Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy.

BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.

Initial AXL and MCL-1 inhibition contributes to abolishing lazertinib tolerance in EGFR-mutant lung cancer cells.

Lazertinib, a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), demonstrates marked efficacy in EGFR-mutant lung cancer. However, resistance commonly develops, prompting consideration of therapeutic strategies to overcome initial drug resistance mechanisms. This study aimed to elucidate the adaptive resistance to lazertinib and advocate novel combination treatments that demonstrate efficacy in preventing resistance as a first-line treatment for EGFR mutation-positive NSCLC. We found that AXL knockdown significantly inhibited lung cancer cell viability in the presence of lazertinib, indicating that AXL activation contributes to lazertinib resistance. However, long-term culture with a combination of lazertinib and AXL inhibitors led to residual cell proliferation and increased the MCL-1 expression level, which was mediated by the nuclear translocation of the transcription factor YAP. Triple therapy with an MCL-1 or YAP inhibitor in combination with lazertinib and an AXL inhibitor significantly reduced cell viability and increased the apoptosis rate. These results demonstrate that AXL and YAP/MCL-1 signals contribute to adaptive lazertinib resistance in EGFR-mutant lung cancer cells, suggesting that the initial dual inhibition of AXL and YAP/MCL-1 might be a highly effective strategy in eliminating lazertinib-resistant cells.

Nationwide data from comprehensive genomic profiling assays for detecting driver oncogenes in non-small cell lung cancer.

Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC). However, there are no reports of nationwide research on the detection of driver oncogenes in patients with advanced NSCLC who undergo CGP assays, especially in those with undetected driver oncogenes at diagnosis. In this study, we investigated the proportion of driver oncogenes detected in patients with advanced NSCLC with undetectable driver oncogenes at initial diagnosis and in all patients with advanced NSCLC who underwent CGP assays. We retrospectively analyzed data from 986 patients with advanced NSCLC who underwent CGP assays between August 2019 and March 2022, using the Center for Cancer Genomics and Advanced Therapeutics database. The proportion of driver oncogenes newly detected in patients with NSCLC who tested negative for driver oncogenes at diagnosis and in all patients with NSCLC were investigated. Driver oncogenes were detected in 451 patients (45.7%). EGFR was the most common (16.5%), followed by KRAS (14.5%). Among the 330 patients with undetected EGFR, ALK, ROS1, and BRAF V600E mutations at diagnosis, 81 patients (24.5%) had newly identified driver oncogenes. CGP assays could be useful to identify driver oncogenes in patients with advanced NSCLC, including those initially undetected, facilitating personalized treatment.

Self-gated free-running 5D whole-heart MRI using blind source separation for automated cardiac motion extraction.

PURPOSE: To compare two blind source separation (BSS) techniques to principal component analysis and the electrocardiogram for the identification of cardiac triggers in self-gated free-running 5D whole-heart MRI. To ascertain the precision and robustness of the techniques, they were compared in three different noise and contrast regimes. METHODS: The repeated superior-inferior (SI) projections of a 3D radial trajectory were used to extract the physiological signals in three cardiac MRI cohorts: (1) 9 healthy volunteers without contrast agent injection at 1.5T, (2) 30 ferumoxytol-injected congenital heart disease patients at 1.5T, and (3) 12 gadobutrol-injected patients with suspected coronary artery disease at 3T. Self-gated cardiac triggers were extracted with the three algorithms (principal component analysis [PCA], second-order blind identification [SOBI], and independent component analysis [ICA]) and the difference with the electrocardiogram triggers was calculated. PCA and SOBI triggers were retained for image reconstruction. The image sharpness was ascertained on whole-heart 5D images obtained with PCA and SOBI and compared among the three cohorts. RESULTS: SOBI resulted in smaller trigger differences in Cohorts 1 and 3 compared to PCA (p < 0.01) and in all cohorts compared to ICA (p < 0.04). In Cohorts 1 and 3, the sharpness increased significantly in the reconstructed images when using SOBI instead of PCA (p < 0.03), but not in Cohort 2 (p = 0.4). CONCLUSION: We have shown that SOBI results in more precisely extracted self-gated triggers than PCA and ICA. The validation across three diverse cohorts demonstrates the robustness of the method against acquisition variability.

