Stress Imaging Research Articles

Feasibility of myocardial flow reserve prediction without the use of dynamic data from myocardial perfusion positron emission tomography

Quantification of myocardial flow reserve (MFR) provides diagnostic value for detection of cardiovascular artery disease. However, the common calculation method for MFR requires dynamic acquisition and specific software. The study aimed to predict coronary artery disease by simpler calculation of myocardial count without the use of dynamic data from 13N-ammonia myocardial perfusion positron emission tomography (MP-PET). This study included 40 consecutive patients suspected of ischemic heart disease and 7 healthy controls (34 men and 13 women, 66 ± 12years). All participants underwent adenosine stress and rest 13N-ammonia MP-PET. From the dynamic images, the MFR in the entire left ventricular myocardium (ELV) and the three-vessel area was calculated by dividing stress myocardial blood flow (MBF) by rest MBF. From the static images, the myocardium-to-background ratio (MBR) was calculated by dividing each area's counts/pixel by background counts in the upper thoracic aorta/pixel in both stress and rest images. The MBR-increasing rate (MBR-IR) was calculated by dividing stress MBR by rest MBR. The relationship between MFR and MBR-IR in each area was examined. The cutoff diagnostic value of MBR-IR corresponding to that of MFR for detection of cardiovascular artery disease was calculated. Each MBR-IR was closely correlated with each MFR (r = 0.830 in ELV, r = 0.864 in LAD, r = 0.829 in LCX, r = 0.757 in RCA). The cutoff values of MBR-IR were 1.45 in ELV, 1.46 in LAD, 1.41 in LCX, and 1.45 in RCA, respectively. This study demonstrated that quantification of MBR-IR may provide diagnostic value for detection of coronary artery disease as well as MFR.

Female False Positive Exercise Stress ECG Testing – Fact Versus Fiction

Exercise stress testing is a well validated cardiovascular investigation. Accuracy for treadmill stress electrocardiograph (ECG) testing has been documented at 60%. False positive stress ECGs (exercise ECG changes with non-obstructive disease on anatomical testing) are common, especially in women, limiting the effectiveness of the test. This study investigates the incidence and predictors of false positive stress ECG findings, referenced against stress echocardiography (SE) as a standard. Stress echocardiography was performed using the Bruce treadmill protocol. False positive stress ECG tests were defined as greater than 1mm of ST depression on ECG during exertion, without pain, with a normal SE. Potential causes for false positive tests were recorded before the test. Three thousand (3,000) consecutive negative stress echocardiograms (1,036 females, 34.5%) were analysed (age 59+/-14 years. False positive (F+) stress ECGs were documented in 565/3,000 tests (18.8%). F+ stress ECGs were equally prevalent in females (194/1,036, 18.7%) and males (371/1,964, 18.9%, p=0.85 for the difference). Potential causes (hypertension, left ventricular hypertrophy, known coronary disease, arrhythmia, diabetes mellitus, valvular heart disease) were recorded in 36/194 (18.6%) of the female F+ ECG tests and 249/371 (68.2%) of the male F+ ECG tests (p<0.0001 for the difference). These data suggest that F+ stress ECG tests are frequent and equally common in women and men. However, most F+ stress ECGs in men can be predicted before the test, while most in women cannot. Being female may be a risk factor in itself. These data reinforce the value of stress imaging, particularly in women.

Contractile reserve as a predictor of prognosis in patients with non-ischaemic systolic heart failure and dilated cardiomyopathy: a systematic review and meta-analysis

