Noninvasive brain biopsy shows improved sensitivity in tumor detection


Date:
November 12, 2021
Source:
Washington University in St. Louis
Summary:
A team of researchers has developed a noninvasive diagnostic method
that may one day replace the biopsy with a simple blood test.



FULL STORY ========================================================================== Glioblastomas are aggressive brain tumors that are commonly diagnosed
through a risky and invasive surgical biopsy. A team of researchers
led by Hong Chen at Washington University in St. Louis has developed a noninvasive diagnostic method that may one day replace the tissue biopsy
with a simple blood test.


========================================================================== Chen, associate professor of biomedical engineering in the McKelvey School
of Engineering and of radiation oncology in the School of Medicine;
Eric Leuthardt, MD, professor of neurosurgery at Washington University
School of Medicine and of biomedical engineering in McKelvey Engineering;
and the team tested the method in both small and large animal models
and found significantly improved detection and diagnostic sensitivity
for brain tumors via a simple blood sample. Results of the study are
published online in Theranostics Nov.

10, 2021.

The method, known as sonobiopsy, uses focused ultrasound to target tumors
deep in the brain. Once located, the researchers inject microbubbles
into the blood that travel to the ultrasound-targeted tissue and pulsate,
which safely opens the blood-brain barrier. The temporary openings allow biomarkers, such as DNA, RNA and proteins, from the tumor to pass through
the blood-brain barrier and release into the blood.

Chen, Leuthardt and the team have been working on their focused
ultrasound- enabled liquid biopsy (sonobiopsy) method for several years,
first conducting a feasibility study in mice, followed by a safety
evaluation study, and most recently, another study in pigs. While
blood-based liquid biopsy has been used in human patients with other
cancers for personalized medicine, progress in extending the method to
human brain cancer has been limited.

In the new research, the team, including Christopher Pacia, first author
and a biomedical engineering doctoral student in the Chen Ultrasound
lab, found that the sonobiopsy method boosted detection of genes highly expressed in the mouse model of glioblastoma, EGFRvIII. The DNA levels
of EGFRvIII circulating in the bloodstream of the group that underwent sonobiopsy was 920 times greater than the group that underwent convention blood-based liquid biopsy. Further, detection of another circulating tumor genetic marker, TERT C228T ctDNA was 10- fold higher after sonobiopsy. In addition, the method improved diagnostic sensitive from 7.14% to 64.71%
for EGFRvIII and from 14.29% to 45.83% for TERT C228T. The team found
no increase in tissue damage in the tumor region of interest after
the sonobiopsy.

In the pig model, sonobiopsy boosted detection of EGFRvIII ctDNA by
270-fold and increased levels of TERT ctDNA nine-fold. It improved
diagnostic sensitivity from 28.57% to 100% for EGFRvIII and from 42.86%
to 71.43% for TERT C228T. No significant tissue damage was found.

"Our study showed that sonobiopsy enriched tumor-specific ctDNA in
the plasma and improved the detection sensitivity for two glioblastoma phenotypes without posing significant safety risks," Chen said. "The integration of sonobiopsy with advanced blood analysis assays has the
promise to provide minimally invasive, spatiotemporal-controlled, and
sensitive diagnosis of brain cancer." This work is a collaborative
effort involving members from both engineering and medical schools,
including Eric Leuthardt, MD, chief of the Division of Neurotechnology
and of the Center for Innovation in Neuroscience and Technology and
professor of neurosurgery and of neuroscience at the School of Medicine,
as well as of biomedical engineering and of mechanical engineering and
of applied science in the McKelvey School of Engineering.

"Besides neuroimaging and surgically-acquired tissue for pathology
and molecular profiling, sonobiopsy has the potential to become the
third pillar for brain tumor management by substantially advancing
brain cancer diagnosis, treatment monitoring, and recurrence
detection," Leuthardt said. "This enhanced capability could
have an important impact throughout the continuum of patient care." ========================================================================== Story Source: Materials provided
by Washington_University_in_St._Louis. Original written by Beth
Miller. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Christopher P. Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri,
Rupen
Desai, H. Michael Gach, Xiaowei Wang, Michael R. Talcott, Aadel A.

Chaudhuri, Gavin P. Dunn, Eric C. Leuthardt, Hong Chen. Sonobiopsy
for minimally invasive, spatiotemporally-controlled, and
sensitive detection of glioblastoma-derived circulating tumor
DNA. Theranostics, 2022; 12 (1): 362 DOI: 10.7150/thno.65597 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211112100547.htm

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