Transmural Changes Research Articles

P0503 Submucosal hyperechogenicity on intestinal ultrasound is associated with fat deposition and is a predictor of endoscopic non-response to anti-inflammatory treatment in Ulcerative Colitis

Abstract Background The submucosa is the most responsive wall layer in the monitoring of treatment response in ulcerative colitis (UC) with intestinal ultrasound (IUS).1 However, persistent submucosal thickening, often seen in combination with hyperechogenicity, could be associated with treatment non-response.2 We aimed to understand these transmural changes in UC by correlating IUS findings with histopathology in colectomy specimens. Methods In total, 118 patients were included: (cohort 1) 19 UC patients and 52 controls without inflammatory bowel disease who all underwent colectomy, and (cohort 2) 47 UC patients in a prospective longitudinal validation cohort receiving anti-inflammatory treatment. In cohort 1, histopathology slides were scored for inflammation, fat, and collagen deposition in the submucosa by two pathologists, independently, using a semi-quantitative scale (0-3) (Figure 1). For the UC patients in cohort 1, images and histopathology slides of the sigmoid were location matched. IUS parameters were assessed by one sonographer, including relative submucosal echogenicity (RSE), quantified in grayscale units. In cohort 2, baseline RSE in the sigmoid was compared between endoscopic responders (≥1 point decrease in endoscopic Mayo score [EMS] after 8-26 weeks), and non-responders. Results In cohort 1, the indication for colectomy in UC was therapy-refractory disease (16/19, 84%), followed by acute severe colitis (2/19, 11%) and dysplasia (1/19, 5%). In the control groups, indications for surgery included cancer (31/52, 59%), diverticulitis (17/52, 33%), and obstipation (4/52, 8%). No significant differences in fat or collagen deposition in the submuosa were observed within cohort 1. In UC colectomy patients with the presence of submucosal fat deposition (score≥1), the submucosal thickness and RSE were significantly increased on IUS (Table 1). Linear regression showed fat deposition was independently associated with RSE (B=31.27, p<0.001), but fibrosis was not (B=14.89, p=0.097). In cohort 2, baseline RSE was significantly higher in endoscopic non-responders (n=17) than responders (146.8 vs. 88.7 grayscale units, p=0.003). A cut-off of >108 grayscale units predicted endoscopic non response with 82% sensitivity, 64% specificity, 58% positive predictive value and 86% negative predictive value. This cut-off was associated with an odds ratio of 0.12 (95% CI: 0.03-0.52, p=0.004) for endoscopic response. Conclusion In UC, hyperechogenicity of the submucosal layer on IUS is caused by fat deposition. Submucosal hyperechogenicity can be quantified and is a predictor of treatment non-response in UC patients.

Endoscopic Skipping, Stricturing, and Penetrating Complications in Crohn's Disease on Tandem Ileo-colonoscopy and Cross-sectional Imaging: A Retrospective Cohort Study.

Crohn's disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management. Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography or magnetic resonance enterography within 6 months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), structuring, and penetrating complications. Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 36.2% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients. Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease might be missed in more than a third of cases if cross-sectional imaging is not performed.

Magnetic resonance enterography findings 46 weeks after initiation of biological therapy predict long-term adverse outcomes in Crohn's disease.

Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes. Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years. A logistic regression analysis was performed to assess the prognostic value of different radiologic findings for various predefined adverse outcomes. Of the 89 patients included, 46 (51.7%) had ≥1 adverse outcome during follow-up: 40 (44.9%) had clinical recurrence; 18 (20.2%) required surgery, 8 (9%) endoscopic balloon dilation, 12 (13.5%) hospitalization and 7 (7.8%) required corticosteroids. In the multivariate analysis, persistence of severe lesions (MaRIA ≥11) in any intestinal segment was associated with an increased risk of surgery [OR 11.6 (1.5-92.4)], of surgery and/or endoscopic balloon dilation [OR 6.3 (1.3-30.2)], and of clinical relapse [OR 4.6 (1.6-13.9)]. Penetrating lesions were associated with surgery [OR 3.4 (1.2-9.9)]. Creeping fat with hospitalization [OR 5.1 (1.1-25.0)] and corticosteroids requirement [OR 16.0 (1.2-210.0)]. The presence of complications (stricturing and/or penetrating lesions) was associated with having ≥1 adverse outcome [OR 3.35 (1.3-8.5)]. MRE findings at week-46 after initiating biological therapy can predict long-term adverse outcomes in CD. Therapeutic intervention may be required in patients with persistence of severe inflammatory lesions, CD-associated complications, or creeping fat.

