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Transmission sources used for image attenuation correction, allowing image quantification, are collimated to reduce scatter. We propose the same effect can be achieved for an uncollimated source by increasing source to patient distance. The aim was to compare planar image performance characteristics and absorbed doses of uncollimated and collimated radioactive printed paper transmission sources. The scatter contribution to the uncollimated (⁹⁹m)Tc source data was evaluated for different combinations of detector phantom distance, detector source distance and phantom source distance. Measurements were performed by increasing the Lucite phantom thickness in 1cm steps to 20 cm. Spatial resolution, detection efficiency and entrance absorbed dose rate were measured for the uncollimated and collimated transmission source images. Results derived from the energy spectra, obtained with the uncollimated transmission source indicate that scatter contribution increases with decreasing detector source distance. The scatter component in the uncollimated transmission images (detector source distances ≥ 60 cm; phantom source distances ≥ 40 cm) was comparable to that obtained with collimated transmission images. Attenuation coefficients obtained compared well (0.168 cm⁻¹ vs. 0.171 cm⁻¹). The full widths at half maxima differed by less than 0.9 mm. The detection efficiency of the uncollimated source was 2.5 times higher than obtained with the collimated source. The entrance absorbed dose obtained from an uncollimated source was 3.75 times larger than that obtained from the collimated source. An uncollimated transmission source (detector source distance ≥ 60 cm) results in acceptable image characteristics and presents a low cost, low dose, high efficiency option for transmission imaging., (© 2010 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

This note proposes the use of a standard inkjet printer to produce radioactive (99m)Tc phantoms that can be used for routine quality control of gamma cameras. The amount of activity that will be deposited on paper per unit area was predicted and compared to the measured activity. The uniformity of the printouts was compared to the uniformity obtained with a standard (57)Co flood source. A scintillation detector connected to a multi-channel analyzer was used to evaluate the uniformity of the printout independently from the gamma camera. Joining two A4 size printed phantoms to create larger sources was evaluated. The spatial resolution obtained with printed sources was compared to that obtained using standard line source techniques. The results indicated that the uniformity of the printed phantoms compared well with those obtained with the (57)Co flood source (integral uniformity 2.29% (printed source) and 2.10% ((57)Co flood source)). There was no difference in the resolution measurements obtained with the printed sources and those obtained with the standard methods. This study demonstrates that affordable phantoms can easily be created to evaluate system uniformity and resolution in any department where a standard PC and inkjet printer are available.

Introduction: The inflammation- and infection-seeking properties of (131)I-labeled ornidazole, a 5-nitroimidazole derivative, have recently been reported. Whole-body images in rabbits showed a more rapid uptake in inflamed areas compared to (67)Ga. In the present study, two novel (123)I-labeled 2-methyl-4-nitroimidazole derivatives were synthesized and their infection-seeking properties compared with those of (67)Ga and (123)I-labeled ornidazole., Methods: Radiolabeling was carried out by means of iodide-for-tosylate, triflate or halogen exchange. Various methods were utilized in order to synthesize the labeling precursors for the (123)I-labeled novel compounds. Serum stability studies on all of the (123)I-labeled tracers were followed by gamma camera imaging studies on rabbits artificially infected with Escherichia coli bacteria., Results and Conclusions: The (123)I-labeled tracers were obtained in moderate to good radiochemical yields (34-80%) and acceptable radiochemical purities (93-99%). In contrast to (123)I-labeled ornidazole, 1-[(1-hydroxy-3-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (2) and 1-[(1-[(123)I]iodoprop-2-yloxy)methyl]-2-methyl-4-nitroimidazole (3) showed high serum stability. Compared to noninfected controls, all of the (123)I-labeled tracers showed increased uptake at the area of induced infection after 6 and 24 h, but the uptake was significantly lower than in the case of (67)Ga over the same period. Tracer 3 showed a slightly superior uptake after 6 h than the other (123)I-labeled tracers over the same period. The advantage of the initially slightly faster rate at which nitroimidazole tracers appear to accumulate in the infection area in comparison to (67)Ga might not outweigh the advantage of the eventual higher target to nontarget ratio displayed by (67)Ga.

Background: The accuracy of the left ventricular ejection fraction (LVEF) calculated from gated single photon emission computed tomography (GSPECT) studies is dependent on the accuracy of the determination of the end-diastolic volume (EDV) and end-systolic volume (ESV) of the left ventricle (LV). In this study we evaluated the feasibility of calculating the EDV, ESV and LVEF from the area under the polar graph (APC) of the edges of the LV image determined by a first derivative edge-detection method., Methods and Results: Technetium-99m ((99m)Tc) sestamibi GSPECT studies and planar equilibrium radionuclide ventriculography (ERNV) were performed on 15 male subjects in whom the LVEF ranged from 19% to 75%. Images were reconstructed to obtain short axis slices of the LV spanning the cardiac cycle. On each slice the LV edge points were determined at 10 degrees intervals using the APC method. The area of each short axis slice was determined by conversion to polar co-ordinates, interpolation and numerical integration of the graphs and multiplication by a pre-determined conversion factor., Results: Edges were successfully determined in all 15 patients using the APC method. The LVEF results correlate well with conventional planar ERNV studies (r = 0.96, LVEF(GSPECT) = 8.80 + 0.66 LVEF( ERNV)). The absolute difference between the LVEF for ERNV and for the APC method was 6.1% with a standard deviation of 7.6%. The reproducibility of SPECT LVEF using the APC method was good (intra-observer r = 0.99, inter-observer r = 0.99)., Conclusions: The APC method provides for easy and accurate ejection fraction determination with limited underlying mathematical assumptions. The ability to interpolate the edge points provides for stable edge detection even in hypoperfused myocardium.

