Development and feasibility of quantitative dynamic cardiac imaging for mice using µSPECT.

BACKGROUND: Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. METHODS: We used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. RESULTS: The recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min-1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and ß = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions. CONCLUSIONS: We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

The association between parents' perceived social norms for toothbrushing and the frequency with which they report brushing their child's teeth.

OBJECTIVES: To determine whether parents' judgements on how often other parents brush their children's teeth are associated with the frequency with which they brush their own children's teeth, and their satisfaction with their child's brushing routine. METHODS: A cross-sectional questionnaire survey completed by 297 parents of children aged 3-6. Parents were asked how often they brushed their own child's teeth per week, how often they thought other parents did so, and how satisfied they were with their child's toothbrushing routine. Demographic data were also collected. RESULTS: The mean frequency that parents brushed their children's teeth was 12.5 times per week. Multiple regression analysis tested the relationship between parents' perceptions of other parents brushing frequency (mean 10.5 times per week) and how often they brushed their own child's teeth, controlling for socio-demographic factors, and yielded a positive association (p < 0.001). There was a positive association between parents' satisfaction with their child's brushing routine and the extent to which they thought it was better than that of the average child (p < 0.001). CONCLUSIONS: Parents' judgements on how frequently other parents brush their children's teeth are associated with their own behaviour and satisfaction. Re-framing oral health messages to include some form of social normative information ("most parents do this") may prove more persuasive than simple prescriptive advice ("you should do this").

Determining the effect of cardiac blood volume on accuracy of uptake rate constants by simulation.

Objective. There is great interest in better understanding coronary microvascular disease using mouse models. Typical quantification requires dynamic imaging to estimate the rate constantK1of the tracer moving from the blood into the myocardium. In addition toK1, it is also desirable to determine blood volume fractionV, which if known allows for more accurate fitting ofK1. Our previously published kinetic modeling software did not consider the effect ofV. To ensure a better fit of experimental data to the model for myocardialµSPECT imaging, in this work we updated our kinetic modeling software to include a blood volume fractionV, which adds a fraction of the arterial activity concentration into the tissue concentration.Approach. The tissue and blood time-activity curves (TACs) used for fit input were generated using ideal equations with known values in MATLAB. This allowed post-fit results to be compared to known values to determine fit errors. Parameters that were varied in generating the TACs included blood volume fraction (0, 0.05, 0.1, 0.2 and 0.3),K1(0.5, 1.5, 2.5 ml min-1g-1), frame length (1, 2, 5, 10, 15, 20 s), FWHM of the input Gaussian (10, 20, 40 s), and time of the injection peak relative to frame duration. Blood volume-fraction results have low error when blood volume is lowest, but results worsen as frame length andK1increase.Main results. We demonstrated that blood volume can be accurately determined, and also show how fit accuracy varies across TACs with different input properties.Significance. This information allows for robust use of the fitting algorithm and aids in understanding fit performance when used in animal studies.

Metabolomics and cancer preventive behaviors in the BC Generations Project.

Metabolomics can detect metabolic shifts resulting from lifestyle behaviors and may provide insight on the relevance of changes to carcinogenesis. We used non-targeted nuclear magnetic resonance to examine associations between metabolic measures and cancer preventive behaviors in 1319 participants (50% male, mean age 54 years) from the BC Generations Project. Behaviors were dichotomized: BMI < 25 kg/m2, ≥ 5 servings of fruits or vegetables/day, ≤ 2 alcoholic drinks/day for men or 1 drink/day for women and ≥ 30 min of moderate or vigorous physical activity/day. Linear regression was used to estimate coefficients and 95% confidence intervals with a false discovery rate (FDR) of 0.10. Of the 218 metabolic measures, 173, 103, 71 and 6 were associated with BMI, fruits and vegetables, alcohol consumption and physical activity. Notable findings included negative associations between glycoprotein acetyls, an inflammation-related metabolite with lower BMI and greater fruit and vegetable consumption, a positive association between polyunsaturated fatty acids and fruit and vegetable consumption and positive associations between high-density lipoprotein subclasses with lower BMI. These findings provide insight into metabolic alterations in the context of cancer prevention and the diverse biological pathways they are involved in. In particular, behaviors related to BMI, fruit and vegetable and alcohol consumption had a large metabolic impact.

