Abstract
Ultrasound imaging is a well-established clinical imaging technique providing real-time, quantitative anatomical and physiological information in humans. The lack of ionising radiation and relative low purchase and maintenance costs results in it being one of the most frequently used clinical imaging techniques with increasing use for guiding interventional clinical procedures. Until 20 years ago, translation of clinical ultrasound practices to preclinical applications proved a significant technological challenge due to the smaller size (25g vs 70kg) and rapid conscious heart-rate (500-700bpm vs 60bpm) of the mouse requiring an increase in both spatial and temporal resolution of 10-20 fold in order to achieve diagnostic information comparable to that achieved clinically. Since 2000 (Foster et al 2000), these technological challenges have been overcome and commercial high frequency ultrasound scanners have enabled longitudinal studies of disease progression in small animal models to be undertaken. Adult, neonatal and embryonic rats, mice and zebrafish can now be scanned with resolutions down to 30 microns and with sufficient temporal resolution to enable cardiac abnormalities in all these species to be identified. In mice and rats, quantification of blood flow in cardiac chambers, renal, liver and uterine vessels and intra-mural tissue movements can be measured using the Doppler technique. Ultrasonic contrast microbubbles used routinely for clinical applications are now being further developed to include targeting mechanisms and drug-loading capabilities and the results in animal models bode well for translation for targeted drug delivery in humans.
Highlights
Ultrasound has been used extensively since its development to study preclinical animal models much of the early work in this field was undertaken using transducers designed for ultrasound scanning of clinical small-parts or intra-operative imaging and operating in the frequency range between 10 and 20 MHz
Since there has been a meteoric rise in the number of biology research publications using preclinical ultrasound imaging to assess adult, neonatal and embyronic rats, mice, and zebrafish with spatial resolutions approaching 30 micron and with frame-rates of up to 350 Hz achievable when imaging adult murine hearts enabling cardiac abnormalities to be identified
Obtaining an ECG signal from adult zebrafish is challenging so the timing of systole and diastole is determined from cardiac chamber size and spectral Doppler traces with adult heart rates ranging from 120 to 180 beats/min
Summary
Ultrasound has been used extensively since its development to study preclinical animal models much of the early work in this field was undertaken using transducers designed for ultrasound scanning of clinical small-parts or intra-operative imaging and operating in the frequency range between 10 and 20 MHz. Sequential Mmodes are acquired across the heart and temporally interleaved into a high temporal resolution 2D B-mode image data set of a cardiac cycle Using this technique enables easier tracking of myocardial borders. Obtaining an ECG signal from adult zebrafish is challenging so the timing of systole and diastole is determined from cardiac chamber size and spectral Doppler traces with adult heart rates ranging from 120 to 180 beats/min. Injections into fetal brains on externalized embryos, into adult kidneys and pancreas for orthotopic tumor cell injections and into the myocardium can all be undertaken Due to their size and location, identification of lymph nodes using high frequency ultrasound can be difficult within the mouse model with many lying deep within the body, encapsulated in fat pads and some, such as the mesenteric lymph node, surrounded by the intestines. These early studies show in exquisite detail the future potential of using ultrasound for neuroscience applications
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