This paper shows the contribution that Monte Carlo methods make in regard to dose distribution calculations in CT based patient models and the role it plays as a gold standard to evaluate other dose calculation algorithms. The EGS4 based BEAM code was used to construct a generic 8 MV accelerator to obtain a series of x-ray field sources. These were used in the EGS4 based DOSXYZ code to generate beam data in a mathematical water phantom to set up a beam model in a commercial treatment planning system (TPS), CADPLAN V.2.7.9. Dose distributions were calculated with the Batho and ETAR inhomogeneity correction algorithms in head/sinus, lung, and prostate patient models for 2 x 2, 5 x 5, and 10 X 10 cm2 open x-ray beams. Corresponding dose distributions were calculated with DOSXYZ that were used as a benchmark. The dose comparisons are expressed in terms of 2D isodose distributions, percentage depth dose data, and dose difference volume histograms (DDVH's). Results indicated that the Batho and ETAR methods contained inaccuracies of 20%-70% in the maxillary sinus region in the head model. Large lung inhomogeneities irradiated with small fields gave rise to absorbed dose deviations of 10%-20%. It is shown for a 10 x 10 cm2 field that DOSXYZ models lateral scatter in lung that is not present in the Batho and ETAR methods. The ETAR and Batho methods are accurate within 3% in a prostate model. We showed how the performance of these inhomogeneity correction methods can be understood in realistic patient models using validated Monte Carlo codes such as BEAM and DOSXYZ.

Image degradation during single photon emission computed tomography (SPECT) due to attenuation and Compton scatter of photons can cause clinical image artifacts and will also result in inaccurate quantitative data. Therefore attenuation correction methods recently received wide interest. Transmission imaging can be performed to obtain the attenuation coefficients of a nonhomogeneous attenuating medium accurately. The aim of this study was firstly to evaluate the imaging characteristics of the scanning line source assembly. The results obtained with Tc-99m and Ce-139 were compared. Secondly the calculated attenuation coefficients were compared with known values from literature, using Tc-99m and Ce-139 as transmission sources. Lastly the method of acquiring simultaneous transmission and emission data was investigated. This study shows that an attenuation coefficient map can be obtained using a scanning line source for transmission imaging with a dual opposing detector camera. The imaging characteristics of Tc-99m and Ce-139 as transmission sources are similar. The resolution obtained with the Ce-139 line source was poorer than that obtained with the Tc-99m line source. A linear relationship was found between CT numbers and attenuation coefficients for transmission images using both Tc-99m and Ce-139 line sources. The attenuation coefficient value for water was underestimated by 1% using the Tc-99m transmission source and underestimated by 10% using Ce-139 as transmission source. This underestimation of attenuation coefficient values was also obtained in the human study. A myocardial perfusion study processed without and with attenuation correction clearly demonstrated the effect of the attenuation correction in the inferior myocardial region. The potential of using a scanning line source as transmission source with a dual opposing detector camera has been demonstrated in this study. The transmission source, Ce-139 was successfully introduced in this investigation for simultaneous acquisition of transmission and emission data.

Red cell volume (RCV) and plasma volume (PV) measurements are performed routinely in nuclear medicine departments to diagnose a number of haematological disorders. Currently, 125I-HSA is used as a plasma tracer and 99Tcm-labelled red cells to determine red cell volume. 125I-HSA is not always readily available, leading to inconvenience for patients and medical practitioners. Due to the availability of 99Tcm in nuclear medicine departments, the use of albumin labelled with 99Tcm was investigated. A new 99Tcm-human serum albumin labelling kit (99Tcm-DMP-HSA) was developed by Verbeke and supplied for use in this study. The main aim of the study was to investigate the use of 99Tcm-DMP-HSA for PV determination. Secondly, the feasibility to determine red cell and plasma volume simultaneously using 99Tcm as radionuclide in both instances was investigated. Fourteen healthy volunteers were enrolled in the dual-phase study. During the first study, 99Tcm-DMP-HSA was used as tracer to calculate PV (PV1a) after intravenous administration. Subsequently, 99Tcm-labelled red cells were administered and the PV (PV1b) and RCV (RCV1) were calculated. The second study was repeated within 2 weeks using the conventional method. 125I-HSA and 99Tcm-labelled red cells were administered simultaneously. The PV (PV2) and RCV (RCV2) were calculated. We found that the redistribution of 99Tcm-DMP-HSA is faster than that of 125I-HSA; therefore, the plasma counts obtained at different times were back-extrapolated to time zero for plasma volume calculations. The mean values for the different calculated PVs were 2964+/-470 ml for PV1a, 3006+/-623 ml for PV1b and 3001+/-530 ml for PV2, the reference PV. The confidence intervals indicate no significant differences between plasma volumes PV1a and PV2 and plasma volumes PV1a and PV1b. The mean calculated RCV1 was 2130+/-322 ml; that of RCV2 was 2128+/-353 ml. The difference between RCV1 and RCV2 was not significant. Our results indicate that 99Tcm-DMP-HSA could be used for plasma volume calculation. Red cell and plasma volumes can be calculated simultaneously using 99Tcm as radionuclide in both cases.

