Motion frozen 18F-FDG cardiac PET

BackgroundPET reconstruction incorporating spatially variant 3D Point Spread Function (PSF) improves contrast and image resolution. "Cardiac Motion Frozen" (CMF) processing eliminates the influence of cardiac motion in static summed images. We have evaluated the combined use of CMF- and PSF-based reconstruction for high-resolution cardiac PET.MethodsStatic and 16-bin ECG-gated images of 20 patients referred for (18)F-FDG myocardial viability scans were obtained on a Siemens Biograph-64. CMF was applied to the gated images reconstructed with PSF. Myocardium to blood contrast, maximum left ventricle (LV) counts to defect contrast, contrast-to-noise (CNR) and wall thickness with standard reconstruction (2D-AWOSEM), PSF, ED-gated PSF, and CMF-PSF were compared.ResultsThe measured wall thickness was 18.9 ± 5.2 mm for 2D-AWOSEM, 16.6 ± 4.5 mm for PSF, and 13.8 ± 3.9 mm for CMF-PSF reconstructed images (all P < .05). The CMF-PSF myocardium to blood and maximum LV counts to defect contrasts (5.7 ± 2.7, 10.0 ± 5.7) were higher than for 2D-AWOSEM (3.5 ± 1.4, 6.5 ± 3.1) and for PSF (3.9 ± 1.7, 7.7 ± 3.7) (CMF vs all other, P < .05). The CNR for CMF-PSF (26.3 ± 17.5) was comparable to PSF (29.1 ± 18.3), but higher than for ED-gated dataset (13.7 ± 8.8, P < .05).ConclusionCombined CMF-PSF reconstruction increased myocardium to blood contrast, maximum LV counts to defect contrast and maintained equivalent noise when compared to static summed 2D-AWOSEM and PSF reconstruction

Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination, clinical, pathological, modified influenza A matrix gene real time RT-PCR and viral genomic analyses have shown that infection results in the induction of clinical signs, viral pathogenesis restricted to the respiratory tract, infection dynamics consistent with endemic strains of influenza A in pigs, virus transmissibility between pigs and virus-host adaptation events. Our results demonstrate that extant H1N1/09 is fully capable of becoming established in global pig populations. We also show the roles of viral receptor specificity in both transmission and tissue tropism. Remarkably, following direct inoculation of pigs with virus quasispecies differing by amino acid substitutions in the haemagglutinin receptor-binding site, only virus with aspartic acid at position 225 (225D) was detected in nasal secretions of contact infected pigs. In contrast, in lower respiratory tract samples from directly inoculated pigs, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]

A robust coregistration method for in vivo studies using a first generation simultaneous PET/MR scanner

Purpose: Hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging systems have recently been built that allow functional and anatomical information obtained from PET and MR to be acquired simultaneously. The authors have developed a robust coregistration scheme for a first generation small animal PET/MR imaging system and illustrated the potential of this system to study intratumoral heterogeneity in a mouse model. Methods: An alignment strategy to fuse simultaneously acquired PET and MR data, using the MR imaging gradient coordinate system as the reference basis, was developed. The fidelity of the alignment was evaluated over multiple study sessions. In order to explore its robustness in vivo, the alignment strategy was applied to explore the heterogeneity of glucose metabolism in a xenograft tumor model, using ^(18)F-FDG-PET to guide the acquisition of localized ^1H MR spectra within a single imaging session. Results: The alignment method consistently fused the PET/MR data sets with subvoxel accuracy (registration error mean=0.55 voxels, <0.28 mm); this was independent of location within the field of view. When the system was used to study intratumoral heterogeneity within xenograft tumors, a correlation of high ^(18)F-FDG-PET signal with high choline/creatine ratio was observed. Conclusions: The authors present an implementation of an efficient and robust coregistration scheme for multimodal noninvasive imaging using PET and MR. This setup allows time-sensitive, multimodal studies of physiology to be conducted in an efficient manner

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Respiration-averaged CT versus standard CT attenuation maps for correction of the 18F-NaF uptake in hybrid PET/CT

BACKGROUND: To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of (18)F-sodium fluoride ((18)F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). METHODS: This study comprised 23 patients who underwent (18)F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBR(MAX)) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. RESULTS: In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBR(MAX) (median [Interquartile range]): CTAC= 1.65[1.23–2.38], RACTAC= 1.63[1.23–2.33], p=0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC= 0.10 [0–1.0], RACTAC= 0.15[0–1.03], p=0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary (18)F-NaF uptake on PET/CT

Duration of adenosine-induced myocardial hyperemia - Insights from quantitative 13N-ammonia positron emission tomography myocardial perfusion imaging

AIMS To assess the impact of adenosine on quantitative myocardial blood flow (MBF) in a rapid stress-rest protocol compared to a rest-stress protocol using 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) and to gain insights into the time dependency of such effects. METHODS AND RESULTS Quantitative MBF at rest (rMBF), during adenosine-induced stress (sMBF) and myocardial flow reserve (MFR) were obtained from 331 retrospectively identified patients who underwent 13N-ammonia PET-MPI for suspected chronic coronary syndrome and who all exhibited no perfusion defects. Of these, 146 (44.1%) underwent a rapid stress-rest protocol with a time interval (Δtstress-rest) of 20 ± 4 minutes between adenosine infusion offset and rest-imaging, as per clinical routine. The remaining 185 (55.9%) patients underwent a rest-stress protocol and served as the reference. Groups did not differ regarding demographics, risk factors, medication, left ventricular function, and calcium scores. rMBF was significantly higher in the stress-rest vs. the rest-stress group (0.80 [IQR 0.66-1.00] vs. 0.70 [0.58-0.83] ml·min-1·g-1, p < 0.001) and, as sMBF was identical between groups (2.52 [2.20-2.96] vs. 2.50 [1.96-3.11], p = 0.347), MFR was significantly lower in the stress-rest group (3.07 [2.43-3.88] vs. 3.50 [2.63-4.10], p < 0.001). There was a weak correlation between Δtstress-rest and rMBF (r = -0.259, p = 0.002) and between Δtstress-rest and MFR (r = 0.163, p = 0.049), and the proportion of patients with abnormally high rMBF was significantly decreasing with increasing Δtstress-rest. CONCLUSIONS Intravenously applied adenosine induces a long-lasting hyperemic effect on the myocardium. Consequently, rapid stress-rest protocols could lead to an overestimation of rMBF and an underestimation of MFR

Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any 'gold standard'. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability

Contrast-enhanced computed tomography assessment of aortic stenosis

Objectives Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. Methods This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. Results Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm 3 /cm 2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). Conclusions Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction