Lars Jødal

Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance.

Background. Total plasma clearance of 51Cr‐EDTA, Cl, is widely used as a measure of GFR. Commonly, only the final part of the plasma concentration curve is measured, and a one‐pool clearance (slope‐intercept clearance), Cl1, is computed. Empirically determined second‐order polynomials of the general form Cl = b⋅Cl1+c⋅Cl12 are usually used to estimate Cl from a measured Cl1. However, theoretical considerations indicate that such corrections underestimate Cl at high values. Aims. To derive an analytically correct relationship between Cl and Cl1 and determine the parameters involved for children and adults. Material and methods. Cl was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma concentration curve followed for 4–5 h after injection of 51Cr‐EDTA (range of clearance: 8–183 mL/min/1.73 m2). Plasma volume, PV and the “missing” area under the plasma fraction curve, a (minutes), not used for determination of Cl1, were measured. Results. The true relationship between Cl and Cl1 is given by Cl = Cl1/(1+f⋅Cl1), where f = a/PV. For men, women and children alike, the equation f = 0.0032⋅BSA−1.3 was applicable (BSA = body surface area in m2). Estimation errors on clearance were within ±8 % for adults and ±13 % for children (95 % limits of agreement). Conclusions. The true relationship between Cl and Cl1 of 51Cr‐EDTA is given, resulting in a common correction equation applicable for children and adults. The new equation has better mathematical behaviour than quadratic equations on very high values of clearance and takes into account dependence on body size.

GFR Prediction From Cystatin C and Creatinine in Children: Effect of Including Body Cell Mass

BACKGROUND Aiming to develop a more accurate cystatin C-based model for estimation of glomerular filtration rate (GFR) in children, we hypothesized that inclusion of body cell mass (BCM) would increase the accuracy of the GFR estimate in comparison to a well-established GFR reference method. STUDY DESIGN Diagnostic test accuracy study. SETTINGS & PARTICIPANTS 119 children (mean age, 8.8; range, 2.3-14.9 years) referred for GFR measurement by chromium 51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance (mean GFR, 98; range, 13.7-147.4 mL/min/1.73 m(2)). INDEX TEST GFR estimations by the 2 prediction models resulting from theoretical considerations corroborated by forward stepwise variable selection: GFR (mL/min) = 0.542 × (BCM/SCysC)(0.40) × (height × BSA/SCr)(0.65) and GFR (mL/min) = 0.426 × (weight/SCysC)(0.39) × (height × BSA/SCr)(0.64), where SCysC is serum cystatin C level, BSA is body surface area, and SCr is serum creatinine level. The accuracy and precision of these models were compared with 7 previously published prediction models using random subsampling cross-validation. Local constants and coefficients were calculated for all models. Root mean square error, R(2), and percentage of predictions within ±10% and ±30% of the reference GFR were calculated for all models. Based on 1,000 runs of the cross-validation procedure, median values and 2.5th and 97.5th quantiles of the validation parameters were calculated. REFERENCE TEST GFR measurement by (51)Cr-EDTA clearance. RESULTS The BCM model predicted 98% within ±30% of reference GFR and 66% within ±10%, which was higher than for any other model. The weight model predicted 97.5% within ±30% of reference GFR and 62% within ±10%. The BCM model had the highest R(2) and the smallest root mean square error. LIMITATIONS Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort. CONCLUSIONS The novel BCM model predicts GFR with higher accuracy than previously published models. The weight model is almost as accurate as the BCM model and allows for GFR estimation without knowledge of BCM. However, endogenous methods are still not sufficiently accurate to replace exogenous markers when GFR must be determined with high accuracy.

Beta emitters and radiation protection

Background. Beta emitters, such as 90Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding. Aim. To discuss practical precautions for handling beta emitters in general, and specifically determine proper shielding for 90Y, while comparing to 177Lu and 131I. The aim is achieved through the application of physical principles combined with results from practical experience. Material and methods. Typical and maximal electron ranges were calculated for 131I, 177Lu, and 90Y, using data from a freely available database. Bremsstrahlung yields were calculated for 90Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from 90Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons preparing 90Y-Zevalin were measured. Conclusions. Good laboratory practice is important to keep radiation doses low. To reduce bremsstrahlung, 90Y should not be shielded by lead but instead perspex (10 mm) or aluminium (5 mm). Bremsstrahlung radiation can be further reduced by adding a millimetre of lead on the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure.

