First validation of a model-based hepatic percutaneous microwave ablation planning on a clinical dataset.

A model-based planning tool, integrated in an imaging system, is envisioned for CT-guided percutaneous microwave ablation. This study aims to evaluate the biophysical model performance, by comparing its prediction retrospectively with the actual ablation ground truth from a clinical dataset in liver. The biophysical model uses a simplified formulation of heat deposition on the applicator and a heat sink related to vasculature to solve the bioheat equation. A performance metric is defined to assess how the planned ablation overlaps the actual ground truth. Results demonstrate superiority of this model prediction compared to manufacturer tabulated data and a significant influence of the vasculature cooling effect. Nevertheless, vasculature shortage due to branches occlusion and applicator misalignment due to registration error between scans affects the thermal prediction. With a more accurate vasculature segmentation, occlusion risk can be estimated, whereas branches can be used as liver landmarks to improve the registration accuracy. Overall, this study emphasizes the benefit of a model-based thermal ablation solution in better planning the ablation procedures. Contrast and registration protocols must be adapted to facilitate its integration into the clinical workflow.

Model-based hepatic percutaneous microwaveablation planning. First validation on a clinical dataset.

A model-based planning tool, integrated in an imaging system, is envisioned for CT-guided percutaneous microwave ablation. This study aims to evaluate the biophysical model performance, by comparing its prediction retrospectively with the actualablation ground truth from a clinical data set in liver. The biophysical model uses a simplified formulation of heat depositionon the applicator and a heat sink related to vasculature to solve the bioheat equation. A performance metric is defined toassess how the planned ablation overlaps the actual ground truth. Results demonstrate superiority of this model predictioncompared to manufacturer tabulated data and a significant influence of the vasculature cooling effect. Nevertheless, vasculatureshortage due to branches occlusion and applicator misalignment due to registration error between scans affects the thermalprediction. With a more accurate vasculature segmentation, occlusion risk can be estimated, whereas branches can be usedas liver landmarks to improve the registration accuracy. Overall, this study emphasizes the benefit of a model-based thermalablation solution in better planning the ablation procedures. Contrast and registration protocols must be adapted to facilitate itsintegration into the clinical workflow.

Study of flow effects on temperature-controlled radiofrequency ablation using phantom experiments and forward simulations.

PURPOSE: Blood flow is known to add variability to hepatic radiofrequency ablation (RFA) treatment outcomes. However, few studies exist on its impact on temperature-controlled RFA. Hence, we investigate large-scale blood flow effects on temperature-controlled RFA in flow channel experiments and numerical simulations. METHODS: Ablation zones were induced in tissue-mimicking, thermochromic phantoms with a single flow channel, using an RF generator with temperature-controlled power delivery and a monopolar needle electrode. Channels were generated by molding the phantom around a removable rod. Channel radius and saline flow rate were varied to study the impact of flow on (i) the ablated cross-sectional area, (ii) the delivered generator power, and (iii) the occurrence of directional effects on the thermal lesion. Finite volume simulations reproducing the experimental geometry, flow conditions, and generator power input were conducted and compared to the experimental ablation outcomes. RESULTS: Vessels of different channel radii r affected the ablation outcome in different ways. For r = 0.275  mm, the ablated area decreased with increasing flow rate while the energy input was hardly affected. For r = 0.9  mm and r = 2.3  mm, the energy input increased toward larger flow rates; for these radii, the ablated area decreased and increased toward larger flow rates, respectively, while still being reduced overall as compared to the reference experiment without flow. Directional effects, that is, local shrinking of the lesion upstream of the needle and an extension thereof downstream, were observed only for the smallest radius. The simulations qualitatively confirmed these observations. As compared to performing the simulations without flow, including flow effects in the simulations reduced the mean absolute error between experimental and simulated ablated areas from 0.23 to 0.12. CONCLUSION: While the temperature control mechanism did not detect the heat sink effect in the case of the smallest channel radius, it counteracted the heat sink effect in the case of the larger channel radii with an increased energy input; this explains the increase in ablated area toward high flow rates (for r = 2.3  mm). The experiments in a simple phantom setup, thus, contribute to a good understanding of the phenomenon and are suitable for model validation.

Spiral blurring correction with water-fat separation for magnetic resonance fingerprinting in the breast.

