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Dual Channel Scanning
Dual Channel Scanning ERVIN KAPLAN, M.D.* MOSHE BEN-PORATH, Ph.D.**
Physical examination of the patient' by visual inspection might be immeasurably enhanced if opacity to internal observation could be penetrated. With the exception of microorganisms, several marine invertebrates, and a small but select representation of the denizens of the tropical fish aquarium, who apparently place little value upon their internal privacy, this transparency does not exist. The contribution of Wilhelm Konrad Roentgen partially alleviated this problem, but only as specifically related to radiodensity. External visualization of the soft tissue persisted as an enigma. Radiodensity was not an adequate discriminating factor. The distribution of selected substances in the human indicates specific concentrations in organs and tissue. The exploitation of such localization was delayed until the availability of an external means of detection. Gamma-emitting radioisotopes provide the necessary detectable label. In the earliest studies, Geiger-Mueller radiation detectors were employed as manual probes. Directional shielding was crude and counting efficiencies were low. The rectilinear scanning device developed by Cassen, using a small scintillation detector with adequate collimation, systematically scanned the area to be observed.lO The readout of this device displayed an image of the organ, in this instance a thyroid gland, proportional to the detected count rate. From this prototype, by a series of technical improvements, the modern rectilinear scintiscanner developed. The efficiency of counting was enhanced by using sodium iodide crystals of larger diameter. Three, five and eight-inch crystals are now From the Radioisotope Service and Research Section, Veterans Administration Hospital, Hines, Illinois; University of Illinois College of Medicine, and Loyola University Stritch School of Medicine. *Professor of Medicine, University of Illinois College of Medicine, Chicago; Chief, Radioisotope Service, Veterans Administration Hospital, Hines, Illinois ':":'Assistant Professor of Medicine (Pharmacology), Loyola University Stritch School of Medicine; Chief, Physics Section, Radioisotope Service, Veterans Administration Hospital, Hines, Illinois Medical Clinics of North America- Vo!. 53, No. 1, January, 1969
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available in commercial systems. The multi-bore focusing collimator, a series of holes through a radio-dense shield converging at a distance from the shield, when used with the large crystal, improved the optical resolution and increased the available count rate. To discriminate the specific energy photopeaks of the gamma-emitting isotopes, the pulse height analyzer became a component of the system. The display originally printed out on paper is now generally presented as a photodisplay on x-ray film. The historical aspects of medical radioisotope scanning have been reviewed by Brucer in appropriate perspective and lucid rhetoric. 9
SUBTRACTING SCAN IMAGES The development of the dual channel scanning system was stimulated by interest in the diagnosis of pancreatic disease. Two problems presented themselves in this regard. Could the pancreas be adequately visualized by external detection of an internal emitter? Would the image have diagnostic relevance if the visualization were possible? Attempts to solve the specific problems have involved the efforts of many workers in the field. Production of an appropriate localizing agent was reported in 1962 by Blau, Mancke, and Bender.s The protein synthesizing capacity of the pancreas exceeds that of any other major organ; an amino acid would be the obvious agent for localization within the pancreas. Incorporation of a radioisotope capable of appropriate gamma emission was solved by the synthesis of 75selenomethionine, an analog of methionine in which sulfur is replaced by selenium. The biosynthesis of the compound in yeast culture using 75 selenite resulted in adequate yield. After intravenous injection approximately 7 per cent of the administered dose concentrated in the pancreas. With approximately 250 jLCi dosage, the organ could be visualized by available scintillation scanning systems. The investigators working with this problem were confronted with the simultaneous localization of 75selenomethionine in the liver. In many projections the two organs overlap, and the delineation of each from the other when scanning the 75 selenium distribution was not possible. Various attempts were made to resolve the anatomical overlay, including shielding of the liver with lead plates,27 increasing the incorporation of selenomethionine in the pancreas by pancreozymin stimulation 15 and by intravenous infusion of amino acids,29 retention of pancreatic secretions by constriction of the sphincter of Oddi with morphine,24 and decreasing the flow of secretion by decreasing the volume with propantheline bromide (Probanthin).29 The liver will localize radioisotopes which have excellent properties for external visualization and which are not concentrated by the pancreas. If the liver is visualized separately from the pancreas and its image superimposed upon the liver-pancreas selenomethionine image, the liver will be isolated, but this does not apply to the pancreas. Two channels of pulse height analysis have been investigated previously, using anticoincidence circuits to selectively subtract the liver image. Attempts have also been made to exploit the pancreatic localiza-
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tion of 65zinc and hepatic localization of 131iodine Rose Bengai.2 Investigation has been reported of a model system for computer derivation of isoresponse figures of the distribution of a liver localizing isotope and 75selenium.26 Spencer has developed a similar system.28 The differential distribution of hepatic radio gold and hepatopancreatic 75selenomethionine are employed in the liver subtraction system the authors have developed.4 • 20. 21 The patient is prepared for pancreatic scanning by eating a regular breakfast, followed in 1 hour by intravenous injection of 100 ~Ci of 1989old in colloidal suspension and 250 ~Ci of 75selenomethionine. One hour after injection the detector of the scintiscanner is placed over the right lobe of the liver in an area remote from the pancreas. The output of the detector is fed into two individual pulse height analyzer count rate meter systems. One is set to detect the 0.411 MeV 198 9old photopeak, the other the 0.280 MeV 75 selenium photopeak. The deflections on the two count rate meters are adjusted so that the gold and selenium deflections are equal. The outputs of the count rate meters are direct currents - time-constant integration eliminates the short pulses of individual scintillation events. If the gold is presented as negative to the selenium output, the sum of the two outputs is zero. The selenium channel output will record only extrahepatic 75selenium activity, which is derived principally from the pancreas. Since the scanner operates on pulse input, the sum of the differences of the direct current outputs of the count rate systems is reconverted to pulses by a D.C.-tofrequency converter, an electronic device in which the pulsed oscillations are proportional to the D.C. input. The pulsed output rate may reach a maximum of 20,000 per minute in the system used. The scanner
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• Figure 1. A typical dual cha nnel subtraction sca n of the pancrea s in which the liver image h as been electronically r emoved by subtraction of " selenium from 1·'gold radioactivity. (Reproduced with the permission of the Journal of Nuclear Medicine.'·)
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will now make a black and white photoscan of the pancreas; an "electronic hepatectomy" has been accomplished (Fig, 1).
COLOR PRESENTATION OF DUAL CHANNEL SCANNING The presentation of scanning information in color was originally used to designate count rate density.2:l This topographical display of count rate was considered to be more readily interpreted than varying density of data or shading of gray. The authors proposed and reported the use of specific color for the presentation of specific radioisotopes. This was accomplished with the dual channel device described above. The pulses of different energies from two isotopes were scanned simultaneously. The printout for each energy in separate color is accomplished with the commercially available color tape printer. A broad tape, modified from the original seven color array to two colors, red and blue, is employed. One energy peak moves the tape to the left for one color, the other energy peak moves it to the right for the opposite color. The count rate of the display is proportional to the count rate detected and is accomplished by a metal tapper similar to a typewriter printout impressing colored ink from the tape onto paper. The details of operation have been previously described by the authors.5 Alternate scan lines are produced by a scan movement from left to right, followed by movement from right to left. Since the time constant of count rate integration is appreciable, a displacement of alternate lines resulted in a poor quality, scalloped image. This was corrected by printing out one isotope in scanning left to right and the other scanning right to left.
