showed good agreement (defined as DSC > 0.7) with post-treatment imaging. All three models examined across the range of commonly applied thresholds consistently showed highly accurate spatial overlap, low variability, and little dependence on temperature uncertainty. DSC values corresponding to cited thresholds were not significantly different from peak DSC values. CONCLUSIONS: Thus, the authors conclude that the all three thermal dose models can be used as a reliable surrogate for postcontrast tissue damage verification imaging in rapid ablation procedures and can also be used to enhance the capability of MRTI to control thermal therapy in real time.

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.

Feasibility of 3.0T magnetic resonance imaging-guided laser ablation of a cadaveric prostate.

OBJECTIVES: To demonstrate the feasibility of 3.0T magnetic resonance imaging (MRI)-guided laser ablation of the prostate. METHODS: MRI-guided laser ablations in the intact prostate gland were performed in 5 cadavers. The cadavers were brought into the MRI suite and placed in a supine headfirst position. A needle guide grid was placed against the perineum, and MRI was performed to co-localize the grid with the prostate imaging data set. Using the guidance grid and 14-gauge Abbocath catheters, the laser applicators were placed in the prostate with intermittent MRI guidance. After confirmation of the position of the laser applicators, 2-minute ablations were performed with continuous MRI temperature feedback. Using the relative change in temperature and the Arrhenius model of thermal tissue ablation, the ablation margins were calculated. RESULTS: Laser ablation was successfully performed in all 5 cadaveric prostates using 15- and 30-W laser generators. Thermal mapping in the axial, sagittal, and coronal planes was performed with calculated ablation margins projected back onto the magnitude MR images. Deviations of the needles from the template projections ranged from 1.0 to 4.1 mm (average 2.1) at insertion depths of 75.5-116.5 mm (average 98.2). In the 2 cadavers for which histologic correlation was available, the extent of the ablation zone corresponded to the temperature mapping findings and the ablation transition zones were identifiable on hematoxylin-eosin staining. CONCLUSIONS: Transperineal laser ablation of the prostate gland is possible using 3.0T MRI guidance and thermal mapping and offers the potential for precise image-guided focal targeting of prostate cancer.

Preclinical assessment of a 980-nm diode laser ablation system in a large animal tumor model.

PURPOSE: To characterize the performance of a 980-nm diode laser ablation system in an in vivo tumor model. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. The ablation system consisted of a 15-W, 980-nm diode laser, flexible diffusing-tipped fiber optic, and 17-gauge internally cooled catheter. Ten immunosuppressed dogs were inoculated subcutaneously with canine-transmissible venereal tumor fragments in eight dorsal locations. Laser ablations were performed at 79 sites where inoculations were successful (99%) at powers of 10 W, 12.5 W, and 15 W, with exposure times between 60 and 180 seconds. In 20 cases, multiple overlapping ablations were performed. After the dogs were euthanized, the tumors were harvested, sectioned along the applicator tract, measured, and photographed. Measurements of ablation zone were performed on gross specimen. Histopathology and viability staining was performed with hematoxylin and eosin and nicotinamide adenine dinucleotide hydrogen staining. RESULTS: Gross pathologic examination confirmed a well circumscribed ablation zone with sharp boundaries between thermally ablated tumor in the center surrounded by viable tumor tissue. When a single applicator was used, the greatest ablation diameters ranged from 12 mm at the lowest dose (10 W, 60 seconds) to 26 mm at the highest dose (15 W, 180 seconds). Multiple applicators created ablation zones as large as 42 mm in greatest diameter (with the lasers operating at 15 W for 120 seconds). CONCLUSIONS: The new 980-nm diode laser and internally cooled applicator effectively create large ellipsoid thermal ablations in less than 3 minutes.

Adaptive real-time bioheat transfer models for computer-driven MR-guided laser induced thermal therapy.

The treatment times of laser induced thermal therapies (LITT) guided by computational prediction are determined by the convergence behavior of partial differential equation (PDE)-constrained optimization problems. In this paper, we investigate the convergence behavior of a bioheat transfer constrained calibration problem to assess the feasibility of applying to real-time patient specific data. The calibration techniques utilize multiplanar thermal images obtained from the nondestructive in vivo heating of canine prostate. The calibration techniques attempt to adaptively recover the biothermal heterogeneities within the tissue on a patient-specific level and results in a formidable PDE constrained optimization problem to be solved in real time. A comprehensive calibration study is performed with both homogeneous and spatially heterogeneous biothermal model parameters with and without constitutive nonlinearities. Initial results presented here indicate that the calibration problems involving the inverse solution of thousands of model parameters can converge to a solution within three minutes and decrease the [see text for symbol](L) (2) (2) ((0, T; L) (2) ((Omega))) norm of the difference between computational prediction and the measured temperature values to a patient-specific regime.

Dermal scatter reduction in human skin: a method using controlled application of glycerol.

BACKGROUND AND OBJECTIVE: Previous studies in a hairless Guinea pig model showed that transdermal application of glycerol effected a temporary reduction in dermal scatter of light. This study focuses on the application of this protocol on human patients. STUDY DESIGN/MATERIALS AND METHODS: After stratum corneal removal, glycerol was applied to human subjects using a low pressure transdermal application device. Optical coherence tomography imaging showed increased intensity of radiation reaching deeper regions in the skin and photographs showed enhanced visualization of dermal structures. RESULTS/CONCLUSION: Topically applied glycerol increased light penetration of in vivo corneal-stripped skin. This minimally invasive approach to temporary dermal scatter reduction has the potential to improve the efficacy of light-based diagnostic or therapeutic devices.

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.

Preclinical in vivo study of a fluorescence affinity sensor for short-term continuous glucose monitoring in a small and large animal model.

