Serena J. Scott

Interstitial ultrasound ablation of vertebral and paraspinal tumours: Parametric and patient-specific simulations

Abstract Purpose: Theoretical parametric and patient-specific models are applied to assess the feasibility of interstitial ultrasound ablation of tumours in and near the spine and to identify potential treatment delivery strategies. Methods: 3D patient-specific finite element models (n = 11) of interstitial ultrasound ablation of tumours associated with the spine were generated. Gaseous nerve insulation and various applicator configurations, frequencies (3 and 7 MHz), placement trajectories, and tumour locations were simulated. Parametric studies with multilayered models investigated the impacts of tumour attenuation, tumour dimension, and the thickness of bone insulating critical structures. Temperature and thermal dose were calculated to define ablation (>240 equivalent minutes at 43 °C (EM43 °C)) and safety margins (<45 °C and <6 EM43 °C), and to determine performance and required delivery parameters. Results: Osteolytic tumours (≤44 mm) encapsulated by bone could be successfully ablated with 7 MHz interstitial ultrasound (8.1–16.6 W/cm2, 120–5900 J, 0.4–15 min). Ablation of tumours (94.6–100% volumetric) 0–14.5 mm from the spinal canal was achieved within 3–15 min without damaging critical nerves. 3 MHz devices provided faster ablation (390 versus 930 s) of an 18 mm diameter osteoblastic (high bone content) volume than 7 MHz devices. Critical anatomy in proximity to the tumour could be protected by selection of appropriate applicator configurations, active sectors, and applied power schemas, and through gaseous insulation. Preferential ultrasound absorption at bone surfaces facilitated faster, more effective ablations in osteolytic tumours and provided isolation of ablative energies and temperatures. Conclusions: Parametric and patient-specific studies demonstrated the feasibility and potential advantages of interstitial ultrasound ablation treatment of paraspinal and osteolytic vertebral tumours.

Approaches for modelling interstitial ultrasound ablation of tumours within or adjacent to bone: Theoretical and experimental evaluations

Abstract Purpose: The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumours within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. Methods: 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7-MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or magnetic resonance temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. Results: High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models. Conclusions: Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumours near and within bone, with applications toward treatment planning.

Quantifying temperature-dependent T1 changes in cortical bone using ultrashort echo-time MRI.

To demonstrate the feasibility of using ultrashort echo‐time MRI to quantify T1 changes in cortical bone due to heating.

Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix.

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling

Abstract Purpose: The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. Materials and methods: Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1–5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (> 240 EM43 °C) and moderate hyperthermia (40–45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70–80 °C for ablation and 45 °C for hyperthermia in target regions. Results: Parametric studies indicated that 1–3 MHz planar transducers are the most suitable for volumetric ablation, producing 5–8 cm3 lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20–45 mm depth from the GI tract and enhance thermal sparing (Tmax < 42 °C) of the luminal wall. Patient anatomy simulations show feasibility in ablating 60.1–92.9% of head/body tumour volumes (4.3–37.2 cm3) with dose < 15 EM43 °C in the luminal wall for 18–48 min treatment durations, using 1–3 applicator placements in GI lumen. For hyperthermia, planar and radial-diverging transducers could maintain up to 8 cm3 and 15 cm3 of tissue, respectively, between 40–45 °C for a single applicator placement. Conclusions: Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.

Interstitial ultrasound ablation of tumors within or adjacent to bone: Contributions of preferential heating at the bone surface

Preferential heating of bone due to high ultrasound attenuation may enhance thermal ablation performed with cathetercooled interstitial ultrasound applicators in or near bone. At the same time, thermally and acoustically insulating cortical bone may protect sensitive structures nearby. 3D acoustic and biothermal transient finite element models were developed to simulate temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation near bone. Experiments in ex vivo tissues and tissue-mimicking phantoms were performed to validate the models and to quantify the temperature profiles and ablated volumes for various distances between the interstitial applicator and the bone surface. 3D patient-specific models selected to bracket the range of clinical usage were developed to investigate what types of tumors could be treated, applicator configurations, insertion paths, safety margins, and other parameters. Experiments show that preferential heating at the bone surface decreases treatment times compared to when bone is absent and that all tissue between an applicator and bone can be ablated when they are up to 2 cm apart. Simulations indicate that a 5-7 mm safety margin of normal bone is needed to protect (thermal dose < 6 CEM43°C and T < 45°C) sensitive structures behind ablated bone. In 3D patient-specific simulations, tumors 1.0-3.8 cm (L) and 1.3-3.0 cm (D) near or within bone were ablated (thermal dose > 240 CEM43°C) within 10 min without damaging the nearby spinal cord, lungs, esophagus, trachea, or major vasculature. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in tumors in and near bone compared to other heating modalities.

