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Effects of local trauma on the cortical cerebral blood flow, studied by infrared thermography During recent years thermographic techniques have found increasing application in several clinical fields3-a,1a-ls,22,25,29, 33. So far, however, this method has only been applied in a limited way to neurological problems1,2,19, 3a. Of special interest are the experimental thermographic studies of Melzack et al. 32 on the cortical circulation. These authors described global cerebral blood flow changes and employed a relatively slow equipment of low sensitivity (resolution power) with a full black to white range of 5°C and requiring a minimal exposure time of 2 min. The recent development of a much faster and more sensitive thermographic equipment (Thermovision, Aga, Liding6, Sweden) seemed to justify a new trial of the method. Thus, in the present study attention was directed to local temperature changes in the cerebral cortex as correlated to changes in regional cerebral blood flow (rCBF). it was also the aim to follow changes in temperature (and blood flow) that accompany mechanical trauma (pressure) to the cortical surface, and which include regional hyperemia and EEG changes around an ischemic focusT,8,10,20,21,23,24,27. The present studies were performed on 6 cats (average weight 2.9 kg) anesthetized with Nembutal (35 mg/kg body weight, intraperitoneally) under artificial respiration (Starling pump) with room air so as to maintain an arterial pCO2 of 28.0 ( ± 4.0) mm Hg (ref. 13). No additional anesthetic was given during the experiments. The animals were immobilized with small doses of gallamine triethiodide (Flaxedil). A craniotomy was made over the lateral aspect of one hemisphere, the dura being opened and the brain surface covered with a 25 # thick gas-tight membrane (Mylar, Dupont). Measurements of rCBF were performed according to a previously described modification6,11 of the isotope clearance technique of Lassen and lngvar 2a,zs. Changes in rCBF were induced by means of cortical compression with 15 g per sq. cm over an area of 0.5 sq. cm during 5 rain, by means of a specially developed device. Changes of rCBF were also induced repeatedly by means of auditory stimulation (2 animals), cortical electrocoagulation (1 animal) or by application of strychnine to the exposed cortex (1 animal). Following the operative procedures, control measurements of rCBF and preliminary thermograms were made. Thereafter the cortical circulation was changed according to one of the above-mentioned procedures. Whenever possible, rCBF measurements and thermography were performed serially. During auditory stimulation only thermography was employed. The thermographic measurements were carried out with an infrared television system with a focal distance of 45-60 cm. It consisted of an infrared camera that scans the object and displays its thermal image on the screen of a modified oscilloscope at a speed of 16 frames per sec, thus producing a practically fused image. The full black to white range employed in these studies was of the order of I°C, thus permitting the detection of temperature differences of the order of 0.2°C. On the screen, warmer regions appeared as brighter areas, while cooler regions were seen darker. Direct as well as isothermal pictures were obtained and the picture on the oscilloscope screen was photographed. (For a more detailed description of the equipment see Backlund I and Notter and Melander3a.) Brain Research, 12 (1969) 238-242
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Fig. 1. Effects of local mechanical pressure on the cerebral cortex upon regional cortical temperature and blood flow (rCBF). A, Thermoscan of the craniotomy field before the procedure. B, Photograph of the same field; pressure was exerted on the encircled and hatched area. C, Thermoscan 90 min after the compression (during 5 min) had been discontinued. Following compression area 'a' is cooler (darker) and has a lower rCBF, while at its periphery, point 'b' is seen as a 'hot spot' (with marked increase in rCBF). Simultaneously, point 'c' at the periphery also shows cooling, with decrease in rCBF. D, Superposition of C and B. Note that the course of the cortical vessels is characterized by a warmer (brighter) image.