Objective: Patients with non-ischaemic systolic heart failure (HF) and idiopathic dilated cardiomyopathy (DCM) are a heterogenous group with varied morbidity and mortality. Prognostication in this group is challenging. We performed a systematic review and meta-analysis to examine the significance of the presence of contractile reserve as assessed via stress imaging on mortality and hospitalisation.Methods: A search for studies that non-invasively assessed contractile reserve in patients with DCM or non-ischaemic HF with reduced ejection fraction, stress imaging with follow-up data comparing outcomes. A range of imaging modalities and stressors were included. We examined primary endpoints of mortality and secondary endpoints of combined cardiovascular events including HF progression or hospitalisation. Our analysis compared endpoints in patients with contractile reserve and those without it.Results: Nine prospective cohort studies were identified describing a total of 787 patients. These studies are methodologically but not statistically heterogenous (I2 = 31%). Using a random effect model, the presence of contractile reserve was associated with a significantly lower risk of mortality and cardiovascular events odds ratios of 0.20 (CI 0.11, 0.39) (P < 0.00001) and 0.13 (CI 0.04, 0.40) (P = 0.0004), respectively.Conclusion: Regardless of stressor and imaging modality and despite the significant methodological heterogeneity within the current data (imaging techniques and parameters), patients with non-ischaemic cardiomyopathy and reduced EF who demonstrate contractile reserve have a lower mortality, and lower events/hospitalisations. The presence of contractile reserve therefore offers a potential positive prognostic indicator when managing these patients.

Monitoring Local Changes in Granite Rock Under Biaxial Test: A Spatiotemporal Imaging Application With Diffuse Waves

AbstractDiffuse acoustic or seismic waves are highly sensitive to detect changes of mechanical properties in heterogeneous geological materials. In particular, thanks to acoustoelasticity, we can quantify stress changes by tracking acoustic or seismic relative velocity changes in the material at test. In this paper, we report on a small‐scale laboratory application of an innovative time‐lapse tomography technique named Locadiff to image spatiotemporal mechanical changes on a granite sample under biaxial loading, using diffuse waves at ultrasonic frequencies (300 kHz to 900 kHz). We demonstrate the ability of the method to image reversible stress evolution and deformation process, together with the development of reversible and irreversible localized microdamage in the specimen at an early stage. Using full‐field infrared thermography, we visualize stress‐induced temperature changes and validate stress images obtained from diffuse ultrasound. We demonstrate that the inversion with a good resolution can be achieved with only a limited number of receivers distributed around a single source, all located at the free surface of the specimen. This small‐scale experiment is a proof of concept for frictional earthquake‐like failure (e.g., stick‐slip) research at laboratory scale as well as large‐scale seismic applications, potentially including active fault monitoring.

RETRACTED: Gadolinium-Free Cardiac MR Stress T1-Mapping to Distinguish Epicardial From Microvascular Coronary Disease

BackgroundNovel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow.ObjectivesThis study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.8 and the index of microcirculatory resistance (IMR ≥25 U), compared with first-pass perfusion imaging.MethodsNinety subjects (60 patients with angina; 30 healthy control subjects) underwent CMR (1.5- and 3-T) to assess left ventricular function (cine), ischemia (adenosine stress/rest T1 mapping and perfusion), and infarction (late gadolinium enhancement). FFR and IMR were assessed ≤7 days post-CMR. Stress and rest images were analyzed blinded to other information.ResultsNormal myocardial T1 reactivity (ΔT1) was 6.2 ± 0.4% (1.5-T) and 6.2 ± 1.3% (3-T). Ischemic viable myocardium downstream of obstructive CAD showed near-abolished T1 reactivity (ΔT1 = 0.7 ± 0.7%). Myocardium downstream of nonobstructive coronary arteries with microvascular dysfunction showed less-blunted T1 reactivity (ΔT1 = 3.0 ± 0.9%). Stress T1 mapping significantly outperformed gadolinium-based first-pass perfusion, including absolute quantification of myocardial blood flow, for detecting obstructive CAD (area under the receiver-operating characteristic curve: 0.97 ± 0.02 vs. 0.91 ± 0.03, respectively; p < 0.001). A ΔT1 of 1.5% accurately detected obstructive CAD (sensitivity: 93%; specificity: 95%; p < 0.001), whereas a less-blunted ΔT1 of 4.0% accurately detected microvascular dysfunction (area under the receiver-operating characteristic curve: 0.95 ± 0.03; sensitivity: 94%; specificity: 94%: p < 0.001).ConclusionsCMR stress T1 mapping accurately detected and differentiated between obstructive epicardial CAD and microvascular dysfunction, without contrast agents or radiation.

