Transthoracic parametric Doppler for bedside diagnosis of pulmonary embolism: A pilot study.

Transthoracic parametric Doppler (TPD), unlike conventional ultrasonography, measures signals originating from movements of pulmonary blood vessel walls. In this pilot study, we tested TPD in 15 patients diagnosed with pulmonary embolism on computed tomography pulmonary angiography. Results were mapped to the upper, middle, and lower thirds of the right lung. In the lower third, TPD yielded 100% specificity and positive predictive value for acute pulmonary embolism. If validated in a larger series, this rapid bedside technique might obviate the need for computed tomography in specific cases. This could be advantageous in patients who are unstable, in intensive care, or have allergies to iodinated contrast material.

Pulmonary lung Doppler signals: normative data in a pediatric population compared with adults.

Lung Doppler signals (LDS) acquired via transthoracic echocardiography is a novel technology previously reported in adults for use in detecting pulmonary hypertension. The aim of this study was to characterize LDS in healthy children to establish normative pediatric LDS data, and compare the pediatric data to the previously published healthy adult LDS. In this prospective, two-center study, LDS were acquired in children without cardiopulmonary disease using a 2 MHz transthoracic pulsed Doppler transducer. The data were processed to obtain Doppler velocity patterns corresponding to phases of the cardiac cycle. Signals were analyzed using a parametric Doppler signal-processing package and performance evaluation of the trained classifiers was performed using cross validation method. Pediatric signals were then compared to a retrospective cohort of healthy adults. Eighty-six healthy pediatric subjects (mean age 9.1 ± 5.1 years) and 79 healthy adult controls (mean age 59.7 ± 10.7 years) were included. The normative LDS velocity profiles were defined for pediatric subjects and then compared to adults; the highest discriminating LDS parameters between healthy children and adults were acceleration of atrial (A) signal contraction (46 ± 18 vs. 90 ± 34; p < 0.001), peak systolic (S) signal velocity (10.0 ± 3.5 vs. 11.7 ± 3.5; p < 0.001), and ratio of peak diastolic (D)-to-atrial (A) signal velocity (1.4 ± 0.5 vs. 0.4 ± 0.3; p < 0.001). The sensitivity and specificity of this LDS based method to discern between healthy children and adult subjects was 98.6% and 97.4%, respectively. Subgroup analyses between younger (2-8 years) and older (9-18 years) pediatric LDS yielded significant differences between atrial (A) acceleration (43.7 ± 33.9 vs. 47.7 ± 42.1; p = 0.04) and diastolic (D)-to-atrial (A) signal velocity (1.2 ± 0.5 vs. 1.5 ± 0.5; p = 0.01) but not systolic (S) signals (0.14 ± 0.05 vs. 0.14 ± 0.05; p = 0.97). In this study, we defined the normal LDS profile for healthy children and have demonstrated differences in LDS between children and adults. Specifically, healthy children had lower atrial contraction power, differences in ventricular compliance and increased chronotropic response. Further studies are warranted to investigate the application of this technology, for example as a tool to aid in the detection of pulmonary hypertension in children.

Non-invasive diagnosis of pulmonary hypertension from lung Doppler signal: a proof of concept study.

Transthoracic Parametric Doppler (TPD) is a novel ultrasound technique recently developed for the investigation of pulmonary blood vessels. Lung Doppler Signals (LDS) recorded from TPD provide information regarding the functional mechanical characteristics of pulmonary blood vessels. We aimed to define the specific profile of LDS generated from TPD imaging in patients with pulmonary hypertension (PH), and to evaluate the diagnostic performance of LDS to detect PH using right heart catheterization (RHC) as gold standard reference. Seventy nine PH patients and 79 healthy controls matched for age, gender and BMI were recruited in a prospective case-control multicenter study. LDS recordings were performed by TPD consisting of a pulsed Doppler with a 2 MHz single element transducer. LDS were recorded within 24 h of RHC. Following LDS extraction, classification and performance evaluation were performed offline using a support vector machine (k-fold cross validation method). The best LDS parameters for PH detection were (1) peak velocity of the systolic (S) and diastolic (D) signals, (2) the rise slope of the S and D signals, and (3) time to peak of the S signal. Overall, the sensitivity and specificity of TPD for detection of PH were 82.7 % (95 % CI 81.3-84.1) and 87.4 % (95 % CI 86.3-88.5), respectively, with an area under the receiver operating curve of 0.95 (95 % CI 0.94-0.96). Detection rate of PH increased progressively with the level of mean pulmonary artery pressure. LDS recorded by TPD display a specific profile in PH and appears to be a promising and reliable tool for PH diagnosis. Further studies are required to confirm the clinical usefulness of LDS.

Footprints of cardiac mechanical activity as expressed in lung Doppler signals.

AIMS: To determine the diagnostic information contained in cardiac pulsatile pressure waves as expressed in the Doppler signals recorded over the right lung. METHODS AND RESULTS: The pulsatile characteristics of the pulmonary vascular system were studied by means of the novel pulse Doppler technology in 38 control volunteers, 31 patients with atrial fibrillation (AF) and 7 patients with atrial flutter. The Doppler velocity waveforms recorded were interpreted in relation to the cardiac cycle mechanical events that generate them: Ventricular systole (S), diastole (D) and presystolic left atrial contraction (A). It was demonstrated that in all cases of AF, wave-A was absent. With longer diastole a high frequency velocity waves were visible. It is assumed that they represent the atrial mechanical fibrillation. In the patients with atrial flutter, the single A-wave was replaced by a waveform termed F, the frequency of which exactly matched that of the flutter wave on the ECG. The F-wave had both a positive and negative component. CONCLUSION: The lung Doppler signals contain distinct signatures typical of arrhythmias such as AF and atrial flutter that can be used for both diagnosis and to gain insight into the nature of the phenomena.

Pulmonary Doppler signals: a potentially new diagnostic tool.

AIMS: To overcome the limitations due to ultrasound attenuation by the air in the lungs, in order to study the pulmonary system using an advanced signal processing technology. METHODS AND RESULTS: Pulsed spectral Doppler signals were obtained over the chest wall using a signal processing and algorithm package (transthoracic parametric Doppler, TPD, EchoSense Ltd, Haifa, Israel) in conjunction with a non-imaging Doppler device (Viasys Healthcare, Madison, WI, USA) coupled with an electrocardiogram. The signals picked up by a transducer positioned at various locations over the chest wall, were treated for noise, analysed parametrically and displayed in terms of both velocity and power originating from moving ultrasound reflectors. Clear reproducible lung Doppler signals (LDS) were recorded. Up to five bidirectional triangular waves with peak velocities of 20-40 cm/s, that survived the 40 dB/cm attenuation of the lung, were recorded during each cardiac cycle. The first signal coincides with early ventricular systole, the second with late systole, the third and fourth with diastole, and the last with atrial contraction. CONCLUSION: LDS originate from different elements and phases of cardiac activity that generate mechanical waves which propagate throughout the lung and are thus expressed in pulsatile changes in ultrasound reflections. While such signals could originate either from pulsatile blood flow or reflections from movement of the blood vessel--alveolar air interface, the experimental evidence points towards the tissue--air interface movements due to vessel expansion as the origin. The LDS can potentially be an important tool for diagnosing and characterizing cardio-pulmonary physiological states and diseases.

Disruption of cancer cell replication by alternating electric fields.

Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.