Key Points
- •
Liquid nitrogen is a difficult cryogen to pump through small channels because its massive volume expansion to nitrogen gas upon evaporation causes “vapor lock” or obstruction to further cryogen flow.
- •
Joule-Thompson cooling generally requires awkward high-pressure storage tanks of various gases that can produce intense cooling at the J-T port, yet gases have poor thermal conductivity, heat capacity, and overall cooling power.
- •
Newer cryotechnologies are emerging that solve the problem of vapor lock yet retain the greater cooling power of a liquid cryogen without the need for high-pressure storage tanks.
- •
Near-critical nitrogen is one such solution that can be pumped down tiny channels without vapor lock, yet has much greater freezing capacity that translates into colder isotherms that can even overcome huge endovascular heat sinks.
The purpose of this chapter is to introduce new cryotechnology that allows for more powerful cryoprobes (catheters), even with diameters smaller than 2 mm. The terms cryotherapy and cryoablation have replaced the older term cryosurgery because therapeutic freezing of nearly any tissue no longer requires an open surgical approach with large-diameter cryoprobes. The development of thinner cryoprobes (i.e., <3-mm outer diameter) and markedly improved image guidance by ultrasound, computed tomography, and magnetic resonance imaging now allow direct placement of cryoprobes through the skin, or a percutaneous approach.
The three potential clinical benefits of cryotherapy over heat-based ablation can be safely considered for any organ system where ablation is appropriate:
- 1
Visualization of the treatment zone, or ice margin
- 2
Minimal discomfort for most outpatient procedures
- 3
Nondestructive tissue healing, or greater ablation volume reduction
Our new concept of near-critical cooling (NCC) can be better understood from reviewing the basic processes involved in removing a heat load, particularly as they relate to cryotechnology. Cooling occurs by a combination of three processes: evaporation, conduction, and convection. Evaporation cooling takes advantage of normally substantial latent heat of liquid and is the basis of liquid cryogen systems, such as those using flowing liquid nitrogen (LN 2 ; e.g., Cryomedical Sciences). Conduction of heat away from an object is a complex process in and of itself, but relies on the surface area ( A s ) of the cryoprobe with the tissue, which is directly proportional to the probe diameter (i.e., A s = 2π r × h ). From a cryogen perspective, its heat capacity (C P ) is a dominant factor that determines the cooling power. Because of its greater density, LN 2 has much greater C P and is a much more potent cryogen than N 2 gas. This helps explain the Leidenfrost effect, whereby spilled LN 2 dances across the floor on a cushion of air (e.g., an air hockey table) and can be poured over your skin without damage. Direct contact use of LN 2 is still popular in dermatology but requires forced contact by a cotton swab or continuous direct spraying to avoid the insulating effect of N 2 gas coming between the skin surface and the LN 2 . Therefore, direct applications of LN 2 appear limited to their emphasis on evaporation and conduction.
NCC relies heavily on continuous and uninterrupted flow of the cryogen that is always maintained close to its critical point through a cryoprobe that is in good thermal contact with tissue because it eliminates the practical problems of trying to pump LN 2 down small channels. Evaporation causes enormous volume expansion as any liquid converts to a gas (i.e., ~1 : 176 for N 2 ). In a small-diameter tube, or cryoprobe, gaseous expansion can simply clog LN 2 flow, causing “vapor lock.” A cryogen cannot continue to flow against a massive volume of gas expanding ahead of itself in a confined space. Prior patents on LN 2 -based cryotherapy systems and probes (Cryomedical Sciences) sought to overcome vapor lock by elaborate mechanisms that allowed continuously flowing LN 2 to overcome the opposing force of gas expansion during evaporation. These sophisticated LN 2 systems and probes had relatively slow “start-stop” times and diameters limited to 3 mm or larger, respectively. This became so problematic for clinical and industrial uses that another form of cooling based on the adiabatic expansion of gas, or Joule–Thompson (JT) effect, became much more acceptable. We therefore describe the function of NCC in relation to JT performance for understanding of the theoretical and NCC prototype comparisons.
