Introduction
Foramen ovale is a physiological
channel of the atrial septum during the embryonic period. After birth,
the primary and secondary septum get close to each other, adhere to each
other, and gradually fuse to form a permanent atrial septum(1) . Suppose the fusion is not complete after three years of
age. In that case, the remaining fissure-like channel is called patent
foramen ovale (PFO), the most common congenital heart abnormality in
adults (2 - 4) .
PFO patients may suffer from low blood oxygen levels and cryptogenic
strokes (CS), leading to serious health issues. (5) .
Neurologists and cardiologists have become increasingly aware of the
symptoms in recent years, and many hospitals have launched different
examination programs.
For detecting PFO, three ultrasound techniques have been developed:
transesophageal echocardiography (TEE) (6, 7) , ”gold standard”
contrast-transthoracic echocardiography (c-TTE) (8, 9) , and
contrast-transcranial doppler (c-TCD) (6) . By contrast, c-TCD
offers a sensitive, easy-to-perform, non-invasive method for assessing
the presence of RLS in the patient’s heart (10, 11) . The c-TCD
method produces less discomfort for the patients during the test, and it
is a useful initial screening tool in determining whether a patient has
RLS. Microbubbles are used as contrast agents in the c-TCD test, which
are prepared by mixing the isotonic saline solution with air, which is
injected into a cubital vein for the test. In the presence of a
right-to-left shunt, the air-containing echo contrast agent will bypass
pulmonary circulation and induces microembolic signals in the basal
cerebral arteries (12) . Nowadays, saline contrast use has been
applied to enhance intracardiac navigation and is recognized as an
effective kind of contrast agent when applying c-TCD for diagnosing PFO(13 – 15) . Importantly, many problems in this detection
process still lead to missed diagnoses, which still needs further
in-depth research. For example: changing the contrast agent(16) , changing the intravenous catheters (17) ,
improving the Valsalva action (18) , and so on, but there are
few studies on the generation of microbubbles.
The behavior of microbubbles in venous blood is of great importance for
testing accuracy. The microbubbles’ size has been shown to affect their
longevity and acoustic behavior significantly (19) . After
infusion of contrast agent, microbubbles can circulate throughout the
body, and the size of the bubbles determines their lifespan and
performance after entering the blood circulation. Large bubbles cannot
pass through capillaries, while small air bubbles have a poor scattering
effect on ultrasound (20) . In addition, the size of the bubble
diameter is also related to tissue penetration because the Laplace
pressure and blood pressure effects will further affect the lifetime of
the microbubbles (21) .
Therefore, the size of microbubbles plays a significant role in
c-TCD as the contrast media for
diagnosing PFO. The recommended manual procedure for generating MBs is
mixing 9ml isotonic saline solution and 1ml air with a three-way
stopcock by exchange of saline/air mixture between the syringes and
injecting the generated MBs into the subject through the cubital vein as
a bolus (22) . Relevant studies are less available on the MBs
generated by this method, especially on the BSD and repeatability of the
BSD.
Herein, we performed a detailed measurement of the BSD
to provide reliable and useful
data for the future enhancement of c-TCD. For the first time, a
microscopic shadow imaging technique was used to observe and record the
MBs generated with the manual
methods, then MBs were subjected to detailed physical characterization.
The overarching aim of the research was to obtain the BSD data and
characterize how much variation there is in c-TCD practice.