Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve.

OBJECTIVES: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS: 51 patients (63 (61-65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by "snapshot" adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. RESULTS: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32-2.20) vs 3.11 (2.44-3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32-2.20) vs 3.12 (2.44-3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71-76) vs 86 (84-88) HU, P < 0.001 and 101 (96-106) vs 111 (107-114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. CONCLUSION: CT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. KEY POINTS: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from "snapshot" imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with 15 O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.

Left ventricular hypertrophy with strain and aortic stenosis.

BACKGROUND: ECG left ventricular hypertrophy with strain is associated with an adverse prognosis in aortic stenosis. We investigated the mechanisms and outcomes associated with ECG strain. METHODS AND RESULTS: One hundred and two patients (age, 70 years [range, 63-75 years]; male, 66%; aortic valve area, 0.9 cm(2) [range, 0.7-1.2 cm(2)]) underwent ECG, echocardiography, and cardiovascular magnetic resonance. They made up the mechanism cohort. Myocardial fibrosis was determined with late gadolinium enhancement (replacement fibrosis) and T1 mapping (diffuse fibrosis). The relationship between ECG strain and cardiovascular magnetic resonance was then assessed in an external validation cohort (n=64). The outcome cohort was made up of 140 patients from the Scottish Aortic Stenosis and Lipid Lowering Trial Impact on Regression (SALTIRE) study and was followed up for 10.6 years (1254 patient-years). Compared with those without left ventricular hypertrophy (n=51) and left ventricular hypertrophy without ECG strain (n=30), patients with ECG strain (n=21) had more severe aortic stenosis, increased left ventricular mass index, more myocardial injury (high-sensitivity plasma cardiac troponin I concentration, 4.3 ng/L [interquartile range, 2.5-7.3 ng/L] versus 7.3 ng/L [interquartile range, 3.2-20.8 ng/L] versus 18.6 ng/L [interquartile range, 9.0-45.2 ng/L], respectively; P<0.001) and increased diffuse fibrosis (extracellular volume fraction, 27.4±2.2% versus 27.2±2.9% versus 30.9±1.9%, respectively; P<0.001). All patients with ECG strain had midwall late gadolinium enhancement (positive and negative predictive values of 100% and 86%, respectively). Indeed, late gadolinium enhancement was independently associated with ECG strain (odds ratio, 1.73; 95% confidence interval, 1.08-2.77; P=0.02), a finding confirmed in the validation cohort. In the outcome cohort, ECG strain was an independent predictor of aortic valve replacement or cardiovascular death (hazard ratio, 2.67; 95% confidence interval, 1.35-5.27; P<0.01). CONCLUSION: ECG strain is a specific marker of midwall myocardial fibrosis and predicts adverse clinical outcomes in aortic stenosis.

Late Peripheral Thoracic Aneurysms following Aortic Root Surgery in Patients with Loeys-Dietz Syndrome.

The Loeys-Dietz syndrome is a multisystem connective tissue disorder characterized by aortopathy, arterial tortuosity, peripheral aneurysms, and skeletal features. The peripheral arteriopathy is an important cause of morbidity and potential mortality. This report presents 2 cases: the first demonstrating a 5-cm pseudoaneurysm of the right internal mammary artery and the second demonstrating a 2.3-cm aneurysm of the left internal mammary artery, each following aortic root surgery. These were successfully treated with percutaneous techniques. No complications were seen at follow-up as long as 2 years. Patients with Loeys-Dietzs syndrome require comprehensive long-term vascular follow-up and are likely to require percutaneous vascular interventions.

Image quality with single-heartbeat 320-multidetector computed tomographic coronary angiography.

