A method for assessment of blood volume parameters in pregnant sheep using fluorescein-labelled dextran.

The assessment of blood volume parameters in clinical and research settings has been limited by methods that involve radioactivity, complex assays or are unreliable. We aimed to design a method for measuring blood volume parameters that was non-radioactive, simple, cheap and reliable. We have used a commercially available fluorescein-labelled 250kDa dextran, a large inert molecule, and have measured dilution of this through the intravascular space of pregnant ewes. From this estimation of plasma volume and measured hematocrit, we have calculated blood volume and red cell volume. The blood volume results are 6% lower than those obtained using radiolabelled red cells, but there is no significant difference in red cell volume between methods. The coefficient of variation for repeated measurements of plasma volume measurements is 3.8%. This is a simple, reliable, cheap and non-radioactive method for estimating blood volume parameters in pregnant sheep, and may prove useful in other settings.

Scintigraphic imaging of the hypoxia marker (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; prognox): noninvasive detection of tumor response to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid.

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This study investigates, using mouse models, whether a new marker for tissue hypoxia, (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; Prognox)] has potential for the scintigraphic monitoring of tumor response to antivascular agents. Determination of radioactivity in dissected tissues 3 h after DMXAA (80 micromol/kg) or CA-4-P (227 micromol/kg) was injected indicated that both drugs inhibited blood flow (86RbCl uptake; 84 and 87%, respectively) and increased 99mTc-labeled HL-91 levels (350 and 300%, respectively) selectively in murine RIF-1 tumors. Planar imaging of 99mTc-labeled HL-91 3 h after DMXAA injection showed a dose-dependent increase in tumor levels above a threshold of 50 micromol/kg; this same threshold was observed for the inhibition of tumor blood flow (determined using Hoechst 33342). DMXAA also inhibited blood flow--and increased 99mTc-labeled HL-91 uptake--in MDAH-MCa-4 mouse mammary carcinomas and in NZMN10 human melanoma xenografts. Whether 99mTc-labeled HL-91 might also be useful as a biomarker for tumor cell killing was investigated by clonogenic assay of surviving cells 15 h after imaging 99mTc-labeled HL-91 in RIF-1 tumors. Log cell kill in individual tumors showed a statistically significant linear correlation (P < 0.001) with 99mTc-labeled HL-91 uptake after 60 micromol/kg (r2 = 0.79) and 70 micromol/kg (r2 = 0.44) but not at 80 micromol/kg DMXAA. The lack of correlation at high doses presumably reflects the insensitivity of the tumor-averaged 99mTc-labeled HL-91 signal to small regions in which tumor blood flow is preserved (which will limit log cell kill). The results indicate the potential of 99mTc-labeled HL-91 for the noninvasive imaging of tumor blood flow inhibition by antivascular drugs in humans.

A comparison of the renal handling of 99Tcm-DTPA and 99Tcm-MAG3 in hypertensive patients using an uptake technique.

The renal uptake and outflow of 99Tcm-DTPA and 99Tcm-MAG3 were compared by analysing renal studies performed in two different departments, but with analysis techniques and computer programs using algorithms that were almost identical. Comparison was performed by a retrospective review of results from patients who were referred for renal investigations because of hypertension but who had apparently normal kidneys. The analysis of tracer outflow rates in the form of whole-kidney transit times and renal cortical transit times showed no significant difference between the two tracers. The fractional uptake rate of tracer for each patient (both kidneys) indicated that MAG3 was extracted from the blood 3.3 times faster than DTPA in patients aged 20-69 years, with a lower ratio above the age of 70. When used to measure relative renal function, there was no overall difference between the two tracers. The fractional uptake rates were also converted to flow rates, producing values of 95.8 +/- 28.0 ml.min(-1).1.73 m-2 for DTPA and 320 +/- 75 ml.min(-1).1.73 m-2 for MAG3, in hypertensive patients aged 20-40 years. These values showed a good correlation with other published GFR and MAG3 clearance rates (obtained using blood sampling methods) in normal patients of similar ages.

HIDA kinetics in children.

