THE JOURNAL OF UROLOGY

Vol. 115, May

Printed in U.S.A.

Copyright© 1976 by The Williams & Wilkins Co.

ANALYSIS OF RADIOHIPPURAN RENOGRAM BY SUBTRACTION OF EXTRARENAL RADIOACTIVITY MUHAMMAD A. RAZ ZAK,* ROBERT E. BOTTI

AND

WILLIAM J. MACINTYREt

From the Case Western Reserve University School of Medicine, Cleveland, Ohio

ABSTRACT

A method is presented for the simple, non-computerized analysis of the radiohippuran renogram by subtraction of the extrarenal radioactivity as monitored simultaneously by a detector centered over the manubrium sterni. This method requires the application of a calibration factor, relating the level of radioactivity recorded by the sternal detector to that over each kidney area at the end point of the phase of initial rise on each side separately. The results in 15 normal individuals showed a narrow range of values, indicating a high degree of resolution. Verification of the basis of this method of analysis was obtained by accounting for all of the counting rate as extrarenal sources in the tracings of nephrectomized subjects. A further advantage is that the tracing recorded by the sternal detector may be used to calculate renal blood flow. Although radioisotope renography has been in use since 1956 1 there has been no over-all agreement regarding the technical details of the procedure nor the interpretation of the curves obtained by the various methods. 2 • 3 It is realized that the conventional radiohippuran renogram represents an integrated response to changing radioactivity levels within the kidney as well as different levels of activity in the blood, which perfuses these organs together with the other tissues included in the area monitored by the detector. Analysis of the obtained tracing must then recognize the contribution of these extrarenal factors•· 7 and, if possible, separate them from the over-all response. Most of these methods have either involved a second injection of a different substance•·• or a rather complex computer analysis. 1 • 1° It is the purpose of our report to demonstrate a simple non-computerized measurement that will determine the extrarenal radioactivity, remove this contribution from the over-all renogram and obtain a derived renogram that reflects the functioning kidney parenchyma alone. This technique is not designed to supplant the more complex multi-parameter analysis of kidney function but to provide greater accuracy in the interpretation of the routine clinical renogram measurement. The simple method of analysis suggested here consists of subtraction of the extrarenal radioactivity contribution as derived from the counting rate monitored by a detector centered over the manubrium sterni, from the simultaneously recorded renogram. 11 • 12 MATERIALS AND METHODS

Our report concerns the findings obtained in 15 normal male volunteers and 6 subjects with unilateral nephrectomy. The normal subjects ranged in age between 19 and 35 years, whereas the nephrectomized subjects ranged in age from 32 to 59 years. The latter group consisted of 4 male and 2 female subjects. To initiate these studies subjects were instructed to drink Accepted for publication August 15, 1975. Supported by Grant HE-06304 from the National Heart and Lung Institute, National Institutes of Health, United States Public Health Service. * Current address: Department of Medicine and Division of Nuclear Medicine, Faculty of Medicine, Cairo University, Cairo, Arab Republic of Egypt. t Requests for reprints: Department of Nuclear Medicine, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44106.

600 to 1,000 ml. water within 1 hour and to evacuate the bladder just before sitting for the test. The water load resulted in diuresis, with a urine flow rate of 2.3 to 21.0 ml. per minute. The dose of radiohippuran varied between 60 and 100 µc. The study was performed in the sitting position, using a pair of well matched collimated scintillation detectors centered over both kidneys, the sites having been determined with a prior injection of a small dose of 197 Hg. A third collimated detector was placed over the manubrium sterni at the level of the second ribs to reflect extrarenal radioactivity. The collimators used had straight bores with 1.5-inch wide apertures, the crystal being recessed 3 inches from the surface. The counting rate from each detector was recorded by an integrating scaler activated at 15-second intervals for 30 minutes. CALCULATIONS

The radiohippuran renogram exhibits an initial abrupt rise in radioactivity, denoting its arrival in the field monitored by the detector. This initial rise is followed by a slower increase in radioactivity (ascending limb) to reach a peak value and ends with a descending limb that represents the difference between continuing renal uptake and the disappearance of activity from the field of view of the detector. In contradistinction the record obtained by the sternal detector represents a multiphasic disappearance curve, starting with a rapid component, followed by a slower segment and ending with a much slower phase. 13 Subtraction of the extrarenal radioactivity as monitored by the sternal detector from the simultaneously recorded renogram requires the application of a calibration factor relating the level of blood radioactivity as recorded by the sternal detector to that over each kidney area at the end point of the phase of initial rise on each side separately. The calibration factor is equal to the counting rate of each renal detector at the point of intersection of the early vascular and accumulation phase, dividing by the counting rate of the precordial detector at this same point in time (fig. 1). The counting rate obtained by the sternal detector is multiplied by the calibration factor calculated for each side and subtracted from the corresponding counting rate recorded by the renal detector. The resultant curve, now called the derived renogram, consists primarily of 2 limbs: 1) an ascending limb that approximates linear increase of the counting rate and 2) a descending limb that is an exponential function of time (fig. 2). Thus, analysis of this