Physical activity, sedentary behaviours, and the prevention of endometrial cancer.

Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate-vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate-vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer.

Height and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.

BACKGROUND: The relationship between prostate cancer and height is uncertain. METHODS: We prospectively examined the association of height with prostate cancer among 34,268 men in the prostate, lung, colorectal, and ovarian cancer trial. Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up. RESULTS: Overall, tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease, but the risk for aggressive prostate cancer tended to be greater in taller men (Gleason score > or = 7 or stage > or = III; P trend=0.05; relative risk (RR) for 190 cm + vs < or = 170 cm = 1.39, 95% confidence interval (95% CI): 0.96-2.01). This association was largely limited to men below the age of 65 years (P trend=0.008; RR for 190 cm + vs < or = 170 cm = 1.76, 95% CI: 1.06-2.93; P for interaction=0.009), although the number of cases was small and risk estimates were somewhat unstable. CONCLUSION: The results of this large prospective prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer.

Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.

INTRODUCTION: Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic. AIMS AND OBJECTIVES: This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation. METHODS: Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked. CONCLUSION: We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.

Past body mass index and risk of mortality among women.

BACKGROUND: Epidemiologic studies of body mass index (BMI) in relation to mortality commonly exclude persons with health conditions and/or a history of smoking to prevent bias resulting from illness-related weight loss ('reverse causation'). Analysis of BMI from an earlier time period may minimize reverse causation without requiring exclusion of participants based on disease or smoking history. METHODS: We prospectively examined BMI based on technician measurements of weight and height from 10 years prior to start of follow-up in relation to subsequent mortality in a cohort of 50 186 women who were 40-93 years old at baseline in 1987-1989. Deaths were ascertained through the US National Death Index. Proportional hazards regression was used to estimate hazard ratios (HRs) of mortality, adjusted for age, education, race/ethnicity, income, menopausal hormone use, smoking and physical activity. RESULTS: During 10 years of follow-up through 1997, 5201 women died. Overall, we observed a J-shaped association between BMI and mortality, with increased risk for women who were underweight, overweight or obese. The HRs and 95% confidence intervals of mortality for BMI categories of <18.5, 18.5-20.9, 21.0-23.4 (reference), 23.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9 and 35.0+ kg m(-2) were 1.43 (1.19, 1.72), 1.07 (0.98, 1.17), 1.00 (reference), 1.10 (1.00, 1.20), 1.20 (1.11, 1.31), 1.23 (1.11, 1.37), 1.60 (1.44, 1.77) and 1.92 (1.64, 2.24). There was little evidence that pre-existing conditions (heart disease, diabetes and/or cancer) or smoking history modified the past BMI and mortality relation (P=0.54 and 0.76). CONCLUSIONS: In this large cohort of women, BMI based on technician measurements of weight and height from 10 years prior to baseline showed increased risk for mortality across the range of overweight and obesity, regardless of disease and smoking history. Observed associations between overweight, obesity and mortality in healthy individuals may also apply to persons with a history of disease or smoking.

Effect of pinhole shape on projection resolution.

We are designing a dual-resolution pre-clinical SPECT system based on square-pinhole apertures for use in applications with a small field-of-view (FOV), such as cardiac imaging of mice. Square pinholes allow for increased sensitivity due to more efficient projection tiling on the detector compared to circular pinholes. Aperture fabrication techniques cannot produce a perfect square, giving the square pinholes some amount of roundedness at the corners. This work investigates how this roundedness affects the physical properties of projection images in terms of spatial resolution. Different pinhole full-acceptance angles and roundedness values were simulated. To facilitate a fair comparison, properties of the non-square pinholes were manipulated to yield pinholes with approximately the same sensitivity (to within 0.1%) and FOV (to within 0.5%) as those of the square pinholes, subsequently referred to as matched apertures. The aperture size (flat-to-flat edge length) of each non-square aperture was increased until its sensitivity was approximately equal to that of the square pinhole. Next, the full acceptance angle was increased until the FOV of each non-square aperture was approximately equivalent to that of the square pinhole. Sensitivity was calculated to include both the geometric and penetrative sensitivity of a point source, as well as the packing faction of the multi-pinhole collimator. Using the sensitivity-matched and FOV-matched apertures, spatial resolution was estimated. For the 0.3 mm, 0.5 mm, and 1 mm edge-length square apertures studied, the full-width at half-maximum widened as pinhole shape changed from square to circle, while full-width tenth-maximum showed little change. These results indicate that a perfect square pinhole shape is more desirable than a rounded-square pinhole with regard to spatial resolution when sensitivity and FOV-matched pinholes are compared.