Unlabelled: The use of 99mTc-labeled red blood cells (RBC) for the evaluation of left ventricular function using equilibrium-gated blood-pool imaging suffers from several problems and potential risks. In this study, we estimated the absorbed radiation dose of 99mTc-labeled dimercaptopropionyl human serum albumin (DMP-HSA) as a potential alternative to 99mTc-RBC., Methods: After the administration of 99mTc-DMP-HSA, whole-body imaging was performed up to 48 h after injection in five volunteers. The heart contents, liver and remainder of the body were used as source organs. Multicompartment modeling of the biodistribution was performed and absorbed radiation dose estimates for 99mTc-DMP-HSA were obtained using the Medical Internal Radiation Dose (MIRD) calculation., Results: Residence times of 0.62 and 0.43 h were obtained for the heart contents and liver, respectively. Radiation dose estimates yielded an effective dose of 0.0055 mSv/MBq., Conclusion: 99MTC-DMP-HSA yielded absorbed radiation doses comparable with those of 99mTc-RBC. Therefore, the radiation properties of 99mTc-DMP-HSA are such that it can be used for clinical diagnostic studies.

Lepirudin has a short half-life, and only 50-60% of the intravenously administered dose is excreted by the kidneys. The fate of the remainder is unknown. We designed a study to determine the fate of this lepirudin. In each of six baboons, [131I]lepirudin was given intravenously as a bolus or infused over 30 min, 24 h apart. The in vivo redistribution of [131I]lepirudin was determined and quantified by scintillation camera imaging. In all studies, the half-life of [131I]lepirudin, as determined from the disappearance of radioactivity, was 21 +/- 3 min. The half-life determined from the disappearance of lepirudin, measured by the Ecarin Clotting Time (ECT) method, was similar at 23 +/- 8 min. Results obtained with the labeled lepirudin are therefore comparable with those obtained using the plasma concentration of lepirudin. When lepirudin was administered as a bolus, the half-life was 18 +/- 4 min, and lepirudin was cleared from the plasma at a rate of 42 +/- 12 mL/min and by the kidneys at 23 +/- 2 mL/min. Following infusion over 30 min, the half-life and total and renal clearances were not significantly different. In both studies, between 50 and 60% of the administered lepirudin was excreted by the kidney. Studies on sacrificed baboons showed that appreciable amounts of lepirudin were present in the bile, indicating the liver as a contributor to the elimination of lepirudin.

A number of Monte Carlo codes are available, which can be used to calculate dose distributions n patients with high accuracy. Patient geometry can readily be derived with adequate spatial resolution from CT scans. To perform the Monte Carlo calculation with the same spatial resolution, it is necessary to enter the atomic composition and density of the tissue in each voxel of the CT image. This means entering 65,536 discrete values for a CT slice with a 256 x 256 matrix size. The need for automated methods of setting up the material data files is obvious. Because there is no direct unique relationship between CT numbers and material composition, the aim of our work was to devise a method whereby the atomic composition and density in each voxel could be assigned automatically by indirect derivation from the CT numbers. The set of all tissues types in the human body was divided into subsets that are dosimetrically equivalent, based on Monte Carlo calculated depth dose curves in homogeneous phantoms of each tissue. CT number ranges corresponding to each tissue subset were determined from the calibration curve linking electron density with CT number for the specific CT scanner. Further subdivision was found to be necessary for the lung and bone type tissues. This was done by keeping the atomic composition constant and varying the physical density. It was found that 57 distinct tissue subsets were needed to represent the 16 main tissue types in the body at a 1% dose level. Corresponding CT number intervals of 30 HU were needed in the lung and soft tissue region, whereas in the bone region the intervals could be increased to 100 HU. A computer algorithm was set up to convert automatically from CT number to corresponding equivalent material number for the Monte Carlo preprocessor code.

A common complication in patients with breast or prostate cancer is bone metastases causing pain. New radionuclide therapy methods have recently been proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re-HEDP). This paper reports on the local development of 186Re-HEDP and the biodistribution studied in animals for eventual use in patients. Adult dose was computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using standard techniques. The biodistribution in five Chacma baboons (Papio ursinus) was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80 mCi). Whole-body images of the animals were obtained with a dual-headed scintillation camera on an hourly basis for 6 h post-injection and then daily for 3 days. The bone, soft tissue, kidneys and urinary bladder were considered source organs and data from these organs were used in a compartmental model to obtain the mean residence times of the radionuclide in the different source organs. Radiation dose estimates for 186Re-HEDP were subsequently obtained with the MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09; liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall 0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation dose delivered to the bone marrow in this study did not cause any detrimental effect to the baboons, indicating that locally produced 186Re-HEDP is suitable for clinical use.

Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation.

Several methods exist to eliminate the contribution of scattered photons during imaging. One of these, the channel ratio (CR) scatter correction technique, uses the change in the ratio of counts from two symmetrical adjacent energy windows straddling the energy photopeak. The accuracy of the results depends upon the assumption that the ratio of the scatter components in the two windows (H value) is constant and is independent of the relative size of the scatter contribution. In this study a Monte Carlo simulation was used to investigate the behaviour of the scatter component for different source sizes at different depths. Four disc sources containing a 99Tcm solution were simulated at different depths as imaged with a scintillation camera. Two 10% energy windows with 5% offsets to either side of the 140 keV photopeak of 99Tcm were used. The ratio of the scattered counts in the lower energy window to the scattered counts in the upper window (true H value) was determined from the simulation for each source at every depth. Since it is impossible to measure the true H value at different organ depths during a clinical study, the use of an average H value was considered. Scatter correction was applied to the images simulated at the various depths in water. The geometric mean was calculated and attenuation correction performed assuming mono-exponential attenuation. For quantitation purposes the corrected counts were expressed in terms of a references source. The choice of the reference source yielding the best quantitative results was also investigated. Results of this Monte Carlo simulation study show that although the true H value depends on both source size and depth of the source in the scattering medium, the CR scatter correction technique can be applied successfully when an average H value is used.

Ferrous-sulfate-doped gelatin gel dosimeters are useful tools for the measurement of three-dimensional absorbed radiation dose distributions. The diffusion of ferric ions through these gels causes degradation with time of the dose distribution image. It would be useful to reduce ferric ion diffusion without decreasing gel sensitivity. The amount of ferric ion diffusion is a function of the time delay after radiation, the gel temperature, and the gel concentration. These effects can be quantified by measuring the ferric ion diffusion coefficient. Determination of the diffusion coefficient by irradiating the lower section of a cylinder of gel, which was then imaged repeatedly over time with a clinical magnetic resonance imager, is described. Analysis of the edge spread function formed at each of several times after irradiation by drawing a profile over the imaged junction between the irradiated and unirradiated halves of the cylinder, gave estimates of the variance of the edge spread function. These variances were used to obtain an estimate of the ferric ion diffusion coefficient for the gel. A method of reducing ferric ion diffusion by adding a chelator and the cross linkage agent formaldehyde is suggested. The chelators investigated were 1,10 phenanthroline, xylenol orange, and bathophenanthroline disulfonic acid. These reduced diffusion to varying extents, and influenced the gel sensitivity. The diffusion coefficient in gels containing xylenol orange was found to be 0.44 mm2h-1. The gel sensitivity was 0.0093 s-1Gy-1. This compared with a diffusion coefficient of 0.82 mm2h-1 for the base line gel that did not contain formaldehyde or chelators. The sensitivity of this base line gel was 0.0129 s-1Gy-1. The addition of xylenol orange produced the most improved gel dosimeter of the gels studied. This gel had a decreased ferric ion diffusion coefficient and a decreased sensitivity. It was still sensitive enough to be useful.

In a study group of 20 healthy young men, splenic volume was determined with SPECT before and after exercise. A randomly chosen control group of 10 comparable men was studied similarly, but without exercise intervention. The mean splenic volume did not change significantly in the control group (i.e., from 292.9 ml to 282.1 ml [P = 0.75]). The mean splenic volume decreased 60.1 ml from 279.4 to 219.3 ml (21.5%) in the study group and this was highly significant (P = 0.01). Although exercise induced splenic autotransfusion is generally considered to be unimportant in humans, significant splenic contractility was observed with this technique. In the normal individual with a large spleen or with functional splenomegaly, the contractility response may become more important and can now be measured in a quick and easy manner.

Objective: The direct urinary activity quantitation method is quick (approximately 40 minutes), requires only a single blood sample, is performed as part of standard renal scanning and shows high accuracy compared with 24-hour creatinine clearance. The purpose was to evaluate the practical application and accuracy of this technique at our clinic., Design: Direct urinary activity quantitation was done in patients scheduled for routine radionuclide renography and compared to standard multiple-blood-sample techniques by means of Cr-51-EDTA and Tc-99m-DTPA., Setting: Academic Medical Complex, Department of Nuclear Medicine, Universitas Hospital, Bloemfontein., Participants: Fifteen patients scheduled for routine radionuclide renography (glomerular filtration rate (GFR) determination) were voluntarily enrolled in the study. The GFRs of selected patients varied over a wide range. Possible obstructive uropathy was excluded., Main Outcome Measures: GFRs obtained by the direct urinary method were compared with GFRs determined by multisample Cr-51-EDTA and Tc-99m DTPA., Results: GFRs from the direct urinary method compared with multisample Tc-99m-DTPA showed differences from -19.85 to 22.95 ml/min with a mean of 0.2 (+/- 12.25) ml/min (r = 0.93). When compared with multisample Cr-51 EDTA, differences ranged from -34.35 to 21.05 ml/min with a mean of -4.25 (+/- 16.08) ml/min (r = 0.90)., Conclusion: The direct urinary activity technique is, Conclusion: The direct urinary activity technique is easily applied and highly accurate compared with previous standardised multisample radionuclide techniques for determination of GFR.

An inexpensive system for obtaining cross-sectional information and accurate body outlines of patients destined for radiotherapy, using a radiotherapy simulator without any major modifications, has been investigated. The image intensifier of the simulator was moved laterally and a narrow fan beam of X-rays passed through the phantom onto the intensifier. Several television (TV) lines of the video signal from the TV camera were digitized by a frame grabber and stored for reconstruction. Multiple projections were acquired by rotating the gantry of the simulator. The field of view was enlarged by increasing the offset distance of the image intensifier and taking two sets of projections. Reconstruction was carried out by using the convolution and back-projection method. The gradient between pixel values in the reconstructed images was used to detect the outlines of structures in the images. The accuracy of outline detection was evaluated with images of a Rando phantom. The outlines of the images were compared with the actual outlines of the phantom. The spatial resolution of the simulator computed tomography (CT) was measured to be 4.05 mm. Large inhomogeneities could be clearly seen. The average difference between the measured and the actual outlines was 3.0 mm with a maximum difference of 10.0 mm at sharp curves in the outline. The simulator CT provides an inexpensive, alternative method of obtaining body outlines and does not require any modifications to the simulator. Data acquisition, processing and display can be performed on a personal computer with image processing facilities.