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495

EXTRARENAL RADIOACTIVITY ANALYSIS

derived renogram is reduced to determination of only 3 parameters: 1) the time for radioactivity to reach half the peak value, 2) the time for peak activity and 3) the radiohippuran disappearance half time. These 3 factors allow reconstruction of the entire curve. RESULTS

The results obtained with our method of calculations in 15 normal male individuals are summarized in table 1 and the EXTERNAL MONITORING OF RADIOHIPPURAN DISAPPEARANCE SY A DETECTOR

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DISCUSSION

In these studies the radiohippuran renogram was performed with water loading to obtain an easier identification of the point of intersection of the initial rise of radioactivity with the succeeding ascending limb of the renogram and also because of the smoothness of the descending limb apparent after a water load. 14 With respect to the choice of collimators to be used it was considered that wide apertures minimize the effects caused by errors in detector placement and patient's movements during the test procedures 1 s but at the expense of inclusion of more extrarenal radioactivity. As others have found an increased skin crystal distance reduced the effect of variability in kidney depth 1 • but with a corresponding decrease in counting rate. Therefore, as a compromise it was decided to PEAK

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FIG. 1. Calculation of calibration factor for correction of extrarenal radioactivity. Calibration factor for each kidney is derived by determining counting rate at intersection of initial rise of renogram with ascending limb and dividing this value by extrapolated counting rate of sternal detector at time of intersection. Since time of intersection varies with each renal detector slightly different counting rates from sternal detector are used in this example.

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FIG. 2. Derived renogram is obtained by subtracting extrarenal contribution, as determined by ratio of sternal detector, from original renogram. Note that with collimator used extrarenal radioactivity is responsible for almost 50 per cent of total counting rate at peak.

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TABLE

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1. Time parameters of derived renogram in 15 normal subjects Lt. Kidney

Pt.No.

Time to Reach ½Peak Value (mins.)

Time to Reach Peak Value (mins.)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mean ± 1 standard deviation Range

0.95 0.85 0.95 1.00 0.93 1.55 1.00 0.67 0.82 0.68 1.40 0.80 1.00 1.15 1.40 1.01 0.26 0.67-1.55

1.95 2.05 2.15 2.00 2.33 3.82 2.50 1.43 1.82 1.70 2.65 1.90 2.25 2.75 3.20 2.30 0.61 1.43-3.82

Rt. Kidney Time to Reach ½ Half Time of Peak Value Clearance (mins.) (mins.) 1.40 2.30 3.20 2.40 2.30 3.20 2.35 1.80 1.50 2.33 2.10 1.40 3.60 5.40 1.90 2.54 1.04 1.40-5.40

0.95 0.90 1.20 0.80 1.15 1.88 1.10 0.63 0.83 1.35 1.10 1.00 1.15 0.95 1.15 1.08 0.29 0.63-1.88

Time to Reach Peak Value (mins.)

Half Time of Clearance (mins.)

Renal Blood Flow (ml./min.)

2.00 2.20 2.77 2.00 2.38 4.15 2.33 1.33 1.77 3.05 2.05 1.95 2.40 2.25 2.10 2.32 0.65 1.33-4.15

1.40 3.00 3.10 2.90 1.60 2.90 3.10 1.90 1.60 2.00 2.00 1.50 4.50 3.90 2.20 2.63 0.94 1.40-4.50

1,208 1,282 951 1,048 1,060 1,040 1,115 1,510 1,280 910 1,148 1,369 712 1,041 1,005 1,105 197 712-1,510

496

RAZZAK, BOTTI AND MACINTYRE

TABLE 2.

Ratio between left and right kidneys of time parameters of derived renograms in 15 normal subjects Ratio of Times Ratio of Times to Reach ½ Peak of Peak Values (lt./rt.) (lt./rt.)

Pt. No.

0.97 0.93 0.78 1.00 0.98 0.92 1.07 1.07 1.03 0.56 1.29 0.97 0.94 1.22 1.52 1.02 0.22

1.00 0.95 0.79 1.25 0.81 0.82 0.91 1.06 0.99 0.50 1.27 0.80 0.87 1.21 1.22 0.96 0.21

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Ratio of Half Times of Clearance (lt./rt.) 1.00 0.77 1.03 0.83 1.37 1.10 0.76 0.95 0.94 1.17 1.05 0.93 0.80 1.38 0.91 1.00 0.19

used as a simple index of abnormality m various diseased states. REFERENCES

1. Taplin, G. V., Meredith, 0. M., Jr., Kade, H. and Winter, C. C.:

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FIG. 3. Original and derived renogram in nephrectomized patient. In this case almost all counting rate of original renogram is accounted for by blood and extrarenal tissue radioactivity. Small residue is usually observed and is attributed to activity in bladder falling within field of view of detectors.

use a straight bore collimator with an aperture diameter of 1.5 inches, the crystal being recessed 3 inches from the surface. In our study radiohippuran renograms were performed for 15 normal individuals and the records were analyzed by subtraction of extrarenal radioactivity as monitored by a detector placed over the manubrium sterni. The results showed a narrow range of values, indicating a high degree of resolution that would help in identifying any departure from normality. A strong support for the basis of the suggested method of analysis was obtained from consideration of the nephrectomy cases. In this particular situation the entire dynamic tracing recorded by the renal probe should be accounted for by extrarenal factors. Consequently, the recorded curve should be canceled out by subtraction of extrarenal radioactivity. As shown in figure 3 this proved to be the case except for a small accumulation of radioactivity in the bladder. A further advantage of this method of analysis is that the tracing recorded by the sternal detector may be used to derive a value for total effective renal blood flow. 13 • 14 Because of the close agreement of the derived parameters between the right and left kidneys in normal patients, deviation from this agreement may now be

11.

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15.

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The radioisotope renogram. An external test for individual kidney function and upper urinary tract patency. J. Lab. Clin. Med., 48: 886, 1956. Koplowitz, J. M., Mitchell, J. F. and Blahd, W. H.: The radioisotope renogram. A comparison of qualitative and quantitative interpretation. J.A.M.A., 192: 1032, 1965. Meade, R. C., Horgan, J. D. and Madden, J. A.: Comparison of methods for renogram evaluation. J. Nucl. Med., 10: 40, 1969. Wax, S. H. and McDonald, D. F.: A quantitative analysis of the I-131 sodium o-iodohippurate renogram in hypertensive patients. J. Urol., 92: 409, 1964. Dore, E. K., Taplin, G. V. and Johnson, D. E.: Current interpretation of the sodium iodohippurate 1131 renocystogram. J .A.M.A., 185: 925, 1963. Hall, F. M. and Monks, G. K.: The renogram. A method of separating vascular and renal components. Invest. Radio!., 1: 220, 1966. Britton, K. E. and Brown, N. J. G.: The clinical use of C.A.B.B.S. renography. Investigation of the "non-functioning kidney" and renal artery stenosis by the use of 131-I hippuran renography modified by computer assisted blood background subtraction (C.A.B.B.S.). Brit. J. Radio!., 41: 570, 1968. Secker-Walker, R.H., Sheperd, E. P. and Cassell, K. J.: Clinical applications of computer-assisted renography. J. Nucl. Med., 13: 235, 1972. Brown, N. J. G. and Britton, K. E.: The theory ofrenography and analysis of results. In: Radionuclides in Nephrology. Edited by M. D. Blaufox and J-L. Funck-Brentano. New York: Grune & Stratton, Inc., pp. 315-324, 1972. Hirakawa, A., Kuwahara, M. and Ueyama, H.: Analog computeraided RI renogram diagnosis. In: Radionuclides in Nephrology. Edited by M. D. Blaufox and J-L. Funck-Brentano. New York: Grune & Stratton, Inc., pp. 303-313, 1972. Razzak, M.A., Botti, R. E., MacIntyre, W. J. and Pritchard, W. H.: Quantitative analysis of the radiohippuran renogram by subtraction of extrarenal radioactivity (abstract). J. Nucl. Med., 9: 371, 1968. Early, P. J., Razzak, M. A. and Sodee, B.: Textbook of Nuclear Medicine Technology. St. Louis: The C. V. Mosby Co., p. 326, 1969. Razzak, M. A., Botti, R. E., MacIntyre, W. J. and Pritchard, W. H.: External monitoring of P"-hippuran disappearance as a measure for renal blood flow. Int. J. Appl. Radiat., 18: 825, 1967. Razzak, M. A., Botti, R. E. and MacIntyre, W. J.: Interrelationship between hydration, urine flow, renal blood flow and the radiohippuran renogram. J. Nucl. Med., 10: 672, 1969. Nordyke, R. A. and Tonchen, A.: The radiohippuran renogram. Enhanced reproducibility by changes in instrumentation and patient position. J.A.M.A., 183: 440, 1963. Tauxe, W. N. and Burke, E. C.: Kidney depth and isotope renography. J. Nucl. Med., 9: 225, 1968.

COMMENT In the authors' words "This technique is not designed to supplant the more complex multi-parameter analysis of kidney function but to provide greater accuracy in the interpretation of the routine clinical renogram measurement". Hopefully, improved techniques of renography with computer analysis to determine differential urine volumes, glomerular filtration rate and renal plasma flow, that is an isotope split function study, will totally supplant the routine renogram and provide the clinician with reproducible quantitative measures of renal function. W.R.F.

Analysis of radiohippuran renogram by subtraction of extrarenal radioactivity.

A method is presented for the simple, non-computerized analysis of the radiohippuran renogram by subtraction of the extrarenal radioactivity as monito...
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