The field of pediatric and adult congenital cardiac catheterization has evolved rapidly in recent years. This review will focus on some of the newer endovascular technological and management strategies now being applied in the pediatric interventional laboratory. Emerging imaging techniques such as three-dimensional (3D) rotational angiography, multi-modal image fusion, 3D printing, and holographic imaging have the potential to enhance our understanding of complex congenital heart lesions for diagnostic or interventional purposes. While fluoroscopy and standard angiography remain procedural cornerstones, improved equipment design has allowed for effective radiation exposure reduction strategies. Innovations in device design and implantation techniques have enabled the application of percutaneous therapies in a wider range of patients, especially those with prohibitive surgical risk. For example, there is growing experience in transcatheter duct occlusion in symptomatic low-weight or premature infants and stent implantation into the right ventricular outflow tract or arterial duct in cyanotic neonates with duct-dependent pulmonary circulations. The application of percutaneous pulmonary valve implantation has been extended to a broader patient population with dysfunctional ‘native’ right ventricular outflow tracts and has spurred the development of novel techniques and devices to solve associated anatomic challenges. Finally, hybrid strategies, combining cardiosurgical and interventional approaches, have enhanced our capabilities to provide care for those with the most complex of lesions while optimizing efficacy and safety. Over the last three decades, the pediatric cardiac catheterization laboratory has undergone a transformation from primarily a diagnostic tool to a modality for therapy. While this is an ongoing process, a variety of signature advances have taken place, altering management strategies. In the next few pages, we hope to highlight a few of those advances, which have improved the outcomes of children born with congenital lesions of the heart.4. Image acquisition is performed by rotation through an arc around the patient of the C-arm of the angiography system, equipped with flat-detector computer tomography (CT)4. The volume set is used to reconstruct the 3D structures of interest. These images can then be overlaid onto live fluoroscopy for road mapping during therapeutic procedures4. The so-registered 3D space can also be integrated with 3D datasets from magnetic resonance imaging (MRI) or CT studies.Three-dimensional rotational angiography (3DRA) is an emerging imaging modality that provides tableside, real-time acquisition of 3D volume rendered and cross-sectional images to aid the visualization of complex cardiac anatomy and navigation during diagnostic or interventional procedures5. For example, in children with cavopulmonary connections, 3DRA can facilitate an understanding of the mechanisms underlying pulmonary artery (PA) stenosis and identify additional discrete proximal lesions at the anastomosis site5. Additionally, the relationship of the trachea and bronchi to surrounding cardiovascular structures allows the assessment of airway anomalies and vascular compression frequently encountered in this population with significant implications for clinical management  using images viewed on 2D screens. As such, these 2D representations make it inherently more difficult to appreciate the 3D relationships of cardiac structures unique to a particular intervention. Three-dimensional printing , while not a new technology, has only recently been used to fabricate physical models from 3D computerized imaging datasets16. While the first medical applications were to produce surgical implants for oral and maxillofacial surgery and prosthetics for orthopedic surgery, the ability to generate a 3D model of complex cardiac anatomy has made this a tool for education, procedural planning, and device testing in both structural and congenital heart disease interventions  and standardization of practice are warranted29. Comparisons between centers also highlight the inadequacy of fluoroscopy time alone as a metric of radiation dose estimate because of differences in programmed fluoroscopy modes, pulse rates, and cine acquisition frame rates33. Instead, recognition and comparison of actual radiation energy exposure such as dose area product and air kerma in relation to procedure types are more appropriate.Radiation safety awareness and techniques to reduce radiation exposure are essential for all procedures but have a special role in children with complex congenital cardiac lesions who often require long, and at times multiple, procedures during their lifetimes36. Innovation in FPD including increased pixel bit depth and usage of crystalline silicon rather than amorphous silicon combined with novel flat emitter X-ray tubes offers further reduction in radiation dose owing to better digitalization and lower detector noise37. Additionally, alternative imaging techniques, such as transesophageal and/or intracardiac echocardiography or fusion of MRI/CT imaging with fluoroscopy, have been successfully used to reduce radiation exposure in various interventional procedures33.Several technical developments have impacted positively on the reduction of radiation exposure, notably the transition to flat panel detector (FPD) technology, which converts X-ray photon energy to digital signals more efficiently than image intensifiers39. Definitive treatment strategies in this group remain debated, as both medical and surgical therapies have attendant risks41. Percutaneous ductal closure in these small newborns is generally limited by delivery sheath size, procedure-related hemodynamic instability, and the anchoring and retrievability characteristics of current devices42. Although manufacturer recommendations for the most commonly used Amplatzer ductal occluders are a weight of 6 kg or more, there is no consensus on the minimum weight limit in practice.A persistent patent ductus arteriosus (PDA) in the preterm newborn is often associated with important comorbidities  and increased mortality47. Technical feasibility has also been demonstrated in extremely preterm (under 28 weeks) or very preterm (28 to under 32 weeks) infants under 2.5 kg, with the smallest noted in the literature weighing 755 g, having an uncomplicated closure with a 4 mm Amplatzer vascular plug II device52. The adverse event rate was higher in the under 4 kg group, which was not unexpected given that premature infants are medically fragile55, in keeping with the known inverse event rate related to patient weight at the time of catheterization56. The increased risk of embolization is also noteworthy in low-weight and premature infants; hence, the retrievability of the occluder and duct morphology needs careful consideration47. There were no deaths attributable to the procedure reported in these studies.Recently, there has been a growing body of evidence supporting the feasibility and efficacy of percutaneous PDA closure in the premature or small infant under 6 kg. The procedural success rates range from 88 to 94% in those with a median weight of between 2.5 and 6 kg58. Some centers have avoided arterial access by adopting a transvenous-only approach guided by fluoroscopy and echocardiography33. The risk of device-induced obstruction to the descending aorta or left PA (LPA) was low in these studies, and the majority tended to resolve over time with growth of the vessels52. However, the severity of LPA stenosis may be underestimated because of outflow diversion to the right lung. Studies using scintigraphic perfusion imaging have shown evidence of decreased perfusion of the left lung after PDA occlusion, but the long-term clinical impact is unknown60. More recently, the introduction of a new microvascular plug  for PDA closure in the extremely premature infant has shown promising results62. Advantages of the device include delivery through a microcatheter (<3 F), a flexible delivery cable, and diskless device design which minimizes the risk of device protrusion to the aorta or LPA.Access-related complications, in particular acute arterial injury leading to vascular compromise of the extremity, is a significant concern when catheterizing these low-weight infants64. Conventional palliation with the Blalock–Taussig (BT) shunt in this high-risk group can result in complications such as shunt stenosis or occlusion, distortion and differential growth of the PAs, and pulmonary overcirculation67. Balloon dilation of the pulmonary valve alone has inconsistent benefit owing to frequently associated muscular obstruction in the infundibulum. Stent implantation to enlarge the right ventricular outflow tract (RVOT) is now increasingly used as a bridging procedure to palliate the cyanosis and promote PA growth  with good-sized confluent central PAs is the standard of care with excellent outcomes. However, the ideal management strategy for the symptomatic (cyanotic) neonate with TOF and one or more adverse risk factors, such as prematurity, low birth weight, unfavorable PA anatomy, or pulmonary atresia or non-cardiac co-morbidities, remains debated growth .72. More recently, Sandoval and colleagues provided comparative data on 180 infants with TOF who underwent RVOT stenting, early primary repair, or standard repair over 3 months of age63. While the RVOT stented group had worse PA anatomy and clinical factors compared to the early intervention group, final clinical outcomes were comparable to infants who underwent standard repair. RVOT stenting resulted in relief of cyanosis and PA growth, allowing time for somatic growth and resolution of non-cardiac comorbidities until definitive repair71. Quandt and colleagues compared outcomes of RVOT stenting and BT shunts, reporting better PA growth and hence shorter duration of palliation before complete repair after stenting. The RVOT stent group also had a shorter intensive care unit (ICU) and hospital stay, whilst mortality until surgical repair was similar in both groups74.Several small studies have documented favorable outcomes of RVOT stents in isolation since 2008, focusing on technical aspects and acute outcomes63. A hybrid perventricular route may offer a more controlled approach to PV perforation and RVOT stent placement while avoiding cardiopulmonary bypass and femoral vessel complications and has been reported in a few case series, including a neonate as small as 1.3 kg76. There is a high re-intervention rate for additional stent implantation  and PA dilation, although in this subset of infants the PAs are hypoplastic and require repeat procedures to encourage growth72.Several disadvantages of RVOT stenting exist, notably the technical complexity and risk of inadvertent perforation of the RVOT in low-weight infants with membranous pulmonary valve (PV) atresia, who undergo radiofrequency perforation to open the RVOT prior to stenting66. However, there are currently no published data comparing the outcomes of early primary repair, BT shunt, and RVOT stent. Ultimately, the preferred palliative option, whether surgical or percutaneous, is likely to depend on local expertise, patient factors, and clinical condition at the time of intervention.Previous retrospective comparisons of early primary repair versus a staged repair with a BT shunt in symptomatic neonatal TOF showed equivalent mortality and outcomes, although shunted patients had a greater likelihood of avoiding a transannular patch at the time of repair78. The technique has been applied in various lesions, either leading to a biventricular repair or destined for univentricular palliation80. Apart from avoidance of surgery and shunt-related adverse events, maintaining duct patency has been shown to promote significant and uniform PA growth compared to a BT shunt alone82. The effective patency of the stented duct or PA growth potential was not significantly different between cases with a single source  of pulmonary blood flow or those with multiple sources of pulmonary blood flow81. In a few retrospective reports, DS has performed favorably and offered early survival advantage with improved hemodynamic stability compared to a BT shunt but with an increased likelihood of re-intervention prior to next-stage surgery83.While ductal stenting (DS) has been applied for well over two decades, the procedure has gained a wider acceptance as a palliative option for the cyanotic infant with a duct-dependent pulmonary circulation deemed unsuitable for primary repair 77,78. 