Clinical and histologic evaluation of heterotopic mucosa transpositioning at teeth and dental implants.

AIM: To investigate the healing after heterotopic mucosa transpositioning at dental implants and teeth. MATERIALS AND METHODS: One hemimandible per dog (n = 4) was allocated to receive 3 implants (test), whereby 3 premolars on the contralateral side served as controls. After osseointegration, a Z-plasty was performed on the buccal aspect of the test and control sites to heterotopically move the zone of keratinized tissue (KT) into a region with non-keratinized tissue (nKT) and vice versa. Clinical measurements were performed before (T0) and at 12 weeks following heterotopic transposition (T1). Thereafter, specimens were processed for histological analysis. RESULTS: Clinical measurements revealed that at T1, a band of KT was reestablished at teeth (mean: 2.944 ± 1.866 mm), whereas at implants, the transpositioned nKT resulted in a mucosa without any signs of keratinization (mean: 0 mm; p < .0001). At implant sites, the probing attachment level loss was more pronounced compared to tooth sites (-1.667 ± 1.195 mm and -1.028 ± 0.878 mm, respectively; p = .0076). Histologically, the transpositioned nKT, was accompanied by the formation of KT at the tooth but not at implant sites. The supracrestal soft tissues were statistically significantly higher at tooth compared to implant sites (2.978 ± 0.483 mm and 2.497 ± 0.455 mm, p = .0083). The transpositioned KT remained mostly unaltered in its morphological characteristics. CONCLUSIONS: The findings of this study indicate that: (a) transpositioned KT may retain its morphological characteristics; and (b) transpositioned nKM was accompanied by the formation of KT at the tooth but not at implant sites.

Myocardial Tissue Characterization in Patients with Hypertensive Crisis, Positive Troponin, and Unobstructed Coronary Arteries: A Cardiovascular Magnetic Resonance-Based Study.

Hypertensive crisis can present with cardiac troponin elevation and unobstructed coronary arteries. We used cardiac magnetic resonance (CMR) imaging to characterize the myocardial tissue in patients with hypertensive crisis, elevated cardiac troponin, and unobstructed coronary arteries. Patients with hypertensive crisis and elevated cardiac troponin with coronary artery stenosis <50% were enrolled. Patients with troponin-negative hypertensive crisis served as controls. All participants underwent CMR imaging at 1.5 Tesla. Imaging biomarkers and tissue characteristics were compared between the groups. There were 19 patients (63% male) with elevated troponin and 24 (33% male) troponin-negative controls. The troponin-positive group was older (57 ± 11 years vs. 47 ± 14 years, p = 0.015). The groups had similar T2-weighted signal intensity ratios and native T1 times. T2 relaxation times were longer in the troponin-positive group, and the difference remained significant after excluding infarct-pattern late gadolinium enhancement (LGE) from the analysis. Extracellular volume (ECV) was higher in the troponin-positive group (25 ± 4 ms vs. 22 ± 3 ms, p = 0.008) and correlated strongly with T2 relaxation time (rs = 0.701, p = 0.022). Late gadolinium enhancement was 32% more prevalent in the troponin-positive group (82% vs. 50%, p = 0.050), with 29% having infarct-pattern LGE. T2 relaxation time was independently associated with troponin positivity (OR 2.1, p = 0.043), and both T2 relaxation time and ECV predicted troponin positivity (C-statistics: 0.71, p = 0.009; and 0.77, p = 0.006). Left ventricular end-diastolic and left atrial volumes were the strongest predictors of troponin positivity (C-statistics: 0.80, p = 0.001; and 0.82, p < 0.001). The increased T2 relaxation time and ECV and their significant correlation in the troponin-positive group suggest myocardial injury with oedema, while the non-ischaemic LGE could be due to myocardial fibrosis or acute necrosis. These CMR imaging biomarkers provide important clinical indices for risk stratification and prognostication in patients with hypertensive crisis.

Lesion effects in terms of local impedance variations after pulsed-field ablation during pulmonary vein isolation: a case report.