Is heart rate response a reliable marker of adenosine-induced coronary hyperemia?

Introduction Growing evidence supports ischemia-guided management of chest pain, with invasive and non-invasive tests reliant upon achieving adenosine-induced coronary hyperemia (defined as increased blood flow to an organ’s perfusion bed). In the non-invasive setting, surrogate markers of hyperemia, such as increases in heart rate, are often used, despite not being formally validated. We tested whether heart rate and other non-invasive indices are reliable markers of coronary hyperemia. Methods The first part involved Doppler flow-based validation of the best pressure-wire markers of hyperemia in 53 patients. Subsequently, using these validated pressure-derived parameters, 265 pressure-wire traces were analysed to determine whether heart rate and other non-invasive parameters correlated with hyperemia. Results In the flow derivation cohort, the best determinant of hyperemia came from having 2 out of 3 of: (1) Ventriculisation of the distal pressure waveform, (2) disappearance of distal dicrotic pressure notch, (3) separation of mean aortic and distal pressures. Within the 244 patients demonstrating hyperemia, non-invasive markers of hyperemia, such as change in heart rate (p = 0.77), blood pressure (p = 0.60) and rate-pressure product (p = 0.86), were poor correlates of coronary hyperemia, with only 37.3% demonstrating a ≥ 10% increase in heart rate that is commonly used to adjudge adenosine-induced hyperemia in the non-invasive setting. Conclusions We demonstrate, by correlation with Doppler-flow data, a validated method of identifying coronary hyperemia within the catheter laboratory using the pressure-wire. We subsequently show that non-invasive parameters, such as heart rate change, are poor predictors of coronary hyperemia during stress imaging protocols that rely upon achieving adenosine-induced hyperemia.

Correction: A self-assessed photosensitizer: inducing and dual-modal phosphorescence imaging of mitochondria oxidative stress.

Correction for 'A self-assessed photosensitizer: inducing and dual-modal phosphorescence imaging of mitochondria oxidative stress' by Jing Yang et al., Chem. Commun., 2018, DOI: .

A self-assessed photosensitizer: inducing and dual-modal phosphorescence imaging of mitochondria oxidative stress.

Two novel Ir(iii)-nitroxide conjugates have been synthesized as mitochondria-targeted multi-functional theranostic photosensitizers, capable of simultaneously inducing and dual-modal phosphorescence imaging of mitochondrial oxidative stress under two-photon excitation, thus realizing the photodynamic therapy of cancer and self-assessment of their PDT efficacies.

Advances in Imaging and Heart Failure: Where are we Heading?

Advanced cardiac imaging, following technological advances, has progressed significantly; it now serves as a diagnostic as well as a prognostic tool. Heart failure patients demand constant follow-up with baseline imaging such as echocardiography or more advanced imaging such as stress imaging. Imaging guides treatment as well as interventional procedures for the improvement of heart failure patients. This review aims to summarise the latest imaging techniques in heart failure diagnosis and treatment.

Multifunctional luminescent magnetic cryocooler in a Gd5Mn2 pyramidal complex.

Magnetic cooling is a highly efficient refrigeration technique with the potential of replacing expensive and rare helium-3 in the field of ultra-low temperature cooling. However, the visualization of a cryogen at an extremely low temperature and in a strong magnetic field is challenging, but it is crucial for the precise positioning and in situ thermal probe measurements in potential practical applications. Here, the activation of a red-emissive Mn(ii) ion using 3d/4f chemistry produces a luminescent molecule cooler, [Gd5Mn2(LOMe)2(OH)4(Ac)6(MeOH)10Cl2]Cl3·2MeOH (1), with the core of an Mn(ii)-anchored heptanuclear [GdIII5MnII2] pyramid. The photoluminescence (PL) of the Mn2+ emission, with a large Stokes shift (λem ∼ 690 nm) from 4T1(4G) → 6A1(6S), shows not only a sensitive temperature sensing property but also reversible mechanoluminescence (ML). More attractively, these findings reveal a considerable magnetocaloric effect (MCE) coupled with a tunable emission window, opening up new opportunities in the multifunctional applications of PL, ML, and the MCE involving red-light sources, thermometers, and stress imaging. In particular, this provides a novel resolution to design visualized PL coolers.