P530 Early Intestinal Ultrasound changes to predict treatment response to anti-TNF therapy in paediatric Inflammatory Bowel Disease; a pilot study

Abstract Background In paediatric Inflammatory Bowel Disease (IBD) selecting the right treatment in the early stages of disease is key to prevent disease progression and to prevent unnecessary exposure to ineffective treatment. Intestinal ultrasound (IUS) is increasingly used to monitor disease activity in response to therapy. However, little is known about the early transmural changes during anti-tumour necrosis factor (anti-TNF) therapy in paediatric IBD. The aim of this study is to assess the early changes in IUS parameters and to evaluate the very early predictive value of IUS for therapy response in paediatric IBD treated with anti-TNF-α therapy. Methods In this pilot study children (aged 3-18 years) starting with anti-TNF therapy (infliximab or adalimumab) were enrolled prospectively if ultrasound at baseline showed bowel wall thickness (BWT) ≥ 2,5mm. IUS was performed at baseline and the most affected bowel segment was identified. Subsequently IUS was repeated in this segment at week 2 and week 13. Response to therapy was determined at week 13. Response and remission was defined as follows. - Therapy response: a ≥50% decrease in faecal calprotectin (FCP) in combination with a decrease in PUCAI (≥20 points or normalisation) /PCDAI (≥12.5 points or normalisation), or normalisation of FCP (<250mg/kg)) - IUS response: decrease in BWT by 25% OR decrease in BWT by >2.0 mm of the most severely affected segment compared to baseline - IUS remission/Transmural healing: BWT<2.0 mm and no Doppler signal(Limberg score) and no mesenteric fat proliferation Results Eleven IBD patients (aged 7 to 12 years; 64% female) were enrolled. IUS response was observed in 5/11 patients at week 2 (decrease in BWT -25% in all). Doppler signal decreased in 3/11(one point in Limberg score in all). After 13 weeks 4/11 patients showed therapy response and 3/11 showed IUS remission. Conclusion Transmural changes were detected by IUS as early as 2 weeks after initiating anti-TNF therapy. This pilot study observed mainly reactivity in BWT, in contrast with previous studies that initially noted changes in Doppler signal. IUS has the potential to predict therapy response at an early stage. A larger sample size is needed to accurately assess its predictive value at week 2 for treatment response.

Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn's disease treated with ustekinumab.

The approval of ustekinumab (UST) has opened new options for the treatment of Crohn's disease (CD), but potential markers predicting the efficacy of this interleukin-12/23 inhibitor are lacking. Contrast-enhanced ultrasound (CEUS) is non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment induction. We conducted a prospective monocentric study aiming to explore the value of multimodal intestinal ultrasound (IUS) in predicting the response to UST in patients with active CD who have been previously exposed to anti-tumour necrosis factor α (TNFα). Consecutive patients with moderate-to-severe CD involving the terminal ileum who were scheduled to begin UST therapy were enrolled between January 2020 and October 2021 in the inflammatory bowel diseases outpatient centre. A complete IUS evaluation, including B-mode, Doppler, dynamic CEUS and elastography, was performed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each IUS parameter and their variations from baseline were correlated with endoscopic response and mucosal healing after 1 year. A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. The univariate analysis revealed that, between T3 and T0, the percentage changes of bowel wall thickness, Limberg score, mean signal intensity, rise time, wash-in rate, C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome. Based on the above parameters, we developed an IUS score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Multimodal ultrasound could be helpful to predict long-term therapeutic outcome in patients with CD treated with UST. NCT05987501.

Diffusion-weighted imaging in Crohn's disease.