Quantitative analyses were performed on paediatric HIDA scans (EHIDA and DISIDA) to measure the flow rates of HIDA into and out of the liver. Analysis of the tracer outflow rate indicated that HIDA appeared to leave the liver even when there was complete biliary obstruction, implying 'leakage' from hepatocytes back into the blood. This potentially explains why a 'hepatogram' does not provide useful information about hepatic obstruction, whereas a renogram does yield useful information about renal outflow obstruction. In a small group of patients with no evidence of either hepatocellular disease or obstruction, the HIDA inflow rate into the liver was 0.003072 s(-1), which is similar to published colloid uptake rates in normal livers. This implies that although the two radiopharmaceuticals are taken up by different mechanisms, both mechanisms have a very similar extraction fraction. Patients with cirrhosis had a considerably reduced HIDA uptake rate (0.001072 s[-1]), and once again this was similar to colloid uptake from the blood in cirrhosis. Patients investigated for neonatal jaundice all showed reduced HIDA inflow, and this reduction was greatest (mean 0.000477 s[-1]) in those neonates whose jaundice was due to hepatocellular impairment. In biliary atresia, the HIDA rate was reduced to approximately 0.001040 s(-1), which was still considerably higher than the rate from patients with neonatal jaundice due to sufficient hepatocellular impairment to cause complete cholestasis.

Transthoracic echocardiography for right ventricular function late after the Mustard operation.

The aim of the study was to assess echocardiographic measurements of right ventricular function in 24 patients aged 10.7 to 28.9 years (mean 18.9 years) receiving the Mustard baffle repair for transposition of the great arteries. Right ventricular ejection fraction (RVEF) from single-plane areas and area length volumes, pulsed Doppler mean aortic acceleration, and tricuspid annular plane systolic excursion were correlated with first-pass radionuclide RVEF. The mean radionuclide RVEF was 39%, the mean echocardiographic apical four-chamber RVEF was 41%, and the mean short-axis RVEF was 37%. Echocardiographic apical four-chamber right ventricular end-diastolic volumes were 102 +/- 24 ml/m2, and RVEF interobserver and intraobserver correlation coefficients were 0.73 and 0.81, respectively. Radionuclide and echocardiographic RVEF correlation coefficients were short axis, 0.40; apical four-chamber, 0.24; average four-chamber and short axis, 0.38; mean aortic acceleration, 0.26; and tricuspid annular plane systolic excursion, 0.06. The range of echocardiographic right ventricular volumes for young adults receiving the Mustard repair is established allowing serial observation of dilatation. However, simple and reliable echocardiographic prediction of RVEF remains elusive in this age group.

Assessing diffuse liver disease with the hepatic uptake rate of 99Tcm-colloids.

The hepatic uptake rate of sulphur or tin colloid was measured in the fasting state in patients who were later identified as belonging to one of three groups: normal, parenchymal liver disease or cirrhosis. Subsequent analysis showed a progressive decline in the hepatic uptake rate of tracer as the severity of hepatocellular damage increased. In particular, there was a positive correlation between the impairment of tracer uptake, and Childs' class A, B or C in the cirrhotic patients. In addition, a very low hepatic uptake rate of tracer was almost as good (80% accuracy) as Child's class C (83% accuracy) in identifying patients likely to die of hepatocellular problems within a year. When compared with needle biopsies or histology, the uptake rate usually proved equally accurate in indicating the severity of diffuse hepatocellular disease, and on occasions it was a better indicator of long-term outcome.

Tracer flows and 'difficult' organs.

This paper describes a method for measuring tracer kinetics in organs which are larger than the field of view of a gamma camera, by performing initial dynamic studies on part of that organ, followed by a later study to determine the tracer content of the entire organ. Information is transferred from the measured data to 'absolute values' by means of a calculated intermediate number which is called the 'MTBE' (mean time in blood, equivalent). Initial testing of the technique with methylene diphosphonate (MDP) bone studies produced tracer flow rates of 0.000366 s-1 into bone and 0.001525 s-1 into interstitial fluid in patients with no known bone disease. Patients with active Paget's disease of bone had higher bone inflow rates, and showed some improvement following therapy with either editronate or pamidronate. The method has the potential to be applied to other situations, particularly SPET, using SPET to calculate tracer content and converting the results to flow rates using the formula: Inflow rate = Content/MTBE.

Correlation of splenic function with the splenic uptake rate of Tc-colloids.

The splenic uptake rate of Tc-sulphur colloid or Tc-tin colloid was measured and found to correlate well with splenic function. The normal tracer uptake rate was 0.0002/s-0.0006/s (measured uptake rate divided by measured injected activity). Lower values indicated hyposplenism (sensitivity = 0.97, specificity = 0.95), and values over 0.0006/s indicated hypersplenism (sensitivity = 0.96, specificity = 0.97). Higher values of splenic uptake were associated with proportional reductions in the white blood cell and platelet counts, and to a lesser extent the haemoglobin concentration in peripheral blood. Patients with rheumatoid arthritis had increased tracer uptake, but still below the criteria for hypersplenism, whereas patients with Felty's syndrome had tracer uptake rates in the 'hypersplenic' range.

