A model evaluation study for treatment planning of laser-induced thermal therapy.

A cross-validation analysis evaluating computer model prediction accuracy for a priori planning magnetic resonance-guided laser-induced thermal therapy (MRgLITT) procedures in treating focal diseased brain tissue is presented. Two mathematical models are considered. (1) A spectral element discretisation of the transient Pennes bioheat transfer equation is implemented to predict the laser-induced heating in perfused tissue. (2) A closed-form algorithm for predicting the steady-state heat transfer from a linear superposition of analytic point source heating functions is also considered. Prediction accuracy is retrospectively evaluated via leave-one-out cross-validation (LOOCV). Modelling predictions are quantitatively evaluated in terms of a Dice similarity coefficient (DSC) between the simulated thermal dose and thermal dose information contained within N = 22 MR thermometry datasets. During LOOCV analysis, the transient model's DSC mean and median are 0.7323 and 0.8001 respectively, with 15 of 22 DSC values exceeding the success criterion of DSC ≥ 0.7. The steady-state model's DSC mean and median are 0.6431 and 0.6770 respectively, with 10 of 22 passing. A one-sample, one-sided Wilcoxon signed-rank test indicates that the transient finite element method model achieves the prediction success criteria, DSC ≥ 0.7, at a statistically significant level.

Stereotactic laser induced thermotherapy (LITT): a novel treatment for brain lesions regrowing after radiosurgery.

Since the inception of radiosurgery, the management of brain metastases has become a common problem for neurosurgeons. Although the use of stereotactic radiosurgery and/or whole brain radiation therapy serves to control the majority of disease burden, patients who survive longer than 6-8 months sometimes face the problem of symptomatic radiographically regrowing lesions with few treatment options. Here we investigate the feasibility of use of MRI-guided stereotactic laser induced thermotherapy (LITT) as a novel treatment option for these lesions. Six patients who had previously undergone gamma knife stereotactic radiosurgery for brain metastases were selected. All patients had an initial favorable response to radiosurgery but subsequently developed regrowth of at least one lesion associated with recurrent edema and progressive neurological symptoms requiring ongoing steroids for symptom control. All lesions were evaluated for craniotomy, but were deemed unresectable due to deep location or patient's comorbidities. Stereotactic biopsies were performed prior to the thermotherapy procedure in all cases. LITT was performed using the Visualase system and follow-up MRI imaging was used to determine treatment response. In all six patients biopsy results were negative for tumor and consistent with adverse radiation effects also known as radiation necrosis. Patients tolerated the procedure well and were discharged from the hospital within 48 h of the procedure. In 4/6 cases there was durable improvement of neurological symptoms until death. In all cases steroids were weaned off within 2 months. One patient died from systemic causes related to his cancer a month after the procedure. One patient had regrowth of the lesion 3 months after the procedure and required re-initiation of steroids and standard craniotomy for surgical resection. There were no complications directly related to the thermocoagulation procedure. Stereotactic laser induced thermotherapy is a feasible alternative for the treatment of symptomatic regrowing metastatic lesions after radiosurgery. The procedure carries minimal morbidity and, in this small series, shows some effectiveness in the symptomatic relief of edema and neurological symptoms paralleled by radiographic lesional control. Further studies are necessary to elucidate the safety of this technology.

Magnetic resonance thermometry-guided laser-induced thermal therapy for intracranial neoplasms: initial experience.

BACKGROUND: Laser-induced thermal therapy is a promising tool in the neurosurgeon's armamentarium. This methodology has seen a resurgence in application as a result of advances in technology. OBJECTIVE: To report our initial experience with the procedure after treating 20 consecutive patients, the largest series to date. METHODS: Patients were selected for laser therapy if they had failed conventional therapies, were unable to tolerate an open cranial procedure, or the tumor was deemed otherwise inoperable. In this series, 980-nm diode laser catheters were placed stereotactically in the operating room. The patients were then transferred to the magnetic resonance imaging suite for thermal ablation. RESULTS: A total of 31 laser applicators were placed in 20 patients with intracranial neoplasms. The majority of patients (17 of 20) had prior treatment for their tumors. The overall accuracy of laser insertion was 83.9%, improving with increased experience. The average lesion volume treated was 7.0 ± 9.0 cm2. With the use of damage estimates from the software provided, the treatment continued until the entire tumor had been irreversibly ablated. The average length of hospitalization was 2.27 days, with the majority of patients going home on postoperative day 1. Complications occurred in 4 patients, typically in those who were in poor health preoperatively. CONCLUSION: Laser-induced thermal therapy is an intuitive procedure for treating difficult intracranial neoplasms. As with any other procedure, patient selection and lesion selection are important factors in determining outcome.