OBJECTIVE: We aimed to establish the feasibility of single-heartbeat 320-multidetector computed tomographic coronary angiography (CTCA) and assess variables affecting image quality. METHODS: Consecutive patients (n = 249, 38% male) underwent CTCA. Two observers assessed image quality using a 4-point scale (1, excellent; 4, poor). RESULTS: Mean heart rate was 60 beats per minute (95% confidence interval, 59-62); body mass index, 29 kg/m (28-30); and dose-length product, 283 mGy·cm (266-301). During scanning, 133 (51%) received sublingual glyceryl trinitrate (GTN), 9 (4%) had ectopics, and 12 (5%) had atrial fibrillation. Diagnostic image quality was obtained in 99% with mean image quality of 1.4 (1.3, 1.5). Age, sex, atrial fibrillation, ectopics, diabetes mellitus (12%), and obstructive disease were not related to image quality. A lower heart rate and GTN were associated with improved image quality (P ≤ 0.001). CONCLUSIONS: Optimal image quality in single-heartbeat 320-multidetector CTCA is achievable in 99% of unselected patients. Image quality is improved by lower heart rate and GTN.

Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis.

BACKGROUND: The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. METHODS AND RESULTS: Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001). CONCLUSIONS: Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Ex vivo water diffusion tensor properties of the fibroid uterus at 7 T and their relation to tissue morphology.

PURPOSE: To investigate the water diffusion tensor properties of ex vivo tissue in the fibroid uterus, including the influence of degeneration, and the relevance of the principal eigenvector orientation to the underlying tissue structure. MATERIALS AND METHODS: Following hysterectomy, high-resolution structural T(2) -weighted and diffusion tensor magnetic resonance imaging (DT-MRI) were performed on nine uteri at 7 T. Mean diffusivity (MD), fractional anisotropy (FA), and principal eigenvector orientation were measured in myometrium and in myxoid and dense tissue in fibroids. Imaging data and measurements of water diffusion parameters were compared with histopathology findings. RESULTS: The nine uteri yielded 23 fibroids. MD was 50% higher in regions of myxoid degeneration compared to dense fibroid tissue (P = 0.001), while myometrium was intermediate in value (dense fibroid tissue, P = 0.15; myxoid degeneration, P = 0.23). FA was lower in dense fibroid tissue than in myometrium (P = 3 × 10(-5) ), but higher than in myxoid tissue (P = 0.003). Principal eigenvector orientation corresponded qualitatively with that of uterine smooth muscle fibers. CONCLUSION: The water diffusion tensor measured ex vivo in the fibroid uterus is a sensitive probe of tissue type, myxoid degeneration, and morphology.

Prevalence of coronary artery calcification in patients undergoing assessment for orthotopic liver transplantation.

Patients with advanced liver disease are at increased risk of cardiovascular events, especially following orthotopic liver transplantation (OLT). Coronary artery calcification (CAC) is a novel and independent predictor of cardiovascular risk, but its prevalence and utility in patients with cirrhosis are unknown. The aim of this study was to define the prevalence of CAC and its association with markers of disease severity and standard measures of cardiovascular risk in a large cohort of patients undergoing OLT assessment. A single-center, prospective, observational study of 147 consecutive patients undergoing assessment for OLT was performed. CAC scores were derived with the Agatston method from thoracic computed tomography scans and correlated with cardiovascular risk factors and measures of liver disease severity. There were 101 patients (66 males) with a mean age of 53.2 years; 46 patients were excluded because the CAC score was not reported. The median CAC score was 40 HU (range, 0-3533). Correlations were identified between the CAC score and age (r = 0.477; P < 0.001), male sex (r = 0.262; P = 0.008), family history of cardiovascular disease (r = 0.208; P = 0.036), Framingham risk score (r = 0.621; P < 0.001), Model for End-Stage Liver Disease score (r = 0.221; P = 0.027), systolic blood pressure (r = 0.285; P = 0.004), diastolic blood pressure (r = 0.267; P = 0.007), cytomegalovirus status (r = 0.278; P = 0.005), fasting glucose (r = 0.330; P = 0.001), number of coronary vessels involved (r = 0.899; P < 0.001), and components of the metabolic syndrome (r = 0.226; P = 0.026). After multivariate analysis, age, systolic blood pressure, fasting glucose, number of features of metabolic syndrome, and number of vessels involved remained significantly associated with CAC. In conclusion, this study identified a high prevalence of occult coronary artery disease in patients undergoing OLT assessment and identified a strong relationship between CAC scores and a limited number of specific cardiovascular risk factors. The usefulness of these factors in predicting perioperative and postoperative cardiovascular events in patients undergoing OLT requires prospective evaluation.