MR guided thermal therapy of pancreatic tumors with endoluminal, intraluminal and interstitial catheter-based ultrasound devices: Preliminary theoretical and experimental investigations.

Image-guided thermal interventions have been proposed for potential palliative and curative treatments of pancreatic tumors. Catheter-based ultrasound devices offer the potential for temporal and 3D spatial control of the energy deposition profile. The objective of this study was to apply theoretical and experimental techniques to investigate the feasibility of endogastric, intraluminal and transgastric catheter-based ultrasound for MR guided thermal therapy of pancreatic tumors. The transgastric approach involves insertion of a catheter-based ultrasound applicator (array of 1.5 mm OD x 10 mm transducers, 360° or sectored 180°, ~7 MHz frequency, 13-14G cooling catheter) directly into the pancreas, either endoscopically or via image-guided percutaneous placement. An intraluminal applicator, of a more flexible but similar construct, was considered for endoscopic insertion directly into the pancreatic or biliary duct. An endoluminal approach was devised based on an ultrasound transducer assembly (tubular, planar, curvilinear) enclosed in a cooling balloon which is endoscopically positioned within the stomach or duodenum, adjacent to pancreatic targets from within the GI tract. A 3D acoustic bio-thermal model was implemented to calculate acoustic energy distributions and used a FEM solver to determine the transient temperature and thermal dose profiles in tissue during heating. These models were used to determine transducer parameters and delivery strategies and to study the feasibility of ablating 1-3 cm diameter tumors located 2-10 mm deep in the pancreas, while thermally sparing the stomach wall. Heterogeneous acoustic and thermal properties were incorporated, including approximations for tumor desmoplasia and dynamic changes during heating. A series of anatomic models based on imaging scans of representative patients were used to investigate the three approaches. Proof of concept (POC) endogastric and transgastric applicators were fabricated and experimentally evaluated in tissue mimicking phantoms, ex vivo tissue and in vivo canine model under multi-slice MR thermometry. RF micro-coils were evaluated to enable active catheter-tracking and prescription of thermometry slice positions. Interstitial and intraluminal ultrasound applicators could be used to ablate (t43>240min) tumors measuring 2.3-3.4 cm in diameter when powered with 20-30 W/cm2 at 7 MHz for 5-10 min. Endoluminal applicators with planar and curvilinear transducers operating at 3-4 MHz could be used to treat tumors up to 20-25 mm deep from the stomach wall within 5 min. POC devices were fabricated and successfully integrated into the MRI environment with catheter tracking, real-time thermometry and closed-loop feedback control.

Relationship between temperature and T2 in subcutaneous fat and bone marrow at 3T

MR-guided high-intensity focused ultrasound (HIFU) for treatment of uterine fibroids and painful bone metastases uses the proton resonant frequency shift (PRF) for temperature monitoring in water-based tissues. However, PRF fails to detect temperature changes in tissues with high lipid content, such as fat and bone marrow. Previous studies have shown a change in T2 of subcutaneous fat, red and yellow bone marrow during treatments with focused ultrasound. The lack of calibration data for 3T acquisitions, however, makes it difficult to convert T2 values into maps of tissue temperature. In this study we investigated the dependence of T2 temperature on temperature in porcine adipose tissue and bovine yellow bone marrow at thermal equilibrium at 3T.

A Pilot Study of Catheter‐Based Ultrasound Hyperthermia with HDR Brachytherapy for Treatment of Locally Advanced Cancer of the Prostate and Cervix

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).

Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (∼7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 – 3 W/cm2 and lasted for 60 – 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 – 12 thermocouple sensors ...