Defect-induced Stress Imaging in Single and Multi-crystalline Semiconductor Materials

Residual stress is a key feature which has to be taken into account in all steps of fabrication and processing of semiconductor materials and devices. The photo-elastic microscope SIREX (Scanning Infrared Stress Explorer) measures the depolarization of the light of an infrared laser probe caused by stress-induced birefringence in the sample. Subsequently, a map visualizes the in-plane optical anisotropy induced by stress. Hence, the system is applied as non-destructive tool to map stress distributions with high lateral resolution (3µm) and highest possible stress sensitivity (0.1 kPa). The so-called multi-polarization analysis results in maps of the in-plane maximum shear stress magnitude Δσ and the direction of the principal stress components. These maps can reveal the local stress fields of buried defects and their alignment in distinctive crystallographic directions. The fields are usually at least one order of magnitude larger in extension than the related defects themselves. Examples of extended defect structures in different crystalline semiconductor materials are presented in this paper. The emphasis has been put on line-shaped structures such as slip lines and twins which are partly accompanied by either tensile or compressive point-like stress sources. These structures are showing model characteristics for developing formal procedures of data and image processing under industrial conditions.

Routine preoperative testing in adults undergoing elective non-cardiothoracic surgery

The Belgian Health Care Knowledge Center (KCE) developed a guideline about routine preoperative testing in adults undergoing elective non-cardiothoracic surgery. The guideline is intended for all care providers involved in the preoperative and perioperative management (incl. anesthesiologists, surgeons, cardiologists, lung specialists, radiologists, clinical biologists, general practitioners, etc). A recent English guideline published by NICE (National Institute for Health and Care Excellence) was used as a starting point and adapted to the Belgian context. Clinical questions not included in the NICE guideline were developed de novo. The following tests are recommended under specific conditions: resting electrocardiogram, full blood count test, kidney function tests, haemostasis tests, urinalysis and urine culture, non-invasive cardiac stress imaging. The following tests are not routinely recommended: resting echocardiography, cardiopulmonary exercise testing, chest X-ray, polysomnography, lung function tests (including arterial blood gas analysis), glycated haemoglobin test, liver function tests, coronary CT angiography. This guideline supports clinicians in the choice of ad hoc preoperative testing based on the most recent evidence and specific history of their patients to ensure optimal quality and safety. Tools are provided with this guideline to improve daily usage.

Two-photon microscopy imaging of oxidative stress in human living erythrocytes.

Red blood cells (RBCs) are known to be the most suitable cells to study oxidative stress, which is implicated in the etiopathology of many human diseases. The goal of the current study was to develop a new effective approach for assessing oxidative stress in human living RBCs using two-photon microscopy. To mimic oxidative stress in human living RBCs, an in vitro model was generated followed by two-photon microscopy imaging. The results revealed that oxidative stress is clearly visible on the two-photon microscopy images of RBCs under oxidative stress compared to no fluorescence in controls (P<0.0001). This novel approach for oxidative stress investigation in human living RBCs could efficiently be applied in clinical research and antioxidant compounds testing.

Performance and safety profile of regadenoson myocardial perfusion imaging: first experience in Greece.

MPI can provide valuable information in the investigation of patients with known or suspected coronary artery disease. The stress component of the studies can be conducted with regadenoson, which was approved for clinical use in Greece in 2016. We investigated the performance and safety profile of regadenoson MPI based on our 7 months institutional experience. We studied 96 consecutive patients (59 males, 37 females, mean age 70.35y.o, range: 46-87y.o.) referred to our department for a clinically indicated MPI study with pharmacological stress. Eleven patients suffered from chronic obstructive pulmonary disease. Patients underwent regadenoson stress test, combined with both stress and rest imaging. Data on the symptoms and electrocardiographic changes due to regadenoson administration were recorded. Symptoms were graded as 1-mild: a symptom that did not distress the patient, 2-moderate: a symptom that distressed the patient but it was self-limiting, or 3-severe: a symptom that distressed the patient requiring medical intervention. Regadenoson-related symptoms were reported in 56 patients and were: dyspnea, discomfort, dizziness, chest pain, epigastric pain, neck pain, headache, flushing, nausea, heartburn, weakness, and upper limbs numbness. The severity of symptoms was recorded as grade 1 in 30 patients, grade 2 in 25 patients, and grade 3 in 1 patient. Two or more different symptoms were reported in 28 patients. Ischemic electrocardiographic changes and arrhythmias were observed in 8 patients. Our findings support previously published data indicating the optimal safety profile of regadenoson MPI, even in the group of patients suffering from chronic obstructive pulmonary disease.

Role of Cardiac PET in Clinical Practice

Early identification of atherosclerosis and at-risk lesions plays a critical role in reducing the burden of cardiovascular disease. While invasive coronary angiography serves as the gold standard for diagnosing coronary artery disease, non-invasive imaging techniques provide visualization of both anatomical and functional atherosclerotic processes prior to clinical presentation. The development of cardiac positron emission tomography (PET) has greatly enhanced our capability to diagnose and treat patients with early stages of atherosclerosis. Cardiac PET is a powerful, versatile non-invasive diagnostic tool with utility in the identification of high-risk plaques, myocardial perfusion defects, and viable myocardial tissue. Cardiac PET allows for comparisons of myocardial function both at time of rest and stress, providing accurate assessments of both myocardial perfusion and viability. Furthermore, novel PET techniques with unique radiotracers yield clinically relevant data on high-risk plaques in active progressive atherosclerosis. While PET exercise stress tests were previously difficult to perform given short radiotracer half-life, the development of the novel radiotracer Flurpiridaz F-18 provides a promising future for PET exercise stress imaging. In addition, hybrid imaging with computed tomography angiography (CTA) and cardiac magnetic resonance (CMR) provides integration of cardiac function and structure. In this review article, we discuss the principles of cardiac PET, the clinical applications of PET in diagnosing and prognosticating patients at risk for future cardiovascular events, compare PET with other non-invasive cardiac imaging modalities, and discuss future applications of PET in CVD evaluation and management.

Stress imaging in structural challenging MEMS with high sensitivity using micro-Raman spectroscopy

The development cycle of microelectromechanical systems (MEMS) includes several numerical simulation and optimization iterations. To verify and calibrate the models with experimental data, the non-destructive measurement and imaging of stress distribution in structural challenging regions with high sensitivity is of great importance. This is possible to achieve using micro-Raman spectroscopy. Due to limitations of commercially available software regarding flexibility and sensitivity, the authors developed an alternative approach which ensures that the quality of spectra is taken into account in the evaluating calculations. In this way a remarkable stress resolution below 20MPa becomes possible even on structural challenging MEMS devices.

Usefulness of Achieving ≥10 METs With a Negative Stress Electrocardiogram to Screen for High-Risk Obstructive Coronary Artery Disease in Patients Referred for Coronary Angiography After Exercise Stress Testing