Critical factors and their impact on bioelectrical impedance analysis in children: a review

Abstract Several guidelines for bioelectrical impedance analysis (BIA) have been prepared for adults, but not for children. For that reason, there is a pressing need to develop a consensus set of guidelines to facilitate standardisation of BIA in this important group. This review provides an introduction to BIA, highlights critical factors that may impact on BIA and identifies areas where there is a need for further research in order to increase the quality of impedance measurements and prediction of body composition in children. Although the results of this review highlights a lack of studies in children to provide definitive BIA guidelines, the technique has, however, still proven valuable for body composition assessment in ill and healthy children. To fill the gaps in our knowledge, future studies should focus on methodological issues, particularly with regard to hydration, voiding, clothing, skin preparation and body position. The review may advantageously be used as a checklist in the planning of future studies. Finally, this review forms the basis for the development of guidelines for BIA assessment in this particular group; a task appropriately to be undertaken by scientific societies within the field.

Precision and within- and between-day variation of bioimpedance parameters in children aged 2–14 years

BACKGROUND & AIMS Bioimpedance spectroscopy (BIS) offers the possibility to perform rapid estimates of fluid distribution and body composition. Few studies, however, have addressed the precision and biological variation in a pediatric population. Our objectives were to evaluate precision, variation within- and between-days for the BIS-determined parameters total body fluid, extra-cellular fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular resistance, intra-cellular resistance and percentage body fat using a Xitron 4200. METHODS All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one series measured on day one (precision population). Forty-four children had a second series on day one (within-day sub-population). Thirty-two children had a series measured on the next day (between-day sub-population). Each measurement series consisted of three repeated measurements. A linear mixed model was used for statistical analysis. RESULTS The precision was 0.3-0.8% in children ≥6 years and 0.5-2.4% in children <6 years with a statistically significant difference between the two age-groups (p<0.001). Within-day variation was 1.1-2.8% and between-day variation 2.4-5.7%. Total variation and reference change values are reported. CONCLUSION The Xitron 4200 has a very good but age-dependent precision. The median value of three repeated measurements is recommended in order to avoid incorrect measurements.

Standardisation of bioelectrical impedance analysis for the estimation of body composition in healthy paediatric populations: a systematic review

Abstract Background: Bioelectrical impedance analysis (BIA) requires a high degree of standardisation in order to ensure valid and reproducible impedance measurements. The overall aim of this review was to study the degree to which BIA papers conducted in healthy paediatric populations (aged 0–17 years) were standardised. Methods: Literature was identified on the basis of a systematic search of internationally-recognised electronic databases and hand searching of the reference lists of the included papers in order to identify additional relevant papers. The review was limited to lead-type BIA devices for whole-body, segmental- and focal impedance measurements. In total, 71 papers published between 1988 and 2016 were included. To evaluate the degree of standardisation of the papers, a recently published review detailing critical factors that may impact on BIA measurements in children was used as a model for structuring and extracting data. Results: There was a general lack of BIA standardisation, or its reporting, in the papers under review, which hinders comparison of data between studies and could potentially lead to erroneous measurements. Conclusions: If the BIA technique should be accepted clinically for routine use in paediatric populations, there is a need for an increased focus on the importance of improved standardisation and its reporting in future studies. Consequently, this review contains recommendations for performing and reporting BIA measurements in a standardised manner.

Bioimpedance Spectroscopy in Healthy Children

Prediction equations compromise the usefulness of bioimpedance spectroscopy (BIS) in children. This preliminary study explored the possibility of establishing reference curves in children, based on BIS-modeled data and/or resistance index (RI) values. In addition, the precision of repeated measurements was calculated. A total of 105 children (2-14 years old) were enrolled. A BIS device was used and a wrist-ankle electrode configuration was applied. Three repeated measurements were performed in each child. Strongest correlations were seen between RI values and weight for both sexes range, r = 0.94 to 0.97, P < .001. The precision (coefficient of variation in percent) of repeated measurements showed to be low (range, 0.4% ± 0.3% to 1.1% ± 3.1%) We established sex-specific reference curves of RI values, and the precision of repeated measurements showed to be excellent.