82. The adequacy of palliation provided by DS, however, depends on the clinical setting. When DS is performed after RVOT intervention for critical PS or PA, short-term patency is usually adequate. In other conditions, such as univentricular palliation prior to a Glenn procedure or biventricular repair of complex anatomy, a longer lifespan of the stented duct from 6 to 12 months is desirable to allow somatic growth82. The impact of drug-eluting stents used in adult coronary artery disease has been investigated in this setting. Sirolimus-eluting stents implanted in the porcine arterial duct had higher patency rates compared with bare-metal stents with anti-proliferative action on ductal smooth muscle84. Early trials of drug-eluting stents in neonates showed no clinically significant adverse outcomes; however, their clinical efficacy has yet to be evaluated85.One major disadvantage of DS is progressive neointimal proliferation and consequent endoluminal narrowing with an unpredictable timecoursePercutaneous pulmonary valve implantation (PPVI) is a recognized alternative to surgical pulmonary valve replacement in selected patients with dysfunctional synthetic right ventricle-to-PA (RV-PA) conduits, bioprosthetic pulmonary valves, or homografts. Currently available percutaneous pulmonary valves include the Melody™ valve , which has a maximum outer diameter of 24 mm, and the Edwards Sapien™ valve system (Edwards Lifesciences Corp), with outer diameters of up to 29 mm.89. Published experience on the Sapien™ valve in the pulmonary position is comparatively less, although there are robust data supporting its use in the aortic position in high-risk or elderly patients with acquired aortic stenosis91. Early results of the COMPASSION  trial reported a good safety and efficacy profile, and several small studies have demonstrated comparable results to the Melody™ valve in the medium term95. With both the Melody™ and the Sapien™ valve, primary valve failure was rare and overall complication rates were low (0–5%) with reported mortality rates of up to 2%95. Coronary compression due to expansion of the implant occurred in less than 1% of cases and was significantly associated with an abnormal coronary artery course. Pre-implantation coronary artery compression testing is mandatory to avoid this potentially catastrophic complication96. Stent fractures which occurred with the Melody™ valve in the early experience have been addressed with routine RVOT pre-device implant stenting. The incidence of infective endocarditis after PPVI is estimated at approximately 3% per year with the Melody™ valve, whilst a lower incidence with the Sapien™ valve is suggested97.Multiple studies have reported excellent procedural success and clinical efficacy of the Melody™ valve with thus far up to 7 years of follow up101. “Native” refers to the non-operated RVOT or one having a previous balloon pulmonary valvuloplasty/valvectomy for pulmonary stenosis or previous transannular patch repair for correction of TOF, which constitutes the vast majority of patients with a dysfunctional RVOT. The potentially distensible tissue in the contractile “native’” RVOT and the absence of a pre-existing “scaffold” such as in a conduit or bioprosthetic valve presents potential problems with implant valve stability, a paravalvular leak, or framework fracture. To overcome such issues, several techniques of pre-stenting the RVOT have been developed to create a “landing zone” for the selected transcatheter valve11. Implantation of the Melody™ valve in the branch PAs has also been described102.More recently, the application of both Melody™ and Sapien™ valves in the so-called “native” RVOT have been described in case reports and case series105. Paralleling the limited application of these first-generation PPVIs in the “native” RVOT is the development of self-expanding percutaneous valves such as the Harmony™ valve , the Venus P™ valve , and a rendezvous Alterra™ stent (Edwards Lifesciences) as a landing zone for a Sapien™ valve111. The flared ends of these systems are designed to provide stability in the large pulsatile outflows, whilst the self-expanding nitinol frames adapt to various outflow anatomies , and over half had tricuspid valve disease associated with congenital heart disease including Ebstein’s anomaly, intrinsic tricuspid valve (TV) abnormalities, or TV injury related to previous surgery or catheter intervention. There was an excellent procedural success of 99%, with significant improvements in the degree of regurgitation or stenosis and symptomatic improvement. The 30-day mortality was 3.3%, and estimated freedom from tricuspid re-intervention at 1 year was 83%. The extension of the tricuspid VIV concept to VIR is considerably more challenging owing to larger diameters and geometric variability of surgically placed rings. Although this approach is technically feasible and clinically effective in reducing tricuspid regurgitation, paravalvular regurgitation has been common120.The rapidly expanding transcatheter heart valve technology has been applied to the treatment of atrioventricular valve dysfunction with a growing experience in the tricuspid valve position. Implantation of percutaneous valves into degenerated bioprostheses  or into annuloplasty rings  is an attractive alternative to surgery in the high-risk and often-debilitated patient with acquired or congenital cardiac disease121. Mitral VIV implantation is more difficult to accomplish owing to difficulty in coaxial alignment of the percutaneous valve within the existing valve. The majority of implantations are performed using a direct transapical approach with the larger diameter Sapien™ valves124. A transvenous, transseptal technique utilizing an apical rail to facilitate the delivery of Melody™ valve into the dysfunctional mitral prosthesis has also been described118. To date, the results of mitral VIV implantations within a high-pressure hemodynamic environment have shown good valve performance with low transvalvular gradients and low rates of paravalvular regurgitation in the short term125. Applying the Sapien™ valve to surgically implanted ring (VIR) is even less appealing because of incomplete sealing of the variable and D-shaped annuloplasty rings and the risk of causing left ventricular outflow tract obstruction. Recent successful case reports of the Melody™ VIR technique, however, offer significant promise127. Compared to Sapien™ valves, the Melody™ valve has a longer stent that is covered throughout its length, which provides good sealing at the subvalvar level128. Transcatheter valve-in-native-ring for calcified native mitral stenosis has also been reported in high-risk adult patients131.Transcatheter mitral valve replacement remains in its early clinical stages133. The Melody™ valve has the potential for future expansions with child growth and is a viable option in the lack of appropriately sized mitral valve prostheses in these small children; however, further study is required to determine longer-term durability and safety.In infants and children with severe mitral stenosis or regurgitation associated with congenital heart disease, the Melody™ valve as a surgical implant has shown promising results after failed attempts at primary mitral valve repairRecent years have seen the rapid development of imaging and device technologies as well as percutaneous interventions in a variety of congenital cardiac lesions, with an increased application of percutaneous therapies to a broad range of patients. It is important, however, to remember that long-term outcomes for many such novel interventions are lacking, and rigorous prospective studies and data surveillance are required to determine safety and efficacy profiles before these become standard of care. Future innovations and growing experience in this field, in addition to increased collaboration between surgeons and interventionists, will undoubtedly continue to expand transcatheter options in the management of congenital heart disease, further improving the quality of life for the child and adult with congenital heart disease. This short review touches on some of the highlights that have been developed over the last decade. A number of percutaneous procedures (not mentioned) have become standard of care in many centers, and with continued diligence we can anticipate the continued application of such therapies.


Surgical repair of isolated congenital tricuspid valve (TV) disease is rare with no well-defined indication and outcomes. Moreover, the role of right ventricle (RV) in this context has not yet been investigated.We sought to assess the impact of congenital TV repair on cardiac remodelling and clinical–functional status and the importance of the RV function in an adult congenital heart disease (ACHD) population.p < 0.01), clinical signs of heart failure , and left ventricular function . The RV and right atrium diameter were significantly reduced after surgery  and , respectively. The degree of postoperative pulmonary hypertension was also significantly reduced . The survival rate was 96.3% at 1 year and 93.7% at 5 years. One patient (3.7%) had early failure of the tricuspid repair requiring a reoperation.From January 2005 to December 2015, 304 patients underwent TV surgery in our centre. Of these, 27 (ACHD) patients had isolated TV repair. Patients were evaluated with preoperative and postoperative transthoracic echocardiogram. Survival rate has been investigated with a mean clinical follow-up (FU) of 3.7 ± 2.3 years, whereas the mean echocardiographic FU was 2.9 ± 1.8 years. The clinical and functional status of patients showed a statistically significant improvement after the surgical repair in terms of New York Heart Association class (66.7 vs 7.4%; Isolated TV repair for adult congenital disease significantly improved patients’ clinical and functional status and allowed right ventricular remodelling and functional improvement. Isolated severe congenital tricuspid regurgitation (TR) is an uncommon condition, most frequently associated with a variety of concomitant heart diseases. Regardless of the presentation, the surgical management is similar , 2. To dThe study was conducted in accordance with the principles of the Declaration of Helsinki. The local audit committee approved the study, and the requirement for individual patient consent was waived.From January 2005 to December 2015, a total of 304 adult patients underwent TV repair or replacement at Bristol Heart Institute. Patients with concomitant left heart valve diseases and/or other cardiac congenital diseases, those who underwent TV replacement and those with endocarditis were excluded  were defined as ACHD patients undergoing surgical TV repair for isolated TR.The clinical conditions were assessed following the classification proposed by the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS). Both preoperatively and at the end of follow-up (FU), patients were assigned to a correlated class. Clinical signs and symptoms of RV failure and onset of newly discovered cardiac arrhythmias were regularly assessed during FU outpatient clinics. Short-term outcomes were derived from clinical notes: acute kidney injury was defined as an increase, during admission, of over 50% in serum creatinine compared to preoperative values, as previously recommended ; acute rAll patients underwent transthoracic echocardiography preoperatively, within 2 weeks after the operation and at FU. The following parameters were assessed: left ventricular ejection fraction (LVEF), left ventricular internal diastolic diameter, left ventricular internal systolic diameter, thickness of the interventricular septum in diastole, diameter of the posterior wall, RV functional assessment (RV failure), right ventricular internal diastolic diameter, right ventricle dilatation (RV dilatation), area of left atrium (LA area), area of right atrium (RA area), pulmonary artery pressure (PAP), grade of pulmonary hypertension, grade of TV regurgitation, tricuspid annular plane systolic excursion (tapse), and presence of haepatic veins backflow.t-test if normally distributed or Mann–Whitney U test if not normally distributed. In the case of dichotomous or categorical variables, Pearson chi-square or Fisher exact tests were used as appropriate. Overall long-term survival was estimated by Kaplan–Meier curve. All tests were two-sided with the alpha level set at 0.05 for statistical significance. The statistical analysis was computed using R version 3.0.2 for Windows .Data are presented as mean ± 1 SD for continuous variables or as number and percentages for dichotomous variables. Continuous variables were tested for normality using the Kolmogorov–Smirnov test and then compared between groups with unpaired Student’s Patient characteristics and preoperative variables are summarised in Table http://www.ctsnet.org/article/cone-reconstruction-tricuspid-valve-repair-ebstein-anomaly), seven patients (25.9%) had annuloplasty ring and the remaining patients (40.7%) had other types of repair . Most patients had isolated TV surgery; concomitant ASD closure was performed in four (14.8%) patients; antiarrhythmic surgery such as MAZE procedure was also performed in four (14.8%) patients. Mean cardiopulmonary bypass time was 104.9 ± 44.7 min, and mean cross-clamp time was 66.3 ± 32.4 min. In one case (3.7%), with Ebstein disorder, it was necessary to re-operate during the postoperative course for failure of TV repair; this patient eventually underwent TV replacement. One patient (3.7%) suffered a postoperative deep wound infection (mediastinitis), which required surgical re-exploration: this condition deteriorated to postoperative sepsis and subsequent death. No patient experienced episodes of cerebral ischaemia (CVA) or renal impairment in the perioperative