PURPOSE: Magnetic resonance fingerprinting (MRF) with spiral readout enables rapid quantification of tissue relaxation times. However, it is prone to blurring because of off-resonance effects. Hence, fat blurring into adjacent regions might prevent identification of small tumors by their quantitative T1 and T2 values. This study aims to correct for the blurring artifacts, thereby enabling fast quantitative mapping in the female breast. METHODS: The impact of fat blurring on spiral MRF results was first assessed by simulations. Then, MRF was combined with 3-point Dixon water-fat separation and spiral blurring correction based on conjugate phase reconstruction. The approach was assessed in phantom experiments and compared to Cartesian reference measurements, namely inversion recovery (IR), multi-echo spin echo (MESE), and Cartesian MRF, by normalized root-mean-square error (NRMSE) and SD calculations. Feasibility is further demonstrated in vivo for quantitative breast measurements of 6 healthy female volunteers, age range 24-31 y. RESULTS: In the phantom experiment, the blurring correction reduced the NRMSE per phantom vial on average from 16% to 8% for T1 and from 18% to 11% for T2 when comparing spiral MRF to IR/MESE sequences. When comparing to Cartesian MRF, the NRMSE reduced from 15% to 8% for T1 and from 12% to 7% for T2 . Furthermore, SDs decreased. In vivo, the blurring correction removed fat bias on T1 /T2 from a rim of ~7-8 mm width adjacent to fatty structures. CONCLUSION: The blurring correction for spiral MRF yields improved quantitative maps in the presence of water and fat.

Bone metastasis treatment using magnetic resonance-guided high intensity focused ultrasound.

OBJECTIVES: Bone pain resulting from cancer metastases reduces a patient's quality of life. Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) is a promising alternative palliative thermal treatment technique for bone metastases that has been tested in a few clinical studies. Here, we describe a comprehensive pre-clinical study to investigate the effects, and efficacy of MR-HIFU ablation for the palliative treatment of osteoblastic bone metastases in rats. MATERIALS AND METHODS: Prostate cancer cells (MATLyLu) were injected intra-osseously in Copenhagen rats. Upon detection of pain, as determined with a dynamic weight bearing (DWB) system, a MR-HIFU system was used to thermally ablate the bone region with tumor. Treatment effect and efficacy were assessed using magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) with technetium-99m medronate ((99m)Tc-MDP), micro-computed tomography (µCT) and histology. RESULTS: DWB analysis demonstrated that MR-HIFU-treated animals retained 58.6 ± 20.4% of limb usage as compared to 2.6 ± 6.3% in untreated animals (P=0.003). MR-HIFU delayed tumor specific growth rates (SGR) from 29 ± 6 to 13 ± 5%/day (P<0.001). Untreated animals (316.5 ± 78.9 mm(3)) had a greater accumulation of (99m)Tc-MDP than HIFU-treated animals (127.0 ± 42.7 mm(3), P=0.004). The total bone volume increase for untreated and HIFU-treated animals was 15.6 ± 9.6% and 3.0 ± 4.1% (P=0.004), respectively. Histological analysis showed ablation of nerve fibers, tumor, inflammatory and bone cells. CONCLUSIONS: Our study provides a detailed characterization of the effects of MR-HIFU treatment on bone metastases, and provides fundamental data, which may motivate and advance its use in the clinical treatment of painful bone metastases with MR-HIFU.

Stability and trapping of magnetic resonance imaging contrast agents during high-intensity focused ultrasound ablation therapy.

OBJECTIVES: The purpose of this study was to investigate the use of Gd-DTPA shortly before magnetic resonance guided high-intensity focused ultrasound MR-HIFU thermal ablation therapy with respect to dissociation, trapping, and long-term deposition of gadolinium (Gd) in the body. MATERIALS AND METHODS: Magnetic resonance-HIFU ablation treatment was conducted in vivo on both rat muscle and subcutaneous tumor (9L glioma) using a clinical 3T MR-HIFU system equipped with a small-animal coil setup. A human equivalent dose of gadopentetate dimeglumine (Gd-DTPA) (0.6 mmol/kg of body weight) was injected via a tail vein catheter just before ablation (≤5 minutes). Potential trapping of the contrast agent in the ablated area was visualized through the acquisition of R1 maps of the target location before and after therapy. The animals were sacrificed 2 hours or 14 days after the injection (n = 4 per group, a total of 40 animals). Subsequently, the Gd content in the tissue and carcass was determined using inductively coupled plasma techniques to investigate the biodistribution. RESULTS: Temporal trapping of Gd-DTPA in the coagulated tissue was observed on the R1 maps acquired within 2 hours after the ablation, an effect confirmed by the inductively coupled plasma analysis (3 times more Gd was found in the treated muscle volume than in the control muscle tissue). Two weeks after the therapy, the absolute amount of Gd present in the coagulated tissue was low compared with the amount present in the kidneys 14 days after the injection (ablated muscle, 0.009% ± 0.002% ID/g; kidney, 0.144% ± 0.165% ID/g). There was no significant increase in Gd content in the principal target organs for translocated Gdions (liver, spleen, and bone) or in the entire carcasses between the HIFU- and sham-treated animals. Finally, an in vivo relaxivity of 4.6 mmols was found in the HIFU-ablated volume, indicating intact Gd-DTPA. CONCLUSIONS: Magnetic resonance-HIFU treatment does not induce the dissociation of Gd-DTPA. In small-tissue volumes, no significant effect on the long-term in vivo Gd retention was found. However, care must be taken with the use of proton resonance frequency shift-based MR thermometry for HIFU guidance in combination with Gd because the susceptibility artifact induced by Gd can severely influence treatment outcome.

