Eileen O. Smith

Computerized three-dimensional segmented human anatomy.

Manual segmentation of 129 x-ray CT transverse slices of a living male human has been done and a computerized 3-dimensional volume array modeling all major internal structures of the body has been created. Each voxel of the volume contains a index number designating it as belonging to a given organ or internal structure. The original x-ray CT images were reconstructed in a 512 x 512 matrix with a resolution of 1 mm in the x,y plane. The z-axis resolution is 1 cm from neck to midthigh and 0.5 cm from neck to crown of the head. This volume array represents a high resolution model of the human anatomy and can serve as a voxel-based anthropomorphic phantom suitable for many computer-based modeling and simulation calculations.

Acute cocaine effects on absolute cerebral blood flow

Abstract Cocaine use has been associated with vasoconstriction and stroke, and several studies have demonstrated that it decreases relative cerebral blood flow (rCBF) in humans. However, rCBF has not been quantitated. We compared 40 mg IV cocaine hydro-chloride to placebo effects on absolute rCBF in four cocaine users using 99mTc-HMPAO SPECT with a modified microsphere model for CBF quantitation. Cocaine produced significant decreases in rCBF in all regions studied with a mean decrease of 30% in absolute whole brain blood flow (P = 0.002) which was 3-fold greater than relative blood flow changes.

Evaluation of the monoamine uptake site ligand [131I]methyl 3β-(4-Iodophenyl)-tropane-2β-carboxylate ([123I]β-CIT) in non-human primates: Pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI

Abstract The in vivo properties of a new radioiodinated probe of the dopamine and serotonin transporter, [123I]methyl 3β-(4-iodophenyl)tropane-2β-carboxylate ([123I]β-CIT) were evaluated in baboons and vervet monkeys. The labeled product was prepared in 65.2 ± 2.8% yield (mean ± SEM; n = 18) by reaction of the tributylstannyl precursor with [123I]NaI in the presence of peracetic acid followed by high pressure liquid chromatography (HPLC) purification to give a product with radiochemical purity of 97.5 ± 0.5% and specific activity of 500–1200 Ci/mmol. After intravenous administration, whole brain activity peaked at 6–10% injected dose within 1 h post injection (p.i.) and washed out in a biphasic manner with clearance half-lives of 1–2 and 7–35 h for the rapid and slow components, respectively. Excretion occurred primarily through the hepatobiliary route, with about 30% of the injected dose appearing in the GI tract after 5 h. Estimates of radiation absorbed dose gave 0.01, 0.1, 0.2 and 0.03 mGy/MBq to the brain, gall bladder wall, lower large intestine wall and urinary bladder wall, respectively. High resolution SPECT imaging in a baboon demonstrated high uptake of tracer in the region of the striatum (striatum: cerebellum ratio 4.0), in the hypothalamus (ratio 2.6) and in a midbrain region comprising raphe, substantia nigra and superior colliculus (ratio 2.0), with regional brain uptakes measured at 210 min p.i. of [123I]β-CIT. The anatomical locations of the regions on the SPECT image were confirmed by coregistration with MRI. Plasma metabolites and pharmacokinetics were analyzed in baboons and vervets by ethyl acetate extraction and HPLC. The major metabolite was a polar, non-extractable fraction, which increased to > 50% of the plasma activity by 30–45 min p.i. A minor lipophilic (extractable) metabolite was also observed, increasing to about 4% at 2–3 h p.i. The plasma protein bound fraction, determined by ultrafiltration, was 74.8 ± 1.4% (n = 6). The arterial input function was characterized by the sum of three exponential terms with half-lives of 0.3–1.7, 9.7–24.9 and 77–166 min, respectively, for the concentration of free parent compound. [123I]β-CIT promises to be a useful marker for SPECT study of the monoamine uptake system in primate brain.

The effect of mode of agitation and type of plastic bag on storage characteristics and in vivo kinetics of platelet concentrates

We studied the characteristics of platelet concentrates stored for 5 days at 22°C. Platelets were prepared in three plastic bags (PL 732, PL 1240, and CLX) and stored on one of four platelet agitators, 1‐ or 6‐rpm elliptical and 2‐ or 6‐rpm circular rotators. A total of 76 studies were divided among 12 groups, each group being composed of a different storage bagrotator combination. In vivo recovery and survival were calculated using Indium‐111 oxine‐labeled platelets injected into autologous volunteers. Platelet recovery was assessed at 2 hours postinjection or as the y‐intercept of the multiple‐hit model survival curve. Survival was calculated using linear, exponential, and multiple‐hit computer models. Linear T 1/2 also was calculated as an index of platelet survival.

Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates

The pharmacokinetics of [123I]iomazenil (Ro 16-0154) in 5 healthy human volunteers were compared to those in 2 hypothermic and 3 normothermic anesthetized monkeys. Following intravenous injection in humans and monkeys, [123I]iomazenil rapidly diffused outside the vascular bed and was cleared from the arterial plasma triexponentially. The clearance half-times in hypothermic animals were protracted to values closer to those of the human. [123I]Iomazenil was metabolized mainly to a polar radiometabolite (not extracted by ethyl acetate) in the human whereas an additional lipophilic radiometabolite was detected in the monkey. In vitro and in vivo studies showed that [123I]iomazenil established equal concentrations in association with the cellular and plasma component of the blood, indicating that the plasma clearance of [123I]iomazenil mirrors that of the blood. Analysis of organs from a monkey given [123I]iomazenil showed that the parent compound was actively taken up by peripheral organs; the polar radiometabolite accumulated mainly in the bile and the kidneys whereas the non-polar radiometabolite accumulated in the urine and kidneys. Greater than 90% of the radioactivity in the different regions of the brain was unchanged parent [123I]iomazenil.

Dynamic SPECT imaging after injection of the benzodiazepine receptor ligand [123I]iomazenil in healthy human subjects

Previous work suggests that iomazenil (formerly known as Ro 16-0154) is a useful ligand for static imaging of the benzodiazepine (BZ) receptor with single photon emission computed tomography (SPECT). The present study evaluated the feasibility of dynamic SPECT imaging of cerebral radioactivity following intravenous [123I]iomazenil injection in healthy human subjects, in preparation for future receptor quantitation studies. Maximal brain uptake was reached approximately 25-30 minutes after i.v. administration of the radioligand and represented approximately 12% of the injected dose. The regional distribution of radioactive densities was consistent with the known distribution of BZ receptors in human brain, with highest uptake localized over the occipital area. Washout of cortical radioactivity was regionally variable but relatively slow, with a half-life of approximately 4 hours after the time of peak radioactivity. In summary, [123I]iomazenil is a promising SPECT radioligand for the BZ receptor, with high brain uptake, relatively slow washout of radioactivity, and appropriate regional distribution.

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.

Abstract Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer’s disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age ± SD = 68.9 ±8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 ± 8.0 years) participated. AD patients were scanned with 20 mCi of Tc-99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 ± 5.8%; whereas those treated with placebo showed a decrease of −2.0 ± 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly “functional” and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.

High resolution anthropomorphic phantom for Monte Carlo analysis of internal radiation sources

A digital voxel phantom which closely resembles a typical male anatomy has been created. Organ outlines were manually drawn with 1-mm resolution in each of 78 transverses of the human torso. Such an anthropomorphic three-dimensional phantom has several interesting applications in the radiological sciences. Monte Carlo simulations can yield diagnostically realistic images of new investigational radiopharmaceuticals. Uptake characteristics approximated from small animal experiments can be used to test the imaging characteristics in human geometries. The resulting images can serve as ideal projection data of known source and attenuator distributions. This can lead to a better understanding of the image formation process for clinically realistic models, and can prove especially interesting in testing and improving tomographic reconstruction algorithms. Dose calculations for internal and external radiation sources using this phantom can give new insights in the field of health physics and therapy.<<ETX>>

Use of an electromechanical infusion pump for transfusion of platelet concentrates

To determine whether platelet concentrates can be administered safely through electromechanical infusion devices, we studied stored platelet concentrates passed through one pump system (Abbott). We measured in vitro changes in platelet count and lactic dehydrogenase (LDH) and beta‐ thromboglobulin (beta‐TG) release which occurred after passing the concentrates through the pump system. To compare in vivo survival, five normal volunteers were given an injection of autologous Indium‐111‐ labeled platelet concentrates at two different times, once using platelets which had been passed through the pump system (test group) and once using platelet concentrates which had not (control group). In vitro studies showed no significant changes (p greater than 0.05) in platelet count, or in LDH or beta‐TG release after passage through the pump system. In vivo platelet recovery at 2 hours was 39.8 +/− 4.7 percent (mean +/− 1 SD) for the control platelets and 40.7 +/− 9.3 percent for the platelets passed through the pump system (p greater than 0.05; n = 5). There was no significant difference in platelet survival measured in days between the control group and the test group using a linear (8.0 +/− 0.9 vs. 7.2 +/− 0.3), exponential (3.7 +/− 0.7 vs. 3.1 +/− 0.5), or multiple hit (5.4 +/− 2.3 vs. 4.8 +/− 1.0) (p greater than 0.05; n = 5) model. We conclude that this pump system is acceptable for use in clinical practice when control over volume and rate of platelet transfusion is important.

Single-photon emission computed tomography in distal field hypoperfusion.

To assess the ability of technetium‐99m hexamethylpropyleneamineoxime single‐photon emission computed tomography (SPECT) imaging to differentiate distal field hypoperfusion from other stroke mechanisms, 24 patients with acute cerebral ischemia were studied. SPECT scans were read by two physicians according to a preestablished set of criteria for distal field hypoperfusion. SPECT patterns read as “probable” or “definite” for distal field hypoperfusion were found in 42% (1 0/24); of these, 80% (8/1 0) had ipsilateral carotid occlusion or highgrade stenosis. Severe carotid stenosis was found in 43% (6/14) with SPECT scans negative for distal field hypoperfusion (Fisher exact test [1‐tailed] p = 0.0796). The results suggest that a distal field hypoperfusion pattern on SPECT may identify patients with hemodynamically significant large vessel disease.