Mitral stenosis is an important cause of heart valve disease globally. Echocardiography is the main imaging modality used to diagnose and assess the severity and hemodynamic consequences of mitral stenosis as well as valve morphology. Transthoracic echocardiography (TTE) is sufficient for the management of most patients. The focus of this review is the role of current two-dimensional (2D) and three-dimensional (3D) echocardiographic imaging for the evaluation of mitral stenosis. Mitral stenosis is an important cause of heart valve disease globally. Rheumatic heart disease is the most common etiology worldwide . Though Echocardiography is the main imaging modality to diagnose and assess the severity and hemodynamic consequences of mitral stenosis ,5 as wel2 (rather than 4–6 cm2 as previously thought) [Knowledge of normal mitral valve anatomy is useful to appreciate the significance of disease-induced changes. The normal mitral valve annulus area is found to be on average 10 cmthought) .Commissural fusion with valvular thickening, particularly at the free edge of the leaflets. This is usually best seen in the parasternal short-axis view. Later, thickening extends towards the base with further restriction of valve motion.Reduced leaflet mobility and restricted opening. The posterior leaflet is usually partially or completely immobile and the anterior leaflet shows a diastolic doming, producing the characteristic “hockey stick” configuration. This is usually best seen in the parasternal long-axis view.Affection of the subvalvular apparatus with thickened, fused, and/or shortened chords.Calcification of the leaflets and the subvalvular apparatus.Echocardiography provides key information regarding valvular morphology, subvalvular apparatus, leaflet thickness and mobility, and degree and location of calcifications. Echocardiographic findings in mitral stenosis are related to etiology. The main echocardiographic characteristic of rheumatic mitral stenosis are:Direct planimetry of mitral valve area is the reference method to evaluate mitral stenosis severity . 2D plan2D planimetry is a direct measurement. It is independent of load conditions, chamber stiffness and concomitant valve disease and reliably correlates with the size of the anatomic orifice . On the PHT refers to the time required for the peak mitral gradient to drop by one half. The more severe the stenosis, the slower the left ventricle will fill and the longer the time required for the transmitral gradient to decrease. PHT has been empirically correlated with mitral valve area with the Hatle formula: mitral valve area = 220/PHT. From the practical point of view, PHT is obtained by tracing the deceleration slope of the E wave. Thus, an accurate recording of the continuous wave Doppler diastolic mitral inflow should be obtained. In non-linear deceleration slopes, such as in cases of a bimodal shape of the E slope, a mid-diastolic line-drawing method is a reliable technique for measuring PHT . FurtherOne advantage of this method is that it can be performed in cases where the acoustic window makes direct planimetry difficult. On the contrary, PHT is not dependent only on the mitral valve area, but also on the left atrium and left ventricle, and peak mitral gradient. Thus, in presence of a left ventricle restrictive filling pattern, low left atrium compliance, atrial septal defect or significant aortic regurgitation, the PHT is shortened and mitral valve area is overestimated.This method assumes that blood flowing towards an orifice accelerates, forming concentric hemispherical layers. These layers are called proximal isovelocity surface areas, and blood velocity is equal for each of them. These areas can be studied by color Doppler. Color baseline should be adjusted to better define a hemisphere.aliasing ∙ πr2/peak Vmitral, where r is the radius of the hemisphere and α is the opening angle of mitral leaflets relative to flow direction.Mitral valve area can be calculated by: mitral valve area = α/180 · VPISA method is rarely used in mitral stenosis, though it can be useful in the presence of significant mitral regurgitation.Mitral · AreaMitral Valve = VTIAorta · AreaLVOT. It is important to note that the velocity time integral of the mitral flow should be obtained at the level of the mitral valve orifice and not at the level of the mitral leaflet tips. Despite the appealing simplicity of this method, it is rarely used in clinical practice. It cannot be used in the presence of significant mitral or aortic regurgitation, and the number of required measurements increases the probability of error.This method assumes that filling volume of diastolic mitral flow is equal to aortic stroke volume. Stroke volume is calculated by multiplying the velocity time integral (pulsed wave Doppler) and left ventricular outflow tract area. Mitral flow can be calculated in the same manner. Thus, VTIMitral gradients play an important role in the assessment of mitral stenosis severity. Peak and mean mitral gradients are obtained by tracing the continuous wave Doppler across the mitral valve in the apical four chamber view using the simplified Bernoulli equation. Careful attention must be paid to beam alignment. Mean gradient is the most important hemodynamic parameter to assess mitral stenosis severity. Peak gradient is more dependent on left atrium and left ventricle compliance and loading conditions, and as such is more variable.Transmitral gradients are highly dependent on heart rate. Changes in hear rate explain a substantial proportion of the variability. Therefore, the heart rate at which the gradients were measured should be reported. In patients with atrial fibrillation, mean gradient should be calculated as the average of five cycles with the least variation of R–R intervals and as close as possible to normal heart rate . The traSignificant mitral stenosis produces gradual left atrium enlargement. When assessing left atrium size, a measurement of the volume is recommended. Left atrial volume is obtained by tracing the endocardial border of the left atrium in both the apical four chamber and two chamber views by the application of the biplane method of discs (modified Simpson’s rule) . The meaIn the absence of an alternative cause, the presence of pulmonary hypertension is an indicator of the hemodynamic consequences of mitral stenosis, and suggests the presence of a significant degree of stenosis. Thus, PSP should be routinely estimated in patients with significant mitral stenosis. It is important to note however, that PSP resting values may be normal even in the presence of severe mitral stenosis.Later in the course of the disease, a dilated and dysfunctional right ventricle and secondary tricuspid regurgitation may be found. Tricuspid regurgitation may also be a result of primary rheumatic involvement of the valve.In recent years, the epidemiological scenario of mitral stenosis has been changing in developed countries: the prevalence of rheumatic disease is decreasing, and the prevalence of degenerative mitral stenosis related to mitral annulus calcification is increasing. This is generally seen in the elderly and in patients with severe renal disease. It is regarded as an active and regulated molecular process of injury, lipid deposition, inflammation and bone formation .There are distinct echocardiographic features that differentiate rheumatic and degenerative mitral stenosis. As opposed to rheumatic stenosis, the main lesion is annular calcification, predominantly along the posterior aspect, resulting in a reduced annular area. Rarely, it extends anteriorly, and severe forms may involve the leaflets. Commissural fusion is not present and leaflet tip motion is relatively preserved. These forms are most often mild or moderate.The echocardiographic evaluation of degenerative mitral stenosis severity is difficult. As previously mentioned, rheumatic mitral stenosis severity can be assessed by planimetry, PHT, the volumetric method, the PISA method, and the mean transmitral gradient. However, these parameters lack validation in degenerative mitral stenosis.Direct planimetry is challenging in these patients because of acoustic shadowing produced by calcium. Moreover, degenerative mitral stenosis is associated with advanced age, and diastolic dysfunction is not uncommon. PHT may lead to an overestimation of mitral valve area in conditions of elevated left ventricle filling pressure or abnormal left atria compliance . The volMean transmitral gradient is a useful parameter for evaluating degenerative mitral stenosis. In patients with mitral valve dysfunction related to annular calcification, mean transmitral gradient is associated with increased mortality after adjustment for age, sex, and risk factors related to mitral annular calcification ,15. It iCongenital mitral stenosis is a rare congenital heart malformation that comprises a heterogeneous group of lesions that usually present in association with other congenital diseases such as left heart underdevelopment, atrioventricular canal defects, left ventricular outflow tract obstruction, or Shone complex. Congenital mitral stenosis rarely occurs in isolation.Shone complex is a rare congenital heart disease that comprises coarctation of the aorta, valvular and subvalvular aortic stenosis, and mitral stenosis either as a parachute mitral valve or as supravalvar mitral membrane .Parachute mitral valve is an anomaly in which all the tendinous chords of the mitral valve are attached to a single papillary muscle and is a common finding in the setting of congenital mitral valve stenosis.Two-dimensional transthoracic echocardiography is the first-line method used to evaluate mitral valve morphology and to diagnose and assess the severity and hemodynamic consequences of mitral stenosis. In order to perform a comprehensive assessment, multiple scanning planes should be explored:The parasternal long-axis view allows for visual assessment of mitral valve morphology and leaflet excursion. It demonstrates A2 and P2 scallops. Leaflet motion and thickness and the presence and extend of calcification should be reported. The characteristic doming of the anterior leaflet is better seen in this view . In mitrThe parasternal short-axis view allows for visual assessment of the leaflets and commissures. Commissural fusion is best seen in this view. The posteromedial (left) and anterolateral (right) commissures are visualized. Scallops one to three are seen from the anterolateral commissure to posteromedial commissure. This view is also used to perform planimetry of the mitral leaflet tips. Tilting from base to apex will demonstrate the narrowest valve orifice .The apical four chamber view typically demonstrates A3, A2, and P1 scallops from left to right A. It allSuitability of mitral valve for percutaneous mitral commissurotomy is based on echocardiographic findings. Scoring systems have been developed to help with this task. The Wilkins score  Table 2Table 2 i2, left atrial thrombus, more than mild mitral regurgitation, severe calcification, absence of commissural fusion, severe concomitant aortic valve disease, severe combined tricuspid stenosis and tricuspid regurgitation requiring surgery or concomitant coronary artery disease requiring surgery [Percutaneous mitral commissurotomy is contraindicated in patients with a mitral valve area >1.5cm surgery .Transesophageal echocardiography should be performed to exclude left atrial thrombus before percutaneous mitral commissurotomy or after an embolic event . Due to It measures all three spatial dimensions. Therefore, it is not reliant on plane positioning and does not require geometric assumptions of cardiac structures.Images can be rotated and viewed from different perspectives. This allows for a better understanding of the relationship between structures and makes 3D images more intuitive.3D echocardiography represents a key innovation in cardiovascular imaging. The development of