It is important that staff radiation doses be kept 'as low as reasonably achievable' (ALARA). Staff working in the radiopharmacy and nursing staff responsible for injecting radionuclides are being monitored constantly in our department. We report here on the effective doses and doses to the hands received by staff at two hospitals during 8 years from January 1985 to December 1992. In addition to the doses determined monthly by the South African Bureau of Standards' Radiation Protection Service (SABS), radiation doses received to the hands and whole body were measured every week using lithium fluoride thermoluminescent dosimetry (TLD). The workload (number of patient studies each year) and the estimated amount of 99Tcm received per month were also established, and results have been expressed in relation to these where possible. The combined radiation doses and the absorbed dose per unit activity a single radiographer would have received, since 1988 when radiopharmacy duties were centralized, were calculated. The highest total radiation dose received in any one year by any one person at hospital A was 223.53 mSv to the hands, and 10.20 mSv and 8.37 mSv to the whole body depending on the dosimeter used. The corresponding values for hospital B were 54.05 mSv to the hands and 6.94 mSv and 4.43 mSv to the whole body. If only one radiographer should do all the work the calculated highest dose received would be 447.06 mSv to the hands and 9.68 mSv SABS effective dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Twelve patients with Dacron aortic grafts participated in a placebo controlled, crossover trial to investigate the effect of Bay u3405, a thromboxane A2 receptor antagonist, on graft thrombogenicity. During each treatment period (seven days, Bay u3405 or placebo), 111In-platelet survival and platelet deposition on the grafts were measured daily by gamma-camera imaging and blood radioactivity analysis. Bay u3405 substantially reduced the deposition of platelets and the thrombogenic index, while platelet survival remained unchanged. The ex vivo platelet aggregation response to ADP and epinephrine was significantly inhibited. The bleeding time increased slightly but not to any clinically relevant extent, and no adverse side effects were recorded. Bay u3405 seems to be a safe and effective drug for the inhibition of platelet deposition on aortic Dacron grafts. The use of quantitative imaging techniques is also more sensitive than the measurement of platelet survival for the assessment of antiplatelet drug efficacy in patients with aortic grafts.

Platelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/10(8) platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p < 0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p < 0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/10(8) platelets was removed (p < 0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

High image quality and low radiation levels are essential in mammography. This study investigates the effect of changes in processor temperatures and developing times on sensitometric findings. These findings were matched with the changes in the image quality during similar changes in the developing parameters. Temperatures ranging between 35 degrees C and 40 degrees C and developing times from 20 s and 50 s were investigated. Higher developing temperatures and increased developing times resulted in an increase in film speed and film contrast. A definite pattern of change could be demonstrated in film speed and film contrast during sensitometry. The same pattern of change could, however, not be demonstrated in the quality of phantom images under similar circumstances. The base plus fog level was not adversely affected. Sensitometric findings of film speed can be effectively used as an indicator of radiation exposure to the patient, but cannot be used to establish the developing parameters that will give the best image quality. Both these methods should be used to determine which processing variables should be used to obtain a combination of the best image with radiation as low as possible. Recommendations for optimum processing parameters are made for the films and processing chemistry investigated.

SPECT enables quantitation of organ volume with radionuclide techniques using threshold edge detection methods. Previous phantom studies showed that a negative correlation exists between volume and threshold value. In those studies, the use of calibration curves were believed to correct for volume dependence on threshold values. The aim of this study was to evaluate the accuracy of spleen volume determination in 20 patients with SPECT by employing a varying threshold edge detection technique with volumes derived from CT. All patients had both radionuclide and CT examinations that were reconstructed with a filtered backprojection algorithm. During SPECT reconstruction, transverse slices were obtained with attenuation correction (Method A) and without attenuation correction (Method B). CT volumes were calculated from manually drawn regions of interest, whereas SPECT volumes were calculated with an automated algorithm using previously determined calibration curves. A confidence interval for calculated SPECT volumes also was calculated because of possible errors in the threshold value. The spleen volumes studied ranged from 91.2 ml to 1660.1 ml. Regression analysis yielded equations of CT = 0.97 SPECT + 7.07 (r = 0.996) and CT = 1.05 SPECT - 19.25 (r = 0.990) between CT and SPECT spleen volumes with a standard error of the y estimates of 31.10 ml and 54.47 ml, respectively. A mean percentage difference of 10.5% +/- 7.6% and 11.4% +/- 6.6% in spleen volume was obtained for Methods A and B in comparison with CT spleen volumes. The threshold value varied between 40.9% and 32.4% for Method A and between 41.2% and 28.5% for Method B because the spleen volume is increased. The varying threshold edge detection technique described in this paper can be implemented successfully in the clinical setting.

Human milk fat globule (HMFG) monoclonal antibodies labelled with 123I and 111In are used for the diagnosis of ovarian and breast cancer. Methods have been developed to label HMFG with 99mTc and this study reports on the subsequent radiation dose delivered. The 99mTc HMFG1 distribution was obtained in 5 normal female baboons up to 71 h after administration. The liver, kidneys, bladder and whole body were identified as source organs and total absorbed doses for the target organs were 0.054 (kidneys), 0.013 (liver), 0.140 (bladder), 0.010 (ovaria), 0.004 (bone marrow), 0.002 (thyroid), 0.003 (heart wall), 0.017 (uterus) and 0.005 mGy/MBq (whole body). The effective dose was 0.014 mSv/MBq.

The accuracy of quantitation of radionuclide distributions in human tissue with the scintillation camera is decreased by attenuation and scatter of photons. If scatter correction is applied satisfactorily, narrow beam attenuation can be applied. In this article, a scatter correction technique, the channel ratio (CR) method, is introduced. The CR scatter correction method is proposed for quantitation of the radionuclide distribution in organs. The improvement in the geometrical resolution was measured and examples of clinical images are presented. In this method, the change in the ratio of counts from two symmetrical adjacent energy windows straddling the energy photopeak was used to eliminate the contribution of scattered photons during imaging with 99mTc. The theory and methods for the empirical affirmation are described. To apply the CR scatter correction method, two constants, the ratio of primary photons G and the ratio of scattered photons H in the same windows, were determined. Different sized sources in varying depths of water were imaged. When the source activities were quantified after scatter correction with the CR method, the measurements ranged from 96%-108% in comparison to the reference value in 100 mm water. The scatter fraction increased from 0.20 in 10 mm water to 1.44 in 200 mm water. The geometrical resolution expressed as full width at tenth maximum in 150 mm water improved by 30.4% and was restored to the value of the geometrical resolution in air. The CR scatter correction method is a simple method to correct for scatter in order to facilitate accurate quantitation of the radionuclide distribution during imaging with a scintillation camera.