Unbiased and efficient estimation of the volume of the fibroid uterus using the Cavalieri method and magnetic resonance imaging.

The aim of our study was to develop a reliable technique for measuring volume of the fibroid uterus using Magnetic Resonance Imaging. We applied the Cavalieri method and standard calliper technique to measure the volume of the uterus and largest fibroid in 26 patients, and results were compared with "gold-standard" planimetry measurements. We found Cavalieri measurements to be unbiased, while calliper measurements systematically underestimated uterine volume (- 13.2%, P < 10(-5)) and had greater variance. Repeatability was similar for the 2 techniques (standard deviation [SD] = 4.0%-6.9%). Reproducibility of Cavalieri measurements was higher for measurement of uterine (SD = 9.0%) than fibroid volume (SD = 19.1%), whereas the reproducibility of calliper measurements was higher for fibroid (SD = 9.1%) than uterine volume (SD = 15.9%). The additional measurement time for the Cavalieri method was approximately 1 to 2 minutes. In conclusion, the Cavalieri method permits more accurate measurement of uterine and fibroid volumes and is suitable for application in both clinical practice and scientific research.

MRI using ultrasmall superparamagnetic particles of iron oxide in patients under surveillance for abdominal aortic aneurysms to predict rupture or surgical repair: MRI for abdominal aortic aneurysms to predict rupture or surgery-the MA(3)RS study.

INTRODUCTION: Population screening for abdominal aortic aneurysms (AAA) halves the associated mortality and has led to the establishment of national screening programmes. Prediction of aneurysm growth and rupture is challenging and currently relies on serial diameter measurements with ultrasound. Recently, a novel MRI-based technique using ultrasmall superparamagnetic particles of iron oxide (USPIO) has demonstrated considerable promise as a method of identifying aneurysm inflammation and expansion. METHODS AND ANALYSIS: The MA(3)RS study is a prospective observational multicentre cohort study of 350 patients with AAA in three centres across Scotland. All participants will undergo MRI with USPIO and aneurysm expansion will be measured over 2 years with CT in addition to standard clinical ultrasound surveillance. The relationship between mural USPIO uptake and subsequent clinical outcomes, including expansion, rupture and repair, will be evaluated and used to determine whether the technique augments standard risk prediction markers. To ensure adequate sensitivity to answer the primary question, we need to observe 130 events (composite of rupture or repair) with an estimated event rate of 41% over 2 years of follow-up. The MA(3)RS study is currently recruiting and expects to report in 2017. DISCUSSION: This is the first study to evaluate the use of USPIO-enhanced MRI to provide additional information to aid risk prediction models in patients with AAA. If successful, this study will lay the foundation for a large randomised controlled trial targeted at applying this technique to determine clinical management. TRIAL REGISTRATION NUMBER: Current Controlled Trials: ISRCTN76413758.

Quantitative serial MRI of the treated fibroid uterus.

OBJECTIVE: There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction. METHODS: Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months). RESULTS: A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061). CONCLUSION: DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids. TRIAL REGISTRATION: ClinicalTrials.gov NCT00746031.

Arterial stiffness and endothelial function in obstructive sleep apnoea/hypopnoea syndrome.

BACKGROUND: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is associated with increased cardiovascular morbidity and mortality. Our study examined arterial stiffness and endothelial function in subjects with OSAHS with no known cardiovascular disease compared to well-matched controls. METHODS: Twenty subjects with OSAHS (defined as apnoea-hypopnoea index [AHI] > or =15 and Epworth Sleepiness Scale score > or =11) without cardiovascular disease and 20 well-matched controls underwent a comprehensive evaluation of arterial stiffness and endothelial function. Arterial stiffness was measured by applanation tonometry and cardiovascular magnetic resonance imaging (MRI) and endothelial function assessed by measuring vascular reactivity after administration of glyceryl trinitrate and salbutamol. RESULTS: Subjects with OSAHS had increased arterial stiffness (augmentation index 19.3 [10.9] vs. 12.6 (10.2)%; p=0.017) and impaired endothelial function (change in augmentation index following salbutamol -4.3 (3.2) vs. -8.0 (4.9)%; p=0.02) compared to controls. Aortic distensibility, a measure of arterial stiffness, was negatively correlated with the AHI. CONCLUSIONS: Our findings suggest that even in the absence of known cardiovascular disease, subjects with OSAHS have increased arterial stiffness and impaired endothelial function and are at increased risk for cardiovascular disease.

