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Conventional pulsed and continuous-wave Doppler applications have been in use since the mid-1970s. The first color flow mapping system was a color m-mode instrument developed by a Swiss engineer named Brandistini. Stevenson and coworkers utilized this system for cardiac sonographic examinations in the late 1970s, but in general, there was very little interest in the method until the early 1980s, when a 2D color flow mapping system became available. With this new technology and the interest it generated, the development in color flow mapping Doppler technology moved at a rapid pace. [ABSTRACT FROM AUTHOR]

After FDA approval of the new-generation contrast agent Optison (Mallinckrodt Medical, St. Louis, MO) January 1998, the use of contrast in echocardiography has become an invaluable tool. A review of 100 patients revealed contrast to be useful for endocardial border definition and wall segment analysis, enhancement of pulsed Doppler, and chamber opacification for the detection of thrombi. Evaluation of wall segments by two observers before and after injection of the contrast agent revealed an increase in the number of wall segments visualized by 4.8. Postinjection readings were consistent between the two observers. Routine contrast echocardiography may provide a more diagnostic study. [ABSTRACT FROM AUTHOR]

In recent years, transcatheter edge-to-edge repair (TEER) has been widely adopted as an effective treatment for mitral regurgitation (MR). The aim of this study is to develop a personalized in silico model to predict the effect of edge-to-edge repair in advance to the procedure for each individual patient. For this purpose, we propose a combination of a valve deformation model for computing the mitral valve (MV) orifice area (MVOA) and a lumped parameter model for the hemodynamics, specifically mitral regurgitation volume (RVol). Although we cannot obtain detailed information on the three-dimensional flow field near the mitral valve, we can rapidly simulate the important medical parameters for the clinical decision support. In the present method, we construct the patient-specific pre-operative models by using the parameter optimization and then simulate the postoperative state by applying the additional clipping condition. The computed preclip MVOAs show good agreement with the clinical measurements, and the correlation coefficient takes 0.998. In addition, the MR grade in terms of RVol also has good correlation with the grade by ground truth MVOA. Finally, we try to investigate the applicability for the predicting the postclip state. The simulated valve shapes clearly show the well-known double orifice and the improvement of the MVOA, compared with the preclip state. Similarly, we confirmed the improved reverse flow and MR grade in terms of RVol. A total computational time is approximately 8 h by using general-purpose PC. These results obviously indicate that the present in silico model has good capability for the assessment of edge-to-edge repair., (Copyright © 2024 by ASME.)

Objective . Accurate extraction of mitral valve shape from clinical tomographic images acquired in patients has proven useful for planning surgical and interventional mitral valve treatments. However, manual extraction of the mitral valve shape is laborious, and the existing automatic extraction methods have not been sufficiently accurate. In this paper, we propose a fully automated method of extracting mitral valve shape from computed tomography (CT) images for the all phases of the cardiac cycle. Approach . This method extracts the mitral valve shape based on DenseNet using both the original CT image and the existence probability maps of the mitral valve area inferred by U-Net as input. A total of 1585 CT images from 204 patients with various cardiac diseases including mitral regurgitation were collected and manually annotated for mitral valve region. The proposed method was trained and evaluated by 10-fold cross validation using the collected data and was compared with the method without the existence probability maps. Main results . The mean error of shape extraction error in the proposed method is 0.88 mm, which is an improvement of 0.32 mm compared with the method without the existence probability maps. Significance . We present a novel fully automatic mitral valve extraction method from input to output for all phases of 4D CT images. We suggest that the accuracy of mitral valve shape extraction is improved by using existence probability maps., (© 2024 Institute of Physics and Engineering in Medicine.)