Background: To date, no information is available on highly localized impedance (LI) measurements during the ablation of pulmonary veins (PVs) via a new form of energy such as electroporation by means of pulsed-field ablation (PFA). Case summary: A 55-year-old man with a history of paroxysmal atrial fibrillation was admitted to our hospital for PV isolation (PVI). The procedure was performed with the new multi-electrode PFA catheter (FARAWAVE™). Before energy delivery, a high-density map of the left atrium was constructed with the Rhythmia™ system, while the IntellaNAV Mifi™ OI catheter was used to assess the baseline LI values of the four PVs. A manual tag was used to record the exact position where the IntellaNAV™ catheter measured the LI values for each segment of the vein before and after PVI. The LI values displayed a significant variation after PFA delivery (124.3 ± 5â€…Ω for baseline LI vs. 96.8 ± 6â€…Ω after PFA, P < 0.0001) with a mean absolute LI variation of 27.5 ± 7Ω and a mean percentage LI variation of 25.8 ± 8%. The differences between the average LI values pre- and post-PFA were 28.0 ± 5, 26.5 ± 9, 26.8 ± 3, and 28.8 ± 10â€…Ω for the superior, anterior, posterior, and inferior portions of the PV. Discussion: This is the first instance of the acute characterization, in terms of LI drop, of antral lesions created by a new PFA system. Local impedance variations at ablation sites seem to be larger than those recorded at successful ablation spots obtained by means of thermal energy sources.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in asymptomatic heart-transplanted patients.

OBJECTIVES: To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). METHODS: From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. RESULTS: During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. CONCLUSION: Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. KEY POINTS: • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

Relationship between tissue characteristics and mechanical properties of coronary plaques: a comparison between integrated backscatter intravascular ultrasound (IVUS) and speckle-tracking IVUS.

High-risk coronary plaques have certain morphological characteristics. Thus, comprehensive assessment is needed for the risk stratification of plaques in patients with coronary artery disease. Integrated backscatter intravascular ultrasound (IB-IVUS) has been used successfully used to evaluate the tissue characteristics of coronary plaques; however, the mechanical properties of plaques have been rarely assessed. Therefore, we developed Speckle-tracking IVUS (ST-IVUS) to evaluate the mechanical properties of coronary plaque. This study aimed to evaluate the relation between the tissue characteristics of coronary plaques using IB-IVUS and their mechanical properties using ST-IVUS. We evaluated 95 non-targeted plaques in 95 patients undergoing elective percutaneous coronary intervention to the left anterior descending artery. We set regions of interest (ROIs) in the cross-sectional images of coronary plaques where we divided 120 degree plaques into four quadrants (every 30 degrees), with the center at the area of maximum atheroma thickness. We measured relative calcification area (%CA, relative fibrous area (%FI) and relative lipid pool area (%LP) in a total of 380 ROIs. In ST-IVUS analysis, we measured strain in the circumferential direction of the lumen area (LA strain: %), the external elastic membrane area strain (EEM strain: %), and strain in the radial direction (radial strain: %). On global cross-sectional area IB-IVUS analysis, the %CA was 1.2 ± 1.2%; the %FI was 49.0 ± 15.9%, and the %LP was 49.7 ± 16.5%. In ST-IVUS analysis, the LA strain was 0.67 ± 0.43%; the EEM strain was 0.49 ± 0.33%, and the radial strain was 2.02 ± 1.66%. On regional analysis, the %LP was not associated with the LA strain (r = - 0.002 p = 0.97), the EEM strain (r = - 0.05 p = 0.35), or with the radial strain (r = - 0.04 p = 0.45). These trends were seen between the %FI and the LA strain (r = 0.02 p = 0.74), the %FI and the EEM strain (r = 0.05 p = 0.35), and the %FI and the radial strain (r = 0.04 p = 0.50). A significant correlation was only observed between the %CA and the LA strain (r = - 0.15 p = 0.0038). Our findings indicate that the associations between mechanical properties and tissue characteristics lacked statistical significance, more often than not, and that it is necessary to evaluate the mechanical properties as well as plaque characteristics for risk stratification of coronary plaques.

Associations between perfusion defects, tissue changes and myocardial deformation in hypertrophic cardiomyopathy, uncovered by a cardiac magnetic resonance segmental analysis.