Influence of Positron Emitters on Standard γ-Camera Imaging

Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ camera imaging (SPECT or planar) because the 511-keV photons can penetrate collimators designed for lower energies. This study investigated how to manage this issue, including what levels of PET radionuclides can be tolerated when a γ-camera investigation is performed. Methods: Different combinations of 68Ga (PET radionuclide), 99mTc (low-energy radionuclide), and 111In (medium-energy radionuclide) were scanned by a γ camera. Standard low-, medium-, and high-energy collimators were used with the γ camera. Dead time and counts near and distant from the sources were recorded. Results: Down scatter from 511 keV can give rise to a considerable number of counts within the 99mTc or 111In energy windows, especially when the PET source is close to the camera head. Over the full camera head, the PET source can result in more counts per megabecquerel than the SPECT source (99mTc or 111In). Counts from the PET source were distributed over a large region of the camera head. With medium- and high-energy collimators, the sensitivity to the PET radionuclide was found to be about 10% of the sensitivity to 99mTc and about 20% of the sensitivity to 111In, as measured within a 3-cm-radius region of interest. Conclusion: If PET radionuclides of activity 1 MBq or higher are present in the patient at the time of SPECT, a medium-energy collimator should be used. Counts from PET sources will in SPECT usually be seen as a diffuse background rather than as foci. The thick septa of high-energy collimators may result in structure in the image, and a high-energy collimator is recommended only if PET activity is greater than 10 MBq.

Reference data for distal blood pressure in healthy elderly and middle‐aged individuals measured with the strain gauge technique. Part I: Resting distal blood pressure

Objective. Most patients referred to our department for distal blood pressure (DBP) determination on suspicion of arterial peripheral vascular disease (apvd) are more than 60 years of age, whereas the only available reference data for resting pressure are based on data from healthy individuals aged between 43 and 57 years. Our aim was to investigate whether newly collected reference data for DBP measured using the strain‐gauge technique in healthy subjects older than 60 years and in others between 45 and 58 years were significantly different from the old reference data used in daily practice. Material and methods. Group I comprised 31 healthy persons aged between 61 and 87 years and group II 14 healthy middle‐aged hospital staff members aged between 45 and 58 years. Strict rules of inclusion were followed. Results. For group I, significantly greater gradients (DBPtoe – systolic arm blood pressure and DBPtoe – DBPankle) were found in the new reference data compared to the old. No significant difference between the mean values of the gradient (DBPankle – systolic arm blood pressure) was found between the old and new reference data, although the variation was significantly wider in the new reference data; the lower level of normality was therefore −15 mmHg compared to 0 mmHg in the old reference data. For group II, no significant differences between the gradients were found comparing the new and old reference data. Conclusion. These new data indicate that reference data gathered from middle‐aged subjects should be changed when DBP measurements are used in patients older than 60 years of age.

Impact of contamination with long-lived radionuclides on PET kinetics modelling in multitracer studies

IntroductionAn important issue in multitracer studies is the separation of signals from the different radiotracers. This is especially the case when an early tracer has a long physical half-life and kinetic modelling has to be performed, because the early tracer can confer a long-lived contaminating background not only to images but also to a measured input function derived from blood samples. In this study, we examined data from a sequential multitracer infection study involving 111In (t1/2=2.8 days), investigating the influence on gamma counting of blood samples and on the kinetic modelling of subsequent PET tracers. Blood sample counts were corrected by recounting the samples a few days later. A more optimal choice of energy window was also explored. The effect of correction versus noncorrection was investigated using a two-tissue kinetic model with irreversible uptake (K1, k2, k3). ResultsK1 was least affected and k3 was most affected by the contamination, corresponding to the effect being relatively larger on the late part of the blood input function. A narrower energy window reduced the problem, but this will not be possible for all types of contaminating background. ConclusionGamma counting of blood samples can lead to a contaminating background not observed in PET imaging and this background can affect kinetic modelling. If the contaminating tracer has a much longer half-life than the foreground tracer, then the problem can be solved by late recounting of the samples.