period.Intraoperative and postoperative findings are shown in Table p < 0.01) and 22.2% in CCS class III–IV preoperatively vs 3.7% at FU (p < 0.01). Also, our study demonstrated a significant reduction of clinical signs of heart failure such as ascites and peripheral oedema . These data are shown in Table The clinical and functional status of patients assessed according to the NYHA and CCS classification shows a statistically significant improvement: 66.7% patients in NYHA class III-IV preoperatively vs 7.4% at FU (p < 0.01), while no significant differences were found regard to the left ventricular diameters and wall thickness. Similarly, no significant differences were found concerning the left atrial volumes. At FU, all patients showed a significant reduction in right ventricular diameters . We also observed a different remodelling in right atrial geometry . Regarding the functionality of TV, a clear reduction of valvular regurgitation has been observed at FU. Furthermore, TR significantly improved both in patients with moderate  and severe baseline TR . In addition, the pulmonary pressure  and the degree of pulmonary hypertension  were significantly reduced. A net reduction was also noticed in the number of patients with haepatic veins backflow . On the other hand, TAPSE values dropped significantly in this period of evaluation .Table p = 0.01) without supplementary modification of wall thickness.In Table p = 0.03) and RV dilatation .Similar to the main analysis, this sub group showed a substantial reduction in right ventricular diameters . Furthermore, the Ebstein population also showed a visible reduction of valvular regurgitation between the preoperative and the FU . In addition, TAPSE values were considerably reduced .An interesting reduction has been observed on right atrial area , and RA area ; this is most likely due to the effect of reduced RV pre-load. On the other hand, there was no significant change in RV function (p = 0.1); this is probably due to advanced structural modification of the RV which may have occurred before the time of the surgery .Annular repair also leads to increased stability of the cardiac skeleton, which might partially explain the reduction of the TAPSE at FU  despite there being no changes in the left ventricular diameters and wall thickness; possibly due to a reduction of volume of the RV which decreases the compression on the left ventricle.There was a marked improvement in left ventricular function , strengthening the idea that structural damage is a non-reversible phenomenon. As reported in the literature, AF has been recognised as an objective predictor of survival, rising mortality and morbidity due to thromboembolism risk and heart failure . The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Modelling and simulation may become clinically applicable tools for detailed evaluation of the cardiovascular system and clinical decision-making to guide therapeutic intervention. Models based on pressure–volume relationship and zero-dimensional representation of the cardiovascular system may be a suitable choice given their simplicity and versatility. This approach has great potential for application in heart failure where the impact of left ventricular assist devices has played a significant role as a bridge to transplant and more recently as a long-term solution for non eligible candidates.© was the software used for this purpose. The study was based on retrospective analysis of haemodynamic data previously discussed at a multidisciplinary meeting. The outcome of the simulations addressed the value of a more quantitative approach in the clinical decision process.We sought to investigate the value of simulation in the context of three heart failure patients with a view to predict or guide further management. CARDIOSIMAlthough previous experience, co-morbidities and the risk of potentially fatal complications play a role in clinical decision-making, patient-specific modelling may become a daily approach for selection and optimisation of device-based treatment for heart failure patients. Willingness to adopt this integrated approach may be the key to further progress. Physiological fluid flow modelling using computational fluid dynamics (CFD) has increased our understanding of complex system interactions with particular reference to problem solving in a clinical environment –6. FunctMathematical modelling and simulation may become clinically applicable tools for detailed evaluation of the cardiovascular system and clinical decision-making to guide therapeutic intervention . Models This approach has great potential for application in heart failure where the impact of left ventricular assist devices (LVADs) has played a significant role as a bridge to transplant and more recently as a long-term solution for non eligible candidates. Continuous flow rotary blood pumps are currently the most popular devices because of their smaller size, increased reliability and higher durability compared to pulsatile-flow devices. The trend towards their use is increasing. Mathematical modelling and computer simulation are invaluable tools to investigate the interactions between LVADs and the cardiovascular system –24. CFD Ees) of the end-systolic pressure–volume relationship (ESPVR) to justify dissociation between contractility and elastance [The native ventricular behaviour can be modelled according to the time-varying elastance theory –30, whiclastance . Althouglastance –35 and alastance , recent lastance  based onlastance –40 has slastance  and ventlastance –44. To alastance  can be mlastance . This islastance , 48. A Llastance  can be alastance  using filastance , 52 to alastance , 54 alrelastance –57 can blastance .A more targeted approach for different group of patients;More quantitative evaluation in the clinical decision process;The predictive value of simulation;Preoperative planning and treatment optimisation.Following these considerations, we sought to investigate the value of simulation in the context of three heart failure patients previously discussed at a multidisciplinary meeting with a view to predict or guide further management. The aim was to compare the outcome of the simulations with the previously made clinical decision in order to find out any relationship that may be applicable on a routine basis in future patient assessment. The key elements would be:We retrospectively analysed the haemodynamic data of three heart failure patients previously discussed at a multidisciplinary meeting and subsequently treated accordingly. Given the retrospective nature of this study, informed consent was waived . The aim©, which is a software package developed by the Cardiovascular Numerical Modelling LAB linked to the Institute of Clinical Physiology, CNR, Rome, Italy [The study was carried out using CARDIOSIMe, Italy . This ise, Italy , 15. Thee, Italy –24, intre, Italy , 61–63.When the native atrial and ventricular behaviour are modelled, the numerical simulator allows choosing between two different modules –19 based follows :\documeneak time , 19.Instantaneous left and right ventricular pressures  follows :1\documeThe same approach is applicable to the atrial chambers, the interventricular (IVS) and interatrial (IAS) septum . The IVSribed in , 19. \doEquation  are esseSimilarly, the following equations were used to reproduce the atrial behaviour , 19:3\doribed in , 19; \doEquation  are esseThe systemic arterial section consists of the aortic, thoracic and abdominal compartment and is modelled as described in , 65 withFigure The inlet and outlet cannulae flows The LVAD flow mentclass2pt{minimThe first order ordinary differential equations of the cardiovascular model were initially solved using both Euler’s and fourth order Runge–Kutta’s methods. The two numerical methods gave the same results under steady state conditions. The Euler’s method with a time step of 1 ms was preferred because of its lower computational cost compared to the Runge–Kutta’s method. The simulation software was written using Visual Basic language. Statistical analysis was carried out using the unpaired “t” test and correlation coefficients were calculated.The retrospective analysis was performed on the haemodynamic data of the following patients:Ea) of arterial elastance (Ea ≈ BPmean/SV) [A 34-year-old patient who sustained an extensive anterior wall myocardial infarction, which was initially treated with a percutaneous interventional procedure and the insertion of a drug eluting stent to the left anterior descending coronary artery. Subsequently, stent occlusion and residual severe left ventricular systolic dysfunction with an ejection fraction of 27% required full anti-failure treatment. Further deterioration required dobutamine infusion and close monitoring. The presence of co-morbidities, particularly high body mass index (BMI), made this patient unsuitable for transplant while the insertion of a left ventricular assist device remained debatable and unlikely to be beneficial. Haemodynamic data from repeated right heart catheter showed persistent elevated pulmonary artery pressures and resistance with significantly reduced right ventricular stroke work index, which increased the need for right ventricular support following LVAD insertion with potential for prolonged intensive care need and increased risk and complications. The final decision following a multidisciplinary team (MDT) meeting was to continue with medical management and palliative treatment. Table mean/SV) , where SLeft was 45% in the context of chronic atrial fibrillation, previous ventricular arrhythmias and renal impairment. Symptoms deterioration required multiple hospital admissions with readjustment of anti-failure treatment and finally commenced on Milrinone (PDE3 inhibitor) infusion. A MDT meeting considered a LVAD not a suitable option and therefore this patient was placed on the transplant list. Table A 55-year-old patient with hypertrophic cardiomyopathy (NYH7 mutation), who previously underwent aortic valve replacement with a mechanical prosthesis and subsequently percutaneous intervention to the left anterior descending coronary artery. Left ventricular ejection fraction EFA 52-year-old patient who previously sustained a myocardial infarction requiring coronary artery bypass grafting and subsequently implantable cardioverter defibrillator (ICD) insertion because of ventricular arrhythmias. Significant deterioration of the clinical picture had already required multiple hospital admission in a background of dilated left ventricle (left ventricular end-diastolic diameter 8.1 cm) with severe systolic (left ventricular ejection fraction 15%) and diastolic dysfunction (E/A ratio 3.4) and severe pulmonary hypertension. Finally, Milrinone and diuretic infusion were commenced and an intra-aortic balloon pump was inserted. Following a MDT meeting, this patient was listed for transplant with a view to LVAD insertion if further deterioration occurred. Table The diseased status for each patient was reproduced starting from the measured parameters. Subsequently, LVAD support without and with drug administration (Milrinone) was applied to each patient. The effects induced by Milrinone administration were simulated with the aim to increase heart contractility by 10% and reduce pulmonary and systemic resistances by 10%.Ees of the end-systolic pressure–volume relationships (ESPVR) and the ratio Ea/Ees. In normal conditions, Ea/Ees ratio represents a reliable index of ventricular–arterial coupling. The estimated and simulated Ea are similar. The last column of the table shows simulated values during LVAD assistance. EDV, ESV and SV decreased with a leftward shift of the left ventricular loop (in the pressure–volume plane) during LVAD support. Moreover, Ea decreased from 3.2 (mmHg/ml) to 2.6 (mmHg/ml) and the Ea/Ees ratio decreased from 3.64 to 2.95 during assistance. Two different values for PVR are reported in Table VENTR), the second one is calculated as the ratio between TPG and LVAD flow (QVAD).Table Ea/Ees ratio decreases from 1.62 to 1.32 when LVAD support is applied. When the effects induced by the simultaneous presence of LVAD and pharmacological treatment are simulated, left ventricular ejection fraction EFLeft increases from 45.1% (“Admission” conditions) to 55.9% and the Ea/Ees ratio decreases from 1.62 (“Admission” conditions) to 1.20. LVAD assistance and Milrinone administration reduce EDV and ESV .Although previous experience, co-morbidities and the risk of potentially fatal complications play a role in the clinical decision process, a simulation setting may well add a more quantitative approach and perhaps reassurance even if the clinician remains the ultimate decision-maker. Interactive software like CARDIOSIMThe development of an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure–volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time. The challenge remains the ability to predict outcome over a longer period of time.Patient-specific modelling may become a daily approach for clinical management and optimisation of device treatment. Willingness to adopt such an integrated approach may be the key to further progress.