In patients with arterial grafts, platelet consumption may be due either to platelet interaction with the graft, and/or concomitant platelet consumption in the rest of the arterial tree. This hypothesis was tested by quantifying the kinetics and platelet-graft interaction of indium-111-labelled platelets with double velour Dacron grafts in 13 patients with arterial insufficiency ascribed to atherosclerosis. Mean platelet lifespan (MPLS), 149 +/- 46 hours, was significantly shorter (P = 0.001) than normal. Labelled platelets were transiently deposited onto the graft surfaces. Peak 111In deposition on the grafts, 1.33 +/- 1.02% of injected labelled platelets, was reached at 70 +/- 33 hours. Thereafter the graft-platelet radioactivity decreased in parallel with platelet radioactivity in the circulation. There was no statistical correlation between MPLS and the factors known to be associated with graft platelet deposition: graft size; peak graft radioactivity; and the time to attain peak graft radioactivity. It is therefore concluded that in patients with arterial disease requiring graft implantation, the observed increased platelet consumption cannot only be ascribed to the interaction of platelets with the graft. Concomitant atherosclerosis is probably the important modifier of platelet consumption. The significant contribution of this factor to the shortening of the MPLS should be taken into account when assessing, by measuring platelet lifespan, the thrombogenicity of grafts.

The purpose of this study was to describe the function of platelets throughout their life span by expressing their in vivo distribution and kinetic behaviour in mathematical terms by using multicompartmental analysis. The distribution of indium-111 labelled platelets in five normal subjects was imaged and quantified with a scintillation camera image processing system. Serial blood samples were also obtained. The data were modelled using the SAAM (Simulation Analysis and Modelling) compartmental computer program. Five models were entertained to evaluate the role of platelets that were either functional or injured during collection and their interaction with the liver, spleen and vascular endothelium. Models were evaluated by comparing F values calculated from the least squares estimate obtained from each model. The Dornhorst function was used to describe the sequestration of platelets in the compartmental model. Results indicated that the data could not be satisfactorily simulated when compartments were included that simulated only functional and sequestered platelets (model 1). It was necessary to include compartments that simulated the kinetics of collection-injured platelets in the liver (model 2) and spleen (model 3). The model that simulated the interaction with the vascular endothelium (model 5) showed a visual but not significant improvement in the fitting of the observed data compared to model 3. The mean organ uptake and range indicated in parentheses were calculated at equilibrium. There were 20% (15%-27%) of the injected platelets in the spleen, 10% (8%-11%) in the liver and 70% (64%-75%) in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The first purpose of this investigation was to investigate in 35 young normal male subjects the use of the Dornhorst function and the weighted-mean method to calculate reference values for mean red cell survival time with and without correction for elution of 51Cr. We compared survival times calculated with the Dornhorst and weighted-mean methods with survival time estimated with linear or exponential models. Two methods to correct for elution of 51Cr from red cells were investigated. For the first method, correction factors were generated using the Dornhorst function fitted to mean survival curves obtained from the normal subjects. In the second method, the new Dornhorst rate constant method, the survival time, corrected for elution of 51Cr, was directly calculated from the experimental survival curve without applying correction factors. Correction for elution using the Dornhorst rate constant method was not successful and resulted in nonphysiologic values. The 95% confidence range of red cell survival time for reference subjects without correction for 51Cr elution was 37-74 days for the weighted-mean method and 37 to 73 days for the Dornhorst method. The 95% confidence range for normal subjects when the survival curves were corrected for elution was 47-179 days for the Dornhorst method and 58-161 days for the weighted-mean method. The poor results obtained with the Dornhorst rate constant method and the large 95% confidence range were due to the rapid and large variation in elution rate of 51Cr from red cells.

Quantitation of planar radionuclide images is hampered by structures containing radioactivity which overlie or underlie the organ of interest. The introduction of single photon emission computerized tomography (SPECT) overcame this problem to a large extent and enhanced the contrast of the images. Attenuation of photons, however, degrades the resultant SPECT images and correction methods for photon absorption and scatter were subsequently proposed. The different correction methods have variable effects on the reconstructed images. If threshold techniques are used to quantitate organ volume, i.e., combining pixels with the same percentage of the maximum pixel count in the volume, the selected threshold values which give the most accurate volume determination, will be affected by the specific correction method used. In this study, the effect of various SPECT image correction methods on threshold was investigated. A thorax phantom containing volumes ranging from 30 to 1200 ml was used. Threshold values varying from 45.6% (210 ml without any correction) to 23.7% (1200 ml with a combination of scatter subtraction and attenuation correction) were used to produce correct quantitation when different methods were investigated. A negative correlation was found between threshold and volume. This reduction in threshold was most prominent when scatter and attenuation correction were combined. This study shows that correction methods for attenuation of photons influence the threshold value for volume quantitation and the use of a constant threshold value could lead to underestimation of larger volumes.

This paper describes data collection during open chest cardiovascular research based on an IBM compatible personal computer. Data from eight analogue data channels are collected at a rate of 500 Hz per channel for a period of more than 40 sec per run. General analysis functions include the integration of the data obtained from any channel as well as an exponential curve fitting routine. Special functions are available for the calculation of cardiac parameters. This includes the automatic determination of end-diastole and end-systole, as well as maximum and minimum values of all curves for both the systolic and diastolic phases of contraction.