The findings of Melzack and coworkers al that in the anesthetized cat the cortex is usually cooler than the arteries was confirmed in the present series (Fig. 1D). This difference, however, is not always pronounced enough to be satisfactorily detected (Fig. 1A) by thermography. Nevertheless, it becomes more evident when - - because of faulty shielding of the observed field against evaporation and convection - - slight movements of air induce a cortical cooling. Gentle blowing of air on the cortical surface clearly reinforces the above contrast. The local temperature (and blood flow) changes caused by cortical compression could be visualized by thermography. As previously shown 7's, 10, following a mechanical pressure applied to the cerebral cortex, rCBF progressively decreases in the formerly compressed area as local edema develops. Concomitantly, the surrounding cortical tissue becomes hyperemic. The corresponding thermal changes, namely low temperatures at the edematous, previously compressed area, and higher temperatures around it, were thus observed in the thermograms.
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Fig. 1 shows the results from one of the experiments. Prior to the cortical compression the thermogram is fairly homogeneous (Fig. IA). rCBF was 113 ml/ 100 g/min. 90 min following compression at the encircled area (Fig. 1B) temperature at this region had fallen (probably due to ensuing edema) and rCBF had decreased to 100 ml/100 g/min. This area ('a', Fig. 1C) is seen as a darker region. At the periphery of the formerly compressed site there was a bright region ('b', Fig. IC) with an rCBF of 198 ml/100 g/min, seen as a 'hot spot'. It is noteworthy, however, that a cold (dark) area could also be found at the periphery of the formerly compressed zone ('c', Fig. 1C) with an rCBF of 104 ml/100 g/min. Thus, it seems that both perifocal hyperemia as well as hypoemia may develop simultaneously in different areas around an ischemic cortical region (see Discussion). Cortical coagulation gave rise to a cooler region on the surface coagulated. At points where vessels were allowed to bleed, however, the picture was reversed and the bleeding appeared as a 'warm spot' (brighter than the surroundings). Changes in cortical temperature caused by auditory stimulation and strychnine application could not be detected by the equipment employed, although the application of strychnine provoked a marked increase in rCBF. The thermovision camera used in these studies does not permit quantitative measurements of temperature (and rCBF) changes. Only relative temperature differences between neighboring areas can be detected. Furthermore, since there is a continuous drift of the camera to a given constant temperature, only momentaneous comparisons are possible. In the present animal experiments it was found necessary to shield the scanned field against the influence of other thermal variations in the laboratory, and also to prevent the accumulation of liquid within this field. Even the 25 ,u thick Mylar film lying on the cortex in these animal experiments exerted a strong isolating effect upon infrared radiation. It therefore had to be removed during each thermographic study which probably explains the high rCBF values recorded. Finally, only thermal changes in the central parts of the scanned region could be reliably taken into account, since radiations coming from the periphery of the convex hemisphere were distorted by the reflexion angle and by thermal influence from the surrounding tissue. These problems do not seem to have been encountered in the studies of Melzack et al. ~'2, probably because of the afore-mentioned lower sensitivity of their equipment.The fact that no temperature differences could be detected upon auditory stimulation of the cerebral cortex in the present study is not surprising. It is known that the changes in cortical temperature induced in this way are of the order of a few hundredths of degree centigrade 3°,al,34 while the maximal sensitivity of the employed thermovision camera is 0.2°C. On the other hand, the thermograms obtained after cortical compression are quite illuminating. They show that, after a circumscribed cortical compression, lower focal temperature develops at the compressed area (paralleling a decrease in rCBF) as well as perifocal hyperthermia (with correspondingly higher rCBF values). These findings are in agreement with previous data 7,8,1°. However, it could also be demonstrated ('c', Fig. IC) that a temperature (and blood flow) increase and a
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t e m p e r a t u r e (and b l o o d flow) decrease can develop simultaneously, side by side, around a region o f cortical injury (pressure, in o u r case). This seems to indicate t h a t the so called ' l u x u r y perfusion' (ref. 27) a r o u n d an ischemic focus p r o b a b l y is a r a t h e r ' p a t c h y ' p h e n o m e n o n , a n d n o t a c o m p l e t e halo. This finding is in a g r e e m e n t with recent clinical observations °,12,2°,21,~4. It is p l a n n e d to use the present t h e r m o g r a p h i c technique to follow the a b n o r malities o f the cerebral circulation which a c c o m p a n y cold lesions o f the b r a i n 23. The technical assistance o f Mrs. B. Olsson a n d o f Miss E. K r o o k is gratefully acknowledged. Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)
M. BROCK* J. RISBERG D. H. INGVAR
1 BACKLUND, E. O., Thermography in neurosurgical diagnosis, (Proc. III. int. Congr. neurol.
Surg.), Excerpta med. (Amst.), Congr. Set., No. 110 (1965) 569-572. 2 BACKLUND, E. O., Thermography in intracranial lesions, J. Radiol. l~lectrol., 48 (1967) 39-41.