Cardiac aging, which can result in subclinical alterations in the heart, is considered a condition that bridges elderly and the incidence of cardiovascular events. Left ventricular (LV) ejection fraction (LVEF) and mass (LVM) are indices presenting ventricular dysfunction and hypertrophy, two important indicators in cardiovascular risk estimation. Heart deformation analysis (HDA) is a recently developed imaging processing technique for the description of global and regional myocardial function and motion on cine MRI. Using a deformation image registration (DIR) algorithm, HDA is able to automatically track the shape of LV through the entire cardiac cycle by calculating deformation fields (forward and backward) of myocardium tissue among sequential cardiac time frames. As such, global cardiac indices  as well as regional myocardial motion indices  can be extracted from cine images using a semi-automatic "one-stop-shop" analysis with minimal user interaction. However, to date the capability of HDA tool for the evaluation of LV global function and morphology has not been validated in a larger clinical study cohort. Therefore, the aim of the present study was to assess the accuracy of automated quantification of left ventricular function and mass based on HDA in asymptomatic older adults by using a standard LV global function analysis as the reference standard.This study complied with HIPAA regulations. Following the approval of the institutional review board (IRB), 160 asymptomatic older participants were recruited for cardiac MRI including two-dimensional (2D) cine images covering the entire left ventricle (LV) in short-axis view. Data analysis included the calculation of left ventricular ejection fraction (LVEF), mass (LVM) and cardiac output (CO) using HDA and standard global cardiac function analysis . The agreement between methods was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CoV).There was good agreement for LVEF , CO  and LVM  acquired with standard method and HDA. There was a systemic bias towards lower LVEF  and CO  by HDA compared to the standard technique. Conversely, HDA overestimated LVM  as compared to the reference method.HDA has the potential to measure LVEF, CO, and LVM without the need for user interaction based on standard cardiac 2D Cine images.


In clinical MRI, T2-weighted techniques are commonly used to visualize myocardial edema. The aim was to study the acute T1 mapping was performed using the Small-Animal Look-Locker Inversion Recovery (SALLI) technique. Short axis SALLI MR imaging was performed using the same short axis orientation in the mid ventricle distal to the occluder, with SALLI parameters as previously described. Without removing the animals from the scanner, the left coronary artery was occluded for 15, 30 or 60 minutes. 2 groups of animals underwent 3 cycles of 5 minutes of preconditioning before 30 and 60 minutes of ischemia. Myocardial T1 was measured was repeated at 15 minutes intervals during the experiment, throughout ischemia and the 90 minutes of reperfusion. MRI was performed on a whole-body 3.0-T MR unit with a dedicated rat coil.5 groups of rats had an inflatable balloon coronary occluder surgically inserted via thoracotomy. They were allowed to recover for 7 days. MRI was performed to obtain baseline measurement of ventricular function. T1 increased in the area-at-risk (AAR) within the first 15 minutes of ischemia. T1 values increased slightly with longer periods of ischemia, but did not change with myocardial reperfusion. Preconditioning led to a more gradual and lesser increase in myocardial T1 in the AAR. Changes in T1 persisted at 3 and 7 days.Myocardial T1 in real time in a model of ischemia/reperfusion. Changes in myocardial T1, likely reflecting myocardial water content, occur early following the onset of myocardial ischemia and values remain elevated for at least seven days following ischemia. Preconditioning appears to lead to less myocardial oedema, which may explain some of its protective effects in myocardial ischemia. T1 mapping might provide an imaging marker for monitoring the quality of myocardial reperfusion.Myocardial T1 mapping is able to study the changes in myocardial T


T1 mapping, has emerged as an accurate, reproducible, highly sensitive, and quantitative technique for the assessment of diffuse myocardial fibrosis in a number of disease states. We comprehensively review the physics behind CMR relaxometry, the evidence base, and the clinical applications of this emerging technique.Cardiac magnetic resonance (CMR) imaging has been widely used to assess myocardial perfusion and scar and is the non-invasive gold standard for identification of focal myocardial fibrosis. However, the late gadolinium enhancement technique is limited in its accuracy for absolute quantification and assessment of diffuse myocardial fibrosis by technical and pathophysiological features. CMR relaxometry, incorporating  T1-weighted images with excellent signal-noise ratios, and this has become the reference standard for non-invasive scar imaging in cardiomyopathies of various causes . Imaging of myocardial fibrosis using relative differences between scar and normal myocardium tissue is therefore qualitative. Semi-quantitative analysis of LGE can be performed using signal thresholding applied to LGE images; however, there are differences in technique for infarct quantitation (Cardiac magnetic resonance (CMR) imaging has been used widely to assess myocardial perfusion and scar –5. It iss causes . Howevers causes , 7. Moretitation , and thiThus, in non-ischemic cardiomyopathies, such as hypertension or diabetes, LGE CMR is unable to detect signal differential where the collagen deposition is diffuse and widespread throughout the myocardium .Cardiac magnetic resonance is an evolving technique, providing valuable and comprehensive data on the anatomy and functional integrity of both the heart and coronary blood vessels. Currently, CMR is performed at magnetic field strengths of 1.5 or 3 T. MR images generate by exploiting the magnetic property  of nuclei that have an odd atomic number or mass number . A protoB0) they will align either parallel or anti-parallel to the magnetic field. Spins that aligned parallel to B0 have a lower energy than those aligned anti-parallel, and therefore more align parallel creating a net magnetization (M0) of the sample in the direction of the magnetic field B0 , at a frequency specific to the strength of (B0)— the Larmor frequency. The Larmor frequency is defined as follows:B0 is the strength of the magnetic field, γ is the gyromagnetic ratio for hydrogen, and γ/2π = 42.57 MHz/T (The interaction of a magnetic moment with 57 MHz/T .xy axis) and be in phase. With cessation of the RF field, the nuclei will realign to their original orientation parallel to B0—a process referred to as relaxation. During the relaxation process, the net relaxation induces an RF signal, at the characteristic frequency, which can be measured by a receiver coil. This signal is known as free induction decay (FID).When a radio frequency (RF) pulse at the Larmor frequency is applied to the nuclei within the magnetic field, nuclei begin to resonate and those in the lower energy state absorb energy. Depending on the RF pulse length, the precession of affected nuclei will be moved into the transverse magnetization plane . T2. T2T2 reT2), together with inhomogeneity in the static magnetic field (ΔB0), which occurs at tissue interfaces. This leads to a more rapid loss of phase coherence and the MR signal. These relaxation times are influenced by several factors, including field strength, blood iron content, blood volume, temperature, and blood oxygenation  sequence. Spin echo uses a 180°RF pulse to invert the spins within the selected slice, followed by a 90°RF pulse rotate the recovered magnetization at TI into the transverse plane, and a further 180° RF pulse to form the spin echo (T1 relaxation (during TI). IR-SE is a gold standard to estimate T1 with a good accuracy. However, the drawback of IR-SE is that the TR of the sequence should be very long, i.e., TR should be at least five times longer T1 to allow full recovery of longitudinal magnetization. To reduce the acquisition time, inversion recovery turbo spin echo is currently used for routine clinical purposes  directly on a standardized scale within a single breath hold. This quantification of T1 mapping provides a benefit over the T1-weighted imaging of the myocardium by giving a quantitative measure of T1 time from multiple scans. A parametric map can be then reconstructed by calculating T1 values on a pixel-by-pixel basis  and modified Look–Locker inversion recovery (MOLLI)  , 18–24.T1 relaxation time values is the eponymously named “LL” sequence . It has been widely used to estimate the optimal TI for assessment of myocardial LGE  or FIDs (pulsed magnetic resonance), it is possible to save time in spin-lattice relaxation measurements due to the fact that it is not necessary to wait for equilibrium magnetization before initiating the train .The most common technique to measure spin-lattice dial LGE , 25. It dial LGE . It cons LGE  was incorporated into the IR LL-based method , by intethan 3 s , using athan 3 s , sacrifithan 3 s  and has than 3 s .The development of LL technique, which is available on Philips, GE, and Siemens platforms, is summarized in Table T1 values in patients with myocardial fibrosis  in myocardial segments requires adjusting for cardiac motion, which result in including blood pool  and artificially increasing the measured T1 , or with different contrast agents; correction factors have been proposed using kinetic modeling for the LL technique  are carried out with three, three, and five single-shot readouts, respectively, at end diastole of consecutive heartbeats to sample the recovery of longitudinal magnetization after the inversion pulse. MOLLI pulse sequence scheme is illustrated  administration  able to be analyzed in a pixel-wise quantitative fashion  had an inverse linear relationship with collagen content in myocardial fibrosis subjects  T1 values had good agreement, but LL had wider limits of agreement, and post-contrast T1 maps also had good agreement but with LL giving higher values than MOLLI, hence they are not interchangeable  within a single breath hold of about 15–20 s. However, the apex T1 values with MOLLI are slightly higher than basal and mid-cavity. The increasing in T1 values may be caused by partial volume effect and some degree of overestimation effect in apical level of left ventricle. These effects occur as a result of the ventricular wall being somewhat tilted toward the apex and no longer being aligned perpendicular to the short axis images    leading th MOLLI , 42.T1 maps). This may be difficult for elderly and pulmonary compromised patients and generates