If you build it, who will use it?

Nanox.Arc device, as it stands today, is fake.  But what if Nanox used its $200+ million cash to actually design and build its proposed device?  Will it be useful?

Nanox claims that its proposed device uses a modality ("imaging technique") - tomosynthesis - that is supposedly "widely used for early detection" of something.

Subject to receiving regulatory clearance, the first version of the Nanox.ARC that we expect to introduce to the market will be a 3D tomosynthesis imaging system. Tomosynthesis is an imaging technique widely used for early detection, that is designed to produce a high-resolution, 3D X-ray image reconstruction of the scanned human body part for review by a professional diagnostics expert (annual report, page 56)

Tomosynthesis (previously called x-ray tomography, focal plane tomography, etc) has been available since 1930s - it should not to be confused with CT or computed tomography, which can visualize axial slices and individual voxels.  

tomosynthesis vs. plain, per Nanox demo at RSNA 2020 

Even though various medical device manufacturers have pushed it over the years, its use has never been wide.  It never added much to simple x-rays taken from different views... 

In 1993, the American College of Radiology (ACR) started work on developing guidelines for radiology to eliminate inappropriate utilization of radiologic services.  Today,

ACR Appropriateness Criteria are evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for a specific clinical condition. Employing these guidelines helps providers enhance quality of care and contribute to the most efficacious use of radiology.

Of the nearly 1,000 radiological procedures covered by the criteria, only three are based on tomosynthesis, and all three involve breast tomosynthesis, which is usually appropriate for breast cancer screening and diagnosis:

• "Digital breast tomosynthesis diagnostic"
• "Digital breast tomosynthesis screening" 
• "Digital breast tomosynthesis short-interval follow-up"

Elsewhere, tomosynthesis is mentioned maybe a couple of times in the narrative discussion or literature search as part of the regular x-ray modality analysis (for example, here and here), but clearly it is not significant enough to deserve any attention as a specific imaging procedure indicated in specific diagnostic scenario.

The real problem is that the proposed Nanox.Arc cannot perform digital breast tomosynthesis, contrary to Nanox claims in March 2020 about no-squish mammography.  In its own mammography white paper, Nanox admits that breast tomosynthesis requires compression (squishing) and a completely different mechanical design, which makes scanning of other organs, such as lungs, impossible.

So here we have it.  According to the American College of Radiology evidence-based guidelines, the use of Nanox.Arc, as proposed, will not be "usually appropriate" under any clinical scenario.

An early easter egg

Nanox removed the link to its Mammography white paper from its webpage sometime in January 2021 (the paper was first published in late November 2020 in the company's RSNA 2020 virtual booth, and then a link to it was posted on the front webpage in December 2020).  There must be something very important there for Nanox to remove it. 

Maybe it is this:

The first application for [Nanox novel x-ray source] technology is breast tomosynthesis using Nanox’s small X-ray sources in an arrayed series.

Proposed stationary array head (design concept)

Doesn't look much like the multi-source Nanox.Arc, which is supposed to be the first commercial device using the proposed Nanox source, does it?

The paper itself is self-contradictory.  It claims on page 14 that the scan time of one 3D image in present breast tomosynthesis is 15 seconds - moving tube between shots.  But on page 17, the paper admits that the gantry of the 10-year old Hologic machine takes only a total of 4 seconds for the scan (this old intro confirms it).

Why is this important?  Fujifilm, the first potential licensee for Nanox source (see page 88 and II-3 in this registration statement), declined to license the technology when its rights expired in June 2020, but Nanox insists that Fujifilm is still its strategic shareholder and a Mammography OEM (presentation slides 3 and 35 from JP Morgan conference in January 2021).  Nanox also told the press in March 2020 that its Nanox.Arc can perform no-squish mammography, which, of course, it can't (not even in theory):

It could perform tests such as ... a no-squish mammogram for women.

More later.

Update March 31, 2021:  Nanox promoters insist that Fujifilm invested in Nanox.  According to Nanox draft registration statement filings with the SEC, that is not really correct.  For example, the December 2019 filing states that in May 2019, Nanox Gibraltar (that is not Nanox, but its predecessor) issued 1,583,710 ordinary shares to FUJIFILM Corporation for an aggregate purchase price of approximately $3.5 million, and in exchange FUJIFILM was granted a right to first negotiation for license - a right that FUJIFILM declined to exercise and it expired.  A draft filed in August 2020 mentions the same number of shares, but the prospectuses filed in August 2020 and February 2021 do not mention any Fuji shares.  It is rather strange that the number of shares remained the same between December 2019 and August 2020, as a January 2020 press release by Nanox implied that Fujifilm participated in another funding round.