A comprehensive analysis of renal DTPA studies. III. Renal artery stenosis.

Renal DTPA studies were analysed to produce numerical data of renal function (blood flow, glomerular filtration, and excretion), and this was used as an adjunct to the routine imaging information in a study of renal artery stenosis (RAS). The results show an overall accuracy of 81%, with a sensitivity of 96% and a specificity of 61%. In patients with RAS, beta-blocking drugs reduced the difference between the two kidneys. ACE-inhibiting drugs appeared to preserve renal blood flow but also to cause a deterioration in the glomerular filtration rate of kidneys with RAS. An explanation is proposed, in which renal capillary pressure is more important for function than is renal blood flow.

Radionuclide cardiac ejection fractions: a useful disparity between LAO and LPO views.

The left ventricular ejection fraction (LVEF) was measured from ECG gated blood pool radionuclide studies. The LAO and LPO views gave different values for the LVEF, however, the difference was not a random error, but was specifically related to the site of impaired myocardial function, implying that the difference may have diagnostic significance.

Extensive pulmonary embolism associated with lupus anticoagulant.

A female patient with extensive pulmonary emboli associated the lupus anticoagulant is described. She made a good recovery with heparin treatment.

A comprehensive analysis of renal DTPA studies. I. Theory and normal values.

Gamma camera renograms, using DTPA, were analysed to obtain flow rates and transit times during the initial arterial phase (0-36 s) and the later glomerular phase (37 s onwards). This paper outlines the underlying theory, and the effect of age on all the variables, calculated from patients with normal renal function.

A comprehensive analysis of renal DTPA studies. II. Renal transplant evaluation.

Renal transplant radionuclide studies, using DTPA, were analysed to produce flow and transit time measurements in both the initial arterial phase, and the later glomerular phase. Results are presented for transplanted kidneys which are normal, infarcted, obstructed, or suffering from rejection or acute tubular necrosis. Sequential studies of the vascular flow and transit time indices showed considerable promise in the detection of acute rejection, even in the presence of acute tubular necrosis. Of the six numerical indices to demonstrate acute rejection, five had accuracies of 74% or more, and all three of the indices which compared a study with a previous one had accuracies of 83% or more.

Congenital aneurysm of the left atrium: diagnosis and management.

A case of congenital aneurysm of the left atrial appendage is presented and previously reported cases are reviewed. The diagnosis can be strongly suspected with the combination of an unusually prominent left heart border in the chest X-ray and two-dimensional echocardiographic findings of a large echo-free space close to the left atrium. The site of communication must be defined accurately and cardiac catheterisation and angiocardiography should be performed. Once the diagnosis is confirmed, surgery is indicated even in the asymptomatic patient because of the risk of systemic embolism.

Perfusion scintigraphy in the diagnosis of pulmonary embolism: a self-assessment quiz.

The authors present ten case reports with lung scintigrams in a format suitable for a self-assessment quiz. The first seven cases include perfusion scintigrams and the final diagnosis was established by postmortem examination. The last three studies include ventilation images (using nebulized Tc-99m tin colloid) and the final diagnosis established by nonradionuclide studies. The authors believe this quiz demonstrates the necessity for ventilation studies when using lung scintigraphy for a positive diagnosis.

Measurement of the effects of a single dose of prazosin on the cerebral blood flow in hypertensive patients.

It was considered that the first dose reaction occurring with prazosin may have been due either to hypotension or to a specific reduction in cerebral blood flow. The development of a quantitative non-invasion nuclear medicine technique for cerebral flow has now made it possible to investigate the effects of prazosin on cerebral blood flow in hypertensive patients. This double-blind study showed a significant decrease in BP and a small just significant increase in cerebral blood flow following a single 1-mg dose of prazosin, when compared with a placebo. From these results, it is unlikely that the first dose reactions which occurred with prazosin were due to a specific reduction in cerebral blood flow.

Retrograde spread of hydrocortisone containing foam given intrarectally in ulcerative colitis.

A method is described of estimating retrograde spread through the colon of a 10% hydrocortisone acetate foam by labelling the foam with technetium-99m sulphur colloid and observing spread after intrarectal administration by serial gamma-camera pictures. The recommended 51 ml dose of foam reached the mid-sigmoid colon in all of the nine patients who had active ulcerative colitis. Furthermore, in seven the foam reached the proximal sigmoid colon. Foam spread less extensively in five patients with quiescent disease than in those with active disease. Increasing the volume of enema to 50 ml did not improve retrograde spread through the colon. These results suggest that 10% hydrocortisone foam may be useful in treating patients with distal ulcerative colitis that is not necessarily limited to the rectum.