Anoctamin-like protein 1 regulates repolarization in Paramecium behavioral responses.

Paramecium exhibits responsive behavior to environmental changes, moving either closer to or further away from stimuli. Electrophysiological experiments have revealed that these behavioral responses are controlled by membrane potentials. Anoctamin, a Ca2+-activated Cl- channel, is involved in the regulation of membrane potential in mammals. However, it remains uncertain whether Cl- channels like anoctamin regulate Paramecium behavior. Herein, replacement of external Cl- ions with acetate ion and application of Cl- channel blocker niflumic acid (NFA, 0.1 µM) increased spontaneous avoiding reactions (sARs). Hence, we hypothesized that anoctamin is involved in the stabilization of membrane potential fluctuation. Paramecium cells in which the anoctamin-like protein 1 gene was knocked down displayed frequent sARs in the culture medium without external stimulation. Treatment of anoctamin-like protein 1-knockdown cells with the Ca2+ chelator BAPTA or Ca-channel blocker nicardipine reversed the increase in sARs. Electrophysiological experiments revealed extension of membrane depolarization when positive currents were applied to anoctamin-like protein 1-knockdown cells. We concluded that anoctamin-like protein 1 works as a Cl-channel and stabilizes the membrane potential oscillation, reducing sARs.

Visceral Adipose Tissue Percentage Compared to Body Mass Index as Better Indicator of Surgical Outcomes in Women With Obesity and Endometrial Cancer.

STUDY OBJECTIVE: To assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DESIGN: Retrospective observational cohort study. SETTING: Mie University Hospital, Japan. PATIENTS: Of the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. INTERVENTIONS: We investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). MEASUREMENTS AND MAIN RESULTS: Abdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = -0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (ß = 0.338 vs 0.267, ß = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. CONCLUSION: VAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.

Complementary prognostic value of stress perfusion imaging and global coronary flow reserve derived from cardiovascular magnetic resonance: a long-term cohort study.

BACKGROUND: Phase-contrast cine cardiovascular magnetic resonance (CMR) quantifies global coronary flow reserve (CFR) by measuring blood flow in the coronary sinus (CS), allowing assessment of the entire coronary circulation. However, the complementary prognostic value of stress perfusion CMR and global CFR in long-term follow-up has yet to be investigated. This study aimed to investigate the complementary prognostic value of stress myocardial perfusion imaging and global CFR derived from CMR in patients with suspected or known coronary artery disease (CAD) during long-term follow-up. METHODS: Participants comprised 933 patients with suspected or known CAD who underwent comprehensive CMR. Major adverse cardiac events (MACE) comprised cardiac death, non-fatal myocardial infarction, unstable angina, hospitalization for heart failure, stroke, ventricular arrhythmia, and late revascularization. RESULTS: During follow-up (median, 5.3 years), there were 223 MACE. Kaplan-Meier curve analysis revealed a significant difference in event-free survival among tertile groups for global CFR (log-rank, p < 0.001) and between patients with and without ischemia (p < 0.001). The combination of stress perfusion CMR and global CFR enhanced risk stratification (p < 0.001 for overall), and prognoses were comparable between the subgroup with ischemia and no impaired CFR and the subgroup with no ischemia and impaired CFR (p = 0.731). Multivariate Cox proportional hazard regression analysis showed that impaired CFR remained a significant predictor for MACE (hazard ratio, 1.6; p = 0.002) when adjusted for coronary risk factors and CMR predictors, including ischemia. The addition of impaired CFR to coronary risk factors and ischemia significantly increased the global chi-square value from 88 to 109 (p < 0.001). Continuous net reclassification improvement and integrated discrimination with the addition of global CFR to coronary risk factors plus ischemia improved to 0.352 (p < 0.001) and 0.017 (p < 0.001), respectively. CONCLUSIONS: During long-term follow-up, stress perfusion CMR and global CFR derived from CS flow measurement provided complementary prognostic value for prediction of cardiovascular events. Microvascular dysfunction or diffuse atherosclerosis as shown by impaired global CFR may play a role as important as that of ischemia due to epicardial coronary stenosis in the risk stratification of CAD patients.

