Lee A. Forstrom

Reproducibility and simplification of 13C-octanoic acid breath test for gastric emptying of solids.

Objective:The accuracy of the 13C-octanoic acid breath test is enhanced by breath sampling over 6 h rather than 4 h, but this increases the cost of the test. Our aim was to validate a less costly but accurate sequence of breath sampling for measuring gastric emptying of solids.Methods:We performed the 13C-octanoic acid breath test and tested its reproducibility relative to simultaneous scintigraphy in 30 healthy volunteers.Results:There was a significant but weak correlation between t1/2 measured by the two tests (rs= 0.54, p < 0.005), but not between the duration of the lag phase. The differences in the t1/2 measurements between the tests were different between subjects but were highly reproducible within subjects. Within- and between-subject variations of measurements of gastric emptying with the 13C-octanoic acid breath test were not significantly different from the variations observed with scintigraphy. A subset of 11 breath samples collected over 6 h (24 samples) predicted (r2 > 0.95) the variables characterizing the cumulative appearance of 13CO2 in breath; these samples were at 35, 50, 95, 110, 140, 155, 215, 245, 260, 290, and 335 min. The accuracy of this subset of sampling times was confirmed in a separate set of breath test samples over 6 h from the same 30 subjects.Conclusions:The 13C-octanoic acid breath test for gastric emptying of solids is as reproducible as scintigraphy. A subset of 11 sampling times provides sufficient information to characterize the whole breath-test curve, but the sampling period should be extended to 6 h after dosing.

Scintigraphy of the whole gut: Clinical evaluation of transit disorders

OBJECTIVE To describe an initial clinical experience with a noninvasive scintigraphic technique for assessing gastrointestinal motility. DESIGN We studied gastric, small bowel, and colonic transit in 109 unselected patients encountered between June and December 1992 at the Mayo Clinic. MATERIAL AND METHODS The study patients were categorized on the basis of major complaint (constipation in 46, upper gastrointestinal symptoms in 45, and diarrhea in 18) and presence or absence of an underlying organic disease. Radioscintigraphy was used to analyze various regions of the gastrointestinal tract; scans were obtained at 2, 4, 6, and 24 hours after ingestion of a radiolabeled test meal. RESULTS Overall, patients with a main complaint of constipation usually had slow or normal gastric, small bowel, and colonic transit, whereas those with diarrhea as the major symptom usually had normal or fast results of these studies. In the 65 patients with no underlying organic disease, inconsistent patterns of gastric emptying and small bowel and colonic transit were noted. CONCLUSION Our results suggest that this 24-hour scintigraphic test may be clinically useful in screening for dysmotility syndromes in patients with nausea, vomiting, diarrhea, or constipation.

Relationship between clinical features and gastric emptying disturbances in diabetes mellitus.

Background and objectives  Gastric emptying (GE) may be delayed or rapid in diabetes mellitus. We sought to ascertain differences in risk factors or associated features (i.e. diabetic ‘phenotype’) among patients with diabetes who have rapid, slow or normal GE.

The effects of anagrelide on human megakaryocytopoiesis

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic‐committed progenitor cells (CFU‐M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU‐M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU‐M in vitro. In‐vivo and in‐vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.

Early redistribution of thallium-201 after temporary ischemia.

To define the time course of redistribution of thallium-201 (251TI), ischemia was induced in seven pigs by temporary occlusion of the circumflex coronary artery. After 1½ min of occlusion 201T1 and labeled microspheres were injected into the left atrium. Flow was re-established 4 min after occlusion. Prior to reflow, the relative activities of 201TI and microspheres in the ischemic area were similar, but as early as 5 min after reflow the relative 201fT activity was considerably higher than the relative microsphere activity and from 15 to 105 min after reflow, relative 201TI activity (average 69% of that in normal myocardium) continued to be higher than relative microsphere activity (average 6% of normal). Myocardial arteriovenous differences for 201TI were followed sequentially after 201Tl injection in normal dogs and in dogs with temporary coronary occlusions. The results suggested both loss of 201TI from normal myocardium beginning 10 min after 205TI injection and increased extraction of 201TI from the blood pool immedately after release of a transient occlusion. Redistribution of 201TI therefore begins very soon after relief of myocardial ischemia and even a short delay in initiating myocardial imaging may decrease the sensitivity of the technique for detecting transient ischemia.

18F-FDG labelling of human leukocytes

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20°C and 37°C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37°C for 30 min (62.7±1.6%), and was further enhanced by mixing during incubation (78.1±3.9%). Cell labelling was predominantly of granulocytes (78.5±1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.

Biodistribution and dosimetry of [18F]fluorodeoxyglucose labelled leukocytes in normal human subjects

This study was performed in order to assess [18F]fluorodeoxyglucose white blood cell (18F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with 18F-FDG at 37°C for 20 min. After washing and resuspension, 18F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of 18F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9±2.3% at 6 h), and brain uptake (1.7±0.4%) were consistent with partial elution of 18F-FDG. Positron emission tomography imaging performed at5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for 18F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of 111In oxine labelled leukocytes. Further studies of 18F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

Medium term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea

Background—Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients. Aims—To evaluate the medium term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. Methods—In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. Results—There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p<0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. Conclusions—Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.

Patient-related pitfalls and artifacts in nuclear medicine imaging

Quality control in nuclear medicine is all important. This applies not only to preparation of the patient and acquisition of the image, but also to interpretation of the study. Although it may seem self-evident, it is important to remain aware of artifacts that are directly related to the patient and need special consideration. Furthermore, at times the distinction between normal variants and artifacts can be difficult. Commonly encountered patient-related artifacts include artifacts caused by attenuation, contamination artifacts, and artifacts caused by intravenous lines, tubes, and catheters. Less commonly, artifacts arise because of the use of multiple isotopes, the presence of fistulas or surgically altered anatomy, and pharmaceuticals and other substances interfering with expected radiopharmaceutical uptake and distribution. The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these patient-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants.

Technical pitfalls in image acquisition, processing and display

Optimal image quality is an ideal in nuclear medicine that is not always realized, being subject to a variety of conditions that can act, either singly or in combination, to undermine its accomplishment. These conditions include potential defects and limitations in both the hardware and software used for the acquisition and reconstruction of nuclear medicine images. Factors relating to individual patients can contribute to these obstacles, including limitations in mobility and compliance. Importantly, suboptimal or erroneous technique is a common source of poor imaging results, with loss of diagnostic efficacy. Appropriate test selection and careful attention to patient preparation and procedural details are essential elements in avoiding image flaws and artifacts in nuclear medicine.