Baljit Jagpal

3D MRI Analysis of the Lower Legs of Treated Idiopathic Congenital Talipes Equinovarus (Clubfoot)

Background Idiopathic congenital talipes equinovarus (CTEV) is the commonest form of clubfoot. Its exact cause is unknown, although it is related to limb development. The aim of this study was to quantify the anatomy of the muscle, subcutaneous fat, tibia, fibula and arteries in the lower legs of teenagers and young adults with CTEV using 3D magnetic resonance imaging (MRI), and thus to investigate the anatomical differences between CTEV participants and controls. Methodology/Principal Findings The lower legs of six CTEV (2 bilateral, 4 unilateral) and five control young adults (age 12–28) were imaged using a 3T MRI Philips scanner. 5 of the CTEV participants had undergone soft-tissue and capsular release surgery. 3D T1-weighted and 3D magnetic resonance angiography (MRA) images were acquired. Segmentation software was used for volumetric, anatomical and image analysis. Kolmogorov-Smirnov tests were performed. The volumes of the lower affected leg, muscle, tibia and fibula in unilateral CTEV participants were consistently smaller compared to their contralateral unaffected leg, this was most pronounced in muscle. The proportion of muscle in affected CTEV legs was significantly reduced compared with control and unaffected CTEV legs, whilst proportion of muscular fat increased. No spatial abnormalities in the location or branching of arteries were detected, but hypoplastic anomalies were observed. Conclusions/Significance Combining 3D MRI and MRA is effective for quantitatively characterizing CTEV anatomy. Reduction in leg muscle volume appears to be a sensitive marker. Since 5/6 CTEV cases had soft-tissue surgery, further work is required to confirm that the treatment did not affect the MRI features observed. We propose that the proportion of muscle and intra-muscular fat within the lower leg could provide a valuable addition to current clinical CTEV classification. These measures could be useful for clinical care and guiding treatment pathways, as well as treatment research and clinical audit.

Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

BackgroundWhilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.Methods and outcomesThe aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6–8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6–8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6–8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6–8 days and six months.Funding, ethics and regulatory approvalsThis study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).Trial registrationClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739

T1 mapping for assessment of myocardial injury and microvascular obstruction at one week post myocardial infarction

OBJECTIVES To compare 3T T1 mapping to conventional T2-weighted (T2W) imaging for delineating myocardial oedema one week after ST-elevation myocardial infarction (STEMI), and to explore the confounding effects of microvascular obstruction (MVO) on each technique. METHODS T2W spectral attenuated inversion recovery and native T1 mapping were applied in 10 healthy volunteers and 62 STEMI patients, and late gadolinium enhancement was included for infarct localisation at 1 week and at 6 months post-STEMI. Segmental T1 values and T2W signal intensity ratios were calculated; oedema volumes and salvage indices were determined in patients using image thresholding-a receiver operator characteristic (ROC) derived T1 threshold, and a 2SD T2W threshold; and the results were compared between patients with/without MVO (n=35/27). RESULTS Native T1 mapping delineated oedema with significantly better discriminatory power than T2W-as indicated by ROC analysis (area-under-the-curve, AUC=0.89 versus 0.83, p=0.009; and sensitivity/specificity=83/83% versus 73/73%). The optimal ROC threshold derived for T1 mapping was 1241ms, which gave significantly larger oedema volumes than 2SD T2W (p=0.006); with this threshold, patients with and without MVO showed similar oedema volumes, but patients with MVO had significantly poorer salvage indices (p<0.05) than those without. Neither method was significantly affected by MVO, the volume of which was seen to increase exponentially with infarct size. CONCLUSIONS Native T1 mapping at 3T can delineate oedema one week post-STEMI, showing larger oedema volumes and better discriminatory power than T2W imaging, and it is suitable for quantitative thresholding. Both techniques are robust against MVO-related magnetic susceptibility.

Right Ventricular Involvement and Recovery After Acute Stress-Induced (Tako-tsubo) Cardiomyopathy.

Acute stress-induced (Tako-tsubo) cardiomyopathy is an increasingly recognized but insufficiently characterized syndrome. Here, we investigate the pathophysiology of right ventricular (RV) involvement in Tako-tsubo and its recovery time course. We prospectively recruited 31 patients with Tako-tsubo with predominantly ST-elevation electrocardiogram and 18 controls of similar gender, age, and co-morbidity distribution. Patients underwent echocardiography and cardiac magnetic resonance (CMR) imaging on a 3T Philips scanner in the acute phase (day 0 to 3 after presentation) and at 4-months follow-up. Visually, echocardiography was able to identify only 52% of patients who showed RV wall motion abnormalities on CMR. Only CMR-derived RV ejection fraction (p = 0.01) and echocardiography-estimated pulmonary artery pressure (p = 0.01) identify RV functional involvement in the acute phase. Although RV ejection fraction normalizes in most patients by 4 months, acutely there is RV myocardial edema in both functioning and malfunctioning segments, as measured by prolonged native T1 mapping (p = 0.02 for both vs controls), and this persists at 4 months in the acutely malfunctioning segments (p = 0.002 vs controls). The extracellular volume fraction was significantly increased acutely in all RV segments and remained increased at follow-up compared with controls (p = 0.004 for all). In conclusion, in a Tako-tsubo population presenting predominantly with ST-elevation electrocardiogram, we demonstrate that although RV functional involvement is seen in only half of the patients, RV myocardial edema is present acutely throughout the RV myocardium in all patients and results in microscopic fibrosis at 4-month follow-up.