3 BARNES,R. B., Thermography of the human body, Science, 140 (1963) 870-877. 4 BARNES, R. B., Determination of body temperature by infrared emission, J. appl. Physiol., 22 (1967) 1143-1146. 5 BECKMANN, L., Bilddarstellung von Oberfl/ichentemperaturen mit Hilfe yon der infraroten Eigenstrahlung, J. Radiol. t~lectrol., 48 (1967) 35-39. 6 BETZ, E., INGVAR, D. H., LASSEN,N. A., AND SCHMAHL, F. W., Regional blood flow in the cerebral cortex, measured simultaneously by heat and inert gas clearance, Acta physiol, scand., 67 (1966) 1-9. 7 BROCK, M., Experimental 'luxury perfusion' in the cerebral cortex of the cat. In W. LUYENDIJK (Ed.), Cerebral Circulation. Progress in Brain Research, Vol. 30, Elsevier, Amsterdam, 1968, p. 125. 8 BROCK, M., Regional cerebral blood flow (rCBF) changes following local brain compression in the cat, Scand. J. clin. Lab. Invest., Suppl. 102 (1968) XIV: A. 9 BROCK, M., HADJIDIMOS,A., AND ELLGER, M., Unpublished data. 10 BROCK, M., HEIPERTZ, R., HADJIDIMOS,A., CHRIST, R., AND SCHORMANN,K., The influence of mild and severe experimental local brain damage on regional cerebral blood flow (rCBF) and electrocorticogram, (Proc. 21. Ann. Meeting of Scand. neurosurg. Soc., Aarhus, 1968), Acta neurol, scand.~ in press. 11 BROCK, M., INGVAR, D. H., AND SEM-JACOBSEN,C. W., Regional blood flow in deep structures of the brain measured in acute cat experiments by means of a new beta-sensitive semiconductor needle detector, Exp. Brain Res., 4 (1967) 126-137. 12 FIESCHI,C., Regional cerebral blood flow in acute apoplexy, including pharmacodynamic studies, Scand. J. clin. Lab. Invest., Suppl. 102 (1968) XVI: E. 13 FINK, B. R., AND SCHOOLMANN, M., Arterial blood acid-base balance in unrestrained waking cats, Fed. Proc., 21 (1962) 440. 14 GERSHON-COHEN,J., Medical thermography, Sci. Amer., 216 0967) 94-102. 15 GERSHON-COHEN,J., AND HABERMAN,J. D., Medical thermography, Amer. J. Roentgenol., 94 (1965) 735-740. 16 GERSHON-COHEN, J., HABERMAN-BRuESCHKE,J. D., AND BRUESCHKE, E. E., Medical thermography: a summary of current status, Radiol. clin. (Basel), 3 (1965) 403-431. 17 GROS, CH., trND BOUJART, P., Die Anwendungsm6glichkeiten der Thermographie, Fortschr. R~.-Strahl., 106 (1967) 765-771. 18 GROS, CH., ET VROUSOS,C., Thermographie m6dicale, Presse m~d., 74 (1966) 2902-2905. 19 GROS,CH., WACKENHEIM,A., VROUSOS,C., ETBOUJART,P., Les premi6res possibilit6s de la thermographie dans l'exploration du cerveau, Neuro-chirurgie, 12 0966) 765-77t. * From the Neurosurgical Department, University of Mainz, Mainz, Germany (for reprints). Brain Research, 12 (1969) 238-242
