Abstract Aims The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET). Methods and results As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland–Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44–55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age. Conclusion Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity.
Abstract Background: Aortic microcalcification activity is a recently described method of measuring aortic 18 F-sodium fluoride uptake in the thoracic aorta on positron emission tomography . In this study, we aimed to compare and to modify this method for use within the infrarenal aorta of patients with abdominal aortic aneurysms. Methods : Twenty-five patients with abdominal aortic aneurysms underwent an 18 F-sodium fluoride positron emission tomography and computed tomography scan. Maximum and mean tissue to background ratios (TBR) and abdominal aortic microcalcification activity were determined following application of a thresholding and variable radius method to correct for vertebral 18 F-sodium fluoride signal spill-over and the non-linear changes in aortic diameter respectively. Agreement between the methods, and repeatability of these approaches were assessed. Results: The aortic microcalcification activity method was three-fold quicker to perform than the TBR method (14 versus 40 min, p<0.001). There was moderate to good agreement between TBR and aortic microcalcification activity measurements for maximum (interclass correlation co-efficient, 0.67) and mean (interclass correlation co-efficient, 0.88) values. These correlations sequentially improved with the application of thresholding (intraclass correlation coefficient 0.93, 95% confidence interval 0.89-0.95) and variable diameter (intraclass correlation coefficient 0.97, 95% confidence interval 0.94-0.99) techniques. The optimized method had good intra-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.36 and limits of agreement -0.43 to 0.43) and inter-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.47 and limits of agreement -0.53 to 0.53) repeatability. Conclusions: Aortic microcalcification activity is a quick and simple method which demonstrates good intra-observer and inter-observer repeatabilities and provides measures of 18 F-sodium fluoride uptake that are comparable to established methods.
Short stature in Turner syndrome (TS) may be accompanied by skeletal disproportion. This retrospective study investigates growth and disproportion from early childhood to adult height.Data were collected from 59 girls prior to growth hormone (rhGH) treatment and in 30 girls followed up longitudinally. Standard deviation scores (SDS) for height (Ht), sitting height (SH) and sub-ischial leg length (LL) were compared and a disproportion score (SH SDS - LL SDS) calculated.In 59 girls, mean (SD) age 6.6 (2.1) years prior to rhGH treatment, LL SDS of -3.4 (1.1) was significantly lower than SH SDS of -1.2 (0.8) [p < .001]. In girls with Ht SDS < -2.0, disproportion score was > +2.0 in 27 (63%), cf eight (50%) with Ht SDS ≥ -2.0. For the longitudinal analysis, skeletal disproportion prior to rhGH was +2.4 (1.1) and +1.7 (1.0) on rhGH but prior to introduction of oestrogen [p < .001]. Disproportion at adult height was +1.1 (0.8), which was less marked than at the earlier time points [p < .001 for both comparisons]. Change in disproportion SDS over the first two years of rhGH predicted overall change in disproportion from baseline to adult height [R2 51.7%, p < .001].TS is associated with skeletal disproportion, which is more severe in the shortest girls and present in only half of those with milder degrees of short stature. Growth-promoting therapy may improve disproportion during both the childhood and pubertal phases of growth. Change in disproportion status two years after starting rhGH helps predict disproportion at adult height.
Abstract Background Novel molecular positron emission tomography (PET) assessments of fibrosis are now available but have not been compared directly to cardiovascular magnetic resonance (CMR), the current reference standard for myocardial scar assessment. Using 68Gallium-fibroblast activation protein inhibitor (FAPI), a radiotracer that binds to activated fibroblasts, we compared CMR and PET assessments of myocardial scar following ST-elevation myocardial infarction. Methods Hybrid 68Ga-FAPI-46 PET/MR with gadolinium-based contrast agent was performed in 40 patients within 4 weeks of acute ST-elevation myocardial infarction (acute STEMI) with 19 returning at 12 weeks for repeat PET/MR (subacute STEMI). Scar burden (%LGE) was measured on late enhancement short axis CMR images (Circle Cardiovascular Imaging software, Canada). Volume and intensity of global myocardial 68Ga-FAPI uptake was quantified (QPET, Cedars Sinai, Los Angeles) to determine the volume myocardium with tracer uptake (%68Ga-FAPI) and intensity of PET signal (target-to-background ratio, TBRmax) after correcting for right atrial blood-pool activity. Results In acute STEMI, high intensity uptake of 68Ga-FAPI was observed localized to the infarct. The area of fibroblast activation greatly exceeded the area of scar detected by late gadolinium enhancement (LGE) (%68Ga-FAPI 26.6+-15.4% vs 14.5+-11.4%, p<0.001). 68Ga-FAPI volume and intensity declined between acute and subacute STEMI (%68Ga-FAPI 26.6+-15.4% vs 12.8+-8.1%, p<0.001, TBRmax 3.9+-1.1 vs 2.7+-0.7, p<0.001). By week 12, there was no difference between the area of fibroblast activation detected by 68Ga-FAPI uptake and area of scar detected by LGE (%68Ga-FAPI 12.8+-8.1% vs %LGE 10.3+-6.1%, ns). Conclusion Molecular PET assessments of myocardial scar formation provide different but complementary information to structural assessments of myocardial scar. Fibroblast activation following myocardial infarction is a dynamic process that can be non-invasively measured for the first time by 68Ga-FAPI PET.
Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship Background Calcification of the thoracic aorta is associated with poor vessel wall health. Early detection of this disease process may highlight those at risk of future cardiovascular events. Purpose To investigate the potential of hybrid 18F-sodium fluoride (18F-NaF, a marker of vascular disease and microcalcification activity) positron emission tomography/computed tomography (PET/CT) to predict aortic disease progression and adverse cardiovascular events in patients with established risk factors. Methods Between 2015 and 2017, 197 patients underwent 18F-NaF PET/CT of the thoracic aorta as part of a randomised controlled trial. Baseline 18F-NaF aortic microcalcification activity (AMA) was calculated as the cumulative uptake in a standardised volume of interest of the arch and ascending aorta. Thirty-seven patients underwent follow up CT enabling aortic calcium score progression calculation. Fatal/non-fatal stroke (primary endpoint) and fatal/non-fatal myocardial infarction (MI, secondary endpoint) were recorded up to May 2020. The association between baseline AMA and both the progression of aortic calcium score and defined endpoints was analysed. AMA was stratified into tertiles (low, moderate or high). Data is presented as mean(SD) or median [IQR]. Results 18F-NaF AMA correlated with the progression of aortic calcium score (R = 0.42, P = 0.01). During 3.8 (0.9) years of follow up, 14 patients experienced the primary (stroke, n = 5) or secondary (MI, n = 9) endpoint. Patients who experienced stroke had higher AMA (171 [162-176] vs 150 [141 - 157], P = 0.0015). Increased cumulative incidence of stroke was seen in the highest AMA tertile (Figure, P = 0.019). There was no association between AMA and MI (P > 0.05). Conclusion Aortic microcalcification activity, as measured using 18F-NaF PET/CT, predicts the progression of aortic wall calcification and is associated with an increased risk of stroke but not MI. Consolidating these findings in further studies will improve stroke risk prediction using 18F-NaF PET/CT. Table Baseline characteristics Overall n = 197 Low AMA (<144) n = 66 Moderate AMA (144-155) n = 66 High AMA (>155) n = 65 p-value (ANOVA / X2) Age (±sd) 65.17 (8.30) 64.02 (9.43) 65.47 (7.40) 66.03 (7.95) 0.364 Male Sex (%) 157 (80.5) 54 (83.1) 52 (78.8) 51 (79.7) 0.808 Ever Smoked (%) 101 (60.5) 37 (71.2) 32 (56.1) 32 (55.2) 0.164 Hypertension (%) 110 (56.4) 31 (47.7) 35 (53.0) 44 (68.8) 0.043 High Cholesterol (%) 188 (96.4) 60 (92.3) 65 (98.5) 63 (98.4) 0.093 Type II Diabetes (%) 37 (19.0) 16 (24.6) 9 (13.6) 12 (18.8) 0.277 AMA = aortic microcalcification activity, MI = myocardial infarction, sd = standard deviation, TIA = transient ischaemic attack, X2 = Chi squared Abstract Figure: AMA and Stroke
In patients with abdominal aortic aneurysms, sodium [18F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [18F]fluoride uptake is unknown. This study aimed to compare aortic sodium [18F]fluoride uptake before and after treatment with EVAR.In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [18F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [18F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [18F]fluoride uptake.Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p<0.001). Following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41).EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [18F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity.
Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and smart contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque.
This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology.
This publication is the reprint with Russian translation from original: Syed MB, Fletcher AJ, Forsythe RO, Kaczynski J, Newby DE, Dweck MR, van Beek EJ. Emerging techniques in atherosclerosis imaging. Br J Radiol. 2019;92(1103):20180309. doi: 10.1259/bjr.20180309.
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