USE OF POLAROID COLOR DISPLAY AND TAPE RECORDING
A modified system has been developed for improvement of the dual channel scanner by enhancing storage, display, and analysis of the information detected. 6 A four-channel tape recorder records the X and Y coordinates of the detector movement and the two channels of gamma energy pulses. Channels one and two record the X and Y deflection, which regulates the position of pulse display upon the screen of a white phosphor cathode ray tube. Channels three and four store the individual pulses from the distributive pattern of two isotopes, or the subtraction of two isotopes in one channel and a single isotope in the other channel. The magnetic tape information is played out 16 times more rapidly than recorded. The information on the face of the cathode ray tube is photographed by an open lens polaroid camera in color, through individual color filters for each stored channel of information. The replay of information may be repeated as many times as desired in varied intensity, contrast, and background threshold cutoff, and at different ratios of the two channels.
THE DISCRIMINATION OF DEPTH BY COLOR MODULATION The depth of a specific concentration of gamma-emitting radioactivity in a patient is difficult to define in a two-dimensional picture of
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the isotope distribution. The real diagnostic significance of the scan picture may depend upon the localization in depth of an organ or a lesion. The usual approach to such discrimination is the making of scans at a right angle projection. Several other methods of solving this problem are available. The determination of depth may be made by using two probes to produce a stereo effect dependent upon parallax. Anger has described a multi plane tomographic scanning procedure using a moving focusing collimator, in which the out-of-focus emitters are projected upon a cathode ray tube and an analog lens system reconstructs the image in focus upon photographic film. 1 Neither of these techniques will be discussed. The use of two isotopes of the same element, detected by a single probe, may display depth as a ratio of two colors, dependent upon the differential attenuation of a low-energy and a high-energy gamma emission. Depth may also be displayed by the detection of the same radioisotope with two faCing probes on opposite sides of the object, the relative attenuation by each probe being the basis of depth discrimination. The development of the last two methods in our laboratories will be discussed.
DEPTH DISCRIMINATION USING TWO ISOTOPES AND ONE PROBE The different penetration of tissue-equivalent material by gamma rays is dependent upon the energy of the emission. Many elements have multiple gamma-emitting isotopes. The selection of two radioisotopes of the same element in which individual gamma emissions have widely different penetrating ability, has been used as a basis for determining the depth of a concentration containing a mixture of the two isotopes. 11.19 Such an isotopic pair is exemplified by '25iodine and 13liodine. To perform the depth discrimination, the dual channel subtraction system described above is employed. The '25iodine is visualized in one color from one channel of the system. This isotope emits a low energy x-ray, which attenuates markedly with depth. The 131 iodine gamma emission is relatively energetic and does not attenuate as readily with depth in material of tissueequivalent radiodensity. The second channel displays '3liodine minus '25iodine in a second color. The '25iodine activity detected at superficial depth is of considerable magnitude. The superficial 1:11 iodine is not displayed, because of the described subtraction in which 1:11iodine is equal to '25iodine activity. Despite the fact that the actual physical ratio between the two isotopes remains identical at any depth, the apparent, or detectable, amounts vary because of attenuation. The detected '25iodine counts decrease with self-absorption and distance, while the count of I:"iodine minus 125iodine increases with depth, revealing little superficial ':l'iodine but an increasing proportion of 131 iodine activity with depth. The graphic relationships between the two channels of information is perhaps more readily understood as displayed in Figure 2. U sing this method the ratio of the two colors is proportional to depth for a distance of approximately 6 cm. Superficial depths, up to 3 cm.,
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can be discriminated with considerable preCISIOn. This approach is therefore especially relevant in scanning the thyroid gland, which is essentially a superficial organ. Similar depth discrimination in color can be made with 1!17mercury and 20~mercury. The energy difference between the two mercury radioisotopes is not as great as for the two iodines, resulting in an effective but lesser accentuation of depth differences.
DEPTH DISCRIMINATION USING ONE ISOTOPE AND TWO PROBES The discrimination of depth by color modulation of differential attenuation of two gamma energies, as described above, has the disadvantage of requiring two radioisotopes of the same element with widely divergent energies of emission. If the concentration of radioactivity is relatively deep, the resolution of depth is poor. The proportionality between color ratio and depth is not linear. To overcome these disadvantages, we have investigated the use of a system in which a single gamma-emitting isotope is viewed by two NaI(Tl) crystal detectors with focusing collimation. The two probes are placed on opposite sides of the object to be scanned. The output of each detector and the X-Y coordinates are recorded on separate channels of the four channel tape recorder previously described. The output is then played out on the
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195 white phosphor cathode ray tube and recorded in color polaroid in separate color for each detector by the use of individual color filters for each channel. This method employs a dual probe Picker Magnascanner with 5 inch detectors and 5 inch focal length focusing collimators. 17 CLINICAL APPLICATION OF DUAL CHANNEL SCANNING21 The use of dual channel scanning technique as a diagnostic modality has made available clinical information not previously obtainable. Such information is exemplified by a total discrimination of the pancreas from the liver in those instances where the organs are either partially or totally superimposed; the visualization of a malignant process in the liver as a positive image; and the visualization of the brain as a positive image contrasting with the accessory structures of the head. The use of dual channel subtraction and color scanning has been most useful in pancreatic and liver disease. The visualization of the two organs is accomplished using the patient preparation described under "Subtraction Scanning." We have subjected 250 patients to pancreatic scanning; approximately 200 of these studies have included simultaneous positive visualization of the liver in contrasting color. In 109 male patients ranging in age from 35 to 76 years, diagnostic efficacy of the scan image has been compared with positive diagnosis of normal pancreas, carcinoma of the pancreas, pancreatic insufficiency, and cirrhosis. '4
Patients Without Pancreatic Disease This group of 36 patients was used as control subjects. Using the described technique the pancreas was well visualized in 31 subjects, who had been hospitalized for a variety of reasons and did not constitute a group of normal persons. The liver was of normal size and configuration of the body where it overlies the abdominal aorta, which should not Several anatomic variants of the pancreas were noted, including the pistol-shaped configuration (Fig. 3). Others were a large head with a small tail, and a relatively small head and large tail with marked attenuation of the body where it overlies the abdominal aorta, which should not be interpreted as a focal defect in the pancreas. Selenium activity was largely confined to the liver and pancreas. Not infrequently, activity thought to lie in the fundus of the stomach was visualized. No significant amount of activity was visualized in the spleen or kidneys. Of the 109 subjects there was evidence of 14 per cent false negative and 18 per cent false positive diganoses of normal pancreas, as determined exclusively by scanning.
Carcinoma of the Pancreas Of the 10 patients with carcinoma of the pancreas confirmed at laparotomy or necropsy, a diagnosis was made in eight patients by interpretation of the dual channel scan only. Figure 4 shows a typical dual channel scan of carcinoma of the pancreas. The characteristic finding in the scan image was the presence of "cold" areas in the pan-
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creas, which did not concentrate 75 selenomethionine. The focal areas of absent uptake were sometimes massive, as in the patient with no image of the body or tail but with a normal-appearing head of the pancreas, in whom the nonvisualized parts were massively replaced with carcinoma. Multiple and diffuse focal areas were noted in other instances, which conformed with the site of involvement. In three instances, a diagnosis of carcinoma of the pancreas was made when the findings with barium meal and radiography were interpreted as normal. The spleen was not visualized. The presence of 75 selenium activity other than in the pancreas and liver was minimal. The simultaneous visualization of liver and spleen in contrasting colors has permitted the diagnosis of primary carcinoma of the pancreas with liver metastasis. Using scan diagnosis exclusively, 20 per cent false negative and 4 per cent false positive results were noted. The lesions demonstrated in the series under discussion were not resectable. The minimal size of detectable pancreatic carcinomas has not been defined. The use of subtraction technique as developed by the authors has been confirmed by other investigators. 7 , 12, 13
Chronic Pancreatitis The characteristic appearance of the scan in patients with chronic pancreatitis and pancreatic insufficiency resulted in a diagnosis by scanning alone in 12 of 19 patients. These patients were devoid of evidence of focal liver disease, and the spleen was not visualized by uptake of radio gold. The 75 selenium activity in the abdomen, presumably in the intestines or possibly not cleared from the blood, increased the background count, often to the point of obscuring the pancreas, which could be visualized by marked enhancement of the background subtraction of the 75 selenium energy. This pattern has not been observed in persons having a normal pancreas, in patients with carcinoma of the pancreas, or in those with cirrhosis. The results by scanning were 37 per cent false negative and 4 per cent false positive. In acute recurrent pancreatitis without pancreatic insufficiency, the described scan pattern noted above was present in four instances and was compatible with normal findings in the remaining four.
