BY KIM BELLARD

AI continues to amaze – ChatGPT is now passing Wharton Business School exams, Microsoft and Google are doubling down in their AI efforts – and I’m as big a fan as anyone, but I want to talk about a technology that has been more under the radar, so to speak: ultrasound.  

Yes, ultrasound.  Most of us have probably had an ultrasound at some point (especially if you’ve been pregnant) and Dr. Eric Topol continues his years-long quest to replace the ancient stethoscope technology with ultrasound, but if you think ultrasound is just another nifty tool in the imaging toolbox, you’ve missed a lot. 

Let’s start with the coolest use I’ve seen: ultrasound can be used for 3D printing.  Inside the body.  

This news on this dates back to last April, when researchers from Concordia University published their findings in Nature (I found out about it last week).  Instead of the more common “Additive Manufacturing” (AM) approach to 3D printing, these researchers use Direct Sound Printing (DSP).  

The paper summarizes their results: “To show unique future potentials of DSP, applications such as RDP [Remote Distance Printing] for inside body bioprinting and direct nanoparticle synthesizing and pattering by DSP for integrating localized surface plasmon resonance with microfluidics chip are experimentally demonstrated.”

As lead author Mohsen Habibi explained it: 

We found that if we use a certain type of ultrasound with a certain frequency and power, we can create very local, very focused chemically reactive regions.  Basically, the bubbles can be used as reactors to drive chemical reactions to transform liquid resin into solids or semi-solids.

The authors believe that DSP can have applications where AM cannot be used, particularly because sound can penetrate objects that light cannot (e.g., the human body).  Bioprinting inside the body is not, in itself, new, but has required open surgery, which DSP would not.  “DSP introduces the possibility of noninvasive deep inside the body printing,” they explicitly point out.  

“Also we can do the repairing of inside bio-organs. That’s a future possibility,” corresponding author Muthukumaran Packirisamy said.  Here’s their video:

I’ve been fascinated with 3D printing for a long time, especially for its healthcare-related uses (e.g.., prescription drugs, blood vessels, prosthetic devices, even organs), but tell me we’ll be able to do those noninvasively, using sound waves – well, consider me entranced.  

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All that is cool enough, but ultrasound is being used for many more healthcare applications, such as destruction of tumors.  In fact, that was one of the motivations for the Concordia efforts; Professor Packirisamy noted: “Ultrasonic frequencies are already being used in destructive procedures like laser ablation of tissues and tumours. We wanted to use them to create something.” 

“Focused ultrasound” is the term commonly used; there is actually a Focused Ultrasound Foundation. “Focused ultrasound is a noninvasive therapeutic technology,” Dr. Neal Kassell, founder and chairman of the Focused Ultrasound Foundation, told CNN. “We’ve said that focused ultrasound is the most powerful sound you will never hear, but sound that someday could save your life.”

Some of the uses include:

• Earlier this month Canadian surgeons used ultrasound to deliver chemotherapy to an inoperable brain tumor, the first time this has been accomplished.  “Focused ultrasound is an innovative and non-invasive approach to more effectively deliver chemotherapy directly to the tumour,” one of the researchers said. “Our hope is that this continued research will bring us closer to enhancing treatments to help change the course of the disease.”
• Focused ultrasound has been shown to be equally effective in pain management and quality of life measures for painful bone metastases as external radiation beam therapy, with low adverse even rates.  
• Late last year the FDA approved focused ultrasound to treat the second side of patients with essential tumors; use for the first side was approved in 2016.  New research confirmed the long term effectiveness of its use for essential tremors.
• Researchers at UT Southwestern are using high-intensity focused ultrasound to treat medication refractory tremor in essential tremor and tremor-dominant Parkinson’s Disease, which the researchers believe “enables more precise targeting of the brain, decreases treatment times, reduces side effects, and improves treatment response.”  
• Researchers at West Virginia University Rockefeller Neuroscience Institute used Low-intensity focused ultrasound (LIFU) in the treatment of Alzheimer’s patients.  “This study is also a major step forward for the exciting possibility of combining focused ultrasound with targeted delivery of medications or antibodies that normally have limited capability to cross the blood brain barrier from the blood to the brain.” 
• Similarly, researchers at Yonsei University College of Medicine (South Korea) found that focused ultrasound improved the delivery of Alzheimer’s drugs by over eight times.  “While there is no complete cure for dementia, we hope that open BBB [blood brain barrier] surgery using FUS surgery can help give hope to dementia patients,” the lead researcher said.
• LIFU is showing “promising results” for treatment of major depressive disorder, according to a paper from Delft University.  The paper describes LIFU as “an emerging neuromodulation method with disruptive potential since it allows for non-invasive stimulation across the whole brain with milimetre precision.”
• Focused ultrasound has been found safe and effective for intermediate risk prostate cancer.  
• A 2020 study suggested that focused ultrasound could be used for patients with depression or obsessive-compulsive disorder.  “We demonstrated that FUS is effective in significantly improving symptoms of patients with treatment-resistant OCD and depression,” the lead author said.

That is by no means a complete list. The Focused Ultrasound Foundation claims that focused ultrasound is currently (at this writing) being used by 65 device manufacturers, for 170 clinical indications, in 424 research sites and 895 treatment sites.  Impressive numbers, but still small in the scheme of healthcare. It warns:

Unfortunately, the evolution of a new therapeutic medical device from concept to standard of care can take decades. Complicated and inefficient, the process requires the interaction of many organizations with differing agendas and timelines. There are also numerous technology, economic, regulatory and reimbursement obstacles to overcome.

Too often, the mechanisms that healthcare has developed supposedly to protect us also work against us.  As the Foundation also warns: “Decades is too long for patients and their families to wait for medical breakthroughs.

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Clifford Marks, MD, writes in The New Yorker about ultrasound replacing the stethoscope, citing miniaturization, lower costs, and application of AI as factors, but I think he’s not being ambitious enough.  As Diku Mandavia, MD, told him, “But ultrasound—it’s low-cost, no radiation, has so much value for patient care . . . it’s going to be ubiquitous.”  

Let’s hope so.  

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor.