Studies on the use of freezing for controlled destruction and preservation of biological tissue.

摘要

Low temperatures have been used in therapeutics since the dawn of human history. Freezing and cooling present a paradox as they can be used both, for preserving and destroying tissue. The destructive ability of freezing is commonly used in "cryosurgery", while the ability to preserve tissues by freezing is used in "cryopreservation". The use of cryosurgery can be traced back to the middle of the 19th century and cryopreservation became extensively used in the late 40's. Evidently, it is important to understand how it is possible to apply freezing for destroying and preserving tissues. The consequences of the freezing process depend on two most important parameters, the thermal history during freezing and thawing and the presence of various cryoprotective additives. With these parameters it is possible to manipulate the freezing process to either preserve or destroy tissue. Obviously to achieve optimal results, it is important to be able to precisely understand the effect of these parameters and to control them. This thesis was performed to gain better control over cryosurgery and cryopreservation through studies on new methods for analyzing the processes of freezing and controlling them.;The study is divided into two parts, one on "cryosurgery" and other on "cryopreservation". In the part on cryosurgery, I will introduce a new numerical method which employs magnetic resonance imaging (MRI) for calculating the temperature history in the frozen region during cryosurgery. Since our goal is to ultimately use cryosurgery for treatment of breast cancer, I will also present the results of a fundamental study on the process of freezing and mechanism of damage in human breast tissue.;The study on "cryopreservation" focuses on the preservation of the liver by freezing. First, I will describe MRI studies and mathematical analysis of the process of freeze tolerant animals such as the wood frog and the painted turtle. These studies were performed to gain a better understanding of how the liver in these freeze tolerant animals survives freezing. Then I will describe a new apparatus and technique that I have developed for preserving mammalian livers using the principles learned from freeze tolerant animals. Finally, I will describe an experiment in which rat livers were successfully preserved in a frozen state for six hours.