Figure 3. Normal pancreas. A dual channel subtraction scan showing a normal liver and pancreas. Figure 4. Carcinoma of the pancreas. The 19S9old scan of the liver and spleen in red is contrasted with the pancreas, which shows numerous focal areas of replacement. Figure 5. Cerebral vascular accident. The accessory structures of the head containing 99mTc are shown in yellow. The brain containing "selenomethionine is in blue, while the lesion with both isotopes is in white. Figure 6. Cardiomegaly. 198Gold in the liver, 131IHSA in the heart blood, and 131IHSA macroaggregate in the lung are displayed in one channel, the myocardium containing "selenomethionine in the other channel. The superimposed heart blood appears in white. (All reproduced with the permission of the International Atomic Energy Agency.1S)
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Cirrhosis The combined liver-pancreas dual channel scan in patients with cirrhosis showed several varieties of liver scans previously described; normal uptake of radio gold, diffuse uptake, diffuse and focal defects, and presence of large focal defects. w, 22, 25 The latter defect is not to be confused with metastatic malignant disease in the liver. All patients showed patchy distribution of 75 selenium activity in the pancreas; the spleen was visualized by radio gold uptake. The differentiation from diffuse involvement of the pancreas with carcinoma is difficult. In the presence of a visualized spleen in a known cirrhotic, the diagnosis of carcinoma of the pancreas should be made with extreme conservatism. The diagnosis of cirrhosis by scan alone was made in 10 of the 17 patients with this disease. The false diagnosis of carcinoma of the pancreas was made in three instances. The incidence of false negative diagnosis was 41 per cent and of false positive diagnosis 2 per cent. Pseudocysts of the Pancreas The presence of pseudocysts of the pancreas is characterized in the scan in several ways. The pseudocyst may be seen as a large, round, focal defect in the scan image of the pancreas (Fig. 9). The liver or the liver and pancreas may be partially displaced by the lesion. The liver is in several instances markedly deformed by the external pressure of the cyst. With resolution of the cyst the deformity of the liver edge is no longer seen. Focal Lesions of the Liver Several types of discrete focal lesions of the liver are visualized by scanning. Metastatic carcinoma in the liver is seen as a focal lesion, generally multiple, but occasionally a single defect (Fig. 7). The presence of n.selenomethionine uptake in such focal areas is variable. It is displayed in contrasting color to that in the liver, but appears in lesser concentration than selenium in the liver tissue itself - which, of course, is not visualized because it is subtracted. The decreased 75 selenium concentration in metastatic lesions is common to lesions of varied primary sites. The shape of the metastatic lesions is often spherical. The uptake of selenomethionine by the metastatic lesion is presumably proportional to its rate of growth. The focal lesion of hepatoma is often in a single massive area of the liver, a considerable portion of the right lobe. The configuration is more often angular than spherical. The focal area is delineated in two ways. The absence of radio gold localization indicates an absence of functional reticuloendothelial cells. Confirmation of the presence of malignant tissue equal in volume of distribution to that of the absence of radiogold is difficult to make, but closed and open biopsy of the focal area does confirm the presence of malignant disease. In five of six hepatomas homogeneity of 75 selenium concentration in the focal area and in liver tissue was ascertained. This concentration was relatively higher than that seen in metastatic lesions (Fig. 8).
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The focal nonmalignant lesions of cirrhosis which have been previously reported show low concentrations of 7s selenium activity. I". 22.", They may be single or multiple and are easily confused with metastatic lesions, as these may certainly occur in the cirrhotic liver. We have not investigated focal lesions of amebic abscess or echinococcus cysts with dual channel scanning.
Myocardial Visualization The concentration of 75 selenium activity in heart muscle following the conventional 250 /LCi intravenous dosage of 75selenomethionine is significantly elevated when compared to skeletal musculature.:l It has been observed that when the tape recorded 75 selenium activity is played out on polaroid with low background erasure, the myocardium is visualized. An example of a myocardial scan is shown in Figure 6. The heart blood and the lungs are respectively visualized with I:l'iodine-Iabeled human serum albumin and l:l1iodine-labeled macroaggregated albumin. The selenium activity in the liver inferior to the heart is eliminated by the subtraction technique, while the liver is positively visualized by radio gold activity. The 7!i selenium in the myocardium is seen in contrasting color, as is activity in the chest wall. The heart blood activity from '31iodine is superimposed upon the myocardial image and is seen in white. This scan shows an example of massive cardiomegaly. The technique is applicable to differentiating the diagnosis of cardiomegaly from pericardial effusion. The usefulness of this technique in scanning for myocardial infarction is suggested.
Dual Channel Brain Scans VISUALIZATION OF BRAIN AND ACCESSORY STRUCTURES WITH Two ISOTOPES. 18 The simultaneous localization of 75selenomethionine and 99mtechnetium as pertechnitate in the head with the dual channel technique indicates a significant difference in distribution of the two isotopes. The 7s selenium concentrates principally in the brain and is apparently not rejected by the blood-brain barrier. The 99mtechnetium is localized in the accessory structure of the head and in brain lesions, including the vascular structure. It is excluded by the blood-brain barrier. Both isotopes are concentrated in lesions in the example seen in Figure 5, a cerebral vascular accident. The same localization is seen in brain tumors. The superimposition of the two isotopes images results in the lesion appearing white. A significant number of cerebral infarcts are not visualized by 99mtechnetium scans. This may be related to minimal inflammatory response about the infarcted area. Current investigation may demonstrate that "cold" focal lesions in the brain may be seen in the 75 selenium portion of the image in such instances. DEPTH DISCRIMINATION OF BRAIN LESIONS IN COLOR. Using two isotopes of the same element and a single probe, a mixture of 197mercury and 2o:lmercury-labeled chlormerodrin has been administered to patients with intracranial lesions. By the process described above, the differential attenuation of the two energies displayed in color will indicate the depth
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of the lesion by the ratio of the two colors, representing respectively 197mercury and 203mercury minus 197mercury. U sing a single isotope and two probes located on either side of the object to be scanned, the localization of the lateral position of an astrocytoma is exemplified in Figure 10. The symmetrical attenuation of gamma emission as detected by each probe is proportional to depth. The ratio of the detected gamma rays is displayed as the ratio of two colors. The head as viewed from the two lateral projections is a symmetrical object. In any brain lesion other than one located precisely in the midline, the lesion is asymmetric. Under these circumstances the accessory structure of the head will be displayed in one color and the lesion in another (Fig. 11.) The technique is applicable to any asymmetric scanning, such as simultaneous anterior and posterior scans of the chest and abdomen. Current investigations in our laboratories indicate the possibility of visualizing thromboembolic lesions in the lung or cold focal lesions in the liver in separate color proportional to the depth of the focal decrease in isotope concentration. The use of this method for simultaneous visualization of the pancreas and liver in separate color using a single isotope, 75selenomethionine, is also being investigated. The discrimination of depth related to different levels of centers of emission from each organ will result in color differentiation of the two organs. Many other applications of the method are possible. Miscellaneous clinical applications of dual channel color scanning have undergone pilot study.5 These include simultaneous visualization of lungs and liver in contrasting color to diagnose right subphrenic abscess, using 131iodine-labeled macroaggregated albumin and radio gold. Visualization of liver and kidneys and of the renal cortex and medulla (as contrasted to the renal pelvis) are of definite clinical value. The presence of so-called autonomous thyroid nodules, which depress the function of the remainder of the thyroid gland, may be well studied. Using 131iodine, thyrotropin, and 125iodine in 24-hour sequence, the autonomous and the stimulated portion of the gland may be individually displayed in contrasting color by the dual channel color subtraction technique. The method is applicable to scintillation cameras for simultaneous sequential studies of several organs or compartments. The sophistication
Figure 7. Hepatomegaly. The large liver with metastatic defects and the spleen appear in red. The pancreas is completely covered by the liver but may be well visualized by dual channel technique. Figure 8. Hepatoma. The liver and a primary hepatoma are well differentiated by color despite a homogeneous distribution of 75selenomethionine in the liver and tumor. Figure 9. Pseudocyst of the pancreas. This dual channel subtraction scan of the liver and pancreas shows a large de,fect in the pancreas due to a pseudocyst. Figure 10. Astrocytoma. A depth discrimination scan of the head with two color-modulated probes. An astrocytoma of the left hemisphere is lateralized by color. (All reproduced with the permission of the International Atomic Energy Agency.")