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.

A single and practical approach to the in vivo quantification of 111indium-oxine labelled blood platelets with a scintillation camera and computer assisted imaging system was evaluated. Radioactivity of the 172 and 247 keV energies was measured in a phantom at various source distances from the collimator and the accuracy of anterior and posterior mode measurements compared with that of the geometrical mean (GM) method, with and without correction for Compton scatter (CS). Organ radioactivity, expressed as a percentage of whole body radioactivity, was determined in vivo in five baboons and the accuracy of the methods verified by post mortem quantification in the animals. Measurements in the anterior mode significantly overestimates hepatic and underestimates splenic radioactivity; posterior mode quantification reverses these results. Correction with the GM method made the accuracy and reproducibility very acceptable. Further correction for anterior-posterior attenuation and/or CS did not improve results materially. The GM method could readily be applied in five human subjects. This study showed that the GM method is an accurate and practical method for the in vivo quantification of organ and regional distribution of 111In-labelled platelets.

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.

The kinetics and sites of sequestration of a fully representative population of In-111-platelets were determined in 11 baboons. The in vivo method of quantification with computer assisted scintillation camera image analysis was validated by sacrificing 5 baboons and measuring and comparing the distribution of organ radioactivity. Recovery of platelets in the circulation was 87% +/- 7, and their mean survival time was 147 hr +/- 15. The mean splenic platelet pool was 16.0 +/- 1.9. At equilibrium 15.8% +/- 2.9 of the In-111-platelets were in the hepatic blood pool. Senescent platelets were destroyed in the reticulo-endothelial system. The major sites of sequestration were: liver (37.6% +/- 6.0), and the spleen (23.3% +/- 4.6). The bone marrow sequestrated 14.4% +/- 1.7 of the labelled platelets, and 15.5% +/- 4.0 were present in various other tissues. We conclude that the in vivo method of In-111-quantification is accurate. Senescent platelets are mainly sequestrated in the reticuloendothelial tissue, with the liver, spleen and the bone marrow important sites of sequestration.

The survival, tissue distribution and fate of 111In-oxine labelled autologous platelets in six normal humans were studied with serial blood sampling, scintillation camera and computer-assisted imaging, whole body profile scanning, and rectilinear scanning. 111In-platelets recovery in the circulation was 72+/-16% and survival was 216+/-17 h. Platelet survival curves fitted a linear function best. Initially platelets pooled rapidly in the spleen as a single exponential function, and at 90 min 26% of the injected 111In was located in this organ. Early hepatic uptake was also significant and at 90 min constituted 16% of total body 111In-activity. As labelled platelets disappeared from the circulation there was a threefold increase of radioactivity in the liver to reach 39% of whole body activity at 216 h. Radioactivity also increased significantly in the spleen (33.3% at 216 h). There was significant residual radioactivity in the thoracic and lower abdominal regions at 216 h, suggesting that platelets are also sequestered in the bone marrow. Radioactivity in the lower limbs almost disappeared with time (0.7% at 216 h), indicating that utilization of platelets in the peripheral vasculature is not marked in normal subjects.

A new approach for the study of the kinetics and quantification of the in vivo and ex vivo sites of sequestration of platelets during cardiopulmonary bypass (CPB) is described. Autologous platelets of four patients were labeled with 111In-oxine and reinfused on the day prior to CPB for coronary artery bypass grafting. Changes in blood 111In-labeled platelet radioactivity and blood platelet counts were monitored during the operation. In vivo 111In-labeled platelet redistribution was quantified with a scintillation camera and a computer-assisted imaging system before and after CPB. Sequestration of 111In-labeled platelets in the bubble oxygenator was measured. 111In-labeled platelet activity in the blood decreased by 46% +/- 5% within 5 minutes of CPB, but this decrease was mostly due to hemodilution; the true loss of platelets from the circulation was 13% +/- 4%. Intraoperatively, whole body 111In activity decreased by oxygenator 10.8% +/- 1.3% of administered platelets were sequestered, especially in the innermost active layers of the defoaming mesh of the bubble oxygenator. Mean survival time of circulating platelets was 58 +/- 8 hours and fitted an exponential function best. The bleeding time increased to 40 minutes during operation and returned to normal within 24 hours. During operation 111In-labeled platelets accumulated somewhat in the liver (10.7%) but not in the spleen, thorax, or head. In the 48 hours after operation, platelets were sequestered mainly in the liver. The scintillation camera with computer-assisted imaging allows in vivo quantitative studies of platelet kinetics of a type which has not been possible with previous techniques.

It is shown how to calculate optimal weights for the weighted mean method which is applied in radioisotope survival studies.

We describe an adapted first-transit (FT) technique to perform left ventricular ejection fraction (LVEF) measurements on patients with Swan-Ganz catheters in the intensive cardiac care unit (ICCU). The radionuclide is introduced directly into the right pulmonary artery through the catheter. High-quality images of the left ventricle are obtained owing to minimal activity in the right ventricle and left lung. LVEF measurements obtained by FT compared well with measurements obtained from gated blood pool studies (r = 0.91) but gave consistently lower values. The adapted FT method improves LVEF determination and left-ventricular wall motion evaluation in the ICCU patient.

