# Ultrasound-Induced Pulmonary Hemorrhage During Diagnostic Examination of the Lung

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $624,947

## Abstract

Ongoing pulmonary capillary hemorrhage (PCH) induced by pulmonary diagnostic ultrasound (PDUS) in
mammals is displayed as growing comet-tail artifacts in the image. This phenomenon represents the only
clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound in medicine. When
discovered in 1990 using laboratory exposure systems, only harmless incidental diagnostic ultrasound
exposure was expected, and no useful safety strategies arose from authoritative reviews in 2000 and 2008.
However, direct PDUS now is becoming routine in formal and bedside clinical settings. Point-of-care
ultrasonography often involves pulmonary examination by physicians not necessarily aware of PCH or the
deficiency in safety. As bedside PDUS becomes routine worldwide, many patients will receive direct lung
exposure and suffer a risk of PCH injury. Our objective is to fully understand PDUS-PCH and find solutions for
this uniquely important safety issue. Novel and unexpected findings thus far have thoroughly revised our
understanding of pulmonary injury by PDUS. PCH thresholds are virtually independent of ultrasound
frequency and well below the Mechanical Index safety limit. Physiological factors, such as clinical sedatives,
can be as important as physical exposure parameters. These worrisome findings overturn present PDUS
safety assumptions and imply that sick people or patients taking certain medications may be most vulnerable
to injury. Initial consideration of my hypothesis of acoustical radiation surface pressure for the physical
mechanism of PCH only partly explained this bioeffect. Our central hypothesis is that PDUS-PCH arises from
the interaction of ultrasound pulses with susceptible alveolar blood-air-barrier structures, generating capillary
stress and failure. Our research has set the stage for rapid progress and three specific aims are planned using
rigorous scientific method to ensure validity and reproducibility: First, the physiological susceptibility to PDUS-
PCH will be determined for inhalation restriction, widely used medications, inflammation by pneumonia and
sex. Second, the remaining physics of PDUS-PCH will be characterized, including the relative efficacy of
imaging modes, the sites of initiation and progression of PCH in microscopical observations and the temporal
evolution of PCH from nanoseconds to minutes. Finally, the propagation and interaction of ultrasound pulses
within lung will be characterized by acoustical modeling at the scale of the acinus, by micro-scale finite element
analysis of alveolar capillary architecture and blood-air-barrier stresses, and by research in swine, together
with chest-wall dosimetry, for realistic translation of risk estimation to human patients. The outcomes expected
from achieving these aims are an understanding of lung susceptibility in different patients, the elucidation of the
physical mechanism causing PDUS-PCH, and a path to clinical safety assurance, with minimal loss of image
q...

## Key facts

- **NIH application ID:** 9838262
- **Project number:** 5R01HL116434-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** DOUGLAS LAWRENCE MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $624,947
- **Award type:** 5
- **Project period:** 2013-08-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838262

## Citation

> US National Institutes of Health, RePORTER application 9838262, Ultrasound-Induced Pulmonary Hemorrhage During Diagnostic Examination of the Lung (5R01HL116434-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9838262. Licensed CC0.

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