Daphne M. Glass

ECAT ART — a continuously rotating PET camera: Performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameter×20 cm long cylindrical phantom, no scatter correction) is 11400 cps·kBq−1·ml−1. This compares with 5800 and 40500 cps·kBq−1·ml−1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350–650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of ~15 kBq·ml−1 in the cylinder. Spatial resolution is ~6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 µSv·h−1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

Lymphatic dysfunction in the apparently clinically normal contralateral limbs of patients with unilateral lower limb swelling.

Purpose: To determine how often lymphatic dysfunction is bilateral when, clinically, lymphedema appears unilateral. Methods: Lymphoscintigraphy was performed after subcutaneous Tc-99m-nanocolloid injection in the first webspaces of both feet. The percentage of injected radioactivity accumulating in the ilioinguinal regions was recorded in dedicated images separately acquired at 60 and 180 minutes after injection. Results: Within a consecutive series of 204 patients, 74 had unilateral clinical lymphedema of whom 68 had abnormal scintigraphy. Of these 68 patients, 46 had unilateral abnormal scintigraphy affecting the clinically abnormal limb, but 20 patients had bilateral abnormal scintigraphy and 2 had unilateral abnormal scintigraphy in the clinically unaffected limb. Thus, 32% (22/68) of patients in whom clinical lymphedema appeared to be unilateral, nevertheless, had abnormal scintigraphy in the clinically normal limb. Twenty-nine patients had no clinical evidence of lymphedema in either limb and were scintigraphically normal bilaterally. Mean ilioinguinal nodal accumulation at 180 minutes in the 44 limbs of 22 of these clinically and scintigraphically normal patients (dedicated ilioinguinal imaging was not performed in all patients) was 13.1% (standard deviation, 8.8%), higher (P = 0.02) than the mean value of 9.3% (standard deviation, 5.0%) in the clinically and scintigraphically normal contralateral limbs of 39 patients with unilateral clinical lymphedema. Conclusions: In the presence of unilateral lymphedema, the contralateral limb is often also abnormal. On lymphoscintigraphy, therefore, care should be taken before diagnosing unilateral lymphatic dysfunction. Quantification should be included in routine lymphoscintigraphy, as reduced ilioinguinal nodal accumulation may be the only apparent abnormality.

Estimated Lean Body Mass Is More Appropriate than Body Surface Area for Scaling Glomerular Filtration Rate and Extracellular Fluid Volume

Background/Aims: To compare body surface area (BSA) with lean body mass (LBM) for scaling extracellular fluid volume (ECV) and glomerular filtration rate (GFR). Methods:Phase 1: Total body water (TBW), bromide space and LBM were measured with 3H-water, 77Br and dual X-ray absorptiometry, respectively, in 6 healthy adults. Phase 2: ECV and GFR were measured with 51Cr-EDTA in 95 healthy adults and 56 children (0.5–13 years). ECV was calculated as GFR divided by GFR/ECV, both corrected for the one-compartment assumption. LBM was estimated (eLBM) in adults from height and weight and in children using a height/weight formula for estimating ECV and a constant derived from a separate adult population relating ECV to eLBM. Results:Phase 1: LBM and BSA correlated closely with TBW and bromide space. With LBM, the regressions passed through the origin, but with BSA, the intercepts were significantly below zero. Phase 2: GFR/BSA and ECV/BSA were higher in men than women but no difference was recorded in GFR/eLBM, GFR/ECV or ECV/eLBM. ECV showed a linear relation with eLBM and a non-linear relation with BSA. GFR/BSA and ECV/BSA correlated significantly with BSA but neither GFR/eLBM nor ECV/eLBM correlated with eLBM. Conclusion: eLBM is preferable to BSA for scaling GFR and ECV.

Extracellular fluid volume and glomerular filtration rate: their relation and variabilities in patients with renal disease and healthy individuals.

IntroductionThe slope-only technique for measuring glomerular filtration rate (GFR) relies on extracellular fluid volume (ECV) remaining within narrow limits. Although this requirement is met in healthy individuals, ECV may deviate or vary more in patients with abnormal renal function. MethodsWe examined the correlation between surface area-scaled ECV and GFR, and their coefficients of variation (CVs), measured from simultaneous, multisample clearances of 51Cr-EDTA and iohexol in 20 healthy volunteers and 60 patients with a range of renal functions. We also compared scaled GFR and ECV, and their CVs, measured from three-sample, slope-intercept clearance of 51Cr-EDTA in 921 patients routinely referred for GFR measurement. ResultsIn the 80 participants undergoing multisample, dual-indicator clearance, there was no correlation between GFR measured with one indicator and ECV measured with the other. CVs of GFR in the 60 patients were 48.1 and 44.6% for 51Cr-EDTA and iohexol, respectively, but the CVs of ECV were only 12.3 and 15.4%. These differences were less marked in the healthy participants with corresponding CVs of 13.9 and 14.9% for GFR, and 11.7 and 12.2% for ECV. There was no correlation between scaled GFR and ECV in patients having slope-intercept clearance; CVs of GFR and ECV were 32.4 and 17.8%, respectively. ConclusionIn unselected patient populations, there is no correlation between GFR and ECV. The CV of ECV is slightly higher in patients than healthy individuals but, in both, is less than the CV of GFR. These data do not detract from the use of slope-only GFR.

Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies

A new technique of labelling granulocytes with both technetium-99m hexamethylpropylene amine oxime (HMPAO) and indium-111 in a single protocol was developed in order to exploit the advantages of each radiolabel in clinical and investigative studies. Fourteen patients were included in this prospective study. Granulocytes were labelled with both111In-tropolonate and99mTc-HMPAO. In vitro shape change assay and in vivo distribution and recovery studies were performed to assess the activation of and damage to these cells due to the labelling procedure. The comparative kinetics of111In and99mTc in the blood, liver, spleen, and bone marrow were studied by blood sampling and dual radionuclide imaging early (1 h) and late (24 h) after injection. The functional integrity of the double-labelled granulocytes and the feasibility of the technique were investigated in 14 patients with a painful prosthetic hip due to causes other than infection. The efficiency of double labelling was 63% (SD 14%) for111In and 39% (SD 12%) for99mTc-HMPAO. In vitro granulocyte activation and ex vivo recovery values were comparable to those from single radionuclide labelling. No artefactual granulocyte sequestration was seen in the lungs or liver. The radioactivity was distributed between the liver, spleen and bone marrow and, to a lesser extent, the lung. Early99mTc counts in the liver, spleen and bone marrow, in relation to background, were significantly higher than111In counts while the reverse was seen in late images. Furthermore, circulating “free”99mTc was significantly higher than free111In at 24 h. Organ99mTc counts, expressed in relation to the activity in early images, decreased in the spleen, increased in the liver and remained unchanged in bone marrow, whereas111In counts increased in the bone marrow and liver, and decreased in the spleen. Granulocytes can be labelled with both111In and99mTc-HMPAO in a single protocol without crosschelation, cellular activation or damage. By favourably exploiting their kinetics for early and late imaging, double-labelled granulocytes may be useful in several clinical and investigative situations.

Use of body surface area for assessing extracellular fluid volume and glomerular filtration rate in obesity.

Objective: To examine body surface area (BSA) for scaling extracellular fluid volume (ECV) in obesity. ECV varies less than glomerular filtration rate (GFR) in a clinical population and was therefore used as a surrogate for GFR on the grounds that if BSA is unsuitable for scaling GFR, it will also be unsuitable for ECV. Methods: GFR was measured in 917 patients using 51Cr-EDTA. GFR scaled to ECV was measured exclusively from the slope rate constant. ECV was calculated as GFR divided by GFR/ECV. Results: BSA correlated strongly with body mass index (BMI). ECV correlated strongly with BSA but the intercept was significantly lower than zero, indicating a disproportionate relation. ECV/BSA correlated with BSA but not with BMI. ECV in obese subjects was significantly less than in non-obese subjects individually matched for BSA. ECV/BSA was similar between obese and lean subjects matched for GFR/ECV and height. Conclusions: For subjects of similar BSA, a high BMI decreases ECV (the ‘obesity effect’). Subjects with high BMI generally have high BSA, which tends to increase ECV/BSA because of the disproportionate relation between ECV and BSA (the ‘BSA effect’). These opposing effects serendipitously and erroneously create the impression that BSA is suitable for scaling ECV (and by implication, GFR) in obesity.

Slope-only glomerular filtration rate and single-sample glomerular filtration rate as measurements of the ratio of glomerular filtration rate to extracellular fluid volume.

Aims:  The Jacobsson single‐sample equation for measuring glomerular filtration rate (GFR) after bolus injection is based on two factors of questionable theoretical validity for correcting the single‐compartment assumption. The aims were to redevelop a more transparent equation, show its fundamental similarity with ‘slope‐only’ GFR and compare it with the original equation and with slope‐only GFR.

Bimodal granulocyte transit time through the human lung demonstrated by deconvolution analysis.