BACKGROUND: Microvascular dysfunction is an often overlooked feature of hypertrophic cardiomyopathy (HCM). Our aim was to assess the association between microvascular dysfunction, wall thickness, tissue characteristics and myocardial deformation in HCM patients, by analyzing individual myocardial segments. METHODS: Prospective assessment including cardiac magnetic resonance to assess wall thickness, T1 and T2 mapping, extracellular volume, late gadolinium enhancement (LGE) and stress perfusion. Results were stratified according to the 16 American Heart Association segments. RESULTS: Seventy-five patients were recruited (1200 segments), 63% male, mean age 54.6±14.8 years, maximal wall thickness of 20.22±4.6 mm. Among the 424 segments (35%) with perfusion defects, 24% had defects only in the endocardial layer and 12% in both endocardial and epicardial layers. Perfusion defects were more often detected in hypertrophied segments (64%). Among the 660 segments with normal wall thickness, 19% presented perfusion defects. Independently of wall thickness, segments with perfusion defects had a higher T1 (ß-estimate 30.28, p<0.001), extracelluar volume (ß-estimate 1.50, p<0.001) and T2 (ß-estimate 0.73, p<0.001) and had late gadolinium enhancement more frequently (odds ratio 4.16, p<0.001). Higher values of circumferential strain (lower deformation) and lower values of radial strain were found in segments with perfusion defects (ß-estimate 2.76, p<0.001; and ß-estimate -10.39, p<0.001, circumferential and radial strain, respectively). CONCLUSION: While microvascular dysfunction was more prevalent in more hypertrophied segments, it also had a major presence in segments without hypertrophy. In this segmental analysis, we found an association between the presence of ischemia and tissue abnormalities, replacement fibrosis as well as impaired strain, independently of the segmental wall thickness.

Evaluation of the effect of tofogliflozin on the tissue characteristics of the carotid wall-a sub-analysis of the UTOPIA trial.

BACKGROUND: Since sodium-glucose cotransporter 2 (SGLT2) inhibitors have a pleiotropic antiatherogenic effect, they are expected to attenuate the progression of atherosclerosis. However, whether SGLT2 inhibitors affect the tissue characteristics of the human arterial wall remains unclear. This study aimed to evaluate the effects of tofogliflozin, a selective SGLT2 inhibitor, on the tissue characteristics of the human arterial wall in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD). METHODS: The present study was a post hoc analysis based on data obtained from the Using Tofogliflozin for Possible Better Intervention against Atherosclerosis for Type 2 Diabetes Patients (UTOPIA) trial, which was a multicenter prospective, randomized, open-label, blinded-endpoint study conducted to evaluate the efficacy of tofogliflozin in preventing the progression of atherosclerosis in patients with T2DM. We evaluated the longitudinal change in the ultrasonic tissue characteristics of the carotid wall using gray-scale median (GSM), an established index of ultrasonic tissue characteristics. The right and left intima-medial areas were delineated, and the GSM values were evaluated (right GSM-CCA and left GSM-CCA). The average values of the right and left carotid arteries were defined as "mean GSM-CCA value." RESULTS: In a mixed-effects model for repeated measures, mean GSM-CCA, along with the right and left GSM-CCA values, did not significantly change in either the tofogliflozin (n = 168) or conventional treatment group (n = 169). In addition, the tofogliflozin and conventional treatment groups did not significantly differ regarding the change of the mean GSM-CCA (mean difference [95% CI] - 1.24[- 3.87, 1.38], P = 0.35), along with the right (mean difference [95% CI] - 2.33[- 5.70, 1.05], P = 0.18) and the left GSM-CCA (mean difference [95% CI] - 0.29 [- 3.53, 2.95], P = 0.86) values. Similar findings were obtained even after adjusting for traditional cardiovascular risk factors and/or the administration of drugs at baseline. CONCLUSIONS: The tissue characteristics of the carotid arterial wall did not change in either the tofogliflozin or conventional treatment group during the 104-week treatment period, and there was no significant difference between the treatment groups. Clinical trial registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).

Left ventricular function, strain, and infarct characteristics in patients with transient ST-segment elevation myocardial infarction compared to ST-segment and non-ST-segment elevation myocardial infarctions.