Telephone review after minor oral surgery.

An audit of outpatient clinic attendances at Cardiff Dental Hospital (between September 2009 and March 2010) showed that 30% of patients failed to attend review appointments after minor operations. To reduce rates of non-attendance we set up a system of telephone review in March 2010. Patients were given a telephone appointment two weeks after their minor operation (mainly removal of lower third molars), instead of an appointment at the outpatient clinic. A trained nurse contacted each patient to complete a structured questionnaire that included questions about numbness, pain, and swelling. During the first year of the project, 1020 patients were booked for telephone review and of these 90% were discharged. 674 (66%) were discharged after telephone review, and 245 (24%) were not contactable. A total of 101 patients (10%) were brought in for clinic review because they reported complications. Estimated staff costs per patient for telephone review and clinic review were £3.05 and £23.55 respectively. Telephone review resulted in a significant reduction in the number of patients who failed to attend the clinic (OR=0.88, 95% CI 0.81 to 0.96) and facilitated audit of complications. The use of telephone review in conjunction with clinical follow-up for those with postoperative problems allows for cost-effective care with reduced rates of non-attendance.

Progressive unilateral damage of the entorhinal cortex enhances synaptic efficacy of the crossed entorhinal afferent to dentate granule cells.

Progressive injury to the mammalian CNS often reduces the severity of lesion-induced deficits or spares the behavior from deficits altogether. The mechanism(s) underlying this behavioral sparing is not clearly understood, but axonal sprouting is a likely candidate. To test this possibility, unilateral, two-stage (progressive) lesions of the entorhinal cortex, which are known to accelerate sprouting by the crossed temporodentate pathway and spare spatial memory function, were made in rats. We examined the changes in synaptic efficacy (as measured by the amplitude and slope of evoked population EPSPs) of the crossed temporodentate projection after either one-stage or progressive unilateral lesions of the entorhinal area. Whereas the synaptic efficacy of the one-stage group did not differ significantly from the control group at 4, 6, or 8 d after the lesion, the synaptic efficacy of the crossed temporodentate pathway in the progressive lesion group significantly increased above the control values as early as 4 d after the lesion and remained stable thereafter. Axonal sprouting thus may provide a mechanism by which to account for behavioral sparing after progressive brain damage.

Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow.

We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.

Mouse macrophages contain a truncated CD4 transcript.

Mouse macrophages do not express CD4 on their surfaces. We used the polymerase chain reaction to investigate CD4 gene transcription in individual clones of primary mouse splenic macrophages and cell lines of spleen and bone marrow macrophages. The results show only the presence of CD4 mRNA transcripts that are truncated in the 3' coding sequence, thus explaining the lack of expression of a mature CD4 gene product by these cells.

Bone marrow natural suppressor cells inhibit the growth of myeloid progenitor cells and the synthesis of colony-stimulating factors.

Natural suppressor (NS) cells, which nonspecifically suppress immune responses, are generally found at sites of hemopoietic generation or regeneration. Murine bone marrow NS cells were activated by recombinant interleukin 3 (rIL-3) or recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and produced a soluble suppressor factor. In the present study, the soluble suppressor factor from bone marrow NS cells was found to be a potent inhibitor of myeloid colony formation at concentrations below those required for immunosuppression. NS cell supernatants inhibited the growth of granulocyte-macrophage colony-forming units (CFU-GM), granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU-GEMM), and erythroid colony-forming units (CFU-E) to a similar extent. Neutralizing anti-transforming growth factor beta (TGF-beta) reversed the suppressive effects of the supernatants, suggesting that TGF-beta was involved in the suppression. The NS cell supernatants also inhibited the production of colony-stimulating activity by bone marrow stromal cells and the transcription of GM-CSF mRNA by activated T cells. These data suggest that NS cells are important regulators of hemopoiesis. NS cells, which are non-adherent, radioresistant non-T cells resident in the bone marrow, were shown to be sensitive to treatment with the lysosomotropic agent, L-leucine methyl ester, suggesting that the NS cells may be of large granular lymphocytic or monocytic lineage. Cytotoxicity studies revealed that cells in the NS population had natural cytotoxic (NC), but not natural killer (NK) activity.