The effect of continuous positive airway pressure therapy on arterial stiffness and endothelial function in obstructive sleep apnea: a randomized controlled trial in patients without cardiovascular disease.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality which may be mediated by increased arterial stiffness and endothelial dysfunction. Continuous positive airway pressure (CPAP) therapy improves excessive daytime somnolence (EDS), but its effect on vascular function in patients without preexisting cardiovascular disease (CVD) is unclear. METHODS: Fifty-three patients with OSA defined as an apnea-hypopnea index (AHI) of ⩾15 and without CVD were recruited into a double-blind, randomized, placebo-controlled, crossover trial of 12weeks of CPAP therapy, of whom 43 participants completed the study protocol. Arterial stiffness was assessed by measuring the augmentation index (AIx) and pulse wave velocity (PWV) by applanation tonometry and cardiovascular magnetic resonance imaging to determine aortic distensibility. Endothelial function was assessed by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. RESULTS: CPAP therapy lowered systolic blood pressure (SBP) (126mmHg [standard deviation {SD}, 12] vs 129mmHg [SD, 14]; P=.03), with a trend towards reduced AIx (15.5 [SD, 11.9] vs 16.6 [SD, 11.7]%; P=.08) but did not modify endothelial function. When subjects with (n=24) and without (n=19) EDS were separately examined, no effect of CPAP therapy on vascular function was seen. CONCLUSIONS: In patients without overt CVD, CPAP therapy had a nonsignificant effect on AIx and did not modify endothelial function.

Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology.

OBJECTIVES: With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively. BACKGROUND: The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation. METHODS: We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0). RESULTS: Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498). CONCLUSIONS: 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).

Ultrasmall superparamagnetic particles of iron oxide in patients with acute myocardial infarction: early clinical experience.

BACKGROUND: Inflammation following acute myocardial infarction (MI) has detrimental effects on reperfusion, myocardial remodelling, and ventricular function. Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide can detect cellular inflammation in tissues, and we therefore explored their role in acute MI in humans. METHODS AND RESULTS: Sixteen patients with acute ST-segment elevation MI were recruited to undergo 3 sequential magnetic resonance scans within 5 days of admission at baseline, 24 and 48 hours following no infusion (controls; n=6) or intravenous infusion of ultrasmall superparamagnetic particles of iron oxide (n=10; 4 mg/kg). T2*-weighted multigradient-echo sequences were acquired and R2* values were calculated for specific regions of interest. In the control group, R2* values remained constant in all tissues across all scans with excellent repeatability (bias of -0.208 s(-1), coefficient of repeatability of 26.96 s(-1); intraclass coefficient 0.989). Consistent with uptake by the reticuloendothelial system, R2* value increased in the liver (84±49.5 to 319±70.0 s(-1); P<0.001) but was unchanged in skeletal muscle (54±8.4 to 67.0±9.5 s(-1); P>0.05) 24 hours after administration of ultrasmall superparamagnetic particles of iron oxide. In the myocardial infarct, R2* value increased from 41.0±12.0 s(-1) (baseline) to 155±45.0 s(-1) (P<0.001) and 124±35.0 s(-1) (P<0.05) at 24 and 48 hours, respectively. A similar but lower magnitude response was seen in the remote myocardium, where it increased from 39±3.2 s(-1) (baseline) to 80±14.9 s(-1) (P<0.001) and 67.0±15.7 s(-1) (P<0.05) at 24 and 48 hours, respectively. CONCLUSIONS: Following acute MI, uptake of ultrasmall superparamagnetic particles of iron oxide occurs with the infarcted and remote myocardium. This technique holds major promise as a potential method for assessing cellular myocardial inflammation and left ventricular remodelling, which may have a range of applications in patients with MI and other inflammatory cardiac conditions.

In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans.

