2 research outputs found
Assessment of abdominal aortic aneurysm biology using magnetic resonance imaging and positron emission tomography-computed tomography.
Background
Although abdominal aortic aneurysm (AAA) growth is non-linear, serial
measurements of aneurysm diameter are the mainstay of aneurysm surveillance and
contribute to decisions on timing of intervention. Aneurysm biology plays a key part
in disease evolution but is not currently routinely assessed in clinical practice.
Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computed
Tomography (PET-CT) provide insight into disease processes on a cellular or
molecular level, and represent exciting new imaging biomarkers of disease activity.
Macrophage-mediated inflammation may be assessed using ultrasmall
superparamagnetic particles of iron oxide (USPIO) MRI and the PET radiotracer 18FSodium
Fluoride (18F-NaF) identifies microcalcification which is a response to
underlying necrotic inflammation. The central aim of this thesis was to investigate
these imaging modalities in patients with AAA.
Methods and Results
USPIO MRI: MULTI-CENTRE STUDY
In a prospective multi-centre observational cohort study, 342 patients (85.4% male,
mean age 73.1±7.2 years, mean AAA diameter 49.6±7.7mm) with asymptomatic
AAA ≥4 cm anteroposterior diameter underwent MRI before and 24-36 hours after
intravenous administration of USPIO. Colour maps (depicting the change in T2*
caused by USPIO) were used to classify aneurysms on the basis of the presence of
USPIO uptake in the aneurysm wall, representing mural inflammation. Intra- and
inter-observer agreement were found to be very good, with proportional agreement
of 0.91 (kappa 0.82) and 0.83 (kappa 0.66), respectively. At 1 year, there was 29.3%
discordant classification of aneurysms on repeated USPIO MRI and at 2 years,
discordance was 65%, suggesting that inflammation evolves over time. In the
observational study, after a mean of 1005±280 days of follow up, there were 126
(36.8%) aneurysm repairs and 17 (5.0%) ruptures. Participants with USPIO
enhancement (42.7%) had increased aneurysm expansion rates (3·1±2·5 versus
2·5±2·4 mm/year; difference 0·6 [95% confidence intervals (CI), 0·02 to 1·2]
mm/year, p=0·0424) and had higher rates of aneurysm rupture or repair
(69/146=47·3% versus 68/191=35·6%; difference 11·7%, 95% CI 1·1 to 22·2%,
p=0·0308). USPIO MRI was therefore shown to predict AAA expansion and the
composite of rupture or repair, however this was not independent of aneurysm
diameter (c-statistic, 0·7924 to 0·7926; unconditional net reclassification -13·5%,
95% confidence intervals -36·4% to 9·3%).
18F-NaF PET-CT: SINGLE-CENTRE STUDY
A sub-group of 76 patients also underwent 18F-NaF PET-CT, which was evaluated
using the maximum tissue-to-background ratio (TBRmax) in the most diseased
segment (MDS), a technique that showed very good intra- (ICC 0.70-0.89) and inter-observer
(ICC 0.637-0.856) agreement. Aneurysm tracer uptake was compared
firstly in a case-control study, with 20 patients matched to 20 control patients for age,
sex and smoking status. 18F-NaF uptake was higher in aneurysm when compared to
control aorta (log2TBRmax 1.712±0.560 vs. 1.314±0.489; difference 0.398 (95% CI
0.057, 0.739), p=0.023), or to non-aneurysmal aorta in patients with AAA
(log2TBRmax 1.647±0.537 vs. 1.332±0.497; difference 0.314 (95% CI 0.0685, 0.560),
p=0.004). An ex vivo study was performed on aneurysm and control tissue, which
demonstrated that 18F-NaF uptake on microPET-CT was higher in the aneurysm
hotspots and higher in aneurysm tissue compared to control tissue. Histological
analysis suggested that 18F-NaF was highest in areas of focal calcification and
necrosis. In an observational cohort study, aneurysms were stratified by tertiles of
TBRmax in the MDS and followed up for 510±196 days, with 6 monthly serial
ultrasound measurements of diameter. Those in the highest tertile of tracer uptake
expanded more than 2.5 times more rapidly than those in the lowest tertile (3.10
[3.58] mm/year vs. 1.24 [2.41] mm/year, p=0.008) and were also more likely to
experience repair or rupture (15.3% vs. 5.6%, log-rank p=0.043). In multivariable
analyses, 18F-NaF uptake on PET-CT emerged as an independent predictor of AAA
expansion (p=0.042) and rupture or repair (HR 2.49, 95% CI1.07, 5.78; p=0.034),
even when adjusted for age, sex, body mass index, systolic blood pressure, current
smoking and, crucially, aneurysm diameter.
Conclusion
These are the largest USPIO MRI and PET-CT studies in AAA disease to date and
the first to investigate 18F-NaF. Both USPIO MRI and 18F-NaF PET-CT are able to
predict AAA expansion and the composite of rupture and repair, with 18F-NaF PETCT
emerging as the first imaging biomarker that independently predicts expansion
and AAA events, even after adjustment for aneurysm diameter. This represents an
exciting new predictor of disease progression that adds incremental value to standard
clinical assessments. Feasibility and randomised clinical trials are now required to
assess the potential of this technique to change the management and outcome of patients with AAA
CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label,parallel-group, multicentre trial
Background The benefi t of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not
been systematically studied. We aimed to assess the eff ect of CTCA on the diagnosis, management, and outcome of
patients referred to the cardiology clinic with suspected angina due to coronary heart disease.
Methods In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18–75 years referred
for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across
Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation
was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis
of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed
in the group they were allocated to, irrespective of compliance with scanning. This study is registered with
ClinicalTrials.gov, number NCT01149590.
Findings Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been
referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic
diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassifi ed
the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart
disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0·0001). Although both the certainty (relative risk
[RR] 2·56, 95% CI 2·33–2·79; p<0·0001) and frequency of coronary heart disease increased (1·09, 1·02–1·17;
p=0·0172), the certainty increased (1·79, 1·62–1·96; p<0·0001) and frequency seemed to decrease (0·93, 0·85–1·02;
p=0·1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%;
p<0·0001) and treatments (23% vs 5%; p<0·0001) but did not aff ect 6-week symptom severity or subsequent
admittances to hospital for chest pain. After 1·7 years, CTCA was associated with a 38% reduction in fatal and nonfatal
myocardial infarction (26 vs 42, HR 0·62, 95% CI 0·38–1·01; p=0·0527), but this was not signifi cant.
Interpretation In patients with suspected angina due to coronary heart disease, CTCA clarifi es the diagnosis, enables
targeting of interventions, and might reduce the future risk of myocardial infarction.
Funding The Chief Scientist Offi ce of the Scottish Government Health and Social Care Directorates funded the trial
with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases
Research Fund