The medical world is increasingly embracing cryotherapy for tumor treatment, but not all cryoablation treatments are created equal. Liquid nitrogen (LN2) cryoablation technology, the coldest of the cryogens, is taking the stage for more effective treatment and outcomes.
Cryoablation has become an established method of therapy in the corridors of oncology, enabling minimally invasive treatment for various types of benign and malignant tumors. In the field of interventional radiology, cryoablation is used for the treatment of tumors found in the kidney, liver, lung, bone, and prostate. Breast surgeons are adopting the method for the treatment of fibroadenomas (benign breast tumors) and are studying cryoablation of small, low-risk, breast cancers in the ICE3 trial.
There are several different methods for producing temperatures cold enough to freeze cancer to death. But which one is the most optimal to achieve the most effective, ultra-cold, lethal conditions?
Guided by CT or ultrasound imaging, a cryoprobe is inserted into the tumor and a coolant (cryogen) is supplied to the cryoprobe active area in a closed-loop system, which cools and forms an ice ball around the diseased area during the heat transfer process. As the ice ball forms around the targeted tissue, intra- and extra-cellular ice crystals are formed that result in cell death. A repeated freeze-thaw-freeze cycle causes intra- and extra-cellular ice crystallization, weakening the cell membrane leading to membrane rupture and cell death. The process also stymies blood supply from capillaries surrounding the tumor, to starve any cells that still remain alive and prevent regrowth. The body’s immune system eliminates the necrotic debris on its own.
Studies suggest that the benefits of cryoablation can even go beyond targeted tumor therapy, as antitumoral immune responses may be stimulated through successful cryoablation (due to large necrosis), thereby preventing the development of new tumors. Learn more about how cryoablation works to destroy tumors by freezing here.
Requirements for Effective Tumor Cryoablation
The effectiveness and efficiency of cryoablation to cause cellular injury and achieve optimal tumor destruction largely depends on three main factors:
- the cooling rate
- achieving ultra-low and stable target temperatures for sufficient time
- the thawing rate.
A faster cooling rate has been shown to maximize intracellular ice crystal formation to produce a larger ice ball for improved tumor destruction . The rate of cooling will be most rapid adjacent to the cryoprobe and lower in the periphery of the ice ball, where the greater surface area lowers the flux of heat removal.
Achieving an ultra-low and stable target temperature for a sufficient time will increase the likelihood that lethal intracellular ice forms also in the peripheral portion of the ice ball for more effective tumor destruction.
Finally, the thawing rate also plays an important role in cryoablation. A slow thawing rate and a long thawing duration are a primary factor for tumor destruction . Rapid thawing can result in ineffective second freezing by limiting the size of intracellular ice crystals and increasing the chance of cell survival. Studies show that repeated freeze-thaw cycles lead to a higher degree of tumor destruction .
While these three criteria are essential for optimal outcomes, the cryoablation system’s ease of use is also of utmost importance. It goes without saying that a system that is non-intuitive or requires a steep learning curve may result in improper use and poor outcomes.
Traditional Cooling Agents
Achieving the optimal freezing temperatures is challenging. Four coolants shown differing capabilities for cryoablation treatment.
Argon, nitrous oxide and carbon dioxide gases
One method found to attain extremely low temperatures for cryoablation is known as the Joule-Thomson process. Here high pressurized gas is delivered to the tip of the cryoprobe and expanded through a minute pore, which in turn produces a fall in temperature in the cooling zone and ice ball formation.
For tumor cryoablation, this method has been applied with argon, nitrous oxide and carbon dioxide. Yet both argon, nitrous oxide and carbon dioxide, being used with current cryoablation systems, have also shown clear disadvantages in their capacity to achieve very low stable temperatures – factors that can impede the effectiveness and efficiency of cryoablation.
Furthermore, while argon gas can achieve freezing levels of up to −140°C in tissue within 60 seconds, a specific safety room is required to house its large and hazardous high-pressure cylinder tanks limiting its use . Argon gas is also banned in some countries due to safety concerns.