We developed an easy-to-operate computer program for the IBM personal computer to calculate, display and store in a database platelet kinetic data determined by analysis of the rate of clearance of radiolabeled blood platelets from the circulation. This was done by curve fitting using the weighted mean method and multiple-hit model. These models are complementary and calculating the mean platelet survival time with both is recommended. Improvement of the weighted mean method was investigated. The optimized weighting and fitting the exponential function with the Marquardt non-linear least squares method improved the weighted mean method. The weighted mean and multiple-hit models fit the survival curve data equally well. The calculation of the mean platelet survival time with the weighted mean method was very fast. The duration of calculation with the multiple-hit model could take up to 2 minutes. Calculation of the mean platelet survival time using both models has the advantage that conditions when calculation of the mean platelet survival time would be invalid, can be detected. The computer program will promote the valid comparison of results obtained at different institutions.

The interpretation of platelet beta-thromboglobulin (BTG) and platelet factor 4 (PF4) levels as indicators of in vivo platelet activation is complicated by the artefactual release of these proteins in vitro. A formula was devised to correct for in vitro platelet activation and release of BTG. Blood was collected from normal volunteers by an ideal method and BTG and PF4 levels determined by radioimmunoassay; these were the reference values. Blood from normal volunteers was activated in vitro by standing at room temperature. The BTG and PF4 released was measured at different time intervals. The relationship between BTG and PF4 released was measured at different time intervals. The relationship between BTG and PF4 was measured mathematically best described by a second degree polynomial function. The true plasma BTG value was then calculated by correcting for in vitro release by the general formula: BTG corrected = BTG measured - BtG for PF4 measured + BtG for PF4 reference The validity of the correction formula was tested in 10 normal subjects and in patients with either recent myocardial infarction(n = 10), familial hypercholesterolaemia(n = 10) or arterial prostheses(n = 14). Correction was adequate in normal subjects if the plasma BTG levels did not exceed 260ng/ml. In patients with a thrombotic tendency, the formula overcorrected for in vitro release. This could be ascribed to increased in vivo PF4 levels in these patients, especially those with prostheses. The reference values for PF4 in these patients, and especially those with vascular prostheses, were also higher than normal. The PF4 measured in their plasma thus reflects both in vivo and in vitro released protein. The hypothesis on which the correction formula was based, is therefore not always applicable. It may be possible to improve the correction by establishing formulae for specific disease groups.

The accurate quantification of the in vivo distribution of 111In labeled platelets, other cells, and proteins with a scintillation camera is important in clinical and experimental medicine. Planar techniques of image quantification were therefore evaluated with the aim of improving on the accuracy, and simplifying the techniques currently in use. The attenuation of the 172- and 247-keV photons of 111In, singly and in combination, was determined for varying diameter flat sources (3.4 to 16.9 cm). The influence of region of interest (ROI) selection on the shape of the attenuation curves was also determined for five different ROI's. Defining the attenuation curves mathematically generated parameters of fit for three approaches to in vivo quantification, namely: a single exponential geometric mean approach that takes into account source size, depth-dependent, and depth-independent buildup factor approaches to account for the contribution of scatter. The accuracy of these techniques was ascertained and compared to the classical geometric mean method. This was done in a waxen phantom of a human thorax with a hollow liver and spleen. The results indicated that the depth-independent buildup factor is the best method; the error for quantification in the spleen was 0.8% +/- 2.2%. The classical geometric mean approach gave a corresponding error of 43.3% +/- 3.4%. Since the attenuation of the two energies of 111In differ, their ratio changes with depth. This phenomenon was investigated with the goal of determining whether the depth of an object can be estimated from one set of planar images. This was not successful.(ABSTRACT TRUNCATED AT 250 WORDS)

A sterile pyrogen-free generator for ultra-short half-life 81mKr has been developed. During initial loading, the binding efficiency of 81Rb is 90--99%. The count rate during perfusion is 3 x 10(5) counts per minute for a 1,9 GBq (50 mCi) 81Rb generator. The generator has been used for routine and special investigations of lung perfusion and ventilation and for myocardial perfusion during catheterization.

We describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 X 10(9)/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% +/- 21 of platelets were harvested from the blood, labelled with 49% +/- 24 efficiency and 15.8 X 10(8) labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.

The pathogenesis of thrombocytopenia induced by intravenous protamine sulphate was studied in six patients who underwent cardiopulmonary bypass surgery, and in three normal volunteers. Autologous platelets were labelled with (111)Indium-oxine. Platelet lifespan was determined. In vivo (111)In-platelet localization, organ redistribution and sites of destruction were quantitated with a scintillation camera and a computer-assisted imaging system. Protamine induced a transient thrombocytopenia, maximal 5-10 min after injection, and 30-40 min in duration. . The thrombocytopenia was accompanied by a transient accumulation of platelets in the liver. The splenic platelet pool remained unaltered and no platelets accumulated in the lungs. Platelet survival, measured in two volunteers, was slightly longer than normal and fitted a linear function best. There was a severe transient neutropenia during the period of thrombocytopenia. We conclude that protamine-induced thrombocytopenia is caused by hepatic accumulation of "activated" platelets or platelet aggregates, the process is reversible, and in the two normal volunteers studied, platelet survival was not affected.

A significant improvement in cardiovascular nuclear medicine has resulted from imaging the beating ventricles by motion-picture display of the intraventricular distribution of 99mTc albumin during 16 phases of the cardiac cycle. We have now begun to make "fast-motion" pictures of other body functions, including the cerebral circulation, pulmonary ventilation, biliary excretion, and renal blood flow. Data obtained over minutes, hours or days are compressed into 16 frames per second. These "compressed-time" images improve our perception of regional dysfunction, and the degree of certainly of our diagnoses. They do so by eliminating the blurring inevitably produced in the usual static images of moving structures, such as the heart, and by revealing small changes in regional function.

Diagnosis of a traumatic aorta-superior vena cava fistula in a 54-year-old man is reported, and the value of radionuclide angiocardiography in detecting and localizing the lesion is described.