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Title: Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

Abstract

Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C.more » With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.« less

Authors:
 [1];  [2];  [3];  [4];  [2]; ;  [5];  [6];  [5];  [1];  [1];  [2];  [6]
  1. Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada)
  2. (Canada)
  3. Clinical Sites Research Program, Philips Research, Cambridge, Massachusetts (United States)
  4. Thunder Bay Regional Research Institute, Thunder Bay, Ontario (Canada)
  5. MR Therapy, Philips Healthcare, Vantaa (Finland)
  6. Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada)
Publication Date:
OSTI Identifier:
22648744
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOMEDICAL RADIOGRAPHY; CHEMOTHERAPY; ETHICAL ASPECTS; EVALUATION; HYPERTHERMIA; NEOPLASMS; PERFORMANCE; RADIOTHERAPY; RECTUM; SWINE; TEMPERATURE MEASUREMENT

Citation Formats

Chu, William, E-mail: William.Chu@sunnybrook.ca, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Staruch, Robert M., Pichardo, Samuel, Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario, Tillander, Matti, Köhler, Max O., Huang, Yuexi, Ylihautala, Mika, McGuffin, Merrylee, Czarnota, Gregory, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, and Hynynen, Kullervo. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.03.019.
Chu, William, E-mail: William.Chu@sunnybrook.ca, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Staruch, Robert M., Pichardo, Samuel, Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario, Tillander, Matti, Köhler, Max O., Huang, Yuexi, Ylihautala, Mika, McGuffin, Merrylee, Czarnota, Gregory, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, & Hynynen, Kullervo. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation. United States. doi:10.1016/J.IJROBP.2016.03.019.
Chu, William, E-mail: William.Chu@sunnybrook.ca, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Staruch, Robert M., Pichardo, Samuel, Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario, Tillander, Matti, Köhler, Max O., Huang, Yuexi, Ylihautala, Mika, McGuffin, Merrylee, Czarnota, Gregory, Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, and Hynynen, Kullervo. 2016. "Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation". United States. doi:10.1016/J.IJROBP.2016.03.019.
@article{osti_22648744,
title = {Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation},
author = {Chu, William, E-mail: William.Chu@sunnybrook.ca and Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario and Staruch, Robert M. and Pichardo, Samuel and Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario and Tillander, Matti and Köhler, Max O. and Huang, Yuexi and Ylihautala, Mika and McGuffin, Merrylee and Czarnota, Gregory and Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario and Hynynen, Kullervo},
abstractNote = {Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.},
doi = {10.1016/J.IJROBP.2016.03.019},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 95,
place = {United States},
year = 2016,
month = 7
}
  • Purpose: To report the first clinical experience with targeted vessel ablation during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) treatment of symptomatic uterine fibroids. Methods: Pretreatment T1-weighted contrast-enhanced magnetic resonance angiography was used to create a detailed map of the uterine arteries and feeding branches to the fibroids. A three-dimensional overlay of the magnetic resonance angiography images was registered on 3D T2-weighted pretreatment imaging data. Treatment was focused primarily on locations where supplying vessels entered the fibroid. Patients were followed 6 months after treatment with a questionnaire to assess symptoms and quality of life (Uterine Fibroid Symptom and Quality of Life)more » and magnetic resonance imaging to quantify shrinkage of fibroid volumes. Results: In two patients, three fibroids were treated with targeted vessel ablation during MR-HIFU. The treatments resulted in almost total fibroid devascularization with nonperfused volume to total fibroid volume ratios of 84, 68, and 86%, respectively, of treated fibroids. The predicted ablated volumes during MR-HIFU in patients 1 and 2 were 45, 40, and 82 ml, respectively, while the nonperfused volumes determined immediately after treatment were 195, 92, and 190 ml respectively, which is 4.3 (patient 1) and 2.3 (patient 2) times higher than expected based on the thermal dose distribution. Fibroid-related symptoms reduced after treatment, and quality of life improved. Fibroid volume reduction ranged 31-59% at 6 months after treatment. Conclusion: Targeted vessel ablation during MR-HIFU allowed nearly complete fibroid ablation in both patients. This technique may enhance the use of MR-HIFU for fibroid treatment in clinical practice.« less
  • Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (<1 Degree-Sign C) and dynamic (<5s) thermal maps in soft tissues. PRFS-MRT is ineffective in fatty tissues such as yellow bone marrow and, since accurate temperature measurements are required in the bone to ensure adequate thermal dose, MR-HIFU is not indicated for primary bone tumor treatments. Magneticmore » relaxation times are sensitive to lipid temperature and we hypothesize that bone marrow temperature can be determined accurately by measuring changes in T{sub 2}, since T{sub 2} increases linearly in fat during heating. T{sub 2}-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T{sub 2}. Calibration of T{sub 2}-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T{sub 2} and temperature with a thermocouple. A positive T{sub 2} temperature dependence in bone marrow of 20 ms/ Degree-Sign C was observed. Dynamic T{sub 2}-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.« less
  • Purpose: High-intensity focused ultrasound (HIFU) ablation is feasible in the head and neck [1]. This study aims to expand upon these findings to assess the feasibility of treatment planning and monitoring via magnetic resonance imaging (MRI) guidance using a clinical MR-guided HIFU platform. Methods: Two 31 kg pigs were anaesthetized, shaved, and positioned prone on the HIFU table (Sonalleve, Philips Healthcare, Vantaa, Finland). The necks were acoustically coupled to the integrated transducer using gel pads and degassed water. MR imaging verified acoustic coupling and facilitated target selection in the thyroid and thymus. Targets were thermally ablated with 130–200 W ofmore » acoustic power over a period of 16 s at a frequency of 1.2 MHz while being monitored through real-time, multi-planar MR-thermometry. Contrast-enhanced MR imaging was used to assess treatment efficacy. Post-treatment, animals were euthanized and sonicated tissues were harvested for histology assessment. Results: MR-thermometry, post-contrast-imaging, and gross pathology demonstrated that the system was capable of causing localized thermal ablation in both the thyroid and the thymus without damaging the aerodigestive tract. In one animal, superficial bruising was observed in the ultrasound beam path. Otherwise, there were no adverse events. Analysis of the tissue histology found regions of damage consistent with acute thermal injury at the targeted locations. Conclusion: It is feasible to use a clinical MR-guided HIFU platform for extracorporeal ablation of porcine head and neck tissues. MR guidance and thermometry are sufficient to target and monitor treatment in the thyroid region, despite the presence of the inhomogeneous aerodigestive tract. Further study is necessary to assess efficacy and survival using a tumor model, and to examine what modifications should be made to the transducer positioning system and associated patient positioning aids to adapt it for clinical head and neck targets.Reference:[1] Esnault et al. (2011). Thyroid, 21(9), 965– 973. Funding support provided by Philips Healthcare. Ari Partanen is a paid employee of Philips Healthcare.« less
  • Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemesmore » utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non-EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm{sup 3} FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C. Conclusions: When segmented EPI readouts are used in conjunction with k-space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.« less
  • To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate registered 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followedmore » for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.« less