The lungs are an important site of granulocyte pooling. The aim of the study is to quantify pulmonary vascular granulocyte transit time using deconvolution analysis, as has previously been performed to measure pulmonary red cell transit time. Granulocyte and red cell studies were performed in separate groups of patients. Both cell types were labelled with Tc-99m, which for granulocyte labelling was complexed with hexamethylpropyleneamine oxime (HMPAO). The red cell impulse response function (IRF) was monoexponential with a median transit time of 4.3 s. The granulocyte IRF was biexponential in 19 of 22 subjects, 18 of whom had systemic inflammation (inflammatory bowel disease, systemic vasculitis or graft-vs-host disease) and four were controls without inflammatory disease. The median transit time of the fast component ranged from 20 to 25 s and of the slow component 120-138 s in the four patient groups. The fraction of cells undergoing slow transit correlated significantly with (a) mean granulocyte transit time and (b) the fraction showing shape change in vitro. We conclude that granulocyte transit time through the pulmonary circulation is bimodal and that shape-changed (activated) cells transit more slowly that non-activated cells. The size of the fraction undergoing slow transit is closely related to mean granulocyte transit time and is an important determinant of the size of the pulmonary vascular granulocyte pool.

Lymph proteins may access peripheral blood without entering thoracic duct in patients with lymphatic dysfunction.

OBJECTIVE The objective was to investigate the hypothesis that lymphovenous communications, which allow lymph proteins to access peripheral blood without first entering the thoracic duct, open in patients with abnormal lymphatic function. METHODS Routine lymphoscintigraphy of 182 patients, including 27 without clinical evidence of lymphedema (controls), was performed immediately and 45 and 150 minutes after subcutaneous injection of technetium Tc 99m nanocolloid into both feet. Counts per pixel in a region of interest over the liver (L) were divided by total counts in bilateral ilioinguinal nodes (N) at 45 minutes (L/N45) and 150 minutes (L/N150). If all activity leaving ilioinguinal lymph nodes entered the thoracic duct, these L/N ratios would be similar from patient to patient. RESULTS Eight patients were excluded because of immediate liver activity suggesting inadvertent intravascular injection of tracer. In controls (group 1), L/N150 displayed a normal distribution with mean (± standard deviation) of 0.16 (0.09) × 10(-4) pixels(-1). Patients with L/N150 >0.34 × 10(-4) pixels(-1) (ie, 0.16 + 2 standard deviations) were assumed to have lymphovenous communications. Of 34 patients with clinical evidence of lymphedema but with normal findings on lymphoscintigraphy (group 2), 3 (9%) had lymphovenous communications; of 114 with abnormalities on lymphoscintigraphy (group 3), 43 (38%) had lymphovenous communications (P = .001). N45/150 was significantly higher than L45/150 in all four groups, indicating arrival of activity in nodes before the liver. Abnormal features of lymphoscintigraphy-lymph transport delay, popliteal node visualization, and diversion of lymph through the skin-showed no association with L/N ratios. CONCLUSIONS Lymphovenous communications exist in about one-third of patients with abnormalities detected on lymphoscintigraphy. The timings of tracer arrival in the liver and lymph nodes is consistent with lymphovenous communication within lymph nodes themselves.

Extracellular fluid volume in patients with cancer.

AimsCancer patients may have extracellular fluid volume (ECV) abnormalities that potentially invalidate glomerular filtration rate (GFR) measured using the slope–intercept technique. The aim was to test this concern by measuring ECV in cancer patients in comparison with noncancer patients and healthy kidney donors. MethodsGFR was measured with 51Cr-EDTA and the slope–intercept technique in patients from two hospitals, the first using three samples (540 adults, including 382 with cancer, and 124 children, including 40 with cancer) and the second using four samples (256 adults, including 132 with cancer and 75 donors), scaled to body surface area (BSA) of 1.73 m2 and corrected using Brochner–Mortensens equations (GFR/BSA). GFR/ECV was measured from the exponential rate constant with an appropriate one-compartment correction. ECV/BSA was calculated as the quotient, GFR/BSA:GFR/ECV. ECV was also expressed in adults in relation to lean body mass and in children as a fraction of ECV estimated from height and weight (eECV). ResultsIn men from both centres, neither ECV/BSA nor ECV/lean body mass showed an increase in cancer patients. In women from both centres, however, they were both significantly higher in cancer patients than in noncancer patients and, in centre 2, than in donors. In children from centre 1, ECV/BSA, but not ECV/eECV, was significantly higher in cancer patients. ConclusionECV is expanded in female cancer patients but not male cancer patients. ECV may be expanded in children with cancer but the recorded difference in ECV/BSA is probably related to differences in patient size and a nonproportionate relationship between ECV and BSA.