P-glycoprotein (P-gp) antagonists inhibit ceramide metabolism at the juncture of glycosylation. The purpose of this study was to test whether targeting P-gp would be a viable alternative to targeting glucosylceramide synthase (GCS) for enhancing ceramide cytotoxicity. A2780 wild-type, and multidrug-resistant 2780AD and NCI/ADR-RES human ovarian cancer cell lines and the cell-permeable ceramide analog, C6-ceramide (C6-cer), were employed. Compared to P-gp-poor A2780 cells, P-gp-rich 2780AD cells converted 3.7-fold more C6-cer to nontoxic C6-glucosylceramide (C6-GC), whereas cell-free GCS activities were equal. 2780AD cells displayed resistance to C6-cer (10 μM) that was reversed by inclusion of the P-gp antagonist tamoxifen (5 μM) but not by inclusion of a GCS inhibitor. Co-administration of C6-cer and P-gp antagonists was also effective in NCI/ADR-RES cells. For example, C6-cer, VX-710 (Biricodar), and cyclosporin A (cyc A) exposure resulted in viabilities of ~90% of control; however, C6-cer/VX-710 and C6-cer/cyc A additions were synergistic and resulted in viabilities of 22% and 17%, respectively. Further, whereas C6-ceramide and cyc A imparted 1.5- and 0-fold increases in caspase 3/7 activity, the combination produced a 3.5-fold increase. Although the upstream elements of cell death have not been elucidated, the novel C6-ceramide/P-gp antagonist combination merits further study and assessment of clinical translational potential., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The role of glucosylceramide synthase (GCS) in regulating ceramide-induced apoptosis has been widely studied. The purpose of this investigation was to evaluate the role of P-glycoprotein (P-gp) in regulating ceramide cytotoxicity by using C6-ceramide. To accomplish this, we employed HeLa cells with conditional expression of the multidrug resistance gene 1/P-gp. HeLa cells expressing P-gp (P-gp/on cells) challenged with [14C]C6-ceramide (6 µM), synthesized 4.5-fold the amount of C6-glucosylceramide (GC) compared to HeLa cells with suppressed expression of P-gp (P-gp/off cells), whereas the generated levels of C6-sphingomyelin were almost equal (33 and 29% of intracellular 14C, respectively). Tamoxifen, a P-gp antagonist, decreased the C6-GC levels from 3.5-1.0% in the P-gp/off and from 17-2.8% of the total lipid 14C levels in the P-gp/on cells. Tamoxifen did not inhibit cell-free C6-GC synthesis in the P-gp/off or P-gp/on homogenates. However, a specific GCS inhibitor, ethylenedioxy-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (ethylenedioxy-P4), blocked synthesis by 90%. In the cytotoxicity assays, the P-gp/off cells were sensitive to C6-ceramide and the P-gp/on cells were resistant. Resistance to C6-ceramide in the P-gp/on cells was reversed by tamoxifen but not by ethylenedioxy-P4. Experiments in another cervical cancer model showed that multidrug-resistant P-gp-rich KB-V1 cells synthesized 3-fold more C6-GC from C6-ceramide than the parental, P-gp-poor KB-3-1 cells, and whereas tamoxifen had no effect on the C6-GC synthesis in the KB-3-1 cells, it inhibited synthesis by 70% in the KB-V1 cells. This study demonstrates that P-gp potentiates C6-ceramide glycosylation and if antagonized augments C6-ceramide sensitivity, both features previously ascribed to GCS. We propose that P-gp can be an effective target for enhancing short-chain ceramide cytotoxicity in the treatment of drug-resistant cancer.

