Purpose
There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of
18
F-FDG-PET/ CT to predict mortality ...in IPF.
Methods
A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for
18
F-FDG-PET/CT. The overall maximum pulmonary uptake of
18
F-FDG (SUV
max
), the minimum pulmonary uptake or background lung activity (SUV
min
), and target-to-background (SUV
max
/ SUV
min
) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary
18
F-FDG-PET measurements and GAP score for risk stratification in IPF patients.
Results
During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (
p
= 0.009), low forced vital capacity (FVC;
p
= 0.001), low transfer factor (TLCO;
p
< 0.001), high GAP index (
p
= 0.003), and high GAP stage (
p
= 0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (
p
= 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.
Conclusions
A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.
Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we ...combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy.
Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression.
The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density.
We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.
Allogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic ...SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.
Intravenous (IV) Delta 9-tetrahydrocannabinol (THC) induces transient psychotic symptoms in healthy subjects and in schizophrenic patients, but the psychotomimetic mechanism is unknown. One ...possibility is that THC stimulates dopamine (DA) release in the striatum. In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide (123IIBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30min following IV THC. There were no significant differences in binding index in the caudate or putamen under THC compared to placebo conditions. Positive psychotic symptoms and DA release were unrelated. THC did not lead to a significant increase in DA release even though the dose was sufficient for participants to have psychotic symptoms. These findings do not support a central role for striatal DA in THC-elicited psychosis.
There are no large studies available to guide the selection of thallium (Tl), methoxyisobutylisonitrile (MIBI) or tetrofosmin (Tf) for myocardial perfusion imaging. Our objective was to compare the ...technical and clinical performance of the three in routine clinical practice. We randomised 2,560 patients to receive Tl, MIBI or Tf. A 1-day stress/rest protocol was used for MIBI and Tf. Tracer uptake was scored using a 17-segment model, quality and artefact scores were assigned, and ratios of heart (H), liver (L), subdiaphragmatic (S) and lung activity were measured. Mean quality scores (stress/rest) were Tl 2.13/2.16, MIBI 2.18/2.39, Tf 2.18/2.42 ( P=ns stress and <0.00001 rest). For attenuation artefact, Tl>MIBI=Tf ( P<0.05) and for low-count artefact Tl>MIBI>Tf ( P<0.001). For H/S, Tl>MIBI=Tf, for H/L Tl>MIBI=Tf, and for H/lung Tl<MIBI=Tf. Stress defects in the patients with reversible or mixed perfusion defects were more severe for Tl than for the other tracers (mean summed score out of 68: Tl 52.3, MIBI 55.7, Tf 54.4, P<0.01), but mean rest scores were more similar (Tl 58.7, MIBI 60.7, Tf 59.4, P=0.02). In the subset of 137 patients undergoing diagnostic perfusion studies without prior infarction, angiography or revascularisation, overall sensitivity for the detection of coronary disease defined by subsequent angiography was 91% with a specificity of 87%. There were no significant differences between the tracers with regard to sensitivity and specificity.
There are technical differences between the tracers. Overall image quality score is superior using technetium, with less low-count artefact and less attenuation. Stress defect depth and extent are slightly greater using thallium, with no difference between MIBI and tetrofosmin. All three tracers perform well in clinical terms, with high sensitivity and specificity for angiographic stenosis and no differences in accuracy between the tracers.
Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes.
The primary objective was to conduct an initial exploratory study ...regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism.
PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen's kappa.
Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating.
The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.
This paper is the second in a series of invited perspectives by four pioneers of nuclear medicine imaging and physics. A medical physicist and a nuclear medicine clinical specialist each take a ...backward look and a forward look at the contributions of physics to nuclear medicine. Here is a backward look from a nuclear medicine physician's perspective.
Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of (18)F-FDG to detect angiogenesis in early breast ...carcinoma using PET/CT.
Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUV(max)) and mean standardized uptake value (SUV(mean)). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1).
The SUV(max) showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUV(mean) showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443
(18)F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, (18)F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease.
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