Chronic heart failure is a major public-health problem with a high prevalence, complex treatment, and high mortality. A careful and comprehensive analysis is needed to provide optimal  therapy to heart failure patients. The main 4 non-invasive imaging techniques  provide information on cardiovascular anatomy and function, which form the basis of the assessment of the pathophysiology underlying heart failure. The selection of imaging modalities depends on the information that is needed for the clinical management of the patients: (1) underlying etiology (ischemic vs non-ischemic); (2) in ischemic patients, need for revascularization should be evaluated ; (3) left ventricular function and shape assessment; (4) presence of significant secondary mitral regurgitation; (5) device therapy with cardiac resynchronization therapy and/or implantable cardiac defibrillator (risk of sudden cardiac death). This review is dedicated to assessment of myocardial viability, however “isolated assessment of myocardial viability” may be clinically not meaningful and should be considered among all those different variables. This complete information will enable personalized treatment of the patient with ischemic heart failure.The online version of this article (doi:10.1007/s12350-015-0096-5) contains supplementary material, which is available to authorized users. Chronic heart failure has become one of the clinically most important diseases of the heart. The prevalence is high; the treatment is complex, and the mortality is significant. The most detailed report comes from the update of heart disease and stroke statistics from the American Heart AssociationImportantly, 5.1 million patients in the United States have heart failure, with a rising prevalence. Moreover, it is indicated that, for the American population, the lifetime risk of developing heart failure is 20% for individuals of age 40 years or more.It has been pointed out that a careful and comprehensive analysis is needed to provide optimal  therapy to these patients.The key information that is needed for comprehensive evaluation (for diagnosis and to determine therapeutic options) is summarized in Table In patients with ischemic cardiomyopathy, the need for revascularization needs to be considered and assessment of ischemia and viability is required. Next, the function, the size and the shape of the left ventricle need to be assessed: function is important for prognosis and potential indication for device therapy, whereas assessment of shape is important to evaluate the presence of severe left ventricular (LV) aneurysms. Also, patients with severe heart failure often have secondary mitral regurgitation: the prevalence of moderate or severe secondary mitral regurgitation in heart failure patients ranges between 24% and 30% and is associated with poor prognosis.This chapter is dedicated to assessment of myocardial viability, but the summary above already indicates that “isolated assessment of myocardial viability” is clinically not meaningful and should be considered among all the different variables that are summarized in Table Chronic contractile dysfunction can not only be related to scar tissue, but can also be related to hibernation or chronic stunning. In the presence of scar tissue, recovery of function will not occur, but in hibernation or chronic stunning, recovery of function may occur after revascularization. Viable myocardium is generally referred to as “alive myocardium,” independent of the contractile status of the myocardium. This however may not be preferred in the clinical setting, since the aim is to eventually predict improvement of function post-revascularization. Accordingly, the starting point in the discussion on viability should be the identification of regional dysfunction .The distinction between hibernation and chronic stunning can be based on the assessment of myocardial blood flow; in hibernation resting blood flow is reduced, whereas in chronic stunning resting flow may still be preserved but flow reserve will be reduced.In contrast, the mixture of normal (non-jeopardized) myocardium and scar tissue  will not improve in function and can be considered as viable, non-jeopardized myocardium Figure .16FigurA variety of non-invasive imaging techniques have been developed to detect viable myocardium in patients with ischemic heart failure. The different imaging techniques target different characteristics of viable myocardium Table  and thusMost experience has been obtained with nuclear imaging using SPECT and PET; both techniques permit assessment of cardiac metabolism and perfusion. With SPECT, cell membrane or mitochondrial integrity can also be assessed.Resting echocardiography or MRI can be used to assess LV end-diastolic wall thickness; it has been demonstrated that thinned myocardium (<6 mm) does not often improve in function after revascularization.In contrast to all the techniques discussed above which detect viable myocardium, contrast-enhanced MRI is the technique of choice, with the highest resolution, to detect scar tissue.Most protocols and techniques have been described extensively over the last decades and have become widely implemented in the clinical setting.15-labeled water, carbon11-acetate, rubidium82), but for viability assessment, most experience has been obtained with metabolic imaging using fluorine18-deoxyglucose (FDG). This tracer is a glucose analog (1 OH-group is replaced by an F18 atom) and reflects cardiac glucose utilization. The first cellular uptake is comparable to glucose, and after phosphorylation to FDG-6-PO4, the tracer remains in the myocyte, which provides a strong signal for imaging. Since cardiac FDG uptake is strongly affected by metabolic circumstances, strict standardization of the metabolic milieu  is needed. To maximize cardiac glucose uptake, low free fatty acid levels with high glucose and insulin levels are required. This can be achieved with hyperinsulinemic euglycemic clamping, but this approach is time-consuming; alternative approaches include oral glucose loading and the use of nicotinic acid derivatives.Various PET tracers have been used (oxygen13-ammonia), and different patterns can be observed in areas of contractile dysfunction. Viable tissue may show normal perfusion and FDG uptake (which reflects chronic stunning) or reduced perfusion and preserved FDG uptake . Scar tissue is characterized by reduced  or absent perfusion and FDG uptake . Of note, FDG imaging with SPECT and 511 keV collimators has also been developed successfully over the last decades  to severely hypoperfused areas.The uptake and retention of the technetium-based tracers depend on perfusion, cell membrane integrity, and mitochondrial function. In areas of contractile dysfunction, a >50-60% tracer uptake on a resting image is frequently used as marker for viability. It has also been proposed to perform During stepwise infusion of dobutamine, echocardiographic images are obtained evaluating regional wall motion. The initial phase includes low-dose dobutamine (5 to 10 mcg/kg/min) infusion, and the hall-mark of viability is “contractile reserve” which is improvement of contractile dysfunction during low-dose dobutamine infusion. The protocol can be extended to high-dose dobutamine infusion (up to 40 mcg/kg/min with addition of atropine), which allows detection of ischemia. The different wall motion responses during low–high dose dobutamine include (A) biphasic response , (B) immediate worsening , (C) sustained improvement , and (D) no change . Pattern A represents viability with superimposed ischemia; pattern B represents severe ischemia due to critical coronary artery stenosis; pattern C relates to subendocardial infarction, and pattern D indicates transmural scar formation.Areas with contractile dysfunction and a very thinned wall  have a low likelihood of viability and functional recovery. Conversely, dysfunctional regions with preserved wall thickness do not always improve in function, and this is related to the presence of subendocardial scar . Contractile reserve can be detected with MRI during dobutamine infusion as described above with echocardiography. An advantage of MRI is that wall thickening and motion can be quantitatively assessed, although in the clinical practice this rarely happens. The main contribution of MRI is the use of gadolinium-based contrast agents to detect scar tissue. Based on the excellent spatial resolution, contrast-enhanced MRI can differentiate between non-transmural and transmural scar tissue Figure .Figure 4A recent, very extensive report summarized the results of the viability studies focusing on prediction of functional recovery, and the results are summarized in Figure The highest sensitivity was obtained by FDG PET (92%), followed by SPECT with thallium-201 (87%) and technetium-99m-labeled agents (83%). The most specific approach was dobutamine stress echocardiography (specificity 78%). Improvement of global LV function (LVEF) is clinically more meaningful than improvement of segmental function. It is unclear how much viable myocardium is needed to result in the improvement of global LV function. Various studies have shown that recovery of global LV function may occur when at least 25% of the dysfunctional segments are viable.P < 0.001). In the substudy, including 601 patients , the relation between viability, therapy , and outcome was evaluated.P = 0.003). Importantly, following correction for other baseline variables, this association with mortality was not significant (P = 0.21): these variables included LVEF, LV volumes, severity of symptoms, all indicators of more severe disease. In addition, there was no significant interaction between viability status and treatment regarding mortality (P = 0.53). Various issues could have affected the results of the STICH trial. First, as was pointed out in the beginning of this chapter, the focus should be on dysfunctional segments and in the STICH analysis all segments were included, and a large percentage of segments may be viable but have normal contractile function . This is also reflected in the distribution between viable and non-viable patients: 487 vs 114, while in the daily practice, the majority of patients with previous infarction does not contain viability in the infarcted area. In the current trial, the small cohort of non-viable patients is then randomized to 60 patients receiving medical therapy and 54 undergoing CABG. In addition, the viability techniques used were dobutamine stress echocardiography and 99technetium SPECT imaging, whereas FDG PET (the most sensitive viability assessment technique) and contrast-enhanced-MRI (the most accurate scar assessment technique) may have been preferred. Probably the most important issue is the beginning of this article: viability is only one part of the diagnostic and prognostic work-up of the patients with ischemic heart failure, and all other factors indicated in Table The most important issue is however the impact of viability on prognosis. A total of 28 retrospective viability studies have been reported including 3848 patients.Left ventricular volumes and LVEF are important parameters for the risk stratification and management (particularly device therapy) of heart failure patients. The wide availability, accuracy, and safety make 2-dimensional transthoracic echocardiography the imaging technique of first choice (video 1).In addition, LV shape is important, and particularly the formation of large LV aneurysms after infarction. Thrombus formation frequently occurs at these aneurysmatic sites, and surgical resection of dysfunctional myocardium and/or scar tissue can reduce LV size and restore normal geometry.2 and a regurgitant volume ≥30 mL/beat quantified using the proximal isovelocity surface area (PISA) method.2 at peak stress has been associated with poor survival.Secondary mitral regurgitation occurs frequently in patients with ischemic heart failure, and is characterized by a combination of reduced LV closing forces (due to LV dysfunction or dyssynchrony) and global and regional LV remodeling which leads to distortion of the subvalvular apparatus of the mitral valve, displacement of the papillary muscles, tethering of the mitral leaflets, and failure of mitral valve coaptation. Secondary mitral regurgitation results in LV volume overload, which further worsens LV remodeling and mitral valve incompetence. The presence of significant secondary mitral regurgitation provides incremental prognostic information over LVEF.The suitability for surgical restrictive mitral valve annulopasty is influenced by several geometrical aspects of the mitral valve and left ventricle, and also by the presence of extensive myocardial scar, which has been associated with increased mortality rates after surgical repair.P = 0.04) independently of LVEF and extent of infarct core.Patients with ischemic heart failure and depressed LVEF (≤35%) have an increased risk of arrhythmic death.11C-meta-hydroxyephedrine (11C-HED) PET, perfusion was assessed with 13nitrogen-ammonia and viability was quantified with FDG. Patients with vs without ICD shocks had significantly larger areas of denervated myocardium  and larger areas of denervated, viable myocardium  despite having comparable LVEF. In addition, the extent of denervated myocardium was independently associated with ICD shocks .123-iodine (123I)-metaiodobenzylguanidine (MIBG) SPECT has been used to evaluate cardiac innervation. From the planar images, the heart-to-mediastinum (H/M) ratio and the washout rate quantify the global myocardial uptake of 123I-MIBG . In addition, from SPECT images, regional abnormalities in 123I-MIBG uptake have been associated with ventricular arrhythmias.123I-MIBG SPECT summed defect score >26 identified a subgroup of patients with high cumulative rates of ventricular arrhythmias at 3 years follow-up .Possibly, another characteristic of the border zone is the presence of viable but  denervated myocardium; the functional integrity of the sympathetic nerve terminals in this area can be evaluated with using radiolabeled norepinephrine analogs.Cardiac resynchronization therapy can also improve clinical outcomes of heart failure patients in NYHA functional class II-IV despite optimal medical therapy, with LVEF <35% and QRS duration >120 ms.P < 0.01) and phase standard deviation . Furthermore, accumulating evidence has shown that an LV lead placed at the latest activated region of the left ventricle is associated with good response to CRT.Phase analysis measures the onset of mechanical contraction by approximating the variation of regional maximal counts over the cardiac cycle  in SPECT myocardial perfusion imaging with Fourier harmonic functions Figure .70 From Eventually, the information on LV dyssynchrony, the site of latest activation, and scar tissue can be fused with fluoroscopic venograms into a 3-dimensional LV epicardial surface extracted from ECG-gated SPECT myocardial perfusion imaging Figure .72 The cThe patient with ischemic heart failure needs careful, stepwise diagnostic analysis; non-invasive imaging can provide much of this information. Myocardial viability assessment is an important component, but should be integrated within all other relevant information. Once all the information is completed, a personalized therapeutic plan can be presented, making a personalized approach feasible to the individual patient.A 59-year-old male presented at the outpatient clinic with heart failure symptoms since 3 weeks. The patient was a smoker and had hypertension treated with angiotensin converting enzyme inhibitors. On transthoracic echocardiography, a dilated left ventricle with a biplane left ventricular ejection fraction of 22% and global hypokinesia were observed video . The invVideo 1Assessment of left ventricular systolic function. Panel A: 2-dimensional transthoracic echocardiography showing an apical 4-chamber view with reduced left ventricular ejection fraction. Panel B: Contrast-enhanced 3-dimensional triplane apical view of the left ventricle. Panel C: ECG-gated single-photon emission-computed tomography of the left ventricle showing apical dyskinesia. Panel D: assessment of left ventricular systolic function with multi-detector row computed tomography. Panel E: Cine magnetic resonance imaging showing the reconstructed 4-chamber view. The left ventricle is dilated, with reduced left ventricular ejection fraction and large thin-walled apical aneurysm (WMV 8802 kb)Video 2Evaluation of secondary mitral regurgitation. Panel A: 2-dimensional transthoracic color Doppler echocardiography showing the apical 4-chamber view and severe secondary mitral regurgitation with large eccentric jet along the lateral wall of the left atrium. Panel B: 2-dimensional transesophageal echocardiography showing the 4-chamber view focused on the mitral valve which shows restriction of the posterior mitral leaflet (arrow) and lack of coaptation. Panel C: 2-dimensional transesophageal color Doppler echocardiography showing the resultant severe secondary mitral regurgitation. Panel D: 3-dimensional full volume en-face view of the mitral valve showing a large area of lack of coaptation of the mitral leaflets. Panel E: On 3-dimensional transesophageal color Doppler echocardiography data, the multiplanar reformations can be oriented across the vena contracta of the regurgitant jet showing the elliptic shape of the regurgitant orifice (WMV 11693 kb)Case 1. Figure 1: Contrast-enhanced magnetic resonance imaging showing selected 2-chamber and short-axis views of the left ventricle. The dilated left ventricle revealed subendocardial scar  in the mid anterior and inferior walls (arrows) (TIFF 1256 kb)Case 1. Video 12-dimensional transthoracic echocardiography showing the apical left ventricular 4-, 2- and 3-chamber views. The left ventricular ejection fraction was 22% (WMV 18966 kb)Case 1. Video 2Invasive coronary angiography showing severe stenosis of the proximal segments of the left anterior descending and circumflex coronary arteries (panel A) and chronically occluded right coronary artery (panel B) (WMV 12888 kb)Case 1. Video 3Cine magnetic resonance imaging showing the 4- and 2-chamber long-axis and the short-axis views of the left ventricle. The left ventricle is significantly dilated and shows global hypokinesia but no significant wall thinning (WMV 5990 kb)Case 1. Video 4Low-dose dobutamine stress echocardiography showing the apical 4-, 2- and 3-chamber views of the left ventricle. The left ventricular function and wall thickening improved at low-dose dobutamine (WMV 9670 kb)Case 1. Video 5After surgical revascularization, significant left ventricular reverse remodeling was observed with subsequent improvement in systolic function. Apical left ventricular 4-, 2- and 3-chamber views are shown (WMV 16591 kb)Below is the link to the electronic supplementary material.


It is well known that arterial function relates to cardiovascular morbidity and mortality. The noninvasive technology for the assessment of arterial function has developed as the importance of prevention of early cardiovascular disease has been emphasized. Over 2-D and Doppler echocardiography, speckle-tracking echocardiography has emerged as a valuable ultrasound imaging technique that allows for an objective and quantitative evaluation of global and regional myocardial function. Recently, several studies have extended its applicability beyond cardiac chambers, such as artery. Measurement of carotid arterial strain with speckle tracking ultrasound has been shown to be feasible and reliable. This review describes the new ultrasound techniques to assess arterial function and their clinical implications. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the industrialized countries . In the Previously, vascular aging, the changes of vascular function and structure, was overlooked in comparison with overt atherosclerosis. The cardiovascular continnum was restricted to atherosclerotic disease , 3. HoweThis review describes the new ultrasound techniques to assess arterial function and their clinical implications.The arterial wall is mainly composed of scaffolding proteins, elastin and collagen . RepetitSince it is non-invasive, reproducible, and simple, measurement of cIMT with ultrasonography is widely used to quantify the extent of subclinical disease in individuals with cardiovascular (CV) risk factors and to follow up in interventional studies. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions. Before the progression of the intima and media thickening, the carotid artery may experience functional alterations, of which the occurrence is also associated with an increased risk of CV morbidity or mortality by augmenting arterial impedance and resultant increase in the afterload of the heart . RecentlOver 2-D and Doppler echocardiography, speckle-tracking echocardiography has emerged as a valuable ultrasound imaging technique that allows for an objective and quantitative evaluation of global and regional myocardial function , 20. SpeMeasurement of carotid arterial strain with speckle tracking ultrasound has been shown to be feasible and reliable . Recent Velocity vector imaging (VVI) is a new method of strain imaging with 2-D speckle tracking , 27. We Arterial function using VVI was also evaluated in patients with vasculopathy such as Takayasu’s arteritis and Marfan syndrome , 30. In Previously, most studies on arterial aging have focused on global changes of arterial function due to lack of test for regional arterial function. Conventional methods for assessment of arterial function usually represent global arterial function, and not regional function. Despite its potential importance, regional structural changes of artery and consequent aynchronicity of arterial expansion has been overlooked. Unlike other assessment technique for arterial function, strain analyses present regional arterial function. Therefore, assessment of vascular function with strain imaging could be expected to offer better understanding into the pathophysiology of vasculopathy.Carotid 2-D ultrasound evaluates not only arterial structure but also arterial function including changes in diameter during the cardiac cycle . HoweverHowever, up to the present, there are some limitations in evaluation of the arterial function with speckle tracking echocardiography. In cases of deep carotid arteries or compression by surrounding structures such as an enlarged thyroid or extended jugular vein, tracing of the carotid artery is technically difficult. Arterial wall is very thin compared to myocardium, so could be difficult to track. Even though, intra and interobserver variability were reliable in small studies, further studies with large subjects are necessary. The superiority of strain analysis compared with other methods of vascular functional assessment has not been confirmed yet. Longitudinal follow-up study with large populations needs to be evaluated to support the clinical usefulness of arterial strain analysis.Recently, new ultrasound techniques have enabled the assessment of arterial mechanics using strain analysis. Several studies reported the feasibility of strain analysis in the evaluation of arterial function. The results of those studies demonstrated that strain analysis of superficial artery could be a valuable method to evaluate arterial function. If some technical problems in acquiring proper images and tracking thin arterial wall are improved, evaluation of arterial strain could be used extensively to assess local arterial function in future.


Hypertrophic cardiomyopathy is a heterogeneous myocardial disorder with a broad spectrum of clinical presentation and morphologic features. Recent reports indicated that some patients with restrictive cardiomyopathy. Comprehensive cardiac magnetic resonance imaging of the restrictive phenotype in HCM patients has not been fully evaluated. The purpose of this study was to investigate the CMR characteristics of hypertrophic cardiomyopathy (HCM) with restrictive phenotype.2 test/Fisher's exact probability method were used for statistical analysis.19 patients of HCM with obviously restrictive characteristics and 19 patients with non obstructive HCM, matched with age and gender, were collected. The differences in clinical features, CMR morphological characteristics, and the function parameters were retrospectively compared of the two groups. The paired sample t test and XRestrictive phenotype of patients with HCM have more severe clinical conditions including sustained atrial fibrillation, pericardial effusion, and lower heart function classifications compared with controls; The left and right atrium diameter were 55.79±5.34 mm and 61.33±11.05 mm, which were significantly greater than the controls (p<0.001); The segments with late gadalinum enhancement were 7.68±2.98, which were significantly more than that in controls . The left ventricular end-diastolic volume index, the cardiac index, and the left heart ejection fraction of patients with restrictive phenotype were all significantly less than those of the controls.Restrictive phenotype is a special subtype of HCM. The CMR features include mild-to-moderate left ventricular hypertrophy, huge atrium, normal or small left ventricular, pericardial effusion and a wide range of late gadalinum enhancement, often with severe clinical symptoms and poor prognosis. MRI has important application value in the diagnosis of the disease.


Determination of the relaxation time constants T1 and T2 with quantitative magnetic resonance imaging is increasingly used for both research and clinical practice. Recently, groups have been formed within the Society of Cardiovascular Magnetic Resonance to address issues with relaxometry. However, so far they have avoided specific recommendations on methodology due to lack of consensus and current evolving research. Standardised widely available software may simplify this process.The purpose of the current study was to develop and validate vendor-independent T1 and T2 mapping modules and implement those in the versatile and widespread software Segment, freely available for research and FDA approved for clinical applications.The T1 and T2 mapping modules were developed and validated in phantoms at 1.5 T and 3 T with reference standard values calculated from reference pulse sequences using the Nelder-Mead Simplex optimisation method. The proposed modules support current commonly available MRI pulse sequences and both 2- and 3-parameter curve fitting. Images acquired in patients using three major vendors showed vendor-independence. Bias and variability showed high agreement with T1 and T2 reference standards for T1 (range 214–1752 ms) and T2 (range 45–338 ms), respectively.The developed and validated T1 and T2 mapping and quantification modules generated relaxation maps from current commonly used MRI sequences and multiple signal models. Patient applications showed usability for three major vendors. Quantitative magnetic resonance imaging (MRI) is increasingly used for several different applications in both research and clinical practice. For cardiac MRI, T1 quantification enables measurement of myocardial extracellular volume , whereasFurther, cancer imaging has benefited from T1 to T2 mapping for determining early tumour progression in brain , and proDifferent numerical algorithms can be used to compute T1 and T2 relaxation maps and therefore inline map generation may vary between MRI vendors. Also, most inline systems do not present the curve fit, which, if visualised, can be used as a marker of accuracy. Moreover, the algorithms used are not openly documented. A previous open-source software overcame these limitations, but is only to be used for research . Last buThe purpose of this study was to develop, validate and openly document T1 and T2 relaxation map modules with multiple signal models, test those in images acquired using three major vendors, and implement the validated modules in freely available software for research .The T1 and T2 mapping modules were developed and validated in phantoms with reference standard T1 and T2 values calculated from reference spin echo (SE) pulse sequences using the Nelder-Mead Simplex optimisation method available in Matlab . The proposed modules support current commonly available MRI pulse sequences and both 2- and 3-parameter curve fitting  [The validated modules were finally implemented in the software Segment, freely available for research (iso.com) .Since Segment already includes a validated module for T2* mapping and quantification , this toA Eurospin  phantom encompassing 12 gadolinium/agarose gel phantoms was used for validation of the proposed modules. The phantoms were scanned at both 1.5 T and 3 T . Single-echo spin-echo sequences were used for acquiring the reference T1 and T2 values. Pulse sequence parameters are presented in Table Commonly available T1 and T2 mapping sequences were used to acquire images of the phantom, and the proposed modules were applied to generate T1 and T2 relaxation constant maps. The sequences were based on a free-breathing single-shot balanced steady-state free precession (bSSFP) sequence.Pixelwise T1 estimates were initialized using a lookup-table search performed in two steps in a T1 interval of 0–4000 ms. First, a step of 50 ms between lookup-table entries was applied for high performance. Thereafter, to find the optimal value, a second search was performed using a 5 ms difference between lookup-table entries within 100 ms of the entry found in the first step. In these two steps, depending on the pulse sequence, ideal inversion/saturation efficiency was assumed and each pixel was normalized with the maximum absolute value within its time-series. The T1 lookup-table entry resulting in the minimum sum of absolute error was chosen as the initial T1 value.Following T1 initialization, pixel T1 values were refined using a C implementation of the Nelder-Mead Simplex nonlinear optimisation algorithm . ConvergFor T1 reference values, an inversion recovery (IR) single-echo spin echo sequence was used with a short echo time and long repetition time Table . Two varThe initial T2 estimate was initialized by a weighted 2-parameter linear regression of the signal logarithm . The estFollowing the T2 initialisation, all pixels with T2 values outside the interval 0 < T2 < 400 ms were excluded from further analysis and the final T2 estimate was refined using the above-mentioned nonlinear optimisation algorithm. Convergence was assumed when the maximum T2 absolute difference between two simplexes was less than 0.10 ms. Pixels that were not refined with nonlinear optimization were set to 0 in the resulting T2 map.For T2 reference values, a single-echo spin echo sequence was used. The free-breathing bSSFP sequence used T2 preparation pulses for T2 mapping. An SR-prepared image with a short saturation time was used for the T2 calculation in order to improve the 3-parameter curve fit . MagnituCurve-fit residuals for T1 and T2 mapping were calculated as the average absolute difference between the fitted curve and corresponding pixel values. Residuals were normalised relative to the maximum absolute pixel value within its time-series and reported as a percentage.The developed and validated T1 and T2 mapping modules were applied on images acquired from three major vendors. Standard available sequences were used on Siemens  with 60-channel phased array coils and a 20-channel head coil; Philips  with 32-channel phased array coils; and on GE  with a GEM flex medium array coil. The local ethics committee approved the research protocol and all subjects provided written consent.Bias and variability were determined using the modified Bland-Altman analysis. The bias and variability percentages were computed as the difference between the proposed method and the reference standard divided with the reference standard values. Values were expressed as mean ± SD and 95 % limits of agreement.Computational times were generally fast independent of amount of information, i.e. for both full image and ROI-based calculations Table .Table 3CThe T1 and T2 reference values ranged from 214 to 1643 ms and 46–338 ms for 1.5 T, and 229–1752 ms and 45–316 ms for 3 T, respectively. Phantom validation results are shown for 1.5 T and 3 T  when applying a 3-parameter fit, whereas a 2-parameter fit yielded 22 ± 13 ms (2.8 ± 1.6 %). Corresponding bias and variability for PSIR-bSSFP at 3 T were −9 ± 13 ms (−1.1 ± 1.0 %) and −36 ± 33 ms (−3.3 ± 2.1 %).The T2 bias and variability were 2.8 ± 2.7 ms (1.9 ± 2.0 %) at 1.5 T and −0.7 ± 3.6 ms (0.2 ± 2.7 %) at 3 T using the 3-parameter fit.Figure The developed and validated T1 and T2 mapping modules generated maps from commonly used MRI sequences and multiple signal models. Generally low bias and variability were found compared with reference standard measurements in phantoms. Patient applications showed usability for three major vendors. The main software is freely available for research and well documented.The proposed algorithms showed particularly good agreement with the reference standard for saturation recovery sequences. However, T1 was underestimated by MOLLI when also phantoms with low T2 values (<60 ms) were included. This is similar to previously published data showing T2 sensitivity for MOLLI T1 mapping, with approximately 5 % error in T1 values for T2 below 30 ms . This unThe slightly higher, albeit not large, variability shown for the T2 prepared sequence may be explained by limited signal-to-noise ratio. The T2 prepared mapping may be improved by acquiring several data points (echoes), especially late TE images since an offset is known to occur. Another solution is to acquire fewer echoes and instead add a saturation recovery acquisition, as performed in the current study . This soThe proposed software modules include both 2- and 3-parameter T1 and T2 fitting. In theory, a reduced number of parameters should result in reduced random errors (i.e. reduced variability) while however also leading to a risk of introducing a bias due to increased sensitivity to measurement imperfections. In cardiac MRI, 3-parameter T1 curve fitting is commonly applied to reduce bias associated with imperfect preparation-pulse efficiency and/or effects from applied readout pulses , 22. TheIn the current modules neither rigid nor non-rigid registration has been implemented. These methods may in some cases improve the diagnostic quality and are subject to future improvements and investigations and will be included in future updates of the modules. Further, some MRI vendors use private dicom headers for data needed for T1 and T2 mapping. These headers may change between MRI vendor software updates. Current known private dicom headers have been implemented in the proposed modules and future updates aim to cover these changes.The developed and validated T1 and T2 mapping modules generated relaxation maps from current commonly used MRI sequences and multiple signal models. Patient applications showed usability for three major vendors. The main software is freely available for research and well documented.bSSFP, balanced steady-state free precession; IR, inversion recovery; MOLLI, modified Look-Locker inversion recovery; MRI, magnetic resonance imaging; PSIR, phase-sensitive inversion recovery; SCMR, society of cardiovascular magnetic resonance; SE, spin echo; SR, saturation recovery.


The availability of pacing configurations offered by quadripolar left ventricular leads could improve patients’ response to cardiac resynchronization therapy; however, the selection of an optimal setting remains a challenge. Echo-particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. These observations are also supported by several numerical models of the left ventricle that have shown the close relationship between wall motion abnormalities, change of intraventricular flow dynamics, and abnormal distribution of forces operating on the ventricular endocardium.A 73-year-old white man in New York Heart Association III functional class with an ejection fraction of 27.5 % did not improve after 1 month of cardiac resynchronization therapy. Five configurations were tested and settings were defined by optimizing intraventricular flow. After 6 months, he became New York Heart Association II class with left ventricular ejection fraction of 53.2 %.The abnormal dynamic of pressure gradients during the cardiac cycle, through biohumoral endocrine, autocrine, and paracrine transduction, may lead to structural changes of the myocardial walls with subsequent left ventricular remodeling. The echo-particle imaging velocimetry technique may be useful for elucidating the favorable effects of cardiac resynchronization therapy on intraventricular fluid dynamics and it could be used to identify appropriate pacing setting during acute echocardiographic optimization of left pacing vector.The online version of this article (doi:10.1186/s13256-016-0965-9) contains supplementary material, which is available to authorized users. Unfavorable response to cardiac resynchronization therapy (CRT) is determined by different causes, such as an inadequate selection of patient, or issues related to the implant of the device such as a non-optimal position of the lead in the coronary sinus or an incorrect programming of biventricular pacemaker.The availability of pacing configurations offered by quadripolar left ventricle (LV) leads could improve a patients’ response; however, selection of an optimal setting remains a challenge. Recent studies suggested that images of LV flow by echo-particle imaging velocimetry (echo-PIV) could be a useful marker of synchrony , which cA 73-year-old white man with non-ischemic dilated cardiomyopathy diagnosed for at least 2 years, in functional New York Heart Association (NYHA) class III despite optimal medical therapy, with left bundle branch block and a QRS duration of 125 msec -to-LV electrical delay  at each At the 1-month post-implant follow-up he showed worsening heart failure symptoms becoming NYHA class IV. Therefore, we performed an echocardiographic examination using contrast agent for the evaluation of intracavity blood motion at mechanical index of approximately 0.4 and high frame rates (70 to 90 Hz). The recorded clips of 1-month post-CRT implant, as well as of basal echocardiographic examination, were processed by echo-PIV, an optical method where the contrast agent bubbles are tracked from one frame to the next to calculate the instantaneous blood velocity fields. From these, the orientation angle (φ) of the global hemodynamic forces exchanged between blood and surrounding tissues is estimated. This angle ranges from zero, when flow force is predominantly along the base–apex direction, up to 90 degrees when it becomes transversal.At pre-implant, the polar histogram showed the orientation and relative magnitude of blood-induced intraventricular forces were not properly aligned along the LV axis  may not be easily detectable in terms of tissue displacement. Hemodynamic forces are known to participate in morphogenesis in embryonic hearts; therefore, they may also be one concurring factor during the pathological development of the grown heart . The vorThe observed changes in the orientation of flow momentum show an increasing longitudinal alignment in correspondence with an increasing volumetric response to CRT. This suggests that the electric changes provided by the therapy are more effective when they reflect into hemodynamic modifications that improve the longitudinal orientation of flow forces; conversely, a blood motion arrangement presenting transversal intraventricular forces is associated with lack of response to CRT. The echo-PIV technique may be useful for elucidating the favorable effects of CRT on intraventricular fluid dynamics and it could be used to identify appropriate pacing setting during acute echocardiographic optimization of quadripolar cardiac resynchronization device.


Cine CMR is the gold standard for evaluation of left ventricular function with high spatial and temporal resolution of the EKG-gated acquisition. Measurements of dyssynchrony have previously been performed using myocardial tagging to measure relative delays in peak shortening of opposing walls. We aim to utilize non-tagged images to quantify dyssynchrony in clinical patients. This is performed by combining aortic valve timing information from a left ventricular outflow tract (LVOT) image series with segmentations of short axis datasets.Short-axis stacks and LVOT images were acquired using standard retrospective EKG-gated bSSFP cine imaging in 63 clinical patients with a range of clinical conditions (mean EF = 44.5 ± 19.0%) as well as 29 patients with prolonged QRS duration. Scan parameters were as follows: in-plane resolution: 1.25 - 2.08 mm, slice spacing: 8 mm with 2 mm gap, reconstructed temporal resolution: 18.2 - 58.8 ms. Aortic valve opening and closing as a percentage of cardiac cycle was identified on LVOT images. Volumetric evaluation of short axis images was performed via semi-automated segmentation for all phases and all left ventricular slices . Dyssynchrony was measured by the standard deviation of the timing difference between each slice minimum area to aortic valve closure as expressed by the equation in Figure The use of patients with prolonged QRS complexes allows for separation of measured dyssynchrony based on both EF and QRS. Patients were categorized into low EF (≤ 35%), mid EF (35% < EF < 50%) and normal EF (≥ 50%). The results are shown in Figure This technique allows for a slice-by-slice timing based regional evaluation of dyssynchrony. In addition, subsequent analysis of particular dyssynchronous slices could be performed to provide additional regional information.K99-HL108157, R01-HL103723, T32HL007954, T32-EB009384.


Coronary artery disease (CAD) is a source of significant mortality and morbidity in diabetes mellitus (DM). Abnormal myocardial perfusion reserve (MPR) has been shown to predict worse outcome in patients with diabetes, but limited data is available using CMR. The correlation of MPR derived from Cardiac Magnetic resonance imaging (CMR) with plaque burden on cardiac computed tomography angiography (CTA) has not been previously evaluated. We aim to look at this correlation in patients undergoing vasodilator stress CMR.Same day Adenosine- stress CMR (Siemens Avanto 1.5 T) and cardiac CTA  were performed on symptomatic diabetics without known coronary artery or valvular heart disease, referred for stress testing. Both qualitative and quantitative perfusion analysis (using Fermi-deconvolution in Matlab and 16 segment AHA model) were performed. Rest and stress myocardial blood flow and MPR were calculated. Patients were divided into three groups based on an MPR of < 2.0, 2 -2.4 and > 2.4. Semi quantitative assessment of plaque using CTA (plaque and segment scores) were calculated as published in the literature and compared using ANOVA and Tukey's analysis.Amongst the 25 patients enrolled, the mean age was 60 +/- 9 yrs., 60% were females, and the mean BMI (kg/m2) was 31.7 +/- 6.56. No coronary plaque was visualized in 9 (36%) of the patients while two patients (4%) had a > 50% plaque in atleast once coronary artery. A qualitative perfusion abnormality was detected in 2 subjects (4%), one of whom had a > 50% plaque on CTA. Reduced flow reserves of < 2.0 and 2-2.4 were present in 5 (20%) and 9 (36%) of patients respectively, leaving 11 (44%) with normal MPR > 2.4. CTA findings as well as stress CMR- MPR analysis are presented in table A reduced MPR < 2.4 was found in the majority of our cohort of symptomatic diabetic patients referred for stress CMR (56%), and 36% had a substantially-decreased MPR of < 2.0. A significant correlation between extent of plaque and MPR was identified in this population with a substantial increase with MPR < 2.0. Long-term follow-up will determine the prognostic utility of these findings.George Beller Research Award, an internal funding award from the Heart Center Advisory Board.


Purpose: Prolonged pacing from the right ventricular apex (RV) is associated with the LV dyssynchrony leading to progressive left ventricular dysfunction and increased morbidity and mortality. Alternate RV pacing sites-in particular the mid- RV septum and the RV outflow tract (RVOT) septum were considered, but no clear benefit was proven till now for this pacing sites. This may be due to the heterogeneity of the RV septal positions and to the significant number of leads placed on the RV free wall.The aim of this study is to find a reliable method of septal lead placement and to identify those pacing sites which provide better LV electrical activationMethods: 50 consecutive patients referred for pacemaker implants due to AV block were included. Patients with history of heart failure or LVEF < 50% at the implant were excluded. All patients had RV leads placed in septal position. This was achieved with a double curved stilet with the distal curve aimed posteriorly. RV septum and RVOT were mapped during implant aiming for a narrow paced QRS with an axis as close to normal as possible. Pacing lead position was evaluated during the implant using fluoroscopy (AP and LAO 40 °) and than by 12 lead ECG and echo. IntraLV dyssynchrony was evaluated during pacing using SPWMD in short axis parasternal view and the TDI septal to lateral ∆ t. Paced QRS duration and axis were also recorded. The correlation was sought between lead position evaluated by Rx and by echo and between paced QRS duration and axis and LV dyssynchrony.Results: 92%(46) of the patients had the lead in septal position RV , while 8% (4 pts) had the lead on the RVOT RV free wall as shown by echo. An anterior-oriented lead in the left anterior oblique fluoroscopic projection was specific for free wall position while positive QRS in DI in RVOT position was suggestive for free wall position on the ECG.No correlation was made between paced QRS axis and LV dyssynchrony while the QRS duration of > 160 ms was associated with significant LV dyssynchrony .Conclusions: RV lead placement on the RV septum can be reliably achieved using a specially curved stilet and the LAO projection for confirmation.The wide paced QRS is correlated with significant intra LV dyssynchrony and therefore the RV pacing site with the narrowest QRS should be sought. Alternative positions have been proposed for the pacing leads, including the right ventricular outflow tract (RVOT), basal and mid-interventricular septum as the most often used [5-8]. These positions aim to obtaining a narrower paced QRS with an electrical axis closer to normal compared to the one obtained by stimulating RVA, but have not shown a consistent benefit for LV activation dyssynchrony or LV systolic dysfunction incidence in clinical trials  . This may be due to heterogeneity of septal ventricular pacing lead positions and implantation of a significant percentage of leads in the free wall of the RV by using the classical methods of implant .Stimulation of the right ventricle apex (RVA) leads to an abnormal electrical activation of ventricular myocardium - starting from the apex towards the base and from the right to the left. This increases the total ventricular activation time and delays the contraction of the lateral wall of LV. Over the long term the RVA pacing is associated with systolic dysfunction of LV, heart failure, increased incidence of atrial fibrillation and increased mortality. Pathophysiological mechanisms proposed to explain these phenomena are the dyssynchrony of contraction of LV, tampering with the cardiac hemodynamics, increased myocardial oxygen consumption and workload of the LV, followed by both structural alterations at the cellular level and macroscopical remodeling of LV .Even if sex did not reach statistical significance, we notice the presence of 63% females in group B, compared with 36% in group A. A larger study sample could provide a statistical power to reach the conclusion the female sex is associated with LV assynchrony during RV pacing. This would correlate well with the fact that females with left bundle branch block and dilative cardiomyopathy are better responders to cardiac resinchronisation theraphy [1. Positioning the pacing lead on the RV septum can be performed accurately using a double curve stilet with a proximal upward curve and a distal posterior curve, using 40° LAO radiological incidence for confirmation.2. Paced QRS duration > 160 ms is significantly associated with presence of intraLV assynchrony, indicating that during the implant must be sought the position with narrowest paced QRS. 3. The axis of the QRS does not influence the assynchronous contraction of LV and should not be used to optimize the position of the RV lead.4. Positions at the level of the RV wall free are associated with a broader QRS and LV assynchrony and should be avoided.5. Age correlates with LV asynchrony during ventricular pacing, so seeking a narrower paced QRS might be even more important in older people.6. Patients with slightly impaired systolic function tend to have more frequently LV dyssynchrony. Echocardiographical follow-up would be recommended in this subset of patients, as to early detect pacing induced cardiomyopathy and promptly provide upgrade to a biventricular system.LimitationsThe major flaws of this study are its transversal design and the relatively small sample size. However the purpose of this research was not to definitely ascertain the risk factors for pacing induced cardiomyopathy but to detect the potential directions which warrant further investigation in this quite frequent and relatively unexplored pathology.


Aim of this study was to provide an echocardiographic protocol for the description of the normal murine venous reservoir  and to investigate the possibility to use this approach to discriminate changes on left atrium (LA) and left atrial appendage (LAA) in a stress-induced model such us myocardial infarction. Global left ventricular function and the venous reservoir were assessed by a Vevo2100 in 20 female C57BL/6N. LA and LAA were also studied in 10 CD-1 and 10 FVB mice, whereas modifications investigated in 15 C57BL/6N subjected to coronary artery ligation. Left ventricle function was evaluated as well as pulsed Doppler mitral valve, pulmonary vein, and LAA velocities. From 2D view monoplane LA volumes were obtained and LAA long axis measured. Macroscopic inspection with casts and immunohistochemistry were performed. Results show that compared to humans, in C57BL/6N mice left atrium was disproportionately smaller (5.2±1.4μL) than the left ventricle (53±8μL) and connected through a duct by a large LAA and posteriorly to three pulmonary veins. The LA volume increased 2-fold during reservoir with two distinct phases, early and late divided by a short pause. LAA long axis (4.1±0.5mm) was almost 2 times longer than the LA. LAA flow volume together with LA volume reservoir account for about 36% of stroke volume and the rest was provided by conduit flow. Linear regressions showed that stroke volume was strongly influenced by LAA flow, LA early filling volume and left ventricle base descent. Moreover, we also report the ability to assess LA and LAA in other mice strains and discriminate size increase following myocardial infarction. In conclusion, we performed a complete characterization of murine left venous reservoir establishing an optimized protocol that can be used in both investigative and pharmacological studies requiring rapid and serial determination of cardiac structure and function. Rodents are a powerful experimental model for a mechanistic understanding of normal cardiovascular function and to identify the molecular mechanisms underlying the pathological basis of cardiovascular diseases. Normal reference values have been established for murine left ventricle (LV) , 2 on thRecent advances in imaging technology provide improved spatial and temporal resolution to visualize rodent myocardium, allowing the investigation of its smallest structures. High-frequency echocardiography is a non-invasive, accurate and reproducible tool for in vivo murine cardiovascular investigation , 2, 5–11ad libitum with standard chow and water. All efforts were made to minimize suffering.The procedures concerning animal care, surgery, and euthanasia were performed in accordance with national  and International laws and policies  and approved and authorized by the National Ministry of Health-University of Milan Committee . Mice  were fed The left venous reservoir was assessed on twenty C57BL/6N 10-week-old female mice (18–20g) and on 10 CD-1 female mice (24–27g) and 10 FVB male mice (26–29g). Stress-induced changes were investigated on 15 C57BL/6N female mice subject to coronary artery ligation and compared with 15 sham-operated mice. Intergender differences were assessed by studing 10 male mice. Vevo 2100 system  equipped with a MS400 30-MHz linear array transducer were used for echocardiography. Induction of anesthesia was accomplished by exposing the mice to 2% isoflurane  in 100% Oxygen (5 mins) in an induction chamber. The mice were then placed in the supine position on a heated (37°C) platform with integrated electrode pads used to obtain electrographic signals and heart rate (HR). The mouse chest area was shaved and a warmed ultrasound gel applied to the thorax surface to optimize the visibility of the cardiac chambers. A nose cone was attached for continuous delivery of isoflurane (1% in 100% oxygen) titrated to maintain HR ≥450 beats per minute (bpm) during acquisition.The Vevo MS400 30-MHz linear array transducer had an axial resolution of 50 μm and lateral resolution of 110 μm. Mean frame duration was 3.8 ms, and mean frames per cardiac cycle was 35.1±7.4. Respiration and ECG tracings were synchronised with imaging, and examinations lasted 30 min. Vevo software  was used for LV M-mode, 2D measurements, and pulsed Doppler velocities; Medimatic software  was used for the LA 2D measurements.Based on a previous pilot study, mice were imaged in: 1) the left parasternal long axis view (2D LV long axis); 2) the parasternal short axis view (M-mode and 2D LV dimensions and systolic function); 3) the standard apical 4-chamber view optimized for the LA cavity  annulus dimensions and mitral pulsed Doppler flow velocity) ; and 4) The R-R intervals were measured, and the Q wave used as a time reference for pulsed Doppler blood flow velocities.The end-diastolic and end-systolic LV areas  were measured, and LV end-diastolic, end-systolic volumes, stroke volume, ejection fraction and cardiac output were calculated using the Simpson’s rule. M-mode LV short axis end-diastolic and end-systolic diameters, and posterior and anterior wall thicknesses, were measured, short axis fractional shortening, and LV mass (Troy formula) were calculated. The end-diastolic and end-systolic LV long axis were measured and long axis systolic shortening was calculated. Isovolumic contraction (IVCT) and relaxation (IVRT) and LV ejection times were measured on pulsed Doppler recordings of simultaneous LV outflow and transmitral flow and used to calculate the myocardial performance index, an indicator of global function, as [(IVCT + IVRT) / LV ejection time].LV base descent was masured as mitral valve (MV) mid point displacement , MV peakIn the apical 4-chamber view, on the basis of frame-by-frame inspection, three frames were identified and their timing recorded: minimum , maximum , and an intermediate frame when there was a pause in the increase in LA dimension, defined as LA “notch” (LAnotch) . MonoplaLA function curve was built using frame-by-frame planimetry; peak systolic area increase , and peak diastolic decrease  were calculated. The ratio between supero-infero and medio-lateral diameters at minimum and maximum LA dimensions was calculated.The LAA maximum long axis (mid-line curve between the LAA apex and duct during LV end-systole) , the minThe flow pattern in the pilot study showed two forward LA filling waves (early S1 and late S2), a single forward diastolic wave (D) often followed by a small pulmonary venous atrial reversed flow wave . The durTotal reservoir volume change was calculated as: total 2D LA reservoir filling + LAA pulsed Doppler reservoir inflow. Total conduit flow was calculated as: LV SV – total reservoir volume change.We evaluated interobserver variability of selected indices by comparing echocardiographic data obtained by 2 independent observers within 1 session of echocardiographic acquisition from 10 mice and intraobserver variability results obtained by the same observer within one session on different days. For intersession variability, indices from the same 10 mice were recorded twice by the same observer with a time interval of 1 week. Interobserver and intraobserver variability within one session and intersession variability with the same observer were expressed as the percent discrepancy between two measurements  .Twenty C57BL/6N 10-week-old female mice were anesthetized and visualized by echocardiography at baseline, then anestetized by intraperitoneal injection of a mixture of ketamine hydrochloride (75 mg/kg) and medetomidine hydrochloride (1 mg/kg), intubated and ventilated with positive airway pressure. After thoracotomy, myocardial infarction was induced by permanent ligation of the left anterior descending (LAD) coronary artery as previously reported . A group2 then retrogradely perfused for 10 mins each with 0.01M phosphate saline buffer (PBS) and 4% (vol/vol) phosphate-buffered formalin, then postfixed in 4% phosphate-buffered formalin for 24 hrs and embedded in Paraplast.After echocardiography, mice were sacrified by intraperitoneal injection with ketamine hydrochloride (75 mg/kg) and medetomidine hydrochloride (1 mg/kg). For macroscopic inspection, hearts (n = 10) were perfused with a silicone elastomer (1 ml/min) through the cannulated abdominal aorta to build a vascular cast. For histology and immunofluorescence, hearts (n = 10) were arrested in diastole with CdClC57BL/6N mice hearts were sectioned coronally (8 μm), deparaffinized and rehydrated. Haematoxylin-eosin staining was performed for morphologic/topologic evaluation, and Masson’s Trichrome staining for collagen detection. Slides were viewed under a light microscope (Zeiss Axioskop) and images were acquired using a digital camera with a 1:1 macro-lens.2O2 in methyl alcohol/PBS 50/50 for 20 min, and then the sections incubated overnight at 4°C with isolectin B4 peroxidase . Appropriate secondary antibodies  were applied. The staining was semi-quantitatively assessed by two blinded operators, and the average of the two analyses was reported.Heart sections, de-waxed/rehydrated, were subject to heat-induced antigen retrieval in sodium citrate buffer  and then incubated for 45 mins at room temperature in 10% normal goat serum (Dako) in PBS 0.01M and 0.1% Triton X-100. Primary antibodies were applied overnight at 4°C and secondary antibodies for 2 hrs at room temperature. All antibodies were prepared in PBS and 0.1% Triton X-100. For nuclear staining, the sections were incubated with Hoechst 33258  in PBS for 15 min, before slide covering and fluorescence miscroscope  observation. For cardiomyocytes, smooth muscle cells and cardiac fibroblasts evaluation, sections were incubated respectively with mouse monoclonal antibody anti-α-sarcomeric actin (1:800), α-smooth muscle actin (1:600), or vimentin (1:1500) . For endothelial cells evaluation, endogenous peroxidase activity was blocked in 3% HAll echocardiographic data are the average of three measurements at end-expiration. Gender differences were compared using unpaired t test, while paired t test was used for baseline versus MI comparisons. Univariate linear regression was performed on selected indices. To obtain a multivariate linear regression of LV SV all the significant univariate predictors of LV SV were combined to define the maximal model that was then simplified by backward elimination to the minimal adequate model of LV SV. All statistical analyses were performed using R 2.15 , and p <0.05 was considered significant. All data are presented as mean ± 1 SD.No significant gender related differences were found therefore we report only female values. HR was 519±34. LV echocardiographic measurements are shown in vs minimum: p<0.001). Early filling is prevalent: in particular its duration and volume increase doubled that of late filling. . LAA SV (11.8±4μl) was about four times the LA total reservoir volume increase (3±0.9 μl). Total (LA+LAA) venous reservoir was 14.7±4.5 μl and conduit volume was 24.4±4.4 μl. Results are presented in LAA could be visualized and measured in all mice. Long axis (4.15±0.5mm) was almost 2 times longer than the LA (2±0.2mm). Its dimension and duct diameter increased during filling and decreased during emptying. The early inflow wave duration, peak velocity, and integral were all greater than those of late inflow wave (p<0.05).Three different PVs entering the LA cavity at different angles were imaged: a right superior (next to the LA septum and opposite to the LAA duct) , a rightA single pulsed Doppler wave was detected in all mice and, as it followed the ECG P wave, it was then labeled as A wave . A conveAt univariate analysis the strongest correlation was found between LV SV and LAA SV while at multivariate analysis the main independent determinants of LV SV were LAA SV and LV base descent. Significant multivariate and univariate linear regression are reported in Resin casts showed that the trabeculated LAA could be identified frontally, lying on the LV base. Removing the pulmonary artery, LA and its connections were visualized: antero-laterally with LAA, inferiorly with the LV through the mitral valve, and postero-medially with the three PVs (60° angle between each PV) . The twovs. 28±7.4% vimentin) and two layers of cardiomyocytes (58±10% vs 44±5.8% α-sarcomeric actin) crossing each other. Both structures showed a dense capillary network (19±8.9% vs 25±6% isolectin-B4) and few well-organised α-smooth muscle actin-positive cells (5.7±4% vs 3.5±1%) (Both LA and LAA consisted of cardiac fibroblasts (respectively 16±6.9%  3.5±1%) . Only miCardiac examination time was around 30–40 min, in all animals. Mean body weight was 26.13±1.59 g and 28±1.3 g for CD-1 and FVB mice respectively, whereas heart rate was 493±28 bpm and 541±29 bpm. Technically adequate images could be obtained in all animals. Left atrium was apically imaged with its connection with the appendage. Three PVs entering in LA were immaged in both strains. These data were also confirmed by gross macroscopic evaluation of the CD-1 and FVB hearts resin casts . All echvs 519±34 bpm). Compare to sham group the LV EF decreased significantly confirming systolic impairment. LA volumes and LAA long axis length increased significantly after 1 week to became prominent at 4 weeks post-MI while the LA-LAA duct fractional shortening gradually decreased showing reduced duct contractility. The LAA SV as well as LV SV were both unchanged. Data of stuctural and functional modification occurring at 1 and 4—weeks after MI induction data are shown in No significant difference was found in HR compare to baseline . Few histological studies describe in mice a single PV entering the LA chamber dorsally , 22; in ingle PV ; howeverIn this experiment the full set of LV parameters analyzed were comparable with those already reported , 24. A sMany studies reported echocardiography as a feasible and valid method to evaluate LV size and function in normal adult mice and in several mouse models of human disease, such as myocardial ischemia , cardiomWe describe a high-frequency ultrasound imaging protocol for the left venous reservoir that allows a comprehensive assessment of the C57BL/6N mouse cardiovascular phenotype. In contrast with humans, mice have a large and functionally important LAA, a disproportionately small LA, and three PVs entering the LA. Atrial relaxation is an important determinant of LV stroke volume variation, although most of LV filling is provided by atrial conduit function at the high heart rates observed in mice.Mitral valve flow, commonly used to evaluate LV diastolic function, is sensitive to heart rate and loading conditions; therefore we suggest the LA, LAA and PV function variables as a potential alternative. However further studies are needed to validate and develop our findings possibly supported by advances in imaging technology with improved spatial and temporal resolution.


Right ventricular (RV) dysfunction occurs in many cardiovascular conditions including pulmonary hypertension, congenital heart disease, and left-sided heart failure (HF), and its presence often alters patient management. Myocardial strain imaging has been used to assess left ventricular (LV) dysfunction; however, due to its thin wall, complex shape, and eccentric motion, strain analysis of the RV is more challenging and typically relies on manual delineation of tissue. Cine Displacement Encoding with Stimulated Echoes (DENSE) provides adequate image quality and spatial resolution to quantify RV function Figure , and theBuilding upon prior methods for LV analysis ,2, we deFor the 34 datasets that were analyzed, no manual editing of the automatically-propagated RV contours was needed. For the 18 subjects without heart disease, the mean contour strain Figure  for the The new DENSE analysis methods successfully propagated RV contours to sequential cardiac frames and computed RV contour strains. Using these methods, cine DENSE detected abnormal RV strain in HF patients compared to subjects without heart disease.NIH K23 grant HL094761 and American Heart Association Grant-in-Aid 12GRNT12050301.


Infarct size (IS) is one of the most important predictors of outcome after acute myocardial infarction (AMI) and can be detected in vivo with Late Enhancement CMR (LGE). However, the most consistent method of LGE quantification is yet to be determined.55 patients with reperfused, first acute ST-elevation AMI underwent LGE-CMR on a Philips Achieva 3T scanner at 1 week and 6 months post AMI. IS was expressed as a percentage of LV volume and measured at both time points using: manual planimetry, signal intensity threshold indicating LGE set at 2, 3 and 5 standard deviations (SD) above the remote myocardium and the full width at half maximum (FWHM) technique, which uses half the maximal signal within the scar as the threshold. The relationship between all measures of IS and final (6 month) LV ejection fraction (LV EF) and LV end diastolic volume (LV EDV) was evaluated using Spearman correlations.Mean age was 61±11 years and 63% were male. All techniques showed a consistent reduction in IS between the early and six month scans  with the difference of early-to-late mean IS in decreasing order of: 10.3% for FWHM, 10% for manual, 8.5% for 2SD, 4.6% for 3SD and 1.4% for 5SD - which showed least time-dependent variation.Inter and intra observer variabilities using Intra-class Correlation (ICC) were ≥0[ddawson1] .9 for all methods (p<0.001).As a general characteristic, all IS methods were better predictors of final LV EF than final LVEDV Tables  and 2. OFWHM, manual planimetry and 5SD had good agreement for final (6 month) IS, and 5SD showed least time-dependent variation. Manual planimetry is a better predictor of final EF when measured early whereas FWHM is a better correlate of EF when measured form late scans.This project was funded by a grant from the MRC(UK).


Myocardial T2- and T1-relaxation times were determined for every voxel. Abnormal voxels as defined by having T2- and T1-values beyond a predefined threshold  were highlighted and compared with LGE as the reference.Eight patients with AMI underwent CMR at 3 T acutely and after >3 months. Imaging techniques included: T2-relaxation times were present in the voxels with AMI  acute infarction only in half of the subjects. Abnormal T2-values were also present in subjects with CMI, thereby matching the chronically infarcted territory in some. Abnormal native T1 times were present in voxels with AMI in 5/8 subjects, but also remote from the infarcted territory in four. In CMI, abnormal native T1 values corresponded with infarcted voxels, but were also abnormal remote from the infarcted territory. Voxels with abnormal post-contrast T1-relaxation times agreed well with LGE in AMI and CMI.Abnormal T2- and T1-mapping with simple thresholds did not facilitate the discrimination of AMI and CMI.In this pilot-study, T Native T2-weighted imaging has been reported to detect myocardial edema [1-weighted late Gadolinium enhancement imaging (LGE) has been established to show necrosis and fibrosis. Recent studies demonstrated that the use of these techniques allows the differentiation of acute from chronic myocardial infarction  [2-weighted edema imaging [1- and T2-mapping were introduced to quantify the T1- and T2-relaxation times, which may be superior to the semiquantitative or qualitative image assessment used with conventional T2-weighted imaging [2- and T1-relaxation times as well as decreased post-contrast T1-relaxation times were reported for the infarcted areas [1-relaxation times were reported [2- and T1-mapping helps to differentiate AMI and CMI in the individual patient has not been examined in detail. We hypothesized that applying T1- and T2-mapping with simple thresholds based on reference values from healthy controls will discriminate AMI and CMI on an individual patient basis.Cardiovascular magnetic resonance enables myocardial tissue characterization by combining native and contrast-enhanced techniques with differences in TMI, CMI) . However imaging , 5. Rece imaging –8. For ped areas –12. In p1- and T2-relaxation times in healthy controls [Eight male patients (mean age 56 ± 13 years) underwent CMR within 9 ± 3 days (range 5-14 <space>days) after acute ST-segment elevation myocardial infarction and in a chronic state 139 ± 50 days (range 92–210 days) after the acute event. Repeated troponin measurements were not performed. But all patients remained clinically without onset of new cardiovascular symptoms or any cardiovascular event between both CMR scans. Patients’ characteristics are described in Table controls .Table 1PAll CMR examinations were performed with a 3 T MR system . The protocol was identical for patients and healthy controls. An integrated body RF coil was employed for RF transmission and a 32-channel cardiac RF coil for signal reception if not otherwise stated. ECG was used for cardiac gating/triggering.Steady-state free-precession (SSFP) 2D cine images were obtained during repeated breath-holds in three long axes and in a stack of short axes (SAX) covering the left ventricle (LV) to assess wall motion and for cardiac chamber quantification. Imaging parameters were as reported recently .2-weighted triple inversion recovery fast-spin-echo based technique: Imaging parameters were: repetition time = 2 × R-R-interval; TE = 43 ms; inversion time for fat (TIfat) = 170 ms, FOV = (340×255)mm2, matrix = 256×192, slice thickness = 10 mm, acquisition voxel size 1.3 × 1.3 × 10 mm3, BW = 235Hz/px, The integrated body RF coil was used for signal transmission and reception.Data were acquired in basal, mid-ventricular, and apical SAX planes in end-diastole using a breath-hold, black-blood, T2-prepared single-shot SSFP technique [2 preparation times were acquired in end-diastole within a single breath-hold. Imaging parameters were: TR = 2.4 ms, TE = 1 ms, FA = 70°, FOV = (340x278) mm2, matrix = 176×144, slice thickness = 6 mm, acquisition voxel size 1.9 × 1.9 × 6 mm3, BW = 1093Hz/px, GRAPPA acceleration factor R = 2. Images were motion corrected and a pixel-wise myocardial T2-map was generated. The principal accuracy of this technique has been demonstrated in previous phantom experiments [Data were acquired in basal, mid-ventricular, and apical SAX planes using a Technique  as descrechnique . Three S1-maps was started in every examination exactly 10 minutes after gadobutrol administration, ensured by a countdown and always beginning with the basal slice. Data were obtained in end-diastole using a cardiac-gated, SSFP-based Modified Look-Locker Inversion Recovery (MOLLI) technique [2, matrix = 156 × 208 to 168 × 224, slice thickness = 6 mm, acquisition voxel size 1.6–1.7 × 1.6–1.7 × 6 mm3, BW = 1045-1028Hz/px, GRAPPA acceleration factor 2. The hypersec adiabatic inversion pulse achieved an inversion factor of about -0.925. To generate a pixel-wise myocardial T1-map, single-shot SSFP images were acquired at different inversion times (pattern 3-3-5) and registered prior to a non-linear least-square curve fitting. The principal accuracy of this technique has been demonstrated in previous phantom experiments [Data were acquired in basal, mid- ventricular, and apical SAX planes before and after administration of 0.2 mmol/kg i.v. gadobutrol . The acquisition of the post-contrast Technique , 8. Imag3 [LGE imaging was performed 15 min after the administration of gadobutrol in the same planes as SSFP CINE imaging using a segmented inversion-recovery gradient-echo sequence. Imaging settings were as reported recently, with an acquisition voxel size 1.4 × 1.6 × 6 mm3 .42  as previously described [Defining the myocardium within the maps was done using CMRescribed . Much at2- and T1-relaxation times from a previous study in healthy controls [1 and T2 were defined. The cut-off for abnormal T2-times was >50 ms, native T1 > 1250 ms and post-contrast T1 < 350 ms. All myocardial pixels that were abnormal based on these thresholds were automatically highlighted in color in the corresponding map. The distribution of abnormal pixels was correlated with the LGE, which was regarded as the reference for the localization and extent of the infarct.Based on the 95 % tolerance interval of the Tcontrols , thresho2- and T1-mapping method, using the same MR scanner and coil as for the in-vivo exams. An agar-based phantom representing a range of T1 and T2 times was used. The T1-values were verified using an inversion recovery sequence with acquisition matrix 256x256, TR 15 s, 1 line/inversion, 90° FLASH readout, T1 range 200 ms–1090 ms. T1 values were calculated using a non-linear least square three-parameter fit. The T2-values were verified using a multi-echo spin echo (MESE) approach with matrix 256×256, TR 15 s, 1 segment, T2-range 16–235 ms. T2 values were calculated using a mono-exponential least square fit. For comparison, the T2- and T1-mappings technique as described for the in-vivo-measurements were applied. All phantom studies were performed with a simulated heart rate of 60 beats per minute. The signal-to-noise ratio (SNR) was estimated as the signal intensity from a manually drawn region of interest within the corresponding compartment of the phantom and the standard deviation of the signal intensity from a region of interest in the background. For T1, the last image of the series was used, for T2 the first.Phantom experiments were done to evaluate the accuracy of the T1- and T2-relaxation times close to the reference technique, with MOLLI underestimating the T1-times. This finding is in concordance with previous studies that tested the same techniques in phantom experiments [The results of the phantom experiments are shown in Table eriments , 7.Table2-weighted imaging during the initial scan. Figure 2- and T1-maps for each patient with all myocardial pixels that were beyond the predefined threshold highlighted in color. The absolute T2- and T1-relaxation times for every subject and every myocardial segment are given in Table All patients had evidence of AMI using LGE and T2-relaxation times corresponded well with the infarcted pixels as defined by LGE [subjects 2-values higher than the normal range were present, but did not match with the infarcted territory as defined clinically and by LGE. In CMI (where no increase of the T2-relaxation time was expected), pixels with T2-values higher than the normal range were present in all subjects. In some of them, these pixels matched with the chronically infarcted territory [subjects Only in half of the subjects with AMI, abnormal Tsubjects –3, 6. Insubjects , 5, 7, 8subjects –3, 6.1 times corresponded with acutely infarcted pixels in five out of eight subjects [subjects 1 values corresponded with infarcted pixels in most of the subjects [subjects 1 vales were also abnormal remote from the infarcted territory [subjects 1-relaxation times matched very well with LGE in all subjects both in AMI and CMI.Similarly, abnormal native Tsubjects , 6–8 in subjects –6, 8. Insubjects , 5–8, busubjects , 4, 6–8.1- and T2-relaxation times between infarcted myocardial segments and remote myocardium [2- or T1-maps if the localization of myocardial infarction is known. However, if the investigator is blinded to any clinical information, the discrimination of normal from abnormal myocardium as well as acutely from chronically injured myocardium solely based on T2- and T1-maps is challenging, as demonstrated in the present case series.Several reports described differences of the Tocardium , 11. It 2-maps and the native T1-maps. In CMI, pixels with elevated T2-value that would indicate edema appeared in the myocardium. And both in AMI and CMI, pixels with abnormal T1- and T2-values appeared also in the remote myocardium, which is supposed to have values widely within the normal range.The observed distribution of abnormal and normal relaxation times did not match closely with the extent of the myocardial lesion as defined by LGE, particularly in the T2- and T1-relaxation times within the myocardium may be attributed to several factors:i.)2- and T1-relaxation times that can be large in relation to the small difference between normal and abnormal myocardium [1-value in healthy controls in the midventricular portion of the LV was reported to range from 1005 ms to 1296 ms at our institution and other sites report mean values of 1169 ± 73 ms mixed standard deviation [1-value of 1257 ± 97 ms for acutely infarcted segments compared to 1196 ± 56 ms for normal unaffected segments in the same subject [2-values in healthy controls ranged from 38 to 59 ms at 3 T and 46 to 69 ms in a study at 1.5 T [2 value of 60 ms has been reported as an adequate cutoff to determine active myocarditis [1-values in the lower range of the reference, the T1-values may still be within the normal range even after an infarct-related increase of 150 ms. This concept certainly needs further analysis in studies with larger samples. The large normal range is presumably attributable to physiological variations as well as to many other influencing factors like a potential heart-rate dependency of some acquisition methods and partial volume effects as outlined below. A detailed description of factors influencing the precision and accuracy of T1-measurements is available elsewhere [1-maps in CMI. CMI was defined as using the mean ±5 standard deviation criterion relative to the respective reference regions of interest. Using this approach, native T1-maps and LGE images showed a close agreement to determine regions with CMI [A challenge of this mapping approach is the inter-individual scatter of myocardial Tocardium : The noreviation , 13. On at 1.5 T . On the carditis . Therefolsewhere . An altewith CMI .ii.)2- and T1-values and are misleadingly classified as abnormal. Even though all attempts were made to minimize this error by drawing the contours exactly within the compact myocardium, a significant influence of partial volume effects still has to be assumed. Higher spatial resolution may solve this problem in the future, and single pixels with abnormal values located at the edge of the myocardium have to be interpreted with caution.Another aspect is the influence of partial volume. Pixels that include blood or epicardial fat quickly reach pathologic Tiii.)2- and T1-values. But generally, both T2- and T1-maps have been reported to be affected by microvascular obstruction leading to “hypoenhancement” within the “hyperenhanced” acute infarction [2- and T1-maps.In this case series microvascular obstruction was detected by LGE images in only one subject, therefore it does not explain the frequent mismatch between the thresholding and the expected distribution of abnormal Tfarction . TherefoThis mismatch between the results of the thresholding and the expected distribution of T1-values by affecting the relaxation between the MOLLI segments. In this study, the heart rate ranged from 50 to 83 bpm. Together with the small sample size (n = 8), these may be the major factors for data overlapping. Using a different mapping sequences with less heart-rate sensitivity, such as the 5(3 s)3 MOLLI variant, could have resulted in an improved performance of T1-mapping [The heart rate can influence T-mapping . A limit-mapping , 21.2- and T1-maps with a simple threshold-based analysis did not facilitate the detection of myocardial infarction and the discrimination of AMI and CMI in the individual patient. Despite all enthusiasm for myocardial mapping, improvements in the technology as well as additional concepts for discriminating normal from abnormal myocardium may be necessary.This pilot study demonstrated that TInformed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee .Not applicable.The datasets supporting the conclusions of this article, including images, contours and databases, are stored on the institutional file server (smb://fs-cmrt.ecrc-berlin.com). The data will not be shared publicly at the current stage, as this study is part of a multi-element project that is still ongoing. Of course, data will be shared on request.