Randomized double-blind placebo- controlled trial of perhexiline in heart failure with preserved ejection fraction syndrome

Recently heart failure with preserved ejection fraction (HFpEF) has emerged as a huge epidemic. Increasing evidence shows the role of energy deficiency in the pathophysiology of HFpEF. In the current study, we hypothesize that the use of metabolic modulator perhexiline would correct myocardial energy deficiency and improve exercise capacity and diastolic abnormalities in patients with this syndrome.

Author's Reply: Persistence of Deformation Abnormalities and Detection of Fibrosis at 4-Month Follow-up in Patients with Takotsubo Syndrome

magnetic resonance imaging and echocardiography at 1-year followup, or at any time between 4months and 1 year (as the authors allude to), to evaluate their course of recovery and the possible presence or absence of restoration to normalcy. Third, a ‘‘chronic TTS condition’’ (i.e., persisting symptoms both at rest andwith exercise) has been suspected, and the authors provide us with the diagnostic blueprint for the objective evaluation of such patients with TTS at follow-up. Fourth, was there any correlation between the acute and 4-month echocardiographic or cardiac magnetic resonance imaging metrics and the peak levels of troponin I, C-reactive protein, and brain natriuretic peptide? Fifth, the intriguing finding of persistently increased extracellular matrix volume at 4-month follow-up on cardiac magnetic resonance imaging testing, attributed tomicroscopic fibrosis, by the timemyocardial edema has probably subsided, and affecting the heart globally (i.e., both the acutely abnormally and normally or supernormally contracting myocardial regions), may have pathophysiologic connotations. Probably there are acute cardiomyocyte injurious influences (no matter the mechanism of TTS) also affecting normally and supernormally (i.e., base of the heart) functioning cardiac territories.

Dynamic changes of the extracellular matrix after acute tako-tsubo cardiomyopathy

Methods Eleven patients (10F, mean age 56±16yrs) with a clear diagnosis of ST-elevation TTC and emotional trigger were prospectively enrolled and underwent cardiac magnetic resonance acutely (day 0-3) and after 4 months on a Philips 3T Achieva scanner. Native 3-3-5 (MOLLI) T1 mapping was applied acutely, and both native and postcontrast T1 mapping were performed at 4 months followup. Eleven healthy controls underwent only native T1 mapping. T1 maps were: generated using in-house software written in IDL (Exelis. Boulder CO, USA); quality controlled with chi-square maps; and imported into Segment (Medviso, Lund University, Sweden), where T1 values were generated for 16 segments. Extracellular volumes (ECV) were calculated for the follow-up scan using: ECV=(1-hermatocrit)(ΔR1myocardium/ ΔR1blood) Segments were grouped according to their wall motion (WM) on the acute scan (normal/abnormal).

Right ventricular involvement in Tako-tsubo cardiomyopathy - insights from cardiovascular magnetic resonance

Methods 21 patients, mean age 66 (range 41-87 years) with a clear diagnosis of TTC (14 with ST-elevation, 16 with apical ballooning ) and emotional trigger were prospectively studied. CMR-derived LV and RV volumes and EF, RV shapes, RV wall motion index (WMSI, 6-segment model) and Echocardiography derived Pulmonary artery pressure (Pap), tricuspid annular E’,A’,S’, pansystolic excursion (TAPSE) were measured acutely (day 0-3) and after 4 months follow-up.

MOLLI T1 mapping versus T2 W-SPAIR at 3T: myocardial area at risk measurements and the influence of microvascular obstruction

Background Robust CMR imaging is required for the delineation of myocardial area at risk (AAR), so that the success of reperfusion therapies can be evaluated. In this work, we investigate the performance of T1 mapping in assessing AAR one week post-STEMI, and explore the effect of microvascular obstruction (MVO) on T1 relaxation times. Methods CMR imaging was conducted on a Philips 3T Achieva MRI scanner. T2W-weighted spectral attenuated inversion recovery (T2WW-SPAIR), modified look-locker inversion recovery (MOLLI) T1 mapping and late gadolinium enhancement (LGE) sequences were applied as short axis stacks in 10 healthy volunteers and 62 STEMI patients. Receiver operator characteristic (ROC) analysis was applied to calculate a cut-off T1 to to discriminate AAR from normal myocardium. The presence of LGE was used as the positive ROC test state, while healthy myocardium, as measured in volunteers, was used as the negative ROC test state. For comparison with T1 mapping, the AAR was also measured on T2WW images using a threshold signal intensity > 2SD greater than remote. The derived myocardial edema volumes and salvage indices were compared between MVO+ and MVO- groups. Results For T1 mapping, ROC analysis gave a significantly larger area-under-the-curve (AUC) as compared to T2WWSPAIR for delineating myocardial edema (AUC = 0.89

Apparent diffusion coefficient of normal breast tissue during the menstrual cycle at 3 Tesla

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a quantitative MRI technique that provides physiological information by measuring the degree of water molecule diffusion within the extracellular space. It gives a quantitative measurement known as the apparent diffusion coefficient (ADC) value. The aim of the study is to show the influence of the menstrual cycle on breast ADC values and the relationship of the ADC to transverse relaxation (T2) value.