Sustainable volume sweep imaging lung teleultrasound in Peru: Public health perspectives from a new frontier in expanding access to imaging.

Background: Pulmonary disease is a common cause of morbidity and mortality, but the majority of the people in the world lack access to diagnostic imaging for its assessment. We conducted an implementation assessment of a potentially sustainable and cost-effective model for delivery of volume sweep imaging (VSI) lung teleultrasound in Peru. This model allows image acquisition by individuals without prior ultrasound experience after only a few hours of training. Methods: Lung teleultrasound was implemented at 5 sites in rural Peru after a few hours of installation and staff training. Patients were offered free lung VSI teleultrasound examination for concerns of respiratory illness or research purposes. After ultrasound examination, patients were surveyed regarding their experience. Health staff and members of the implementation team also participated in separate interviews detailing their views of the teleultrasound system which were systematically analyzed for key themes. Results: Patients and staff rated their experience with lung teleultrasound as overwhelmingly positive. The lung teleultrasound system was viewed as a potential way to improve access to imaging and the health of rural communities. Detailed interviews with the implementation team revealed obstacles to implementation important for consideration such as gaps in lung ultrasound understanding. Conclusions: Lung VSI teleultrasound was successfully deployed to 5 health centers in rural Peru. Implementation assessment revealed enthusiasm for the system among members of the community along with important areas of consideration for future teleultrasound deployment. This system offers a potential means to increase access to imaging for pulmonary illness and improve the health of the global community.

Vascular Imaging in the Asymptomatic High-risk Cancer Population: A Role for Thrombosis Screening and Therapy Management.

OBJECTIVES: We retrospectively examined the venous thromboembolism (VTE) events diagnosed in the Prophylaxis of High-Risk Ambulatory Cancer Patients Study (PHACS), a multi-center randomized trial, to assess the value of screening vascular imaging for the diagnosis of incidental VTE in high-risk cancer patients. METHODS: A total of 117 asymptomatic cancer patients with a Khorana score ≥3 starting a new systemic chemotherapy regimen were enrolled in a prospective randomized control trial. Patients underwent baseline venous ultrasound (US) of the lower extremities (LEs) and screening contrast-enhanced chest computed tomography (CT). Those without preexisting VTE were then randomized into observation or dalteparin prophylaxis groups and were screened with serial US every 4 weeks for up to 12 weeks and imaged with contrast-enhanced chest CT at 12 weeks. Any additional imaging performed during the study period was also evaluated for VTE. RESULTS: Baseline prevalence of incidental VTE was 9% (n = 10) with 58% percent of VTEs diagnosed by screening US. Incidence of VTE in the randomized phase of the trial was 16% (n = 16) with 21% (n = 10) of patients in the control arm and 12% (n = 6) of patients in the dalteparin arm developing VTE, a non-significant 9% absolute risk reduction (HR = 0.69, 95% CI 0.23-1.89). Sixty-nine percent of these patients were asymptomatic with 31% of patients diagnosed by screening US. CONCLUSIONS: Adding screening US to routine oncologic surveillance CT in high-risk ambulatory cancer patients with a Khorana score ≥3 can lead to increased VTE detection, with potential for decreased morbidity, mortality, and health care spending.

Lung Ultrasound: The Essentials.

Although US of the lungs is increasingly used clinically, diagnostic radiologists are not routinely trained in its use and interpretation. Lung US is a highly sensitive and specific modality that aids in the evaluation of the lungs for many different abnormalities, including pneumonia, pleural effusion, pulmonary edema, and pneumothorax. This review provides an overview of lung US to equip the diagnostic radiologist with knowledge needed to interpret this increasingly used modality. Supplemental material is available for this article. © RSNA, 2021.

Lung Ultrasound Volume Sweep Imaging for Pneumonia Detection in Rural Areas: Piloting Training in Rural Peru.

