Accuracy of 64-slice CT angiography for the detection of functionally relevant coronary stenoses as assessed with myocardial perfusion SPECT

Purpose CT angiography (CTA) offers a valuable alternative for the diagnosis of CAD but its value in the detection of functionally relevant coronary stenoses remains uncertain. We prospectively compared the accuracy of 64-slice CTA with that of myocardial perfusion imaging (MPI) using ^99mTc-tetrofosmin-SPECT as the gold standard for the detection of functionally relevant coronary artery disease (CAD). Methods MPI and 64-slice CT were performed in 100 consecutive patients. CTA lesions were analysed quantitatively and area stenoses ≥50% and ≥75% were compared with the MPI findings. Results In 23 patients, MPI perfusion defects were found (12 reversible, 13 fixed). A total of 399 coronary arteries and 1,386 segments was analysed. Eighty-four segments (6.1%) in 23 coronary arteries (5.8%) of nine patients (9.0%) were excluded owing to insufficient image quality. In the remaining 1,302 segments, quantitative CTA revealed stenoses ≥50% in 57 of 376 coronary arteries (15.2%) and stenoses ≥75% in 32 (8.5%) coronary arteries. Using a cut-off at ≥75% area stenosis, CTA yielded the following sensitivity, specificity, negative (NPV) and positive predictive value (PPV), and accuracy for the detection of any (fixed and reversible) MPI defect: by patient, 75%, 90%, 93%, 68% and 87%, respectively; by artery, 76%, 95%, 99%, 50% and 94%, respectively. Conclusion Sixty-four-slice CTA is a reliable tool to rule out functionally relevant CAD in a non-selected population with an intermediate pretest likelihood of disease. However, an abnormal CTA is a poor predictor of ischaemia.     

Validation of a new cardiac image fusion software for three-dimensional integration of myocardial perfusion SPECT and stand-alone 64-slice CT angiography

Purpose Combining the functional information of SPECT myocardial perfusion imaging (SPECT-MPI) and the morphological information of coronary CT angiography (CTA) may allow easier evaluation of the spatial relationship between coronary stenoses and perfusion defects. The aim of the present study was the validation of a novel software solution for three-dimensional (3D) image fusion of SPECT-MPI and CTA. Methods SPECT-MPI with adenosine stress/rest ^99mTc-tetrofosmin was fused with 64-slice CTA in 15 consecutive patients with a single perfusion defect and a single significant coronary artery stenosis (≥50% diameter stenosis). 3D fused SPECT/CT images were analysed by two independent observers with regard to superposition of the stenosed vessel onto the myocardial perfusion defect. Interobserver variability was assessed by recording the X, Y, Z coordinates for the origin of the stenosed coronary artery and the centre of the perfusion defect and measuring the distance between the two landmarks. Results SPECT-MPI revealed a fixed defect in seven patients, a reversible defect in five patients and a mixed defect in three patients and CTA documented a significant stenosis in the respective subtending coronary artery. 3D fused SPECT/CT images showed a match of coronary lesion and perfusion defect in each patient and the fusion process took less than 15 min. Interobserver variability was excellent for landmark detection (r = 1.00 and r = 0.99, p < 0.0001) and very good for the 3D distance between the two landmarks (r = 0.94, p < 0.001). Conclusion 3D SPECT/CT image fusion is feasible, reproducible and allows correct superposition of SPECT segments onto cardiac CT anatomy.     

Cigarette smoke facilitates allergen penetration across respiratory epithelium

Background:  The association between cigarette smoke exposure and allergic airway disease is a matter for debate. We sought to investigate in an in vitro system whether active smoking reduces the integrity and barrier function of the respiratory epithelium and thus facilitates allergen penetration.
Methods:  We cultured the human bronchial epithelial cell line 16HBE14o− in a transwell culture system as a surrogate for the intact respiratory epithelium. The cell monolayer was exposed to standardized cigarette smoke extract (CSE). The extent and effects of trans-epithelial allergen penetration were measured using ¹²⁵I-labelled purified major respiratory allergens (rBet v 1, rPhl p 5 and rDer p 2) and histamine release experiments.
Results:  Exposure of cells to concentrations of CSE similar to those found in smokers induced the development of para-cellular gaps and a decrease in trans-epithelial resistance. CSE exposure induced a more than threefold increase in allergen penetration. Increased subepithelial allergen concentrations provoked a substantial augmentation of histamine release from sensitized basophils.
Conclusions:  Our results indicate that cigarette smoke is a potent factor capable of reducing the barrier function of the respiratory epithelium for allergens and may contribute to increased allergic inflammation, exacerbation of allergic disease and boosting of IgE memory.     

