Simultaneous estimation of SAR, thermal diffusivity, and damping using periodic power modulation for MRgFUS quality assurance

Purpose: A crucial aspect of quality assurance in thermal therapy is periodic demonstration of the heating performance of the device. Existing methods estimate the specific absorption rate (SAR) from the temperature rise after a short power pulse, which yields a biased estimate as thermal diffusion broadens the apparent SAR pattern. To obtain an unbiased estimate, we propose a robust frequency-domain method that simultaneously identifies the SAR as well as the thermal dynamics. Methods: We propose a method consisting of periodic modulation of the FUS power while recording the response with MR thermometry (MRT). This approach enables unbiased measurements of spatial Fourier coefficients that encode the thermal response. These coefficients are substituted in a generic thermal model to simultaneously estimate the SAR, diffusivity, and damping. The method was tested using a cylindrical phantom and a 3 T clinical MR-HIFU system. Three scenarios with varying modulation strategies are chosen to challenge the method. The results are compared to the well-known power pulse technique. Results: The thermal diffusivity is estimated at 0.151 mm 2s -1 with a standard deviation of 0.01 mm 2s -1 between six experiments. The SAR estimates are consistent between all experiments and show an excellent signal-to-noise ratio (SNR) compared to the well established power pulse method. The frequency-domain method proved to be insensitive to B 0-drift and non steady-state initial temperature distributions. Conclusion: The proposed frequency-domain estimation method shows a high SNR and provided reproducible estimates of the SAR and the corresponding thermal diffusivity. The findings suggest that frequency-domain tools can be highly effective at estimating the SAR from (biased) MRT data acquired during periodic power modulation. </p

Model predictive control for MR-HIFU-mediated, uniform hyperthermia

Purpose: In local hyperthermia, precise temperature control throughout the entire target region is key for swift, safe, and effective treatment. In this article, we present a model predictive control (MPC) algorithm providing voxel-level temperature control in magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) and assess the improvement in performance it provides over the current state of the art. Materials and methods: The influence of model detail on the prediction quality and runtime of the controller is evaluated and a tissue mimicking phantom is characterized using the resulting model. Next, potential problems arising from modeling errors are evaluated in silico and in the characterized phantom. Finally, the controller’s performance is compared to the current state-of-the-art hyperthermia controller in side-by-side experiments. Results: Modeling diffusion by heat exchange between four neighboring voxels achieves high predictive performance and results in runtimes suited for real-time control. Erroneous model parameters deteriorate the MPC’s performance. Using models derived from thermometry data acquired during low powered test sonications, however, high control performance is achieved. In a direct comparison with the state-of-the-art hyperthermia controller, the MPC produces smaller tracking errors and tighter temperature distributions, both in a homogeneous target and near a localized heat sink. Conclusion: Using thermal models deduced from low-powered test sonications, the proposed MPC algorithm provides good performance in phantoms. In direct comparison to the current state-of-the-art hyperthermia controller, MPC performs better due to the more finely tuned heating patterns and therefore constitutes an important step toward stable, uniform hyperthermia

Simultaneous estimation of SAR, thermal diffusivity, and damping using periodic power modulation for MRgFUS quality assurance

AbstractPurpose: A crucial aspect of quality assurance in thermal therapy is periodic demonstration of the heating performance of the device. Existing methods estimate the specific absorption rate (SAR) from the temperature rise after a short power pulse, which yields a biased estimate as thermal diffusion broadens the apparent SAR pattern. To obtain an unbiased estimate, we propose a robust frequency-domain method that simultaneously identifies the SAR as well as the thermal dynamics.Methods: We propose a method consisting of periodic modulation of the FUS power while recording the response with MR thermometry (MRT). This approach enables unbiased measurements of spatial Fourier coefficients that encode the thermal response. These coefficients are substituted in a generic thermal model to simultaneously estimate the SAR, diffusivity, and damping. The method was tested using a cylindrical phantom and a 3 T clinical MR-HIFU system. Three scenarios with varying modulation strategies are chosen to challenge the method. The results are compared to the well-known power pulse technique.Results: The thermal diffusivity is estimated at 0.151 mm2s–1 with a standard deviation of 0.01 mm2s–1 between six experiments. The SAR estimates are consistent between all experiments and show an excellent signal-to-noise ratio (SNR) compared to the well established power pulse method. The frequency-domain method proved to be insensitive to B0-drift and non steady-state initial temperature distributions.Conclusion: The proposed frequency-domain estimation method shows a high SNR and provided reproducible estimates of the SAR and the corresponding thermal diffusivity. The findings suggest that frequency-domain tools can be highly effective at estimating the SAR from (biased) MRT data acquired during periodic power modulation

Offset-Free Model Predictive Temperature Control for Ultrasound-Based Hyperthermia Cancer Treatments

