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.

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.

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.

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.

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.

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.

Temporary dermal scatter reduction: quantitative assessment and implications for improved laser tattoo removal.

BACKGROUND AND OBJECTIVES: Temporary dermal clearing, i.e., reduction in the attenuation coefficient of the dermis and epidermis, may lead to improved laser tattoo removal by providing increased efficiency of laser delivery to embedded ink particles and enabling the use of shorter wavelength visible lasers more effective on certain inks. STUDY DESIGNS/MATERIALS AND METHODS: In a hairless guinea pig model of human tattoo, we tested both intradermal and transdermal application of glycerol, using visual inspection, spectral analysis, and optical coherence tomography techniques to assess effectiveness. In controlled experiments, we compared the outcomes of single laser treatment sessions for both cleared and uncleared tattoo sites using Q-switched 755 and 532 nm lasers on three different inks. RESULTS: Intradermal injection of clearing agents induced dermal clearing but resulted in necrosis and scar. Transdermal application of clearing agents resulted in moderate reversible clearing, which was localized to the superficial layers of the skin and did not result in complications. Statistically significant differences in laser treatment outcome were observed relative to a number of treatment parameters including the treatment of certain tattoos by short wavelength lasers. CONCLUSIONS: Temporary clearing of superficial skin layers may be performed in an apparently safe and reliable manner. Clearing should lead to increased penetration of laser light to tattoos and should, therefore, increase treatment efficiency. Further study is needed to determine the degree to which this change is of clinical value.

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.

Thermal therapy of canine cerebral tumors using a 980 nm diode laser with MR temperature-sensitive imaging feedback.

BACKGROUND AND PURPOSE: The laser-induced thermal therapy (LITT) of cerebral tumors has conventionally been performed using Nd:YAG lasers and is associated with a risk of high focal temperatures potentially followed by cavitation that could result in boiling and/or explosive char. We have developed small diffusing laser fiber tips to better distribute the energy deposition and a computer controlled feedback system to monitor therapy and prevent excess temperature buildup. In this study, we evaluated the feasibility of using magnetic resonance temperature imaging (MRTI)-based feedback system for the thermal treatment of experimental intracerebral tumors using 980 nm laser irradiation delivered through these diffusing tips. STUDY DESIGN/MATERIALS AND METHODS: Transmissible venereal tumors (TVTs) were grown via inoculation in the right cerebral hemisphere of seven canines. The laser fiber tips were inserted into a total of 10 independent TVT-suspected regions in the seven animals. Margins for the target area in each animal were prescribed on the basis of pretreatment MR images. MRTI-based feedback software was used to measure and regulate both temperature and the delivered thermal dose to achieve the desired thermal ablation and prevent excess heating. The effects of treatment were verified by results of histologic analyses. RESULTS: Treatments resulted in contiguous areas of thermal necrosis in tumors and adjacent brain margin. The feedback software successfully cut off the laser power once the desired treatment volume was achieved, and prevented focal temperatures from exceeding predefined thresholds. Follow-up MRI studies showed 1.4- to 2.9-fold LITT-induced lesion expansion within 1-6 days after treatment. CONCLUSIONS: Targeted thermal coagulation of small intracerebral tumors is feasible using MRTI-based feedback and diffused 980 nm diode laser light.

MR thermometry-based feedback control of laser interstitial thermal therapy at 980 nm.

BACKGROUND AND OBJECTIVES: The goal of this study was to explore the feasibility of magnetic resonance thermal imaging (MRTI)-based feedback control of intracerebral laser interstitial thermal therapy (LITT), using a computer workstation and 980-nm diode laser interfaced to an MR scanner. STUDY DESIGN/MATERIALS AND METHODS: A computer-controlled laser thermal therapy system was used to produce 12 ex vivo lesions in 3 canine and porcine brains and 16 in vivo lesions in 6 canines with diffusing tip fiberoptic applicators and energies from 54 to 900 J. MRTI predictions of thermal damage were correlated with histopathologic analysis. RESULTS: Under feedback control, no carbonization, vaporization, or applicator damage was observed. MRTI-based prediction of thermal dose was not significantly different from histological evaluation of achieved thermal necrosis. CONCLUSIONS: The computer-controlled thermal therapy system was effective at regulating heating, eliminating carbonization and vaporization, and protecting fiberoptic applicators. MRTI estimation of thermal dose accurately predicted achieved thermal necrosis.