respiratory and motion artifacts (T1 maps (motion corrected or “MoCo MOLLI”). This will minimize the sensitivity of T1 mapping to motion artifacts and heart rate. Also, various acquisition sequences with short breath hold, such as shortened modified Look–Locker inversion recovery, have been validated and recently applied for cardiomyopathies  are significantly longer than those of normal myocardium   were significantly shorter in chronic infarct scar compared with normal myocardium at 0.15 mmol/kg   . The lonT1 times . Howeverolecules , 54. Mesd on LGE . Howeverctively) .T1 mapping with high magnetic field (3 T) has been reported in a few studies of interstitial myocardial fibrosis. It was similar to 1.5 T, the pre-contrast T1 was longer, and post-contrast T1 was shorter in myocardial fibrosis patients compared to normal myocardium. Puntmann et al. . Also, the post-contrast T1 values (10 min) at 3 T were shorter in hypertrophic and dilated cardiomyopathies compared to healthy  ; thus, post-contrast Box 1Pre-contrast “Native” T1 = predominant signal from myocytes . Post-contrast T1 = predominant signal from interstitial space .T1 mapping data can be used to calculate ECV fraction, using the pre- and post-contrast T1 times and hematocrit. Details of this technique and its uses are beyond the scope of this review; SCMR guidelines exist to guide application of T1 mapping and ECV quantitation , to inform treatment decisions, and their ability to predict or alter clinical outcomes.Challenges remain with myocardial relaxometry for T1 mapping using quantitative relaxometry is an emerging and important tool in the assessment of global myocardial fibrosis. It is a highly sensitive marker of disease but is not specific, with changes in myocardial T1 occurring in many different conditions. Nevertheless, the high sensitivity and excellent reproducibility of the technique offers a tool for the early detection of myocardial damage, over-and-above techniques such as the CMR LGE technique and other modalities such as speckle tracking echocardiography, pulse wave velocity, and tissue tagging. Native T1 mapping is proving to be a robust indicator of early myocardial disease in many conditions, and normal ranges and guidelines for post-processing have been published by the Society of Cardiovascular Magnetic Resonance (T1 mapping is a rapidly evolving technique, now with longitudinal prognostic data emerging, and normal ranges established at 1.5 and 3.0 T in healthy humans and in aging. Further questions remain as to the standardization of pulse sequences across field strengths and between vendors, the affect of contrast type, dose and timing, the post-processing software, and the interpretation of T1 mapping results to inform clinical practice.Myocardial esonance . MyocardCH-C, MS, and GG: main contributions to the conception or design of the work; the interpretation of data for the work; drafted the work and revised it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Adverse outcomes are increasingly common in patients after the Fontan operation as they approach adulthood. Right ventricular (RV) morphology, ventricular dilation, and diminished ventricular strain have all been independently associated with death or heart transplant. The aim of this study was to assess the impact of ventricular morphology on ventricular stress/strain relationship in patients late after the Fontan operation using cardiac magnetic resonance (CMR).Clinical CMR studies in patients with Fontan circulation between January 1, 2005 and June 30, 2013 were retrospectively analyzed. Ventricular mass and volumes were calculated using commercially available software . Global circumferential strain (GCS) was measured for the single or dominant ventricle at the mid ventricular level using commercial software . End systolic wall stress (WS) was calculated for the ventricle using a thick-walled sphere model. Arm cuff mean arterial blood pressure was used as a surrogate for left ventricular end-systolic pressure.The study population consisted of 126 patients  with median age of 16.9 years (IQR 12.3-23.3) and a median age at Fontan surgery of 3.2 years (IQR 2.3-5). The dominant ventricular morphology was left (LV) in 52% and RV in 48%. Compared with LV dominant Fontan patients, RV-dominant patients were younger , had a higher heart rate , and lower mean arm blood pressure . RV-dominant patients also had higher WS  and lower GCS . Multivariable linear regression analysis controlling for age, heart rate, and body surface area demonstrated that each unit reduction in GCS was associated with an increase in WS of 0.8 KPa , and RV morphology was associated with higher WS independent of GCS (p = 0.003). Relationships between WS and strain in the left and right ventricles are shown in Figure Compared to Fontan patients with a functional single LV, those with a dominant RV have an adverse stress-strain relationship. Inadequate ventricular hypertrophy is the primary driver for higher WS in single RVs. This may, in part, explain the previously reported unfavorable outcomes in Fontan patients with RV morphology as compared to LV morphology.


To quantitatively assess changes in cartilage matrix after acute anterior cruciate ligament (ACL) rupture using T2- and T2⁎ values were measured in full-thickness as well as superficial and deep layers of each cartilage compartment. Differences of T2 and T2⁎ values between patients and controls were compared using unpaired Student's t-test, and the correlation between their reciprocals was analyzed using Pearson's correlation coefficient. Twenty-three patients and 23 healthy controls were enrolled and underwent quantitative MRI examination. The knee cartilage was segmented into six compartments, including lateral femur (LF), lateral tibia (LT), medial femur (MF), medial tibia (MT), trochlea (Tr), and patella (Pa). T2 and T2⁎ values in full-thickness and superficial layers of medial and lateral tibiofemoral joint. Meanwhile, patients exhibited higher T2⁎ values in deep layers of lateral tibiofemoral joint. The elevated percentages of T2 and T2⁎ value in superficial LT were most significant . The reciprocal of T2⁎ value was correlated with that of T2 value . ACL-ruptured patients showed higher T2 and T2⁎-mapping might be more sensitive in detecting deep layer of cartilage than T2-mapping. The early degeneration could occur in various knee cartilage compartments after acute ACL rupture, especially in the superficial layer of LT. T2 The anterior cruciate ligament (ACL) is the primary constraint to the anterior translation and internal rotation of the tibia and acts as an important stabilizer of the knee. ACL sprain or tear constitutes one of the most common types of knee injuries during sports . Acute AMagnetic resonance imaging (MRI) has been demonstrated to be a useful and noninvasive imaging tool for the assessment of pathological alterations in cartilage morphology , 8. In t∗-mapping has demonstrated a number of benefits including short scan time and high resolution. Recent studies on the application of quantitative T2∗-mapping have shown promising results for the evaluation of cartilage matrix [∗ is defined as the observed rate constant for the decay of transverse magnetization that includes both T2 relaxation and coherent dephasing effects as a result of local magnetic field inhomogeneity. The relationship between T2∗ and T2 follows the equation 1/T2∗ = 1/T2 + γΔB [B0), T2∗ would depend on both T2 and local susceptibility-induced magnetic fields. In the context of cartilage imaging, it has been suggested that these fields often play a significant role at the bone-cartilage interface and within the fundamental cartilage microarchitecture, which could translate into changes in T2∗ readings [∗-mapping might be a more sensitive imaging strategy for identifying cartilage degeneration of calcified layers [∗-mapping was found to offer the advantages of shorter scan time and compatibility with 3D acquisition over T2-mapping in the visualization of articular cartilage [Compared to T2-mapping, quantitative T2e matrix . T2∗ is T2 + γΔB . Thus, areadings . This thd layers . Indeed,artilage . The metartilage , 18.∗- and T2-mapping techniques in the assessment of cartilage matrix changes after acute ACL rupture. In addition, little is known regarding the detailed topographic degeneration of knee cartilage after acute ACL rupture. To address these needs, the current study applies T2- and T2∗-mapping to the visualization of cartilage matrix in patients with acute ACL rupture and healthy controls and analyzed the correlation of the results of two methods. We hypothesized that patients with acute ACL rupture would show an elevated T2 and T2∗ value at various compartments of knee cartilage when compared with healthy subjects. Additionally, the reciprocal of T2∗ value might closely correlate with that of T2 value.To date, very few studies have compared T22. Exclusion criteria comprised knee OA, inflammatory arthritis, knee trauma, posterior cruciate ligament tear, medial or lateral collateral ligament injury, and serious meniscus corner injury that required surgery. Patients who had previously received knee surgery were also eliminated from consideration. For the selection of healthy volunteers, who served as controls, candidates were excluded if they had a history of disease, injury, or surgical intervention in the knees, or if their MRI scans revealed any of the abovementioned knee abnormalities. The eligible healthy participants were matched to the patients according to sex, age, and BMI. One knee of each healthy subject was randomly selected for MRI examination. Thirty patients were diagnosed by standard MRI as having ACL rupture without tear of collateral or posterior cruciate ligament, among whom 27 subsequently were confirmed by arthroscopy during reconstruction surgery. Among the 27 patients, four were excluded due to the detection of serious meniscal injury that warranted surgical treatment. On the other hand, three of the 26 asymptomatic healthy volunteers were also excluded, including one with ACL abnormality and another two with meniscal injury showed by MRI examination. After the prescreening, the final study cohort consisted of an ACL rupture group of 23 patients and a control group of 23 healthy adults, with no significant difference in sex, age, or BMI between the two. The mean interval time from rupture to MRI scan was 3.5 months, whereas the mean interval period between MRI examination and surgery was 2.5 months. Participants' demographic data was shown in The study was performed according to guidelines approved by the health sciences institutional review board of our hospital. Written consent was obtained from all participants prior to the experiments. The selection criteria for patients included clear evidence of unilateral