Heating cancer cells over an extended period of time, referred to as hyperthermia, has been proven to enhance the effects of chemotherapy and radiotherapy without inducing additional toxicity or undesirable side effects, and is therefore considered a highly valuable adjuvant therapy in cancer treatment. In this work, a model predictive control (MPC) setup is developed for improving performance and robustness in regulating the temperature for magnetic-resonance-guided high-intensity focused ultrasound (MR-HIFU) hyperthermia treatments. The proposed control design incorporates a disturbance estimator as encountered in offset-free MPC that is able to remove the steady-state temperature error caused by plant-model mismatch. For the considered healthcare application, such modeling errors are inevitable in practice due to the high variability of tissue properties in patients, some of which even exhibit time- and temperature-dependent behavior due to the body's thermoregulatory response, combined with the fact that extensive model identification is undesirable in the clinic. The controller's performance is demonstrated by means of in vivo experiments on a porcine thigh muscle using a clinical MR-HIFU treatment setup

Feasibility study of MR-guided pancreas ablation using high-intensity focused ultrasound in a healthy swine model

Purpose:Pancreatic cancer is typically diagnosed in a late stage with limited therapeutic options. For those patients, ultrasound-guided high-intensity focused ultrasound (US-HIFU) can improve local control and alleviate pain. However, MRI-guided HIFU (MR-HIFU) has not yet been studied extensively in this context. To facilitate related research and accelerate clinical translation, we report a workflow for thein vivoHIFU ablation of the porcine pancreas under MRI guidance. Materials and methods:The pancreases of five healthy German landrace pigs (35-58 kg) were sonicated using a clinical MR-HIFU system. Acoustic access to the pancreas was supported by a specialized diet and a hydrogel compression device for bowel displacement. Organ motion was suspended using periods of apnea. The size of the resulting thermal lesions was assessed using the thermal threshold- and dose profiles, non-perfused volume, and gross examination. The effect of the compression device on beam path length was assessed using MRI imaging. Results:Eight of ten treatments resulted in clearly visible damage in the target tissue upon gross examination. Five treatments resulted in coagulative necrosis. Good agreement between the four metrics for lesion size and a clear correlation between the delivered energy dose and the resulting lesion size were found. The compression device notably shortened the intra-abdominal beam path. Conclusions:We demonstrated a workflow for HIFU treatment of the porcine pancreas in-vivo under MRI-guidance. This development bears significance for the development of MR-guided HIFU interventions on the pancreas as the pig is the preferred animal model for the translation of pre-clinical research into clinical application

Visualization of thermal washout due to spatiotemporally heterogenous perfusion in the application of a model-based control algorithm for MR-HIFU mediated hyperthermia

Purpose This article will report results from the in-vivo application of a previously published model-predictive control algorithm for MR-HIFU hyperthermia. The purpose of the investigation was to test the controller's in-vivo performance and behavior in the presence of heterogeneous perfusion. Materials and methods Hyperthermia at 42 degrees C was induced and maintained for up to 30 min in a circular section of a thermometry slice in the biceps femoris of German landrace pigs (n=5) using a commercial MR-HIFU system and a recently developed MPC algorithm. The heating power allocation was correlated with heat sink maps and contrast-enhanced MRI images. The temporal change in perfusion was estimated based on the power required to maintain hyperthermia. Results The controller performed well throughout the treatments with an absolute average tracking error of 0.27 +/- 0.15 degrees C and an average difference of 1.25 +/- 0.22 degrees C between T 10 and T 90 . The MPC algorithm allocates additional heating power to sub-volumes with elevated heat sink effects, which are colocalized with blood vessels visible on contrast-enhanced MRI. The perfusion appeared to have increased by at least a factor of similar to 1.86 on average. Conclusions The MPC controller generates temperature distributions with a narrow spectrum of voxel temperatures inside the target ROI despite the presence of spatiotemporally heterogeneous perfusion due to the rapid thermometry feedback available with MR-HIFU and the flexible allocation of heating power. The visualization of spatiotemporally heterogeneous perfusion presents new research opportunities for the investigation of stimulated perfusion in hypoxic tumor regions

Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model

Purpose: Encapsulation of cytotoxic drugs for a localized release is an effective way to increase the therapeutic window of such agents. In this article we present the localized release of doxorubicin (DOX) from phosphatidyldiglycerol (DPPG(2)) based thermosensitive liposomes using MR-HIFU mediated hyperthermia in a swine model. Materials and methods: German landrace pigs of weights between 37.5 and 53.5 kg received a 30-min infusion of DOX containing thermosensitive liposomes (50 mg DOX/m(2)). The pigs' biceps femoris was treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided high intensity focused ultrasound, starting 10 min and 60 min after initiation of the infusion, respectively. The pharmacokinetics and biodistribution of DOX were determined and an analysis of the treatment parameters' influence was performed. Results: Compared to untreated tissue, we found a 15-fold and a 7-fold increase in DOX concentration in the muscle volumes that had undergone hyperthermia starting 10 min and 60 min after the beginning of the infusion, respectively. The pharmacokinetic analysis showed a prolonged circulation time of DOX and a correlation between the AUC of extra-liposomal DOX in the bloodstream and the amount of DOX accumulated in the target tissue. Conclusions: We have demonstrated a workflow for MR-HIFU hyperthermia drug delivery that can be adapted to a clinical setting, showing that HIFU-hyperthermia is a suitable method for local drug release of DOX using DPPG(2) based thermosensitive liposomes in stationary targets. Using the developed pharmacokinetic model, an optimization of the drug quantity deposited in the target via the timing of infusion and hyperthermia should be possible