Foxconn is joining Fujifilm, SK Telecom, and other private investors, who have previously invested in the project, as part of a round that is aimed to support Nanox’s development, commercialization, and deployment of its Nanox System.

The press release, issued just before the supposed submission for FDA clearance, is also remarkable because it proves that the Nanox device (presumably, the multi-source one) cannot be cleared. 

The Nanox System is composed of the Nanox.Arc, a novel digital X-ray device...

Novel devices, by the dictionary definition, are obviously not substantially equivalent to any device on the market. 

Update April 12, 2021:  Nanox promoters continue to insist that Fujifilm invested in Nanox, citing a crunchbase entry about the Series B round.   However, it appears crunchbase simply misread the tricky Nanox press release.  

Foxconn is joining Fujifilm, SK Telecom, and other private investors, who have previously invested in the project, as part of a round that is aimed to support Nanox’s development, commercialization, and deployment of its Nanox System.

See, the press release never states that Fujifilm invested or is about to invest in Nanox.  It says that Fujifilm invested in "the project" (that is, Nanox Gibraltar, a Nanox predecessor).  And it does not say that Fujifilm is participating in this round.  In any case, all subsequent SEC filings confirm that Fujifilm did not invest in Nanox - either in that round or thereafter.  As confirmed by the recent annual report, Fujifilm is neither a strategic investor in Nanox nor a Mammography OEM for Nanox, contrary to all investor presentations. 

see, for example, page 3 and 35 in January 2021 presentation at JPM conf.

Full-body scan vision

According to Nanox CEO, 

"Nanox.Arc could provide a full-body digital X-ray scan ... Most, if not all, cancers can be treated rather easily if found early enough through medical imaging. The World Health Organization says if every person had a full-body scan once a year, potentially millions could be saved by early detection." (Israel21c, March 23, 2020)

The problem is that the World Health Organization never said that.  In fact, it said exactly the opposite:

Whole body CT for IHA [individual health assessment] of asymptomatic individuals should cease.

Nanox vision is based on a lie.  

Nanox has backtracked since - now it is early detection of SYMPTOMATIC PATIENTS only!

Here is what the American Academy of Family Physicians says:

"Whole-body scanning is not recommended by medical professional societies for individuals without symptoms, nor is it a routinely practiced screening procedure in healthy populations."

Choosing Wisely, an initiative of the American Board of Internal Medicine, in cooperation with Consumer Reports and American and American College of Preventive Medicine has this to say about whole-body scans:

 "They don’t help find cancer—and may do more harm than good... No medical societies recommend whole-body scans. That’s because there is no evidence that the scans are a good screening tool.  Whole-body scans can lead to unnecessary follow-up tests."

Further reading:

Radiation Risk From CT: Implications for Cancer Screening, Jeffrey M. Albert

The available data suggest a small but real risk of radiation-induced malignancy from CT that could become significant at the population level with widespread use of CT-based screening. However, a growing body of literature suggests that the benefits of CT screening for lung cancer in high-risk patients and CT colonography for colorectal cancer may significantly outweigh the radiation risk. Future studies evaluating the benefits of CT screening should continue to consider potential radiation risks.

See also CT Radiation Dose and Risk: Fact vs Fiction 

 technologists also must consider the risks of reducing dose to the point that image quality falters or diagnoses are delayed or missed.

Average doses.

Pro mammo screening.

On mammograms and AI, rather than full-body, but article wrong about tomo for screening (note: Nanox.Arc can't do mammograms, compare to no squish, January 29, 2021):

More-aggressive screening strategies aim to maximize the benefits of early detection, whereas less-frequent screenings aim to reduce false positives, anxiety, and costs for those who will never even develop breast cancer.

“We know MRI can catch cancers earlier than mammography, and that earlier detection improves patient outcomes,” says Yala. “But for patients at low risk of cancer, the risk of false-positives can outweigh the benefits. With improved risk models, we can design more nuanced risk-screening guidelines that offer more sensitive screening, like MRI, to patients who will develop cancer, to get better outcomes while reducing unnecessary screening and over-treatment for the rest.”