Donald Sashin

Attenuation correction for a combined 3D PET/CT scanner

In this work we demonstrate the proof of principle of CT-based attenuation correction of 3D positron emission tomography (PET) data by using scans of bone and soft tissue equivalent phantoms and scans of humans. This method of attenuation correction is intended for use in a single scanner that combines volume-imaging (3D) PET with x-ray computed tomography (CT) for the purpose of providing accurately registered anatomical localization of structures seen in the PET image. The goal of this work is to determine if we can perform attenuation correction of the PET emission data using accurately aligned CT attenuation information. We discuss possible methods of calculating the PET attenuation map at 511 keV based on CT transmission information acquired from 40 keV through 140 keV. Data were acquired on separate CT and PET scanners and were aligned using standard image registration procedures. Results are presented on three of the attenuation calculation methods: segmentation, scaling, and our proposed hybrid segmentation/scaling method. The results are compared with those using the standard 3D PET attenuation correction method as a gold standard. We demonstrate the efficacy of our proposed hybrid method for converting the CT attenuation map from an effective CT photon energy of 70 keV to the PET photon energy of 511 keV. We conclude that using CT information is a feasible way to obtain attenuation correction factors for 3D PET.

The effects of walking on the cross-sectional dimensions of the radius in postmenopausal women

SummaryThis report deals with the analysis of data from a 3-year clinical trial on the effect of walking on postmenopausal bone loss. Two hundred fifty-five women, with an average age of 57 at entry, were randomized into two groups, a walking and a control group. Bone measures in the shaft of the radius were carried out with a CT scanner in search of generalized skeletal effects rather than effects localized to the bones of the leg. Although bone density losses were comparable in the two randomized groups, changes in the crosssectional area of the radius were significantly greater in the walkers with high grip strength (>25 Kg) than in the controls with comparable high grip strength which corresponded to the upper half range of the grip-strength distribution. It is concluded that the moderate activity of walking exerted systemically positive effects on the radius which, within the protocol of the study, could be substantiated only when synergized with inherent muscle strength.

Test–retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test–retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5‐HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2–16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16–20%). For all regions, the absolute value of the test–retest differences in the Logan DV values averaged 12% or less. The test–retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature‐based values of the regional concentrations of 5‐HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3–25% of the total radioactivity in human plasma 10–120 min postinjection) were able to penetrate the blood–brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5‐HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin‐specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test–retest variability of [18F]altanserin‐specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5‐HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5‐HT2A receptors. Synapse 30:380–392, 1998.

Identification of Hemodynamic Compromise by Cerebrovascular Reserve and Oxygen Extraction Fraction in Occlusive Vascular Disease

Cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) are used to identify hemodynamic compromise in symptomatic patients with carotid occlusive vascular disease, but evidence suggests that they are not equivalent. The authors studied the relationship between CVR and OEF to evaluate their equivalence and stages of hemodynamic compromise. Symptomatic patients (N = 12) with carotid occlusion were studied by stable xenon–computed tomography CBF after intravenous acetazolamide administration for CVR, followed within 24 hours by positron emission tomography (PET) for OEF. Middle cerebral artery territories were analyzed by hemisphere and level. Hemispheric subcortical white matter infarctions were graded with magnetic resonance imaging. Both hemispheric and level analysis of CVR and OEF showed a significant (P = 0.001), negative linear relationship [CVR (%) = −1.5 (OEF) + 83.4, (r = −0.57, P = 0.001, n = 24]. However, 37.5% of the hemispheres showed compromised CVR but normal OEF and were associated (P = 0.019) with subcortical white matter infarction. CMRO2 was elevated in stage II hemodynamic compromise (CVR < 10%, OEF > 50%). CVR and OEF showed a significant negative linear relationship in stage II hemodynamic compromise but revealed hemispheres in hemodynamic compromise by CVR but normal OEF that were associated with subcortical white matter infarction.

Determinants of bone mass in menopause

Abstract Osteoporosis, one of the most prevalent diseases of the aged, is characterized by a reduced bone mass which increases the risk for skeletal fracture. The current research was designed to examine determinants of bone mass in 59 postmenopausal women. Information was obtained at baseline concerning anthropometric, nutritional, and physical activity factors. Bone mass in the arm and leg was measured by a computerized tomography (CT) scanner at baseline and 8 months later. The study revealed that the CT scanner is an effective, precise instrument for measuring bone mass, and significant bone loss was found over the 8-month period. The cross-sectional results indicated that the primary determinants of bone mass were age and physical activity.

CHAPTER 16 – Scatter Correction for Brain Receptor Quantitation in 3D PET

This chapter investigates the performance of the two correction algorithms when applied to scatter from activity outside the field of view. Two studies with the Utah phantom have been presented in the chapter: In the first, the entire water-filled phantom contains uniform activity with the exception of the short cylinder, which contains only water, and a chamber, which is empty. The fraction of scattered events in the image can then be estimated from the mean value in a region of interest placed on the short (cold) cylinder expressed as a fraction of the activity in the inner cylinder. In the second study, the annulus contains approximately four times the activity in the inner cylinder to simulate increased cortical uptake. In addition, the long cylinder contains twice the background activity to simulate uptake in subcortical structures. This chapter also explores the quantitative potential of 3D positron emission tomography (PET), and in particular the efficacy of the two scatter correction procedures, when applied to neuroreceptor ligand studies. For this, a ligand for imaging central benzodiazepine receptors is used.

