Renewal Research Proposal for the Evaluation of the Absorbed Dose from the Diagnostic Use of Radiopharmaceuticals

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RENEWAL RESEARCH PROPOSAL EVALUATION OF THE ABSORBED DOSE FROM THE DIAGNOSTIC USE OF RADIOPHARMACEUTICALS on of Nuclear Medicine, Department of Rad ity of Miami School of Medicine, Miami, F Vice President for Financial Affairs and Treasurer, University of Miami Asst. Professor of Radiology University o f Miami School The investigations encompassed by this application have been o r will be approved by the Committee of Associates of the Investigator(s) in accordance with this institutions assurance on clinical research

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1. TITLE OF PROJECT : Evaluation of tile absorbed dose from the diagnostic use of radio pharmaceuticals 2 . INSTITUTION: University of Miani School o f Medicine, Department o f Radiology, Division of Nuclear Medicine a t : A . Mount Sinai Hospital, 4300 Alton Road, Miami School o f Medicine, P.O. Box 8 7 5 , Biscayne Ar,nex, 3 . PROJECT ABSTRACT: With the tremendous increase (1) in the use of radio nuclides in diagnostic nuclear medicine,it has become very necessary to study the most efficient and economical use of these materials from the2oint of view of maximum diagnostic information yield per unit of radiation dose to the patient. of the project the response of the scintillation camera to point sources of radioactivity in tissue the experimental measurements of the Point Source Response Function (PSRF), the Volume Source Response Function (VSRF) ofthe camera will be calculate a. The VSRF will then be used t o demodulate the scan and to predict the three dimensional distribution of radio - activity in an organ. The above studies on the can era will be compared with the studies carried out1ast.year on a rectilinear scanner. For a given specific alteration inactivity concentration,it will be decided which of the detector - colli mat or systems would provide better diagnostic information with the highest confidence lin its. amount of activity necessary for this confidence limit will be determined. will be calculated for this amount of activity and the biological data on the patient. The absorbed dose tothe pa:ient .Studies will be continued to accumulate biological data necessary for the calculation of absorbed dose.

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A) Diagnostic Nuclear Nedicine vs. Diagnostic Radiology A t a recent symposium on Reduction of Radiation Dose from Dlsgnoszlc >(-Rays (July, 1971; Houston, Texas), many scientists espressed t h e i r concern about the radiation dose to the patient in diagnostic radiology. Many new techniques ( 2 , 3 ) that wouid reduce the radiation dose were presented. a r e sone standard techniques for adjusting the kvp, mas, FSD, etc., from patient to patient to achieve a better yield of diagnostic information per unit of radiation dose. diagnostic nuclear medicine the activity administered to a particular patient to obtain an answer to a specific clinical question is n o t s o judiciously controlled. The level of administered activity used f o r imaging procedures today - with the rectilinear scanner and the stationary imaging systems - is based usually on the experience of the physician using a specific imaging system. The administered dose varies from one institution to another. a real need for relating the administered activity to the resulting In diagnostic radiology there On the other hand, in Thus, there exists B) Objective of the Proposal: Our objective is to determine before the fact, the quantity of administered activity required to detect a specified alteration in the distribution of a radionuclide in a patient by a particular A) General: The above objective is to be achieved in the following five major steps: (i) Determine the Volume Source Response Function (VSRF)- - of the imaging system; Reconstruct the.response o f the imaging system to the specified three dimensional distribution of activity representaticve of a clinical situation; Find the imaging system which can detect certain alterations with the minimum amount o f activity; Collect t h e biological data such as body distribution and biological turnover rates in each individual Calculate the .absorbed dose t o the. patient.

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These various stages o f the project are discussed in detail beiow. By VSRF we mcan the total response of the system to a mall unit volume of uniformly distributed activity situated in a tissue equivalent material. volume since any larger volume distributions can b e made up as a sum of unit volumes ,and it is relatively easy to calculate the response o f the system t o such a unit cubicai volume from the measured line source response function (LSRF). The various steps taken to obtain the VSRF are summarized below. equivalent medium (TEN). It was discovered this year (4), at o u r laboratory, that thelength of the line source as reconaended by the Subgroup reporting to the International Commission on Radiation Units and Measurements (5) was not the optimum length for taking data in a tissue equivalent medium. Thus the LSRFs are taken by using a line source whose length is calculated from the estimate o f septum penetration and scattering in the *medium. The data are then processed for background subtraction and decay correction. o f more than one Gaussian component. These Gaussian components are stripped by computer codes developed (6) f o r this purgose. The point source response function (PSRF) is then computed from the Gaussian parameters o f the LSRF. as well as its superiority over other methods o f obtaining the PSRF are discussed in detail in a paper submitted for publication this year from o u r laboratory (7). A copy of this paper is attached with this Proposal f o r reference purposes. These various stages of going from the experimentally measured i S 2 F to the computed PSRF are shown in Fig.1. The two curves on the left side o f the figure show the relative response of the collimator as a function o f the radial distance from the central axis o f the collimator; the two curves OA the right side show the relative response as a function of the square o f the radial distance. Thus, if the LSRF was composed of only one Gaussian component, one would have had a straight line in the upper right plot.’ The upper left figure ais0 shows how closely the three Gaussian component LSRF matches the experimental LSRF. Once the PSRFs are obtained the calculation of VSRF is very straight forward. We chose a 1-cm cube as the unit First, the LSRFs are measured at various depths in a tissue It is assumed that the LSRF is a composite The details of this nethod In calculating the VSRF the main point to decide is whether to integrate the PSRF over the unit volume o r to average the values of the PSRFs at some specific points such as at a i l the ’ corners of the cube. We have investigated this by simulzzing the response of a square sheet source. Fig.2 compares the response of the 1-cm square sheet source as calculated by summing and averaging the value o f the PSRF at the four corners vs. the response calculated by integrating the PSRF over the entire area. The figure shows that there is not much difference

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bctwccn the two methods. Hence, in the interest of scvij..g con3uter tirne , we calculate the vol ux c response by averaging the value of ;;-.e PSRI: at the eight corners of the cube. To do this, we have plotted in Fig.3,the is orcs ? onse curves in four diff c rent situations. Thc t o ? left figure shows iso - response curves in air as obtained from LSRF data.Iso response cui-ves obtained from PSRF data in air do not look any different than the LSRF derived curves because in air the LSRF is very close to a single Gaussian and therefore the PSRF is also a Gaussian ofthe same width - in other words, their shape i s the same. However, in the presence of a scattering medium, such as tissue, ' the LSRF is not as in gie Gaussian. Therefore, the shapes of the LSRF and the PSRF are not the sane. As can be seeri by comparing the top right and lower left carves,the iso response curves drawn from the LSRF look different than those drawn from the PSRF. Note two important points : (a) The LSRF data indi,cate that low values of the iso responses have been spread out. towards the face of the colli mat or. The PSRF data do not support either of these indications. The response curves have been stretched a little, compared toair data but not as much a s tE,e LSRF data shows. Moreover, the focal plane is not shifted towards the colli mat or face. These results were further investigated on theoretical grounds and the details are being submitted for publication(8). The iso - response curves on the lower right - are drawn from LSRF data which was taken with an asymmetric window. As one would expect, scatter is reduced. Fora one dimensional, sinusoidal ly varying source inTEN, Beck (9)has shown that to reconstruct the image, the modulation transfer function (MTF) t o be used must be the one derived from the LSRF measured inthe mediun and not in air. When o m has a three - dimensional non - periodic source, as in all pr z ct ical. situations,this method of reconstructing the image is difficult. Since the three dimensional PSRF is a transfer characteristic o f the system (7), its measurement is the most direct way or' reconstructing the image. This fact,as pointed out by Beck (lo), has long been recognized. However, not much progress has been made on either deriving the PSRF from the measured LS2F o r on accurate experimental methods of obtaining it.in our laboratory we have developed computer codes t o deduce the PSRFs from the measured LSRFs. In order toes tabl isn the fact that one can reconstruct an inage of a certain clinical situation. by using the PSRFs, we have constructed a simple cubical phantom

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nade of Lucite. of varying lcvels in 3-cm cubes arranged in a 4 x 7 ~ 7matrix. The cubical phzatom can be fiiled with water o r appropriate levels of activity and then surrounded by TEM to simulate a This phantom allows one to place activity In Fig.4 the experimental responsc of the scanner when a single hot cube is scanned across its rnidline is compared with the calculated response. We have shown two types of calcuiations. The open circles are the result of a calculation using VSRF data, which were deduced from the measured LSRF. A s can be seen, the agreement is not very good. The solid circles show the response calculated from VSRF data dedaced from the PSRF. Here, there is perfect agreement thus cor,firmlng the validity of using the PSRF and the concept of the VSRF. Fig.5 shows the comparison o f experimental vs. conputei responses in 3 different cases. A l l the computations were nade the three scans is in the axis on which the scan was ma6e. The other two curves on the right were scans made on an axis away from the midline of the cube. The agreement between the experimental response and the computed response is excellent. Fig.6 shows a further comparison of experiment and corr,?utation in a slightly more complicated case, viz. two hot cubes in a TEM at different levels. Again an axis and an off-axis scan - both show good agreement between the measured and predicted (or computed) values. A different clinical situation, viz. scanning a cold spo ~ is shown in Fig.7. This was simulated by a 3-cm cube defect in a thick volume source. The defect was made o f paraffin and positioned at the center of the source. The conparison ofthe measured response and prediction again shows that the agreement is excellent. In Figs. 4 through 7 we have demonstrated that the image of an experimental distributkon o f radioactivity - similar to a clinical situation - can be reconstructed if the totai response of the inaging system to a unit-volume of activity is knonn. In other words, ifthe VSRI" is known, one can r e - construct the original activity distribution. The difference between . curve t o the left is the same as that shown in Fig.4. TZe The TEK depth is 14c;n. (iii) Determination of the Imaging System Giving the Best Statistics A comparison will be made of the scanner and the camera to determine which system yields the best statistics for equal mounts of administered activity in selected clinical applications. Specific clinical situations such as a brain scan and a liver scan with hot and/or cold 9pot.s will be studied.

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civ) and (v) 3iological Data Collection and Absorbed Dose Ca I cul at ion The details on these two sections are being submitted 6 , EQU IP EXT During the period 1 0 / 1 5 / 7 0 to 10/l4/71 we have studied the VSRF for a 140 keV, 99Tcm collinator of a 5 inch rectilinear scanner detector system (ll,12,13). F o r the period 10/15/71 to lO/l4/72 we propose to extend these studies to the sclntillasystems to accomplish this. We have two digital data acquisition and processing At Jackson Memorial Hospital we have three scintillation csmeras with video tape store/playback accessories. We also have a clinical data system - 4096 word accessory f o r processing video tapes digitally. At Mount Sinai Hospital we have a Hewlett Packard 2116B computer with disc and tape storage interfaced to a The simulation of scan images and reconstruction of activity distribution is done on aG.E. time-share computer (6). ' C) Facilities f o r the collection of biological turnover data o n adninistered radionuclides include a low background counter (iron room) with two S I 1 diameter by 4" thick NaI(T1) crystals which are mounted above and below the patient. These crystals can scan over a distance of 70". F o r localized measurements on organs a dual 8'' diameter rectilinear scanner with quantitative readout w i l l be used. The curriculum vitae of all the scientific personnel are

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of Health, Educatior, and Welfare, 1970. Possibilities and Limitations, Abstract, AAPN Quarterly Reduction in Diagnostic Radiology by Electronic Image Storage Techniques; Abstract, AAPN Quarterly Sulletin, Vol. 5, No. 2 , N.E. Read, S.R. Amtey and R.R. Sankey: Errors Introduced by the Finite Length of Line Sources; 3aper to be presented at the December meeting of the AAPM, Chicago, 1971 (Abstract J.R. Mallard: Sensitivity and Resolution in Radioisotope Scanning, in Medical Radioisotope Scintigraphy, Vol. 1, and J.H. Crisp: Use of a Time-share Computer System in. the Department of Nuclear Medicine, presented as a scientific exhibit at the 18th annual meeting of the Society of Suclear Medicine, Los Angeles, 1971. M.E. Read, S.R. htey : On the Shape of the Paint Sotirco Response Function, a paper submitted to the journal of Physics in Xedicine and Biology, 1971 (copy of paper enclosed). S.R. Amtey, W.E. Read and R.R. Sankey: New Definition of the Focal …