The present study with cardiac magnetic resonance (CMR) imaging is the first to use a contrast-enhanced approach to assess cardiac involvement, including tissue characterisation of the LV wall.In chronic fatigue syndrome (CFS), only a few imaging and histopathological studies have previously assessed CMR measurements of 12 female CFS patients were compared with data of 36 age-matched, healthy female controls. With cine imaging, LV volumes, ejection fraction (EF), mass, and wall motion abnormalities were assessed. T2-weighted images were analysed for increased signal intensity, reflecting oedema (i. e. inflammation). In addition, the presence of contrast enhancement, reflecting fibrosis , was analysed.p < 0.01), end-diastolic diameter , as well as body surface area corrected LV end-diastolic volume , stroke volume , and mass  were significantly lower in patients. Wall motion abnormalities were observed in four patients and contrast enhancement (fibrosis) in three; none of the controls showed wall motion abnormalities or contrast enhancement. None of the patients or controls showed increased signal intensity on the T2-weighted images.When comparing CFS patients and healthy controls, LVEF (57.9 ± 4.3 % vs. 63.7 ± 3.7 %; In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function. The presence of myocardial fibrosis in some CFS patients suggests that CMR assessment of cardiac involvement is warranted as part of the scientific exploration, which may imply serial non-invasive examinations. Chronic fatigue syndrome (CFS) is relatively common with an estimated worldwide prevalence of 0.4–1 % . VariousCardiac magnetic resonance (CMR) imaging may be useful for the non-invasive assessment of cardiac involvement in patients with CFS. This technique permits the examination of cardiac morphology and function, and even tissue characterisation of the LV wall to identify oedema or myocardial fibrosis – the consequences of myocardial inflammation . ContrasTherefore, in the present study with CMR imaging in patients with confirmed CFS, we used a combined approach of cine, contrast-enhanced, and T2-weighted imaging to assess LV tissue characteristics in addition to cardiac dimensions and function. Data from 12 patients with CFS were then compared with data from an age- and gender-matched group of 36 healthy controls, who were examined with the same imaging protocol.We studied 48 females with a combined CMR approach. A consecutive series of 12 patients with CFS were recruited from a specialised CFS centre, to be examined with CMR. The diagnosis of CFS was based on the revised case definition by Fukuda et al.  after ruCMR examination was performed on a 1.5-T whole body scanner  using commercially available cardiac CMR software. For signal reception, a five-element cardiac synergy coil was used. Electrocardiogram triggering was done with a vector electrocardiogram setup. Subjects were examined in the supine position. Morphological images in the standard views were acquired by using fast field echo cine images .Subsequently, a breath-hold, black-blood, T2-weighted double-inversion recovery sequence with a fat-saturation pulse was performed in 8–10 short-axis slices, with the following parameters: repetition time 1800–2400 ms; echo time 80 ms; matrix 256 × 256; field of view 32–40 cm; slice thickness 12 mm; number of excitations 1. Myocardial scar was assessed on contrast-enhanced multislice standard views, obtained approximately 10 minutes after intravenous bolus injection of 0.2 mmol gadolinium per kilogram body weight . A three-dimensional Turbo Field Echo inversion recovery T1-weighted sequence was used with the following parameters: repetition time 4.0 ms; echo time 1.3 ms; flip angle 15°; inversion time individually optimised to null myocardial signal ; matrix 157; slice thickness 10–12 mm).CMR data were analysed on a workstation using dedicated software for cardiac analysis . Left ventricular end-diastolic (ml) and end-systolic volumes (ml), stroke volume (ml), LVEF (%) cardiac output (l/min), and end-diastolic wall mass (g) were calculated from contiguous short-axis loops by segmentation of endocardial and epicardial borders on each frame. Papillary muscles were regarded as part of the ventricular cavity.The left ventricular wall regions were divided into 17 segments according to a standardised myocardial segmentation model . Normal The contrast-enhanced images were independently evaluated by three experienced observers, who were blinded to patient/control characteristics and to the evaluations of each other. Contrast enhancement was defined as a zone of hyperenhancement on the late contrast-enhanced images . The studies were considered abnormal when at least two independent observers described the same abnormalities with agreement in both the presence of contrast enhancement and its location (same segment), reproducible in more than one contiguous slice and in more than one projection.p value < 0.05 was considered statistically significant.Continuous variables had a normal distribution and were expressed as mean ± standard error. Categorical data were expressed as frequencies and percentages. To compare our CMR findings in CFS patients, we used age- and gender-matched controls. Student’s t‑test and the Mann-Whitney U test were used to compare continuous variables, and chi-square test and Fisher’s exact test were used to compare categorical variables. A Twelve female CFS patients and 36 age- and gender-matched controls were analysed in this study. The patients and controls were relatively young (36 ± 13 vs. 29 ± 8 years). All but one CFS patient had a history of infectious mononucleosis disease with IgG antibodies to Epstein-Barr virus or human cytomegalovirus capsid antigen; all of these eleven patients had antibodies to Epstein-Barr virus nuclear antigen. Demographics and baseline characteristics did not differ between both groups , end-diastolic diameter (44 ± 3.7), as well as body surface area corrected end-diastolic LV volume , LV stroke volume , and LV wall mass  were significantly lower than age- and gender-matched controls. Mild wall motion abnormalities were observed in four CFS patients in the basal and/or mid inferoseptal wall, leading to a wall motion score index of 0.02 ± 0.04; none of the controls showed wall motion abnormalities. Myocardial damage (i. e. fibrosis), as indicated by the presence of contrast enhancement, was observed in three patients who showed such lesions in the basal inferoseptal, septal, and anteroseptal midwall segments. An example is presented in Fig. The complete CMR examination protocol was followed in all CFS patients and controls; image sequences of a high quality could be obtained in all cases. CMR data of our CFS population are presented in Table The present CMR study used a combined CMR approach of cine, contrast enhancement, and T2-weighted imaging to assess cardiac dimensions, function, and myocardial tissue characteristics in patients with confirmed CFS and healthy controls. Our data demonstrate a left ventricular size, mass, and function that were lower than in age- and gender-matched controls, although still within the normal range. Theoretically, this difference could partially explain some mild fatigue in these patients, but it may also be suggested that the reduction in LV dimensions and function is the result of reduced physical activity. In this respect, Takenaka et al. found significantly reduced ventricular diastolic dimensions and cardiac output after 20 days of bed rest . These fRecently, Hollingsworth et al. investigated geometrical and functional LV parameters with CMR, including strain analysis, in 12 CFS patients and 10 healthy controls . Althougisolated midwall contrast enhancement  [In the present study, we also performed contrast-enhanced imaging in both CFS patients and a control group. We found no increase in signal intensity (i. e. oedema) on the T2-weighted CMR images, which demonstrates that our patients did not suffer from an active state of viral myocardial infection at the time of CMR. Midwall contrast enhancement, a finding that has frequently been observed in patients with histopathological evidence of chronic active or borderline myocarditis , was fou oedema)  as obserPrevious myocarditis CMR studies demonstrated a relation between the type of virus and the pattern of myocardial damage . AccordiIn the present study, in patients with CFS, diagnosis was based on the diagnostic criteria of Fukuda et al. . Future We did not perform serial serological tests or myocardial biopsies. It would have been ideal to correlate CMR findings with targeted endomyocardial biopsies. However, this would have involved an invasive procedure without a direct therapeutic implication. In patients with myocarditis, the value and interpretation of contrast enhancement can be difficult because of heterogeneous scar distribution and the generally lower signal intensities , 24–26. In patients with chronic fatigue syndrome, CMR demonstrated relatively lower dimensions and a mildly reduced function of the left ventricle. The presence of myocardial fibrosis in some CFS patients suggests that further assessment of cardiac involvement may be warranted as part of a further scientific exploration of the CFS disease. This may imply serial non-invasive examinations with CMR.