PET OEF Reactivity for Hemodynamic Compromise in Occlusive Vascular Disease

Background and Purpose. Hemodynamic compromise in symptomatic patients with occlusive vascular disease (OVD) identified by cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) is an independent predictor of high stroke risk. However, up to 60% of patients compromised by CVR have normal OEF indicating a high rate of discordance. CVR is measured with an acetazolamide challenge, and OEF reactivity (OEFR) to acetazolamide, ie, a hemodynamic challenge, may reveal hemodynamic compromise and less discordance with measurements of CVR. Methods. Nine symptomatic patients with OVD were studied by positron emission tomography before and 15 minutes after 15 mg/kg intravenous acetazolamide in the middle cerebral artery territories of each hemisphere. Results. A close correlation between hemispheric CVR and OEFR was observed. Two hemispheres from two different patients showed an increase in OEF to acetazolamide challenge despite a normal baseline OEF. The two hemispheres showing an increase in OEF in response to acetazolamide were also associated with the lowest CVR and severest white matter hyperintensities. Conclusions. These observations suggest that positive OEFR may distinguish hemispheres in hemodynamic compromise despite normal OEF and show less discordance with CVR. However, these preliminary observations require confirmation in a larger study.

Computer Electronic Radiography For Early Detection Of Vascular Disease

A computerized electronic radiography system is being developed for early non-invasive detection, characterization and quantification of atherosclerotic lesions. The method uses a conventional x-ray source combined with a solid state detector system which is coupled to a digital computer for processing and display of the radiographic information. The computer stores and optimizes the image for improved interpretation of the image detail. The computer assisted image enhancement, vessel localization and pattern analysis is an integral part of the instrumentation system. The system has been evaluated in preliminary studies to determine contrast sensitivity, radiation exposure, resolution and diagnostic quality. Even at this early developmental stage of this technique, very low contrasts have been visualized. The arterial images obtained with intravenous injections in dogs have demonstrated the potential of this method for the non-invasive detection and quantification of atherosclerotic disease.

Efficiency normalization techniques for 3D PET data

Determination of the individual geometrical and efficiency normalization factors is a more involved procedure in 3D than in 2D because of the incorporation of oblique lines-of-response which results in an order of magnitude increase in the number of correction factors required. Techniques using rotating rod source scans in both 2D and 3D, and a uniform cylinder scan in 3D, have been developed for estimating normalization factors. However, a uniform plane source is generally considered the best combination of a low scatter environment and a centrally-located isotope distribution. Plane sources are difficult and expensive to construct with the required uniformity and long half-life. The authors have investigated the use of a scanning germanium line source which simulates a plane source distribution by slowly traversing across the field-of-view. They compare 3D reconstructions using estimates of the geometrical and efficiency correction factors for normalization obtained from rotating rod, plane (scanning line) and cylinder source distributions. No significant difference is found to distinguish the 3D reconstructions of the uniform cylinder.

Identifying regions of compromised hemodynamics in symptomatic carotid occlusion by cerebrovascular reactivity and oxygen extraction fraction

Abstract Objectives: Oxygen extraction fraction (OEF) and cerebrovascular reserve (CVR) are both proven predictors of stroke risk in symptomatic patients with carotid occlusion. Accordingly, hemispheric comparisons of CVR and OEF are significantly correlated. However, there was also substantial disagreement: hemispheres identified as compromised by CVR were normal by OEF. Our aim was to determine whether regional comparisons could resolve the CVR–OEF discordance. We also studied the relationship between white matter (WM) infarction and hemodynamic compromise. Methods: Quantitative CVR and OEF were measured in 12 symptomatic patients with internal carotid artery occlusion. CVR and OEF comparisons were made in the anterior watershed (AWS), middle cerebral artery (MCA) and WM territories using various thresholds for hemodynamic compromise. Associations with WM infarction were also recorded. Results: Comparison of CVR and OEF for the AWS and MCA showed high sensitivity (100%) with specificities of 83 and 40%, respectively. There was also agreement (k=Cohens Kappa) for the AWS (k=0.83) and MCA (k=0.39) territories. CVR–OEF discordance was reduced with regional analysis. Hemodynamic compromise was more often found in patients with WM infarction. Discussion: Regional comparison of CVR and OEF reduced the discordance compared with hemispheric analysis, especially for the AWS territory. Despite the persistence of some regions with compromised CVR and normal OEF, CVR is able to identify all regions with elevated OEF making it a useful screening technology. Future studies are needed to understand whether those remaining regions with compromised CVR are also at increased stroke risk despite normal OEF.