Diffusion-weighted MRI (DWI) is routinely used in abdominal imaging. In addition to neoplastic diseases, inflammatory changes can be delineated and diagnosed based on diffusion restriction in DWI. DWI is also increasingly used in the context of MRI of the small and large intestine. This article focuses on the technical aspects of DWI and its role in the diagnosis of Crohn's disease (CD) as well as in the grading of disease severity and in treatment monitoring. Guidelines, basic research papers, and review articles were analyzed. Diffusion-weighted MRI is aspecialized MRI technique that visualizes the diffusion of water molecules in biological tissues. In the context of MRI of the small and large intestine, DWI facilitates the diagnosis of inflammatory bowel disease and assessment of treatment response. DWI enables detection of not only intra- and transmural changes, but also extramural pathologies and complications. However, DWI also has its limitations and challenges. This article provides acomprehensive overview of the use of DWI for diagnostic evaluation of bowel wall changes and extramural complications in the setting of CD. It also summarizes the relevant evidence available in the literature.

Magnetresonanz-Enterographie/Enteroklysma

Magnetic resonance enterography/enteroclysma (MRE) is an examination technique without ionizing radiation that allows assessment of bowel wall changes and extraluminal pathologies/complications such as in chronic inflammatory bowel diseases, among others. To discuss requirements for optimal MR imaging of the small bowel, technical basis of MRE and principles for the development and optimization of aMRE protocol, and clinical indications for this specific imaging technique. Guidelines, basic and review papers will be analyzed. MRE enables the diagnosis of inflammatory bowel diseases and neoplasms and their evaluation during therapy. In addition to intra- and transmural changes, extramural pathologies and complications can also be detected. Standard sequences include steady-state free precession sequences, T2-weighted single-shot fast spin echo sequences, and three-dimensional (3D) T1-weighted gradient echo (GRE) sequences with fat saturation after contrast administration. Prior to image acquisition, optimal patient preparation and distension of the bowel using intraluminal contrast agents is necessary. Careful patient preparation for MRE, understanding of optimal imaging technique, and appropriate clinical indications are essential to achieve high-quality images of the bowel for accurate assessment and diagnosis as well as therapy monitoring of small bowel disease.

Histological changes of vascular clipping in Wistar rats.

During aneurysm microsurgery, the aneurysmal sac is excluded from circulation by placing one or more clips at the base of the aneurysm. In some cases of complex aneurysms or subarachnoid hemorrhage history, transient clipping before definitive clipping is necessary. The closing force of the transient clip is less than the permanent clip; however, it is sufficient to stop circulation to the aneurysmal sac. The aim of the following work is to analyze and describe histological changes caused by transient and permanent clipping of the abdominal aorta in Wistar-type rats, to study the correlation between the closing force of the clip and the time, it remains on the vascular tissue structures. Six groups were formed, with 10 rats each, whereby temporary clipping of the abdominal aorta was performed with subsequent sampling of the site where the vascular clip was placed. The groups were: control and temporary clipping with: 2, 5, 10, and 15 and permanent clipping with 5 min. Resection samples of the 3 μm thick aorta were obtained through the routine histological technique and special histochemical techniques (Masson's Trichrome and orcein) from the six groups. Transmural changes were found from Group II-VI. There is a vascular histological effect after both transient and permanent clipping. The sum of time and strength of the clip induce vascular changes visible at 5 min.

Intestinal Ultrasound Early on in Treatment Follow-up Predicts Endoscopic Response to Anti-TNFα Treatment in Crohn's Disease.