AIMS: This study aims to explore cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) function, strain, and infarct size characteristics in patients with transient ST-segment elevation myocardial infarction (TSTEMI) compared to patients with ST-segment and non-ST-segment elevation myocardial infarctions (STEMI and NSTEMI, respectively). METHODS AND RESULTS: In total, 407 patients were enrolled in this multicentre observational prospective cohort study. All patients underwent CMR examination 2-8 days after the index event. CMR cine imaging was performed for functional assessment and late gadolinium enhancement to determine infarct size and identify microvascular obstruction (MVO). TSTEMI patients demonstrated the highest LV ejection fraction and the most preserved global LV strain (longitudinal, circumferential, and radial) across the three groups (overall P ≤ 0.001). The CMR-defined infarction was less frequently observed in TSTEMI than in STEMI patients [77 (65%) vs. 124 (98%), P < 0.001] but was comparable with NSTEMI patients [77 (65%) vs. 66 (70%), P = 0.44]. A remarkably smaller infarct size was seen in TSTEMI compared to STEMI patients [1.4 g (0.0-3.9) vs. 13.5 g (5.3-26.8), P < 0.001], whereas infarct size was not significantly different from that in NSTEMI patients [1.4 g (0.0-3.9) vs. 2.1 g (0.0-8.6), P = 0.06]. Whilst the presence of MVO was less frequent in TSTEMI compared to STEMI patients [5 (4%) vs. 53 (31%), P < 0.001], no significant difference was seen compared to NSTEMI patients [5 (4%) vs. 5 (5%), P = 0.72]. CONCLUSION: TSTEMI yielded favourable cardiac LV function, strain, and infarct-related scar mass compared to STEMI and NSTEMI. LV function and infarct characteristics of TSTEMI tend to be more similar to NSTEMI than STEMI.

Age-dependent mechanical and microstructural properties of the rabbit soleus muscle.

During growth there are serious changes in the skeletal muscles to compensate for the changed requirements in terms of body weight and size. In this study, the age-dependent (between 21 and 100 days) mechanical and microstructural properties of rabbit soleus muscle tissue were investigated. For this purpose, morphological properties (animal mass, soleus muscle mass, tibial length) were measured at 5 different times during aging. On the other hand, fibre orientation-dependent axial and semi-confined compression experiments were realised. In addition, the essential components (muscle fibres, extracellular matrix, remaining components), dominating the microstructure of muscle tissue, were analysed. While the mechanical results show hardly any age-dependent differences, the morphological and microstructural results show clear age-dependent differences. All morphological parameters increase significantly (animal mass by 839.2%, muscle mass 1050.6%, tibial length 233.6%). In contrast, microstructural parameters change differently. The percentage of fibres (divided into slow-twitch (ST) and fast-twitch (FT) fibres) increases significantly (137.6%), while the proportions of the extracellular matrix and the remaining components (48.2% and 46.1%) decrease. At the same time, the cross-sectional area of the fibres increases significantly (697.9%). The totality of this age-dependent information provides a deeper understanding of age-related changes in muscle structure and function and may contribute to successful development and validation of growth models in the future. STATEMENT OF SIGNIFICANCE: This article reports the first comprehensive data set on age-dependent morphological (animal mass, soleus muscle mass, tibial length), mechanical (axial and semi-confined compression), and microstructural (muscle fibres, extracellular matrix, remaining components) properties of the rabbit soleus muscle. On the one hand, the results of this study contribute to the understanding of muscle mechanics and thus to understanding of load transfer mechanisms inside the muscle tissue during growth. On the other hand, these results are relevant to the fields of constitutive formulation of age-dependent muscle tissue.

Extended Kalman filter for online soft tissue characterization based on Hunt-Crossley contact model.

Real-time soft tissue characterization is significant to robotic assisted minimally invasive surgery for achieving precise haptic control of robotic surgical tasks and providing realistic force feedback to the operator. This paper presents a nonlinear methodology for online soft tissue characterization. An extended Kalman filter (EKF) is developed based on dynamic linearization of the nonlinear H-C contact model in terms of system state for online characterization of soft tissue parameters. To handle the resultant linearization modelling error, an innovation orthogonal EKF is further developed by incorporating an adaptive factor in the EKF filtering to adaptively adjust the innovation covariance according to the principle of innovation orthogonality. Simulation and experimental results as well as comparison analysis demonstrate that the proposed methodology can effectively characterize soft tissue parameters, leading to dramatically improved accuracy comparing to recursive least square estimation. Further, the proposed methodology also requires a smaller computational load and can achieve the real-time performance for soft tissue characterization.

Associations of continuous glucose monitoring-assessed glucose variability with intima-media thickness and ultrasonic tissue characteristics of the carotid arteries: a cross-sectional analysis in patients with type 2 diabetes.