Due to recent use of short-chain ceramides in preclinical studies, we characterized C6-ceramide metabolism in cancer cell lines and assessed metabolic junctures for enhancing efficacy. MDA-MB-231 breast cancer cells decreased the amount of C6-ceramide metabolized to C6-sphingomyelin (C6-SM) and increased the amount metabolized to C6-glucosylceramide (C6-GC) in response to increasing concentrations. A similar trend was seen in DU-145 (prostate cancer), PANC-1 (pancreatic cancer), and LoVo (colorectal cancer) cells. KG-1 leukemia cells favored C6-SM synthesis at low (0.6muM) and high-dose (12muM) C6-ceramide. Partnering C6-ceramide with tamoxifen, a P-glycoprotein antagonist that impedes ceramide glycosylation, was an effective regimen for enhancing cytotoxicity in cells. Experiments to assess the mechanism of cell death using KG-1 cells showed that tamoxifen inhibited synthesis of C6-GC and C6-SM from C6-ceramide by 80% and 50%, respectively, which was accompanied by enhanced apoptosis. Radiolabeling of KG-1 cells with [(3)H]palmitic acid produced a 2-fold increase in (3)H-long-chain ceramides when unlabeled C6-ceramide was added and a 9-fold increase when C6-ceramide and tamoxifen were added. The increase in (3)H-palmitate radiolabeling of long-chain ceramides was blocked by inclusion of a ceramide synthase inhibitor; however, inhibiting synthesis of long-chain ceramide did not rescue cells. These studies show that tamoxifen enhances the apoptotic effects of C6-ceramide. The proposed mechanism involves blocking short-chain ceramide anabolism to favor hydrolysis and generation of sphingosine. We propose that use of tamoxifen and other P-glycoprotein antagonists can be an effective means for enhancing cytotoxic potential of short-chain ceramides in the treatment of cancer., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

We combined electrophysiological and freeze-fracture methods to estimate the unitary turnover rate of the gamma-aminobutyric acid (GABA) transporter GAT1. Human GAT1 was expressed in Xenopus laevis oocytes, and individual cells were used to measure and correlate the macroscopic rate of GABA transport and the total number of transporters in the plasma membrane. The two-electrode voltage-clamp method was used to measure the transporter-mediated macroscopic current evoked by GABA (I(NaCl)(GABA)), macroscopic charge movements (Q (NaCl)) evoked by voltage pulses and whole-cell capacitance. The same cells were then examined by freeze-fracture and electron microscopy in order to estimate the total number of GAT1 copies in the plasma membrane. GAT1 expression in the plasma membrane led to the appearance of a distinct population of 9-nm freeze-fracture particles which represented GAT1 dimers. There was a direct correlation between Q (NaCl) and the total number of transporters in the plasma membrane. This relationship yielded an apparent valence of 8 +/- 1 elementary charges per GAT1 particle. Assuming that the monomer is the functional unit, we obtained 4 +/- 1 elementary charges per GAT1 monomer. This information and the relationship between I(NaCl)(GABA) and Q (NaCl) were used to estimate a GAT1 unitary turnover rate of 15 +/- 2 s(-1) (21 degrees C, -50 mV). The temperature and voltage dependence of GAT1 were used to estimate the physiological turnover rate to be 79-93 s(-1) (37 degrees C, -50 to -90 mV).

Thrombotic obstruction of mechanical prosthetic valves is a frequently encountered cause of prosthetic valve dysfunction, which can result in stenosis and regurgitation. We present a case of thrombotic obstruction of a bileaflet mechanical aortic valve prosthesis that resulted in severe stenosis and regurgitation. Considering the known risk factors associated with both surgical and thrombolytic treatments, a decision was made to use tissue plasminogen activator therapy to relieve the burden of the thrombotic valvular obstruction. In this case review, we use continuous wave Doppler to demonstrate recovery of normal valve function despite suboptimal two-dimensional imaging.

Twenty nine patients (aged from three months to 37 years) with confirmed or suspected ventricular septal defects were studied separately by three examiners who used colour flow mapping and imaging, or continuous wave Doppler and imaging, or a combined reference examination. Colour flow mapping identified 19 of the 25 patients with a ventricular septal defect, continuous wave Doppler echocardiography identified 18, and the combined reference examination identified 24. Two of four patients without ventricular septal defect had a false positive result with colour flow mapping and none had a false positive result with continuous wave Doppler examination. During the reference examination continuous wave Doppler identified 24 patients with ventricular septal defects and colour flow mapping identified 23. In two patients a second ventricular septal defect was found by colour flow mapping, and confirmed by continuous wave Doppler. There was no significant difference in time to diagnosis between the two techniques. Colour flow mapping aids identification of multiple ventricular septal defects but is not faster and has lower specificity than continuous wave Doppler. A combination of the two techniques gave the highest sensitivity and specificity.

