GENERAL DISCUSSION 465 



reported to us by Dr. Haymaker, Dr. Tobias, Dr. Van Dyke, and Dr. Clemente on 

 the difficult problem of trying to quantitate irradiation changes in the blood-brain 

 barrier. To emphasize the point made by one of the discussants, most of the dyes 

 that are used are bound by serum protein, and therefore changing permeability to 

 them represents a gross breakdown in the barrier. One question for Dr. Clemente: 

 In the classic descriptions of the use of trypan blue, it has been observed that 

 normally some areas of the brain are permeable to trypan blue, namely, the 

 superoptic and infundibular regions, the area postramus and the locus cinereus in 

 the fourth ventricle. It seemed to me from your shdes that these areas were 

 strongly represented in those shown after low dosage radiation. I had the privilege 

 of participating with Dr. Lee Farr and Dr. William Sweet in the second series of 

 neutron capture radiation at Brookhaven, a series of 10 radiations, to study intra- 

 cranial neutron flux during treatment and to make some physiologic studies of 

 possible changes in the blood-brain barrier. This is of crucial importance in that 

 type of treatment because its success is contingent on a ratio of concentration of 

 boron or other capturing agent within the tumor cells and in normal tissue. With 

 boron, this has been established to be about 3 or 5 to 1. The high ratio is main- 

 tained for a short time, perhaps half an hour, which limits the duration of 

 radiation. The question that arose was this: Does the patient after one treatment 

 have sufficient changes in the blood-brain barrier to reduce the therapeutic ratio, 

 that is, to reduce the concentration between tumor and brain, which might com- 

 promise subsequent treatments in the same patient? We considered the possibility 

 of using dyes, but felt this would represent too gross a test. Extending some tech- 

 niques for studying the dynamics of cerebrospinal fluid formation and absorption 

 developed by Dr. William Sweet and myself, simultaneous isotopic tracer studies 

 were made in patients with tumors before and after neutron capture radiation 

 using isotopes K-24, sodium-24, heav^ water, P-32 and chloride-38. In patients 

 who had received possibly 1,000 to 3,000 rep of neutron capture therapy, there 

 was no consistent detectable change in the blood cerebrospinal fluid barrier to 

 these isotopic tracers. 



Ray S. Snider (Northwestern University): I found this afternoon's group of 

 papers stimulating. I don't think I have ever sat through a half-day session among 

 the radiologists and found it more rewarding from the standpoint of getting new 

 ideas for future experiments. That is a bold statement, even for a chairman to 

 make. I would like to point out that we are dealing here with an exquisite 

 microradiologic tool that can destroy not only single cells, but even parts of cells. 

 I would like to ask what happens when this radiation goes in a cell and tickles it 

 gently without destroying it. I ask that because of the microchemical methods 

 now at our disposal, especially those of Lowry and associates, where they do 

 chemical reactions on single cells and parts of cells. I also ask it because of the 

 newer electron microscopic methods that we have, especially in relation to the 

 study of the structure of protein membranes. I ask it because of Dr. Magoun's 

 question on neurophysiologic activity, where we are measuring activities of single 

 cells, parts of cells, and the cellular environment. I ask it from the standpoint of 

 regrowth of the cell and emphasize again a point made by Dr. Mettler. I would 

 like to know what is happening to the behavior of this cell not only electrically, 