However, applying a general calibration factor derived from in vitro experiments can lead to inaccurate and largely varying SvO2 estimates in the target population. We aim to show that based on the Luz-Meiboom relation 1/T2 = 1/T2o + Hct(1-Hct) τex[(1-%SO2/100)αω0]2(1-2*τex/τ180 tanh(τ180/2*τex))[2 can be determined from multiple T2 maps, each acquired at a specific inter-echo spacing (τ180).Dependence of blood T2 on O2 saturation has led to non-invasive MRI-based techniques for determining venous O2 saturation (SvO0/2*τex)), individ180=10, 12 and 15 ms, TR >3000 ms, FA = 400, 2.8 × 2.8 × 10 mm3, 2NEX, free breathing) were acquired in seven volunteers (age: 32.6 ± 12.2 yrs) on a 3T MRI system . T2 preparation involved an MLEV refocusing pulse train with 2, 4, 8 and 12 composite pulses. Venous and arterial blood T2 were measured in each map in an ROI in the ventricles. For each subject, the multiple τ180 measurements were processed jointly to estimate SvO2 along with other nuisance parameters (T2o and τex) via constrained nonlinear least squares fitting in Matlab . The values of hematocrit (Hct), arterial O2 saturation (SaO2), and α were fixed at 41%, 97%, and 0.4 ppm respectively.Three T2 prepared SSFP quantitative T2 maps .Figure 180. We have shown that if these parameters are known, SvO2 can be non-invasively determined from arterial and venous blood T2 maps acquired at multiple τ180. This provides in-vivo, patient-specific calibration, and may reduce the uncertainty and error in SvO2 estimation from applying a general calibration factor to the entire patient population. Although in this preliminary study we have assumed a fixed Hct and SaO2 for all subjects, greater accuracy may be achieved by measuring individual Hct and SaO2 from a blood sample and a pulse oximeter respectively. Nevertheless, our results show that the proposed approach is feasible, giving reasonable SvO2 estimates. Future studies will involve validation of the single assumed parameter, α, in the T2-SO2 model, optimization of the set of τ180 times, and further evaluation of the accuracy and precision of T2 mapping in determining blood O2 saturation. This would lead to the development of rapid, accurate, non-invasive, in-vivo quantification of SvO2 from T2 maps, which would be highly beneficial for heart failure and congenital heart disease patients.The measured T2 of blood is dependent on Hct, O2 saturation, and τ


Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis.Eighty-two patients  and 20 healthy subjects  were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves.P = 0.001) and ECV  compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E’ and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0%  1.751–13.179, P = 0.002) and global LGE  were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality .The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor. Immunoglobulin light chain (AL) type amyloidosis is characterized by monoclonal plasma cells and the deposition of insoluble fibrils formed by immunoglobulin light chains in various organs . In apprCardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) is the most commonly performed non-invasive protocol for myocardial tissue characterization in a wide spectrum of cardiomyopathies. A typical pattern of global, predominately subendocardial LGE, serves not only as a diagnostic marker for cardiac AL amyloidosis but also as a prognostic marker for mortality –14. HoweMyocardial CMR T1 mapping methods are used for native  and for post-contrast T1 measurements. In combination with the hematocrit, pre- and post-contrast measurements enable the quantification of the extracellular volume fraction (ECV). Native myocardial T1 values reflect a composite signal from both the intracellular (predominantly myocytes) and extracellular compartments –20. PrevThis prospective study was approved by the Institutional Ethnics Committee for Human Research at Peking Union Medical College Hospital . All participants were required to provide written informed consent prior to recruitment. AL amyloidosis patients who were referred for CMR imaging at Peking Union Medical College Hospital between August 1, 2014 and August 31, 2016 were included in the study. Approximately 20% of the patients who had contraindications either to CMR imaging  or contrast administration  were excluded.n = 29), myocardium (n = 19), bone marrow (n = 7), fat (n = 7), tongue (n = 7), liver (n = 4), upper gastrointestinal tract (n = 3), buccal mucosa (n = 3), lung (n = 1), rectum (n = 1) and skin (n = 1). All patients underwent laboratory examination of the cardiac biomarkers Troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), serum immunoglobulin free light chain difference (dFLC) at baseline and were categorized based on revised Mayo Stage published in 2012 [Eighty-two AL amyloidosis patients  were consecutively recruited. All patients had biopsy evidence of AL amyloidosis with positive Congo red stain and light chain deposition confirmed by immunohistochemistry, immunofluorescence or mass spectrometer. The assays were performed in the tissues listed as follows: kidney  with normal CMR imaging results were recruited, who had neither history nor symptoms of cardiovascular disease or diabetes mellitus.CMR was performed on a 3 T whole-body scanner . The system is capable of operating at a maximum slew rate of 200 mT/m/ms and a maximum gradient strength of 45 mT/m. An 18-element body matrix coil and a 32-element spine array coil were used for data acquisition. A four-lead vector cardiogram was used for ECG gating.Two-dimensional (2D) scout images in transversal, coronal and sagittal views were first acquired for localization of the heart. The cine images were acquired with an ECG-gated 2D balanced steady-state free precession (bSSFP) sequence during multiple breath holds. To evaluate cardiac motion and function, two-, three-, and four-chamber long-axis and 10–12 short-axis slices covering the LV were acquired. The key parameters were as follows: repetition time (TR)/echo time (TE), 3.3/1.43 msec; flip angle (FA), 55°–70°; voxel size, 1.6 × 1.6 × 6.0 mm; temporal resolution, 45.6 msec; bandwidth, 962 Hz/pixel. Native and 15–20 min post-contrast T1 mapping were acquired using a MOLLI sequence in identical imaging locations, including a four-chamber long-axis slice and three short-axis slices  . AcquisiCMR images were independently analyzed by two experienced radiologists. The LV LGE pattern was classified into three groups referred to Araoz Criteria  and MoonCardiac function, native T1 and ECV were measured semi-automatically using a dedicated CMR software cvi42 . Standard parameters of cardiac structure  and ventricle ejection fraction were measured by contouring the endocardium and epicardium on long-axis and short axis cine images at the end-systolic and end-diastolic stage. Native T1 and ECV of the 16 American Heart Association (AHA) segments and global LV were measured, by contouring the endocardium and epicardium and indicating the inter-ventricular septum on pre-contrast and post-contrast T1 mapping images with indexing for the hematocrit. Global LV native T1 and ECV were used for further analysis. The average values of native T1 and ECV measured by the two radiologists were used.A physician blinded to the results of CMR imaging conducted the telephone and clinical follow-up each month. Unless the outcome was death from any cause, patients were censored at the end of the study. If patients were lost to follow-up, their last clinic visit record was used. A follow-up CMR scan was performed after a complete standard course of chemotherapy, with an interval of about approximately one year.P < 0.05.Statistical analysis was performed using SPSS Statistics  and R programming language for statistical computing . The agreement between two observers was assessed using the interclass correlation coefficient. Correlation between native T1 and ECV with continuous variables or categorical variables was assessed using the Pearson’s r correlation or Spearman ρ correlation, respectively. Comparison between groups and the control was performed by one-way analysis of variance (ANOVA) with post-hoc Bonferroni correction. Statistical significance was defined as Survival was evaluated with Cox proportional hazards regression analysis, providing estimated hazard ratios (HR) with 95% confidence intervals (CI) and Kaplan-Meier curves. All variables were first analyzed with univariate Cox regression. Multivariate models were then used to evaluate the independent prognostic value of native T1, ECV or LGE above other clinically and statistically significant covariates. The median value of native T1 and ECV was used as cut-off values. The Harrell’s C statistic was calculated for different models.Table P = 0.024) and NT-proBNP  compared to healthy controls. There were 22 (27%), 18 (22%), 29 (35%) and 13 (16%) patients in Mayo Stage I, II, III and IV, respectively. Table P = 0.023), NYHA Classification , log (cTnI) , log (NT-proBNP) , Mayo Stage  and E/E’ .All continuous variables were normally distributed (Kolmogorov-Smirnov test) and presented as the mean ± SD, except for cTnI, NT-proBNP and dFLC, which were log transformed for bivariate testing and presented as medians (quartiles 1-quartiles 3). As shown in Tables 2 vs. 74.5 ± 17.1 ml/m2, P = 0.001) and LV ejection fraction (LVEF) , as well as an increase in indexed LV mass index  and inter-ventricular septal thickness  compared to healthy controls. Univariate analysis showed that LVEF  and septal thickness  were significant predictors of mortality.As shown in Tables P = 0.001) and ECV  compared to healthy controls. The intra-observer and inter-observer variabilities as well as native T1 reproducibility are shown in Table Representative examples of LGE pattern, native T1 and ECV values from a healthy subjects and AL amyloid patients with different disease burdens are shown in Fig. P = 0.001) and global LGE  were significantly prognostic for mortality. Patients categorized by median native T1 (1456 ms) did not differ significantly in survival probability (Tarone-Ware P = 0.069)  and the other with no/patchy LGE . In subgroups with the same LGE pattern, patients with ECV < 44.0% and ECV ≥ 44.0% differed significantly in survival probability (log rank P = 0.029), as shown in Fig. Univariate analysis showed that both ECV ≥ 44.0%  underwent follow-up CMR scans. The median interval between baseline and follow-up CMR scans was 12 months. All subjects completed a standard course of BCD chemotherapy and achieved a complete response (CR) or very good partial response (VGPR). For the patient with no LGE, the dynamic changes of LGE, native T1 and ECV are shown in Fig. P = 0.002) in a multivariate Cox model correcting for age  and septal thickness . The Harrell’s C statistic was 0.62. Global LGE  was significantly prognostic for mortality in a multivariate Cox model correcting for NYHA  and septal thickness . The Harrell’s C statistic was 0.60.ECV and LGE were analyzed in separate multivariate Cox models because they had a correlation value ρ of 0.889. As shown in Table P = 0.008) and global LGE  were independently prognostic for mortality, while median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware P = 0.108). In the 59 patients received therapy during the follow-up, 46 (78%) patients were alive. ECV ≥ 44.0%  and global LGE  were prognostic for mortality in univariate Cox model, but not prognostic in any multivariate Cox model. Median native T1 was not prognostic for mortality (Tarone-Ware P = 0.105).Survival analysis separated by therapy status were performed. In the 71 patients without therapy at baseline, 52 (73%) patients were alive at the time of last follow-up. As shown in Table In this study, we examined the prognostic value of CMR ECV, LGE and native T1 in a Chinese population with AL amyloid. To the best of our knowledge, this is the first study to concurrently assess the prognostic value of T1 mapping parameters with LGE in AL amyloid. Our findings indicate that, while ECV and LGE functioned as independent prognostic factors for mortality in AL amyloid patients, native T1 did not display prognostic value. We also showed that in subgroups with the same LGE pattern, ECV remained prognostic.We found AL amyloid patients with no LGE demonstrated increased native T1 and ECV, highlighting the importance of native T1 and ECV over LGE in early detection of myocardial involvement in this disorder. In agreement with other studies , 12, we The current study is also the second overall study that focuses on the prognostic value of T1 mapping parameters in AL amyloid. A previous study demonstrated the prognostic value of native T1 and ECV for mortality using a 1.5 T scanner with a shMOLLI sequence , but LGEMoreover, we also found that native T1 did not act as a prognostic factor, which is controversial with previous study. Previous studies have shown variations in ECV values using different scanning sequences including MOLLI and shMOLLI , and varECV calculation requires the administration of an IV contrast agent. However, renal function impairment is often seen in AL amyloid patients, since the kidney is one of the most commonly involved organs , 2. ThisOur study has several limitations. One is the short follow-up with a median time of 8 months and a relatively low event proportion of 25.6%. Another limitation is that we do not have additional parameters to fully characterize the diastolic function. The third limitation is about the therapy status of the patients at baseline and during the follow-up, given the cardiotoxic effects of chemotherapy agents may be confounding factors. Besides, we found increased native T1 and ECV values in patients with no LGE, but only one such patient underwent myocardial biopsy verifying the result. Thus ours, like most studies in this area, suffer from the lack of diagnostic pathology.For myocardial tissue characterization, while LGE is a classic and most commonly performed parameter, ECV is a recently developed quantitative CMR parameter. The current study is the first to compare the prognostic value of T1 mapping parameters with LGE in AL amyloid. During a short follow-up interval, we showed that both ECV and LGE were promising prognostic factors for mortality in AL amyloid. Further, in patients with the same LGE pattern, ECV remained prognostic, suggesting the merit of using T1 mapping scanning in conjunction with LGE in this population. Native T1, however, was found to be not as equally prognostic as ECV or LGE. Thus, for suspected AL amyloid patients without contraindications, it is better to perform contrast enhancement scanning.


PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR.Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2–3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow‐up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end‐diastole to end‐systole in the cardiac short axis and long axis.Piglets were divided into a control . Furthermore, a compensatory increase in septal contribution to RVSV was observed . The left ventricle (LV) showed counter‐regulation with an increased longitudinal LVSV. Changes in RV longitudinal function were reversed by PPVR.PR resulted in a lower longitudinal contribution to PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients.These findings suggest that  Ventricular function is a complex process, which is comprised of multiple sequential and parallel contractile events. In a simplified model, one can distinguish between a longitudinal – that is the movement of the atrioventricular plane (AVP) towards the apex of the heart – and a radial – that is the aggregate of the concentric contractions of both the lateral wall and the septum in the short‐axis plane – contribution to cardiac pumping. We have demonstrated that on average, 60% of left ventricular pumping and 80% of right ventricular pumping are attributable to longitudinal contraction by means of AVP displacement in the healthy human heart.It has become apparent that the analysis of the longitudinal contractile function is of clinical relevance in the assessment and prediction of cardiac pathologies, such as myocardial infarction, dilated cardiomyopathy, congenital heart disease and cardiac arrhythmias.The pathophysiological changes underlying cardiac dysfunction in patients with Tetralogy of Fallot  have been the subject of ongoing investigation, as the optimal timing of follow‐up surgeries in these patients remains to be clearly defined.et al. recently reported impaired right atrial filling, which is functionally linked to AVP displacement, in TOF patients.The development of tools to further characterize cardiac function with the aim to aid in the clinical management of TOF patients with PR is therefore of importance and has been explored in several studies. For example, investigators observed reduced right ventricular AVP movement in patients with PR following corrective surgery for TOF.To address this controversy, the aim of this study was to investigate the effects of isolated PR on longitudinal and radial contributions to ventricular pumping in a porcine model. A better understanding of the pathophysiological changes underlying PR may lead to improved risk stratification and may aid in the clinical management of TOF patients with regard to timing of pulmonary valve replacement.To quantify the degree of PR, phase‐contrast imaging was conducted over the pulmonary artery. The average regurgitant fraction over the pulmonary valve was 42.9 ± 2.7% in the PR group Table . TricuspP < 0.0001; LVESVi: 6.4 ± 0.4% vs. 9.0 ± 0.4%; P < 0.001), while indexed right ventricular end‐diastolic volume (RVEDVi) and indexed right ventricular end‐systolic volume (RVESVi) were increased  and led to an increase in LVEDVi . However, LVESVi remained unchanged .Ventricular volumes were indexed to total heart volume (THV). Both indexed left ventricular end‐diastolic volume (LVEDVi) and indexed left ventricular end‐systolic volume (LVESVi) showed a significant reduction in conditions of PR compared to control animals , while septal contribution to RVSV was strongly increased in comparison with the physiological negative contribution to RVSV in healthy animals  and septal  RV function  in the RV compared to control animals , an increase in lateral LVSV  and a decreased septal LVSV , lateral  and septal  LV contraction   between the corrected RV ejection fraction (EF), that is net pulmonary forward flow/RVEDV and the longitudinal contribution to LVSV  and end‐systole (ES). For the LV, the summation of individual SVs amounted to 93.8 ± 2.2% in control, 101.0 ± 2.4% in PR and 93.3 ± 3.1 in PPVR animals respectively. In the RV, summation of individual SVs yielded a total of 104.9 ± 3.8% (control), 97.8 ± 1.7% (PR) and 98.6 ± 3.0% (PPVR) respectively.Invasive pressure measurements were conducted in seven of eight animals in the control group (except for pulmonary capillary wedge pressure (PCWP) measurements: 6/8), eight of 12 pigs in the PR group and six of six animals in the PPVR group. Data are summarized in Table R2 = 0.940; P < 0.001)  Fig. a. No corThe average interobserver variability for both ventricular volumes combined was 0.6 ± 5.1% and for AVP measurements 4.9 ± 13.7% (data presented as mean ± SD).This study analyses the individual contributions of longitudinal, lateral and septal contraction to LVSV and RVSV in pigs suffering from isolated PR. The results suggest that decreased longitudinal function in the RV is a result of PR and corresponding RV volume overload and not only a consequence of cardiac surgery.Severe PR is a common feature following corrective surgery for TOF and entails numerous long‐term complications, including exercise impairment, ventricular dysfunction, arrhythmias and sudden cardiac death.et al.et al. and this study remains to be elucidated. Alas Riesenkampff et al.Limitations), it is worth noting the following: the cohort with isolated PR (non‐TOF patients) in Riesenkampff et al.'s study did not have significantly enlarged RVEDV (indexed to body surface area), compared to control subjects, while the TOF patients with PR did.Recently, it has become evident that assessment of AVP displacement or longitudinal contraction, whether by CMR or echocardiography, serves as a potent predictor of adverse events in a range of cardiac pathologies including TOF.The degree of reduction in longitudinal RVSV in this porcine model is consistent, albeit to a lesser extent, with our observations made in TOF patients with PR.We have previously postulated that the reduction in RV longitudinal pumping may be an adaptive mechanism with the aim of more adequately matching right atrial (RA) inflow to net RVSV, that is SV minus regurgitant volume, as a preserved longitudinal function would result in overfilling of the atria and a concomitant pendulum volume.We have also observed a correlation between the degree of RV longitudinal pumping and PCWP Fig. a. AlthouTo compare ventricular volumes between different experimental groups, we have indexed ventricular volumes as fractions of THV. As THV remains almost constant during the cardiac cycle and the four chambers of the heart are volumetrically coupled, THV can be used as a volumetric control accounting for different animal growth rates.Limitations). Ultimately, the underlying cause of this difference cannot be conclusively elucidated at this point; however, the correlation between the amount of right ventricular impairment and the degree to which the left ventricle increases its longitudinal contribution to SV may point towards a functional importance of this adaptive mechanism in this model where there is an acute onset of PR. A potential explanation for this observation may be found in the physiology of systolic left atrial filling, which is primarily driven by ventricular longitudinal pumping. With progressing right ventricular functional impairment, the left ventricle may support left atrial filling by increasing its longitudinal contribution to SV, with the overall aim of maintaining energetically favourable constant total heart volume.As septal contraction contributes to LVSV in the healthy heart, paradoxical septal movement will negatively affect LVSV. We have previously observed an increase in lateral contribution to LVSV in TOF patients to compensate for the loss of septal contribution to LVSV.This study further demonstrates a general reversibility of the changes in cardiac pumping induced by PR and allows speculation about the nature of the adaptive mechanism. The observed changes may be a result of cardiac remodelling or alternatively a purely mechanical response to altered volume/pressure relationships. While this study cannot conclusively delineate between both mechanisms, it can be noted that 1 month of restored valve function, which in turn can be considered a short to medium time period for reversal of remodelling effects, almost entirely normalized cardiac pumping. Previous histological studies in this animal model further demonstrate that the muscle hypertrophy resulting from PR is still present 1 month after valve insertion.P = 0.026). We attribute this difference to the need for generation of a larger SV during conditions of TR, in order to maintain a constant net pulmonary forward SV. While other isolated effects of TR could not be identified, an influence on pumping mechanics cannot be conclusively excluded due to the small number of animals available for subgroup analysis.We observed TR in seven of 12 pigs with PR. It can be assumed that TR manifests in these cases secondarily to PR‐induced RV distension. Subgroup analysis between TR vs. non‐TR animals revealed a statistical difference in RVESVi in the PR group . This is attributable to the fact that the original experimental protocol aimed at answering a different scientific question, namely the effectiveness of PPVR to rescue different degrees of RV dysfunction after induction of PR.While insertion of a stent is an effective way of inducing isolated PR an influence of the stent on AVP movement or other pumping mechanics cannot be excluded.This study underlines the value of characterizing the individual contributions to SV, as functional impairments, particularly in longitudinal pumping, are present before more global parameters, such as EF, are affected. While not offering prospective information, this study shows the value of longitudinal contractile function as a routine marker in the assessment of RV function, particularly in TOF patients. Measurement of longitudinal RVSV may support risk stratification and facilitate timing for interventional correction of PR. Furthermore, this study demonstrates that the observed changes are inherent to PR and therefore occur independently of previous corrective surgery.n = 8) and treatment (n = 12) groups. At baseline, piglets were 8–9 weeks old. Animals in the treatment group received a bare metal stent in the pulmonary valve orifice via percutaneous right heart catheterization, inducing free PR, while animals in the control group underwent sham interventions. PR was maintained for 2 or 3 months, before re‐examination. A subset of animals in the treatment group (n = 6) underwent PPVR after 2–3 months of PR and was subjected to re‐examination 1 month after valve repair. The animal study was approved by the Animal Experiments Inspectorate .The design of the experimental study has been previously published.2); however, intubation was performed to secure the