Application of Deep Learning-Based Denoising Technique for Radiation Dose Reduction in Dynamic Abdominal CT: Comparison with Standard-Dose CT Using Hybrid Iterative Reconstruction Method.

The purpose is to evaluate whether deep learning-based denoising (DLD) algorithm provides sufficient image quality for abdominal computed tomography (CT) with a 30% reduction in radiation dose, compared to standard-dose CT reconstructed with conventional hybrid iterative reconstruction (IR). The subjects consisted of 50 patients who underwent abdominal CT with standard dose and reconstructed with hybrid IR (ASiR-V50%) and another 50 patients who underwent abdominal CT with approximately 30% less dose and reconstructed with ASiR-V50% and DLD at low-, medium- and high-strength (DLD-L, DLD-M and DLD-H, respectively). The standard deviation of attenuation in liver parenchyma was measured as image noise. Contrast-to-noise ratio (CNR) for portal vein on portal venous phase was calculated. Lesion conspicuity in 23 abdominal solid mass on the reduced-dose CT was rated on a 5-point scale: 0 (best) to -4 (markedly inferior). Compared with hybrid IR of standard-dose CT, DLD-H of reduced-dose CT provided significantly lower image noise (portal phase: 9.0 (interquartile range, 8.7-9.4) HU vs 12.0 (11.4-12.7) HU, P < 0.0001) and significantly higher CNR (median, 5.8 (4.4-7.4) vs 4.3 (3.3-5.3), P = 0.0019). As for DLD-M of reduced-dose CT, no significant difference was found in image noise and CNR compared to hybrid IR of standard-dose CT (P > 0.99). Lesion conspicuity scores for DLD-H and DLD-M were significantly better than hybrid IR (P < 0.05). Dynamic contrast-enhanced abdominal CT acquired with approximately 30% lower radiation dose and generated with the DLD algorithm exhibit lower image noise and higher CNR compared to standard-dose CT with hybrid IR.

Different Types of Myocardial Injury due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant.

Coronavirus disease 2019 (COVID-19) associated myocardial injury was caused by various mechanisms. We herein describe 2 cases presenting different types of myocardial injury due to Omicron variant. In both patients, diffuse reduced left ventricular (LV) wall motion in transthoracic echocardiography, electrocardiographic abnormality, and elevated myocardial enzymes were demonstrated. In addition, cardiovascular magnetic resonance (CMR) findings fulfilled the 2018 Lake Louise Criteria (LLC) for myocarditis. However, histological findings in 1 patient showed inflammatory cell infiltration with myocyte degeneration, while those in the other showed interstitial edema without inflammatory cell infiltration. Histological findings were crucial for a differential diagnosis of myocardial injury due to Omicron variant.

Deep learning image reconstruction for improving image quality of contrast-enhanced dual-energy CT in abdomen.

OBJECTIVES: To evaluate the usefulness of deep learning image reconstruction (DLIR) to improve the image quality of dual-energy computed tomography (DECT) of the abdomen, compared to hybrid iterative reconstruction (IR). METHODS: This study included 40 patients who underwent contrast-enhanced DECT of the abdomen. Virtual monochromatic 40-, 50-, and 70-keV and iodine density images were reconstructed using three reconstruction algorithms, including hybrid IR (ASiR-V50%) and DLIR (TrueFidelity) at medium- and high-strength level (DLIR-M and DLIR-H, respectively). The standard deviation of attenuation in liver parenchyma was measured as image noise. The contrast-to-noise ratio (CNR) for the portal vein on portal venous phase CT was calculated. The vessel conspicuity and overall image quality were graded on a 5-point scale ranging from 1 (poor) to 5 (excellent). The comparative scale of lesion conspicuity in 47 abdominal solid lesions was evaluated on a 5-point scale ranging from 0 (best) to -4 (markedly inferior). RESULTS: The image noise of virtual monochromatic 40-, 50 -, and 70-keV and iodine density images was significantly decreased by DLIR compared to hybrid IR (p < 0.0001). The CNR was significantly higher in DLIR-H and DLIR-M than in hybrid IR (p < 0.0001). The vessel conspicuity and overall image quality scores were also significantly greater in DLIR-H and DLIR-M than in hybrid IR (p < 0.05). The lesion conspicuity scores for DLIR-M and DLIR-H were significantly higher than those for hybrid IR in the virtual monochromatic image of all energy levels (p ≤ 0.001). CONCLUSIONS: DLIR improves vessel conspicuity, CNR, and lesion conspicuity of virtual monochromatic and iodine density images in abdominal contrast-enhanced DECT, compared to hybrid IR. KEY POINTS: • Deep learning image reconstruction (DLIR) is useful for reducing image noise and improving the CNR of visual monochromatic 40-, 50-, and 70-keV images in dual-energy CT. • DLIR can improve lesion conspicuity of abdominal solid lesions on virtual monochromatic images compared to hybrid iterative reconstruction. • DLIR can also be applied to iodine density maps and significantly improves their image quality.

Characterization of a novel type of carbonic anhydrase that acts without metal cofactors.

BACKGROUND: Carbonic anhydrases (CAs) are universal metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO2) and bicarbonate (HCO3-). They are involved in various biological processes, including pH control, respiration, and photosynthesis. To date, eight evolutionarily unrelated classes of CA families (α, ß, γ, δ, ζ, η, θ, and ι) have been identified. All are characterized by an active site accommodating the binding of a metal cofactor, which is assumed to play a central role in catalysis. This feature is thought to be the result of convergent evolution. RESULTS: Here, we report that a previously uncharacterized protein group, named "COG4337," constitutes metal-independent CAs from the newly discovered ι-class. Genes coding for COG4337 proteins are found in various bacteria and photosynthetic eukaryotic algae. Biochemical assays demonstrated that recombinant COG4337 proteins from a cyanobacterium (Anabaena sp. PCC7120) and a chlorarachniophyte alga (Bigelowiella natans) accelerated CO2 hydration. Unexpectedly, these proteins exhibited their activity under metal-free conditions. Based on X-ray crystallography and point mutation analysis, we identified a metal-free active site within the cone-shaped α+ß barrel structure. Furthermore, subcellular localization experiments revealed that COG4337 proteins are targeted into plastids and mitochondria of B. natans, implicating their involvement in CO2 metabolism in these organelles. CONCLUSIONS: COG4337 proteins shared a short sequence motif and overall structure with ι-class CAs, whereas they were characterized by metal independence, unlike any known CAs. Therefore, COG4337 proteins could be treated as a variant type of ι-class CAs. Our findings suggested that this novel type of ι-CAs can function even in metal-poor environments (e.g., the open ocean) without competition with other metalloproteins for trace metals. Considering the widespread prevalence of ι-CAs across microalgae, this class of CAs may play a role in the global carbon cycle.

Peripartum Mid-Ventricular-Type Takotsubo Cardiomyopathy After Cesarean Delivery.

There are several causes of heart failure during pregnancy and the peripartum period, which include peripartum cardiomyopathy, Takotsubo cardiomyopathy or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, and acute myocarditis. It is important to determine the cause of the heart failure as the medical treatment may be different based on the diagnosis. However, it has been sometimes challenging to diagnose the cause because of the limited diagnostic tools, especially in pregnant women. Cardiac MRI can characterize myocardial injury and can be used to track the changes in myocardial tissue. We herein report a 35-year-old woman diagnosed with peripartum mid-ventricular-type Takotsubo cardiomyopathy, who was referred to our hospital due to worsening dyspnea the day after cesarean delivery. On admission, electrocardiography showed sinus tachycardia and poor progression of R waves in the precordial leads. Bedside echocardiography revealed severe hypokinesis in the mid- and apical left ventricle (LV) with a LV ejection fraction of 20%. Cardiac catheterization showed normal coronary arteries, and myocardial biopsy revealed contraction band necrosis. On acute phase (Day 4), cardiac MRI showed prolonged native T1 and T2, and severe hypokinesis and decreased regional longitudinal peak strain in the mid-anterior LV wall. During the 1st week, precordial ST fluctuation was observed, and LV wall motion had gradually recovered. Repeat cardiac MRI revealed normalized LV wall motion and shortened values for global native T1 and T2. Thus, she was diagnosed with peripartum Takotsubo cardiomyopathy. Serial cardiac MRI may be able to differentiate Takotsubo cardiomyopathy during pregnancy and the peripartum period from other preexisting cardiomyopathies.

A Functional Aqp1 Gene Product Localizes on The Contractile Vacuole Complex in Paramecium multimicronucleatum.

In a ciliate Paramecium, the presence of water channels on the membrane of contractile vacuole has long been predicted by both morphological and physiological data, however, to date either the biochemical or the molecular biological data have not been provided. In the present study, to examine the presence of aquaporin in Paramecium, we carried out RT-PCR with degenerated primers designed based on the ParameciumDB, and an aquaporin cDNA (aquaporin 1, aqp1) with a full-length ORF encoding 251 amino acids was obtained from Paramecium multimicronucleatum by using RACE. The deduced amino acid sequence of AQP1 had NPA-NPG motifs, and the prediction of protein secondary structure by CNR5000 and hydropathy plot showed the presence of six putative transmembrane domains and five connecting loops. Phylogenetic analysis results showed that the amino acid sequence of AQP1 was close to that of the Super-aquaporin group. The AQP1-GFP fusion protein clearly demonstrated the subcellular localization of AQP1 on the contractile vacuole complex, except for the decorated spongiome membrane. The functional analyses of aqp1 were done by RNA interference-based gene silencing, using an established feeding method. The aqp1 was found to be crucial for the total fluid output of the cell, the function of contractile vacuole membranes.

Long-term prognostic value of whole-heart coronary magnetic resonance angiography.

BACKGROUND: Coronary magnetic resonance angiography (CMRA) allows non-ionizing visualization of luminal narrowing in coronary artery disease (CAD). Although a prior study showed the usefulness of CMRA for risk stratification in short-term follow-up, the long-term prognostic value of CMRA remains unclear. The purpose of this study was to evaluate the long-term prognostic value of CMRA. METHODS: A total of 506 patients without history of myocardial infarction or prior coronary artery revascularization underwent free-breathing whole-heart CMRA between 2009 and 2015. Images were acquired using a 1.5 T or 3 T scanner and visually evaluated as the consensus decisions of two observers. Obstructive CAD on CMRA was defined as luminal narrowing of ≥ 50% in at least one coronary artery. Major adverse cardiac events (MACE) comprised cardiac death, nonfatal myocardial infarction, and unstable angina. RESULTS: Obstructive CAD on CMRA was observed in 214 patients (42%). During follow-up (median, 5.6 years), 31 MACE occurred. Kaplan-Meier curve analysis revealed a significant difference in event-free survival between patients with and without obstructive CAD for MACE (log-rank, p = 0.003) and cardiac death (p = 0.012). Annualized event rates for MACE in patients with no obstructive CAD, 1-vessel disease, 2-vessel disease, and left-main or 3-vessel disease were 0.6%, 1.5%, 2.3%, and 3.6%, respectively (log-rank, p = 0.003). Cox proportional hazard regression analysis showed that, among obstructive CAD on CMRA and clinical risk factors (age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of CAD), obstructive CAD and diabetes were significant predictors of MACE (hazard ratios, 2.9 [p = 0.005] and 2.2 [p = 0.034], respectively). In multivariate analysis, obstructive CAD remained an independent predictor (adjusted hazard ratio, 2.6 [p = 0.010]) after adjusting for diabetes. Addition of obstructive CAD to clinical risk factors significantly increased the global chi-square result from 8.3 to 13.8 (p = 0.022). CONCLUSIONS: In long-term follow-up, free breathing whole heart CMRA allows non-invasive risk stratification for MACE and cardiac death and provides incremental prognostic value over conventional risk factors in patients without a history of myocardial infarction or prior coronary artery revascularization. The presence and severity of obstructive CAD detected by CMRA were associated with worse prognosis. Importantly, patients without obstructive CAD on CMRA displayed favorable prognosis.

Roles of Adenylate Cyclases in Ciliary Responses of Paramecium to Mechanical Stimulation.

Paramecium shows rapid forward swimming due to increased beat frequency of cilia in normal (forward swimming) direction in response to various kinds of stimuli applied to the cell surface that cause K+ -outflow accompanied by a membrane hyperpolarization. Some adenylate cyclases are known to be functional K+ channels in the membrane. Using gene-specific knockdown methods, we examined nine paralogues of adenylate cyclases in P. tetraurelia to ascertain whether and how they are involved in the mechanical stimulus-induced hyperpolarization-coupled acceleration of forward swimming. Results demonstrated that knockdown of the adenylate cyclase 1 (ac1)-gene and 2 (ac2)-gene inhibited the acceleration of forward swimming in response to mechanical stimulation of the cell, whereas that spared the acceleration response to external application of 8-Br-cAMP and dilution of extracellular [K+ ] induced hyperpolarization. Electrophysiological examination of the knockdown cells revealed that the hyperpolarization-activated inward K+ current is smaller than that of a normal cell. Our results suggest that AC1 and AC2 are involved in the mechanical stimulus-induced acceleration of ciliary beat in Paramecium.

Cardiovascular magnetic resonance feature tracking for characterization of patients with heart failure with preserved ejection fraction: correlation of global longitudinal strain with invasive diastolic functional indices.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is the main cause of heart failure with preserved ejection fraction (HFpEF), and is characterized by LV stiffness and relaxation. Abnormal LV global longitudinal strain (GLS) is frequently observed l in HFpEF, and was shown to be useful in identifying HFpEF patients at high risk for a cardiovascular event. Cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT) enables the reproducible and non-invasive assessment of global strain from cine CMR images. However, the association between GLS and invasively measured parameters of diastolic function has not been investigated. We sought to determine the prevalence and severity of GLS impairment in patients with HFpEF by using CMR-FT, and to evaluate the correlation between GLS measured by CMR-FT and that measured by invasive diastolic functional indices. METHODS: Eighteen patients with HFpEF and 18 age- and sex-matched healthy control subjects were studied. All subjects underwent cine, pre- and post-contrast T1 mapping and late gadolinium-enhancement CMR. In the HFpEF patients, invasive pressure-volume loops were obtained to evaluate LV diastolic properties. GLS was quantified from cine CMR, and extracellular volume fraction (ECV) was quantified from pre- and post-contrast T1 mapping as a known imaging biomarker for predicting LV stiffness. RESULTS: GLS was significantly impaired in patients with HFpEF (- 14.8 ± 3.3 vs.-19.5 ± 2.8%, p < 0.001). Thirty nine percent (7/18) of HFpEF patients showed impaired GLS with a cut-off of - 13.9%. Statistically significant difference was found in ECV between HFpEF patients and controls (32.2 ± 3.8% vs. 29.9 ± 2.6%, p = 0.044). In HFpEF patients, the time constant of active LV relaxation (Tau) was strongly correlated with GLS (r = 0.817, p < 0.001), global circumferential strain (GCS) (r = 0.539, p = 0.021) and global radial strain (GRS) (r = - 0.552, p = 0.017). Multiple linear regression analysis revealed GLS as the only independent predictor of altered Tau (beta = 0.817, p < 0.001) among age, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, GCS, GRS and GLS. CONCLUSIONS: CMR-FT is a noninvasive approach that enables identification of the subgroup of HFpEF patients with impaired GLS. CMR LV GLS independently predicts abnormal invasive LV relaxation index Tau measurements in HFpEF patients. These findings suggest that feature-tracking CMR analysis in conjunction with ECV, may enable evaluation of diastolic dysfunction in patients with HFpEF.

Improving Image Resolution of Whole-Heart Coronary MRA Using Convolutional Neural Network.

Whole-heart coronary magnetic resonance angiography (WHCMRA) permits the noninvasive assessment of coronary artery disease without radiation exposure. However, the image resolution of WHCMRA is limited. Recently, convolutional neural networks (CNNs) have obtained increased interest as a method for improving the resolution of medical images. The purpose of this study is to improve the resolution of WHCMRA images using a CNN. Free-breathing WHCMRA images with 512 × 512 pixels (pixel size = 0.65 mm) were acquired in 80 patients with known or suspected coronary artery disease using a 1.5 T magnetic resonance (MR) system with 32 channel coils. A CNN model was optimized by evaluating CNNs with different structures. The proposed CNN model was trained based on the relationship of signal patterns between low-resolution patches (small regions) and the corresponding high-resolution patches using a training dataset collected from 40 patients. Images with 512 × 512 pixels were restored from 256 × 256 down-sampled WHCMRA images (pixel size = 1.3 mm) with three different approaches: the proposed CNN, bicubic interpolation (BCI), and the previously reported super-resolution CNN (SRCNN). High-resolution WHCMRA images obtained using the proposed CNN model were significantly better than those of BCI and SRCNN in terms of root mean squared error, peak signal to noise ratio, and structure similarity index measure with respect to the original WHCMRA images. The proposed CNN approach can provide high-resolution WHCMRA images with better accuracy than BCI and SRCNN. The high-resolution WHCMRA obtained using the proposed CNN model will be useful for identifying coronary artery disease.

Myocardial tissue characterization and strain analysis in healthy pregnant women using cardiovascular magnetic resonance native T1 mapping and feature tracking technique.

BACKGROUND: Peripartum cardiomyopathy is a life-threatening condition that occurs during the peripartum period in previously healthy women. Cardiovascular magnetic resonance (CMR) T1 mapping permits sensitive detection of tissue edema and fibrosis, and it may be useful in identifying altered myocardial tissue characteristics in peripartum cardiomyopathy. However, left ventricular (LV) volumes and mass increase considerably even in normal pregnancy, and it is not known whether altered tissue characteristics can be found in normal pregnancy. The aim of this study was to investigate whether the LV remodeling observed in normal pregnancy is associated with altered tissue characteristics determined by CMR. METHODS: Twelve normal pregnant women and 15 non pregnant women underwent cine CMR and myocardial T1 measurement at 1.5 T. Pregnant women were scanned three times, in the 2nd and 3rd trimesters of pregnancy and at 1 month postpartum. LV volumes, LV mass (LVM), and global longitudinal strain (GLS) were analyzed by cine CMR. Native myocardial T1 was determined using modified Look-Locker inversion recovery (MOLLI) images. RESULTS: LV end-diastolic volume (EDV) was significantly greater in the 3rd trimester (126 ± 22 mL) than in non-pregnant women (108 ± 14 mL, p < 0.05). LVM was significantly greater in the 3rd trimester (88.7 ± 11.8 g) than at 1 month postpartum (70.0 ± 9.8 g, p < 0.05) and in non-pregnant women (66.3 ± 13.9 g, p < 0.05). Myocardial native T1 among the 2nd and 3rd trimesters, 1 month postpartum, and non-pregnant women were similar (1133 ± 55 ms, 1138 ± 86 ms, 1105 ± 45 ms, and 1129 ± 52 ms, respectively, p = 0.59) as were GLS (- 19.5 ± 1.8, - 19.7% ± 2.2, - 19.0% ± 2.0%, and - 19.3% ± 1.9%, respectively, p = 0.66). CONCLUSIONS: LV remodeling during normal pregnancy is associated with myocardial hypertrophy, but not with edema or diffuse fibrosis of the myocardium or LV contractile dysfunction. These results observed in normal pregnancy will serve as an important basis for identifying myocardial abnormalities in patients with peripartum cardiomyopathy and other pregnancy-related myocardial diseases.