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of storage, display, and detection will continue to improve. It can be anticipated that we have crossed the threshold which will allow us to visualize multiple organs simultaneously; determine the depth and volume of organs and lesions, and quantify the amount of administered radioactivity in organs or lesions, as well as the rate of change brought about by interaction between bodily compartments. ACKN()WLED(;MENT
We wish to cite cooperation of the Picker Nuclear Division, Picker Corporation, in supplying equipment to be modified for dual channel application. E. R. Squibb & Company and Abbott Laboratories supplied isotopes used in these investigations.
REFERENCES 1. Anger, H. 0.: Multiplane tomographic gamma-ray scanner. Medical Radioisotope Scintigraphy 1 (Proceedings of a Symposium held in Salzburg). Vienna, International Atomic Energy Agency, (in press).
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2. Bender, M. A.: Medical radioisotope scanning, 105. Vienna, International Atomic Energy Agency, 1959. 3. Ben-Porath, M.: The radiopharmacological evaluation of "'Se-selenomethionine in man. Doctoral Thesis, Stritch School of Medicine, Loyola University, 1968. 4. Ben-Porath, M., Clayton, G., and Kaplan, E.: Selective visualization of the pancreas by subtractive radioisotope scanning technique. Trans. Amer. Nuclear Soc., 9:76, 1966. 5. Ben-Porath, M., Clayton, G., and Kaplan, E.: Modification of a multi-isotope color scanner for multi-purpose scanning. J. Nuclear Med., 8:411, 1967. 6. Ben-Porath, M., Clayton, G., and Kaplan, E.: Tape recording of dual channel energy modulated color scanning. J. Nuclear Med. (in press). 7. Blanquet, P. C., Beck, C. R., Fleury, J., and Palais, C. J.: Pancreas scanning with 75Seselenomethionine and '·'Au using digital-data-processing techniques. J. Nuclear Med., 9:486,1968. 8. Blau, M., Mancke, R. F., and Bender, M. A.: Clinical experience with selenomethionine for pancreas visualization. J. Nuclear Med., 3 :202, 1962. 9. Brucer, M.: Vignettes in nuclear medicine. Sixty-five years of medical radioisotope scanning. St. Louis, Nuclear Consultants Division, Mallinckrodt Chemical Works, 1966. 10. Cassen, B., Curtis, L., Reed, C., and Libby, R.: Instrumentation of 13'1 use in medical studies. Nucleonics, 9:46-50, 1951. 11. Dolan, C. T., and Tauxe, W. N.: Estimation of organ depth by a double isotope technique. Bull. Path., 8:45,1967. 12. Eaton, S. B., Fleischli, D. J., Pollard, J. J., Nebesar, R. A., and Potsaid, M. S.: Comparison of current radiologic approaches to the diagnosis of pancreatic disease. New Eng. J. Med., 279:389,1968. 13. Eaton, S. B., Potsaid, M. S., Lo, H. H., and Beaulien, E.: Radioisotope "subtraction" scanning for pancreatic lesions. Radiology, 89:1033, 1967. 14. Fink, S., Ben-Porath, M., Jacobson, B., Clayton, G., and Kaplan, E.: Current status of dual channel pancreatic scanning. J. Nuclear Med. (in press). 15. Haynie, T. P., Svoboda, K. C., and Zuidema, G. D.: Diagnosis of pancreatic disease by photoscanning. J. Nuclear Med., 5:90,1964. 16. Johnson, P. M., and Sweeney, W. A.: The false-positive hepatic scan. J. Nuclear Med., 8 :451, 1967. 17. Kaplan, E., and Ben-Porath, M.: Depth discrimination in scanning by dual channel color modulation of two probes. J. Nuclear Med., 9:330,1968. 18. Kaplan, E., and Ben- Porath, M.: Clinical application of color modulation of gamma energy and depth by dual channel scanning. Medical Radioisotope Scintigraphy 1 (Proceedings of a Symposium held in Salzburg). Vienna, International Atomic Energy Agency (in press). 19. Kaplan, E., Ben-Porath, M., and Clayton, G.: Depth discrimination in color by dual channel scanning. J. Nuclear Med., 8:322, 1967. 20. Kaplan, E., Ben-Porath, M., Fink, S., Clayton, G., and Jacobson, B.: Elimination of liver interference from the selenomethionine pancreas scan. J. Nuclear Med., 7:807, 1966. 21. Kaplan, E., Ben-Porath, M., Fink, S., Clayton, G., and Jacobson, B.: A dual channel technique for elimination of the liver image from the selenomethionine pancreas organ scan. In Fogel, L. U., and George, F. W., eds.: Progress in Biomedical Engineering. Spartan, MacMillan, Washington, 1967. 22. Klion, F. M., and Radavsky, A. Z.: False-positive liver scans in patients with alcoholic liver disease. Ann. Int. Med., 69 :283,1968. 23. Mallard, J. R., and Peachey, C. J.: A quantitative automatic body scanner for the localization of radioisotopes in vivo. Brit. J. Radiol., 32:652, 1959. 24. Rodriguez-Antunez, A.: The use of morphine in pancreatic scanning with ;"Se methionine. J. Nuclear Med., 5:729, 1964. 25. Rozental, P., Miller, E. B., and Kaplan, E.: The hepatic scan in cirrhosis: Biochemical and histological correlation. J. Nuclear Med., 7:868, 1966. 26. Schepers, H., and Winkler, C.: An automatic scanning system using a tape perforator and computer technique. Medical Radioisotope Scanning 1 :321. Vienna, International Atomic Energy Agency, 1964. 27. Sodee, D. B.: Radioisotope scanning of the pancreas with selenomethionine se'. Medical Radioisotope Scanning, 2:289. Vienna, International Atomic Energy Agency, 1964. 28. Spencer, R. P.: Simultaneous use of two radioisotopes by scanner plus analogue computer coupling. J. Nuclear Med., 6:844,1965. 29. Tabern, D. L., Kearney, J., and Dolbow, A.: The use of intravenous amino acids in the visualization of the pancreas with seleno" methionine. J. Nuclear Med., 6:762, 1965. Radioisotope Service Veterans Administration Hospital Hines, Illinois 60141
Physical examination of the patient' by visual inspection might be immeasurably enhanced if opacity to internal observation could be penetrated. With the exception of microorganisms, several marine invertebrates, and a small but select representation of the denizens of the tropical fish aquarium, who apparently place little value upon their internal privacy, this transparency does not exist. The contribution of Wilhelm Konrad Roentgen partially alleviated this problem, but only as specifically related to radiodensity. External visualization of the soft tissue persisted as an enigma. Radiodensity was not an adequate discriminating factor. The distribution of selected substances in the human indicates specific concentrations in organs and tissue. The exploitation of such localization was delayed until the availability of an external means of detection. Gamma-emitting radioisotopes provide the necessary detectable label. In the earliest studies, Geiger-Mueller radiation detectors were employed as manual probes. Directional shielding was crude and counting efficiencies were low. The rectilinear scanning device developed by Cassen, using a small scintillation detector with adequate collimation, systematically scanned the area to be observed.lO The readout of this device displayed an image of the organ, in this instance a thyroid gland, proportional to the detected count rate. From this prototype, by a series of technical improvements, the modern rectilinear scintiscanner developed. The efficiency of counting was enhanced by using sodium iodide crystals of larger diameter. Three, five and eight-inch crystals are now From the Radioisotope Service and Research Section, Veterans Administration Hospital, Hines, Illinois; University of Illinois College of Medicine, and Loyola University Stritch School of Medicine. *Professor of Medicine, University of Illinois College of Medicine, Chicago; Chief, Radioisotope Service, Veterans Administration Hospital, Hines, Illinois ':":'Assistant Professor of Medicine (Pharmacology), Loyola University Stritch School of Medicine; Chief, Physics Section, Radioisotope Service, Veterans Administration Hospital, Hines, Illinois Medical Clinics of North America- Vo!. 53, No. 1, January, 1969