BACKGROUND: The performance of a fiber-coupled fluorescence affinity sensor (FAS) was studied in vivo in small and large animal models, in order to assess its feasibility and safety for short-term glucose monitoring in humans. METHODS: Determination of interstitial glucose concentrations in skin tissue of hairless rats and small pigs was facilitated by measuring the fluorescence response of the implanted FAS over several hours and multiple days. Blood sugar changes in animals were induced by injections of insulin and dextrose. The Medtronic Minimed CGMS (Medtronic Diabetes, Northridge, CA) was used for comparison. RESULTS: The acute in vivo performance study of the fiber-coupled FAS showed that more than 96% of the paired FAS/venous blood glucose readings were in the clinically acceptable A and B regions of the Clarke Error Grid. Mean absolute relative difference (MARD) and root mean squared error (RMSE) values for small and large animal models were 18.5% and 19.8 mg/dL and 15.9% and 16.3 mg/dL, respectively. In comparison, MARD and RMSE for the Medtronic Minimed CGMS in small and large animal models were similar (in rats, 25.4% and 19.8 mg/dL, respectively; in pigs, 18.4% and 16.2 mg/dL, respectively). No instance of irritation or infection was observed at any implantation site. The in vivo performance of FAS over a 3-day period was successfully demonstrated in both animal models. CONCLUSIONS: Overall, the fiber-coupled FAS was safe, and its performance during 4-h and 3-day testing compared favorably to the commercially available Medtronic Minimed CGMS, indicating its potential value for diabetes management.

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.

Toward universal flavivirus identification by mass cataloging.

Development of rapid and specific molecular diagnostics for flaviviruses remains an important global health challenge. Herein a platform technology using mass spectrometry that can be used for universal identification and genotyping of these viruses is described. The feasibility of the approach is demonstrated by using it to correctly identify and serotype two strains of dengue virus. Predictive calculations show that the approach can be expected to be equally efficacious for the identification and epidemiological tracking of other flaviviruses including West Nile, Japanese encephalitis, and Yellow Fever. In the case of dengue at least, the method can also distinguish major subgroupings within each serotype. All process steps are amenable to high-throughput, automated implementation. The assay protocol is also compatible with miniature mass spectrometers currently in development, thereby allowing the assay to be brought to remote locations for rapid response to and tracking of outbreaks.

Affinity-based turbidity sensor for glucose monitoring by optical coherence tomography: toward the development of an implantable sensor.

We investigated the feasibility of constructing an implantable optical-based sensor for seminoninvasive continuous monitoring of analytes. In this novel sensor, analyte concentration-dependent changes induced in the degree of optical turbidity of the sensing element can be accurately monitored by optical coherence tomography (OCT), an interferometric technique. To demonstrate proof-of-concept, we engineered a sensor for monitoring glucose concentration that enabled us to quantitatively monitor the glucose-specific changes induced in bulk scattering (turbidity) of the sensor. The sensor consists of a glucose-permeable membrane housing that contains a suspension of macroporous hydrogel particles and concanavalin A (ConA), a glucose-specific lectin, that are designed to alter the optical scattering of the sensor as a function of glucose concentration. The mechanism of modulation of bulk turbidity in the sensor is based on glucose-specific affinity binding of ConA to pendant glucose residues of macroporous hydrogel particles. The affinity-based modulation of the scattering coefficient was significantly enhanced by optimizing particle size, particle size distribution, and ConA concentration. Successful operation of the sensor was demonstrated under in vitro condition where excellent reversibility and stability (160 days) of prototype sensors with good overall response over the physiological glucose concentration range (2.5-20 mM) and good accuracy (standard deviation 5%) were observed. Furthermore, to assess the feasibility of using the novel sensor as one that can be implanted under skin, the sensor was covered by a 0.4 mm thick tissue phantom where it was demonstrable that the response of the sensor to 10 mM glucose change could still be measured in the presence of a layer of tissue shielding the sensor aiming to simulate in vivo condition. In summary, we have demonstrated that it is feasible to develop an affinity-based turbidity sensor that can exhibit a highly specific optical response as a function of changes in local glucose concentration and such response can be accurately monitored by OCT suggesting that the novel sensor can potentially be engineered to be used as an implantable sensor for in vivo monitoring of analytes.

Fiber-coupled fluorescence affinity sensor for 3-day in vivo glucose sensing.

BACKGROUND: To evaluate the feasibility of an implantable fiber-coupled fluorescence affinity sensor (FAS) for glucose monitoring in humans, we studied the acute and chronic in vivo performance in hairless rats and pigs. METHODS: The implantable fiber-coupled FAS was constructed by filling a dialysis chamber made of a regenerated cellulose membrane mounted to the distal tip of an optical fiber with fluorescent chemistry based on concanavalin A. Blood sugar changes in animals were induced by injections of insulin and dextrose. Determination of interstitial glucose concentrations in skin tissue was facilitated by measuring the fluorescence response of the FAS. RESULTS: The acute in vivo response of the fiber-coupled FAS exhibited good correlation coefficients (>0.77) with blood sugar changes and minimal lag times (2-10 min) after 2 hours of sensor implantation. Equilibrium of the sensor signal with interstitial fluid was required less than 60 min after implantation. For both rats and pigs, chronic response of the FAS to blood sugar modulations measured during the third day of implantation successfully demonstrated proof-of-concept for short-term glucose monitoring. A slight decrease in sensitivity after 3 days in the small animal model was assumed to be caused by excessive mechanical forces on the implanted device because of high animal motility. CONCLUSIONS: Overall, the chronic in vivo performance of the FAS in two different animal models over 3 days was clinically acceptable and comparable to other continuous glucose monitoring platforms. The major benefit of the FAS is the absence of "autodestructive" side products and any device-related warm-up time after sensor reconnection.