Examination of errors caused by random summing in in vivo prompt gamma ray analysis.

A technique is described for examining the mode of operation of radiation detectors and estimating the losses and gains caused by random summing effects in spectra acquired at high counting rates. The technique is applied to estimating the errors caused by random summing when measuring the amounts of carbon and nitrogen in the human body by the prompt gamma ray neutron activation analysis system installed in Leeds, UK. Our examination shows that the counting rate would have to increase to more than twice the value used at the method's calibration, before an error of greater than 10% is caused in the estimation of carbon by random summing effects, whilst for nitrogen a change of only 18% in the counting rate will cause a 10% error in its estimation.

Body composition of fasting obese patients measured by in vivo neutron activation analysis and isotopic dilution.

The masses of fat, water, protein and minerals in ten obese patients (seven women and three men) have been measured, by in vivo neutron activation analysis and isotopic dilution, before and after four weeks of starvation. Mass of skeletal muscle was estimated from measured total body potassium (TBK) and nitrogen (TBN). Before starvation the patients weighed, on average, 56.5 kg more than predicted from sex, age and height. The composition of their excess tissue was consistent with that of adipose tissue. During starvation the patients lost, on average, 12.1 kg of tissue containing more water and potassium than adipose tissue. Regression analysis of the measured changes in potassium and protein suggested that approximately 230 mmol of potassium was lost independently of protein, the remainder being lost with 'non-muscle' fat-free tissue. Because some potassium was lost without protein, the change in muscle mass calculated from the changes in TBK and TBN overestimated the true mass of muscle lost. After starvation the patients still had 44.5 kg of excess tissue. Their composition was consistent with an excess of adipose tissue and a deficit of potassium.

Measurement of short-term changes in the fat content of the body: a comparison of three methods in patients receiving intravenous nutrition.

Three methods of measuring changes in body fat were compared in seventeen patients undergoing a 2-week course of intravenous nutrition. Patients received all nutrition intravenously at a steady rate of infusion, calculated to supply energy at a rate equal to 1.5 times the resting metabolic expenditure measured before feeding. Fat change was estimated from measurements of skinfold thickness, by isotopic methods (neutron-activation analysis and dilution of tritiated water) and by daily analysis of expired gases. The mean (with 1 SEM) gain in fat over the 2-week period was 1.14 (0.30) kg for skinfold measurement, 0.53 (0.62) kg for isotopic determination and 1.29 (0.22) kg for expired-gas analysis. There were no significant differences between the mean gains in fat measured by the three methods. The results show that expired-gas analysis is the most sensitive technique, measuring change in fat content with an estimated precision of 0.26 kg. The isotopic method is less sensitive, with a precision of 2.38 kg, but provides a detailed description of body composition. In contrast to these highly-specialized techniques, both of which have limited application, the simple technique of measurement of skinfolds occupies an intermediate position of sensitivity, with a precision for measuring change in fat content of 0.85 kg, and also has the potential to measure total body fat content.

Calculation of short-term changes in body fat from measurement of respiratory gas exchange.

A method is presented where the gain in body fat of patients receiving intravenous nutrition (IVN) may be computed using indirect calorimetry. When patients are administered their nutritional requirements soley in the form of glucose and amino acids, metabolism of these will result in changes in the exchange of carbon dioxide and oxygen. Since net fat synthesis results in the production of excess carbon dioxide whereas degradation results in a net reduction in the production of carbon dioxide, changes in RQ will reflect underlying changes in net fat balance. A correction may be applied to these measurements to allow for net protein balance. The basic equations and stoichiometry for the synthesis of tripalmitin from glucose are shown together with the derivation of the formulae that enable the calculation of fat changes to be made. A group of 13 patients was used to assess the technique and given energy at 1.5 times resting metabolic expenditure together with adequate nitrogen as amino acids to maintain protein balance. The patients were monitored daily in the resting state and fed at a constant rate so that errors due to discontinuous intake or exercise were avoided. The group was found to gain 874 +/- 243 g fat during the 14 day study. Although individual changes of fat in patients ranged from -169 to +2487 g, net synthesis of fat was found in ten of them. It is suggested that indirect calorimetry is useful not only in the assessment of actual expenditure in patients but can also be used to quantify the fate of administered fuels during intravenous nutrition.

Multi-element analysis of the obese subject by in vivo neutron activation analysis.

