Our patients are treated in a wide variety of conditions. We use some objective quality scores to quantify the quality of preservation in each patient, track our effectiveness, etc. We assign quality scores to each patient in different areas. These scores are retroactively applied to older cases as the scoring system is updated over time.
The quality scores are not usually applied to extremely poor cases because we can't make any meaningful measurements.
We are interested in scoring ischemic damage mostly because it impairs subsequent cryoprotective perfusion, and by extension, results in ice crystal formation. The Q10 concept states that metabolic activity decreases by a certain rate in relation to a temperature change of 10 degrees C. For cerebral tissue, Q10 is approximately 2.3 , meaning that at 27 deg C, the metabolic rate is about 1/2 (1 / 2.3) of that at 37 deg C.
We use Q10 to assign an ischemic damage score to each patient that represents the equivalent number of hours and minutes of normothermic ischemia that was endured . In an attempt to keep the score simple, it does not take into account the known additional cerebral protective effect of hypothermia. This score is calculated by feeding the numbers into a computer algorithm that computes the integral of the Q10 values over the time period.
Each one minute slice of time is run through this formula
(2.3 ^ ((Temp-37)/10))/60
and then the slices are all added together.
As the simplest example, if the temperature is constant at 27 for one hour:
score=2.3 ^ ((27-37)/10)
score=2.3 ^ -1
score=1 / 2.3
score=.43 hrs = 26 minutes
This means that the metabolic activity during that hour of ischemia was equivalent to 26 minutes at normothermic temperature.
For dogs, we use 38.6 as normothermic temperature rather than 37.
Time 0 is when cerebral perfusion is first interrupted, usually a few minutes prior to time of pronouncement. If there was premortem hypoperfusion, then time 0 may be moved earlier to capture that. If truly effective CPS is initiated after pronouncement, then the time period from initiation of CPS to loss of cerebral perfusion may be eliminated from the score.
Ending time for this score is when cryoprotective perfusion begins.
The score is converted from decimal format to a descriptive hours minutes format for display.
An ideal score might be less than about 60 minutes, a very difficult-to-achieve target which is almost always exceeded.
This is calculated exactly the same as Ischemic Time Preperfusion, but also includes the ischemia that happens during cryoprotective perfusion. Ending time for this score is when subzero cooling begins.
It's difficult to say what an ideal score would be. The smaller, the better.
While currently only in the preliminary phase, we do have the ability to perform a CT Scan on every patient prior to subzero cooling. This could potentially give us some metrics on extent and quality of cryoprotection.
Mild shrinkage of the brain is desirable to help reduce water content, provide stability, and facilitate vitrification. Moderate to severe shrinkage causes physical trauma and damage to the structures we are trying to preserve. It also damages the vasculature, interfering with the ability of the cryoprotectant to penetrate into all tissues. Any swelling compresses capillary beds, and prevents areas of the brain from getting adequately perfused. Shrinkage also distorts subsequent electron micrographs, making it very difficult to interpret quality of structural preservation.
For this score, the change in volume is computed. First, the average diameter of the brain is estimated. Then the shrinkage is measured from the interior of the skull to the surface of the brain. This is typically measured through a burr hole. These are converted to radius1 and radius2, and then the change is calculated using:
For example, if the initial average diameter is estimated to be 130mm, and shrinkage is measured as 5mm, then r1=65 and r2=62.5.
change in V=(244141-274625)/244141
Ideal scores might be in the range of 10% to 20% shrinkage.
We would like to obtain electron micrographs of every patient. Our plan is to remove tissue from the spinal cord immediately after cryoprotective perfusion and place it with the patient for subzero cooling. We would remove the tissue prior to transferring the patient to storage, and some of the tissue would be sent out for electron microscopy. Some of the tissue would also be stored for later, in case improved imaging techniques become available.
1. Greeley W, Kern, FH, Ungerleider, RM. et al.: Cerebral metabolic suppression during hypothermic circulatory arrest in humans. The Annals of Thoracic Surgery 1999, 67(6):1895-1899.
2. Perry RM: Toward a Measure of Ischemic Exposure. Cryonics 1996, 17(2):21.