Nitrous oxide’s lowest attainable temperature is -88°C. It is the main coolant used in atrial fibrillation.
Carbon dioxide’s lowest attainable temperature is -78°C. Common clinical uses include lung biopsy and tumors, and non-muscle-invasive bladder cancer.
Liquid Nitrogen (LN2)
Liquid nitrogen achieves its cooling effect when transformed from liquid to gas by the process of boiling. Once its respective boiling point is reached, the gas form can be used for various applications including cryoablation.
LN2 boils at an extremely low -196°C, surpassing the cooling levels reached by argon, nitrous oxide and carbon dioxide making it the coldest cryogen for cryoablation. (4)
With its increased heat extraction capability, LN2 can deliver ablative doses deeper into the tissue resulting in larger ablative zones and can create frozen masses more rapidly based on the Joule-Thomson effect. (5)
Image source: Ķīsis J and Zavorins A. Cryosurgery: A Practical Manual. Springer
Next Generation Liquid Nitrogen Cryoablation with IceCure’s ProSense™
IceCure’s ProSense™ liquid nitrogen technology has been developed to harness the strong advantages of LN2 over other methods of cryoablation in treating benign and malignant tumors.
Larger lethal zone at lower temperatures in less time. The ProSense™ liquid nitrogen cryoablation system produces a very rapid temperature drop. This generates a large lethal ice ball area quickly and destroys the tumor efficiently. In comparison to argon gas, LN achieves a larger ice ball in a warm environment 
Stable low temperatures. The system maintains very low stable temperatures: -160⁰C to -170⁰C. This compares to other Argon-gas-based cryoablation systems that achieve constant temperatures in the range of -120⁰C to -135⁰C.
Streamlined storage. Unlike the hazards associated with Argon gas use, IceCure’s ProSense™ uses a small refillable low-pressure Dewar. The solution is non-restricted with no gas lines for ease of maneuverability while being an environmentally friendly, safe system.
(The compact system also allows in-office procedures when treating breast tumors.)
Friendly user interface. Each procedure is easily customized and controlled from the ProSense™ liquid nitrogen console. The system enables multiple cycles and cryoprobe relocation.
Selecting the Right Cryoablation System for Optimal Tumor Destruction
Cryoablation offers a minimally invasive procedure for treating a wide variety of benign and malignant tumors. Yet, selecting the right cryoablation system and associated coolant can determine whether optimal tumor destruction is achieved. Understanding the properties of each of the coolants used in cryoablation alongside how the various systems have applied this technology, is therefore critical for enabling treatment success.
To learn more about the benefits of the ProSense™ liquid nitrogen cryoablation system, please schedule contact us here https://www.icecure-medical.com/contact-us/
- Erinjeri JP. & Clark TW. (2010). Cryoablation: Mechanism of Action and Devices. J Vasc Interv Radiol; 21(8 Suppl): S187–S191.
- Gage AA., Baust JM., & Baust JG. (2009). Experimental cryosurgery investigations in vivo. Cryobiology, 59(3), 229-243.
- Chang D., Mohan P., Amin A., et al. (2020). Liquid Nitrogen-Based Cryoablation in In Vivo Porcine Tissue: A Pilot Study. Asian Pac J Cancer Prev. 2020 Oct 1;21(10):3069-3075.
- Ķīsis J and Zavorins A. Chapter 2: Cryobiology and Thermodynamics. In Pasquali, Paola, ed. (2015). Cryosurgery: A Practical Manual. Springer. 10.1007/978-3-662-43939-5.
- John M. Baust et. al. (2018) Evaluation of a new epicardial cryoablation system for the treatment of Cardiac Tachyarrhythmias. 10.1177/2050312118769797
- P M Hewitt et.al. (1997) A comparative laboratory study of liquid nitrogen and argon gas cryosurgery systems. 10.1006/cryo.1997.2039