To determine the value of a recently developed 7.5 MHz annular array two-dimensional and color flow Doppler transducer for examination of the proximal parts of the left coronary artery, 25 patients were studied immediately after coronary artery bypass surgery, and the findings were compared with preoperative coronary angiograms. With two-dimensional imaging, the left main coronary artery was visualized in 22 patients (88%), left anterior descending in 13 patients (52%), and circumflex in 22 patients (88%). Stenoses were correctly identified in four of four left main coronary arteries, in five of seven left anterior descending arteries, and in none of four left circumflex arteries. Adding color flow to two-dimensional imaging in 20 patients, we found a disturbed flow signal, as a sign of stenosis, in five of five left anterior descending artery and two of four left circumflex artery stenoses. We concluded that these initial findings with this new 7.5 MHz annular array two-dimensional and color flow Doppler transducer, are promising in imaging and detection of stenoses in the proximal parts of the left coronary artery.

Somatic hybrid plants were regenerated following the fusion of leaf mesophyll protoplasts of P. parodii with those isolated from a nuclear-albino mutant of P. parviflora. Attempts at sexual hybridization of these two species repeatedly failed thus confirming their previously established cross-incompatibility. Selection of somatic hybrid plants was possible since protoplasts of P. parodii would not develop beyond the cell colony stage, whilst those of the somatic hybrid and albino P. parviflora produced calluses. Green somatic hybrid calluses were visible against a background of albino cells/calluses, and upon transfer to regeneration media gave rise to shoots. Shoots and the resultant flowering plants were confirmed as somatic hybrids based on their growth habit, floral pigmentation and morphology, leaf hair structure, chromosome number and Fraction 1 protein profiles. The relevance of such hybrid material for the development of new, and extensively modified cultivars, is discussed.

Somatic hybrid plants regenerated following the fusion of leaf mesophyll protoplasts of Petunia parodii with those isolated from a cell suspension of albino P. inflata. These two species exhibit a unilateral cross-incompatability with a pre-zygotic mode of reproductive isolation preventing hybridizations with P. inflata as the maternal parent. Selection of somatic hybrids relied on the fact that unfused or homokaryon protoplasts of P. parodii did not develop beyond the cell colony stage while those of the putative somatic hybrids and albino P. inflata parent produced callus. Green somatic hybrid calluses were readily identified against the white background of P. inflata following complementation to chlorophyll synthesis proficiency and continued growth in hybrid cells. Shoots, and ultimately flowering plants, were identified as somatic hybrids based on their floral morphology and colour, chromosome number and the fact that they segregated for parental characters. The frequency of somatic hybrid production was comparable to that previously established for two sexually compatible Petunia species.

The application of transesophageal echocardiography (TEE) offers access to a great deal of important clinical information regarding cardiovascular anatomy and physiology. Two applications which have not been reported and would appear to be of interest are continuous wave Doppler capabilities and the implementation of higher frequency transducers. A TEE system designed at the Institute of Biomedical Engineering in Trondheim, which is based on an annular array technology, offers these capabilities. We evaluated this instrument in the clinical setting in a series of 30 patients to test the probe function in terms of the tissue and flow imaging quality with a 7.5 MHz carrier frequency, and to report on the implementation of a continuous wave Doppler modality in a TEE probe. We found that the annular array method permitted the use of high frequency probes for tissue and flow imaging which resulted in excellent image resolution, and that shifting the carrier frequency of the transducer to a lower frequency permitted the optimization of the Doppler sensitivity. The continuous wave Doppler was used to measure abnormal blood flow velocities in excess of 5.0 m/s, and was particularly useful in the operating room as velocity measurements could be obtained without compromising the sterile field. The results of our evaluation indicate that high imaging frequencies and continuous wave Doppler can be applied by an annular array TEE transducer.