Transcranial U S helps solve COVID-19 mystery

By Theresa Pablos, AuntMinnie staff writer

August 21, 2020 -- Ultrasound scans with a robotic transcranial Doppler device provided a clue into why patients with COVID-19 experience severe hypoxemia without lung stiffness. In a serendipitous discovery, researchers linked the ultrasound findings to suspiciously low oxygen levels in patients with severe cases of COVID-19.

The researchers used a robotic transcranial Doppler (TCD) ultrasound system to assess cerebral blood flow in 18 patients with severe COVID-19 pneumonia. They had been looking for stroke and other cranial abnormalities, but they instead found that the majority of patients had detectable microbubbles, a finding that indicates abnormally dilated pulmonary blood vessels.

"This study helps explain the strange phenomenon seen in some COVID-19 patients known as 'happy hypoxia,' where oxygen levels are very low, but the patients do not appear to be in respiratory distress," stated senior author Dr. Hooman Poor, an assistant professor at the Icahn School of Medicine at Mount Sinai in a press release. Poor and colleagues published their research on August 6 as a letter in the American Journal of Respiratory and Critical Care Medicine.

In patients with classic acute respiratory distress syndrome (ARDS), pulmonary inflammation results in blood vessel changes that make the lungs stiff and impair oxygenation. But the amount of hypoxemia seen in patients with COVID-19 is often drastically out of proportion with lung stiffness.

The new pilot study revealed that vasodilation could help explain why COVID-19 pneumonia differs from classic ARDS. Using transcranial Doppler ultrasound scans, the researchers found that 83% of patients had detectable microbubbles. In addition, the number of microbubbles correlated with hypoxemia severity in patients with severe COVID-19.

In comparison, only about 26% of patients with classic ARDS show detectable microbubbles on transcranial Doppler scans. The number of microbubbles also did not correlate with hypoxemia severity for patients with classic ARDS.

"It is becoming more evident that the virus wreaks havoc on the pulmonary vasculature in a variety of ways," stated Poor.

The study included 18 patients with severe COVID-19 pneumonia who also had altered mental status and required mechanical ventilation. The patients underwent robotic transcranial Doppler ultrasound (Lucid Robotic System by NovaSignal) with an agitated saline solution.

The researchers injected the contrast agent in an upper extremity or through a central line in the internal jugular vein. NovaSignal's ultrasound software automatically counted the number of microbubbles detected over 20 seconds, and the researchers manually counted and confirmed the number of microbubbles as a precaution.

In healthy patients, the contrast microbubbles enter the lung blood vessels and get filtered out by pulmonary capillaries. If bubbles are detected in the brain, it indicates that the patient either has a hole in the heart or that the capillaries are abnormally dilated, which the researchers believe might be contributing to hypoxemia in patients with COVID-19.

Poor and his team at Mount Sinai are continuing their research and have thus far collected data from roughly 80 patients with various COVID-19 severity. The team plans to analyze microbubble transit, including how transit varies throughout the course of the disease.

"If these findings are confirmed in larger studies, pulmonary microbubble transit may potentially serve as a marker of disease severity or even a surrogate endpoint in therapeutic trials for COVID-19 pneumonia," Poor stated. "Future studies that investigate the use of pulmonary vascular constrictors in this patient population may be warranted."

Doppler U S helps assess cervical cancer stage

By Theresa Pablos, AuntMinnie staff writer

August 18, 2020 -- Researchers in China found a link between findings on Doppler ultrasound scans and characteristics of cervical cancer. Blood flow seen through color ultrasound was tied to tumor clinical stage, cancer type, and pathology in a study published on August 10 in PLOS One.

Imaging to assist with cancer staging is crucial, and there have been calls to include more radiological imaging in cervical cancer diagnosis and staging. The new findings suggest Adler grades -- a scoring system that reflects tumor vascularization -- may help physicians assess cervical cancers using color ultrasound.

"Adler grades are closely associated with the clinical pathology of cervical cancer, which may be a convenient and effective approach for the assisting assessment of cervical cancer," wrote the authors, led by Dr. Dehong Che from the department of obstetrics and gynecology at the Second Affiliated Hospital of Harbin Medical University in Harbin, China.

Prior research found that color Doppler ultrasound scans may accurately determine tumor size, invasiveness, and vascular patterns. But while Doppler ultrasound is used in the assessment of other cancers, it is not as common for gynecological cancer assessment, the authors noted.

To determine the effectiveness of Doppler ultrasound on cervical cancer assessment, the authors enrolled 162 patients in their study. The patients had pathologically confirmed cervical cancer cases and no prior history of malignancy, cervical surgery, or uterine malformations.

A sonographer first performed a grayscale sonography examination to evaluate the cervical area and surrounding tissue before studying blood flow with Doppler ultrasound. A radiologist and a gynecologist determined an Adler grade for the tumor based on the blood flow to the lesion.

Adler score and ultrasound findings on cervical cancer tumors
Adler score	Definition	Ultrasound findings
Grade 0	No obvious blood flow	• Normal appearance
Grade 1	1-2 blood vessels with a diameter of < 1 mm	• Slightly thickened morphology • More enhanced intra-cervical echo • Spot-like blood flow signals
Grade 2	3-4 blood vessels with a diameter of < 1 mm	• Uneven or thickened cervical echo • Strip blood flow
Grade 3	More than 4 blood vessels or vessels are intertwined into a network	• Parauterine and extrauterine invasion • Reticular blood flow

Click image to enlarge.

Doppler ultrasound images of cervical cancers with different Adler scores: (A) Grade 0, (B) Grade 1, (C) Grade 2, and (D) Grade 3. Images courtesy of Che D, Yang Z, Wei H, Wang X, Gao J (2020) The Adler grade by Doppler ultrasound is associated with clinical pathology of cervical cancer: Implication for clinical management. PLOS ONE, 15(8): e0236725. https://doi.org/10.1371/journal.pone.0236725.

Patients with a higher Adler score had higher clinical stages of cervical cancer, the authors found. Adler score was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) clinical stage, pathological tumor type, and squamous cell carcinoma subtypes.

Compared with FIGO stages, Adler grade achieved an area under the curve (AUC) of 0.811, with a sensitivity of 55% and specificity 90%. Compared with pathological stage results, Adler grade achieved an AUC of 0.76, with a sensitivity of 52% and specificity of 88%.

"Those results indicated that Adler grade could provide valuable reference for the diagnosis of cervical cancer," the authors wrote.

Cervical cancer is known for its rapid proliferation and active cell division -- two characteristics related to blood vessel proliferation. As a result, this type of cancer may translate particularly well to Doppler imaging, the authors noted.

"On color Doppler ultrasound images, there are often abundant different types of blood flow signals in tumor tissues, which correspond to its rich vascular network and are related to the special structure and blood flow characteristics of tumor blood vessels," they wrote.

The authors cautioned their study had a small sample size and that subjective factors can influence the Adler score. Nevertheless, they concluded that the use of Doppler ultrasound should be considered when working with patients with suspected or newly diagnosed cervical cancer.

"With the continuous development of ultrasound technology and population of clinical ultrasound applications, Adler grade should be promoted in the application of color Doppler ultrasound for the diagnosis and treatment of cervical cancer," the authors wrote.