ExAblate

The ExAblate (also known as ExAblate 2000) is a non-invasive medical device manufactured by InSightec, a company based in Haifa, Israel with its US office in Dallas, TX. The ExAblate uses MRI guided Focused Ultrasound Surgery (MRgFUS) technology, which combines magnetic resonance imaging (MRI) with focused ultrasound. The MRI is used to visualize anatomy, aid in planning the treatment, and monitoring temperatures and thermal dose in real time during the treatment. This thermal feedback allows the physician to control and adjust the treatment in real time to ensure that the targeted tumor is fully treated and surrounding tissue is spared. Focused ultrasound is capable of ablating tumors inside the body without the need for an incision.

Use of MRI during treatment
Magnetic Resonance imaging provide a means to safely direct the focused ultrasound energy. MR images are acquired in 3 orientations (coronal, axial, and sagittal) to give the user a complete anatomical survey of the treatment area. Targeted tissue and surrounding structures such as intestine or nerves are clearly visible on MR images. The images are used for treatment planning and to assist the treatment team in proper positioning of the patient over the focused ultrasound transducer.

Temperature maps display the relative tissue temperature as a color map superimposed on an anatomical MR image. This allows the physician to observe temperature changes in real time during treatment. Based on these observed temperature changes, treatment parameters can be adjusted to ensure safe and effective thermal ablation.
 * Real time thermometry

T1 weighted MR images with Gadolinium contrast acquired post-treatment enable the physician to immediately assess the treatment outcome and determine which regions are non-perfused (ablated).
 * Outcome assessment

Use of ultrasound during treatment
Ultrasound is a form of energy that passes through skin, muscle, fat and other soft tissue. When used for diagnostic imaging, the low intensity ultrasound waves have little to no biologic effect on cells or tissues. Similar to how a magnifying glass focuses sunlight, ultrasound energy is focused to a small target volume on the order of 10 mm in diameter by 30 mm in length. Therapeutic effect is created by raising the tissue temperature of the targeted volume over the duration of the energy delivery (sonication). By a thermal dose relationship (a combination of exposure temperature and duration), cell necrosis in the heated volume will occur. The predictable nature and accuracy of MRgFUS enables physicians to effectively treat tumors without damaging surrounding tissue or structures.

The ultrasound waves are directed from a transducer (which converts electrical energy into ultrasound energy) into a small focal volume. The cone-shaped ultrasound beam penetrates through soft tissue and produces well defined regions of protein denaturation, irreversible cell damage, and coagulative necrosis, at specific target locations. Tight focusing is designed to limit the ablation to the targeted location. Cells as close as 0.1 mm from the focal spot remain undamaged. A treatment consist of multiple exposures of focused energy or sonications.

Device approvals
ExAblate was approved by the U.S. Food and Drug Administration (FDA) in October 2004 to treat symptomatic uterine fibroids. As of May 2007, over 5000 uterine fibroid treatments have been performed worldwide. InSightec has begun clinical trials to study the technology’s use for other indications including breast, bone, liver and brain tumors.

The device received the European CE mark and ISO 13485 and is commercially available in the United States, Israel, Europe, and Asia. ExAblate received the European CE mark for the palliation of pain caused by bone metastases which represents the potential to expand this non-invasive technology to oncology applications.

USA indications
In the US, ExAblate is undergoing FDA clinical studies for the following applications:


 * pain palliation for bone Metastases (clinical study)
 * brain tumors (phase I feasibility study)

International indications
In Europe, Asia, and Israel, the ExAblate is being used to treat the following:


 * Breast cancer
 * Adenomyosis
 * Bone metastases

Treatment planning
The ExAblate treatment for Uterine Fibroids (reference) is an FDA approved outpatient procedure. Patients arrive at the treatment location generally one hour prior to the procedure for pre-treatment preparation which includes: a pregnancy test to ensure that the patient was not pregnant, shaving and cleaning the patient’s abdomen to ensure acoustic coupling, and introduction of IV. Conscious sedation (fentanyl, Midazolam, Toradol) is used during the treatment as needed.

Patients are positioned in a prone position on the ExAblate table, and T2 weighted MRI scans of the pelvic region are initially taken to plan the treatment. A region of treatment is drawn directly on the MRI images using the ExAblate software, indicating the volume of fibroid to be treated. LEDRs (Limited Energy Density Regions), which are used to mark regions that are not intended for treatment (such as bowel and bone) are also placed on the images to ensure safety of treatment. Then, a test sonication (single delivery of focused ultrasound energy) using a sub-lethal dose is administered to ensure the system is properly calibrated prior to initiating treatment.

Treatment execution
The treatment consists of multiple sonications each approximately the size of a small jelly bean. The number of sonications and hence the duration of treatment depends on the size of the tumor to be treated. The energy delivered with each sonication is capable of raising the temperature of the tissue upwards of 65 degrees Celsius resulting in coagulative necrosis. During each sonication, real-time thermal images generated from the MRI are used to ensure sonication accuracy and confirm that sufficient dose has been delivered. In the event of severe pain or heating at any time during the delivery of energy, the patient can stop the sonication by pressing a handheld button.

Treatment evaluation
At the end of the MRgFUS procedure, the patient is injected with gadolinium contrast agent and T1w post-contrast MRI scans are performed. These images are used to determine the NPV (Non-Perfused Volume) of the fibroid, which is the volume of tissue that is non-viable (has no blood flow to it). The NPV ratio of a fibroid is defined as the non-perfused tissue volume measured by the T1w post contrast scans, divided by the fibroid volume measured by the T2w images pre treatment.

ExAblate components
The ExAblate 2000 system consists of the following components:


 * Operating Console. The ExAblate 2000 console allows the operator to control and monitor both the system and the treatment. It is positioned alongside the GE SIGNA workstation in the control room.


 * Patient table. The patient table is a modified GE MRI table which contains a phased array transducer in a sealed water bath. The transducer is mounted on a motion system which moves left-right, head-toe and tilts in two axes. Treatments are conducted with the patient lying on the patient table inside the MR scanner.


 * Equipment cabinet. The equipment cabinet includes the interface electronics to the patient table, to the MR scanner and to the operating console. This unit is usually located in the MRI equipment room.

System versions

 * The current FDA approved ExAblate model is the version 2000 (hardware) running software version 4.2. This device is utilized in the US for treating uterine fibroids and around the world for treating uterine fibroids, pain palliation of bone metastases and is being investigated in breast cancer, prostate cancer and neuro programs.


 * The version 2000 is compatible with either 1.5T, 3.0T MRI systems running GE MRI software version 9.1 and higher.


 * The ExAblate 4000 is the Brain system.


 * The ExAblate Prostate system is currently being tested in feasibility trials.