Improved quantification for local regions of interest in preclinical PET imaging.

In Positron Emission Tomography, there are several causes of quantitative inaccuracy, such as partial volume or spillover effects. The impact of these effects is greater when using radionuclides that have a large positron range, e.g. (68)Ga and (124)I, which have been increasingly used in the clinic. We have implemented and evaluated a local projection algorithm (LPA), originally evaluated for SPECT, to compensate for both partial-volume and spillover effects in PET. This method is based on the use of a high-resolution CT or MR image, co-registered with a PET image, which permits a high-resolution segmentation of a few tissues within a volume of interest (VOI) centered on a region within which tissue-activity values need to be estimated. The additional boundary information is used to obtain improved activity estimates for each tissue within the VOI, by solving a simple inversion problem. We implemented this algorithm for the preclinical Argus PET/CT scanner and assessed its performance using the radionuclides (18)F, (68)Ga and (124)I. We also evaluated and compared the results obtained when it was applied during the iterative reconstruction, as well as after the reconstruction as a postprocessing procedure. In addition, we studied how LPA can help to reduce the 'spillover contamination', which causes inaccurate quantification of lesions in the immediate neighborhood of large, 'hot' sources. Quantification was significantly improved by using LPA, which provided more accurate ratios of lesion-to-background activity concentration for hot and cold regions. For (18)F, the contrast was improved from 3.0 to 4.0 in hot lesions (when the true ratio was 4.0) and from 0.16 to 0.06 in cold lesions (true ratio = 0.0), when using the LPA postprocessing. Furthermore, activity values estimated within the VOI using LPA during reconstruction were slightly more accurate than those obtained by post-processing, while also visually improving the image contrast and uniformity within the VOI.

Simulation of triple coincidences in PET.

Although current PET scanners are designed and optimized to detect double coincidence events, there is a significant amount of triple coincidences in any PET acquisition. Triple coincidences may arise from causes such as: inter-detector scatter (IDS), random triple interactions (RT), or the detection of prompt gamma rays in coincidence with annihilation photons when non-pure positron-emitting radionuclides are used (ß(+)γ events). Depending on the data acquisition settings of the PET scanner, these triple events are discarded or processed as a set of double coincidences if the energy of the three detected events is within the scanner's energy window. This latter option introduces noise in the data, as at most, only one of the possible lines-of-response defined by triple interactions corresponds to the line along which the decay occurred. Several novel works have pointed out the possibility of using triple events to increase the sensitivity of PET scanners or to expand PET imaging capabilities by allowing differentiation between radiotracers labeled with non-pure and pure positron-emitting radionuclides. In this work, we extended the Monte Carlo simulator PeneloPET to assess the proportion of triple coincidences in PET acquisitions and to evaluate their possible applications. We validated the results of the simulator against experimental data acquired with a modified version of a commercial preclinical PET/CT scanner, which was enabled to acquire and process triple-coincidence events. We used as figures of merit the energy spectra for double and triple coincidences and the triples-to-doubles ratio for different energy windows and radionuclides. After validation, the simulator was used to predict the relative quantity of triple-coincidence events in two clinical scanners assuming different acquisition settings. Good agreement between simulations and preclinical experiments was found, with differences below 10% for most of the observables considered. For clinical scanners and pure positron emitters, we found that around 10% of the processed double events come from triple coincidences, increasing this ratio substantially for non-pure emitters (around 25% for (124)I and > 50% for (86)Y). For radiotracers labeled with (18)F we found that the relative quantity of IDS events in standard acquisitions is around 18% for the preclinical scanner and between 14 and 22% for the clinical scanners. For non-pure positron emitters like (124)I, we found a ß(+)γ triples-to-doubles ratio of 2.5% in the preclinical scanner and of up to 4% in the clinical scanners.

Analysis of the cos region of the Lactococcus lactis bacteriophage sk1.