Materials and Methods
Compared with evaporative cooling with LN 2 , JT cooling avoids vapor lock by using a completely different cooling cycle. When a high-pressure gas expands adiabatically through a tiny port (i.e., JT port, or throttle), rapid cooling occurs, dependent on the type of gas. Some small devices use less expensive gases such as carbon dioxide (CO 2 ) or nitrous oxide (N 2 O), but do not achieve the extremely low temperatures obtainable with argon (Ar) ( Table 9–1 ). The coldest temperatures that can be generated at the JT nozzle approach the liquid values of −79°C, −89°C, and −187°C for CO 2 , N 2 O, or Ar, respectively (see Table 9–1 ). Yet, worldwide use of cryotherapy has been severely limited by regulations of high-pressure Ar tanks (e.g., 6000 psi [pounds per square inch]) because they could become ~400-lb. projectiles if a regulator got knocked off in transport or during an earthquake. Despite the greater costs and storage dangers of Ar tanks, the rapid initiation and termination of freezing outweighed the major flow problems seen with LN 2 .
| STATE | PHYSICAL PROPERTIES | ARGON (Ar) | NITROGEN (N 2 ) | NITROUS OXIDE (N 2 O) | CARBON DIOXIDE (CO 2 ) |
|---|---|---|---|---|---|
| Solid | Melting temperature (°C) | −189 | −210 | −91 | −79 |
| Liquid | Boiling point (bp) (°C) | −186 | −196 | −89 | −79 |
| Density (g/mL) | 1.393 | 0.808 | 1.223 | 1.032 | |
| Latent heat (J/mol) @ 1 bar | 6432 | 5560 | 16548 | 25130 | |
| Critical | Density (g/mL) | 0.538 | 0.314 | 0.498 | 0.464 |
| Pressure (bar) | 48.4 | 33.5 | 72.1 | 73.0 | |
| Pressure (psi) | 711 | 492 | 1059 | 1074 | |
| Temperature (°C) | −122 | −147 | 36 | 31 | |
| Gaseous | Density (g/cc) @ bp | 0.0058 | 0.0046 | 0.0031 | 0.0028 |
| Specific gravity (air = 1) | 1.38 | 0.97 | 1.53 | 1.53 | |
| Heat capacity (C p ; J/mol) | 12 | 29 | 38 | 37 | |
| Transitions | Liquid/Gas density ratio @ bp | 240 | 176 | 395 | 369 |
| Liquid/Gas density ratio @15°C | 819 | 673 | 679 | 543 | |
| Liquid/Critical density ratio @ cp | 2.6 | 2.6 | 2.5 | 2.2 |
JT cooling mainly relies on evaporation and convection, because conduction by a low-density gas has low C P , producing much worse cooling efficiency than liquid cryogens. This helps explain why JT produces massive gas consumptions when using multiple cryoprobes, thereby exhausting several Ar tanks for even a single session requiring a large-volume clinical freeze. Therefore, NCC was developed to eliminate high-pressure tanks, provide an efficient cryogen in a self-contained system, and generate potentially greater freeze capacity for small diameter channels for both medical and nonmedical applications.
Joule–Thompson Cooling Process
In JT cooling ( Figure 9–1 ), argon gas arrives in a highly compressed state near 20 MPa (i.e., ~3000 psi) and then is adiabatically expanded to near-ambient pressure through the throttle, where the gas stream partially liquefies. During this expansion, the cryogen falls to the liquid-vapor line at a pressure that is only slightly greater than ambient pressure and well away from the critical point of the liquid-vapor system. As indicated by the sequence of arrows in Figure 9–1 , temperature and pressure decline as the gas flows along the inlet line because of a counterflow heat exchanger inside the cryoprobe. This counterflow of returning low-pressure gas thus cools the incoming high-pressure gas before expansion. The returning gas flow encounters high flow impedance from the counterflow heat exchanger, causing the pressure to decline further as the temperature increases toward room temperature. JT cooling thus never approached the critical point of a liquid-vapor system. Cooling power is derived from only a relatively inefficient combination of miniscule amounts of argon immediately evaporating at the JT port, as well as conduction from the large amounts of cold, low-density gas.