airways. During intervention, amiodarone 5 mg/kg was administered intravenously to reduce occurrence of cardiac arrhythmias. Heparin was given as an anticoagulant . Percutaneous right heart catheterization was performed through the femoral vein. Following angiography , a bare CP® stent  mounted on a 22‐mm BIB® dilation catheter (NuMED) was advanced to the pulmonary valvular annulus inducing free PR. Invasive pressure measurements  and PCWP) were conducted during catheterization using a fluid‐filled transducer. For animals in the PPVR group, a Medtronic Melody® valve  was placed inside the CP® stent following 2–3 months of free PR. Adequate valve function was confirmed with pulmonary angiography and echocardiography.Before intervention, animals received sedation with midazolam 0.5 mg/kg. Subsequently, anaesthesia was induced and maintained with intramuscular injection of a mixture of tiletamine, zolazepam, xylazine, ketamine and methadone. Animals breathed spontaneously , equipped with a standard phased array chest coil. Imaging was performed after two (n = 7) and three (n = 5) months of PR. Control animals (n = 8) were imaged at corresponding time points. For animals in the PPVR group , imaging was repeated 1 month after valve insertion. Short‐ and long‐axis images were acquired with a cinematographic gradient echo pulse sequence . To calculate pulmonary regurgitation volume, velocity‐encoded phase‐contrast cine images were acquired over the main pulmonary artery .Cardiac magnetic resonance imaging was conducted on a 1.5T scanner (Siemens MAGNETOMwww.medviso.com).et al. Image analysis was performed using the image analysis software Segment . Welch's unpaired Lars Sondergaard is a consultant for and has received unrestricted research grants from Medtronic. Philipp Bonhoeffer is a consultant to Medtronic and NuMED and has received honoraria and royalties for the device described. Einar Heiberg is founder and owner of Medviso AB producing the Segment software for medical image analysis. NuMED, Hopkinton, NY, USA, and Medtronic Minneapolis/St Paul, MN, USA, are acknowledged for financial support to the study.This work was supported by the Swedish Research Council, Swedish Heart Lung Foundation, the Swedish Medical Association, Lund University, the Region of Skåne and the Danish Heart Foundation. NuMED, Hopkinton, NY, USA, and Medtronic Minneapolis/St Paul, MN, USA, are acknowledged for financial support to the study.


Diff) to a quiescent diastolic phase, but this approach is burdensome and highly sensitive to heart-rate changes. More recently, motion compensated (MOCO) diffusion encoding gradients with nulled first (M1) and second (M2) moments have demonstrated good robustness to cardiac motion  but they necessarily increase the echo time (TE) compared to monopolar encoding (MONO), which reduces SNR and/or limits spatial resolution. We have developed a MOCO cDWI sequence that employs Convex Optimized Diffusion Encoding (CODE) to reduce bulk motion sensitivity and shorten TE compared to existing MOCO schemes.Cardiac Diffusion Weighted MRI (cDWI) has the potential to characterize myocardial infarction (MI) without contrast. However, the clinical utility of cDWI has been limited by severe sensitivity to cardiac motion that manifests as signal dropouts which corrupt measures of myocardial diffusivity. This can be managed by carefully timing the diffusion encoding gradients  and pulse sequence constraints. Imaging: Healthy volunteers (N = 5) were scanned on a 3.0T scanner (Siemens Prisma) after providing written informed consent for an IRB approved study. High resolution cDWI were acquired in the left ventricular (LV) short-axis with b = 350 s/mm2, 1.5 × 1.5 × 5.0 mm spatial resolution, 2x GRAPPA acceleration, three orthogonal diffusion encoding directions and three signal averages in a single 15-heartbeat breath hold. Both MONO (TE/TR = 67 ms/1R-R) and CODE encoding (TE/TR = 76 ms/1R-R) were acquired, but MOCO (TE = 94 ms) was not. All cDWI were acquired at eight subject-specific cardiac phases distributed across systole and diastole. Reconstruction and Data Analysis: Apparent diffusion coefficient (ADC) maps were reconstructed at each phase. Motion corrupted voxels were identified by ADC values exceeding 3.0 × 10-3mm2/s  in the LV. The mean LV ADC and the percentage of motion corrupted LV voxels were then calculated at each phase. Statistical analyses were performed using t-tests with Holm-Sidak post hoc corrections.2, resulting in ~49% increase in SNR  for 87.5% of phases with CODE (p < 0.01) and 0% of phases with MONO (p = N.S.)   is substantially shorter than asymmetric bipolar MOCO  (TE = 94 ms) for 1.5 × 1.5 mm in plane resolution and b = 350 s/mmS.) Fig. . CODE cD03) Fig. .Figure 11 and M2 moment nulling with a shorter TE than existing MOCO cDWI methods.CODE cDWI significantly improved robustness to cardiac motion compared to MONO cDWI. CODE cDWI also permits M


Native T1 time (no contrast agent), changes with myocardial extracellular water , fat, iron, and amyloid protein content. After contrast, the extracellular volume fraction (ECV) estimates the size of the extracellular space and identifies interstitial disease. Spatially resolved quantification of these biomarkers  are steadily becoming diagnostic and prognostically useful tests for several heart muscle diseases, influencing clinical decision-making with a pending second consensus statement due mid-2017. This review outlines the physics involved in estimating T1 times and summarizes the disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting some of the remaining challenges such as their community-wide delivery, quality control, and standardization for clinical practice.Quantitative myocardial and blood T Cardiovascular magnetic resonance (CMR) research data accrued in both animals and humans convincingly demonstrate that native T1, in the absence of gadolinium-based contrast agents (GBCA), lengthens with interstitial expansion caused by edema, infarction, amyloid infiltration, and fibrosis [1 shortens in the presence of fat and iron accumulation. The left ventricular (LV) myocardial native T1 signal, from a single region of interest on a T1 map, could therefore serve as a simple, on-the-fly, non-invasive discriminator of heart muscle health and disease.In magnetic resonance imaging, the longitudinal (spin-lattice) relaxation time T is a fun1-weighted signal also forms the basis of the late gadolinium enhancement (LGE) imaging technique. This technique was the most disruptive tissue characterization method. LGE can quantify focal scar and fibrosis in both ischemic and non-ischemic cardiomyopathies. It works by the principle that scarred tissue passively accumulates more GBCA which shortens its T1 compared to adjacent normal healthy myocardium, and this is visible with a particular imaging sequence (inversion recovery) [1 mapping adds to this. It has evolved from T1-weighted imaging, to native T1 measurement alone, to post-GBCA T1 measurement in isolation, or through the partition coefficient to measurement of the extracellular volume (ECV) [1 is measured before and after GBCA using a correction for the hematocrit (measured separately or in-line automated) [1 and ECV permit earlier diagnosis and quantitative assessment of focal as well as diffuse myocardial disease  . T1 mappme (ECV) . The lattomated) , 5. Nati1 mapping and discusses disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting the challenges of community-wide delivery, quality control, and standardization in clinical practice.This review outlines the basic physics of T1 mapping sequences have three parts: (1) the T1 magnetization preparation pulse, (2) a single image acquisition (readout) after a variable delay, and (3) variable repetitions of (1) and (2) to sample the longitudinal magnetization recovery curve after the magnetization preparation. Raw images are then reconstructed by post-processing into a single T1 map using a theoretical model of the expected signal intensity [Broadly, Tlay, and  variablen pulse,  a single1 map is a two-dimensional  slice image where each image pixel displays the T1 relaxation time (ms) using a color look-up table to facilitate visual assessment [1 [1 measurement approaches did not do this and became obsolete [A Tsessment . Imagingsment [1 . Earlierobsolete . When coobsolete , 20. Acqobsolete . A typicobsolete .1 mapping is complex as different approaches are taken with different names. The original Look-Locker sequence developed in the 1970s [1-weighted images. The inversion pulse inverted the net magnetization by 180° and was followed by multiple readout pulses interspersed with longitudinal magnetization recovery periods. However, as the relaxation curve was repeatedly perturbed by radiofrequency (RF) pulses of the imaging readout, an “apparent” T1 (T1*) was assessed and it required further correction for relaxation time measurement [1 maps, as acquisition, lasting 20 min, spanned multiple phases of the cardiac cycle [MOdified Look-Locker Inversion Recovery (MOLLI) [b)3(3b)5 protocol, with numbers outside of parentheses indicating the number of images acquired after each magnetization preparation pulse, and numbers in parentheses indicating the length of the pause separating image acquisition and any subsequent magnetization preparation pulse, defined either in terms of number of recovery beats (b) or number of seconds (s). MOLLI’s bSSFP readout also estimates an “apparent” T1 (T1*) which is influenced by imaging RF pulses, so a Look-Locker correction is still needed to correct for it and deliver a more accurate T1 estimate [s)3 variant [b)1(1b)1 scheme to acquire images over nine heartbeats making it more suitable for breathless patients [1 estimation, for large T1 values [1 estimate tends toward a smaller value [SAturation Recovery Single SHot Acquisition [1 can be estimated directly from pixel-wise curve fitting [SAturation Pulse Prepared Heart-Rate Independent Inversion REcovery Sequence (SAPPHIRE) uses a hybrid combination of both inversion and saturation pulses that increases the dynamic range . Additional comparator sequences are elaborated in Table .The 1970s  applied surement , 24. Theac cycle . Use of ac cycle  permitteac cycle , and con (MOLLI)  approach (MOLLI) . New MOLestimate . Later v variant , which spatients . The resuisition  (SASHA)  fitting , but it  fitting . SAturatThe myocardium can be considered as two main compartments: the “intracellular cellular volume” , dominated by myocytes but also including all other cells ; and the “extracellular volume,” dominated water associated with the extracellular matrix but also including the intracapillary plasma volume . The norλ), and (3) the patient’s hematocrit (Hct) representing the cellular fraction of blood [Mathematical derivation of the ECV Eq.  relies oof blood .1\docume1 to be low, and the result is that T1 mapping can reliably differentiate between FD, other forms of LVH, and healthy controls [1 lowering is seen in 50–60% of subjects before LVH  and these correlate with blood troponin suggesting that chronic inflammation may be contributing [1 mapping, capable of detecting early cardiac involvement in FD, could therefore have a major role in guiding timing of commencement of ERT and drug monitoring [Fabry disease (FD) is an intracellular lysosomal storage disease caused by the accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A . Cardiaccontrols . T1 loweLVH Fig. , so it iributing . Enzyme ributing , but ERTnitoring .Fig. 3Th2-weighted imaging, non-ischemic mid-wall LGE, and hyperemia/capillary leak on early gadolinium enhancement imaging [1 detects both intracellular and diffuse myocardial change , and no imaging . Native nge Fig. , so it hcarditis . A multil injury .1 mapping and ECV provide complementary information, both diagnostically and prognostically. In acute myocardial infarction (MI), myocardial edema elevates the native T1 signal and the ECV. Native T1 in the infarct core can predict 6-month post-ST-elevation myocardial infarction (STEMI) mortality even after adjustment for LV ejection fraction [1 is independently associated with LV systolic dysfunction [1 may also identify the area at risk and salvaged myocardium [2-weighted imaging can. In chronic MI, native T1 and ECV are increased, but values are lower than those observed in acute MI [1 values in chronic MI by widely used bSSFP mapping methods should be interpreted with caution as T1 values may be subject to additive or subtractive bias when water and fat coexist in the myocardium—intramyocardial fat due to lipomatous metaplasia in chronic myocardial scar potentially predisposes to such T1 biases [1 mapping of the spleen is being explored as a surrogate indicator of adequacy of vasodilator stress with adenosine [1 decreases as a result. This makes native splenic T1 in the course of the adenosine infusion (and before GBCA administration) a potential surrogate marker of stress adequacy [Acute and chronic infarct imaging is done by standard LGE techniques, but Tfraction , and in function . In repefunction , 62. Natocardium  better tacute MI . Native 1 biases . In the denosine . The spladequacy .1 and ECV may have more discriminatory and predictive power than LGE [1  and transthyretin (ATTR) amyloidosis, which has two subtypes, wildtype and mutant . Amyloidthan LGE , 70, andthan LGE . The curthan LGE . Convers [1 Fig.  can be hmportant .1, T2, and T2* [2* at 1.5 Tesla (T)  is the t at 3 T . T1 mappary tool . Native d by T2* , 77–79. d by T2* .1 for cardiac iron assessment include the known variation of absolute T1 between sequences and scanners [2* is more disease specific [1 changes of significant iron completely swamp all other pathologies—the T1 can lower by an impressive 25 standard deviations in severe iron overload, for example. The ECV can be used in iron overload, although there are concerns when iron loading is significant. The ECV can be increased in thalassemia major patients with documented cardiac iron overload, and it correlates with T2* but not with LV systolic function and global longitudinal strain [Challenges facing the roll-out of native myocardial Tscanners  and its specific . This adl strain . The impl strain .1 mapping in DCM [1 signal change in DCM is not large and conventional T1 mapping approaches have in-plane resolution limitations when applied to thin-walled hearts , wall thickness may or may not decline with significant partial volume implications. ECV was shown to correlate with clinical prognosis in DCM [1 mapping consensus document [2 mapping can detect myocardial inflammation that appears to play an important role in non-ischemic DCM [In dilated cardiomyopathy (DCM), diffuse myocardial fibrosis may be a prominent feature during disease progression and cardiac remodeling, which eludes depiction by LGE imaging. Early myocardial fibrosis detected by native Tg in DCM  can predg in DCM  allowinge in DCM ). Nativehickness , 85 whers in DCM  and withs in DCM , and altdocument , it is sdocument , 31, 88.emic DCM .1 mapping can have additive value [1 is modestly elevated in HCM as compared to healthy controls and highest in the areas of maximal hypertrophy [1 may also be elevated in HCM patients without overt LV hypertrophy, suggesting potential clinical utility as an early disease biomarker [1 was better than ECV at discriminating HCM from hypertensive heart disease [1 correlated with LV remodeling and global systolic function [Myocardial disarray, small vessel disease, and fibrosis are histopathological hallmarks of familial sarcomeric HCM. In HCM, LGE is a risk factor for heart failure and an additional risk factor for SCD . T1 mappve value . Native ertrophy . T1 may iomarker . Native  disease  and it i disease , althougfunction . ECV canfunction , but it function .1 mapping studies for valvular heart disease have focused on aortic stenosis (AS). AS is associated with two forms of myocardial fibrosis: diffuse  fibrosis that may appear prior to symptom manifestation and architectural change, and the more focal, late irreversible replacement fibrosis. Our understanding of fibrosis in AS is incomplete. Some fibrosis is clearly advantageous, but maladaptive fibrosis also occurs and the myocardial adaptation to the narrowed valve is key to the clinical impact [1 mapping can quantify the diffuse myocardial fibrosis in AS providing an indication of AS severity and cardiac function [1 and ECV were shown to be increased in AS [1 and ECV did not differ significantly from those in age-matched controls at 3 T [Most Tl impact . T1 mappfunction , 96 and function , 97. Milfunction . Native ed in AS  especialed in AS , but in s at 3 T .1 mapping in chronic mitral regurgitation may also have clinical utility to guide timing of intervention [Current guidelines classify AS severity mostly by echocardiography via trans-valvular pressure and aortic valve area measurements, and intervention is recommended based on LV ejection fraction and the presence of symptoms, ignoring the myocardial state, in spite of myocardial fibrosis having been shown to determine outcomes in AS patients  and ECV rvention .1 mapping and ECV are typically first established as useful complementary tools for new biological insights before becoming surrogate secondary endpoints in clinical studies. They must then cross the “translational gap” before they can become clinical decision-making tools [1 mapping and ECV, three parallel, not entirely sequential processes, are needed: technical validation  and non-CMR imaging biomarkers, as well as biospecimen-derived biomarkers  [Familiar imaging biomarkers used daily in cardiac imaging include LV ejection fraction, wall thickness, and left atrial size. New imaging biomarkers such as Tng tools  Fig. 4)1 mappingphantoms , 104), be, etc.) .Fig. 4Ov1 mapping sites [1 mapping as measurements differ between CMR scanners, manufacturers, field strengths, protocols, pulse sequences [1 mapping has specific limitations . Still clinical utilization is proceeding with the use of these tools daily in many centers, so more is needed including a wider range of research  and further consensus/summary processes [1 mapping field. Roadmapping these excellent biomarkers into healthcare for evidence-based patient management is an arduous, time-consuming, but important task. The CMR community needs such guidance.Ttatement  with a srocesses  to illum


Critically ill patients require close hemodynamic monitoring to titrate treatment on a regular basis. It allows administering fluid with parsimony and adjusting inotropes and vasoactive drugs when necessary. Although invasive monitoring is considered as the reference method, non-invasive monitoring presents the obvious advantage of being associated with fewer complications, at the expanse of accuracy, precision, and step-response change. A great many methods and devices are now used over the world, and this article focuses on several of them, providing with a brief review of related underlying physical principles and validation articles analysis. Reviewed methods include electrical bioimpedance and bioreactance, respiratory-derived cardiac output (CO) monitoring technique, pulse wave transit time, ultrasound CO monitoring, multimodal algorithmic estimation, and inductance thoracocardiography. Quality criteria with which devices were reviewed included: accuracy , precision (closeness of agreement between replicate measurements on the same or similar objects under specified conditions), and step response change . Our conclusion is that the offer of non-invasive monitoring has improved in the past few years, even though further developments are needed to provide clinicians with sufficiently accurate devices for routine use, as alternative to invasive monitoring devices. Hemodynamic instability requires cardiac output (CO) measurement and tracking to assess severity of disorders and to adjust treatments on a continuous basis. Invasive monitoring is widely used but is associated with inherent iatrogenic complications, notably for pulmonary catheters, esophageal probes, or arterial catheters –3. ThereThis article aims to review such non-invasive methods of CO monitoring excluding echographic, thermodilution, and pulse contour methods, already described in other sections. We will cover electrical bioimpedance and bioreactance, respiratory-derived CO monitoring technique, ultrasound CO monitoring, multimodal algorithmic estimation, and inductance thoracocardiography.trueness , precision (random error assessed by the closeness of agreement between replicate measurements on the same or similar objects under specified conditions), and step response change  (Devices are reviewed using three main metrologic criteria required for CO measurement: ication) . Table 1I) across the thorax and received voltage (V) by electrodes. Hemodynamic variables: stroke volume (SV), CO, and thoracic fluid content (TFC) are then derived from the output signal fluctuation. Thoracic impedance (Z) is defined by the ratio V/I. At baseline (Zo) is the ratio of maximum values of V and I (Vo/Io) and closely correlated changes in TFC . Since these changes only indicate relative changes of CO, a calibration factor (CF) is necessary, based on an initial cohort of patients to derive absolute valuesA basic hypothesis to derive CO from both impedance and reactance is that the heart chambers are electrically isolated. Indeed, relatively to the chest with the lungs, the myocardial wall effectively provides electrical isolation to the content of the heart; therefore, changes in chest impedance and reactance are closely linked to variations of aortic volume. SV