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available in commercial systems. The multi-bore focusing collimator, a series of holes through a radio-dense shield converging at a distance from the shield, when used with the large crystal, improved the optical resolution and increased the available count rate. To discriminate the specific energy photopeaks of the gamma-emitting isotopes, the pulse height analyzer became a component of the system. The display originally printed out on paper is now generally presented as a photodisplay on x-ray film. The historical aspects of medical radioisotope scanning have been reviewed by Brucer in appropriate perspective and lucid rhetoric. 9
SUBTRACTING SCAN IMAGES The development of the dual channel scanning system was stimulated by interest in the diagnosis of pancreatic disease. Two problems presented themselves in this regard. Could the pancreas be adequately visualized by external detection of an internal emitter? Would the image have diagnostic relevance if the visualization were possible? Attempts to solve the specific problems have involved the efforts of many workers in the field. Production of an appropriate localizing agent was reported in 1962 by Blau, Mancke, and Bender.s The protein synthesizing capacity of the pancreas exceeds that of any other major organ; an amino acid would be the obvious agent for localization within the pancreas. Incorporation of a radioisotope capable of appropriate gamma emission was solved by the synthesis of 75selenomethionine, an analog of methionine in which sulfur is replaced by selenium. The biosynthesis of the compound in yeast culture using 75 selenite resulted in adequate yield. After intravenous injection approximately 7 per cent of the administered dose concentrated in the pancreas. With approximately 250 jLCi dosage, the organ could be visualized by available scintillation scanning systems. The investigators working with this problem were confronted with the simultaneous localization of 75selenomethionine in the liver. In many projections the two organs overlap, and the delineation of each from the other when scanning the 75 selenium distribution was not possible. Various attempts were made to resolve the anatomical overlay, including shielding of the liver with lead plates,27 increasing the incorporation of selenomethionine in the pancreas by pancreozymin stimulation 15 and by intravenous infusion of amino acids,29 retention of pancreatic secretions by constriction of the sphincter of Oddi with morphine,24 and decreasing the flow of secretion by decreasing the volume with propantheline bromide (Probanthin).29 The liver will localize radioisotopes which have excellent properties for external visualization and which are not concentrated by the pancreas. If the liver is visualized separately from the pancreas and its image superimposed upon the liver-pancreas selenomethionine image, the liver will be isolated, but this does not apply to the pancreas. Two channels of pulse height analysis have been investigated previously, using anticoincidence circuits to selectively subtract the liver image. Attempts have also been made to exploit the pancreatic localiza-
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tion of 65zinc and hepatic localization of 131iodine Rose Bengai.2 Investigation has been reported of a model system for computer derivation of isoresponse figures of the distribution of a liver localizing isotope and 75selenium.26 Spencer has developed a similar system.28 The differential distribution of hepatic radio gold and hepatopancreatic 75selenomethionine are employed in the liver subtraction system the authors have developed.4 • 20. 21 The patient is prepared for pancreatic scanning by eating a regular breakfast, followed in 1 hour by intravenous injection of 100 ~Ci of 1989old in colloidal suspension and 250 ~Ci of 75selenomethionine. One hour after injection the detector of the scintiscanner is placed over the right lobe of the liver in an area remote from the pancreas. The output of the detector is fed into two individual pulse height analyzer count rate meter systems. One is set to detect the 0.411 MeV 198 9old photopeak, the other the 0.280 MeV 75 selenium photopeak. The deflections on the two count rate meters are adjusted so that the gold and selenium deflections are equal. The outputs of the count rate meters are direct currents - time-constant integration eliminates the short pulses of individual scintillation events. If the gold is presented as negative to the selenium output, the sum of the two outputs is zero. The selenium channel output will record only extrahepatic 75selenium activity, which is derived principally from the pancreas. Since the scanner operates on pulse input, the sum of the differences of the direct current outputs of the count rate systems is reconverted to pulses by a D.C.-tofrequency converter, an electronic device in which the pulsed oscillations are proportional to the D.C. input. The pulsed output rate may reach a maximum of 20,000 per minute in the system used. The scanner
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will now make a black and white photoscan of the pancreas; an "electronic hepatectomy" has been accomplished (Fig, 1).
COLOR PRESENTATION OF DUAL CHANNEL SCANNING The presentation of scanning information in color was originally used to designate count rate density.2:l This topographical display of count rate was considered to be more readily interpreted than varying density of data or shading of gray. The authors proposed and reported the use of specific color for the presentation of specific radioisotopes. This was accomplished with the dual channel device described above. The pulses of different energies from two isotopes were scanned simultaneously. The printout for each energy in separate color is accomplished with the commercially available color tape printer. A broad tape, modified from the original seven color array to two colors, red and blue, is employed. One energy peak moves the tape to the left for one color, the other energy peak moves it to the right for the opposite color. The count rate of the display is proportional to the count rate detected and is accomplished by a metal tapper similar to a typewriter printout impressing colored ink from the tape onto paper. The details of operation have been previously described by the authors.5 Alternate scan lines are produced by a scan movement from left to right, followed by movement from right to left. Since the time constant of count rate integration is appreciable, a displacement of alternate lines resulted in a poor quality, scalloped image. This was corrected by printing out one isotope in scanning left to right and the other scanning right to left.
USE OF POLAROID COLOR DISPLAY AND TAPE RECORDING
A modified system has been developed for improvement of the dual channel scanner by enhancing storage, display, and analysis of the information detected. 6 A four-channel tape recorder records the X and Y coordinates of the detector movement and the two channels of gamma energy pulses. Channels one and two record the X and Y deflection, which regulates the position of pulse display upon the screen of a white phosphor cathode ray tube. Channels three and four store the individual pulses from the distributive pattern of two isotopes, or the subtraction of two isotopes in one channel and a single isotope in the other channel. The magnetic tape information is played out 16 times more rapidly than recorded. The information on the face of the cathode ray tube is photographed by an open lens polaroid camera in color, through individual color filters for each stored channel of information. The replay of information may be repeated as many times as desired in varied intensity, contrast, and background threshold cutoff, and at different ratios of the two channels.