OBJECTIVE: Pneumonia is the leading cause of pediatric mortality worldwide among children 0-5 years old. Lung ultrasound can be used to diagnose pneumonia in rural areas as it is a portable and relatively economic imaging modality with ~95% sensitivity and specificity for pneumonia in children. Lack of trained sonographers is the current limiting factor to its deployment in rural areas. In this study, we piloted training of a volume sweep imaging (VSI) ultrasound protocol for pneumonia detection in Peru with rural health workers. VSI may be taught to individuals with limited medical/ultrasound experience as it requires minimal anatomical knowledge and technical skill. In VSI, the target organ is imaged with a series of sweeps and arcs of the ultrasound probe in relation to external body landmarks. METHODS: Rural health workers in Peru were trained on a VSI ultrasound protocol for pneumonia detection. Subjects were given a brief didactic session followed by hands-on practice with the protocol. Each attempt was timed and mistakes were recorded. Participants performed the protocol until they demonstrated two mistake-free attempts. RESULTS: It took participants a median number of three attempts (range 1-6) to perform the VSI protocol correctly. Time to mastery took 51.4 ± 17.7 min. There were no significant differences among doctors, nurses, and technicians in total training time (P = 0.43) or number of attempts to success (P = 0.72). Trainee age was not found to be significantly correlated with training time (P = 0.50) or number of attempts to success (P = 0.40). CONCLUSION: Rural health workers learned a VSI protocol for pneumonia detection with relative ease in a short amount of time. Future studies should investigate the clinical efficacy of this VSI protocol for pneumonia detection. KEY MESSAGE: A volume sweep imaging (VSI) protocol for pneumonia detection can be taught with minimal difficulty to rural health workers without prior ultrasound experience. No difference was found in training performance related to education level or age. VSI involves no significant knowledge of anatomy or technical skill.

Contrast opacification on thoracic CT angiography: challenges and solutions.

Contrast flow and enhancement patterns seen on thoracic CT angiography (CTA) can often be challenging and may often reveal more than is immediately apparent. A non-diagnostic CTA following the initial contrast injection can be secondary to many causes; these include both extrinsic factors, such as injection technique/equipment failure (iv cannula, power injector), and intrinsic, patient-related factors. Contrast pressure and flow graphs often contain useful information regarding the etiology of a non-diagnostic scan. Understanding these graphs will help the radiologist plan a repeat contrast injection to overcome the deficiencies of the first injection and thus obtain a diagnostic scan. The current review article outlines normal and abnormal intravenous contrast dynamics, discusses how to recognize etiologies of non-diagnostic scans, and ultimately addresses techniques to overcome obstacles towards obtaining normal contrast opacification of the target vessel. In addition, there are some life-threatening findings, which unless sought for, may remain hidden in plain sight. Key Points • Using contrast enhancement and flow patterns to identify the cause of a non-diagnostic CTA.• Recognize life threatening causes of altered contrast dynamics such as cardiac asystole.• Non-target vessel opacification may hold key to underlying pathophysiology.

The essentials of extracranial carotid ultrasonographic imaging.

In this article, the standard ultrasonographic scanning techniques and Doppler settings necessary to produce reliable and reproducible carotid imaging are discussed. The normal carotid anatomy is reviewed, including grayscale, color Doppler, and spectral Doppler imaging appearances, is reviewed. The vascular abnormalities caused by atherosclerosis are examined, including plaque morphology characterization as well as waveform and velocity changes caused by stenosis, are examined. In addition, special situations are explored, such as imaging in the presence of an arrhythmia or cardiac assist devices. Imaging after carotid intervention is discussed, including the complications associated with these procedures.

Phospholipase C delta 1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity.

In the present study, we examined the role of PLC delta 1 (phospholipase C delta 1) in the regulation of cellular proliferation. We demonstrate that RNAi (RNA interference)-mediated knockdown of endogenous PLC delta 1, but not PLC beta 3 or PLC epsilon, induces a proliferation defect in Rat-1 and NIH 3T3 fibroblasts. The decreased proliferation was not due to an induction of apoptosis or senescence, but was associated with an approx. 60% inhibition of [(3)H]thymidine incorporation. Analysis of the cell cycle with BrdU (bromodeoxyuridine)/propidium iodide-labelled FACS (fluorescence-activated cell sorting) demonstrated an accumulation of cells in G(0)/G(1)-phase and a corresponding decrease in cells in S-phase. Further examination of the cell cycle after synchronization by serum-starvation demonstrated normal movement through G(1)-phase but delayed entry into S-phase. Consistent with these findings, G(1) cyclin (D2 and D3) and CDK4 (cyclin-dependent kinase 4) levels and associated kinase activity were not affected. However, cyclin E-associated CDK2 activity, responsible for G(1)-to-S-phase progression, was inhibited. This decreased activity was accompanied by unchanged CDK2 protein levels and paradoxically elevated cyclin E and cyclin E-associated CDK2 levels, suggesting inhibition of the cyclin E-CDK2 complex. This inhibition was not due to altered stimulatory or inhibitory phosphorylation of CDK2. However, p27, a Cip/Kip family CKI (CDK inhibitor)-binding partner, was elevated and showed increased association with CDK2 in PLC delta 1-knockdown cells. The result of the present study demonstrate a novel and critical role for PLC delta 1 in cell-cycle progression from G(1)-to-S-phase through regulation of cyclin E-CDK2 activity and p27 levels.