Near-infrared light modulated photothermal effect increases vascular perfusion and enhances polymeric drug delivery.

Hyperthermia, which is heating of tumors above 43°C for about 30min, has been known to modulate vascular permeability for enhanced chemotherapy. However, it is not clear whether a similar effect exists when temperature at tumor sites is elevated above 43°C, such as temperature achieved in laser-induced photothermal ablation (PTA) therapy. Also, the effect of timing of chemotherapeutic drug administration following heating in the efficiency of drug delivery is not established. In this study, we investigated the impact of near infrared (NIR) laser irradiated anti-EGFR monoclonal antibody C225-conjugated hollow gold nanospheres (C225-HAuNS) on vascular permeability and subsequent tumor uptake of a water-soluble polymer using combined MRI, ultrasound and optical imaging approaches. Magnetic temperature imaging showed a maximum temperature of 65.2±0.10 °C in A431 tumor xenograft of mice treated with C225-HAuNS plus laser and 47.0±0.33 °C in tumors of mice treated with saline plus laser at 4 W/cm² for 3 min (control) at 2 mm from the light incident surface. Dynamic contrast enhanced (DCE) MRI demonstrated greater than 2-fold increase of DTPA-Gd in the initial area under the curve (IAUC90) in mice injected with C225-HAuNS and exposed to NIR laser compared with control mice at 3 min after laser treatment. Similarly, Power Doppler (PD) ultrasound revealed a 4- to 6-fold increase in percentage vascularization in mice treated with C225-HAuNS plus NIR laser compared to control mice and confirmed increased vascular perfusion immediately after laser treatment. Twenty-four hours later, the blood perfusion was shut down. On optical imaging, tumor uptake of PG-Gd-NIR813, which is the model polymeric drug used, was significantly higher (p-value<0.05) in mice injected with PG-Gd-NIR813 at 5 min after laser treatment than in mice injected with PG-Gd-NIR813 at 24h after laser treatment and the saline-treated mice. In conclusion, laser irradiation of tumors after intravenous injection of C255-HAuNS induces a thermally mediated modulation of the vascular perfusion, which enhances the delivery of polymeric drugs to the tumors at the time phototherapy is initiated.

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.

Use of gold nanoshells to constrain and enhance laser thermal therapy of metastatic liver tumours.

PURPOSE: To investigate the impact of intravenously injected gold nanoparticles on interstitially delivered laser induced thermal therapy (LITT) in the liver. METHODS: 3D finite element modelling, ex vivo canine liver tissue containing gold nanoparticles absorbing at 800 nm, and agar gel phantoms were used to simulate the presence of nanoparticles in the liver during LITT. Real-time magnetic resonance temperature imaging (MRTI) based on the temperature sensitivity of the proton resonance frequency shift (PRFS) was used to map the spatiotemporal distribution of heating in the experiments and validate the predictions of 3D finite element simulations of heating. RESULTS: Experimental results show good agreement with both the simulation and the ex vivo experiments. Average discrepancy between simulation and experiment was shown to be 1.6 degrees C or less with the maximum difference being 3.8 degrees C due to a small offset in laser positioning. CONCLUSION: A high nanoshell concentration in the surrounding liver parenchyma, such as that which would be expected from an intravenous injection of gold nanoshells ( approximately 120 nm) acts as both a beam stop for the laser and secondary heat source for the treatment, helping to better heat the lesions and confine the treatment to the lesion. This indicates a potential to use nanoparticles to enhance both the safety and efficacy of LITT procedures in the liver.

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.

Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an integrated antihypoxic and localized vascular disrupting targeting strategy.

We report noninvasive modulation of in vivo tumor radiation response using gold nanoshells. Mild-temperature hyperthermia generated by near-infrared illumination of gold nanoshell-laden tumors, noninvasively quantified by magnetic resonance temperature imaging, causes an early increase in tumor perfusion that reduces the hypoxic fraction of tumors. A subsequent radiation dose induces vascular disruption with extensive tumor necrosis. Gold nanoshells sequestered in the perivascular space mediate these two tumor vasculature-focused effects to improve radiation response of tumors. This novel integrated antihypoxic and localized vascular disrupting therapy can potentially be combined with other conventional antitumor therapies.