The location, structure and nature of the cos site of the Lactococcus lactis bacteriophage sk1 was determined using a Taq DNA polymerase runoff sequencing technique. The cos site contains a single-stranded 3' overhang of 11 nucleotides. The region surrounding cos contains several features which may be involved in the binding and catalytic action of a phage terminase. These include four putative terminase-binding sites which show some homology to lambda R-sites, an 11-bp direct repeat, a 10-bp inverted repeat, a string of eight consecutive C residues and six copies of the pentanucleotide, AATCT. The spacing between adjacent copies of the pentanucleotides would place them on the same side of the DNA helix.

Phenotypes and alloantigen-presenting activity of individual clones of microglia derived from the mouse brain.

To clarify the origin and function of the microglia residing in the central nervous system, we cloned brain cells from newborn and adult mice in soft agar containing the macrophage-specific growth factor, colony-stimulating factor-1 and expanded the cells from individual colonies in liquid culture medium. The results of molecular, immunophenotypic and functional analyses showed that the clones consisted of microglia derived from the macrophage family of cells. For instance, the microglia contain mRNA transcripts for the receptor for colony-stimulating factor-1 and truncated CD4 transcripts similar to those found in mouse macrophages but not T helper cells. About a third of the microglial progenitors gave rise to progeny that constitutively induced the selective proliferation of naive allogeneic CD8+ T cells in a CD4+ T cell-independent manner, a response that was inhibited by monoclonal antibodies to major histocompatibility complex (MHC) class I molecules on the microglia. Since all microglia expressed similar levels of MHC class I molecules, the basis for the alloantigen presentation likely resides in the ability of some clones of microglia to synthesize co-stimulator molecules that are required for CD8+ T cell proliferation. Thus, at least some microglia in mouse brain arise from endogenous progenitors and appear capable of specialized functions.

Nonuniform collimator sensitivity: improved precision for quantitative SPECT.

UNLABELLED: Attenuation of photons degrades both the accuracy and the precision of SPECT images; attenuation correction algorithms correct the bias but cannot improve precision. Increased noise due to photon attenuation is most pronounced in regions deep in solid body sections, such as the brain and abdomen. We have quantified the degradation in performance in several estimation tasks that can be attributed to photon attenuation and determined the degree to which performance might be improved by a collimator with a nonuniform sensitivity profile. METHODS: The analysis used ideal-observer models of performance in tasks involving estimation of the activity and size of a focal lesion. The models were based on the Cramer-Rao lower bound on the variance with which lesion activity and size can be estimated by an unbiased procedure. To quantify the effects of attenuation, values of the Cramer-Rao bound were calculated for each estimation task as a function of location of the lesion in circularly-shaped attenuators of 10- and 20-cm radii, with and without attenuation. Values of the bound were also determined for two nonuniform sensitivity profiles, one of which was designed to equalize (or nearly equalize) task performance throughout the image. RESULTS: For 99mTc, photon attenuation increased the variance of the estimates by factors of up to 4.5 for the 10-cm radius attenuator and up to 20.0 for the 20-cm radius attenuator. A collimator with a nonuniform sensitivity function reduced variance by factors of up to 1.8 for the 10-cm radius attenuator and up to 2.8 for the 20-cm radius attenuator. These gains in estimation performance were insensitive to the imaging task and to deviations from the assumed attenuator size and shape. CONCLUSION: Performance in estimation tasks using images from SPECT systems with uniform sensitivity collimators is considerably lower than the theoretical optimum. We have derived a sensitivity function, realizable using existing technology, that improves performance substantially.

Quantitative multi-detector emission computerized tomography using iterative attenuation compensation.

An iterative procedure to correct for attenuation has been developed for a multidetector, single-photon emission tomographic scanner. The difference between measured and estimated data projections is used at each iteration to form an error image which is used, in turn, to correct the image. A damping factor that minimizes chi2 is applied after each iteration to speed convergence. Several phantoms of different size, with various concentration distributions, have been used to compare this method with a first-order multiplicative attenuation correction used previously with this scanner. The first-order correction is inadequate for most of the phantoms studied, whereas relative and absolute quantitative capability is demonstrated for the iterative attenuation correction. The reconstructed average number of counts per pixel is a linear function of activity concentration up to 5 muCi/ml for all regions of uniform activity whose size is greater than or equal to 5 cm. The importance of using an accurate attenuation distribution with this method is demonstrated with a torso-like phantom.