ExAblate

Exablate is a family of non-invasive medical devices manufactured by Insightec, a company headquartered in Haifa, Israel with regional offices in USA (Dallas, Texas), China, Japan and Europe. The Exablate and Exablate Neuro use MRI-guided Focused Ultrasound (MRgFUS) technology, which combines focused ultrasound with Magnetic resonance imaging (MRI). Focused ultrasound is capable of ablating tissue inside the body without the need for an incision. The MRI is used to visualize anatomy, aid in planning the treatment and monitoring temperatures 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 tissue is completely ablated without impacting adjacent healthy tissue.

Technology overview

Use of focused ultrasound during treatment

Ultrasound is a form of energy that passes through skin, muscle, fat and other soft tissue. Low intensity ultrasound waves have been safely used for years in diagnostic imaging devices. With higher energy levels, ultrasound waves can generate enough heat to cause thermal ablation, which destroys cells.

With focused ultrasound, the ultrasound waves are directed from a transducer (which converts electrical energy into ultrasound energy) to a focal target. The ultrasound beams pass through soft tissue and only at the focal point where they converge is heat generated. The therapeutic effect is created by raising the tissue temperature during energy delivery (sonication) which causes thermal ablation and defined regions of protein denaturation, irreversible cell damage and coagulative necrosis at the target. The accuracy of MRgFUS enables physicians to effectively treat tumors and other tissue without damaging surrounding tissue or structures.^[1] Cells as close as 0.1 mm from the target remain undamaged. A treatment consist of multiple exposures of focused energy or sonications.^[2]

Use of MRI during treatment

Magnetic resonance imaging provides high resolution visualization, patient-specific treatment planning and continuous monitoring of the Exablate procedure. 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 on the treatment bed.

Real time thermometry

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 that the targeted tissue is completely ablated without impacting adjacent healthy tissue.

Outcome assessment

T1 weighted MR images with Gadolinium contrast acquired post-treatment enable the physician to immediately assess the treatment outcome and verify complete ablation.

Indications for use

Device approvals

Exablate Neuro was approved by the U.S. Food and Drug Administration (FDA) in July, 2016 to treat essential tremor in patients who have not responded to medication. The device received Health Canada and KFDA approval for the same indication and CE mark for essential tremor, tremor dominant Parkinson’s disease and neuropathic pain.

Exablate was approved by the FDA for the ablation of uterine fibroids including for women who desire to retain fertility and spare their uterus and received CE mark for the ablation of soft tissue for treatment of benign tumors, including uterine fibroids ^[3] and adenomyosis. As of 2016, over 14000 uterine fibroid treatments have been performed worldwide.^[4]

Exablate has FDA approval for the pain palliation of metastatic bone cancer in patients for whom radiation therapy is not an alternative and CE Mark for pain palliation of painful bone metastases and local treatment of cancerous and benign primary and secondary bone tumors.

USA indications

In the US, Exablate is approved for the following applications:

• Essential tremor in medication refractory patients
• Pain palliation of bone Metastases
• Symptomatic uterine fibroids

International indications

In Europe, the Exablate is being used to treat the following:

• Essential tremor
• Parkinson's Disease
• Neuropathic pain
• Adenomyosis ^[5]
• Bone metastases ^[6]
• Desmoid tumors
• Osteoid Osteoma

Uterine fibroid patient procedure

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.^[7] 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 procedure, a gadolinium contrast agent is administered and T1w post-contrast MRI scans are performed.^[7] These images are used to verify complete ablation. For uterine fibroids, the images 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.^[7]

Exablate components

The Exablate system consists of the following components:

• Console. The Exablate console allows the operator to control and monitor both the Exablate system and the treatment. It is positioned alongside the GE MRI workstation in the control room.
• Treatment bed. The treatment bed of the Exablate 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 on two axes. The Exablate Neuro contains a helmet with a phased array transducer. Treatments are conducted with the patient lying on the treatment bed inside the MR scanner.
• Equipment cabinet. The equipment cabinet includes the interface electronics to the treatment bed, to the MR scanner and to the console. This unit is usually located in the MRI equipment room.

References

See also

• uterine fibroids
• HIFU