The Leeds facility for in vivo neutron activation analysis has been modified and calibrated for the simultaneous measurement of nitrogen, potassium, sodium, chlorine, phosphorus and calcium in obese patients weighing up to 210 kg. The effects of body size and shape were incorporated into the calibration by measuring 14 anthropomorphic phantoms of known composition representing individual patients being treated for obesity. The phantoms were constructed from tissue substitutes representing lean, skeletal and adipose tissues, arranged to simulate the distributions of the corresponding tissues within the patients, as visualised by CT scanning. The precision of the method, determined by measuring a single phantom ten times over a period of ten weeks, is between two and three per cent for all elements except calcium, for which it is 11.3%. Accuracy is estimated to be similar to precision. The procedure has been used to study changes in body composition of patients undergoing therapeutic starvation.

Multi-element analysis of the human body using neutron activation.

The calibration described is of the Leeds in vivo neutron activation facility for the simultaneous measurement of total body Na, Cl, P, Ca, N and K. The effects of body size and shape have been incorporated into the calibration using a variable anthropomorphic phantom. The main interfering reactions are considered, and the method by which the results are corrected for these interferences described. The accuracy and precision of the technique have been determined. The procedure is suitable for measuring the critically ill since both irradiation and counting are performed with the patient lying supine. For a whole body dose equivalent of 0.5 mSv nitrogen was measured with a coefficient of variation (CV) of 2.2%; potassium was measured in the same counting period with a CV of 1.6%. Using a dose equivalent of 5 mSv sodium (2.2%), chlorine (1.6%) and phosphorus (2.9%) were also determined; for a 10 mSv dose equivalent calcium was measured with a CV of 3%.

Estimating total body calcium from peripheral bone measurements.

In a heterogeneous group of 12 male and 30 female patients, total body calcium (TBCa) was measured by neutron activation analysis, and bone mineral content of the distal femur and six regions of the distal radius and ulna were measured by photon absorptiometry. TBCa was an average of 71 g (9%) lower than normal in the females and 119 g (11%) lower than normal in the males. Of the forearm measurements, those of the radial shaft provided the best estimate of TBCa with a standard error of estimation (SEE) of 88 g (14% of the mean value) for female patients alone, and 113 g (16%) for the whole group. The measurement on the femur provided a better estimate with SEE 80 g (13%) for female patients and 90 g (13%) for the whole group. These SEE are comparable with the variability in TBCa between normal subjects, which has a coefficient of variation of the order of 20% in both sexes. A slightly better estimate of TBCa can be obtained by using a multiple regression equation involving both the femur and radial shaft measurements with a SEE of 74 g (12%) for female patients and 81 g (11%) for the whole group. The correlation between the estimated deficit of TBCa and the estimated deficit of bone mineral from the forearm and the femur has been calculated.

Interferences in in vivo neutron activation analysis.

Significant errors can occur in the measurement of the total amounts of N, P, Cl, Na, Ca and K in the human body by in vivo neutron activation analysis because of the presence of interfering activity in the gamma-ray energy spectrum. The interfering activity may be present for two reasons: firstly, patients may have received an administered radioisotope in an unrelated investigation; secondly, activation of elements not normally present in the body in large quantities may have occurred. The size and duration of these errors have been examined for two administered radioisotopes, 67Ga and 47Ca. The interferences due to activated iron and chromium from stainless steel prostheses have been examined, as well as those due to activated iodine and barium in radiographic contrast media. A description of the method by which we correct for those interferences is given. The effects of the shape of the standard spectra used in least squares analysis of the results have been examined.

The feasibility of measuring total body carbon by counting neutron inelastic scatter gamma rays.

A technique is examined for measuring the mass of carbon of both ambulatory and non-ambulatory subjects. The method is based upon the detection of the 4.43 MeV gamma rays emitted from carbon nuclei when the body is irradiated with fast neutrons. The supine subject is irradiated laterally by a horizontal collimated beam of 14 MeV neutrons and the emitted gamma rays are counted by a shielded NaI(Tl) detector placed underneath the subject. The method has been calibrated for all sizes of subjects from 30 to 90 kg and there appears to be no significant interference from the other bulk elements of the body. Body carbon has been measured in six normal volunteers; body nitrogen was also determined by measuring the 13N induced in each subject in a second irradiation. Body fat was estimated from the measured carbon and nitrogen, and the values compared with those derived from skinfold thicknesses. The technique is proposed as a method of estimating long-term energy expenditure.

The accuracy of total body nitrogen determined by neutron activation analysis.

