Continued studies in cognitive function in problem solving of graded difficulty (1) has now proceeded through several thousand tests of high school students in a six weeks period last summer. The optical imager uses 9 sources and 23 detectors operated in time multiplex to give an image of the prefrontal region in several seconds. Thus, the image can be acquired in the state prior to activation, during and following activation. The images are acquired at two wavelengths, 750 and 850 nm, from which the changes of blood concentration (blood pooling) and relative oxygenation/deoxygenation state (metabolic activity) can be obtained and with suitable calibrations converted into micromolar changes of total Hb concentration and fractional changes of oxygenation, respectively. The imager has a flexible, wearable pad applied to the forehead and the electronics presents the running average of the two quantities mentioned above in the 16 voxels which cover the prefrontal region. The protocol involves a scanning through multi-letter anagrams of graded difficulty which include problems ellicitating maximal activation (>3 solutions in the 30 sec test interval) or are to easy, or too difficulty. Anagrams are presented in a sequence of three, four, five letter anagrams of to the maximal level of difficulty and back to the starting point. Each anagram is displayed for approximately one minute. Computer scanning of the results gives histograms of the several hundred tests per individual in the "training" interval (for three weeks) and in the post training interval (3 weeks). Usually two or three complete trials per day were achieved with the result that the group of 7 students produced over 2600 test results. The histogram displays were studied to determine a) the most fruitful voxels, b) the approximate of the total tests that appeared in those voxels and c) the maximum signal level observed in the histogram display in units of micromolar hemoglobin. The product these two was taken as the Figure of Merit and their displays of the 16 voxels gave patterns for trained and untrained responses. The preliminary conclusions of this study were: a) that the training effect was very large, pre-training exhibited a chaotic voxel distribution for all difficulty levels while trained students gave a higher output and activated only one or two of the 16 voxels. If the tests was too easy, too hard, i.e., an ability/difficulty mismatch, frustration or disattention gave similar chaotic patterns; b) a match between difficulty and ability activated only one or two voxels in similar locations for the group. Since attention and success measure appear to be of interest in school room studies, a wearable imager with local LCD display is being supplied to the Senior class of the local high school for those individuals who have already had last Summer's training in anagrams. It is concluded that wearable NIR measurements of metabolic activation and blood flow may be a useful educational aid.

The measurement of dynamic changes in the blood oxygenation of tumor vasculature could be valuable for tumor prognosis and optimizing tumor treatment plans. In this study we employed near-infrared spectroscopy (NIRS) to measure changes in the total hemoglobin concentration together with the degree of hemoglobin oxygenation in the vascular bed of breast and prostate tumors implanted in rats. Measurements were made while inhaled gas was alternated between 33% oxygen and carbogen (95% O(2), 5% CO(2)). Significant dynamic changes in tumor oxygenation were observed to accompany respiratory challenge, and these changes could be modeled with two exponential components, yielding two time constants. Following the Fick principle, we derived a simplified model to relate the time constants to tumor blood-perfusion rates. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive means of monitoring the vascular oxygenation dynamics of tumors and facilitate investigations of tumor vascular perfusion. This may have prognostic value and promises insight into tumor vascular development.

Studies have shown that hypoxic tumor cells are relatively more resistant to radiotherapy, chemotherapy, and photodynamic therapy. Tumor oximetry, e.g., measurement of oxygen tension (PO2) of tissue and/or blood oxygenation (SO2) of the vascular bed, could be valuable for optimizing treatment plans.In this study, we employed a recently developed homodyne system to measure changes in hemoglobin saturation (502) and concentration in the vascular bed of rat prostate and breast tumors. For comparison, tissue P°2 values were measured using '9F MR EPI of hexafluorobenzene, providing a map of regional tumor oxygenation tension. Both 502 and P°2 measurements were taken while the inhaled gas was alternated between 33% oxygen, 100% oxygen and carbogen (95% oxygen, 5% C02).The results obtained for both techniques showed significant changes in tumor oxygenation accompanying respiratory challenge, with changes in vascular 502 preceding tissue P02 change. The combined use of these two techniques provides new insight into the dynamics of tumor oxygenation by making available a method of obtaining regional information of the state of the tissue, as well as a non-invasive, real-time method for determining changes in the vascular bed.

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