Accuracy of quantitative coronary angiography with computed tomography and its dependency on plaque composition

Objective: To determine the impact of plaque composition on accuracy of quantitative 64-slice computed tomography coronary angiography (CTCA). Methods: The institutional review board approved this study; written informed consent was obtained from all patients. One hundred consecutive patients (42 women, mean age 64.6 ± 9.4 years, age range 39–87 years) underwent CTCA and invasive quantitative coronary angiography (QCA) to determine (a) the diagnostic accuracy of CTCA for the detection of significant stenosis (diameter reduction of ≥50%), and (b) the accuracy of stenosis grading. In CTCA stenosis severity was graded in 10% steps and evaluated separately for calcified and non-calcified coronary lesions using Pearson-linear-regression analysis, Bland/Altman-analysis (BA), and Mann-Whitney-U-test. Results: In 60/100 patients 139 significant coronary artery stenoses were identified with QCA. On a per-segment analysis, sensitivity of CTCA was 75.5%, and specificity was 96.6% (positive predictive value: 72.9%, negative predictive value: 97.0%). Quantification of stenosis grading correlated moderately between methods (r = 0.60; P < 0.001), with an overestimation by CTCA of 5.5% (BA limits-of-agreement −29 to 39%). BA limits-of-agreement were greater in calcified lesions (−29.2 to 45.6%; mean error 8.2%) than in non-calcified lesions (−25.9 to 30.2%; mean error 2.2%) and differed significantly (P < 0.05). Conclusions: Diagnostic accuracy of CTCA is high, however agreement for quantitative lesion severity assessment between CTCA and QCA is moderate for calcified but superior for non-calcified lesions.     

Micro‐arrayed wheat seed and grass pollen allergens for component‐resolved diagnosis

Background: Wheat is a potent allergen source and can cause baker’s asthma, food and pollen allergy. The aim of the study was to develop an allergen micro‐array for differential diagnosis of baker’s asthma, wheat‐induced food allergy and grass pollen allergy. Methods: We analysed the immunoglobulin‐E reactivity profiles of patients suffering from baker’s asthma, wheat‐induced food allergy and grass pollen allergy to micro‐arrayed recombinant wheat flour allergens and grass pollen allergens and compared these results with clinical results and diagnostic tests based on crude wheat flour, wheat pollen and grass pollen allergen extracts. Results: We identified recombinant wheat flour allergens, which are specifically recognized by patients suffering from baker’s asthma, but not from patients with food allergy to wheat or pollen allergy. rPhl p 1 and rPhl p 5 were identified as marker allergens specific for grass pollen allergy. They can be used to replace grass pollen extracts for allergy diagnosis and to identify grass pollen allergic patients among patients suffering from baker’s asthma and wheat‐induced food allergy. Profilin was identified as a cross‐reactive allergen recognized by patients suffering from baker’s asthma, food and pollen allergy. Conclusions: Our results indicate that it will be possible to design serological tests based on micro‐arrayed recombinant wheat seed and grass pollen allergens for the discrimination of baker’s asthma, wheat‐induced food allergy and grass pollen allergy.     

A hybrid molecule resembling the epitope spectrum of grass pollen for allergy vaccination

BACKGROUND: Allergy vaccines based on natural allergen extracts contain greatly varying amounts of individual allergens with different immunogenicity. OBJECTIVE: To develop a novel type of allergy vaccine for complex allergen sources that combines defined amounts of the major allergens in the form of single hybrid molecules. METHODS: A hybrid molecule was engineered by PCR-based mending and expression of the cDNAs coding for the 4 major grass pollen allergens and compared with its single components by circular dichroism analysis, T-cell proliferation, ELISA competition, and histamine release assays. Immune responses to the hybrid molecule were studied in BALB/c mice and rat basophil leukemia assays. RESULTS: The hybrid contained most of the B-cell epitopes of grass pollen and could be used to diagnose allergy in 98% (n = 652) of patients allergic to grass pollen. Immunization of mice and rabbits with the hybrid induced stronger and earlier IgG antibody responses than equimolar mixtures of the components, which can be explained by the induction of stronger T-cell responses by the hybrid versus the individual components. IgG antibodies induced by vaccination with the hybrid blocked immediate allergic reactions, as demonstrated by rat basophil degranulation assays in a murine model of grass pollen allergy. CONCLUSION: We demonstrate for grass pollen allergy that recombinant hybrid molecules covering the spectrum of the disease-eliciting epitopes of complex allergen sources can be engineered.     

Structural epicardial disease and microvascular function are determinants of an abnormal longitudinal myocardial blood flow difference in cardiovascular risk individuals as determined with PET/CT

Background

The aim of this study was to determine whether epicardial structural disease may affect the manifestation of a longitudinal decrease in myocardial blood flow (MBF) or MBF difference during hyperemia in cardiovascular risk individuals, and its dependency on the flow increase.

Methods and Results

In 54 cardiovascular risk individuals (at risk) and in 26 healthy controls, MBF was measured with ¹³N-ammonia and PET/CT in mL/g/min at rest and during dipyridamole stimulation. Computed tomography coronary angiography (CTA) was performed using a 64-slice CT of a PET/CT system. Absolute MBFs during dipyridamole stimulation were mildly lower in the mid-distal than in the mid-LV myocardium in controls (2.20 ± .51 vs 2.29 ± .51, P < .0001), while it was more pronounced in at risk with normal and abnormal CTA (1.56 ± .42 vs 1.91 ± .46 and 1.18 ± .34 vs 1.51 ± .40 mL/g/min, respectively, P < .0001), resulting in a longitudinal MBF difference that was highest in at risk with normal CTA, intermediate in at risk abnormal CTA, and lowest in controls (.35 ± .16 and .22 ± .09 vs .09 ± .04 mL/g/min, respectively, P < .0001). On multivariate analysis, log-CCS and mid-LV hyperemic MBF increase, indicative of microvascular function, were independent predictors of the observed longitudinal MBF difference (P ≤ .004 by ANOVA).

Conclusions

Epicardial structural disease and microvascular function are important determinants of an abnormal longitudinal MBF difference as determined with PET/CT.