ACL rupture as shown by MRI or clinical examination and confirmed by arthroscopy , no prio∗-mapping. The MRI parameters were optimized in order to achieve the highest signal noise ratio (SNR) and image quality. T2- and T2∗-mapping were conducted using similar imaging parameters to enable comparison. The knees were positioned in parallel to the direction of B0 [All MRI scans were performed on a 3T MRI unit  with a gradient strength of 40 mT/m an 8-channel phase array knee coil. Imaging sequences included fat-saturated proton-density weighted imaging (PD-FS), three-dimension double echo steady state sequence (3D-DESS), and quantitative MRI T2- and T2on of B0 . Each paon of B0 . The mor∗-mapping . T2 and T2∗ values were obtained using a pixel-wise, monoexponential nonnegative least squares (NNLS) fit analysis.Quantitative assessment of knee cartilage was performed in the sagittal plane using both T2-mapping  and T2∗ relaxation times were measured from the images of each cartilage compartment and then averaged to obtain the mean T2 and T2∗ values, respectively. Subsequently, colored T2 and T2∗ maps were generated using NUMARIS/4 and Syngo MR B17 , which could reflect the detailed topographic distribution of T2 and T2∗ values.The knee cartilage was partitioned into six compartments: lateral femur (LF), lateral tibia (LT), medial femur (MF), medial tibia (MT), trochlea (Tr), and patella (Pa). In addition, LF, MF, LT, and MT were each further segmented semiautomatically by in-house software into two equal layers, the superficial layer and the deep layer . T2 and ∗ measurement was performed by a main observer and repeated by another observer in order to assess the interobserver reliability. The main observer reanalyzed these subjects after 2 weeks in a randomized order to evaluate intraobserver reproducibility. In both cases, interclass correlation coefficients (ICC) were calculated and graded as follows: poor (<0.4), marginal (0.4–0.75), and good (>0.75) [In 10 randomized selected patients and controls, each T2 and T2 (>0.75) .∗ values were calculated for each cartilage compartment. Comparison of two groups was conducted using unpaired Student's t-test. Pearson's correlation coefficient was used to evaluate correlation between the reciprocals of T2 and T2∗ values. P < 0.05 was considered statistically significant.Statistical analysis was performed using SPSS version 18.0 software and Microsoft Excel. Means and standard deviations (SD) of T2 and T2∗ measurements were above 0.75 for all cartilage compartments in both groups. The mean T2 and T2∗ values calculated for all cartilage compartments in both groups were summarized in ∗ maps were showed in ∗ values than the control group in the full-thickness and superficial layers of MT and MF (P < 0.05). However, no significant statistical difference in T2 or T2∗ values was observed between the two groups in the deep layers of MT and MF (P > 0.05). For the lateral tibiofemoral joint, significant increases of T2 and T2∗ values were detected in the full-thickness and superficial layers of LT and LF of the patients compared to the healthy volunteers (P < 0.05). It is particularly noteworthy that significantly elevated T2∗ values were also registered in the deep layers of LT and LF of the patients compared to the controls (P < 0.05), whereas no statistically significant augmentation of T2 values was found in the same regions between the two groups (P > 0.05). Meanwhile, no statistically significant differences in T2 or T2∗ values were identified in the Pa or Tr compartment of the patellofemoral joint between ACL rupture patients and the controls (P > 0.05). The percentage increases of T2 and T2∗ values in all cartilage compartments of acute ACL rupture group over those of the control group were calculated and summarized in ∗ value in superficial LT were most significant , while those in Pa and Tr showed the smallest change .The ICC indexes of interobserver reliability and intraobserver reproducibility of T2 and T2∗ values of all cartilage compartments were shown to be positively correlated with each other for the acute ACL rupture group , the control group , and both groups , which were showed in The reciprocals of T2 and T2∗-mapping. The acute ACL rupture group exhibited significantly higher T2 and T2∗ values than the control group in full-thickness and superficial layers of cartilage in medial and lateral tibiofemoral joint, which suggested that the early degeneration can occur in cartilage matrix in these compartments before the morphological changes occur. These results were in general agreement with several previous studies that observed higher T2 and/or T2∗ values in patients with OA compared to healthy individuals [∗ values were found between the two groups in either Pa or Tr cartilage compartment, which means early cartilage degeneration may not occur in Pa and Tr after acute ACL rupture. As previously reported, a higher change in T2 value and T2∗ value of cartilage suggests a higher risk of OA [In this study, we compared subdefined cartilage compartments in patients with acute ACL rupture to those in healthy individuals using quantitative T2- and T2ividuals , 13, 18.sk of OA –18 or ev∗ differences between the two groups were generally more pronounced in the cartilage of tibial plateau than in that of femoral condyle suggested that the tibial cartilage could be more susceptible to early degeneration of cartilage matrix following acute ACL rupture. Moreover, the cartilage of LT exhibited the greatest T2 and T2∗ increases. This finding is echoed by several previously published studies. For example, Nishimori et al. [ρ mapping, Bolbos et al. [ρ values in the posterolateral tibial cartilage of patients with ACL injuries compared to healthy individuals. In addition to the above reports, our study further found that the superficial layer of LT has the highest increased T2 and T2∗ values compared with other cartilage compartments. The result showed that the superficial layer of LT may be more susceptible to reflect the ultra-early cartilage matrix degeneration after acute ACL rupture and it may play an important role in the onset and progression of OA after ACL rupture. However, it is noteworthy that a recent arthroscopic study conducted by Spindler et al. on a cohort of 54 ACL-ruptured patients found considerably more instances of cartilage lesion in the LF condyle than in the LT plateau [∗-mapping could complement arthroscopy in detecting pathological alterations of knee cartilage matrix, especially those occurring in the LT plateau.The observation that T2 and T2i et al.  reporteds et al.  suggestes et al.  revealed plateau . We spec∗ values in all cartilage compartments showed a satisfactory correlation for the ACL rupture group, the control group, and for both groups combined, which responded to the physical equation 1/T2∗ = 1/T2 + γΔB. In addition, both mapping methods showed similar statistical differences between the two groups in the full-thickness and superficial layers of the whole tibiofemoral joint. Consistent results were described by Welsch et al. in their evaluation of cartilage repair in knee and by Marik et al. on osteochondrosis dissecans in talocrural joint [∗ values between the ACL rupture group and the control group exhibited statistically significant differences not observed in T2-mapping. T2 value reflects the concentrations and orientations of collagen and the content of water in cartilage matrix, whereas T2∗ is influenced by T2 and additional factors related to the macromolecular content of cartilage based on microsusceptibility effects [∗-mapping. Therefore, T2∗-mapping could demonstrate greater sensitivity in identifying cartilage degeneration in deep layer compared to T2-mapping. However, T2∗-mapping is also more sensitive to susceptibility artifacts, which might limit its use in patients wearing metallic joint implants [∗-mapping can serve as a useful addition to the current imaging toolbox for evaluating articular cartilage in patients with acute ACL rupture. Further studies will be needed to fully validate and optimize this technique.In our current clinical study, the reciprocals of T2 and T2al joint , 27. How effects , 18, 27.implants . In gene∗-mapping for ACL rupture patients.The most obvious pitfall associated with this study is the relatively small sample size, which precluded us from probing the relationship between cartilage matrix changes and meniscal status. It has been argued that even minor meniscal injuries could be considered a risk factor of OA , which w∗ values in various cartilage compartments of the affected knee, especially in the superficial layer of LT. Moreover, A good correlation between reciprocals of T2∗ and T2 values was observed, and T2∗-mapping was shown to be more sensitive in detecting cartilage matrix changes that occurred in deep layers than T2-mapping. T2∗-mapping was also shown to confer the advantages of faster imaging and greater spatial resolution. These results lent support to the employment of T2∗-mapping as a useful imaging tool for early detection of OA after acute ACL rupture.In conclusion, our results revealed that the early degeneration can take place within cartilage matrix after acute ACL rupture indicated by different increased T2 and T2


Heart failure (HF) patients present with a spectrum of phenotypes, including preserved ejection fraction (HFpEF) and reduced EF (HFrEF). The underlying mechanisms of HFpEF and HFrEF may be related to mechanical factors such as stiffness and stress. This study aimed to quantify passive mechanical properties in HFrEF and HFpEF patients using personalised left ventricular (LV) biomechanical analysis.Data from 9 HFrEF patients, 4 HFpEF patients, and 4 non-HF patients with normal LV function (control) were analyzed. LV finite element mechanical models were personalized using LV surface data segmented from cine cardiac magnetic resonance (CMR) images. All subjects underwent same day left and right cardiac catheterization. Beat-averaged intra-ventricular pressures were extracted from LV catheter traces and temporally aligned with the CMR images. A mechanical simulation of LV diastolic filling was optimized to each patient-specific geometry and pressure loading, incorporating non-linear myocardial anisotropic tissue behavior and myocyte fiber orientation derived from our published work. Global myocardial passive stiffness was estimated by optimization of the predicted LV surface displacements between diastasis and end-diastole to the observed CMR motion. Mid-ventricular end-diastolic fiber stress was also derived from the model.Volume and pressure changes between diastasis and end-diastole, and LV mass measurements are shown in Table Our findings suggest that personalized LV mechanical modeling may provide important diagnostic and therapeutic targets for HF management.


Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls  were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism.Trial registration NCT00766857 Type 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure (HF), even after adjusting for coronary artery disease (CAD) and hypertension . The optPreliminary studies have shown recovery of left ventricular (LV) function during glucagon-like peptide-1 (GLP-1) administration in HF patients irrespective of the diabetic status , 8. Howe−2, hemoglobin A1C (HbA1c) of 6.5–10.0% (48–86 mmol mol−1), were randomized, at an allocation ratio of 1:1, open-label, to exenatide or insulin glargine on top of ongoing use of oral glucose-lowering agents (metformin or metformin and sulfonylurea) after a run-in period of 10 weeks. Exclusion criteria were renal or liver impairment, malignancy, cardiovascular events <3 months, insulin, thiazolidinediones, incretin-based therapies <4 months and chronic glucocorticoid use. Patients with contraindication for positron emission tomography (PET) or CMR  were excluded. Healthy BMI-matched subjects with normal glucose metabolism  served as controls. All participants gave written informed consent. The study protocol was approved by the Medical Ethics Review committee of the VU University Medical Center, and was performed in full compliance with the declaration of Helsinki.T2DM patients with LV dysfunction, LV ejection fraction (LVEF) < 50% , above 18 years, body mass index (BMI) of 25–40 kg m−1) according to a prespecified treat-to-target algorithm acetate and perfusion using [15O]H2O.PET assessments were performed using a hybrid PET/computed tomography (CT) scanner . Oxidative metabolism was measured using [11C]acetate was injected intravenously  followed by a saline flush . Simultaneously, an emission scan was started, acquiring list mode data for 50 min. Using a low-dose respiration-averaged CT scan  tissue density was measured and [11C]acetate scan was corrected for tissue attenuation. Dynamic images were reconstructed using 3D-row action maximum likelihood algorithm into 36 frames , applying all appropriate corrections.After a survey scan to position the patient, 370 MBq of H2O was injected intravenously  followed by a saline flush . Both scans were followed by a low-dose respiration-averaged CT scan . Images were reconstructed using 3D-row action maximum likelihood algorithm into 22 frames , with application of all appropriate corrections. BP was measured every 3 min during the entire scan. An interval of at least 10 min was used between the end of the first and the start of the second [15O]H2O scan to allow for decay of radioactivity to background levels.Hyperemic scan was performed during adenosine intravenously at a rate of 140 mcg kg11C]acetate image during maximum myocardial uptake according to the standardized AHA 17-segment model [11C]acetate scan to generate time-activity curves (TAC). A single-tissue compartment model with model based corrections for spillover, partial volume and recirculating [11C] activity was used to derive k2, representing the rate constant for tracer washout from myocardial tissue, described previously NH3 PET, increased after exenatide during a pancreatic-pituitary clamp as compared to placebo [Twenty-six weeks of exenatide did not affect resting or hyperemic MBF. After correction for RPP, however, resting MBF was decreased at follow-up. Clinical studies examining effects of GLP-1(RA) on coronary vascular function are scarce. In 8 T2DM patients without cardiovascular disease, resting MBF, measured using [ placebo . However placebo . Others  placebo  or 26 we placebo  in T2DM. placebo . Togethe2 and myocardial efficiency were unaffected by exenatide. Reports on chronic administration of GLP-1 infusion in dogs [Enhancing myocardial glucose metabolism, thereby improving myocardial efficiency, has been proposed as a therapeutic strategy in HF . However in dogs  with dil in dogs . Compara in dogs . Further in dogs . No chan in dogs . No chan in dogs . None ofIn contrary to the proposed therapeutic strategy in HF, enhancing myocardial glucose metabolism, it has been hypothesized that insulin resistance could protect the heart from substrate overload in the diabetic heart by decreasing the excess energy as myocytes are unable to convert this excess energy into mechanical energy . Agents The limited sample size may have obscured potential cardiac effects of exenatide. Furthermore, 2 T2DM patients had severe LV systolic dysfunction. It is indeed well known that diastolic dysfunction frequently occurs in patients with diabetes . Unfortunately, specific diastolic function parameters were not included in the current study protocol. Besides, CAD may have additionally influenced CFR, as obstructive coronary lesions were not excluded in the present study. However, these effects are likely to be small as this randomized pilot trial did not indicate any significant alterations on the investigated parameters. Furthermore, participants were all male. Therefore, these results cannot be extrapolated to female T2DM patients without further studies. Although, metabolic effects of exenatide are likely to be independent of sex . To evalIn T2DM patients with modest systolic dysfunction, myocardial efficiency was not impaired compared to BMI-matched healthy controls. Furthermore, 26 weeks of exenatide or insulin glargine did not result in changes in cardiac function, MBF, or oxidative metabolism.


Balance impairments, falls, and spasticity are common after stroke, but the effect of spasticity on balance control after stroke is not well understood. In this cross-sectional study, twenty-seven participants with stroke were divided into two groups, based on ankle plantar flexor spasticity level. Fifteen individuals with high spasticity  score of ≥2) and 12 individuals with low spasticity (MAS score <2) completed quiet standing trials with eyes open and closed conditions. Balance control measures included centre of pressure (COP) root mean square (RMS), COP velocity, and COP mean power frequency (MPF) in anterior-posterior and mediolateral (ML) directions. Trunk sway was estimated using a wearable inertial measurement unit to measure trunk angle, trunk velocity, and trunk velocity frequency amplitude in pitch and roll directions.spasticity by vision interaction). ML COP MPF was greater in the high spasticity group. The high spasticity group demonstrated greater ML COP velocity, trunk roll velocity, trunk roll velocity frequency amplitude at 3.7 Hz, and trunk roll velocity frequency amplitude at 4.9 Hz, particularly in the eyes closed condition ( Individuals with high spasticity after stroke demonstrated greater impairment of balance control in the frontal plane, which was exacerbated when vision was removed. Stroke can result in neurological damage of the upper motor neurons (UMNs) leading to spasticity , with stA common challenge in persons with stroke is impaired balance control, which affects independence in ADLs . MeasureIt is established that the action of ankle musculature is important in the control of postural sway during quiet standing, through the action of centre of pressure (COP) movement , and thaThe focus of the current study was to investigate how severity of spasticity can affect quiet standing balance control in individuals following stroke. It was hypothesized that persons with stroke with high levels of spasticity would demonstrate greater balance control impairment and lower balance confidence measures as compared to poststroke persons with low levels of spasticity. Since balance control is more impaired in absence of vision in persons after stroke , it was Individuals with spasticity after stroke who were receiving treatment in an outpatient spasticity clinic were invited to participate in this cross-sectional study. Inclusion criteria were the ability to stand independently, with and without eyes open for at least 10 minutes. Exclusion criteria were an inability to stand unassisted, inability to follow simple instructions due to cognitive impairments as determined by clinicians, fixed ankle contracture, or being treated with botulinum toxin injections within the past 3 months of study participation. All participants provided informed consent to participate, and this study received ethical approval in accordance with the hospital and university guidelines. Twenty-seven individuals volunteered to participate in the study and met the inclusion/exclusion criteria.n = 15) and low spasticity (n = 12), based on the severity of ankle spasticity. Sample sizes were slightly different between groups because of the greater prevalence of individuals with high spasticity being treated in the clinic, despite rigorous recruitment methods. In this study, high ankle spasticity was defined as MAS scores of ≥2 in the ankle plantar flexors  muscles, and low ankle spasticity was defined by MAS scores of <2 in these same muscles. In the spasticity assessments of ankle plantar flexors, subjects were tested in the supine position while testing spasticity in the gastrocnemius muscle was with the knee extended and testing spasticity in the soleus muscle was with the knee in flexed positions. MAS scores in knee flexor, knee extensor, and hip adductor muscle groups of the affected limb were also measured and compared as knee and hip muscle groups are also important in balance control of quiet standing.The severity of ankle spasticity on the affected limb was determined using the Modified Ashworth Scale (MAS)  and scorA single AMTI force plate  was used to calculate COP as participants stood quietly on the force plate. Trunk sway was simultaneously measured using a wearable inertial measurement unit , which has embedded angular velocity sensors to measure trunk angular velocity and displacement in the pitch (anterior-posterior) and roll  directions. SwayStar has been shown to provide repeatable, reliable, and sensitive measures in trunk sway of population of individuals with balance problems –25.In each trial, participants stood quietly for 80 seconds on the force plate with the SwayStar system mounted near the lumbar region of the trunk. Participants were instructed not to talk, to remain as still as possible with their feet shoulder width apart, arms hanging by the side, and to look straight at a marker placed on the wall 3 metres ahead during trials with eyes open. For no-vision trials, participants were asked to close their eyes for the duration of the trial. Two clinic staff members stood near each side of participants to stabilize participants in the event of a loss of balance during testing. Each participant completed four trials starting with an eyes open trial for their safety, followed by trials with eyes closed, then eyes open, and then eyes closed. Since the effect of vision is known to affect balance control, the same order of vision testing conditions was used among all participants to keep difficulty level of trials consistent across all participants.All data, from the force plate and SwayStar, were collected using a sampling rate of 100 Hz. In postprocessing, the first and last 10 seconds of all time-series signals were removed, leaving 60 seconds of data to analyze quiet standing . ResiduaAngular displacements of the trunk in the pitch and roll directions were calculated online by the SwayStar system software from trapezoid integration of trunk angular velocity measures . SummaryThe Activities-specific Balance Confidence (ABC) scale was used to estimate balance confidence. Previous research has demonstrated balance confidence to be an important determinant of balance and mobility in population of individuals with spasticity  and high Discovering JMP 12®. Cary, NC: SAS Institute Inc.). To test the hypotheses that balance impairments would be greater in (a) the high spasticity group in comparison to the low spasticity group and (b) in eyes closed conditions in comparison to the eyes open conditions, a 2 × 2 mixed model univariate analysis of variance (ANOVA) was performed using the following factors: (a) spasticity (high spasticity versus low spasticity) as the between-subject factor and (b) vision (eyes open