To assess treatment response, objective measures are superior to clinical improvement in Crohn's disease [CD]. Intestinal ultrasound [IUS] is an attractive, non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment initiation. Therefore, we investigated IUS and contrast-enhanced ultrasound [CEUS] to predict [early] endoscopic treatment response. Consecutive patients with endoscopically active CD, starting anti-TNFα therapy, were included. Clinical, biochemical, IUS, and CEUS parameters at baseline [T0], after 4-8 weeks [T1] and 12-34 weeks [T2] were collected. The most severely inflamed segment at endoscopy (highest segmental Simplified Endoscopic Score for Crohn's Disease [SES-CD]) and IUS (highest segmental bowel wall thickness [BWT]) was identified. At T2, endoscopic response [decrease in SES-CD ≥ 50%] and remission [SES-CD = 0] were scored. A total of 40 patients were included: 14 reached endoscopic remission and 17 endoscopic response. At T1 (3.1 mm [1.9-4.2] vs 5.3 mm [3.8-6.9], p = 0.005) and T2 (2.0 mm [1.8-3.1] vs 5.1 [3.0-6.3] mm, p = 0.002) BWT was lower in patients with endoscopic remission. At T1 and T2, 18% (area under the receiver operating curve [AUROC]: 0.77; odds ratio [OR]: 10.80, p = 0.012) and 29% [AUROC: 0.833; OR: 37.50, p = 0.006] BWT decrease predicted endoscopic response, respectively. To determine endoscopic remission, BWT 3.2 mm was most accurate [AUROC: 0.94; OR: 39.42, p < 0.0001] at T2. In addition, absence of colour Doppler signal [OR: 13.76, p = 0.03] and the CEUS parameter wash-out rate [OR: 0.76, p = 0.019] improved the prediction model. Reduction in BWT, already after 4-8 weeks of follow-up, predicted endoscopic response and remission. CEUS parameters were of limited value. Furthermore, we have provided accurate cut-offs for BWT reflecting endoscopic response and remission at different time points.

P580 Early intestinal ultrasound assessment predicts endoscopic response and remission on anti-TNF treatment in Crohn’s Disease – a prospective longitudinal cohort study

Abstract Background In the assessment of treatment response in Crohn’s Disease (CD) objective measures are superior to clinical improvement. Intestinal ultrasound (IUS) is an emerging modality with high accuracy to detect CD disease activity. Less is known about early transmural changes at IUS in treatment follow-up. Therefore, we aimed to investigate conventional IUS and contrast-enhanced ultrasound (CEUS) parameters and how they are associated with endoscopic treatment response. Methods In this longitudinal prospective cohort study, consecutive patients with active CD according to the simplified endoscopic score (SES-CD≥3) starting anti-TNF-α treatment were included. We recorded clinical, biochemical, IUS and CEUS parameters at baseline (T0), after 4–8 weeks (T1) and at 12–34 weeks (T2). IUS parameters were scored as previously established1. The SES-CD was scored per segment by a gastroenterologist immediately after endoscopy. The bowel segment with highest SES-CD score and thickest wall on IUS was identified. At T2, endoscopic response (decrease SES-CD≥50%) and endoscopic remission (SES-CD=0) were scored per segment. IUS and CEUS were scored blindly by two readers using recorded videos. Results 40 patients were included (Table 1) with 23 completing follow-up. The other 17 patients had side-effects and stopped treatment (n=9), underwent bowel surgery (n=5) or were lost to follow-up (n=3). At T2, 14 reached endoscopic remission, 17 had endoscopic response. The absolute decrease in BWT at T1 and T2 paralleled endoscopic response (Figure 1). Decrease in BWT of 18% at T1 (Fig 2) predicted endoscopic response accurately (OR: 10.8, 95%CI: 1.7–69.0, p=0.012). For T2, 29% decrease in BWT (Fig 2) was most accurate to determine endoscopic response (OR: 37.5, 95%CI: 2.8–507.5, p=0.006). At T2, a BWT of 3.2 mm was most accurate (AUROC: 0.940, 95%CI: 0.862–1.000, p&amp;lt;0.0001, sensitivity: 92%, specificity: 85%) to determine endoscopic remission (OR: 39.4, 95%CI: 7.7–202.6, p&amp;lt;0.0001). Normalization of Colour Doppler Signal (CDS) (no signal or single vessel) (OR: 13.8, 95%CI: 1.3–147.8, p=0.03) or Wash-out Rate (WoR) at CEUS (1 dB increase: OR: 0.8, 95%CI: 0.60–0.96, p=0.019) added significantly to BWT to determine endoscopic remission at T2. Conclusion Decrease of BWT 4–8 weeks after treatment initiation predicted endoscopic response later during follow-up. In addition, we have provided accurate cut-off values for (Δ)BWT associated with endoscopic response and remission at different time-points. CDS or WoR were both of additional value to determine endoscopic remission after 12–34 weeks. As CEUS is time consuming, CDS might be sufficient in the close follow-up of CD patients. Reference 1. Novak et al, JCC 2021

Cardiovascular risk is associated with a transmural gradient of myocardial oxygenation during adenosine infusion.