BACKGROUND: The association between glucose variability and the progression of atherosclerosis is not completely understood. We aimed to evaluate the associations of glucose variability with the progression of atherosclerosis in the early stages. METHODS: We conducted a cross-sectional analysis to investigate the associations of glucose variability, assessed by continuous glucose monitoring, with intima-media thickness (IMT) and gray-scale median (GSM) of the carotid arteries, which are different indicators for the progression of atherosclerosis. We used baseline data from a hospital-based multicenter prospective observational cohort study among Japanese patients with type 2 diabetes without a history of cardiovascular diseases aged between 30 and 80 years. Continuous glucose monitoring was performed by Freestyle Libre Pro, and glucose levels obtained every 15 min for a maximum of eight days were used to calculate the metrics of glucose variability. IMT and GSM were evaluated by ultrasonography, and the former indicates thickening of intima-media complex in the carotid artery wall, while the latter indicates tissue characteristics. RESULTS: Among 600 study participants (age: 64.9 ± 9.2 (mean ± SD) years; 63.2%: men; HbA1c: 7.0 ± 0.8%), participants with a larger intra- and inter-day glucose variability had a lower GSM and most of these associations were statistically significant. No trend based on glucose variability was shown regarding IMT. Standard deviation of glucose (regression coefficient, ß = - 5.822; 95% CI - 8.875 to - 2.768, P < 0.001), glucose coefficient of variation (ß = - 0.418; - 0.685 to - 0.151, P = 0.002), mean amplitude of glycemic excursion (ß = - 1.689; - 2.567 to - 0.811, P < 0.001), mean of daily differences (ß = - 6.500; - 9.758 to - 3.241, P < 0.001), and interquartile range (ß = - 4.289; - 6.964 to - 1.614, P = 0.002) had a statistically significant association with mean-GSM after adjustment for conventional cardiovascular risk factors, including HbA1c. No metrics of glucose variability had a statistically significant association with IMT. CONCLUSIONS: Continuous glucose monitoring-assessed glucose variability was associated with the tissue characteristics of the carotid artery wall in type 2 diabetes patients without cardiovascular diseases.

Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids.

With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.

The Impact of Ischemia Assessed by Magnetic Resonance on Functional, Arrhythmic, and Imaging Features of Hypertrophic Cardiomyopathy.

Aims: The aim of the study is to investigate the association between the degree of ischemia due to coronary microvascular dysfunction (CMD) and the left ventricular (LV) tissue characteristics, systolic performance, and clinical manifestations in hypertrophic cardiomyopathy (HCM). Methods and Results: This prospective study enrolled 75 patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential, and radial strains analysis. Electrocardiogram, 24-h Holter recording, and cardiopulmonary exercise testing (CPET) were performed to assess arrhythmias and functional capacity. In total, 47 (63%) patients were men with the mean age of 54.6 (14.8) years, 51 (68%) patients had non-obstructive HCM, maximum wall thickness (MWT) was 20.2 (4.6) mm, LV ejection fraction (LVEF) was 71.6 (8.3%), and ischemic burden was 22.5 (16.9%) of LV. Greater MWT was associated with the severity of ischemia (ß-estimate:1.353, 95% CI:0.182; 2.523, p = 0.024). Ischemic burden was strongly associated with higher values of native T1 (ß-estimate:9.018, 95% CI:4.721; 13.315, p < 0.001). The association between ischemia and LGE was significant in following subgroup analyses: MWT 15-20 mm (ß-estimate:1.941, 95% CI:0.738; 3.143, p = 0.002), non-obstructive HCM (ß-estimate:1.471, 95% CI:0.258; 2.683, p = 0.019), women (ß-estimate:1.957, 95% CI:0.423; 3.492, p = 0.015) and age <40 years (ß-estimate:4.874, 95% CI:1.155; 8.594, p = 0.016). Ischemia in ≥21% of LV was associated with LGE >15% (AUC 0.766, sensitivity 0.724, specificity 0.659). Ischemia was also associated with atrial fibrillation or flutter (AF/AFL) (OR-estimate:1.481, 95% CI:1.020; 2.152, p = 0.039), but no association was seen for non-sustained ventricular tachycardia. Ischemia was associated with shorter time to anaerobic threshold (ß-estimate: -0.442, 95% CI: -0.860; -0.023, p = 0.039). Conclusion: In HCM, ischemia associates with morphological markers of severity of disease, fibrosis, arrhythmia, and functional capacity.