is obtained from the product of the ventricle ejection time and the slope of the initial change of the aortic volume obtained from the first derivative of the impedance or reactance signal , when hematocrit is very low, when pulmonary arterial pressure is elevated  or because of physical abnormalities such as obesity and dehydration .Devices using bioimpedance include NCCOM , BioZ , NICCOMO , ICON , ICG , NICOMON , the CSM3000 , and PHYSIOFLOW . The NICaS system  uses the same principles but applied to the whole body. In the ECOM system , the transmitting and receiving electrodes are located on the cuff of an endotracheal tube, therefore close to the ascending aorta, in order to minimize the impact of analogous signals from other cardiac structures. Bioreactance is used by two products from the same company NICOM and Starling .Bioimpedance and bioreactance have the strong advantage of being totally non-invasive and low costs. Literature on bioimpedance includes hundreds of articles, dozens of which are clinical trials set in a wide range of situations from ambulatory patients at home, to patients in a physiology laboratories, during surgery and in a ICU. Results are somewhat contradictory . At leasBioreactance on the other hand has scarcer documentation. Theoretical superiority of bioreactance over bioimpedance was hinted in small sample studies set, in quite homogeneous patients of cardiac surgery ICU where the CF was derived , 34. In Further developments may be required to improve bioimpedance and bioreactance performance focusing or better understanding of the signal composition and better extraction of the aortic expansion signal. The auto calibration process may also be improved to fit better the studied population.2) and the difference of arterial (CaO2) and venous (CvO2) blood oxygen contents. This method was first described for intubated, sedated and ventilated patients , using either oxygen (O2) or carbon dioxide (CO2) exhaled gas, and requires invasive arterial and mixed venous blood sampling, obeying the following equations  and the end tidal CO2 concentration (S. etCO2) as a surrogate of CaCO2. Since the CvCO2 is more difficult to estimate, it is derived considering two periods of time: normal respiration (n) and a 30-s period of rebreathing (r). Assuming that the CO and the CvCO2 remain unchanged during the two periods of time, the two equations become as follow:2 can be measured in exhaled gas with a sealed facial mask. This partial CO2-rebreathing method hence allows measuring CO without the need of intravascular monitoring devices. Practical use involves an extra loop of ventilatory circuit to create a transient partial CO2 rebreathing system   changes in ventilation modify end-tidal CO2 requiring patient respiratory state to be steady, i.e., not applicable in ICU, and (c) differences in VCO2 and end-tidal CO2 only account for that part of the lung which is ventilated, hence, atelectasis or intrapulmonary shunts need to be adjusted for, which in an ICU setting can prove difficult when patients present with several lung diseases  and INNOCOR  are based on these principles , 39. Sevdiseases –42. The diseases , 44.A very recent retrospective study, in more than 12,000 patients who underwent right heart catheterization but were not necessarily hospitalized in ICU, found between thermodilution and an oxygen-uptake-based Fick method, an acceptable systematic bias of 0.4% but poor limits of agreement from −1.31 to +1.27 l/min; and a difference of more than 20% between measured CO in 40% of patients .2-rebreathing is still hard to routinely use in ICU but fields of development include better rebreather-face interface to avoid leaks  and correction algorithms which may take into account changes in end-tidal CO2, all the more in ICU setting. Indeed, this latter concern seems particularly difficult to address, as acute respiratory disease  represents the most prevalent cause of admission in ICU.Hence, partial COV = initial vessel volume; dP = the change in pressure; and dV = the change in vessel volume.Pulse wave transit time is the time required for a pulse pressure wave to travel between two points. It can be estimated from the time interval between the development of the R-wave on the electrocardiogram and its peripheral detection  and the initial measurement of the pulse pressure. Interestingly, initial CO was estimated only by this non-invasive patient information calibration . Continuous CO is estimated with a multimodal algorithm PWV and using patients’ characteristics and several measurements such as pulse oximeter waveform, non-invasively measured blood pressure and electrocardiogram. The final formula is given by:ibration . Even ifibration –55. Indeibration . Limitatibration . Finallyibration , 57.While EsCCO has not been quite validated in ICU, devices using pulse wave contour analysis, working quite closely to pulse wave velocity analysis are more promising. EsCCO suffers mainly from initial individual calibration issues, which are reduced to a crude algorithm aggregating a few variables which may not be sufficient to account for the wide variability of patients presenting in ICU. Indeed, the two main issues are (i) the heterogeneity of patients’ profiles, for which an overall algorithm may be statistically true for most but containing an inherent percentage error, making individual prediction hard to assess and (ii) the interpatient variability in the course of his treatment and care in ICU .Product of aortic blood flow velocity and area of a section of the aorta equals to the CO measured in the aorta. Blood flow velocity can be measured using ultrasound and Doppler effectA few articles highlight the feasibility of using USCOM in ICU, with a systematic bias of −0.36 l/min however limits of agreement were poor ranging from −2.34 to 1.62 l/min and the reported percentage error (29%) seemed too high for daily use .To put it in a nutshell, although point-of-care ultrasonic evaluation of CO is widely used in ICU, continuous echocardiographic monitoring of CO by USCOM remains largely debated. Indeed, a high percentage error, either due to errors in valve area estimation or probe displacement, make it hard to routinely apply. However, initial calibration on actual echocardiographic assessment of the valve area and regular signal-quality checks may improve this technique.This method allows the computation of ventricular volume curves from ECG-triggered ensemble respiratory waveform of an inductive plethysmographic transducer. The latter is placed on the thorax by surrounding with a belt. Impedance varies according to respiration and cardiac ejection. Because the transducer is positioned in front of the heart, heartbeat-related ventricular volume variations are detected and adjusting the signal on respiratory-related impedance signal allows computing specific cardiac changes. The only device using this technology is Respitrace  .Main limitation of this method resides in the fact that it only detects relative variations in cardiac volumes , 67, henThe need for a non-invasive, true and precise CO measurement in the ICU is, as of yet, still unsatisfied , 70, desaccuracy, i.e., how close a single measurement value is to the true value of the measurand can never be numerically assessed. Indeed, the true value of the measurand can only be approximated by a reference method or, when available, a gold-standard. Theoretically, if someone could repeat the measurement an infinite number of times to estimate the same measurand value, the only difference between the averaged observed value and the true value would equal the systematic measurement error . Statistical analyses are aimed for adjusting for such bias, however, most methods derive from population-based algorithms, hence do not account for individual variability. Therefore, non-invasive devices are characterized by acceptable mean interpatient bias but poor individual calibration. Precision, as defined by metrological standards, represents the repeatability and reproducibility of the method, i.e., the degree to which repeated measurements using the same method to estimate the same measurand value, produce the same observed value. Inherently, it relates to random measurement error (as opposed as systematic measurement error represented by the bias). As such, most publications do not specify precision but rather publish the standard deviation of the bias in the cohort, i.e., interpatient bias. A higher precision allows for fewer measurements in order to have an estimation of the measurand. Hence, precision has a direct practical impact on the usability of devices, especially in the step time response of the device. Indeed, very few articles describe how many measurements were taken to obtain a value, and similarly, manufacturers do not always specify how many measurements are necessary to be within acceptable error limits. In practice, non-invasive devices present the obvious advantage of allowing repeated measures to obtain more accurate value, given they would be adequately calibrated. However, if a given device takes too long to estimate a measurand, its usefulness may be challenged, however accurate it can be.Extensive reviewing of published data on diagnostic performance of monitoring devices, be they invasive or not, shows heterogeneity in reporting of performance. Specifically, Hence, the risk of misdiagnosis or delay to diagnosis from an insufficiently accurate non-invasive device remains real. Indeed, they represent the counterparts of invasive device-related complications, be they infections or hemorrhages. Consequently, properly assessing the need for invasive monitoring remains a clinical challenge in ICU, to which, the only acceptable solution would be equally efficient non-invasive devices.Interestingly, obtaining the true value of a measurand would not necessarily be the most important feature that one might require from a hemodynamic monitoring device. Indeed, ability to observe variations in hemodynamics is equally important, if not more; implying fast step-time response and precision. Observing the decrease in CO may be as useful as knowing this exact value. In the end, the difference between trueness and precision may be analogous to that of diagnosis or monitoring.Non-invasive monitoring has evolved in the past few years, seeing the appearance of promising new devices. Further developments may be warranted to validate their use and increase their metrologic performance in ICU. Even though some have successfully deployed such device, the need for a non-invasive, true and precise CO measurement in ICU is, as of yet, still unsatisfied.LN and PS contributed equally to the manuscript.LN has no conflict of interest regarding this publication. PS perceived consulting fees from Edwards and Cheetah Medical prior to 2000.