THE DISCRIMINATION OF DEPTH BY COLOR MODULATION The depth of a specific concentration of gamma-emitting radioactivity in a patient is difficult to define in a two-dimensional picture of
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the isotope distribution. The real diagnostic significance of the scan picture may depend upon the localization in depth of an organ or a lesion. The usual approach to such discrimination is the making of scans at a right angle projection. Several other methods of solving this problem are available. The determination of depth may be made by using two probes to produce a stereo effect dependent upon parallax. Anger has described a multi plane tomographic scanning procedure using a moving focusing collimator, in which the out-of-focus emitters are projected upon a cathode ray tube and an analog lens system reconstructs the image in focus upon photographic film. 1 Neither of these techniques will be discussed. The use of two isotopes of the same element, detected by a single probe, may display depth as a ratio of two colors, dependent upon the differential attenuation of a low-energy and a high-energy gamma emission. Depth may also be displayed by the detection of the same radioisotope with two faCing probes on opposite sides of the object, the relative attenuation by each probe being the basis of depth discrimination. The development of the last two methods in our laboratories will be discussed.
DEPTH DISCRIMINATION USING TWO ISOTOPES AND ONE PROBE The different penetration of tissue-equivalent material by gamma rays is dependent upon the energy of the emission. Many elements have multiple gamma-emitting isotopes. The selection of two radioisotopes of the same element in which individual gamma emissions have widely different penetrating ability, has been used as a basis for determining the depth of a concentration containing a mixture of the two isotopes. 11.19 Such an isotopic pair is exemplified by '25iodine and 13liodine. To perform the depth discrimination, the dual channel subtraction system described above is employed. The '25iodine is visualized in one color from one channel of the system. This isotope emits a low energy x-ray, which attenuates markedly with depth. The 131 iodine gamma emission is relatively energetic and does not attenuate as readily with depth in material of tissueequivalent radiodensity. The second channel displays '3liodine minus '25iodine in a second color. The '25iodine activity detected at superficial depth is of considerable magnitude. The superficial 1:11 iodine is not displayed, because of the described subtraction in which 1:11iodine is equal to '25iodine activity. Despite the fact that the actual physical ratio between the two isotopes remains identical at any depth, the apparent, or detectable, amounts vary because of attenuation. The detected '25iodine counts decrease with self-absorption and distance, while the count of I:"iodine minus 125iodine increases with depth, revealing little superficial ':l'iodine but an increasing proportion of 131 iodine activity with depth. The graphic relationships between the two channels of information is perhaps more readily understood as displayed in Figure 2. U sing this method the ratio of the two colors is proportional to depth for a distance of approximately 6 cm. Superficial depths, up to 3 cm.,
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can be discriminated with considerable preCISIOn. This approach is therefore especially relevant in scanning the thyroid gland, which is essentially a superficial organ. Similar depth discrimination in color can be made with 1!17mercury and 20~mercury. The energy difference between the two mercury radioisotopes is not as great as for the two iodines, resulting in an effective but lesser accentuation of depth differences.
DEPTH DISCRIMINATION USING ONE ISOTOPE AND TWO PROBES The discrimination of depth by color modulation of differential attenuation of two gamma energies, as described above, has the disadvantage of requiring two radioisotopes of the same element with widely divergent energies of emission. If the concentration of radioactivity is relatively deep, the resolution of depth is poor. The proportionality between color ratio and depth is not linear. To overcome these disadvantages, we have investigated the use of a system in which a single gamma-emitting isotope is viewed by two NaI(Tl) crystal detectors with focusing collimation. The two probes are placed on opposite sides of the object to be scanned. The output of each detector and the X-Y coordinates are recorded on separate channels of the four channel tape recorder previously described. The output is then played out on the
DUAL CHANNEL SCANNING
195 white phosphor cathode ray tube and recorded in color polaroid in separate color for each detector by the use of individual color filters for each channel. This method employs a dual probe Picker Magnascanner with 5 inch detectors and 5 inch focal length focusing collimators. 17 CLINICAL APPLICATION OF DUAL CHANNEL SCANNING21 The use of dual channel scanning technique as a diagnostic modality has made available clinical information not previously obtainable. Such information is exemplified by a total discrimination of the pancreas from the liver in those instances where the organs are either partially or totally superimposed; the visualization of a malignant process in the liver as a positive image; and the visualization of the brain as a positive image contrasting with the accessory structures of the head. The use of dual channel subtraction and color scanning has been most useful in pancreatic and liver disease. The visualization of the two organs is accomplished using the patient preparation described under "Subtraction Scanning." We have subjected 250 patients to pancreatic scanning; approximately 200 of these studies have included simultaneous positive visualization of the liver in contrasting color. In 109 male patients ranging in age from 35 to 76 years, diagnostic efficacy of the scan image has been compared with positive diagnosis of normal pancreas, carcinoma of the pancreas, pancreatic insufficiency, and cirrhosis. '4
Patients Without Pancreatic Disease This group of 36 patients was used as control subjects. Using the described technique the pancreas was well visualized in 31 subjects, who had been hospitalized for a variety of reasons and did not constitute a group of normal persons. The liver was of normal size and configuration of the body where it overlies the abdominal aorta, which should not Several anatomic variants of the pancreas were noted, including the pistol-shaped configuration (Fig. 3). Others were a large head with a small tail, and a relatively small head and large tail with marked attenuation of the body where it overlies the abdominal aorta, which should not be interpreted as a focal defect in the pancreas. Selenium activity was largely confined to the liver and pancreas. Not infrequently, activity thought to lie in the fundus of the stomach was visualized. No significant amount of activity was visualized in the spleen or kidneys. Of the 109 subjects there was evidence of 14 per cent false negative and 18 per cent false positive diganoses of normal pancreas, as determined exclusively by scanning.
Carcinoma of the Pancreas Of the 10 patients with carcinoma of the pancreas confirmed at laparotomy or necropsy, a diagnosis was made in eight patients by interpretation of the dual channel scan only. Figure 4 shows a typical dual channel scan of carcinoma of the pancreas. The characteristic finding in the scan image was the presence of "cold" areas in the pan-
196
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creas, which did not concentrate 75 selenomethionine. The focal areas of absent uptake were sometimes massive, as in the patient with no image of the body or tail but with a normal-appearing head of the pancreas, in whom the nonvisualized parts were massively replaced with carcinoma. Multiple and diffuse focal areas were noted in other instances, which conformed with the site of involvement. In three instances, a diagnosis of carcinoma of the pancreas was made when the findings with barium meal and radiography were interpreted as normal. The spleen was not visualized. The presence of 75 selenium activity other than in the pancreas and liver was minimal. The simultaneous visualization of liver and spleen in contrasting colors has permitted the diagnosis of primary carcinoma of the pancreas with liver metastasis. Using scan diagnosis exclusively, 20 per cent false negative and 4 per cent false positive results were noted. The lesions demonstrated in the series under discussion were not resectable. The minimal size of detectable pancreatic carcinomas has not been defined. The use of subtraction technique as developed by the authors has been confirmed by other investigators. 7 , 12, 13
Chronic Pancreatitis The characteristic appearance of the scan in patients with chronic pancreatitis and pancreatic insufficiency resulted in a diagnosis by scanning alone in 12 of 19 patients. These patients were devoid of evidence of focal liver disease, and the spleen was not visualized by uptake of radio gold. The 75 selenium activity in the abdomen, presumably in the intestines or possibly not cleared from the blood, increased the background count, often to the point of obscuring the pancreas, which could be visualized by marked enhancement of the background subtraction of the 75 selenium energy. This pattern has not been observed in persons having a normal pancreas, in patients with carcinoma of the pancreas, or in those with cirrhosis. The results by scanning were 37 per cent false negative and 4 per cent false positive. In acute recurrent pancreatitis without pancreatic insufficiency, the described scan pattern noted above was present in four instances and was compatible with normal findings in the remaining four.