BACKGROUND: Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice-compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans. METHODS AND RESULTS: Peripheral blood mononuclear cells 1-5 × 10(9) were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10(8) SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10(9) SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin. CONCLUSIONS: Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells. Clinical Trial Registration- URL: http://www.clinicaltrials.gov; Unique identifier: NCT00972946, NCT01169935.

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Abdominal aortic aneurysm growth predicted by uptake of ultrasmall superparamagnetic particles of iron oxide: a pilot study.

BACKGROUND: Abdominal aortic aneurysms are a major cause of death. Prediction of aneurysm expansion and rupture is challenging and currently relies on the simple measure of aneurysm diameter. Using MRI, we aimed to assess whether areas of cellular inflammation correlated with the rate of abdominal aortic aneurysm expansion. METHODS AND RESULTS: Stable patients (n=29; 27 male; age, 70±5 years) with asymptomatic abdominal aortic aneurysms (4.0 to 6.6 cm) were recruited from a surveillance program and imaged using a 3-T MRI scanner before and 24 to 36 hours after administration of ultrasmall superparamagnetic particles of iron oxide (USPIO). The change in T2* value on T2*-weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. Histological examination of aneurysm tissue confirmed colocalization and uptake of USPIO in areas with macrophage infiltration. Patients with distinct mural uptake of USPIO had a 3-fold higher growth rate (n=11, 0.66 cm/y; P=0.020) than those with no (n=6, 0.22 cm/y) or nonspecific USPIO uptake (n=8, 0.24 cm/y) despite having similar aneurysm diameters (5.4±0.6, 5.1±0.5, and 5.0±0.5 cm, respectively; P>0.05). In 1 patient with an inflammatory aneurysm, there was a strong and widespread uptake of USPIO extending beyond the aortic wall. CONCLUSIONS: Uptake of USPIO in abdominal aortic aneurysms identifies cellular inflammation and appears to distinguish those patients with more rapidly progressive abdominal aortic aneurysm expansion. This technique holds major promise as a new method of risk-stratifying patients with abdominal aortic aneurysms that extends beyond the simple anatomic measure of aneurysm diameter. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794092.

Non-invasive assessment of coronary artery bypass graft patency using 16-slice computed tomography angiography.

BACKGROUND: Invasive coronary angiography is the gold standard means of imaging bypass vessels and carries a small but potentially serious risk of local vascular complications, including myocardial infarction, stroke and death. We evaluated computed tomography as a non-invasive means of assessing graft patency. METHODS: Fifty patients with previous coronary artery bypass surgery who were listed for diagnostic coronary angiography underwent contrast enhanced computed tomography angiography using a 16-slice computed tomography scanner. Images were retrospectively gated to the electrocardiogram and two dimensional axial, multiplanar and three dimensional reconstructions acquired. Sensitivity, specificity, positive and negative predictive value, accuracy and level of agreement for detection of graft patency by multidetector computed tomography. RESULTS: A total of 116 grafts were suitable for analysis. The specificity of CT for the detection of graft patency was 100%, with a sensitivity of 92.8%, positive predictive value 100%, negative predictive value 85.8% and an accuracy of 94.8%. The kappa value of agreement between the two means of measuring graft patency was 0.9. Mean radiation dose was 9.0 +/- 7.2 mSv for coronary angiography and 18.5 +/- 4 mSv for computed tomography. Pooled analysis of eight studies, incorporating 932 grafts, confirmed a 97% accuracy for the detection of graft patency by multidetector computed tomography. CONCLUSION: Computed tomography is an accurate, rapid and non-invasive method of assessing coronary artery bypass graft patency. However, this was achieved at the expense of an increase in radiation dose.

Septic arthritis of the manubriosternal joint.

Pyarthrosis of the manubriosternal joint is exceedingly rare. Its rarity defies an early diagnosis, and other causes of chest pain would normally be ruled out first. We describe a patient with a short history of chest pain, pyrexia, and raised inflammatory markers. A destroyed manubriosternal joint with a large abscess was found during surgical exploration. This case illustrates an unusually rapid development of septic arthritis involving a fibrocartilaginous joint in an otherwise healthy young man. Nine other cases have been described in the literature and are reviewed. Early diagnosis followed by adequate surgical drainage and antibiotic therapy led to a good outcome.