Lung diseases, like asthma, cystic fibrosis (CF) and COPD, affect millions of people worldwide. However, current diagnostics don’t necessarily provide enough data to support the best possible care. Spirometry tests how much air a patient can forcefully exhale. They provide good global information but don’t show which lung regions are most affected. CT scans can measure lung damage but are a trailing indicator and expose patients to significant radiation.
Melbourne, Australia-based 4Dx may have a new approach. The company has developed 4DxV, which converts x-ray images into more detailed airflow studies. The founder believes the additional information will improve diagnosis and disease control.
“As a mechanical engineer, the most obvious aspect of function is movement, especially in the heart and the lungs,” said 4Dx founder and CEO Andreas Fouras in a phone interview. “Our technology tries to create the highest resolution image of tissue movement. Once you have a detailed map of tissue motion in the lungs, from there, it’s a pretty simple step of calculating airflow.”
The idea germinated around 15 years ago while Fouras was a research assistant in a wind tunnel lab at Monash University. He was working on new algorithms to improve wind tunnel imaging when colleagues suggested his ideas could be applied to medical diagnostics.
The company’s algorithms leverage existing fluoroscopy technology, which captures structures in motion and is commonly used to image the cardiovascular system or direct invasive procedures. Retasking the existing technology could make it easier for hospitals to adopt the approach without a major capital investment.
“The kind of equipment we need in the hospital is only used about 60 percent of the time, which reduces the barrier to entry,” said Fouras. “Flouro allows us to get the (radiation) dose well below a CT scan.”
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
From a diagnostic standpoint, this approach could provide much richer information about disease progression. Spirometry measures forced expired volume (how much air a patient can blow out) in one second (FEV1), but this doesn’t necessarily provide the detailed studies pulmonologists need to identify severe regional disease.
“You have a developing problem in your lungs, 20 percent loss of ventilation in a region that covers 20 percent of your lungs,” said Fouras. “Well, 20 percent of 20 percent is only 4 percent. So, the best-case scenario on an FEV1 is a 4 percent reduction. An FEV1 isn’t considered clinical until you get to a 20 percent loss of ventilation.”
As a result, spirometry generally identifies problems after damage has become quite severe, but the 4Dx technology could potentially provide more precise regional data.
“In preclinical studies we’ve shown that we can detect the onset of conditions six or 12 times earlier than the old techniques,” said Fouras.
The 4DxV has generated interest from a variety of hospitals, including Cleveland Clinic and Children’s Hospital Los Angeles. Clinicians could use these studies to quantify a treatments efficacy or direct therapy. For example, for children with CF, treatment could be focused on the mucus plug rather than generalized throughout the lung.
“I think this is the future of trying to maximize getting functional information from your imaging studies,” said Marvin Nelson, who chairs the Department of Radiology at Children’s Hospital Los Angeles, in a phone interview. “It’s not just a structural study, you’re actually being able to use the technology to generate quantitative functional value.”
The company is closing out a Series B round and has been in talks with the FDA to pave the way for a 510(k) submission. They are also working on products to measure blood flow for the heart, as well as the lungs. Ultimately, these functional studies could provide a big boost in patient care.
“Being able to take a breath in while the x-ray is on,” said Nelson, “and being able to do all the calculations to generate that functional ventilation data off of that study, it’s going to be a tremendous advancement in doing high-throughput screening in populations for all these lung diseases.
