Richard S. Lawson

Attenuation correction of myocardial Spect studies using low resolution computed tomography images

ObjectivesArtefacts caused by tissue attenuation can create problems in the interpretation of myocardial perfusion studies. This study aimed to determine if attenuation correction using the ‘Hawkeye’ low-resolution X-ray computed tomography facility attached to a GE Millennium VG gamma camera reduced attenuation artefacts in our patient group. This technique offers potential advantages over isotope transmission methods of attenuation correction because of the lack of noise in the transmission images. MethodsNinety-four patients (64 males, 30 females) underwent stress/rest myocardial perfusion imaging using 99mTc tetrofosmin (188 studies). Semi-quantitative analysis of the attenuation corrected and non-corrected perfusion images was carried out using proprietary software (Emory ECToolbox). ResultsNo significant differences between attenuation corrected and non-corrected images were seen in the septal, lateral or apical segments. Attenuation correction produced a significant reduction in the defect scores in the inferior segment indicating the presence of attenuation artefacts. This was more marked in male patients. The incidence of attenuation artefacts in the inferior segment increased with weight although patients of normal weight also showed attenuation artefacts. The changes in the anterior segment were more difficult to interpret particularly in females, with attenuation correction increasing the defect score in some patients. Minor degrees of mal-registration (even of 1 pixel) between emission and transmission images increased the likelihood of creating a defect. ConclusionAttenuation correction using Hawkeye is likely to improve diagnostic accuracy in men, but is less likely to be useful in women.

Probing the Biogeochemical Behavior of Technetium Using a Novel Nuclear Imaging Approach

Dynamic gamma-camera imaging of radiotracer technetium ((99m)Tc) was used to assess the impact of biostimulation of metal-reducing bacteria on technetium mobility at 10(-12) mol L(-1) concentrations in sediments. Addition of the electron donor acetate was used to stimulate a redox profile in sediment columns, from oxic to Fe(III)-reducing conditions. When (99m)Tc was pumped through the columns, real-time gamma-camera imaging combined with geochemical analyses showed technetium was localized in regions containing biogenic Fe(II). In parallel experiments, electron microscopy with energy-dispersive X-ray (EDX) mapping confirmed sediment-bound Tc was associated with iron, while X-ray absorption spectroscopy (XAS) confirmed reduction of Tc(VII) to poorly soluble Tc(IV). Molecular analyses of microbial communities in these experiments supported a direct link between biogenic Fe(II) accumulation and Tc(VII) reductive precipitation, with Fe(III)-reducing bacteria more abundant in technetium immobilization zones. This offers a novel approach to assessing radionuclide mobility at ultratrace concentrations in real-time biogeochemical experiments, and confirms the effectiveness of biostimulation of Fe(III)-reducing bacteria in immobilizing technetium.

Application of mathematical methods in dynamic nuclear medicine studies

Dynamic nuclear medicine studies can generate large quantities of data, and their analysis consists essentially of a reduction of these data to a small number of relevant parameters which will assist in clinical decision making. This review examines some of the mathematical techniques that have been used in the process of data reduction and attempts to explain the principles behind their application. It particularly identifies the techniques that have stood the test of time and demonstrated their usefulness, many of which are now available as standard tools on nuclear medicine processing computers. These include curve processing tools such as smoothing, fitting and factor analysis, as well as tools based on empirical models, such as the Patlak/Rutland plot and deconvolution. Compartmental models and vascular models are also examined and the review finishes with a summary of some functional images and condensed images. It is concluded that an appreciation of the principles and limitations of these mathematical tools is valuable for their correct usage and interpretation of the results produced.

Technegas and pertechnegas particle size distribution

Technegas and Pertechnegas are radioactive aerosols produced in a commercial generator and used for lung scintigraphy. The aerosols are produced by first evaporating to dryness standard technetium-99m generator eluate (99m-TcO4 in normal saline) in a graphite crucible (thesimmer stage) and then heating this to 2500° C (the „burn” stage). The aim of this work was to measure the particle size distributions of these agents and relate this to regional lung deposition. Factors that may vary during production of the aerosol in routine use were investigated to determine whether they influenced the particle size. Activity size distributions were measured using a serial wire-screen diffusion battery. The Technegas size distribution was approximately log-normal with an activity median diameter of 158 nm and a geometric standard deviation of 1.5. The results for Pertechnegas were similar. The median size increased with the number of simmers and with the time from generation. The increase in size with the number of simmers is thought to be due to the increased salt content in the crucible prior to the „burn”. The predicted lung deposition is 37% in the alveolar region and 5% in the bronchial region. Significant changes in deposition are not predicted over the range of particle sizes measured.

Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling

UNLABELLED Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION There are several significant differences in GFR and ECV between healthy men and women.

The importance of using anterior and posterior views in the calculation of differential renal function using 99Tcm-DMSA

Radionuclide techniques for determining relative renal function are well established. One simple method uses the count rate from static images obtained using 99Tcm-dimercaptosuccinic acid (DMSA). We have reviewed 277 DMSA scans and shown that it is important to obtain the geometric mean of counts from the anterior and posterior views in order to correct for the different amounts of attenuation for each kidney. If counts were obtained from the posterior view only, erroneous results would be obtained in 8% of children under 13 years, in 28% of patients aged between 13 and 20 years and in 32% of patients over 20 years of age.

Evaluation of 99mTc(CO)5I as a potential lung perfusion agent

INTRODUCTION The use of (99m)Tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its potential as a lung perfusion agent. METHODS (99m)Tc(CO)(5)I was synthesized by carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using (99m)Tc-MAA. RESULTS Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood, 0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney, 0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney, 1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake. CONCLUSION (99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.

Cellular dosimetry of diagnostic radionuclides for spherical and ellipsoidal geometry

Radionuclides which emit Auger electrons are widely used in diagnostic nuclear medicine. Studies have shown possible uptake of these in developing germ cells within the testes. In addition, mature sperm within the reproductive tract may be subject to uptake of radionuclides from the circulating blood pool. Though much work has been carried out concerning cellular dosimetry applied to spherical sources, such an approach may lead to significant errors when considering spermatids and spermatozoa, which are almost ellipsoidal in shape (with the long axis twice the short). A numerical method for determining geometrical reduction factors has been developed and used in conjunction with experimentally determined range-energy relationships for electrons, to determine dose gradients and S factors for homogeneous distributions of four commonly used diagnostic radionuclides (99mTc, 111In, 123I and 201Tl) throughout source regions of both spherical and ellipsoidal geometry at typical cellular dimensions. The results indicate that assumption of spherical geometry is acceptable when determining S factors for late-type germ cells, but introduces error into calculations of dose distribution towards the edge of the cell.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors

PurposeThe objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV.MethodsFifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28–146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV.ResultsThe departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR.ConclusionThe CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

The use of the L-curve method in the inversion of diffusion battery data

Regularisation techniques are often employed to find a unique solutions to the diffusion battery data inversion problem. This involves minimising a function of the form A + λB, where A measures the fit to the data and B measures the smoothness of the solution. The quality of the solution is critically dependent on the choice of λ. if A is plotted against B for all λ values then a curve with a characteristics L-shape is obtained and the solution at the corner has an optimum balance of fit and smoothness. We demonstrate the usefulness of the L-curve method in this application and show that it provides a good means of choosing λ. It has the particular advantage that solutions are independent of error estimates. We also show that the solutions obtained are superior to those obtained by Twomeys non-linear inversion algorithm.