versus eyes closed) as the within-subject factor with JMP's application of Kenward-Roger correction for all COP and trunk sway dependent measures. Tukey's HSD post hoc test was used to further analyze any significant (spasticity by vision) interaction effects. Least square means comparisons using Tukey's HSD were also used to compare differences in age and ABC scores between high and low spasticity groups.All statistical analyses were conducted using JMP 12 (SAS Institute Inc. 2015.S) was used instead of a mean value to better represent the MAS scores of muscles with spasticity between groups [n = 25 was determined as adequate, based on preliminary data of the first six participants, to achieve power of 0.8. For all statistical testing, α was set at 0.05.MAS scores of the hip and knee muscles of the high and low spasticity groups were not normally distributed; therefore, MAS scores between high and low spasticity groups were compared using the nonparametric Wilcoxon rank-sum test. Wilcoxon rank-sum value , except when stated otherwise. Participants' characteristics are presented in F-statistics, and p values are presented in Tables spasticity by vision interaction) in ML COP velocity, trunk roll velocity, trunk roll velocity frequency amplitude at 3.7 Hz, and trunk roll velocity frequency amplitude at 4.9 Hz measures  and ML (roll) and their corresponding mean ± SEM values, s Tables . Individs Tables . Irrespes Tables .F = 2.35; p = 0.14). The MAS scores of the high spasticity group were significantly higher in the gastrocnemius , soleus , knee flexors , and knee extensors  when compared to MAS scores of the low spasticity group. There was no significant difference between hip adductor MAS scores of the high and low spasticity groups . Differences in balance control measures observed between spasticity groups in different vision conditions were not influenced by the specific order of testing conditions; dependent measure values were not different between trials 1 and 3 (eyes open) and between trials 2 and 4 (eyes closed).There was no significant difference between high and low ankle spasticity groups in ABC scores  or roll (ML) directions. These results closely resemble the findings in Singer and colleagues, where it was reported that there were no differences between persons with and without spasticity after stroke in either AP or ML COP RMS . It may In the literature, higher COP velocity values in individuals with stroke , 35 and Current findings may support Horak's explanation of intact somatosensory and visual sensory strategies in balance control of the body  and suggIn addition to higher trunk sway and COP velocity, the high ankle spasticity group also had higher mediolateral MPF measures than the low ankle spasticity group, regardless of the effect of vision. Higher MPF measures have been associated with greater balance control impairments in populations with balance problems including studies of older versus younger adults  and in iIt has previously been demonstrated by Winter and colleagues that the frequency of oscillations during quiet standing movement is proportional to velocity of oscillations which is also proportional to a stiffness measure of a spring model that represents the tone of muscles in control of balance . Hence, Spasticity is a stretch dependent phenomenon and can be clinically elicited by stretching the affected muscles and the hyperexcitable stretch reflexes are responsible for excessive muscle tone. The natural postural sway, which occurs in both AP and ML directions, can trigger the ankle stretch reflex and in persons with high spasticity can produce excessive increases in tone and enhance the postural sway. We did not see any increase in postural sway in AP direction most likely because the stretch reflex on the nonaffected side may have minimized the impact of the more hyperexcitable stretch reflex on the affected side with high ankle spasticity. Ankle plantar flexor spasticity can also induce invertor moments resulting in equinovarus postures seen in persons with high ankle plantar flexor spasticity . The invThe current findings show clear differences between groups in the frontal plane. The mediolateral balance control impairments in persons after stroke have been well established in the literature , and WinIn the current study, hip adductor and knee flexor/extensor spasticity scores were assessed. Interestingly, the high ankle spasticity group also had higher spasticity scores in the knee flexor and extensor muscles with no difference in hip adductor spasticity between groups. Higher spasticity in gastrocnemius muscle which spans both ankle and knee joints may have also contributed to the higher knee flexor spasticity of the high spasticity group. It may be possible that higher spasticity in muscles around the ankle and knee joints together could result in greater off-axis moments around these joints, altering the net direction of mediolateral forces and moments that start distally and act proximally towards the centre of mass of the body. Hence, it may be useful to also consider lower limb kinematics and spasticity levels on other muscle groups that are important for balance control in future studies.We expected that the balance confidence scores would be lower in the high spasticity group; however, no significant difference was observed between balance confidence scores of the groups. It may be that these scores were slightly (but not significantly) higher in the high spasticity group as this group was significantly younger (mean difference: 12.5 ± 4.5 years) and balance confidence scores tend to be typically higher in younger populations , though,One limitation of the study was use of a single force platform; therefore, current results cannot further explain the kinetics under each foot. Had this study included use of two force plates, it could have been possible to further investigate the spatiotemporal COP characteristics of the foot with spasticity versus the foot without spasticity in both spasticity groups in addition to net COP characteristics. Severity of spasticity was specifically chosen in the ankle muscles for study design, since standing balance control of the body is mainly under the control of ankle plantar flexors and dorsiflexors with the base of support directly under the ankle joint. Study findings suggested, however, that proximal muscles with spasticity should not be overlooked in better understanding of balance impairments in this population. Limitations in ankle range of motion which may have occurred because of soft tissue changes such as contracture were not measured, and these changes may explain the lack of change in sway in the AP direction. Future studies may also include measures of sensory impairments such as proprioception of the paretic limb between spasticity groups as this was not included in this study. Lastly, the findings of this study are limited to static balance control strategies, whereas dynamic balance control strategies are as important to consider in population of individuals with stroke.The results of the current study suggest that individuals with high spasticity have greater balance control impairments in quiet standing, compared to individuals with low spasticity, particularly in the absence of vision. Moreover, the greater postural sway observed in individuals with high spasticity was specific to the mediolateral direction. An increase in muscle tone of the ankle plantar flexors and proximal muscle groups or a stiffening strategy in more difficult balance control tasks can be suggested from findings in individuals with high spasticity. The findings of this study can further be implemented in clinical research and rehabilitation of individuals with spasticity after stroke for a better understanding and treatment of balance control problems in this population. Future studies may also consider the effect of treatment options such as botulinum toxin injections or specific mediolateral balance control training strategies in rehabilitation of individuals with spasticity and balance problems after stroke.


T1ρ MRI is an emerging method for high spatial resolution tissue characterization of myocardial infarct (MI), but the evolution of T1ρ in the first month after reperfused MI is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ relaxation times at baseline, 1 and 4 weeks post-MI and correlated these results with T2, native T1, and histological findings.x - SLy - 180y - SL-y - 90-x) with the following parameters: TSL = 2-50 ms, B1 = 500 Hz. T2 MRI was obtained 90x - 180y - 90-x using the same readout parameters. T1 maps were obtained with a modified Look-Locker sequence , utilizing a single-shot acquisition with 8 inversion times. For LGE MRI, the animal received 0.1 mmol/kg intravenous injection of gadolinium contrast (MultiHance). Late-gadolinium enhanced (LGE) MRI was obtained using a 3D multishot phase-sensitive inversion recovery (PSIR) sequence with bSSFP spatial encoding. Ex vivo MRI and histology was performed at each terminal time point. Fibrotic tissue was assessed with trichrome staining. In vivo MRI was spatially correlated with ex vivo imaging and histopathology.13 pigs underwent 90 minutes of occlusion of the circumflex artery branches. T1ρ, T2 and native T1 MRI data were collected at terminal 1 week (n = 6) and 4 weeks (n = 7) post-MI studies. 2D T1ρ single-shot balanced steady-state free precession (bSSFP) sequences were performed using a spin echo, spin lock T1ρ pulse cluster , remote and infarcted tissue at 1 and 4 weeks (p < 0.05). Native T1 increased 288.0 and 212.4 ms at 1 and 4 weeks post-infarction (p < 0.05). The percent increase in T1ρ, T2 and T1 from baseline was 76, 48 and 24% at 1 week and 56, 36 and 21% at 4 weeks in the infarct region. T1ρ post-infarction area at 1 week was highly correlated with infarct fibrosis (p < 0.05).Infarct T1ρ increased 39.0 (1 week) and 32.1 ms (4 weeks) and T2 increased 21.0 ms (1 week) and 16.2 (4 weeks) after infarction. T1ρ relaxation times were highly correlated with alterations in post-MI pathology at 1 and 4 weeks and therefore it may be a useful method for non-contrast enhanced imaging of infarction.


Myocardial oedema  is typically imaged using a pre-contrast T2-weighted short tau inversion recovery (T2w-STIR) sequence on cardiovascular magnetic resonance (CMR) imaging. However, this sequence is prone to motion and rhythm artefact, signal dropout, blood-pool artefact, surface coil signal inhomogeneity and potentially prohibitive long breath-hold duration. This susceptibility to artefacts limits utility of T2w-STIR in large clinical trials where attainment of diagnostic quality oedema imaging in the majority is necessary to determine myocardial salvage: a measure of reperfusion success and a strong predictor of adverse remodeling and prognosis post ST-segment elevation myocardial infarction (STEMI). We compare AAR quantified on T2w-STIR imaging with novel T1-mapping on 3.0T CMR post STEMI.Fifty-five patients underwent CMR 1-5 days following presentation with STEMI. AAR was quantified using semi-automatic thresholding on T2w-STIR images and resulting parametric colour maps from T1 Modified Look Locker Inversion Recovery (MOLLI) sequences performed with the patient breathing freely and with motion correction algorithm applied (MOCO-T1). Paired t-tests were used to compare AAR derived using the two sequences. Pearson's correlation coefficient was used to assess correlation. Inter-sequence agreement was assessed using the Bland-Altman method, coefficient of variation (CoV) and two-way mixed-effect intra-class correlation coefficient (ICC) for absolute agreement.See Table MOCO-T1-mapping is more robust than T2w-STIR for identification of reversible myocardial injury and prediction of functional recovery following STEMI. Furthermore, MOCO-T1 imaging may allow AAR to be accurately determined without long breath holds, often required for the acquisition of oedema imaging, in acutely unwell patients. This requires validation in larger studies and may have implications for sample size calculations in trials using CMR surrogate markers of myocardial injury.