Noninvasive detection of myocarditis is a unique feature of Cardiovascular Magnetic Resonance (CMR), but conventional CMR-imaging suffers from different challenges including imaging quality. It has already been shown, that T1 mapping has the potential to identify acute myocarditis .We aim to differentiate the course of disease and to identify the acute stage by combining mapping techniques.Eighteen patients with clinically defined acute myocarditis were prospectively examined three times during follow up using a 1.5 T Scanner . They were compared to a healthy sex- and age matched control group. Severity of disease was rated in NYHA and CCS score. Left ventricular (LV) volumes, mass and function were assessed using steady-state free precession (SSFP) cine imaging in short axis. Parametric mapping was applied using T2 maps in three short axis  and native T1 mapping using modified look-locker inversion recovery (MOLLI 5(3)5) sequence  in a basal and a midventricular slice. Furthermore, T1 mapping was performed during contrast media wash-out (Gadobutrol 0.15 mmol/kgBW) at minute 1,3,5,7,10. Late gadolinium enhancement (LGE) was performed after minute 12 for myocardial fibrosis detection. Blood collection was done for haematocrit assessment. Data were analyzed using CVI42 , Mann-Whitney U test was used.All 18 patients and healthy volunteers completed all examinations . NYHA score decreased from 1.8 ± 0.95 (FU0) to 0.5 ± 0.5 (FU2), CCS score decreased from 2.3 (FU0) to 0.3 (FU2).14(78%) patients showed focal fibrosis (LGE pos).Global T2 relaxation times decreased during follow up (p < 0.001 from FU0 to FU2). ROC analysis revealed a area under the curve of 0.9 for cutoff 51.92 ms  to differentiate diseased from healthy volunteers. Global native T1 remains stable , however, native T1 was significantly higher in patients than in healthy volunteers (p=0.003). Difference in T1 during contrast media washout between patients and healthy volunteers was significant at minute 3 at FU0 . Global ECV was increased at FU0 (p=0.021) and normalized at FU2 (p=0.164) compared to control group. See table T1 mapping allows the identification of diseased in comparison to healthy volunteers. Additional use of T2 mapping enables to detect disease acuity and so far to identify reversibility. Further follow up examinations would be necessary to identify its prognostic values. Parametric mapping may replace parts of conventional imaging techniques.


Critical care echocardiography is developing rapidly with an increasing number of specialists now performing comprehensive studies using Doppler and other advanced techniques. However, this imaging can be challenging, interpretation is far from simple in the complex critically ill patient and mistakes can be easy to make. We aim to address clinically relevant areas where potential errors may occur and suggest methods to hopefully improve accuracy of imaging and interpretation. Cardiac dysfunction is commonly associated with critical illness and often involves both ventricles. It can result from chronic underlying conditions (often unknown prior to the ICU admission), the acute disease itself (e.g. sepsis ), compliLarge amounts of published data demonstrate the benefit of ultrasound imaging in the critically ill: as a diagnostic tool (detecting right ventricle (RV) dysfunction from mechanical ventilation ), providCritical care physicians can use comprehensive echocardiography as an extension of examination and further as a sophisticated tool when routine haemodynamics do not offer a clear solution for the specific abnormality or pathology. In this regard integration of history, physical examination, other investigations as well as 2D/Doppler echocardiography findings is needed to determine the most appropriate management for our patients. In this review, we address areas where those learning comprehensive critical care echocardiography can ensure accurate imaging and interpretation of findings. This list is not exhaustive and merely reflects the more common themes.Stroke volume (SV) assessment in the critically ill patient is an essential part of the cardiovascular examination with echocardiography: for haemodynamic assessment, analysis of severity of valvular lesions and cardiac performance . In thisSV is determined by left ventricle outflow tract (LVOT) diameter (assumed to be circular) multiplied by the LVOT velocity time integral (VTI):zoomed parasternal long-axis view at mid-systole. Correct plane orientation is important in order to identify the largest apparent diameter of LVOT. A foreshortened plane will lead to under-estimation of the stroke volume. Importantly, any inaccuracy in the diameter measurement will be squared (LVOTarea = π × LVOTradius2) increasing the impact of the error on estimation of SV. LVOT VTI assessment is made with a 5–7-mm pulsed wave Doppler (PW Doppler) gate in the LVOT and an aortic valve ‘closing click’ should be seen. This ensures LVOT VTI estimation is at the same site as the LVOT diameter measurement. The PW Doppler settings should be optimised for accurate LVOT VTI estimation: wall filters should be set to low levels and the gain reduced until the brightest (or densest) portion of the spectral tracing is seen, known as the ‘modal velocity’, which represents the velocity of the majority of blood cells  is the product of SV and heart rate and considering CO without having an estimate of SV can be misleading. For example, a cardiac output of 5 L with a SV of 70 ml may be considered reasonable in a patient on no cardiovascular support with a heart rate of 70 beats per minute (bpm); however, in a patient requiring 25 μg/min of Noradrenaline with a heart rate of 120 bpm and a stroke volume of 40 ml, interpretation would change to ‘a heart under considerable strain’.Caution should also be exercised when considering valvular dysfunction in a hyperdynamic state where a sclerotic or mildly stenotic aortic valve can be wrongly assumed to be significantly stenotic if the transvalvular pressure gradient is elevated due to the high flow, as estimated by the continuous wave (CW) Doppler trace, if considered in isolation Fig. .Fig. 2CoIn the critically ill patient significant valvular dysfunction can be perilous if the diagnosis is missed . Relying on colour Doppler analysis alone is insufficient for moderate or severe valvular regurgitation due to inaccuracies from gain, scale or eccentrically directed flows and with possible difficulty with imaging. Assessment of flows with continuous wave Doppler is an essential part of valvular lesion severity analysis; however, flows are very much dependent on fluid status as well as cardiac output, i.e. overestimation of regurgitation severity in a fluid overloaded or high cardiac output state. Reviewing the upstream or downstream flows can be a useful technique and relatively simple method of analysis to review if the valvular regurgitation is severe. For example, with severe mitral or tricuspid valve regurgitation there would be systolic flow reversal in the pulmonary or hepatic veins, respectively (upstream flow assessment); with severe aortic valve regurgitation diastolic flow reversal in the proximal aorta is measured from the suprasternal window (downstream flow assessment) Fig. . SpecifiThe passive leg raising (PLR) manoeuvre has become one of the reference standards in the ICU to assess fluid-responsiveness at the bedside –8. It haTo be accurate the manoeuvre should follow a strict protocol. If the patient is receiving mandatory mechanical ventilation, tidal volumes of 8 ml/kg should be transiently used. The PLR is performed as shown in Fig. Anchor your hand on the patient to keep the same position pre- and post-PLR to ensure efficient imaging and the same pulsed Doppler gate position and angle of Doppler interrogation Fig.  insetsame time in the respiratory cycle, using an increase (and subsequent decrease to baseline once supine again) of 15% as a marker of a responder . Th. Th35]. The mitral ‘L-wave’ is a relatively common, useful and often ignored finding  where miIntra-cavity obstruction of the LV was initially described in patients with hypertrophic cardiomyopathy and asymmetric LV hypertrophy , 40. HowSupra sternal view. The probe is positioned behind the suprasternal notch and allows visualization of the great vessels arising from the heart. This view may be considered a part of a standard study in cardiology but is often forgotten in the ICU population. The aortic arch can be examined and aortic flow can be assessed. Aortic arch dissection can be seen, diastolic flow reversal assessed to help quantify aortic regurgitation  or potenApical RV-centric views. The probe is moved medially from the apical position Fig. , potentiWith dilated cardiomyopathy, blood flow from the left atrium into the LV can become increasingly eccentric and directed towards the lateral wall. Using colour Doppler to view direction of blood flow into the LV and placing the probe more laterally can help ensure an accurate Doppler angle.Clinically important information can be missed by using the conventional echocardiography views only. Non-standard imaging windows may be important, particularly to optimize Doppler angles.The apex of the heart can be particularly challenging to assess. In patients with apical akinesia  the presence of thrombus needs to be excluded. Reducing imaging depth, focus position and increasing frequency can all help visualize the apex from standard apical views, but by moving the probe laterally or medially and angling back towards the apex the entire structure may be visualized Fig. . If avaiInferior vena cava (IVC) assessment is a standard part of most comprehensive studies and is used most commonly in assessing fluid responsiveness and in determining right atrial pressure. The evidence for this, however, is often conflicting and shows weak correlation  and studIn our practice we find the IVC is useful for right atrial pressure (RAP) estimation but is only reliable in spontaneously breathing patients  and is aIn assessment of fluid responsiveness, IVC size and response to respiration is fraught with multiple confounders which need to be considered when making interpretations. RV dysfunction and tricuspid regurgitation can impede venous return and result in a plethoric IVC which shows no correlation with fluid responsiveness . IncreasFrom a technical perspective, measuring the IVC too close to the right atrium, hepatic vein or diaphragm should be avoided and whichever methodology is being used to measure the IVC should be used every time. 2D assessment is likely better than M-mode as it avoids translational error .Comprehensive critical care echocardiography is a useful, rapid and non-invasive method to both diagnose pathology and monitor treatment response in the critically ill. Although growing dramatically in use around the world, it is not without its limitations and user dependency is a significant challenge. The two primary objectives of accurate imaging and accurate interpretation are vital and should underpin future growth in the speciality. Good knowledge and attention to detail are vital to avoid mistakes.


