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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Bacterial genotyping by 16S rRNA mass cataloging.

BACKGROUND: It has recently been demonstrated that organism identifications can be recovered from mass spectra using various methods including base-specific fragmentation of nucleic acids. Because mass spectrometry is extremely rapid and widely available such techniques offer significant advantages in some applications. A key element in favor of mass spectrometric analysis of RNA fragmentation patterns is that a reference database for analysis of the results can be generated from sequence information. In contrast to hybridization approaches, the genetic affinity of any unknown isolate can in principle be determined within the context of all previously sequenced 16S rRNAs without prior knowledge of what the organism is. In contrast to the original RNase T1 cataloging method, when digestion products are analyzed by mass spectrometry, products with the same base composition cannot be distinguished. Hence, it is possible that organisms that are not closely related (having different underlying sequences) might be falsely identified by mass spectral coincidence. We present a convenient spectral coincidence function for expressing the degree of similarity (or distance) between any two mass-spectra. Trees constructed using this function are consistent with those produced by direct comparison of primary sequences, demonstrating that the inherent degeneracy in mass spectrometric analysis of RNA fragments does not preclude correct organism identification. RESULTS: Neighbor-joining trees for important bacterial pathogens were generated using distances based on mass spectrometric observables and the spectral coincidence function. These trees demonstrate that most pathogens will be readily distinguished using mass spectrometric analyses of RNA digestion products. A more detailed, genus-level analysis of pathogens and near relatives was also performed, and it was found that assignments of genetic affinity were consistent with those obtained by direct sequence comparisons. Finally, typical values of the coincidence between organisms were also examined with regard to phylogenetic level and sequence variability. CONCLUSION: Cluster analysis based on comparison of mass spectrometric observables using the spectral coincidence function is an extremely useful tool for determining the genetic affinity of an unknown bacterium. Additionally, fragmentation patterns can determine within hours if an unknown isolate is potentially a known pathogen among thousands of possible organisms, and if so, which one.

Concanavalin A for in vivo glucose sensing: a biotoxicity review.

Over the last two decades there as has been surging scientific interest in employing the glucose- and mannose-specific lectin Concanavalin A (ConA) in affinity biosensors for in vivo glucose monitoring in diabetics. Numerous research groups have successfully shown in in vitro and in vivo studies that ConA-based affinity sensors can monitor glucose very accurately and reproducibly over many months, making ConA-based sensors an extremely interesting prospect for long-term implantation in humans. Despite this progress, there remains concern over the safety of ConA, which has widely been reported as a toxin in the literature. In this article, we review in vitro and in vivo studies related to ConA toxicity in order to assess the health risks posed by ConA in the context of an implantable biosensor. Based on the wealth of information available and on data from our own studies, we can conclude that the site of implantation (subcutaneous skin tissue) and the small amount of ConA (<10 microg/microl) being used in implantable glucose-sensitive detector devices like those proposed by various research groups would pose little or no health risk to its bearer even in the event of unexpected sensor rupture.

In vivo performance evaluation of a transdermal near- infrared fluorescence resonance energy transfer affinity sensor for continuous glucose monitoring.

The in vivo performance of a transdermal near-infrared fluorescence resonance energy transfer (FRET) affinity sensor was investigated in hairless rats, in order to validate its feasibility for glucose monitoring in humans. The sensor itself consists of a small hollow fiber implanted in dermal skin tissue, containing glucose-sensitive assay chemistry composed of agarose-immobilized Concanavalin A (ConA) and free dextran. The glucose-dependent fluorescence change is based on FRET between near-infrared-compatible donor and quencher dyes that are chemically linked to dextran and ConA, respectively. We conducted an acute in vivo evaluation of transdermal sensors with an optical fiber-coupled setup over 4 h, and a chronic in vivo evaluation of fully implanted sensors for up to 16 days. The fiber-coupled sensors followed trends of blood glucose concentrations very well with a delay of less than 5 min. The acute performance of the implanted sensors at the day of implantation was similar to that of the fiber-coupled sensors. After 2 weeks the implanted sensors remained functional, evidenced by an adequate correlation between sensor signal and changes in blood glucose excursions, but exhibited delays of approximately 10-15 min. Preliminary characterization of host response showed signs of mild inflammations around the implanted sensor, which were characterized by formation of a 10-20-microm-thick collagen band, typical for capsule formation. An acute study of systemic ConA biotoxicity was also conducted. A histological analysis of various organs and of clinical chemistry data showed no significant differences between rats receiving intradermal injections of ConA at 10 times the concentration in the sensor and rats in a control group (injection of saline solution). The absence of a toxicological or systemic response to ConA at a 10-fold larger amount than in the sensor should dispel concerns over the in vivo safety of ConA-based sensors. This study clearly demonstrates the feasibility of the proposed transdermal FRET-based sensor interrogation concept for glucose monitoring.

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.

The use of the hairless guinea pig in tattoo research.

The study and optimization of tattoo removal continues to be of importance in the dermatology community. Robust animal models whose skin is physiologically similar to humans and who are easily handled are desirable. To this end, we report on our experience with the hairless guinea pig as a model for tattoo research. This research was conducted as part of a larger study toward increased efficacy of laser tattoo removal. Here we report on procedures for both placement and aftercare of tattoos which result in superior tattoo quality and retention.

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.

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.

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.