Figure 3. Normal pancreas. A dual channel subtraction scan showing a normal liver and pancreas. Figure 4. Carcinoma of the pancreas. The 19S9old scan of the liver and spleen in red is contrasted with the pancreas, which shows numerous focal areas of replacement. Figure 5. Cerebral vascular accident. The accessory structures of the head containing 99mTc are shown in yellow. The brain containing "selenomethionine is in blue, while the lesion with both isotopes is in white. Figure 6. Cardiomegaly. 198Gold in the liver, 131IHSA in the heart blood, and 131IHSA macroaggregate in the lung are displayed in one channel, the myocardium containing "selenomethionine in the other channel. The superimposed heart blood appears in white. (All reproduced with the permission of the International Atomic Energy Agency.1S)
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Cirrhosis The combined liver-pancreas dual channel scan in patients with cirrhosis showed several varieties of liver scans previously described; normal uptake of radio gold, diffuse uptake, diffuse and focal defects, and presence of large focal defects. w, 22, 25 The latter defect is not to be confused with metastatic malignant disease in the liver. All patients showed patchy distribution of 75 selenium activity in the pancreas; the spleen was visualized by radio gold uptake. The differentiation from diffuse involvement of the pancreas with carcinoma is difficult. In the presence of a visualized spleen in a known cirrhotic, the diagnosis of carcinoma of the pancreas should be made with extreme conservatism. The diagnosis of cirrhosis by scan alone was made in 10 of the 17 patients with this disease. The false diagnosis of carcinoma of the pancreas was made in three instances. The incidence of false negative diagnosis was 41 per cent and of false positive diagnosis 2 per cent. Pseudocysts of the Pancreas The presence of pseudocysts of the pancreas is characterized in the scan in several ways. The pseudocyst may be seen as a large, round, focal defect in the scan image of the pancreas (Fig. 9). The liver or the liver and pancreas may be partially displaced by the lesion. The liver is in several instances markedly deformed by the external pressure of the cyst. With resolution of the cyst the deformity of the liver edge is no longer seen. Focal Lesions of the Liver Several types of discrete focal lesions of the liver are visualized by scanning. Metastatic carcinoma in the liver is seen as a focal lesion, generally multiple, but occasionally a single defect (Fig. 7). The presence of n.selenomethionine uptake in such focal areas is variable. It is displayed in contrasting color to that in the liver, but appears in lesser concentration than selenium in the liver tissue itself - which, of course, is not visualized because it is subtracted. The decreased 75 selenium concentration in metastatic lesions is common to lesions of varied primary sites. The shape of the metastatic lesions is often spherical. The uptake of selenomethionine by the metastatic lesion is presumably proportional to its rate of growth. The focal lesion of hepatoma is often in a single massive area of the liver, a considerable portion of the right lobe. The configuration is more often angular than spherical. The focal area is delineated in two ways. The absence of radio gold localization indicates an absence of functional reticuloendothelial cells. Confirmation of the presence of malignant tissue equal in volume of distribution to that of the absence of radiogold is difficult to make, but closed and open biopsy of the focal area does confirm the presence of malignant disease. In five of six hepatomas homogeneity of 75 selenium concentration in the focal area and in liver tissue was ascertained. This concentration was relatively higher than that seen in metastatic lesions (Fig. 8).
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The focal nonmalignant lesions of cirrhosis which have been previously reported show low concentrations of 7s selenium activity. I". 22.", They may be single or multiple and are easily confused with metastatic lesions, as these may certainly occur in the cirrhotic liver. We have not investigated focal lesions of amebic abscess or echinococcus cysts with dual channel scanning.
Myocardial Visualization The concentration of 75 selenium activity in heart muscle following the conventional 250 /LCi intravenous dosage of 75selenomethionine is significantly elevated when compared to skeletal musculature.:l It has been observed that when the tape recorded 75 selenium activity is played out on polaroid with low background erasure, the myocardium is visualized. An example of a myocardial scan is shown in Figure 6. The heart blood and the lungs are respectively visualized with I:l'iodine-Iabeled human serum albumin and l:l1iodine-labeled macroaggregated albumin. The selenium activity in the liver inferior to the heart is eliminated by the subtraction technique, while the liver is positively visualized by radio gold activity. The 7!i selenium in the myocardium is seen in contrasting color, as is activity in the chest wall. The heart blood activity from '31iodine is superimposed upon the myocardial image and is seen in white. This scan shows an example of massive cardiomegaly. The technique is applicable to differentiating the diagnosis of cardiomegaly from pericardial effusion. The usefulness of this technique in scanning for myocardial infarction is suggested.
Dual Channel Brain Scans VISUALIZATION OF BRAIN AND ACCESSORY STRUCTURES WITH Two ISOTOPES. 18 The simultaneous localization of 75selenomethionine and 99mtechnetium as pertechnitate in the head with the dual channel technique indicates a significant difference in distribution of the two isotopes. The 7s selenium concentrates principally in the brain and is apparently not rejected by the blood-brain barrier. The 99mtechnetium is localized in the accessory structure of the head and in brain lesions, including the vascular structure. It is excluded by the blood-brain barrier. Both isotopes are concentrated in lesions in the example seen in Figure 5, a cerebral vascular accident. The same localization is seen in brain tumors. The superimposition of the two isotopes images results in the lesion appearing white. A significant number of cerebral infarcts are not visualized by 99mtechnetium scans. This may be related to minimal inflammatory response about the infarcted area. Current investigation may demonstrate that "cold" focal lesions in the brain may be seen in the 75 selenium portion of the image in such instances. DEPTH DISCRIMINATION OF BRAIN LESIONS IN COLOR. Using two isotopes of the same element and a single probe, a mixture of 197mercury and 2o:lmercury-labeled chlormerodrin has been administered to patients with intracranial lesions. By the process described above, the differential attenuation of the two energies displayed in color will indicate the depth
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of the lesion by the ratio of the two colors, representing respectively 197mercury and 203mercury minus 197mercury. U sing a single isotope and two probes located on either side of the object to be scanned, the localization of the lateral position of an astrocytoma is exemplified in Figure 10. The symmetrical attenuation of gamma emission as detected by each probe is proportional to depth. The ratio of the detected gamma rays is displayed as the ratio of two colors. The head as viewed from the two lateral projections is a symmetrical object. In any brain lesion other than one located precisely in the midline, the lesion is asymmetric. Under these circumstances the accessory structure of the head will be displayed in one color and the lesion in another (Fig. 11.) The technique is applicable to any asymmetric scanning, such as simultaneous anterior and posterior scans of the chest and abdomen. Current investigations in our laboratories indicate the possibility of visualizing thromboembolic lesions in the lung or cold focal lesions in the liver in separate color proportional to the depth of the focal decrease in isotope concentration. The use of this method for simultaneous visualization of the pancreas and liver in separate color using a single isotope, 75selenomethionine, is also being investigated. The discrimination of depth related to different levels of centers of emission from each organ will result in color differentiation of the two organs. Many other applications of the method are possible. Miscellaneous clinical applications of dual channel color scanning have undergone pilot study.5 These include simultaneous visualization of lungs and liver in contrasting color to diagnose right subphrenic abscess, using 131iodine-labeled macroaggregated albumin and radio gold. Visualization of liver and kidneys and of the renal cortex and medulla (as contrasted to the renal pelvis) are of definite clinical value. The presence of so-called autonomous thyroid nodules, which depress the function of the remainder of the thyroid gland, may be well studied. Using 131iodine, thyrotropin, and 125iodine in 24-hour sequence, the autonomous and the stimulated portion of the gland may be individually displayed in contrasting color by the dual channel color subtraction technique. The method is applicable to scintillation cameras for simultaneous sequential studies of several organs or compartments. The sophistication
Figure 7. Hepatomegaly. The large liver with metastatic defects and the spleen appear in red. The pancreas is completely covered by the liver but may be well visualized by dual channel technique. Figure 8. Hepatoma. The liver and a primary hepatoma are well differentiated by color despite a homogeneous distribution of 75selenomethionine in the liver and tumor. Figure 9. Pseudocyst of the pancreas. This dual channel subtraction scan of the liver and pancreas shows a large de,fect in the pancreas due to a pseudocyst. Figure 10. Astrocytoma. A depth discrimination scan of the head with two color-modulated probes. An astrocytoma of the left hemisphere is lateralized by color. (All reproduced with the permission of the International Atomic Energy Agency.")