Epac-mediated activation of phospholipase C(epsilon) plays a critical role in beta-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac myocytes.

Recently we demonstrated that PLC(epsilon) plays an important role in beta-adrenergic receptor (betaAR) stimulation of Ca(2+)-induced Ca(2+) release (CICR) in cardiac myocytes. Here we have reported for the first time that a pathway downstream of betaAR involving the cAMP-dependent Rap GTP exchange factor, Epac, and PLC(epsilon) regulates CICR in cardiac myocytes. To demonstrate a role for Epac in the stimulation of CICR, cardiac myocytes were treated with an Epac-selective cAMP analog, 8-4-(chlorophenylthio)-2'-O-methyladenosine-3',5'-monophosphate (cpTOME). cpTOME treatment increased the amplitude of electrically evoked Ca(2+) transients, implicating Epac for the first time in cardiac CICR. This response is abolished in PLC(epsilon)(-/-) cardiac myocytes but rescued by transduction with PLC(epsilon), indicating that Epac is upstream of PLC(epsilon). Furthermore, transduction of PLC(epsilon)(+/+) cardiac myocytes with a Rap inhibitor, RapGAP1, significantly inhibited isoproterenol-dependent CICR. Using a combination of cpTOME and PKA-selective activators and inhibitors, we have shown that betaAR-dependent increases in CICR consist of two independent components mediated by PKA and the novel Epac/(epsilon) pathway. We also show that Epac/PLC(epsilon)-dependent effects on CICR are independent of sarcoplasmic reticulum loading and Ca(2+) clearance mechanisms. These data define a novel endogenous PKA-independent betaAR-signaling pathway through cAMP-dependent Epac activation, Rap, and PLC(epsilon) that enhances intracellular Ca(2+) release in cardiac myocytes.

G-protein-coupled receptor agonists activate endogenous phospholipase Cepsilon and phospholipase Cbeta3 in a temporally distinct manner.

Phospholipase Cepsilon (PLCepsilon) is one of the newest members of the phosphatidylinositol-specific phospholipase C (PLC) family. Previous studies have suggested that G-protein-coupled receptors (GPCRs) stimulate phosphoinositide (PI) hydrolysis by activating PLCbeta isoforms through G(q) family G proteins and Gbetagamma subunits. Using RNA interference to knock down PLC isoforms, we demonstrate that the GPCR agonists endothelin (ET-1), lysophosphatidic acid (LPA), and thrombin, acting through endogenous receptors, couple to both endogenous PLCepsilon and the PLCbeta isoform, PLCbeta3, in Rat-1 fibroblasts. Examination of the temporal activation of these PLC isoforms, however, reveals agonist- and isoform-specific profiles. PLCbeta3 is activated acutely within the first minute of ET-1, LPA, or thrombin stimulation but does not contribute to sustained PI hydrolysis induced by LPA or thrombin and accounts for only part of ET-1 sustained stimulation. PLCepsilon, on the other hand, predominantly accounts for sustained PI hydrolysis. Consistent with this observation, reconstitution of PLCepsilon in knockdown cells dose-dependently increases sustained, but not acute, agonist-stimulated PI hydrolysis. Furthermore, combined knockdown of both PLCepsilon and PLCbeta3 additively inhibits PI hydrolysis, suggesting independent regulation of each isoform. Importantly, ubiquitination of inositol 1,4,5-trisphosphate receptors correlates with sustained, but not acute, activation of PLCepsilon or PLCbeta3. In conclusion, GPCR agonists ET-1, LPA, and thrombin activate endogenous PLCepsilon and PLCbeta3 in Rat-1 fibroblasts. Activation of these PLC isoforms displays agonist-specific temporal profiles; however, PLCbeta3 is predominantly involved in acute and PLCepsilon in sustained PI hydrolysis.