Magnetic resonance guided high-intensity focused ultrasound mediated hyperthermia improves the intratumoral distribution of temperature-sensitive liposomal doxorubicin.

OBJECTIVES: The aim of this study was to investigate the intratumoral distribution of a temperature-sensitive liposomal carrier and its encapsulated compounds, doxorubicin, and a magnetic resonance (MR) imaging contrast agent after high-intensity focused ultrasound (HIFU)-mediated hyperthermia-induced local drug release. MATERIALS AND METHODS: (111)In-labeled temperature-sensitive liposomes encapsulating doxorubicin and [Gd(HPDO3A) (H(2)O)] were injected intravenously in the tail vein of rats (n = 12) bearing a subcutaneous rhabdomyosarcoma tumor on the hind leg. Immediately after the injection, local tumor hyperthermia (2 × 15 minutes) was applied using a clinical 3 T MR-HIFU system. Release of [Gd(HPDO3A)(H(2)O)] was studied in vivo by measuring the longitudinal relaxation rate R(1) with MR imaging. The presence of the liposomal carriers and the intratumoral distribution of doxorubicin were imaged ex vivo with autoradiography and fluorescence microscopy, respectively, for 2 different time points after injection (90 minutes and 48 hours). RESULTS: In hyperthermia-treated tumors, radiolabeled liposomes were distributed more homogeneously across the tumor than in the control tumors (coefficient of variation(hyp, 90 min) = 0.7 ± 0.2; coefficient of variation(cntrl, 90 min) = 1.1 ± 0.2). At 48 hours after injection, the liposomal accumulation in the tumor was enhanced in the hyperthermia group in comparison with the controls. A change in R(1) was observed in the HIFU-treated tumors, suggesting release of the contrast agent. Fluorescence images showed perivascular doxorubicin in control tumors, whereas in the HIFU-treated tumors, the delivered drug was spread over a much larger area and also taken up by tumor cells at a larger distance from blood vessels. CONCLUSIONS: Treatment with HIFU hyperthermia not only improved the immediate drug delivery, bioavailability, and intratumoral distribution but also enhanced liposomal accumulation over time. The sum of these effects may have a significant contribution to the therapeutic outcome.

The magnetic susceptibility effect of gadolinium-based contrast agents on PRFS-based MR thermometry during thermal interventions.

BACKGROUND: Proton resonance frequency shift (PRFS) magnetic resonance (MR) thermometry exploits the local magnetic field changes induced by the temperature dependence of the electron screening constant of water protons. Any other local magnetic field changes will therefore translate into incorrect temperature readings and need to be considered accordingly. Here, we investigated the susceptibility changes induced by the inflow and presence of a paramagnetic MR contrast agent and their implications on PRFS thermometry. METHODS: Phantom measurements were performed to demonstrate the effect of sudden gadopentetate dimeglumine (Gd-DTPA) inflow on the phase shift measured using a PRFS thermometry sequence on a clinical 3 T magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) system. By proton nuclear magnetic resonance spectroscopy, the temperature dependence of the Gd-DTPA susceptibility was measured, as well as the effect of liposomal encapsulation and release on the bulk magnetic susceptibility of Gd-DTPA. In vivo studies were carried out to measure the temperature error induced in a rat hind leg muscle upon intravenous Gd-DTPA injection. RESULTS: The phantom study showed a significant phase shift inside the phantom of 0.6 ± 0.2 radians (mean ± standard deviation) upon Gd-DTPA injection (1.0 mM, clinically relevant amount). A Gd-DTPA-induced magnetic susceptibility shift of ΔχGd-DTPA = 0.109 ppm/mM was measured in a cylinder parallel to the main magnetic field at 37°C. The temperature dependence of the susceptibility shift showed dΔχGd-DTPA/dT = -0.00038 ± 0.00008 ppm/mM/°C. No additional susceptibility effect was measured upon Gd release from paramagnetic liposomes. In vivo, intravenous Gd-DTPA injection resulted in a perceived temperature change of 2.0°C ± 0.1°C at the center of the hind leg muscle. CONCLUSIONS: The use of a paramagnetic MR contrast agent prior to MR-HIFU treatment may influence the accuracy of the PRFS MR thermometry. Depending on the treatment workflow, Gd-induced temperature errors ranging between -4°C and +3°C can be expected. Longer waiting time between contrast agent injection and treatment, as well as shortening the ablation duration by increasing the sonication power, will minimize the Gd influence. Compensation for the phase changes induced by the changing Gd presence is difficult as the magnetic field changes are arising nonlocally in the surroundings of the susceptibility change.