In patients with coronary artery disease (CAD), a transmural gradient of myocardial perfusion has been repeatedly observed, with the subendocardial layer showing more pronounced perfusion deficits. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) allows for monitoring transmural changes of myocardial oxygenation in vivo. We hypothesized that OS-CMR could help identify a transmural oxygenation gradient as a disease marker in patients at risk for CAD. We assessed 34 patients with known CAD and 28 subjects with coronary risk factors but no evidence of significant CAD. Results were compared with 11 healthy volunteers. OS-CMR was performed at 1.5 T, applying a T2*-weighted cine steady state free precession sequence at baseline and during infusion of adenosine. A reader blinded to patient data quantified the relative change of myocardial oxygenation in OS-CMR, defined by the change of signal intensity (ΔSI%) between baseline and during adenosine infusion in the entire myocardium, the subepicardial layer, and the subendocardial layer. SI changes were homogenous throughout the myocardium in healthy subjects, whereas both, patients with risk factors only and patients with CAD, had a significantly smaller ΔSI% in the subendocardial layer than in the subendocardial layer. Both patient groups had an overall decreased ΔSI% across all layers when compared with healthy subjects (P < 0.05). Even in the absence of overt CAD, cardiovascular risk factors are associated with a transmural gradient of the myocardial oxygenation response to adenosine as assessed by OS-CMR. An inducible transmural oxygenation gradient may serve as a non-invasive marker for cardiovascular risk.

How to perform gastrointestinal ultrasound: Anatomy and normal findings.

Gastrointestinal ultrasound is a practical, safe, cheap and reproducible diagnostic tool in inflammatory bowel disease gaining global prominence amongst clinicians. Understanding the embryological processes of the intestinal tract assists in the interpretation of abnormal sonographic findings. In general terms, the examination principally comprises interrogation of the colon, mesentery and small intestine using both low-frequency and high-frequency probes. Interpretation of findings on GIUS includes assessment of bowel wall thickness, symmetry of this thickness, evidence of transmural changes, assessment of vascularity using Doppler imaging and assessment of other specific features including lymph nodes, mesentery and luminal motility. In addition to B-mode imaging, transperineal ultrasonography, elastography and contrast-enhanced ultrasonography are useful adjuncts. This supplement expands upon these features in more depth.

Computational Investigation of Transmural Differences in Left Ventricular Contractility.

Myocardial contractility of the left ventricle (LV) plays an essential role in maintaining normal pump function. A recent ex vivo experimental study showed that cardiomyocyte force generation varies across the three myocardial layers of the LV wall. However, the in vivo distribution of myocardial contractile force is still unclear. The current study was designed to investigate the in vivo transmural distribution of myocardial contractility using a noninvasive computational approach. For this purpose, four cases with different transmural distributions of maximum isometric tension (Tmax) and/or reference sarcomere length (lR) were tested with animal-specific finite element (FE) models, in combination with magnetic resonance imaging (MRI), pressure catheterization, and numerical optimization. Results of the current study showed that the best fit with in vivo MRI-derived deformation was obtained when Tmax assumed different values in the subendocardium, midmyocardium, and subepicardium with transmurally varying lR. These results are consistent with recent ex vivo experimental studies, which showed that the midmyocardium produces more contractile force than the other transmural layers. The systolic strain calculated from the best-fit FE model was in good agreement with MRI data. Therefore, the proposed noninvasive approach has the capability to predict the transmural distribution of myocardial contractility. Moreover, FE models with a nonuniform distribution of myocardial contractility could provide a better representation of LV function and be used to investigate the effects of transmural changes due to heart disease.