Functional capacity in exercise stress testing is an independent predictor of cardiac events. Routine use of nuclear perfusion imaging increases radiation burden and cost. Our goal was to assess the clinical utility of exercise functional capacity with stress electrocardiogram (ECG) as an adjunct in predicting the presence of high-risk obstructive coronary artery disease (CAD) on diagnostic coronary angiography. We performed a retrospective study of patients who underwent exercise stress testing for the evaluation of chest pain and underwent diagnostic coronary angiography within the subsequent 3 months. High-risk CAD was defined as coronary artery diameter stenosis of ≥70% in the proximal left anterior descending artery, ≥70% diameter stenosis in 3 major epicardial arteries, or ≥50% diameter stenosis in the left main artery. Univariable and multivariable analyses were performed to identify predictors of high-risk CAD. Of the 412 patients, 105 (25%) had high-risk CAD on coronary angiography. On multivariate logistic regression, we found that positive stress ECG, abnormal stress imaging, left ventricular ejection fraction, and male gender were independent predictors of high-risk CAD. The strongest predictor was positive stress ECG (hazard ratio 3.16, 95% confidence interval 1.90 to 5.27, p <0.001). Functional capacity measures alone were not independent predictors of high-risk CAD. Achieving ≥10 METs with a negative stress ECG resulted in 94% sensitivity and 97% negative predictive value in identifying high-risk CAD. This supports the strategy for provisional use of myocardial perfusion imaging in patients with low functional capacity and/or abnormal stress ECG to minimize cost and radiation exposure.

ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury.

Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the underlying mechanisms of skeletal muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4-phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER), burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1, 4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for transmission electron microscopy, calcium imaging, gene expression and protein analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain activity measurement. The results showed that ER stress markers were increased in the burn group compared with the sham group, especially at post-burn days 4 and 7, which might consequently elevate cytoplasmic calcium concentration, promote calpain production as well as activation, and cause skeletal muscle damage/wasting of TA muscle after severe burn injury. Interestingly, treatment with 4-PBA prevented burn-induced ER swelling and altered protein expression of ER stress markers and calcium release, attenuating calpain activation and skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3-I ratio were also increased in the burn group compared with the sham group, while MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken together, these findings suggested that severe burn injury induces ER stress, which in turns causes calpain activation. ER stress and subsequent activated calpain play a critical role in skeletal muscle damage/wasting in burned rats.

Coronary Computed Tomography Angiography in Patients with Stable Coronary Artery Disease

The guidelines on the management of stable coronary artery disease (SCAD) recommend the use of coronary computed tomography angiography (CTA) in the process of diagnosing coronary artery disease in patients with low intermediate pre-test probability for SCAD. Particularly in cases where stress electrocardiogram or stress imaging provides unclear results, a computed tomographic examination can be considered as a reliable alternative to invasive coronary angiography. Due to its high negative predictive value, coronary CTA can provide accurate information on the presence of coronary artery stenosis and thus coronary artery disease can be reliably excluded without the risks associated with invasive procedures. Similarly, patients with unstable angina or chest pain without typical alterations in the electrocardiogram and without an elevation of troponin can also benefit from a non-invasive coronary CTA-based diagnostics as first approach as it allows ruling out the presence of disease or planning an intervention without the risks associated with a potentially inappropriate invasive approach.

Computer derived transient ischemic dilation ratio for identifying extensive coronary artery disease using a CZT camera and imaging in the upright position

BackgroundTransient ischemic dilation (TID) of the left ventricle (LV) has not been validated as a marker of extensive coronary artery disease (CAD) for studies using a cadmium-zinc-telluride (CZT) camera with upright imaging. MethodsTID ratios were obtained from upright stress and rest images on a CZT camera. Separate cut-off values were determined for exercise and for regadenoson stress. The cutoffs were then applied to 28 patients with extensive CAD and 101 patients without extensive CAD. ResultsWith treadmill exercise, an upright TID ratio ≥1.16 provided a positive predictive value of 50% and a negative predictive value of 85.4% for the identification of extensive CAD. In the regadenoson group, an upright TID ratio of 1.29 provided a positive predictive value of 20% and a negative predictive value of 75.9%. Although not an independent predictor of extensive CAD in all subjects, in subjects with a normal upright LVEF, it provided a predictive value by receiver operating characteristics comparable to the SSS. ConclusionsIncreased upright TID measurements on a CZT camera are associated with extensive CAD. The upright TID measurements can serve in an adjunctive role to SSS, and may be most effective in patients with a normal upright exercise LVEF.