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of storage, display, and detection will continue to improve. It can be anticipated that we have crossed the threshold which will allow us to visualize multiple organs simultaneously; determine the depth and volume of organs and lesions, and quantify the amount of administered radioactivity in organs or lesions, as well as the rate of change brought about by interaction between bodily compartments. ACKN()WLED(;MENT
We wish to cite cooperation of the Picker Nuclear Division, Picker Corporation, in supplying equipment to be modified for dual channel application. E. R. Squibb & Company and Abbott Laboratories supplied isotopes used in these investigations.
REFERENCES 1. Anger, H. 0.: Multiplane tomographic gamma-ray scanner. Medical Radioisotope Scintigraphy 1 (Proceedings of a Symposium held in Salzburg). Vienna, International Atomic Energy Agency, (in press).
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2. Bender, M. A.: Medical radioisotope scanning, 105. Vienna, International Atomic Energy Agency, 1959. 3. Ben-Porath, M.: The radiopharmacological evaluation of "'Se-selenomethionine in man. Doctoral Thesis, Stritch School of Medicine, Loyola University, 1968. 4. Ben-Porath, M., Clayton, G., and Kaplan, E.: Selective visualization of the pancreas by subtractive radioisotope scanning technique. Trans. Amer. Nuclear Soc., 9:76, 1966. 5. Ben-Porath, M., Clayton, G., and Kaplan, E.: Modification of a multi-isotope color scanner for multi-purpose scanning. J. Nuclear Med., 8:411, 1967. 6. Ben-Porath, M., Clayton, G., and Kaplan, E.: Tape recording of dual channel energy modulated color scanning. J. Nuclear Med. (in press). 7. Blanquet, P. C., Beck, C. R., Fleury, J., and Palais, C. J.: Pancreas scanning with 75Seselenomethionine and '·'Au using digital-data-processing techniques. J. Nuclear Med., 9:486,1968. 8. Blau, M., Mancke, R. F., and Bender, M. A.: Clinical experience with selenomethionine for pancreas visualization. J. Nuclear Med., 3 :202, 1962. 9. Brucer, M.: Vignettes in nuclear medicine. Sixty-five years of medical radioisotope scanning. St. Louis, Nuclear Consultants Division, Mallinckrodt Chemical Works, 1966. 10. Cassen, B., Curtis, L., Reed, C., and Libby, R.: Instrumentation of 13'1 use in medical studies. Nucleonics, 9:46-50, 1951. 11. Dolan, C. T., and Tauxe, W. N.: Estimation of organ depth by a double isotope technique. Bull. Path., 8:45,1967. 12. Eaton, S. B., Fleischli, D. J., Pollard, J. J., Nebesar, R. A., and Potsaid, M. S.: Comparison of current radiologic approaches to the diagnosis of pancreatic disease. New Eng. J. Med., 279:389,1968. 13. Eaton, S. B., Potsaid, M. S., Lo, H. H., and Beaulien, E.: Radioisotope "subtraction" scanning for pancreatic lesions. Radiology, 89:1033, 1967. 14. Fink, S., Ben-Porath, M., Jacobson, B., Clayton, G., and Kaplan, E.: Current status of dual channel pancreatic scanning. J. Nuclear Med. (in press). 15. Haynie, T. P., Svoboda, K. C., and Zuidema, G. D.: Diagnosis of pancreatic disease by photoscanning. J. Nuclear Med., 5:90,1964. 16. Johnson, P. M., and Sweeney, W. A.: The false-positive hepatic scan. J. Nuclear Med., 8 :451, 1967. 17. Kaplan, E., and Ben-Porath, M.: Depth discrimination in scanning by dual channel color modulation of two probes. J. Nuclear Med., 9:330,1968. 18. Kaplan, E., and Ben- Porath, M.: Clinical application of color modulation of gamma energy and depth by dual channel scanning. Medical Radioisotope Scintigraphy 1 (Proceedings of a Symposium held in Salzburg). Vienna, International Atomic Energy Agency (in press). 19. Kaplan, E., Ben-Porath, M., and Clayton, G.: Depth discrimination in color by dual channel scanning. J. Nuclear Med., 8:322, 1967. 20. Kaplan, E., Ben-Porath, M., Fink, S., Clayton, G., and Jacobson, B.: Elimination of liver interference from the selenomethionine pancreas scan. J. Nuclear Med., 7:807, 1966. 21. Kaplan, E., Ben-Porath, M., Fink, S., Clayton, G., and Jacobson, B.: A dual channel technique for elimination of the liver image from the selenomethionine pancreas organ scan. In Fogel, L. U., and George, F. W., eds.: Progress in Biomedical Engineering. Spartan, MacMillan, Washington, 1967. 22. Klion, F. M., and Radavsky, A. Z.: False-positive liver scans in patients with alcoholic liver disease. Ann. Int. Med., 69 :283,1968. 23. Mallard, J. R., and Peachey, C. J.: A quantitative automatic body scanner for the localization of radioisotopes in vivo. Brit. J. Radiol., 32:652, 1959. 24. Rodriguez-Antunez, A.: The use of morphine in pancreatic scanning with ;"Se methionine. J. Nuclear Med., 5:729, 1964. 25. Rozental, P., Miller, E. B., and Kaplan, E.: The hepatic scan in cirrhosis: Biochemical and histological correlation. J. Nuclear Med., 7:868, 1966. 26. Schepers, H., and Winkler, C.: An automatic scanning system using a tape perforator and computer technique. Medical Radioisotope Scanning 1 :321. Vienna, International Atomic Energy Agency, 1964. 27. Sodee, D. B.: Radioisotope scanning of the pancreas with selenomethionine se'. Medical Radioisotope Scanning, 2:289. Vienna, International Atomic Energy Agency, 1964. 28. Spencer, R. P.: Simultaneous use of two radioisotopes by scanner plus analogue computer coupling. J. Nuclear Med., 6:844,1965. 29. Tabern, D. L., Kearney, J., and Dolbow, A.: The use of intravenous amino acids in the visualization of the pancreas with seleno" methionine. J. Nuclear Med., 6:762, 1965. Radioisotope Service Veterans Administration Hospital Hines, Illinois 60141