Novel Ultrasonic Methods for the Assessment of Pulmonary Edema

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We propose to develop novel ultrasound-based methods for the detection and quantification of pulmonary edema due to congestive heart failure (HF), affecting 6.2 million Americans. Conventional ultrasound is unsuitable for imaging the lung, due to the large amount of ultrasound multiple scattering from the millions of air-liquid interfaces between alveolar walls and air filled alveoli. We propose to take advantage of this feature. Indeed, each scattering event can be seen as an opportunity for the ultrasound wave to embed information on the micro- architecture of the lung parenchyma. We have developed novel methods to calculate the scattering mean free path (SMFP) of ultrasound waves in lung tissue. We showed that the scattering of ultrasound by the alveoli can be exploited to characterize lung parenchyma. In the proposed effort, we hypothesize that measured SMFP will quantify edema in lung tissue. Three methods are currently used to image lungs to diagnose and follow lung disease: chest X-rays (CXR), CT scan, and nuclear magnetic resonance (NMR) scan. None of these imaging modalities are typically used to provide information about improving or worsening pulmonary congestion due to HF. Serial quantitative ultrasound lung assessments (not imaging) would be particularly helpful for evaluation of progression or resolution of pulmonary edema due to HF. We hypothesize that ultrasound scattering can be exploited to quantify pulmonary edema. This novel hypothesis will be explored by accomplishing these specific aims: Aim 1. To develop ultrasonic methods for the assessment and staging of edema in a rat model of pulmonary edema by using a lung hilar clamp model creating ischemia-reperfusion injury that reliably results in pulmonary edema. Ultrasound methods exploiting the presence of multiple scattering will be implemented in in- vivo edematous and normal lungs. Wet:dry weight ratio (W/D), CT scans, and inflation-fixed lung histology will be used to quantify pulmonary edema. Changes in multiple scattering of ultrasound waves in lung due to edema are not related to the type of edema and protein content. Aim 2. To develop methods for the assessment of pulmonary edema in human lungs at lower frequency. Because cardiologists commonly use low frequency ultrasound probes, the methods developed in Aim 1 would be better suited for use in human lungs if implemented in the 3 to 5 MHz range. Aim 3. To validate the proposed methods for quantification of pulmonary edema in human patients. Ten HF patients will be studied after admission for a HF exacerbation. SMFP will be measured at 3 intercostal spaces on each side serially over 3-5 days and compared to other clinical parameters of pulmonary edema and to SMFP of normal lung obtained from 5 healthy volunteers. In the proposed study, we use ultrasound to generate a number reflecting the amount of fluid (the SMFP), not an image. This translational project is responsive to this RFA because it pairs a bioengineer with two clinician-scientists to develop innovative, new, inexpensive methods to quantify pulmonary edema associated with HF. Future large multicenter studies could be performed to assess utility of an inexpensive novel technology to monitor patients with HF.