Challenges Faced by Cross-sectional Imaging and Histological Endpoints in Clinical Trials.

In patients with inflammatory bowel disease, a dissociation can occur between symptoms and presence of inflammatory lesions. This dissociation has led to the recognition that objective measures of disease activity together with clinical assessment should be co-primary endpoints in clinical trials. Objective assessment of inflammatory lesions has classically relied on ileocolonoscopy. However, examination with endoscopy cannot always be complete and does not evaluate transmural changes. Furthermore, histological alterations may persist in the presence of mild or even absent endoscopy lesions. For these reasons cross-sectional imaging, particularly magnetic resonance imaging [MRI] and histology, are being considered as potential new tools for objective assessment of lesions.In patients with Crohn's disease, it has been shown that MRI has a high degree of accuracy for the evaluation of presence and severity of inflammation, and that validated indices of activity such as the Magnetic Resonance Index of Activity [MaRIA] are responsive to effective therapeutic interventions. In the context of clinical trials, MRI may help in patient selection by providing always a complete assessment of the small bowel and colon and detecting the presence of complications.A generally accepted definition of histological mucosal healing, to be used in clinical trials on Crohn's disease or ulcerative colitis, does not exist. Several histological scoring systems are available, most of these based on the evaluation the presence of neutrophils, epithelial cell damage, and an increase in lymphocytes and plasma cells. At present, histological remission is not included as primary endpoint for therapeutic trials, but better outcomes associated with achievement of histological healing favours the consideration of histology as an endpoint in the future.

Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model.

In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall. Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4% DSS over a period of 5days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically. MRI, CT, US, and histological data revealed increased colon wall thickness in DSS-treated mice compared to healthy controls. Elevated 2-deoxy-2[(18)F]fluoro-D-glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitis mice. The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting.

Evaluation of left ventricular transmural mechanics after anthracycline chemotherapy in patients with breast cancer by speckle tracking imaging

Objective To evaluate the left ventricular transmural mechanics changes of breast cancer patients between before and after anthracycline chemotherapy by two-dimensional speckle tracking imaging (2D-STI), and to predict early cardiotoxicity caused by anthracycline. Methods Forty-six breast cancer patients with postoperative anthracycline-based chemotherapy were recruited. Echocardiography were performed on all subjects before and at 1, 3 and 6 anthracycline-based chemotherapeutic cycle. Global longitudinal strain(GLS), endocardial longitudinal strain(LS-endo), epicardial longitudinal strain(LS-epi), global radial strain(GRS), endocardial radial strain(RS-endo), epicardial radial strain(RS-epi), global circumferential strain(GCS), endocardial circumferential strain(CS-endo) and epicardial circumferential strain(CS-epi) were assessed by 2D-STI and transmural myocardial strain gradient-longitudinal strain(TMSG-LS), transmural myocardial strain gradient-radial strain(TMSG-RS), transmural myocardial strain gradient-circumferential strain(TMSG-CS) were calculated. Conventional echocardiographic parameters and strain-related parameters before and after chemotherapy were compared. The receiver operating characteristics(ROC)curve was performed to determine sensitivity and specifity of strain parameters for prediction value of cardiotoxicity induced by anthracycline chemotherapy. Results ①After the sixth cycle of anthracycline chemotherapy, 9 patients (16.4%) had developed anthracycline-induced cardiotoxicity, and 37 patients (80.4%) did not meet the criteria for cardiotoxicity. ②There were no significant differences in conventional echocardiography parameters between before and after chemotherapy (P>0.05). Left ventricular ejection fraction (LVEF), fractional shortening (FS) and E/A significantly decreased, but E/e significantly increased after six cycles of chemotherapy (P LS-endo> GLS> LS-epi. Conclusions After three cycles of chemotherapy, the decreases of TMSG-LS, LS-endo, GLS and LS-epi preceded the change of LVEF and other strain parameters, TMSG-LS and LS-endo can accurately and early detect anthracycline chemotherapy-induced cardiotoxicity. Key words: Echocardiography; Breast neoplasms; Anthracyclines; Transmural myocardial strain gradient; Two-dimensional speckle tracking imaging