Experiments have been performed to validate the technique of determining total body nitrogen by measuring the induced activity of 13N produced by the reaction of 14 MeV neutrons with nitrogen. Firstly, the accuracy of determining the counts due to nitrogen was studied by measuring the activities of the positron-emitting nuclides of C, Cl, K, P, and O, as well as N, produced by the irradiation of anthropomorphic phantoms with a surface neutron dose equivalent of 0.5 mSv (50 mrem). Secondly, the effect of variation of spatial sensitivity was studied by measuring the activation and detection efficiencies of small samples at many positions within an anthropomorphic phantom, and also by comparing the known amounts of nitrogen within a new type of phantom in which the elements are fixed, with the amounts measured using a calibration based on experiments with a Bush phantom in which the elements are freely diffusible within each phantom part. There was a maximum difference of only 4% between the measured and known amounts of nitrogen. It is therefore concluded that this technique provides a simple and accurate way of measuring total body nitrogen.

Multi-element analysis of the living body by neutron activation analysis-application to critically ill patients receiving intravenous nutrition.

Neutron activation analysis has been used to determine the total content in the body of N, K, Na, Cl, P and Ca in 25 critically ill surgical patients before and after a 14-day course of intravenous nutrition. Muscle elemental composition was also determined in these patients at the same time as the total body analysis. Over the 14-day period of intravenous feeding the total body contents of all the measured elements increased (2-9.7 per cent) but only the increase in K was statistically significant. Muscle chemistry suggested an intracellular K depletion which was corrected over the study period. The results of the total body multi-element analysis were interpreted to show a mean gain of 1.25 l of extracellular fluid and 0.51 l of intracellular fluid and direct measurement of total body water suggested that this interpretation was probably valid. The first application of the technique to patients with nutritional and metabolic problems has quantified the weight gained by two body compartments during a 2-week period of intravenous nutrition. Its further application should help to solve a number of nutritional and metabolic problems in clinical surgery.

Changes in body weight and body protein with intravenous nutrition.

Body weight, protein, fat and water were measured before and after intravenous nutrition in 20 surgical patients. The group included both young and old patients who were suffering from a wide variety of catabolic illnesses and the period of intravenous feeding ranged from 11 to 40 days. Eight of the patients were able to take small amounts of food orally. During the period of intravenous nutrition ten patients gained significant weight although only two of these gained significant protein. Most of the weight gain was due to an increase of water. There was also a gain of water in the patients who lost weight; this water gain occurred in small daily increments over the course of treatment. It is concluded that weight gain can occur without protein gain in patients who are being fed intravenously and that body weight is not a reliable guide to changes in body protein or fat in critically ill patients receiving intravenous nutrition.

Intravenous aminoacids and intravenous hyperalimentation as protein-sparing therapy after major surgery. A controlled clinical trial.

A solution of aminoacids without a calorie source was infused postoperatively in ten patients undergoing proctocolectomy or rectal excision and the results were compared with those in ten matched controls and ten patients who received intravenous hyperalimentation. Aminoacid infusion prevented the nitrogen and potassium loss that occurred in the untreated group but no clinical advantage could be seen. Nitrogen and potassium loss was also prevented in the patients treated with intravenous hyperalimentation but these patients had significantly fewer postoperative complications than either the controls or those given aminoacid infusion. It is suggested that aminoacid infusion is of very little benefit after major surgery. On the other hand the skilled administration of intravenous hyperalimentation to patients after major surgery can be of real benefit.

Fat-free body mass from skinfold thickness: a close relationship with total body nitrogen.

Fat-free body mass is an important component of body composition which is of particular interest to nutritionists and related workers. Fat-free mass has been determined from the simple measurement of skinfold thickness and it has been demonstrated that there is a close correlation with total body nitrogen even though the test subjects had a wide range of nutritional status.

Counting losses in multidetector radiation counters.

We examined the reasons for the reduction in response of a multidetector radiation counting system when operated at high count-rates and established a convenient method of correction which is accurate to within +/- 1% up to 0-6 X 10(5) counts per second. In its application the method uses the observed count-rates from each detector at the time of measurement and previously determined values of critical time intervals of the electronic system. The detected signals establish these intervals in which further signals occurring within them are lost from the response. These further signals can also cause the loss of the signals establishing the intervals. The correction is of particular value when high-sensitivity whole-body counters are used to measure the activity of administered isotopes in metabolic studies.