Enhanced Pancreatic Cytopathology
The Adenocyte™ Solution
Low Intensity Non-Focused Ultrasound (“LINFU®”)
Adenocyte scientists and engineers have addressed
the common problem of cytologic samples that are “insufficient for analysis” through its development of
Low Intensity Non-Focused Ultrasound or LINFU®.
LINFU® utilizes a natural side effect of standard ultrasound microbubble contrast agents to increase by over 100X the number of ductal cells and intact ductal
cell clusters that are naturally found in the pancreatic fluid sample.
Adenocyte's
discovery —
The intended vibration
of the
capillary bed automatically loosens the intercellular bonds between the ductal cells
In the last twenty years FDA approved, microbubble based, ultrasound contrast agents have been administered millions of times and have an excellent safety profile. Microbubbles are inert gas filled bubbles that are injected intravenously, fill the circulatory system within seconds, and naturally disappear within five minutes. Microbubbles work by resonating in an ultrasound beam and vibrate particularly strongly at the frequencies (2-3 MHz) used for diagnostic ultrasound imaging. The vibration of the microbubbles is detected by the sonographer on the ultrasound system display and this can provide vital diagnostic information.
Microbubbles are approximately the size of a red blood cell and are therefore limited to blood vessels including capillaries. While the epithelium itself is avascular, in order to satisfy its high metabolic requirements glandular epithelium is typically located directly over a rich capillary bed.
Glandular epithelium, such as the lining of the pancreatic ducts, generally consists of a single layer of columnar cells. As part of normal epithelial regeneration, this entire cellular layer is naturally exfoliated and replaced over a period of days (duodenum) to weeks (pancreas). In the pancreas these cells are exfoliated over a period of 3-4 weeks into the pancreatic ductal fluid (or pancreatic “juice”) which exits the pancreas for the duodenum through the ampulla.
LINFU® makes use of Adenocyte’s discovery of an unintended side effect of contrast microbubbles in that the intended vibration of the capillary bed also loosens the intercellular bonds between the ductal cells in the directly adjacent epithelium. This results in increasing the rate of exfoliation into the pancreatic juice of both individual ductal cells and of large, intact and unabraded, ductal cell clusters.
The result:
A pancreatic fluid sample
with unprecedented
cellularity
Over five years of preclinical and clinical development and testing has resulted in a patented, FDA cleared, LINFU ultrasound waveform, that is optimized for inducing cellular exfoliation during a brief, 15-minute, extracorporeal application. Waveform optimization included increasing the standard ultrasound imaging pulse width by two orders of magnitude, from 2 to 200 microseconds, resulting in pancreatic cytology specimens that typically contain well over the number of ductal cells required for laboratory reporting.
In addition to providing a pancreatic fluid sample with abundant individual ductal cells, LINFU® also produces numerous intact, unabraided ductal cell clusters each containing hundreds of cells. These intact, uncut, cell clusters provide an enface view that clearly displays the normal “honeycomb” pattern associated with benign pancreatic ductal epithelium, allowing appreciation of the effacement of that pattern associated with dysplasia.
“The demonstrated ability of LINFU to safely obtain a robust cytological sample of pancreatic ductal cells without entering the ampulla is unprecedented.
This has the potential to fundamentally change the daily practice of both interventional and community practice GI as there is no screening test availabe to diagnose high grade ductal dysplasia and pancreatic cancer at a very early, potentially curable stage.”
Dr Gregory Haber
Professor of Medicine
Chief of Endoscopy
Director of the Center for Advanced Therapeutics and Innovation
NYU Langone Health