Laura G. Merckel

MR-guided high-intensity focused ultrasound ablation of breast cancer with a dedicated breast platform.

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

MRI‐guided ablation of breast cancer: Where do we stand today?

The treatment of patients with localized breast cancer has changed considerably over the past few decades. The next challenge is to use image‐guided minimally invasive tumor ablation techniques. The fact that MRI is the most accurate imaging modality for visualization and delineation of breast tumor margins in three dimensions and provides MRI‐based temperature mapping, makes it particularly applicable for monitoring during minimally invasive ablation techniques. The overall result of the studies performed on MRI‐guided minimally invasive tumor ablation studies are varying, with reported total tumor ablation rates ranging between 20% and 100%. Strict selection of patients, consensus on the treatment zone margin and optimization of MR‐imaging, should make MRI‐guided breast cancer tumor ablation a useful tool in clinical practice. J. Magn. Reson. Imaging 2011;.

Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients

MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation <3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

Correction of proton resonance frequency shift MR-thermometry errors caused by heat-induced magnetic susceptibility changes during high intensity focused ultrasound ablations in tissues containing fat

In this study, we aim to demonstrate the sensitivity of proton resonance frequency shift (PRFS) ‐based thermometry to heat‐induced magnetic susceptibility changes and to present and evaluate a model‐based correction procedure.

The effects of magnetic resonance imaging-guided high-intensity focused ultrasound ablation on human cadaver breast tissue

Magnetic Resonance Imaging-guided High-Intensity Focused Ultrasound (MR-HIFU) is a promising technique for non-invasive breast tumor ablation. The purpose of this study was to investigate the effects of HIFU ablation and thermal exposure on ex vivo human breast tissue. HIFU ablations were performed in three unembalmed cadaveric breast specimens using a clinical MR-HIFU system. Sonications were performed in fibroglandular and adipose tissue. During HIFU ablation, time-resolved anatomical MR images were acquired to monitor macroscopic tissue changes. Furthermore, the breast tissue temperature was measured using a thermocouple to investigate heating and cooling under HIFU exposure. After HIFU ablation, breast tissue samples were excised and prepared for histopathological analysis. In addition, thermal exposure experiments were performed to distinguish between different levels of thermal damage using immunohistochemical staining. Irreversible macroscopic deformations up to 3.7 mm were observed upon HIFU ablation both in fibroglandular and in adipose tissue. No relationship was found between the sonication power or the maximum tissue temperature and the size of the deformations. Temperature measurements after HIFU ablation showed a slow decline in breast tissue temperature. Histopathological analysis of sonicated regions demonstrated ablated tissue and morphologically complete cell death. After thermal exposure, samples exposed to three different temperatures could readily be distinguished. In conclusion, the irreversible macroscopic tissue deformations in ex vivo human breast tissue observed during HIFU ablation suggest that it might be relevant to monitor tissue deformations during MR-HIFU treatments. Furthermore, the slow decrease in breast tissue temperature after HIFU ablation increases the risk of heat accumulation between successive sonications. Since cell death was inflicted after already 5 minutes at 75°C, MR-HIFU may find a place in non-invasive treatment of breast tumors.

The added diagnostic value of dynamic contrast-enhanced MRI at 3.0 T in nonpalpable breast lesions

Objective To investigate the added diagnostic value of 3.0 Tesla breast MRI over conventional breast imaging in the diagnosis of in situ and invasive breast cancer and to explore the role of routine versus expert reading. Materials and Methods We evaluated MRI scans of patients with nonpalpable BI-RADS 3–5 lesions who underwent dynamic contrast-enhanced 3.0 Tesla breast MRI. Initially, MRI scans were read by radiologists in a routine clinical setting. All histologically confirmed index lesions were re-evaluated by two dedicated breast radiologists. Sensitivity and specificity for the three MRI readings were determined, and the diagnostic value of breast MRI in addition to conventional imaging was assessed. Interobserver reliability between the three readings was evaluated. Results MRI examinations of 207 patients were analyzed. Seventy-eight of 207 (37.7%) patients had a malignant lesion, of which 33 (42.3%) patients had pure DCIS and 45 (57.7%) invasive breast cancer. Sensitivity of breast MRI was 66.7% during routine, and 89.3% and 94.7% during expert reading. Specificity was 77.5% in the routine setting, and 61.0% and 33.3% during expert reading. In the routine setting, MRI provided additional diagnostic information over clinical information and conventional imaging, as the Area Under the ROC Curve increased from 0.76 to 0.81. Expert MRI reading was associated with a stronger improvement of the AUC to 0.87. Interobserver reliability between the three MRI readings was fair and moderate. Conclusions 3.0 T breast MRI of nonpalpable breast lesions is of added diagnostic value for the diagnosis of in situ and invasive breast cancer.

Histopathology of breast cancer after magnetic resonance-guided high-intensity focused ultrasound and radiofrequency ablation.

Magnetic resonance‐guided high‐intensity focused ultrasound (MR‐HIFU) ablation and radiofrequency ablation (RFA) are being researched as possible substitutes for surgery in breast cancer patients. The histopathological appearance of ablated tissue has not been studied in great detail. This study aimed to compare histopathological features of breast cancer after MR‐HIFU ablation and RFA.

Results from clinical phase I study on breast tumor ablation with dedicated breast MR-HIFU system

We have recently conducted a clinical phase I study to assess the safety and spatial accuracy and precision of a newly developed dedicated MR-HIFU system for lateral breast tumor ablation [1]. Here, we report on patient inclusion, treatment efficacy and safety.

Eligibility of patients for minimally invasive breast cancer therapy based on MRI analysis of tumor proximity to skin and pectoral muscle

There is growing interest in minimally invasive breast cancer therapy. Eligibility of patients is, however, dependent on several factors related to the tumor and treatment technology. The aim of this study is to assess the proportion of patients eligible for minimally invasive breast cancer therapy for different safety and treatment margins based on breast tumor location. Patients with invasive ductal cancer were selected from the MARGINS cohort. Semiautomatic segmentation of tumor, skin, and pectoral muscle was performed in Magnetic Resonance images. Shortest distances of tumors to critical organs (ie, skin and pectoral muscle) were calculated. Proportions of eligible patients were determined for different safety and treatment margins. Three‐hundred‐forty‐eight patients with 351 tumors were included. If a 10 mm safety margin to skin and pectoral muscle is required without treatment margin, 72.3% of patients would be eligible for minimally invasive treatment. This proportion decreases to 45.9% for an additional treatment margin of 5 mm. Shortest distances between tumors and critical organs are larger in older patients and in patients with less aggressive tumor subtypes. If a 10 mm safety margin to skin and pectoral muscle is required, more than two‐thirds of patients would be eligible for minimally invasive breast cancer therapy.

Performance analysis of a dedicated breast MR-HIFU system during ablation of breast tumors in patients

correction method was used to correct on-line for respiration-induced magnetic field fluctuations.[2] The performance of the correction method was assessed in absence of HIFU heating. The temporal standard deviation (SD) in temperature maps calculated before and after applying the correction method and the number of dynamics needed before switching to the intervention phase were used as a measure of performance. The targeting accuracy and precision of the system was assessed using MR thermometry data. For each sonication the trajectory of the center of mass of the heating pattern in the focal area over time was calculated. The standard deviation of the distribution of the distances between the center of mass in time and the mean center of mass was defined as precision. The distance between the mean center of mass and the planned treatment position was defined as accuracy.