RVOT and MRV chamber area correlated with gel mass. Doppler RV stroke volume was 0.32±0.08ml, cardiac output (CO) 110±27 ml.min-1 and RV free wall contractility assessed using 2D-strain analysis was demonstrated. We have shown that modified MRV and RVOT views can provide detailed assessment of the RV in rodents, with 2D-strain analysis of the RV free wall potentially feasible.Echocardiography plays a major role in assessing cardiac function in animal models. We investigated use of a modified parasternal mid right-ventricular (MRV) and right ventricle (RV) outflow (RVOT) view, in assessing RV size and function, and the suitability of advanced 2D-strain analysis. 15 WKY rats were examined using transthoracic echocardiography. The left heart was assessed using standard short and long axis views. For the right ventricle a MRV and RVOT view were used to measure RV chamber and free wall area. 2D-strain analysis was applied to both ventricles using off-line analysis. RV chamber volume was determined by injection of 2% agarose gel, and RV free wall dissected and weighed. Echocardiography measurement was correlated with necropsy findings. The RV mid-ventricular dimension (R1) was 0.42±0.07cm and the right ventricular outflow tract dimension (R2) was 0.34±0.06cm, chamber end-diastolic area measurements were 0.38±0.09cm Animal models provide valuable insight into the pathophysiology of chronic lung disease, and enable assessment of potential therapeutics for conditions such as chronic obstructive pulmonary disease (COPD) –3. AnimaIn an alternative approach, Scherrer-Crosbie et al developed a transoesophageal technique in mice, where the right ventricular wall and chamber were evaluated in the mid-right ventricular SAX view . SignifiIn this study we aim to adapt the Scherrer-Crosbie mid-right ventricular (MRV) view to transthoracic examination in the rat, and compare RV assessment at the mid-ventricular SAX level, with the aortic SAX view of the right ventricular outflow tract (RVOT). The rat was the rodent of choice as it has a bigger heart than the mouse and it would therefore be easier to measure and detect small changes in size, structure and function. The RVOT view is a valuable window for assessing Doppler-derived RV ejection. In addition we plan to investigate whether the modified MRV view is suitable for 2D-strain analysis.Studies were conducted in accordance with National Health and Medical Research Council of Australia guidelines, and approved by the University of Melbourne Animal Ethics Committee (Ethics No. 1212675). All animals were acquired from the Animal Resource Center, Perth, Australia.Fifteen male WKY rats (300-350g) were anesthetized with 2.5% isoflurane, spontaneously ventilated and placed on a heated pad in the semi-left lateral position with upright tilt, suitable for echocardiographic examination. Pulse rate, oxygen saturation and temperature were continuously monitored. After shaving, a sequential examination of the left and right ventricles was performed using a Vivid E9 with i13-L (6-14MHz) linear array transducer . Each study imaged the parasternal long axis (PLAX) and mid-papillary SAX views of the left ventricle (LV), and the modified MRV and aortic RVOT/pulmonary artery SAX view of the RV . LV morpEchocardiographic measurements in this study included:Fractional Shortening (FS) = LVIDD-LVISD/LVIDDFractional Area Change (FAC) = LVEDA-LVESA/LVEDALV volume/Stroke volume (SV) = based on geometric truncated ellipsoid modelRV Free Wall Area = Epicardial area–endocardial areaRVOT Free Wall Area = Epicardial area–endocardial areaRV ejection stroke volume RVESV = PA area. VTI. HR, where PA area is the cross-sectional area of the main pulmonary artery, VTI is the area beneath the PA pulsed-wave velocity waveform or velocity-time integral and HR is heart rate.Real-time imaging loops of ventricular motion during the cardiac cycle were recorded for off-line analysis. The RV was imaged in the adapted MRV view and the LV in the mid-ventricular SAX view. High frame rates necessitated manual tracing of epicardial and endocardial walls for 2D-strain analysis . Segmental and global wall motion was then analyzed.2, the heart immediately excised and injected with KCl. To correlate RV chamber size and wall thickness with echocardiographic measurement agarose gel  was injected (using a 1ml syringe and 21G needle) into the RV chamber  and left to fix at room temperature. The gel was suspended in Hank’s Balanced Salt Solution 40 mM HEPES (sHBSS). Following injection (at 10 min) the RV wall was excised from the heart, exposing the hardened agarose gel mould of the RV chamber . Linear regression was used for correlation between echocardiographic findings and agarose gel mass, and RV wall mass at necropsy. P<0.05 was taken as significant (Graphpad Prism version 6 was used).Echocardiography was performed in 15 animals, and autopsy performed in 14 due to poor image quality in one animal. Animals were of similar age with mean body weight 332 ± 22 g, and heart rate 347 ± 23 bpm. Cardiac measurement of ventricular chamber size and function were within the normal range for our laboratory, and consistent with previous reports .3. Fractional shortening was 48.25± 8.90%, FAC measured as 72%, and calculated stroke volume 0.20 ± 0.05 ml, indicating normal systolic function.Left ventricle: LVIDD and LVISD were 0.72± 0.09 and 0.37± 0.07cm respectively, and using the hemisphere-cylinder model equation [2 and 0.29± 0.08cm2 for MRV and RVOT views respectively.Right ventricle: due to the geometrical shape of the RV, the MRV view imaged a larger proportion of the RV chamber than the outflow RVOT view. The MRV chamber dimension (R1) was 0.42± 0.07cm, the RVOT dimension (R2) was 0.34± 0.06cm, and chamber end-diastolic area measurements were 0.38± 0.09 cm2 for MRV and RVOT views respectively, corresponded to a total RV free wall mass of 0.19±0.04g at necropsy. There was no correlation between wall mass and RV wall area in either view, R 0.004 and 0.009, p = 0.84 and 0.77 respectively (Correlation with necropsy: RV chamber dimension R1 and R2 had no correlation (p = 0.41 and 0.73 respectively), whereas RVOT and MRV chamber area did correlate with gel mass  with RVOT Doppler measurement, compared to LV measurement based on geometric estimation alone. Further the RVOT view enables analysis of the pulmonary spectral velocity waveform, with measurement of the pulmonary artery acceleration time (PAAT), an index of elevated pulmonary arterial pressure in rodent models . Both viCurrent clinical guidelines advise the use of multiple echocardiographic views, for comprehensive assessment of right ventricular function . This reo / Lo, where L is the final length and Lo the initial length of a myocardial wall speckle. Strain measures vector movement in relation to myofibril architecture: deformation is negative with longitudinal and circumferential strain, and positive for radial strain relating to wall thickening. Strain rate is the velocity of deformation, or ε/time between frames.2D-strain is a further analysis of cardiac motion based on the tracking of “speckle” movement within the myocardial wall during the cardiac cycle. Naturally occurring bright speckles within the myocardium act as acoustic markers for tracking, and are generated by backscatter signal during ultrasound examination . AnalysiThe value of LV global longitudinal strain (GLS) is evident in clinical studies, where strain deformation has an earlier prognostic value than ejection fraction, particularly in predicting major adverse cardiac events . Strain The use of animal models of disease has direct translational value in assessing the efficacy of potential therapeutic agents . In COPDA limitation to this study was the variation in image quality between animals. Technical accuracy is dependent on anatomical recognition and orientation, which ensures standardization of echocardiographic views. Incomplete or oblique views, poor definition of endocardial or epicardial borders, as well as Doppler mal-alignment, are all potential sources of error. Our experience indicates incomplete imaging to occur in only 1 of the 15 animals. However strain analysis was particularly affected by poor border definition and high frame rates, and prevented analysis in many animals. With respect to gel injection and RV wall dissection at autopsy, a potential error was the failure to index measurements to animal body surface area. A further limitation in methodology is that CO was not validated with ultrasound measurement of PA flow. However our values were consistent with reported values. Transthoracic examination was well tolerated, with hemodynamic stability throughout anesthesia.In summary, we have demonstrated that examination using the MRV and RVOT views has the potential to provide a comprehensive assessment of the RV particularly when standard 4C or 2C apical views are often suboptimal. These views enable a large section of the RV free wall to be imaged, enabling assessment of dilatation, wall hypertrophy and strain analysis. Further examination of the RVOT allows RV morphology, and contractile function to be serially assessed. In rodents 2D-strain imaging of the RV is feasible, and with appropriate study design has the potential to identify early systolic dysfunction.S1 Text(XLSX)Click here for additional data file.