Ventricular fiber optimization utilizing the branching structure

In this paper, we propose an algorithm that optimizes the ventricular fiber structure of the human heart. A number of histological studies and diffusion tensor magnetic resonance imaging analyses have revealed that the myocardial fiber forms a right-handed helix at the endocardium. However, the fiber formation changes its orientation as a function of transmural depth, becoming a left-handed helix at the epicardium. To determine how nature can construct such a structure, which obtains surprising pumping performance, we introduce macroscopic modeling of the branching structure of cardiac myocytes in our finite element ventricular model and utilize this in an optimization process. We put a set of multidirectional fibers around a central fiber orientation at each point of the ventricle walls and simulate heartbeats by generating contraction forces along each of these directions. We examine two optimization processes using the workloads or impulses measured in these directions to update the central fiber orientation. Both processes improve the pumping performance towards an optimal value within several tens of heartbeats, starting from an almost-flat fiber orientation. However, compared with the workload optimization, the impulse optimization produces better agreement with experimental studies on transmural changes of fiber helix angle, streamline patterns of characteristic helical structures, and temporal changes in strain. Furthermore, the impulse optimization is robust under geometrical changes of the heart and tends to homogenize various mechanical factors such as the stretch and stretch rate along the fiber orientation, the contraction force, and energy consumption. Copyright © 2015 John Wiley & Sons, Ltd.

In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy.

BackgroundCardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).MethodsWe performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.ResultsVoxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p = 0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p = 0.0028, LGE absent 54.8°, p = 0.0022 vs normal thickness 38.1°).ConclusionsIn healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-014-0087-8) contains supplementary material, which is available to authorized users.

Myocardial hypertrophy reduces transmural variation in mitochondrial function.

Myocardial hypertrophy reduces transmural variation in mitochondrial function.

Echocardiographic study of ultrasound irradiation induced left ventricular myocardial transmural mechanical changes

Objective To evaluate the changes of segmental and the transmural myocardial peak circumferential strain (CS) of left ventricular(LV) wall with ultrasound irradiation and conbined with ultrasound contrast agent.To provide a reliable database to optimize mechanical effect of LV myocardium.To determine whether diagnostic and therapeutic dosage of ultrasound irradiation or combined with ultrasound contrast agent could induce a positive inotropic action on LV myocardium.Methods The standard short-axis gray scale views at levels of mitral annulus (MV),papillary muscle (PW) and apex (AP)during three complete cardiac cycles in open-chest Beagle canine models were acquired.The beagles were assigned into two groups randomly,group A (n =6) for baseline,baseline low dose ultrasound irradiate(3～300 mW) 5 min,combined with contrast agent 5 min and 20 min conditions,group B (n =6) for high dose ultrasound irradiation(1 W,2 W and 3 W)conditions.The CS and time to peak of CS at 18 segments and its subendomyocardium (subendo) and subepimyocardium (subepi) of LV myocardium were measured and analyzed using a dedicated Syngo VVI workstation.Results ①The CS was increased significantly (P ＜ 0.05) on different conditions of ultrasound irradiation in group A compared with CS on baseline condition at the most myocardial segments of LV under different conditions.The CS at four myocardial segments of LV was increased significantly (P ＜0.05) with 1 W ultrasound irradiation dose in group B compared with CS on baseline condition.In group B,2 W and 3 W ultrasound irradiation doses induced a siginificant decreased CS (P ＜0.05) compared with CS on baseline condition at the most myocardial segments of LV.② The difference of time to peak of CS at subendo and subepi of a few segments under different irradiation conditions was demonstrated (P ＜0.05) in the same group.Difference of time to peak of CS of subendo and subepi at the same myocardial segments in group B was bigger than those in group A.Conclusions The CS of LV was increased significantly under low dose ultrasound irradiation and combined with ultrasound contrast agent and decreased under high dose ultrasound irradiation.These findings might indicate a potential positive and negetive inotropic effects on LV myocardial deformation could be induced using ultrasound irradiation. Key words: Ultrasonography; Microbubbles ; Ventricular function,left ; Circumferential strain