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20 HAOJ1DIMOS,A., CHRIST, R., HEIPERTZ, R., AND BROCK, M., Acute electrocorticographic changes following localized cortical freezing in the cat, Scand. J. olin. Lab. Invest., Suppl. 102 (1968) XIV : E. 21 HADJIDIMOS,A., OECONOMOS,n . , LASSEN,N. A., ET INGVAR, D. H., D6bit sanguin cdrdbral et ses aspects cliniques, Rev. neurol. (Paris), (in press). 22 HARDERS,H., TILSNER,V., HEISIG,N., UND HAAN, D., Wirkungsnachweis vasoaktiver Substanzen durch lnfrarotthermographie, Med. Kiln., 62 (1967) 566-567. 23 HEIPERTZ, R., The effects of local cortical freezing on rCBF in the cat, Scand. J. olin. Lab. Invest., Suppl. 102 (1968) XIV: D. 24 HOEDT-RASMUSSEN,K., SKINHOJ,E., PAULSON,O., EWALD, J., BJERRUM,J. K., FAHRENKRUG,A., AND LASSEN, N. A., Regional cerebral blood flow in acute apoplexy. The 'luxury perfusion syndrome' of brain tissue, Arch. Neurol. (Chic.), 17 (1967) 271-281. 25 HOFFMAN, R., Thermography in the detection of breast malignancy, Amer. J. Obstet. Gynec., 98 (1967) 681-686. 26 INGVAR, D. H., AND LASSEN, N. A., Regional blood flow of the cerebral cortex determined by Krypton 85, Acta physiol, stand., 54 (1962) 325-338. 27 LASSEN, N. A., The luxury perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain, Lancet, 2 (1966) 1113 1115. 28 LASSEN, N. A., AND [NGVAR, n . H., The blood flow of the cerebral cortex determined by radioactive Krypton 85, Experientia (Basel), 17 (1961) 42-43. 29 LAWSON, R. N., Implications of surface temperature in the diagnosis of breast cancer, Canad. reed. Ass. J., 75 (1956) 309-318. 30 MCELLIGOT, J. G., AND MELZACK, R., Localized thermal changes evoked in the brain by visual and auditory stimulation, Exp. Neurol., 17 (1967) 293-312. 31 MELZACK, R., AND CASEY, K. L., Localized temperature changes evoked in the brain by somatic stimulation, Exp. Neurol., 17 (1967) 276-292. 32 MELZACK, R., STEWART, J., AND BAMBRIDGE, R., Infrared thermograph studies of cortical circulation: evaluation of the method, Electroenceph. clin. Neurophysiol., 20 (1966) 614-617. 33 NOTTER, G., UND MELANDER, O., Thermographische Untersuchung bei Erkrankungen der Brustdriise, Fortschr. R/L-Strahl., 105 (1966) 657-664. 34 SEROTA, H. M., AND GERARD, R. W., Localized thermal changes in the cat's brain, J. Neurophysiol., 1 (1938) 115-124 35 WOOD, E. H., Thermography in the diagnosis of cerebrovascular disease, Radiology, 85 (1965) 270-283.
(Accepted October 5th, 1968) Brain Research, 12 (1969) 238-242
Studies on in vitro RNA synthesis in human brain tumor nuclei Studies on RNA polymerase (nucleoside triphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) from various mammalian cell nuclei 1,7 have revealed that the characteristics of in vitro RNA synthesis are similar. However, RNA polymerase activities in tumors and virus infected tissues 2,5 have shown significant differences. To our knowledge, no studies on in vitro RNA synthesis in human brain tumors have yet been reported. This communication describes some characteristics of RNA polymerase from 3 types (meningioma, gliobtastoma multiforme and undifferentiated glioma, degree IV) of human brain tumors. Tumor tissue, obtained from the Neurosurgery Department, Sahlgrenska Hospital, was transferred to ice-cold homogenization medium (0.32 M sucrose, 0.001 M MgCI2 and 0.001 M potassium phosphate, pH 6.5) immediately after surgery. Brain Research, 12 (1969) 242-245