matrix-array transducers has allowed for real-time acquisition and online display of 3D images. Nowadays, 3D echocardiography is available on most ultrasound machines, and current transducers are able to acquire both 2D and 3D images. These technological advances have led to a progressive implementation of 3D echocardiography in routine clinical practice. Its main advantages are:On the contrary, limitations of 3D echocardiography include reduced spatial and temporal resolution compared to 2D echocardiography and suboptimal images in patients with arrhythmias.First, 2D images should be used to locate the planes for imaging the mitral valve. Later, 3D imaging of the mitral valve can be performed using multiple 3D imaging modalities.Biplane mode allows for the use of a dual screen to display the mitral valve in two planes in real time. The second plane is usually orthogonal, though any rotation angle can be used. Color Doppler imaging can also be used together with biplane imaging. This mode is useful for a preliminary evaluation of the mitral valve. Scallops and segments of the mitral valve can be investigated by manipulating the lateral plane in different angle orientations in order to provide detailed information regarding mitral valve anatomy and the mechanism and etiology of mitral stenosis. In transthoracic echocardiography, biplane imaging can help ensure that planimetry takes place at the leaflet tips. An orthogonal plane can be obtained placing the cursor at the leaflet tips in the parasternal long-axis view. However, in order to avoid an oblique short-axis view, adequate alignment of the mitral orifice in the long-axis view is required.Full volume imaging provides the largest sector and allows for an evaluation of the entire mitral valve apparatus. Real-time full volume acquisitions generally result in poor spatial and temporal resolution. Therefore, whenever possible, ECG gating acquisitions should be used. A full volume with gated acquisition is reconstructed by merging several individual volume slices gated to the ECG. This results in high temporal and spatial resolution. However, it can also be susceptible to artefacts due to arrhythmias and/or respiratory motions. ECG should be optimized to show a distinct R wave and the number of acquisition beats should be adjusted attending to the patient’s circumstances. Moreover, images should be obtained with breath-holding. Once acquired, the full volume dataset can be cropped, rotated, viewed in multiple perspectives, or decomposed into 2D cross-sections.Real-time 3D imaging permits a narrow sector and therefore higher spatial and temporal resolution. However, the sector is generally insufficient to visualize the entire mitral valve apparatus. The pyramidal volume should be acquired at a decreased depth and focused on the mitral valve. This allows for an initial 3D evaluation of the mitral valve.Focused wide-sector imaging allows for a 3D focused view of the mitral valve. In transthoracic echocardiography, 3D zoom of the mitral valve can be acquired from both the parasternal and the apical views . The antThree-dimensional echocardiography is superior in evaluating mitral stenosis severity, because direct visualization of the valve orifice in multiple planes ensures that the planimetry takes place at the level of the mitral leaflet tips, where the valve orifice is narrowest. Indeed, 3D planimetry has been reported as the most accurate method for mitral valve area evaluation ,21, and In order to perform 3D planimetry, the 3D zoom dataset should include the entire mitral annulus and the leaflet height. Later, the frame when leaflet excursion is greater should be identified and multiplane reconstruction should be used to achieve a parallel alignment with the narrowest portion of the mitral valve orifice. Finally, the mitral valve area is obtained tracing the inner edge of the orifice . Modern A scoring system based on 3D echocardiography, the Anwar score, has been developed for the evaluation of patients before percutaneous mitral commissurotomy  Table 3Table 3.Echocardiography is the main imaging modality to diagnose and assess the severity and hemodynamic consequences of mitral stenosis as well as valve morphology. Transthoracic echocardiography is sufficient for the management of most patients. Direct planimetry of the mitral valve area is the reference method used to evaluate mitral stenosis severity. The mean gradient is the most important hemodynamic parameter to assess mitral stenosis severity, and is a key parameter for evaluating degenerative mitral stenosis, where direct planimetry is difficult. Transesophageal echocardiography should be performed to exclude left atrial thrombus before percutaneous mitral commissurotomy or after an embolic event. Three-dimensional echocardiography is superior in evaluating mitral stenosis severity, because the direct visualization of the valve orifice in multiple planes ensures that the planimetry takes place at the level of the mitral leaflet tips, where the valve orifice is narrowest.


Despite important advancements in acute myocardial infarction (AMI) management, it continues to represent a leading cause of mortality worldwide. Fast and reliable AMI diagnosis can significantly reduce mortality in this high-risk population. Diagnosis of AMI has relied on biomarker evaluation for more than 50 years. The upturn of high-sensitivity cardiac troponin testing provided extremely sensitive means to detect cardiac myocyte necrosis, but this increased sensitivity came at the cost of a decrease in diagnostic specificity. In addition, although cardiac troponins increase relatively early after the onset of AMI, they still leave a time gap between the onset of myocardial ischemia and our ability to detect it, thus precluding very early management of AMI. Newer biomarkers detected in processes such as inflammation, neurohormonal activation, or myocardial stress occur much earlier than myocyte necrosis and the diagnostic rise of cardiac troponins, allowing us to expand biomarker research in these areas. Increased understanding of the complex AMI pathophysiology has spurred the search of new biomarkers that could overcome these shortcomings, whereas multi-omic and multi-biomarker approaches promise to be game changers in AMI biomarker assessment. In this review, we discuss the evolution, current application, and emerging blood biomarkers for the diagnosis of AMI; we address their advantages and promises to improve patient care, as well as their challenges, limitations, and technical and diagnostic pitfalls. Questions that remain to be answered and hotspots for future research are also emphasized. Cardiovascular diseases are responsible for almost half of all fatalities worldwide, causing more than four million deaths each year in Europe alone . Among tRecognition that AMI most commonly occurs as a result of intracoronary thrombosis and that early opening of the occluded coronary artery significantly ameliorates outcomes in this high-risk population has reshaped AMI diagnosis over the years. Major interest emerged in developing strategies that would allow both early recognition and exclusion of AMI. The former would enable rapid, often life-saving interventions; the latter would allow rapid and safe patient discharge, considerably reducing healthcare costs. Diagnosis of AMI continues to be mainly driven by the occurrence of acute chest pain in the presence of typical ECG changes. However, approximately 90% of patients presenting with chest pain do not have AMI, and the sensitivity and specificity of ECG changes in AMI are rather low ,5. MoreoInitially, serial, daily measurement of cardiac biomarkers served only as a strategy to retrospectively confirm AMI diagnosis. Since then, their role has become increasingly larger, and cardiac biomarker changes are now included as major diagnostic criteria in AMI  6]..6].This article reviews the evolution, current application, and emerging biomarkers for the diagnosis of AMI, addressing their advantages and promises to improve patient care, as well as their challenges, limitations, and technical and diagnostic pitfalls. Questions that remain to be answered and hotspots for future research are also emphasized.Severe myocardial ischemia and the consequent myocardial necrosis lead to the release of a plethora of cardiac enzymes into the circulation. Thus, markers such as myoglobin, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and creatine kinase (CK), including the concept of delta change, were introduced as initial indicators of AMI. Historically, AST and LDH were the first cardiac enzymes used for AMI diagnosis .Aspartate aminotransferase is a ubiquitous, soluble, intracellular enzyme critical in amino acid metabolism. The largest amounts of AST are expressed in the liver, the myocardium, the kidney, and the skeletal muscle. In 1954, Ladue et al. demonstrated a significant rise in AST 3–4 h after an AMI, beginning the age of enzyme-based AMI diagnosis [The ubiquitous expression of AST in a wide variety of tissues significantly affects its specificity for myocardial injury, limiting its use as a cardiac biomarker. Currently, AST is no longer used for AMI diagnosis.Only one year after the advent of AST as an AMI biomarker, LDH, an enzyme that reversibly converts lactate to pyruvate, emerged as a new promising indicator of AMI . Blood l4); the isomeric form LDH-2 exists in a tetrameric combination of three heart and one muscle subunit (H3M1) [Of the five LDH izoenzymes, the heart expresses LDH-1 with four heart subunits (Ht (H3M1) . Hence, t (H3M1) .Nowadays, the only use of LDH is in distinguishing between acute and subacute AMI in the late stage of the ischemic event when other cardiac markers have already returned to their normal levels.Myoglobin is a low molecular weight iron- and oxygen-binding protein abundantly expressed in the myocardium and skeletal muscle. Myoglobin is rapidly released by the injured myocardium. Its blood levels start to increase within the first 30 min to 2 h after the onset of ischemia, which makes myoglobin an important marker for the early detection/exclusion of cardiac injury. Its levels increase during the first 6–10 h after AMI, reach a peak ≈12 h after the acute event, and return to baseline by 24 h after AMI . MyoglobCreatine kinase is an enzyme abundantly expressed in the myocardial cells, where it catalyzes reversible transfer of high-energy phosphate from ATP to creatine, producing creatine phosphate. Since the early 1970s, and particularly since the 1980s, with the advent of the ELISA technique, CK has become a crucial laboratory parameter for the identification of myocardial damage and AMI. The enzyme is present, however, in a large variety of other tissues , stronglAlong with the introduction of new myocardial injury biomarkers, the sensitivity for the diagnosis of AMI also recorded an important rise. However, because all previously identified markers were also expressed in a variety of other tissues, specificity continued to be problematic see . Hence, Nevertheless, values above the upper reference limit of cardiac troponins can be detected in other circumstances unrelated to a thrombotic acute coronary event .Patients with moderate chronic kidney disease or dialyzed patients present persistent elevated cTn values, associated with increased cardiac death and all-cause mortality . In clinHowever, the prognostic role of cardiac troponins in the assessment of other potential causes of elevation showed an important independent value, such as in acute heart failure. Serial measurements of troponin can be used for risk assessment in heart failure out-patients, because regular or persistent elevations of cTn are corelated with high risk of death or hospital readmission . The cutElevated plasma troponin levels in acute phase of pulmonary embolism are defined as concentrations above upper reference limits; these limits are assay dependent .The rule-in or rule-out of AMI diagnosis based entirely on positive values of troponins addresses challenges, and these values should be interpreted considering clinical presentation, serial ECGs, and other patient variables.In the myocardium, troponin exists as a hetero-trimer composed of troponin I (TnI), T (TnT), and C (TnC) as subunits. The troponin complex interacts with tropomyosin as part of the thin filaments of the cardiac sarcomere, regulating the calcium-dependent interaction of actin and myosin in response to cytosolic calcium changes. TnC also exists in the striated muscle, rendering it unsuitable for AMI diagnosis, whereas TnT and TnI are specific to the heart and are therefore termed “cardiac troponins”. Although TnI assays have generally been affected by more technical problems, this isoform has been shown to have greater early diagnostic accuracy and to be more specific for myocardial injury than TnT, which has also been shown to increase in settings such as skeletal muscle injury, kidney disease, malignancy, or sepsis ,23. In aWith the advent of high-sensitivity cTn (hs-cTn) assays, sensitivity has become even higher, enabling the detection of troponin levels 10-fold lower than the initial values . By defiMortality attributable to AMI has significantly declined over the years, mainly due to early recognition and rapid, effective, myocardial revascularization. Repeated testing by principal laboratories is a significant logistic challenge, however, that cannot be overcome by many of the diagnostic laboratories. Implementation of algorithms requiring fast decision-making thus had to be paralleled by earlier access to biomarkers, particularly troponin. Point-of-care tests (POCTs) for cTnI with diagnostic sensitivity comparable to that of central laboratory testing have become available, allowing markedly improved turnaround times and immediacy of results, along with improved therapeutic decision-making, patient flow and experience, and reduced costs . CurrentThe introduction of cTn testing has dramatically changed the diagnosis of AMI, allowing earlier therapeutic interventions in AMI patients and the more rapid discharge of patients without AMI. Although clearly superior to earlier AMI biomarkers in detecting myocardial ischemia, cTn are far from ideal. The level of oxidation/reduction of the troponin molecule, phosphorylation, fibrin strands, and heterophilic antibodies have the potential to interfere with TnI assays . CirculaThe continuous progress in the treatment of cardiac diseases and the introduction of new therapeutic approaches has imposed the rapid and continuous development of new laboratory assays . The widRecent studies have supplemented the set of classic biomarkers of myocardial necrosis with a number of additional biomarkers, including the heart-type fatty acid binding protein (hFABP), the ischemia-modified albumin (IMA), and the sarcomeric cardiac myosin-binding protein C (cMyC).Similarly to myoglobin, hFABP, a low-molecular-weight, non-enzymatic protein involved in the intracellular buffering and transport of long-chain fatty acids, is rapidly  released into the circulation after the onset of myocardial injury, its levels returning to baseline 12–24 h after the acute ischemic event . AlthougAcute myocardial ischemia induces major protein changes, including alterations of the N-terminus of albumin, leading to the formation of IMA. In the same manner to myoglobin and hFABP, IMA levels also increase rapidly  after AMI onset. A combined approach, using IMA and TnT at presentation for chest pain, appeared to increase AMI diagnostic accuracy compared with TnT alone . HoweverSarcomeric cMyC is one of the most promising novel myocardial necrosis biomarkers. This myosin-binding protein isoform is exclusively expressed at the level of the heart, making it a specific marker of myocardial injury; it is more rapidly released into the bloodstream as a result of myocardial necrosis than troponin, allowing earlier detection of myocardial injury and disease . The carOver the years, cardiovascular medicine has seen numerous, often major, paradigm changes. In atherosclerosis, concepts have moved from a purely lipid-related, to a more complex, lipid-inflammatory pathophysiology . In atriThe observation that neurohormonal activation is a major change occurring in AMI patients has drawn attention to potentially novel AMI biomarkers, including the B-type natriuretic peptide (BNP) and the N-terminal fragment of its precursor (NT-proBNP), copeptin, and the midregional proadrenomedullin (MR-proADM).Secreted by the ventricular myocytes in response to stretch, the proBNP precursor is cleaved into BNP and the inactive fragment NT-proBNP. Once released, BNP exerts vasodilating, natriuretic, hypocoagulative, inotropic, antiarrhythmic, and anti-renin–angiotensin–aldosterone and sympathoadrenal system effects, while promoting cell differentiation and tissue repair and supporting immunity, metabolic responses, and inflammation . In patiCopeptin, a stable glycopeptide derived from the C-terminal fragment of the vasopressin prohormone, has been shown to be co-released with arginine vasopressin within the first 4 h after AMI. Circulating copeptin levels have been shown to exhibit linear correlation with those of arginine vasopressin, a key regulator of water homeostasis and plasma osmolality . This maAdrenomedullin is a stress hormone expressed in a large variety of tissues, including the brain, kidney, vasculature, and adrenal medulla, involved in diuresis and natriuresis, vasodilation, and inotropism regulation. Adrenomedullin is generated from its more stable precursor MR-proADM. In clinical studies, MR-proADM has been shown to significantly increase in AMI patients, particularly in those developing post-AMI heart failure, and high MR-proADM levels have been associated with significant increases in short- and long-term mortality and hospitalization for heart failure following AMI ,55. IncrImmediately after the onset of AMI, the renin–angiotensin–aldosterone system (RAAS) is activated, and this phenomenon is linked with an unfavorable prognosis . High leHeightened RAAS activity demonstrates a determining implication not only within the pathogenesis of AMI, but also as an estimated model with 5 years post-AMI mortality, as revealed by the RAAS polymorphisms in the presence of AGT CC genotype and ACE allele, individual or in association .Increased plasma renin activity (PRA) values were detected in both hypertensive and normotensive patients, in whom the diagnosis of AMI was ruled in; these were independently associated with a poor prognosis in AMI patients ,60. In tMyocardial inflammation is a critical process occurring in the setting of AMI that has been related to a variety of deleterious consequences, including electrical instability and increased risk of cardiac arrhythmias, autonomic dysfunction, and fibrosis development ,62,63,64Increased CRP levels have been linked with the extent of myocardial injury and with poorer prognosis in AMI patients. In animal studies, CRP removal was able to significantly reduce infarct size and improve outcomes . Ries etIn the setting of AMI, increased IL-6 levels favor activation and recruitment of inflammatory cells, promote CRP release, and exert cardiac negative inotropic effects, predicting poor prognosis in this population . MeanwhiThe peptide precursor of the hormone calcitonin, PCT, has also been shown to increase in inflammatory settings, including AMI, and to have prognostic value in ischemic heart disease .The potential role in the development of atherosclerosis and acute coronary syndromes of a group of zinc-dependent endopeptidases, namely, matrix metalloproteinases (MMPs), was investigated in previous studies ,71,72.The increased circulating levels of MMP 2, 3, 9 and 28 in AMI do not distinguish between atherothrombotic and non-atherothrombotic events. ,73. Due to matrix metalloproteinase-9 linking with plaque rupture and myocardial necrosis, MMP-9 has demonstrated its position as an early-stage biomarker of AMI . It was Other inflammatory biomarkers, including IL-1β, IL-37, and angiopoietin-like protein 2, have also been shown to increase in AMI patients, but further studies are needed before drawing a definitive conclusion in their regard .Myeloperoxidase (MPO), a component of neutrophil granules, is abundantly released from unstable atherosclerotic plaques and plays a critical role in myocardial inflammation and oxidative stress. When used alone, MPO does not seem to be appropriate for AMI diagnosis . HoweverCluster of differentiation 40 protein, CD40, and its soluble ligand, sCD40L, are expressed by a wide variety of cell types and have been shown to be released during cardiac myocyte rupture. Both molecules are involved in inflammation and thrombosis and have been proposed as diagnostic AMI biomarkers . HoweverBiomarkers, including lipid markers , endothelial cells- (endocan) and platelet-  related markers have been proposed as AMI biomarkers ,51. FurtThe main characteristics of newer biomarkers potentially used in the diagnosis of AMI are depicted in Studies about other newer biomarkers, such as CRP, IL-6, procalcitonin, CD40, myeloperoxydase, and sCD40L, could be valuable in the diagnosis and prognosis of AMI, although further studies are needed ,35. GuidThe development of new, high-technology laboratory methods continues to improve therapy monitoring, as well as diagnostic and prognostic accuracy in cardiovascular medicine ,82. WithGrowth differentiation factor 15 (GDF-15), galectin-3 , and soluble suppression of tumorigenicity factor 2 (sST2) appear to be among the most promising novel AMI biomarkers and have been extensively studied over the past years.Circulating levels of GDF-15, a member of the transforming growth factor beta cytokine superfamily expressed in a wide variety of cardiovascular and non-cardiovascular cells, have been shown to increase in inflammatory and high oxidative stress states and tissue injury, including AMI, and to predict prognosis in this population . GalectiBy allowing rapid assessment of various products of cell metabolism, including during acute events, metabolomics has emerged as a promising new source of highly specific diagnostic AMI biomarkers. Studies in patients with septal ablation-induced AMI identified several myocardial cells metabolites released very early  after AMI onset . These iNon-coding RNAs, including microRNAs (miRNAs), circular RNAs, and long non-coding RNAs (lncRNAs), act as strong, tissue- and cell-specific epigenetic regulators of cardiac gene expression, homeostasis, and function, and have recently emerged as promising biomarkers in a wide variety of cardiovascular diseases. These molecules circulate in the peripheral blood, either bound to transport proteins or packaged in microparticles, thus being stably transported in the blood, protected from degradation, and detectable in blood samples. A number of these circulating non-coding RNAs have been or are currently under investigation as potential diagnostic AMI biomarkers.5) levels, and returning to baseline within hours or days after the acute event, while also reaching high  sensitivity and specificity [MicroRNAs are small, single-stranded RNA molecules that work as post-transcriptional protein synthesis suppressors via gene silencing. Four miRNAs—miR-1, miR-133a/b, miR-208b, and miR-499, the latter two being expressed solely in the cardiac myocytes—have been consistently reported to increase in AMI patients, although controversies still remain regarding the value of individual miRNAs as AMI biomarkers . With 78gh i.e., % and 87%cificity . Certaincificity . In addicificity . Severalcificity ,93,94,95The widespread use of cTn has revolutionized AMI diagnosis. Particularly, with the advent of hs-cTn, we can confidently say that sensitivity is no longer an issue in AMI diagnosis. However, two problems remain to be solved. Firstly, the increased sensitivity provided by hs-cTn assays came with a cost—an inevitable decrease in diagnostic specificity. Secondly, although cTn increase relatively early after the onset of AMI, they still leave a time gap between the onset of myocardial ischemia and our ability to detect it, thus precluding very early management of AMI. Historical markers, such as myoglobin, increase much faster than cTn, but they do not provide sufficient diagnostic specificity.To date, all AMI biomarkers have focused on molecules released by the cardiac myocytes as a result of myocardial necrosis. More recently, understanding of the complex AMI pathophysiology has opened the way for new biomarker identification. Acknowledgment that processes such as inflammation, neurohormonal activation, or myocardial stress occur much earlier than myocyte necrosis has allowed us to expand biomarker research in these areas . AlthougMulti-omic approaches hold great promise for more accurate and faster AMI diagnosis. MicroRNAs appear to be particularly promising in this regard, given that myocyte stress induced by anoxia, acidosis, and/or edema precedes myocardial necrosis in AMI patients and is rapidly reflected in circulating miRNAs levels. The rapid progress in molecular biomarker research must be matched, however, by similar progresses in laboratory techniques. Indeed, bioluminescence, solution-phase bioluminescence, and high-throughput sequencing methods have been developed for miRNA detection, but improvement is still necessary to provide instruments that can accurately, conveniently, inexpensively, and rapidly quantify circulating miRNAs in a large number of hospital laboratories. Integrated interpretation of multi-omics data also remains rather difficult at present, and may require machine learning to transform this approach into a clinically useful diagnostic tool.Multi-biomarker strategies that reflect several AMI-related pathophysiological processes and include several enzymatic, non-enzymatic, and/or molecular markers may provide the solution for obtaining highly sensitive, highly specific, and very rapid AMI diagnoses. Such an approach was already shown to be superior to individual marker assessment for predicting post-AMI outcomes . In a piRegardless of future AMI diagnoses relying on single- or multi-marker approaches, any new approach will have to provide more readily available, more affordable, and more clinically relevant information than the strategies currently used in clinical practice, while also complying with high standards of precision and accuracy. Markers that do not fulfill these requirements will most likely not find their place in clinical practice. The ideal AMI biomarker, which is exclusively expressed in the myocardial tissue and whose plasma levels are not affected by any other pathology, remains to be identified. MicroRNAs could prove of invaluable help in this regard. It is unlikely that a single miRNA will prove superior to the traditional markers for AMI diagnosis. However, a combination of miRNAs, reflecting cardiomyocyte stress, inflammation, endothelial cells, and fibroblast damage, and/or other AMI-related pathophysiological processes, could change the future of AMI diagnosis. Moreover, miRNA-based therapies have the potential to modulate an entire pathway by regulating multiple genes at the same time. The advent of such therapies, and particularly of anti-miRNA strategies, is therefore expected to spur further research in this area.The massive number of emerging biomarkers and the impressive progress achieved over the past decades in AMI diagnosis were spurred by a revolutionary paradigm shift—one that has drawn AMI diagnosis out of the ‘myocardial necrosis box’. Further understanding of AMI pathophysiology is expected to open new directions of research and enable the identification of even better diagnostic AMI biomarkers. Laboratory techniques will have to parallel this effort and ideally provide POCT systems able to detect single analytes as well as panels of circulating markers, and thus to enable accurate and rapid AMI diagnosis, including during patient transport to hospital. This would allow further cutting down time in AMI management, which in turn is expected to result in considerable improvement in AMI outcomes, both over the short and the long term.Circulating biomarkers are key to AMI diagnosis. With their increased specificity, cTn have revolutionized the diagnosis, as well as the management of AMI. The advent of hs-cTn covered an unmet need and boosted diagnostic sensitivity, allowing more rapid therapeutic interventions. Unfortunately, this increased sensitivity was accompanied by a drop in specificity, not for the analyte, but for the diagnosis of AMI. Up to two-thirds of patients presenting with cTn levels that overtly exceed the threshold for AMI diagnosis do not have AMI and undergo costly, time-consuming, often invasive, although completely futile investigations. Further advancement in AMI diagnosis is therefore required. Traditional markers have all been focused on detecting myocardial necrosis. Acknowledgment that other processes, such as inflammation, neurohormonal activation, or myocardial stress, occur much earlier than myocyte necrosis, has opened the way for new approaches in AMI biomarker research. The ideal biomarker, that would allow rapid and reliable AMI rule in and rule out, is still to be discovered. However, biomarker research in AMI has massively advanced over the past years, and a solution to this problem is expected to be found in the near future, most likely in the form of multi-marker assessment, based on a combination of biomarkers that reflect several axes involved in the natural evolution of AMI. Future clinical trials, with large sample sizes, will have to confirm the utility of biomarkers that are currently under investigation, to identify novel potential biomarkers, and to validate the clinical impact of multi-biomarker-based AMI diagnosis.


Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site (Supplementary information accompanies this paper at 10.1186/s12968-020-00671-7. Firstly, a huge thank you to our wonderful team of associate editors and reviewers for the Society for Cardiovascular Magnetic Resonance (SCMR) website “Case of the Week” series. This past year, the cases were predominantly from the United States, with international cases from Egypt, Canada and Australia. There was a mixture of adult and paediatric cases, showcasing the utility of cardiovascular magnetic resonance (CMR) in assessing and diagnosing disease. The importance of CMR in mass differentiation, particularly in the paediatric population where solitary masses/tumours are rare, was well demonstrated. Early CMR diagnosis was demonstrated despite seemingly negative testing by other methods including tissue biopsy. The use of a research tool in the clinical setting was also reported, giving a glimpse of its potential use in early identification of a pathological process and therefore help guide clinical management. Here are the SCMR Case of the Week series of 2019. Please continue to submit your instructive cases to: scmr.org/page/SubmitCase.A 19-year-old woman presented with a 2-week history of painful atraumatic left ankle swelling associated with painful plantar-flexion and petechial rash on the left foot. Six weeks prior to presentation, she experienced a flu-like illness with headache, fevers, myalgias, and athralgias. On examination, there was a non-blanching petechial rash over the dorsum of the left foot with associated edema and warmth, but no erythema. Peripheral pulses were normally palpable with normal capillary refill. Neurological exam of the foot was normal except for 4/5 power on plantar flexion due to pain. Ultrasound of the leg showed a thrombus in the lateral tarsal artery raising a possibility of an embolus.Her past medical history was remarkable for mild childhood asthma that was associated with viral infections and exercise; and allergic rhinitis. She had no prior hospitalizations. Chest X-ray was unremarkable. Electrocardiogram (ECG) showed T-wave inversion in most precordial leads (V2–V6) and some inferior leads (III and aVF) Fig. .Fig. 1.CRoutine blood work was unremarkable except for eosinophilia which was attributable to asthma. Inflammatory markers (erythrocyte sedimentation rate (ESR) 41 mm/h and C-reactive protein (CRP) 22 mg/l were mildly elevated. Troponin was negative. Transthoracic echocardiogram (TTE) performed to evaluate for a possible cardiac embolic source was unremarkable except for mildly increased left ventricular (LV) apical wall thickness  showed normal biventricular size and systolic function with only minimal increase in the LV apical wall thickness  of 57%. The right ventricular (RV) size and systolic function were normal with an RV end diastolic volume index of 74 ml/m2 and RV ejection fraction (RVEF) of 51%. LV tissue characterization revealed subtle sub-endocardial abnormalities. T2-weighted (T2w) imaging showed somewhat diffuse sub endomyocardial edema in mid to distal LV segments  imaging using T1-weighted (T1w) imaging in short axis showed subendocardial enhancement in the mid to distal LV segments Fig. . These fMulti-parametric CMR: Pre- and post- contrast T1 mapping was performed a using modified Look-Locker inversion (MOLLI) sequence . Region of interest involving apical septum had an elevated T1 of 1385 ms  as well as extracellular volume (ECV) of 39% . In the remote myocardium  native T1 was in the normal range (1279 ms) and ECV was within normal limits (25%) . Chest computed tomography (CT) identified non-specific sub-pleural inflammatory changes Fig. . CT guidRepeat CMR 6 months after treatment showed almost complete resolution of previously noted subendocardial abnormalities . The etiology of EGPA remains unknown. Asthma is the cardinal feature (occurring in more than 95% of patients) and usually precedes the vasculitic phase by approximately 8 to 10 years.The American College of Rheumatology criteria for the classification of EGPA requires at least four of the following six criteria: asthma, eosinophilia > 10%, mononeuritis or polyneuritis, non-fixed pulmonary infiltrates, paranasal sinus abnormality and extravascular eosinophils .Cardiac involvement is one of the more serious manifestations of EGPA, accounting for approximately half of attributable mortality. It should be suspected in the presence of refractory dyspnea, pericarditis related symptom, clinical evidence of heart failure (HF), or cardiac rhythm abnormalities, but can also be asymptomatic. Endomyocarditis may represent the most severe manifestation with eventually fatal outcome. A structured clinical assessment incorporating cardiac imaging with TTE and CMR can identify impaired cardiac function and endomyocardial abnormalities . CMR is CMR is a useful tool for the differential diagnosis of HCM, as it can differentiate HCM from other mimicking conditions because of its superior spatial resolution and its ability to tissue characterize. Tissue characterization by CMR can differentiate eosinophilic endomyocarditis from apical HCM. Unlike apical HCM which usually has midmyocardial apical LGE, eosinophilic endomyocarditis typically has diffuse subendocardial enhancement, often associated with thrombus . Furtherhttps://www.precessionsaas.com/0757-1973-0753-0139/).The CMR of Case 1 , cyclophosphamide and trastuzumab . She also received ADO–trastuzumab emtansine  for a history of metastatic breast cancer previously receiving treatment with trastuzumab. During her chemotherapy regimen, a TTE revealed reduced LV systolic function (LVEF 48%). She was subsequently evaluated for the possibility of chemotherapy induced cardiomyopathy. Due to her decreased LVEF, continuous measurements of LVEF accompanied the trastuzumab treatment. Prior to chemotherapy, she had a past medical history of hypertension, left bundle branch block (LBBB) and hyperlipidemia. Medications included atorvastatin and carvedilol , T1/T2 mapping, and LGE were not performed. Comprehensive analysis of her LV contractile parameters included CMR-based computations of 3D myocardial strains and torsion to predict the extent of dysfunction in a manner more quantitatively detailed than conventional LVEF measurements. CMR data were obtained with the Displacement Encoding with Stimulated Echoes (DENSE) sequence .The CMR of Case 2 . CT also revealed a possible 2 × 4.1 cm “mass” within the LV. Empiric anticoagulation with heparin was started and she underwent urgent exploratory laparotomy, small bowel resection, SMA embolic material removal and patch angioplasty of the SMA.TTE on the day after admission showed an LVEF of 65% without regional dysfunction. It also confirmed an LV “mass” near the outflow tract which measured 3.2 × 2.3 cm Fig. . The masInitial interpretation of the “mass” favored a myxoma but a thrombus was also suspected. A CMR performed a week after her admission showed findings consistent with a thrombus that had embolized from the LV into the aortic arch. On the following day a brain magnetic resonance imaging (MRI) revealed multiple cerebral infarctions in her internal carotid artery territory Fig. . PatholoHer anticoagulation was then changed to fondaparinux, to be continued indefinitely. She was ultimately discharged to inpatient rehabilitation with plans to be evaluated later for intestinal transplant due to short gut syndrome. After rehabilitation, she was able to walk but used a wheelchair and walker for ambulating a longer distance.The CMR revealed a LVEF of 60% with normal dimensions and regional systolic function without any LV mass  2 mutation.Imaging plays a critical role in establishing a diagnosis and planning management. TTE, TEE, and CMR have all been used to detect the presence of cardiac tumors and thrombi . CMR hasIt is important to establish whether the mass is a tumor, thrombus or vegetation due to their different complications and therapeutic implications. Treatment of thrombi includes adequate anticoagulation. In our patient, no intervention was performed as the thrombus had already embolized into the aortic arch.https://www.cloudcmr.com/1518-5003-5038-1960/).The CMR of Case 3  mass with no right heart involvement detected. As renal cell carcinomas most commonly involve the heart by extension through the inferior vena cava (IVC) and right-side chambers, a LA thrombus was initially suspected in this case. The patient was referred for CMR to verify the diagnosis prior to starting anticoagulants.CMR was performed using at 1.5 T . Given the patient’s shortness of breath, real time axial cine and black blood axial images were acquired through the chest and upper abdomen. These images revealed widespread metastatic masses involving the liver, mediastinum and lungs with extension through the pulmonary veins , 1, 5 and 10 min after contrast injection images were acquired. ECG gated delayed post contrast images were acquired with high inversion time (700 ms) to assess for possible thrombus.A single, well defined, infiltrative mass was seen in the LA measuring 5.7 × 5.3 × 3.6 cm .The CMR of Case 4  and 8 × 12 mm  , malignant vascular tumors , vascular malformations, and tumors with ample vascular supply . Primary vascular cardiac tumors such as hemangiomas are extremely rare . Congenital cardiac hemangiomas can present as fetal arrhythmia, hydrops fetalis and intrauterine fetal demise. Neonates can be asymptomatic, but can also present with cardiac tamponade, arrhythmias, congestive heart failure or sudden death .Asymptomatic children are best managed conservatively by closely monitoring for development of complications. The role of medical therapy is limited; there is no proven role for beta blockers, while steroids have mixed results. Surgery is only offered for rapidly growing or symptomatic tumors and, steroid therapy is reserved for patients with unresectable tumors . The prehttps://www.precessionsaas.com/3657-1973-9453-0171/).The CMR of Case 5 , and essential hypertension presented to the emergency department after a near syncopal episode while he was uploading boxes. Upon emergency medical services (EMS) arrival, he was noted to be in monomorphic ventricular tachycardia (VT) Fig.  that neeLab analysis revealed sub-therapeutic prothrombin time and international normalized ratio (INR). Initial work up with coronary angiography revealed trivial coronary artery disease and possible congenital coronary anomaly. TTE on the day after admission demonstrated a LV apical aneurysm with mural thrombus formation. Chest X-ray showed a calcified nodule at the cardiac apex, which correlates to the calcified intramural thrombus. Subsequently, coronary CT angiography Fig.  revealedTTE with an ultrasound enhancing agent showed mid-LV hypertrophy and an apical LV aneurysm with an apical mass suspicious for a thrombus.Subsequent CMR showed mid LV hypertrophy consistent with HCM and LV apical aneurysm with intramural thrombus. LGE imaging revealed full thickness scarring in the LV apex. Ultimately, an automated implantable cardioverter defibrillator (ICD) was placed, and the patient was sent home with oral anticoagulation and antiarrhythmic therapy. Patient was counseled and recommended to undergo genetic testing for HCM.The CMR bSSFP cine images revealed an LVEF of 60% with an apical LV aneurysm measuring 3.9 × 3.2 cm, with moderate hypertrophy of the mid-ventricular myocardium measuring 1.6 cm in maximal thickness consistent with HCM. A 1.2 × 1.0 cm lesion was noted within the apical aneurysm, consistent with intramural thrombus , coronary artery anomalies, dilated cardiomyopathy, HCM, arrhythmogenic right ventricular dysplasia, and infiltrative diseases like sarcoidosis in addition to non-structural heart diseases like in long QT syndromes. Hence, in patients with new-onset VT, it is vital to pinpoint the source of the aberrant rhythm to prevent the recurrence of potentially life-threatening arrhythmias. As was true in this case, multi-modality imaging plays a major role in evaluation and management of this arrhythmia.Anomalous RCAWhile most of coronary artery anomalies are not associated with myocardial ischemia and clinical events, some anomalies can potentially result in myocardial ischemia depending on the location and course of the anomaly; thus, they can manifest with angina pectoris, syncope, myocardial infarction and VT; however, coronary anomalies are considered an under-diagnosed cause of sudden cardiac death (SCD) in young athletes .Anomalies of RCA include ectopic origin from the right sinus of Valsalva, posterior sinus of Valsalva and left sinus of Valsalva. Our patient has ectopic RCA originating from left sinus of Valsalva which has an incidence rate of 0.03% to 0.92% on coronary angiograms . In our Coronary anomalies can be seen on echocardiography, angiography, coronary CT and CMR with coronary CT being the clinical standard due to its widespread availability, ease of use, high spatial resolution and very short acquisition time .Left ventricular apical scarVentricular scar or fibrosis most commonly forms as a consequence of myocardial infarction, but it can be also caused by non-ischemic insults like myocarditis. These scars are composed of fibrous tissue with intervening cardiomyocytes, and because fibrous tissue is unexcitable, it represents a substrate for re-entry circuits leading to ventricular arrhythmia. As was true in this case, LGE in CMR is the gold-standard imaging for diagnosis of myocardial scar. Normal and viable myocardium appears black on LGE imaging while myocardial scar appears bright or enhanced. Myocardial scar detected on imaging is considered a strong predictor for cardiac death and major adverse cardiac events .In our patient, the apical scarring was thought to be related to either HCM or less likely thrombotic or embolic event causing infarction in the distal left anterior descending coronary artery (LAD) territory given patient’s history of anti-phospholipid syndrome in setting of sub-therapeutic anticoagulation. It is thus important that the patient be continued on anticoagulation as he would be at risk for further embolic phenomenon.Hypertrophic cardiomyopathyHCM is the most common cause of SCD in young athletes. It is mostly asymmetric with most cases having involvement of the basal inter-ventricular septum. However, hypertrophy can exclusively involve the apex, or mid-portion or posterior wall of the LV .Diagnosis of HCM can be made by demonstrating a wall thickness > 15 mm in one more LV myocardial segments by any cardiac imaging modality, not explained solely by loading conditions . AlthougThe following will be a discussion of the three potential origins:Although TTE is considered a good assessment tool for LV wall thickness and LV outflow tract pressure gradient, CMR should be considered for accurate assessment of LV wall thickness in patients with poorly visualized LV regions on echocardiogram, and particularly in HCM cases that are confined to one or two segments of LV like apical or anterolateral variants because of its superior characteristics including lack of attenuation, great spatial resolution in addition to its ability to image in any plane . Also, Lhttps://www.cloudcmr.com/9457-1973-5768-0185/).The CMR of Case 6  in lead II and biphasic P-waves in lead V1, suggesting LA enlargement Fig. . These rThe cine bSSFP short axis view clearly demonstrates a large, smooth, pedunculated and mobile mass .The CMR of Case 7 . He had been diagnosed with anti-neutrophil cytoplasmic antibody (ANCA) negative EGPA with cardiac involvement 2 years prior, in 2015. Having been managed well on oral methotrexate 25 mg weekly and weaning dose of oral prednisolone, relapse occurred once his prednisolone was decreased to 4 mg daily.A 23-year-old migrant native of Zimbabwe presented with a 10 day history of flu-like symptoms, myalgias, chest pain, palpitations, Troponin I of 1.8 mcg/l  and peripheral eosinophilia of 3.42 × 10Cardiac investigations were carried out including ECG which demonstrated normal sinus rhythm, normal axis, no PR depression. TTE showed a mildly dilated LV cavity with normal regional/global systolic function. The 3D LVEF was 67%. Trivial loculated pericardial effusions without evidence of hemodynamic compromise  = 21 mmHg). Endomyocardial biopsy had been carried out in 2015 and was normal, showing no morphological abnormality, no fibrosis or fibrin. No myocyte damage or necrosis was noted. No granulomata or giant cells and no evidence of vasculitis.Ultimately, his diagnosis of EGPA was made in 2016 following extensive investigation when he presented with dyspnea, chest and abdominal pain on a background of adult onset asthma. He was found to have bilateral pleural effusions and a raised peripheral blood eosinophil count. Diagnosis was ultimately made based on biopsy of skin lesions (which developed in early 2016) and gastrointestinal tract which demonstrated an eosinophilic vasculitis pattern. Cardiac involvement at initial presentation included pericardial effusion as outlined above.CMR imaging  was carried out at first presentation in 2015 showing a moderate pericardial effusion Fig. , withoutCMR was repeated in April 2018 upon re-presentation which now showed multifocal myocardial hyper-intensity in the basal to mid anterior, lateral and inferior LV walls on T2 double inversion recovery (DIR) sequences suggesting edema Fig. . RelativThis case highlights the importance of CMR in the diagnosis of myocardial involvement in a biopsy negative case of EGPA.Myocardial involvement was proven on CMR when TTE findings were unhelpful. It also avoided the requirement for repeat cardiac biopsy thereby obviating the necessity for an invasive procedure. Accurate diagnosis allowed for appropriate prognostication and ultimately guided therapy. The patient was subsequently treated with intravenous methylprednisolone and rituximab therapy with excellent clinical response over 6 months and continues to be followed up under the care of rheumatology.EGPA  is a rare, vasculitic condition which can affect small and medium sized arteries. It is associated with adult onset asthma, allergic rhinitis and a peripheral blood eosinophilia. It can be associated with multi-organ involvement including cardiac as demonstrated above. Approximately 40–60% of patients with EGPA have positive ANCA . ANCA neFindings of myocarditis on CMR can include increases in T2 signal intensity and increased native myocardial T1 mapping relaxation times consistent with myocardial edema, increase in early myocardial contrast enhancement relative to skeletal muscle consistent with hyperemia, and presence of LGE consistent with necrosis or scarring . CMR allCardiac involvement in EGPA is associated with poor prognosis. Prognostication is based on the number of organs involved and scoring systems such as the five factor score rely heavily on this for prognostication and to guide treatment .CMR was pivotal in this particular case as diagnosis of myocardial involvement demonstrated a changing clinical picture and allowed for prognostication in the setting of relapsing EGPA. This ultimately highlighted failure of maintenance therapy and guided treatment response.Additional file 1: Movie S1. TTE apical 4 chamber view. Systolic obliteration of the LV apex. Although LV apical diastolic thickness was only minimally increased, apical hypertrophic cardiomyopathy (HCM) remained a concern because of suspected LV apical foreshortening.Additional file 2: Movie S2. Cine bSSFP LV 2 chamber.Additional file 3: Movie S3. Cine bSSFP LV 3 chamber.Additional file 4: Movie S4. Cine bSSFP LV 4 chamber.Additional file 5: Movie S5. Rest perfusion imaging of LV basal-, mid- and apical- short axis. Subtle subendocardial hypo-perfusion predominately in mid to apical wall segments.Additional file 6: Movie S6. Rest perfusion imaging 4-chamber view. Subtle subendocardial hypo-perfusion predominately in mid to apical inferoseptal and anterolateral wall segments.Additional file 7: Movie S7. Post-treatment resting perfusion imaging of LV base, mid and apical short axis. Complete resolution of previously noted subtle subendocardial hypo-perfusion.Additional file 8: Movie S8. Post-treatment resting perfusion imaging 4-chamber view. Complete resolution of previously noted subtle subendocardial hypo-perfusion.Additional file 9: Movie S9. Displacement Encoding with Stimulated Echoes (DENSE) sequence mid short axis.Additional file 10: Movie S10. Four chamber cine bSSFP. Normal LV function and absence of mass in the LV cavity.Additional file 11: Movie S11. Basal short axis cine bSSFP. Normal LV function and absence of mass in the LV cavity.Additional file 12: Movie S12. Mid short axis cine bSSFP. Normal LV function and absence of mass in the LV cavity.Additional file 13: Movie S13. Apical short axis cine bSSFP. Normal LV function and absence of mass in the LV cavity.Additional file 14: Movie S14. Cine bSSFP axial aortic arch. Low signal intensity mass in the aortic arch.Additional file 15: Movie S15. Cine bSSFP sagittal aortic arch. Low signal intensity mass in the aortic arch, entering and occluding the brachiocephalic trunk.Additional file 16: Movie S16. T1 fast spin echo sagittal aortic arch. The thrombus had a short T1 consistent with methemoglobin.Additional file 17: Movie S17. T2 fast spin echo sagittal aortic arch. The thrombus had a short T1 consistent with methemoglobin.Additional file 18: Movie S18. Coronal CMR angiogram.Additional file 19: Movie S19. Long inversion time (600 ms) delayed enhancement sagittal aortic arch.Additional file 20: Movie S20. Axial black blood stack demonstrating widespread masses involving the chest and abdomen.Additional file 21: Movie S21. Axial cine SSFP inferior. Complex mediastinal mass infiltrating the left pulmonary veins, extending to the LA and compromising mitral valve inflow.Additional file 22: Movie S22. Axial cine SSFP mid. Complex mediastinal mass infiltrating the left pulmonary veins, extending to the LA. Remaining cardiac chambers are free from infiltration.Additional file 23: Movie S23. Axial cine SSFP superior. Complex mediastinal mass causing near complete occlusion of the left pulmonary artery.Additional file 24: Movie S24. Axial first pass perfusion. Hypovascular nature of the tumor with faint enhancement.Additional file 25: Movie S25. Axial first pass perfusion. Infiltration of the left pulmonary artery.Additional file 26: Movie S26. Fetal echocardiogram four chamber view. Single, large, homogeneous, hyperechoic bi-atrial mass.Additional file 27: Movie S27. Fetal echocardiogram four chamber view with color Doppler. No evidence of obstruction from the large bi-atrial mass.Additional file 28: Movie S28. TTE four chamber view. Large homogeneous, hyperechoic mass mainly in the right atrium.Additional file 29: Movie S29. TTE four chamber with color Doppler. No LA obstruction from the atrial mass.Additional file 30: Movie S30. TTE subcostal sagittal color compare. Large homogeneous, hyperechoic mass arising from the Eustachian valve. Patent foramen ovale with left to right shunting.Additional file 31: Movie S31. Axial cine SSFP stack. A right atrial mass attached to the Eustachian valve with no evidence of obstruction.Additional file 32: Movie S32. Axial first pass perfusion. Contrast uptake of the atrial mass present.Additional file 33: Movie S33. Cine bSSFP 4 chamber. Mid LV thickening with apical aneurysm.Additional file 34: Movie S34. Cine bSSFP 3 chamber. Apical LV aneurysm.Additional file 35: Movie S35. TTE parasternal long axis with color Doppler. Obstruction of mitral valve inflow from the mass with mitral valve insufficiency.Additional file 36: Movie S36. TTE four chamber. The LA mass extending past the mitral valve annulus during diastole.Additional file 37: Movie S37. Short axis cine bSSFP. A large, relatively smooth, pedunculated mass attached to the interatrial septum.Additional file 38: Movie S38. Axial cine bSSFP. A large hypointense LA mass likely attached to interatrial septum at the superior edge of the fossa ovalis close to the pulmonary vein entrance.Additional file 39: Movie S39. Cine bSSFP four chamber view showing large variably hypointense mass bulging into the LV during diastole causing dynamic mitral stenosis.


To compare volumetric and functional parameters of the atria derived from highly accelerated compressed sensing (CS)–based cine sequences in comparison to conventional (Conv) cine imaging.CS and Conv cine sequences were acquired in 101 subjects  and 19 patients with heart failure with reduced ejection fraction (HFrEF)) using a 3T MR scanner in this single-center study. Time-volume analysis of the left (LA) and right atria (RA) were performed in both sequences to evaluate atrial volumes and function . Inter-sequence and inter- and intra-reader agreement were analyzed using correlation, intraclass correlation (ICC), and Bland-Altman analysis.p < 0.0001) or passive emptying fraction (PEF) (Conv 53.9% (46.7–58.4), CS 49.0% (42.0–54.1), p < 0.0001). However, there was high correlation between the techniques, yielding good to excellent ICC (0.76–0.99) and small mean of differences in Bland-Altman analysis . Measurements showed high inter- (ICC > 0.958) and intra-rater (ICC > 0.934) agreement for both techniques. CS-based parameters  showed equivalent diagnostic ability compared to Conv cine imaging  to differentiate between HV and HFrEF.CS-based cine imaging led to a 69% reduction of acquisition time. There was significant difference in atrial parameters between CS and Conv cine, e.g., LA minimal volume (LAVmin) (Conv 24.0 ml (16.7–32.7), CS 25.7 ml (19.2–35.2), Atrial volumetric and functional evaluation using CS cine imaging is feasible with relevant reduction of acquisition time, therefore strengthening the role of CS in clinical CMR for atrial imaging.Reliable assessment of atrial volumes and function based on compressed sensing cine imaging is feasible.• Compressed sensing reduces scan time and has the potential to overcome obstacles of conventional cine imaging.• No significant differences for subjective image quality, inter- and intra-rater agreement, and ability to differentiate healthy volunteers and heart failure patients were detected between conventional and compressed sensing cine imaging.• The online version contains supplementary material available at 10.1007/s00330-021-07830-z. Left and right ventricular volumes and function are important indicators for the severity of cardiac diseases, and cardiac magnetic resonance imaging (CMR) is considered reference standard for volumetric assessment . QuantifThus, an efficient and accurate way to determine atrial volumes and function is crucial to enable optimal patient management. The calculation of atrial volumes can be performed by echocardiography, computed tomography angiography (CTA), and CMR. CTA carries the risk of radiation and contrast exposure, while echocardiography is highly user dependent and suffers from patient-specific factors such as poor acoustic windows. As of today, CMR is considered the non-invasive reference standard for atrial volumetric assessment –15. The The protocol of this single-center study was approved by our institutional ethics committee, and all participants provided written informed consent. A total of 101 subjects were enrolled including 82 HVs and 19 consecutive patients with non-ischemic HFrEF. HFrEF patients were recruited between August 2018 and January 2019. Subjects with no history of cardiovascular events or symptoms, no cardiovascular risk factors , and normal cardiac parameters  were considered healthy. No HV was excluded from the study due to abnormal CMR findings. HFrEF patients with a broad range of atrial volumes and function were selected to ensure validation of CS cine images that includes healthy to severely impaired atria.All patients underwent conventional cine and CS cine imaging on a 3T system . Standard cardiac views (2- and 4-chamber) were recorded using a unified imaging protocol with a conventional accelerated  product sequence and a CS-accelerated cine prototype pulse sequence (CS acceleration factor: 6.5), both using retrospective ECG gating during expiratory breath-hold. The total acquisition time including scan time and pauses for recovery and breathing commands for both sequences was recorded. Additional pulse sequence parameters are reported in Table In addition to the CMR sequences used for atrial assessment, the following acquisitions were performed. A short-axis stack of conventional cine images in expiratory breath-hold was acquired to obtain ventricular volumes and function. T1 mapping (modified Look-Locker inversion-recovery with 5(3)3-scheme, TR/TE 280.56/1.12 ms; FOV 360 mm; slice thickness 8 mm; and flip angle 35°), T2 mapping , and post-contrast (0.2 mmol/kg gadoteric acid) late gadolinium enhancement images using a phase-sensitive inversion-recovery technique were acquired in long- and short-axis orientations for myocardial characterization.Image analysis was performed by a radiology resident with 1 year of experience in CMR, including  > 100 CMR examinations and SCMR Level 1 certificate. Dedicated cardiovascular software  was used for post-processing of cine and mapping sequences according to SCMR guidelines , 26–28. n = 20 HV and n = 19 HFrEF patients) were evaluated by a consultant radiologist with  > 10 years of experience in CMR. Qualitative image quality was subjectively rated by three independent readers  on a 4-point Likert scale: (1) anatomic and functional evaluation not assessable due to severe image artifacts; (2) anatomic and functional evaluation assessable despite relevant image artifacts; (3) good image quality with minor artifact; (4) excellent image quality without artifacts. Image sharpness was evaluated using the methodology proposed by Larson et al [From a (patho-)physiological point of view, TEF represents the atrial reservoir, while PEF represents conduit, and AEF the booster function of the atria . In ordeon et al . The edgon et al , an edgeon et al , the shaU test. Correlation was evaluated by the coefficient of determination (R2). Agreement between the cine sequences and inter- and intra-rater agreement were judged by using intraclass correlation (ICC) analysis with two-way mixed effects and focus on absolute agreement with the level of agreement as follows: poor, ICC < 0.5; moderate, ICC = 0.5–0.75; good, ICC = 0.76–0.9; excellent, ICC > 0.9 [p values less than 0.05 on a local level.Statistical analyses were performed using SPSS Statistics . The Kolmogorov-Smirnov test was used to assess normal distribution of the continuous data. Continuous variables were reported as mean ± standard deviation if normally distributed, and as median/interquartile range in case of non-normal distribution. Categorical variables were displayed as absolute frequencies and proportions. Differences between conventional cine and CS cine parameters and subjective image quality were assessed using the Mann-Whitney CC > 0.9 . FurtherCC > 0.9 . Agreemep < 0.05 for all). Mean total acquisition time for the 2- and the 4-chamber views was 41 s using the conventional cine and 13 s with CS cine imaging, translating into a 69% time saving using CS cine imaging.The overall study population consisted of 101 patients (median age: 27 years), including 63 men and 38 women. Detailed baseline characteristics of the study population are displayed in Table p = 0.387 for RAVmax, otherwise p < 0.0001). However, an excellent correlation for maximal and minimal volumes of the left and right atrium (R2 > 0.90) and good to excellent correlation for functional parameters TEF and PEF (R2 = 0.88–0.90) were observed. AEF showed a moderate correlation between conventional and CS cine imaging (R2 = 0.55). These results were confirmed by good to excellent ICC values : ICC = 0.99) and small mean differences and upper and lower limits of agreement . A detailed overview, scatterplots, and Bland-Altman-plots of representative parameters are presented in Table Volumetric and functional assessments of the left and right atria were available in all 101 cases. Overall, there were significant differences for all assessed variables between conventional and CS cine–based evaluation beside right atrial maximal volume (RAVmax) (g R2 = 0.5. These p = 0.159), with a slightly higher but not statistical different rating for HV in comparison to HFrEF patients  vs 3.33 (3.0–4.0), p = 0.271; CS HV vs HFrEF: 3.67 (3.0–4.0) vs 3.0 (3.0–4.0), p = 0.205). Inter-reader agreement for subjective image quality was almost excellent for both techniques . Image sharpness was higher for the conventional cine sequence . An overview of image artifacts is provided in Figure SExcellent agreement was observed in left  and right atrial  volumetric parameters between the readers. Similarly, strong ICCs were found for the same parameters in the intra-observer analysis. Further details are provided in Table p = 0.288; LAVmin: AUC  = 0.859; AUC (CS) = 0.864; p = 0.833)  = 0.989 vs AUC (CS) = 0.965; In this study, we investigated the agreement in atrial volumes and function between conventional cine and novel, highly accelerated CS-based cine imaging in HV and HFrEF patients. We found that the assessment of CS-based atrial parameters is comparable to conventional cine imaging with a high level of agreement between the techniques. Atrial evaluation using CS-based cine images showed excellent inter- and intra-reader agreement in comparison with conventional cine imaging–based assessment. There were no significant differences in the ability to differentiate HV and HFrEF patients between the techniques.As atrial imaging is getting more and more clinically important, the implementation of advanced cardiac imaging for assessment of atrial anatomy and function is intriguing . ClinicaThe basic principle of CS is built on random k-space under-sampling, a method that creates noise-like artifacts. These artifacts are successfully reduced utilizing wavelet regularization during the non-linear iterative reconstruction . CS acceWith the use of CS acceleration, we were able to demonstrate a reduction of mean acquisition time from 41 to 13 s (− 69%) in this study for long-axis imaging of the heart. An even higher reduction rate can be achieved when applying CS to short-axis acquisitions, as short-axis coverage of the ventricles needs more slices than long-axis, generally reducing imaging time by  > 90% . OverallIn our study, subjective and objective image quality was slightly higher for the conventional technique in comparison to CS-accelerated cine imaging. This can be explained by the combination of several factors, including lower CNR in CS cine due to the lower flip angle and reduced image sharpness. In addition, the majority of our cohort included healthy volunteers with regular sinus rhythm and without breathing artifacts. The number of patients with reduced breath-hold capabilities and/or arrhythmias, who would profit most from CS-accelerated cine imaging, was limited in our study cohort.The overall correlation and reproducibility of atrial CS imaging in our study was good to excellent with comparable effects to published data from LV and RV analysis . DespiteDespite the significant differences in atrial volumes between CS and conventional cine imaging, the disparity was not clinically relevant. The mean difference of the maximum biplane measurements was 3.0 ml, whereas the difference of the minimum biplane measurements was only 2.0 ml. These differences can be attributed to the combination of technical aspects such as lower CNR and decreased image sharpness of CS-accelerated cine imaging. However, absolute differences between the two cine techniques were comparable to differences between human readers of the same sequences. Clinically, these differences are not likely to affect clinical management of patients. In general, volumetric analyses were more reliable than functional analysis, which incorporates volumes and small volume fractions from different time points of the cardiac cycle. AEF showed the highest deviation and lowest correlation between conventional and CS cine imaging. This may be explained by the nature of this parameter, as small errors in volumetric assessments have a higher impact on parameters that rely on the detailed acquisition of small volumes (differences of around 5 ml). In addition, our findings corroborate previous studies which have identified AEF as the parameter with the least diagnostic value in comparison to the other functional parameters , 49. FinThis study has several limitations. Despite the uneven distribution of healthy volunteers and HFrEF patients in this study, we were still able to demonstrate the applicability of CS cine imaging over a wide range of atrial volumes ranging from 32.6 to 222.8 ml. We have chosen a cohort of patients with advanced heart failure as our reference disease cohort and used time-volume analysis for the functional assessment of the atria. Another cohort with less advanced disease and modest effect on atrial size and function, and a more sophisticated functional evaluation, such as atrial strain , could bVolumetric and functional atrial evaluation using CS cine imaging is feasible and can be integrated in clinical routine. The implementation of CS cine imaging in clinical routine will allow relevant reduction of CMR examination times, increase productivity of imaging centers while maintaining the assessment of relevant (patho-)physiologic information, therefore strengthening the role of CMR imaging as a reliable diagnostic tool.ESM 1(DOCX 1259 kb)


An 82-year-old woman with uncontrolled hypertension and occasional exertional dyspnea was found to be in intermittent left bundle branch block (LBBB). Her laboratory results, echocardiogram, and ischemic workup were unremarkable. This case highlights that intermittent LBBB is not always associated with coronary ischemia, vasospasm, blunt cardiac injury, drugs, and high catecholaminergic or inflammatory states.  Bundle branch blocks and hemiblocks are usually stable and remain unchanged irrespective of the cardiac cycle length. Left bundle branch block (LBBB) usually results from conduction system degeneration or myocardial pathology . PatientIntermittent LBBB is an uncommon conduction disturbance with very few cases reported in the literature. It was first described by Vessel in 1949 as unstable bundle branch block ,6. The mAn 82-year-old Caucasian female was referred to cardiology clinic for an abnormal EKG. She reported rare episodes of dyspnea on exertion but denied chest pain, palpitations, lightheadedness, syncope, and fatigue. EKG showed intermittent LBBB Figure . Her bloEchocardiogram demonstrated a left ventricular ejection fraction of 70%. All chamber sizes were within normal range with normal diastolic and valvular functions. Interventricular septal motion on echocardiogram was also unremarkable as she was in sinus rhythm with narrow QRS complexes. Holter monitor (24 hours) showed sinus rhythm with narrow QRS complexes alternating with intermittent LBBB at faster heart rates. Patient remained asymptomatic during monitoring. Myocardial perfusion single-photon emission computed tomography (SPECT) showed normal and homogeneous perfusion of all left ventricular wall segments at rest as well as with stress. On the quantitative gated SPECT study, there was normal myocardial thickening and contractility of all ventricular wall segments. Calculated ejection fraction was 70%. She was started on lisinopril 10 mg along with lifestyle modification for optimal blood pressure control. She continued to do well as she was followed closely in clinic for three years. Subsequent routine EKGs had either normal conduction or intermittent LBBB pattern with faster heart rates. Patient's electrocardiogram revealed a normal QRS complex alternating with an LBBB in a 2:1 pattern due to intermittent delay in the left bundle branch with constant PR, PP, and RR intervals. LBBB typically has a QRS duration of greater than 120 ms, and in comparison to ventricular ectopy, it has dominant S wave in V1, broad monophasic R wave in leads I and V6, and prolonged R wave peak time of greater than 60 ms in lead V6.Intermittent LBBB is a rare occurrence. In literature, it has been reported with exercise, tachycardia, ischemic and hypertensive heart disease, hyperkalemia, drugs, anesthesia, pulmonary embolism, chest trauma, and cardiac interventional procedures ,6. PatieNormally the activation of the left ventricle takes place by impulses entering the ventricle via the bundle of His; they then travel to the left and right bundle branches in the septum and from there into the intricate system of Purkinje fibers depolarizing both the ventricles Figure  8]. Whe. Whe8]. There are two proposed mechanisms of intermittent LBBB: tachycardia-dependent bidirectional block and supernormal conduction . In tachSupernormal conduction results in a 2:1 LBBB pattern when a beat is conducted better than expected in patients with LBBB pattern . In thisIn patients with intermittent LBBB, it is not uncommon to observe periods of sinus rhythm with alternating (2:1) bundle branch block pattern at faster heart rates as in our patient, and they essentially may not have any underlying pathological phenomenon. Till her last visit she had been doing well without progression of her intermittent LBBB to complete bundle branch block. Owing to our patient’s rare symptom of dyspnea on exertion and the association of her intermittent LBBB commonly with coronary artery disease, echocardiogram and myocardial perfusion imaging were ordered. Both the studies were unremarkable. EKGs on subsequent visits did not progress to complete LBBB. With optimal management of blood pressure, her dyspnea resolved.


Conventional echocardiography is an essential tool for the diagnosis, bedside management and follow-up evaluations of children with multisystem inflammatory syndrome associated with COVID-19. However, a more comprehensive echocardiographic exam, including myocardial deformation parameters, may allow early identification of subtle changes in ventricular function, provide risk stratification and, identify sub-clinical cardiac dysfunction at follow-up. Thus, myocardial deformation analysis should be routinely integrated to conventional echocardiography assessment in these patients. Between December 2019 and January 2020, a novel coronavirus (SARS-CoV-2) outbreak started in China and rapidly spread worldwide, leading the World Health Organization (WHO) to declare on 30 January 2020 a Health Emergency, and then, on 11 March 2020, a pandemic  are significantly below the normal ranges and should prompt therapeutic interventions , left ventricle longitudinal systolic strain (LVLS), global circumferential strain (GCS), end-diastolic longitudinal strain rate  at 10 weeks follow-up, suggesting that a subclinical myocardial dysfunction is still present. Awareness of these findings may support prolonged pharmacological therapy with angiotensin-converting enzymes inhibitors, beta-blockers or mineral corticoid antagonists and guide continuous monitoring over time [Early follow-up studies with conventional echocardiography have shown that MIS-C patients returned to normal left ventricle ejection fraction within days or a couple of weeks . Howeverver time . Follow-ver time .A comprehensive clinical evaluation with echocardiography may be useful to support the clinical diagnosis of MIS-C, prompt the initiation of immunomodulatory interventions and cardiac treatments , and help to monitor their effect, informing follow-up care.


Brucella spondylitis (BS) and tuberculous spondylitis (TS), caused initially by bacteremia, are the two leading types of granulomatous spinal infections. BS is easy to miss or may be misdiagnosed as TS. Our purpose aims to differentiate BS from TS in conventional MR imaging and MR T2 mapping.We performed on 26 BS and 27 TS patients conventional MR imaging and MR T2 mapping. We analyzed the features in conventional MR imaging and measured T2 values of the lesion vertebrae (LV) and unaffected adjacent vertebrae (UAV) in BS and TS patients, respectively.p  <  0.001, p  =  0.048, p  <  0.001, p  <  0.001, respectively). The vertebral hyperplasia was significantly higher in BS when compared to TS (p  <  0.001). The T2 value of the LV with BS was markedly higher than that in the UAV with BS and that in the LV and UAV with TS . The T2 value of the LV with TS was significantly higher than that of the UAV in TS and BS . There were no significant differences in the T2 value of the UAV between BS and TS (p  =  0.568).There were no significant differences in sex, age, national between BS and TS. There was significantly lower severity of vertebral destruction, vertebral posterior convex deformity, dead bone, and abscess scope in BS when compared to TS (The qualitative and quantitative evaluation may differentiate BS from TS. The conventional MR imaging helps to distinguish BS from TS by several distinctive features. MR T2 mapping has the additional potential to provide quantitative information between BS and TS. Conventional MR imaging has several distinctive features to distinguish BS from TS.MR T2 mapping has the additional potential to provide quantitative information between BS and TS.MR T2 mapping might be a valuable tool for a non-invasive and quantitative technique.Brucella spondylitis (BS) and tuberculous spondylitis (TS), caused initially by bacteremia, are the two leading types of granulomatous spinal infections . They han  =  68). All participants provided written informed consent. Ethical approval for the study was obtained from the ethical review committee for our hospital. Inclusion criteria were as follows [n  =  26) and TS patients (n  =  27)  Conventional magnetic resonance imaging (MRI) and MR T2 mapping sequences were carried on in all patients and whole spine MRI studies were performed. MRI scans were performed using a 1.5-T MR scanner . The parameters for conventional MRI and MR T2 mapping sequences are shown in Table MRI finding included the level of involvement, number of the affected vertebra, MRI signal , vertebral change , intervertebral space, and abscess , vertebral appendage lesion. Vertebral destruction was defined as a vertebral structure loss of worm-etched or patchy. Vertebral wedge was defined as the front edge of the vertebra is narrower than the back edge, and the vertebra was flattened. The spinal posterior convex deformity was defined as severe vertebral damage, with significant vertebral wedge changes, resulting in considerable kyphosis of the spine. Vertebral appendage lesion was defined as bone edema or bone destruction of the appendage. Bead bone was defined as necrotic bone. Vertebral hyperplasia was defined as the appearance of a spur or osteophyte. MR images were analyzed by an attending physician and an associate chief physician, and the consistency of image evaluation was evaluated, being blinded to histopathological results.2 on the T2 mapping image and generated T2 values automatically. The ROI was placed in the middle three layers, where the lesion showed the best. Then, we obtained the T2 average value three times, which was measured repeatedly for the lesion vertebra (LV) and the unaffected adjacent vertebra (UAV) with BS and TS patients.Using the Function Tool 2 software on the post-processing workstation, we selected a region of interest (ROI) with an area of 60 mmt test analyzed all mean value of the differences between the two groups. A p value of less than 0.05 indicated a significant difference. The Kappa coefficient was calculated by two physicians using a consistency test.The information of sex, national, and MRI finding was expressed as the percentages and frequencies. In addition, we collected the information of age and measured T2 values of LV and UAV in the BS and TS patients. And these data concerning age and T2 values of LV and UAV were expressed as mean values and standard deviations. The Chi-square analyzed the differences between the two groups, and the Student’s The demographic characteristics in the two groups are shown in Table p  <  0.05). It was significantly lower in the severe vertebral destruction, vertebral posterior convex deformity, dead bone, and abscess beyond the vertebra lesion with BS when compared to TS . The vertebral hyperplasia was significantly higher in BS when compared to TS (p  <  0.001). The lumbar vertebras (69.23%) were the most common in BS. The thoracolumbar vertebras (33.33%) and lumbar vertebras (33.33%) were the most common in TS. It was significantly higher in the normal intervertebral space with BS (42.31%) when compared to TS (7.41%) (p  <  0.05), and the narrow intervertebral space was distinctly lower with BS (57.69%) when compared to TS (81.48%) (p  <  0.05). The paravertebral abscess was higher with BS (65.38%) when compared to TS (22.22%) (p  <  0.05), and it was markedly lower in the psoas abscess with BS (0.00%) when compared to TS (66.67%) (p  <  0.05). There were no significant differences in the number of the affected vertebra, MRI signal, vertebral wedge, vertebral appendage lesion between BS and TS (p  >  0.05).The image quality of the two physicians was consistent, and the Kappa coefficient was 0.875. MRI findings in the two groups are shown in Table p  <  0.001, p  <  0.037, p  <  0.001, respectively). The T2 value of the LV with TS was significantly higher than those of the UAV with TS and BS . There were no significant differences in T2 values of the UAV between BS and TS (p  =  0.568). Figure The T2 values of the LV and UAV with BS and TS are shown in Fig. This study demonstrated that the qualitative and the quantitative evaluation might differentiate BS from TS. Several distinctive features  were identified. They can distinguish BS from TS in conventional MR imaging. The T2 value of the LV with BS was markedly higher than that in the LV with TS by using the T2 mapping technique.BS and TS are still considered public health problems worldwide, particularly in developing countries , 12. In The early diagnosis and effective cure become critically important to minimize spinal deformity and permanent neurologic deficiencies. Due to the similarities in the clinical signs and laboratory data, a proportion of patients may be misdiagnosed , it is cThe abscess, around the vertebra, is a common feature in BS and TS. Our study found that the paravertebral abscess was significantly higher with BS (65.38%) when compared to TS (22.22%), but the psoas abscess was markedly lower with BS (0.00%) when compared to TS (66.67%). There is a significant difference between BS and TS in terms of abscess spread. The abscess beyond the range of vertebral lesions was significantly higher in TS (94.44%) when compared to BS (5.88%). Small abscesses were frequently found by Tali et al. . becausep  <  0.05) and that in the UAV with BS (p  <  0.05). The T2 value of the LV was high in BS and TS. The reason may be the bacteria entering the vertebra through the blood to undergo a complex pathological inflammatory process . With the inflammatory pathological lesions developing, the extracellular water content increases, and the injured locations present congestion and edema of different degrees. As the vertebas have abnormal pathological changes, MR T2 value was increased by T2 relaxation time extended. In our work, the T2 value of the LV in BS was higher than that in TS. So, we had a preliminary result that T2 mapping may quantitatively differentiate BS from TS.Previous studies , 25, 26 Due to the small sample size included in this study, MR T2 mapping sequence scanning needs to be further studied by expanding the sample size in the diagnosis and differential diagnosis with BS and TS. Another limitation was that we did not determine the stage of disease between BS and TS in this series. Therefore, the T2 value may be potentially inaccurate.The qualitative and quantitative evaluation may differentiate BS from TS. The conventional MR imaging helps to distinguish BS from TS by several distinctive features. MR T2 mapping has the additional potential to provide quantitative information between BS and TS.