The combined effects of cardiac geometry, microcirculation, and tissue characteristics on cardiac systolic and diastolic function in subclinical diabetes mellitus-related cardiomyopathy.

BACKGROUND: Diabetes mellitus-related cardiomyopathy has recently been described as a distinct progression of left ventricular (LV) systolic and diastolic dysfunction. Pathological changes in the myocardium may explain the development of two different phenotypes. We evaluated the effects of LV geometry, myocardial microcirculation, and tissue characteristics on cardiac deformation in patients with subclinical type 2 diabetes mellitus (T2DM) utilizing multiparametric cardiac magnetic resonance (CMR) imaging. METHODS: A total of 135 T2DM patients and 55 matched controls were prospectively enrolled and performed multiparametric CMR examination. CMR-derived parameters including cardiac geometry, function, microvascular perfusion, T1 mapping, T2 mapping, and strain were analyzed and compared between T2DM patients and controls. RESULTS: The univariable and multivariable analysis of systolic and diastolic function revealed that longer duration of diabetes was associated with decreased longitudinal peak systolic strain rate (PSSR-L) (ß = 0.195, p = .013), and higher remodeling index and higher extracellular volume (ECV) tended to correlate with decreased longitudinal peak diastolic strain rate (PDSR-L) (remodeling index, ß = -0.339, p = .000; ECV, ß = -0.172, p = .026), whereas microvascular perfusion index and T2 value affected both PSSR-L (perfusion index, ß = -0.328, p = .000; T2 value, ß = 0.306, p = .000) and PDSR-L (perfusion index, ß = 0.209, p = .004; T2 value, ß = -0.275, p = .000) simultaneously. CONCLUSIONS: The LV concentric remodeling and myocardial fibrosis correlated with diastolic function, and perfusion function and myocardial edema were associated with both LV systolic and diastolic function.

Influence of heritability on craniofacial soft tissue characteristics of monozygotic twins, dizygotic twins, and their siblings using Falconer's method and principal components analysis.

OBJECTIVE: The purpose of this study was to investigate the influence of heritability on the craniofacial soft tissue cephalometric characteristics of monozygotic (MZ) twins, dizygotic (DZ) twins, and their siblings (SIB). METHODS: The samples comprised Korean adult twins and their siblings (mean age, 39.8 years; MZ group, n = 36 pairs; DZ group, n = 13 pairs of the same gender; and SIB group, n = 26 pairs of the same gender). Thirty cephalometric variables were measured to characterize facial profile, facial height, soft-tissue thickness, and projection of nose and lip. Falconer's method was used to calculate heritability (low heritability, h2 < 0.2; high heritability, h2 > 0.9). After principal components analysis (PCA) was performed to extract the models, we calculated the intraclass correlation coefficient (ICC) value and heritability of each component. RESULTS: The MZ group exhibited higher ICC values for all cephalometric variables than DZ and SIB groups. Among cephalometric variables, the highest h2 (MZ-DZ) and h2 (MZ-SIB) values were observed for the nasolabial angle (NLA, 1.544 and 2.036), chin angle (1.342 and 1.112), soft tissue chin thickness (2.872 and 1.226), and upper lip thickness ratio (1.592 and 1.026). PCA derived eight components with 84.5% of a cumulative explanation. The components that exhibited higher values of h2 (MZ-DZ) and h2 (MZ-SIB) were PCA2, which includes facial convexity, NLA, and nose projection (1.026 and 0.972), and PCA7, which includes chin angle and soft tissue chin thickness (2.107 and 1.169). CONCLUSIONS: The nose and soft tissue chin were more influenced by genetic factors than other soft tissues.

Evaluation of the Effect of Alogliptin on Tissue Characteristics of the Carotid Wall: Subanalysis of the SPEAD-A Trial.

INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray-scale median (GSM) reflects its composition and low-GSM plaque is considered to be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue characteristics of the carotid wall, in patients with type 2 diabetes (T2DM). METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A trial, a randomized controlled trial that demonstrated the beneficial effect of alogliptin treatment on the progression of carotid intima-media thickness in patients with T2DM with no past history of apparent cardiovascular disease. A total of 322 subjects (161 in the alogliptin treatment group and 161 in the conventional treatment group) were enrolled. The primary outcome was the change from baseline in mean GSM-CCA (common carotid artery) during the 104-week observation period. RESULTS: Both alogliptin treatment and conventional treatment significantly increased the mean GSM-CCA (from 60.7 ± 12.3 to 65.9 ± 10.1, p < 0.001 and 58.8 ± 14.4-65.2 ± 12.2, p < 0.001, respectively) and there was no significant difference in changes in mean GSM-CCA between the treatment groups (p = 0.95). Additionally, there were no differences in the changes in the left and right GSM-CCA between the groups. CONCLUSIONS: A post hoc subanalysis revealed an improvement of tissue characteristics in the carotid arterial wall in both the alogliptin treatment group and the conventional treatment group during the 104-week treatment period and that there was no significant difference between the treatment groups. CLINICAL TRIAL REGISTRATION: UMIN000019951.

Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice.

Background: Targeted capture sequencing can potentially facilitate precision medicine, but the feasibility of this approach in gastrointestinal (GI) malignancies is unknown. Patients and methods: The FOrMAT (Feasibility of a Molecular Characterisation Approach to Treatment) study was a feasibility study enrolling patients with advanced GI malignancies from February 2014 to November 2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin-embedded diagnostic/resection samples) was carried out to detect mutations, copy number variations and translocations in up to 46 genes which had prognostic/predictive significance or were targets in current/upcoming clinical trials. Results: Of the 222 patients recruited, 215 patients (96.8%) had available tissue samples, 125 patients (56.3%) had ≥16 genes successfully sequenced and 136 patients (61.2%) had ≥1 genes successfully sequenced. Sample characteristics influenced the proportion of successfully sequenced samples, e.g. tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas 27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P ≤ 0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type of sample (resection versus biopsy: 82.4% versus 47.6%, P ≤ 0.001). Currently, actionable alterations were detected in 90 (40.5%) of the 222 patients recruited (66% of the 136 patients sequenced) and 2 patients subsequently received a targeted therapy. The most frequently detected currently actionable alterations were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival samples, the median time to obtain sequencing results was 18.9 weeks, including a median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing. Conclusions: Targeted sequencing detected actionable alterations in formalin-fixed paraffin-embedded samples, but tissue characteristics are of critical importance in determining sequencing success. Routine molecular profiling of GI tumours outside of clinical trials is not an effective use of healthcare resources unless more targeted drugs become available. ClinicalTrials.gov identifier: NCT02112357.

High-SNR multiple T2 (*)-contrast magnetic resonance imaging using a robust denoising method based on tissue characteristics.

PURPOSE: To develop an effective method that can suppress noise in successive multiecho T2 (*)-weighted magnetic resonance (MR) brain images while preventing filtering artifacts. MATERIALS AND METHODS: For the simulation experiments, we used multiple T2 -weighted images of an anatomical brain phantom. For in vivo experiments, successive multiecho MR brain images were acquired from five healthy subjects using a multiecho gradient-recalled-echo (MGRE) sequence with a 3T MRI system. Our denoising method is a nonlinear filter whose filtering weights are determined by tissue characteristics among pixels. The similarity of the tissue characteristics is measured based on the l2 -difference between two temporal decay signals. Both numerical and subjective evaluations were performed in order to compare the effectiveness of our denoising method with those of conventional filters, including Gaussian low-pass filter (LPF), anisotropic diffusion filter (ADF), and bilateral filter. Root-mean-square error (RMSE), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were used in the numerical evaluation. Five observers, including one radiologist, assessed the image quality and rated subjective scores in the subjective evaluation. RESULTS: Our denoising method significantly improves RMSE, SNR, and CNR of numerical phantom images, and CNR of in vivo brain images in comparison with conventional filters (P < 0.005). It also receives the highest scores for structure conspicuity (8.2 to 9.4 out of 10) and naturalness (9.2 to 9.8 out of 10) among the conventional filters in the subjective evaluation. CONCLUSION: This study demonstrates that high-SNR multiple T2 (*)-contrast MR images can be obtained using our denoising method based on tissue characteristics without noticeable artifacts. Evidence level: 2 J. MAGN. RESON. IMAGING 2017;45:1835-1845.

Technical note: Recommendations for a standard procedure to assess cortical bone at the tissue-level in vivo using impact microindentation.

Impact microindentation is a novel method for measuring the resistance of cortical bone to indentation in patients. Clinical use of a handheld impact microindentation technique is expanding, highlighting the need to standardize the measurement technique. Here, we describe a detailed standard operation procedure to improve the consistency and comparability of the measurements across centers.