The sequence of a multiecho gradient recalled echo (GRE) T2*-weighted imaging (T2*WI) is a relatively new magnetic resonance imaging (MRI) technique. In contrast to T2 relaxation, which acquires a spin echo signal, T2* relaxation acquires a gradient echo signal. The sequence of a GRE T2*WI requires high uniformity of the magnetic field. GRE T2*WI can detect the smallest changes in uniformity in the magnetic field and can improve the rate of small lesion detection. In addition, the T2* value can indirectly reflect changes in tissue biochemical components. Moreover, it can be used for the early diagnosis and quantitative diagnosis of some diseases. This paper reviews the principles and clinical applications as well as the advantages and disadvantages of GRE T2*WI. The sequence of a multiecho gradient recalled echo (GRE) T2*-weighted imaging (T2*WI) acquires a gradient echo signal, and depending on the technical characteristics, there are some advantages of this technique. On the one hand, the sequence of GRE T2*WI requires high uniformity of the magnetic field, independent of the paramagnetic substance or diamagnetic substance. With changes in the uniformity of the magnetic field, the sequence is sensitive for detection and can improve the detection rate of small lesions . On the The principles of multiple echo GRE T2*WI sequence are similar to that of conventional T2-weighted imaging (T2WI) [The T2* value is a quantifiable indicator of GRE T2*WI that is related to the T2 value. It is presented in the following equation, which can be expressed as the interrelationship between T2 and T2* :(1)1T2∗Note. γ represents the magnetogyric ratio and ΔBinhom represents the magnitude of the magnetic field changes. Assuming that the applied static magnetic field is uniform (B0 = 0), then the T2* term is only affected by the “γ*ΔBinhom,” which is influenced only by local susceptibility fields. Thus, the T2* term is affected by the local susceptibility fields. This is the theoretical basis by which the GRE T2*WI can detect the smallest changes in uniformity in a magnetic field [Compared with T2 relaxation, which is based on the principle of the sequence of GRE T2*WI, the decay of T2* relaxation was added as a factor of the main magnetic field. On the one hand, for the same tissue, the decay time of T2* relaxation is shorter compared to the T2 relaxation. On the other hand, the sequence of GRE T2*WI requires high uniformity of the magnetic field. GRE T2*WI can detect the smallest changes in uniformity in the magnetic field and can improve the detection rate of a small lesion, such as the paramagnetic substance deposition, similar to iron deposition .T2* relaxation acquires the gradient echo signal. First, it acquires a series of T2* images using the same TR scan time and a series of TE times. Subsequently, the T2* value of each pixel was calculated by selecting the appropriate regions of interest (ROI). Finally, T2* relaxation constitutes the color gradation, which can be quantitatively analyzed, and it is also called the T2* relaxation time figure or T2* map. This process is completed using postprocessing software directly after scanning.Iron is present throughout the human body in tissue cells and is indispensable to human survival. However, the abnormal deposition of iron can disrupt the balance of iron homeostasis in a number of tissues. Iron deposition is common in clinical diseases, such as chronic liver disease , 10 and As a quantitative indicator, the T2* value is widely used in clinical applications. In addition, the measurement of the T2* value of tissues on the GRE T2*WI can indirectly reflect the iron content of the tissues, which demonstrates two advantages: noninvasiveness and rapidness. The applied MRI GRE T2*WI technique has been previously validated for the quantitative determination of changes in tissue biochemical components . The incAlthough the determination of the liver iron concentration (LIC) is the gold standard to evaluate the body iron load conditions via liver biopsies, this examination is invasive and is limited by its sample size and thus is not conducive for the expansion of clinical application. Queiroz-Andrade et al.  studied Chronic anemia can cause iron deposition in the heart. In 2012, Barzin et al.  reportedGRE T2*WI can also evaluate the iron deposition caused by some nervous system diseases, such as brain iron deposition in Alzheimer's disease. Qin et al.  quantitaMihai et al.  studied GRE T2*WI may also detect disease progression and may be combined with other related indicators to evaluate the changes in the organ functional state, such as the T2* value, which can be combined with P-wave changes to assess the myocardial iron load status . In someCerebral microbleeds (CMBs) are commonly and frequently encountered in small vessel diseases among elderly people with hypertensive arteriopathy and cerebral amyloid angiopathy . CMBs arThe intracranial manifestation of blood on an MRI is complicated and is dependent on its evolution over time and its location –30. OxygOn the basis of imaging characteristics, the GRE T2*WI can diagnose microbleeds early, which is more conducive for clinical treatment. In 1996, Patel et al.  studied GRE T2*WI has a higher detection rate than conventional MRI sequences and CT examinations for cerebral hemorrhages, taking advantage of its ability to detect small bleeding lesions . CompareThe intervertebral disc mainly consists of the nucleus pulpous, annulus fibrous, and cartilage endplate. Its degeneration is affected by robust factors and physiological degeneration. Degeneration can result in altered biochemistry, thereby affecting the mechanical competence , 40. TheGRE T2*WI can provide a new examination method for the early diagnosis of degenerative diseases caused by changes in the biochemical composition and lack of functional changes in early disease . It provOsteoarthritis is common articular cartilage degeneration that is accompanied by changes in the chronic degeneration of the subchondral bone joint and surrounding tissue. This type of degenerative change is most common in the knee joint. In addition, early changes in lesions include changes in the collagen fiber , which rMicrodamage in the bone and joint is accumulated due to high-intensity training or normal daily activity , 52. TheGRE T2*WI is able to detect microdamage that causes changes or imbalances in the tissue biochemical composition. It has a high spatial resolution image , 56. WheGRE T2*WI can be applied in tumors based on its high spatial resolution and sensitivity in nonhomogeneous tissues in the magnetic field.Regarding its high spatial resolution, T2*WI is conducive in revealing the tumor mass and its adjacent invasion, such as a spinal tumor. Spinal tumors always invade accessories of the vertebral body, and GRE T2*WI shows a strong advantage in the imaging of accessories, which are similar to small lesions. The tumor has three clinical types, osteolytic type, osteoblastic type, and mixed type, and different tumors have different compositions oftumor body based on its pathology. The T2* value of the tumor mass can be quantitatively measured on the GRE T2*WI sequence, which may identify the differentiation of the tumor and can detect the paramagnetic substance, similar to the same type of tumor with a hemorrhage or with iron deposition.Regarding its sensitivity for nonhomogeneous tissues in the magnetic field, the T2*-weighted first-pass perfusion imaging (T2*-PWI) and blood oxygenation level dependent (BOLD) imaging are both based on the GRE T2*WI technique, which are referred to as functional magnetic resonance imaging (fMRI) . As noniT2*-PWI is widely used in breast tumors Figures  and 8. BIn the same respect, when the oxygenated hemoglobin is deoxygenated, it results in a significant magnetic field inhomogeneity in the vicinity . GRE T2*GRE T2*WI is a fast, convenient, noninvasive, and feasible technique that demonstrates obvious advantages in clinical applications. First, selecting shorter TR and TE can accelerate the pace of imaging and shorten the time of data collection. Second, in contrast with T2 relaxation, which acquires a spin echo signal, T2* relaxation acquires a gradient echo signal. Thus, in the echo formation process, without the phase reunion by the 180° focused pulse of SE sequence, GRE T2*WI is more sensitive to the nonuniformity of the magnetic field compared to conventional MRI scanning. Thus, the sequence of GRE T2*WI requires high uniformity of the magnetic field and can detect small changes in the uniformity in the magnetic field to improve the detection rate of small lesions . Thus, iHowever, currently, GRE T2*WI has some limitations that need to be improved in the future. Because the gradient echo sequence often uses the low-angle shot, the echo amplitude is often less than that of the SE sequence; thus, the GRE sequence image inherent signal-to-noise ratio is lower compared to the SE sequence. Therefore, it may be affected by the respiratory mobility in an abdomen MRI examination. In the postprocessing measurement, the results will be different due to the selection of regions of interest (ROI). In addition, the choice of parameters is important. For example, the TE echo time cannot be too long or too short. To properly extend the TE, we can achieve good T2* imaging, but an extension of TE must be under control. It causes a decrease in the signal intensity of the image and a more obvious deformation for unlimited extension. Thus, we should emphasize these related factors, which will affect the T2* value. Ultimately, the T2* value will be measured and will be available and convincing.GRE T2*WI appears to be a promising MRI sequence for iron deposit and microbleeds. GRE T2*WI also facilitates the study on degenerative diseases, microdamage, and tumors. In this paper, we highlight the clinical applications of GRE T2*WI. As a noninvasive, reliable, sensitive MRI technique, GRE T2*WI not only improves the detection rate of small lesions but also provides physiological or pathological status indicators in the clinic for the quantitative evaluation of certain organs or tissues. GRE T2*WI is more useful for the diagnosis of a disease when combined with conventional MRI sequences, and GRE T2*WI will be widely used in clinical applications.


Pulmonary Hypertensive (PH) is an incurable , and often fatal disease. Currently a patient's treatment requires periodic office visits to evaluate their progression of right heart failure and increased pulmonary arterial pressures associated with this disease. Invasive and serial right heart catherization (RHC) is the current accepted method for assessing pulmonary arterial pressures and objectively tracking a patient over time. There is an obligate morbidity and mortality associated with serial RHC's. Further, with an estimated >1000 new diagnoses yearly and their requirement for serial RHC's, a novel approach to measuring pulmonary arterial pressures that might have added utility beyond a simple manometer is warranted.Use of a unique implantable device, CardioMEMs®, recently approved by the FDA (Feb 2014), permits real time evaluation of a patient's pulmonary pressures on a minute-by-minute basis. Novel integration of CMR data with the manometer capacity permits comparison and tracking of pulmonary pressure changes under certain applied stressors.Patients with the CardioMEMs implant, inserted via a RHC in the left pulmonary artery branch, are evaluated following a complex, derived protocol schema Figure .Direct comparison of data acquired from the baseline, nitric oxide (iNO), dobutamine and volume challenge were compared to determine the impact various ‘stressors' had on the right ventricle/pulmonary arteries via volume, area, flow change and the direct pulmonary pressure measured with the CardioMEMs® implant. This novel approach allows us to obtain immediate pulmonary pressure monitoring and comparative CMR data within a contracted time. A key question is: How do we obtain RV end-diastole volume rapidly? We measure the stroke volume (SV) from the MPA using phase contrast velocity imaging and the LVEF estimated from the 4 chamber (HLA)-SSFP using the Sandler-Dodge formula. Thus, Rearranging this formula, we have: (this is a key factor making the dynamic imaging faster). This now provides a new opportunity for sophisticated analytics Figure .This CMR and CardioMEMs® showed strong pressure correlation ( 0.91).A comprehensive evaluation of the RV/PA system is possible using CMR and the implanted CardioMEMs® pressure measuring device. Given the many stressors, it now possible to use CMR in a most efficient manner to obtain heretofore invasively-mandated clinical information in completely non-invasive manner.Internal funding.